Chronic Myeloid Leukaemia

Name: Chronic Myeloid Leukaemia: Mini Review for Clinicians, Algorithms & Cases
Creator: Dr. Haritha Chiramana
License: https://creativecommons.org/licenses/by-nc-nd/4.0/

Haematological cancers, part 9 · Chronic, accelerated and blast phases · TKI choice and molecular milestones · Resistance, ponatinib and asciminib · Treatment-free remission · Pregnancy · Transplant · Key points for clinicians · Last updated 17 October 2026

For health professionals. This section uses clinical terms and is general education for doctors, nurses and students, not advice for an individual patient. Patients and families: please read our patient guides instead, Cancer Myth Busters · Understanding your cancer report · Living through cancer treatment, or speak with your own doctor.

Who this page is for, and where to start

Printable PDFs for this moduleMini reviews, slides, algorithms, quick references and the MCQ booklet are on the Printable Teaching Resources page. No PDF downloads are kept on this page.

Printable Teaching Resources →

For your patientsPlain-language Telugu–English answers for patients and families: the Leukaemia Myth Busters (20 myths), symptoms and warning signs and the Telugu handouts.

Open the leukaemia myths →

SurgeonsScreening and workup (03), local therapy with surgery types (05), algorithms (07), cases (11)

Physicians & oncologistsBiomarkers (04), systemic therapy (06), algorithms (07), survivorship (08), cases (11)

Postgraduate residentsOncology and other specialities: case vignettes (11), landmark trials (09) and 0 cited trials (12) for exams and journal clubs

Medical studentsAt a glance (01), presentation and common traps (02), the figures, and follow-up (08)

Prepared and reviewed by Dr. Haritha Chiramana, MD, DM, Senior Medical Oncologist & Hemato-Oncologist, C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India. She teaches oncology to postgraduates and medical students; colleges and departments may write to info@drharitha.co.in for teaching sessions. Printable Teaching Resources and how to cite → Phone 0861 232 5344 · WhatsApp +91 79896 42272.

01 At a glance

CML is a myeloproliferative neoplasm driven by one fusion gene: t(9;22) (the Philadelphia chromosome) joins BCR to ABL1 and makes an always-active tyrosine kinase. It is 15–20% of adult leukaemias, 1–2 per 100,000 a year, with a median age in the 60s in Western registries; Indian hospital series see patients about a decade younger (Bansal 2013^[1]).
Suspect it from an unexplained high white count with myelocytes and basophils, often with a big spleen; up to half have no symptoms at diagnosis.
Confirm in blood, stage in marrow: BCR::ABL1 by PCR (record the transcript type and a baseline on the International Scale) or FISH; marrow morphology and karyotype decide the phase and find extra chromosomes; the ELTS score sets the risk.
Treat every phase with a TKI. In chronic phase, imatinib (generic, by far the cheapest), a second-generation (2G) TKI or asciminib give the same long-term survival; high ELTS favours a 2G TKI or asciminib. Comorbidity decides among them.
Follow the BCR::ABL1 test: every 3 months until major molecular response (MMR, ≤0.1%), then every 3–6 months. Milestones ≤10% at 3 months, ≤1% at 6 and ≤0.1% at 12 are "favourable" (ELN 2025^[2]).
Off track? Adherence and interactions first, then karyotype and a kinase-domain mutation test. T315I → ponatinib or asciminib; after a 2G TKI fails, another 2G TKI rarely works. Start a donor search early.
Stopping is possible: after more than 5 years of TKI (4 for a 2G TKI) and more than 2 years of deep response, 40–50% stay in treatment-free remission.
Pregnancy: women stop TKIs (plan from diagnosis; interferon if counts need control; imatinib or nilotinib only after week 16); men can continue.
Advanced phases: myeloid blast phase is treated like AML (AML module) and lymphoid blast phase like Ph+ ALL (ALL module), always with a TKI, then allogeneic transplant if possible.
India: generic imatinib made CML treatable for most; the gaps are adherence (up to one-third miss doses), standardised PCR and access to later-line TKIs and transplant.

Figure 1. The four steps (UpToDate CML diagnosis, overview and chronic phase reviews; Bower 2016; Marin 2010; ELN 2025).

02 Clinical presentation, common traps & causes

Figure 2. Presentation (UpToDate CML diagnosis review, citing Savage 1997; Indian data from Bansal 2013 and Ganesan 2016).

Who gets it, and why

Incidence: 1–2 per 100,000 a year with a slight male excess; median age 66 at diagnosis in the United States. More than one-third of patients in a European population registry were of reproductive age, which makes fertility and pregnancy everyday questions.
India: CML is the commonest adult leukaemia in Indian hospital series. Estimated incidence 0.8–2.2 per 100,000; the Mumbai registry reported age-adjusted rates of 0.71 (men) and 0.53 (women) per 100,000 with the usual peak at 55–74 years, while hospital series report median ages of 32–42 and more symptomatic, high-risk presentations (Ganesan 2016^[3]; Bansal 2013^[1]).
Causes: ionising radiation is the only known risk factor. There is no familial tendency, and it is not inherited by children.
Why advanced presentations still occur: where access to care is limited, diagnosis is late and more patients present in accelerated or blast phase.

Common traps

Weeks of antibiotics for a "leukemoid reaction". A persistent high count with myelocytes and basophils needs BCR::ABL1 testing; toxic granules and Döhle bodies favour infection.
Hydroxyurea before the spleen is measured. Record spleen size in centimetres and send samples first: ELTS is not valid after treatment.
Blood PCR alone, no marrow. PCR confirms CML but the marrow finds accelerated or blast phase and extra chromosomes.
"PCR negative, so not CML." Routine kits detect p210 and p190 only; p230 and rare transcripts need FISH, and some Ph-negative cases have cryptic fusions.
Changing laboratories. Results are comparable only on the International Scale in a standardised laboratory; use one laboratory throughout.
Low platelets at diagnosis. Uncommon in chronic phase: think of MDS or an advanced phase.
Lymphoblasts on the film. In a patient with CML this is lymphoid blast phase until proved otherwise.
Herbal and over-the-counter medicines. Some reduce TKI levels (CYP3A4 inducers such as St John's wort) or add to QTc prolongation; acid-suppressing drugs reduce dasatinib and nilotinib absorption.

Figure 3. Differential diagnosis (UpToDate CML diagnosis and blast phase reviews). MPNs are covered here only as differentials.

03 Diagnosis, workup & staging essentials

Figure 4. Work-up (UpToDate CML diagnosis, overview and chronic phase reviews; ELN 2025, Table 1).

Making the diagnosis

CML is a pathological diagnosis: t(9;22)(q34;q11.2) by banding or FISH and/or BCR::ABL1 by RT-PCR, in blood or marrow. More than 90% show the Ph chromosome on banding; in one large study 15% lacked it (complex or cryptic rearrangements). With high suspicion and a negative karyotype, FISH is mandatory.
Marrow at diagnosis (ELN 2025^[2] recommends banding analysis on marrow): hypercellular, granulocytic hyperplasia, myeloid:erythroid ratio up to 20:1, small megakaryocytes, sometimes reticulin fibrosis; about 2% blasts in chronic phase. A marrow can be omitted only when the result would not change treatment (frailty).
Atypical transcripts (about 2%) must be identified at diagnosis: they need FISH, a personalised assay or digital PCR for monitoring.
Phase: ICC keeps three phases (accelerated 10–19% blasts, basophils ≥20%, high-risk extra chromosomes); WHO 2022 recognises only chronic and blast phase, listing high-risk features instead; older ELN criteria (blast phase ≥30%) were used in most trials (ICC 2022^[4]; WHO 2022^[5]).
Leukostasis is uncommon in chronic phase but can occur with extreme counts (priapism, breathlessness, transient ischaemic attack): hydroxyurea lowers the count within 1–2 days; leukapheresis for symptomatic cases. Emergency care is shared with the acute leukaemias (AML module, emergencies).

Figure 5. Phases (UpToDate CML diagnosis and accelerated phase reviews; ICC 2022; WHO 2022; ELN 2025, Table 2).

Risk at diagnosis

ELTS (age, spleen size, blood blasts, platelets) was built on TKI-treated patients and best predicts death from CML (Pfirrmann 2016^[6]; Pfirrmann 2020^[7]). ELN 2025 replaces Sokal, Euro and EUTOS with ELTS; UpToDate accepts any validated score.
Comorbidity now predicts survival more than CML itself for many patients: 8-year survival fell from 94% to 46% across Charlson index groups in CML Study IV (Saussele 2015^[8]).
Extra chromosomes at diagnosis (about 7%): major-route changes (+8, +Ph, i(17q), +19) and 3q26.2, −7/7q−, complex karyotype carry a worse outlook (Fabarius 2011^[9]; Wang 2016^[10]).

Figure 6. Risk (UpToDate CML diagnosis and chronic phase reviews; Pfirrmann 2016 and 2020; Yun 2016; Saussele 2015; Millot 2026 for children).

04 Biology and biomarkers that change treatment

Figure 7. Biology (UpToDate CML diagnosis review; ELN 2025; Fabarius 2011; Wang 2016).

Biomarkers that change treatment

BCR::ABL1 itself: the target of every TKI and the marker followed for life.
Transcript type: decides how to monitor (rare transcripts need FISH or personalised assays); e14a2 is associated with more successful treatment-free remission; transcripts without ABL1 exon 2 (e13a3, e14a3) are expected to resist asciminib (ELN 2025^[2]).
Extra chromosomes in Ph+ cells: a warning at diagnosis and a sign of progression if they appear on treatment. Changes in Ph-negative cells (for example trisomy 8) can wax and wane without affecting outcome, but −7/7q− needs marrow follow-up.
Kinase-domain mutations: the only actionable resistance mechanism; tested at warning or unfavourable responses and at progression, not at diagnosis in chronic phase. NGS finds emerging clones earlier than Sanger sequencing and identifies compound mutations.
Other somatic mutations (20–30%; ASXL1 in about 10%): research tools in chronic phase; targeted NGS is recommended at blast phase.

How response is measured

Haematological: complete haematological response = WBC <10,000/µL, platelets <450,000/µL, no immature cells, basophils <5%, spleen not palpable.
Cytogenetic (≥20 marrow metaphases): complete = no Ph+ cells; major = 1–35%; minor 36–65%; minimal 66–95%; none >95%. Interphase FISH with <1% positive nuclei (≥200 counted) can document complete response. Rarely needed now that PCR is standardised.
Molecular (International Scale, relative to the IRIS baseline): MMR (MR3) ≤0.1%, MR4 ≤0.01%, MR4.5 ≤0.0032%, MR5 ≤0.001%; deep molecular response = MR4 or deeper (Cross 2012^[11]).

Figure 8. Molecular response (UpToDate overview and chronic phase reviews; Cross 2012; ELN 2025, Table 3; Balasubramanian 2012; Ganesan 2016). Log scale.

05 Local therapy: radiotherapy, surgery & procedures

Radiotherapy

No routine role in chronic phase CML in the supplied sources. In blast phase, myeloid sarcoma and CNS disease are managed as in the acute leukaemias (AML module, radiotherapy; ALL module, radiotherapy).

Procedures and their pitfalls

Bone marrow aspirate and biopsy: at diagnosis (phase, karyotype) and at resistance or progression; not for routine follow-up of a patient responding on PCR, unless there are unexplained cytopenias or dysplasia.
Leukapheresis: for symptomatic leukostasis when hydroxyurea is not enough, and in pregnancy (alone or with interferon), depending on venous access and availability.
Pleural effusions on dasatinib: chest X-ray, exclude infection, heart failure, kidney disease and progression; some need thoracentesis, a chest drain or pleurodesis, with interruption or dose reduction.
Lumbar puncture: in lymphoid blast phase or with neurological signs; not in neurologically well patients with myeloid blast phase. CNS disease is treated as in ALL or AML (intrathecal therapy, high-dose methotrexate); dasatinib, bosutinib, nilotinib and ponatinib cross the blood-brain barrier.
Allogeneic HCT: reduced-intensity or non-myeloablative conditioning for older (over about 55) or less fit patients; ELN 2025^[2] prefers myeloablative conditioning where possible because relapse rises with reduced intensity. Matched sibling or unrelated donors preferred; haploidentical or cord blood acceptable. The TKI may be held during transplant and restarted at count recovery (around day 30–60).

06 Systemic therapy: indications & options

Chronic phase: the first TKI

Figure 9. First-line choice (UpToDate chronic phase and overview reviews; Hochhaus 2016 ENESTnd; Yun 2016; ELN 2025). No doses.

Why TKIs: in IRIS, imatinib beat interferon plus cytarabine (18-month PFS 97% vs 92%) with better quality of life; 10-year OS was 84% (most of the control arm crossed over) (IRIS^[12], Hochhaus 2017^[13]). Life expectancy now approaches that of the general population (Bower 2016^[14]), although ELN 2025 notes small residual losses in Swedish data.
Imatinib: the longest safety record; generic; slower to deep response. Fluid retention, periorbital oedema, cramps, nausea, diarrhoea; hypophosphataemia and bone changes. Taken with food.
Dasatinib: once daily with or without food; pleural/pericardial effusions, pulmonary arterial hypertension, bleeding from a platelet defect, QTc. Avoid in lung disease, effusions, bleeding disorders; acid-suppressing drugs reduce absorption (a formulation that tolerates them exists in some markets).
Nilotinib: twice daily with strict food rules (formulations are not interchangeable); arterial occlusive disease, QTc and rare sudden death, raised glucose and cholesterol, pancreatitis. Avoid with diabetes, high cardiovascular risk or a past vascular event (ENESTnd^[15]).
Bosutinib: diarrhoea (mostly early) and raised liver enzymes; some start low and escalate to improve tolerance. Avoid with bowel, liver or kidney disease.
Asciminib: binds the myristoyl pocket rather than the ATP site; taken without food. Lipase rise, hypertension, musculoskeletal pain. ASC4FIRST: MMR at 96 weeks 74.1% vs 52.0% with investigator-chosen TKIs, event-free survival 85.6% vs 70.6%, fewer discontinuations; overall survival not yet reported (ASC4FIRST^[16]). FDA-approved first line; EMA only after ≥2 TKIs.
2G vs imatinib: 16 or more trials, faster and deeper responses and fewer transformations with 2G TKIs, no overall survival gain; in a meta-analysis of 8 trials (2974 patients) progression was 0.8% vs 3.0% (Yun 2016^[17]). Nilotinib and dasatinib were equivalent in the Japanese JALSG CML212 trial (Matsumura 2024^[18]).
Cytoreduction before confirmation: hydroxyurea for symptomatic splenomegaly or very high counts; it does not affect later milestones (Kockerols 2022^[19]). Interferon added to a TKI is not recommended (more toxicity, little gain).
Lower starting doses (dasatinib, bosutinib) are being studied to reduce side effects; ELN 2025 cannot yet recommend them routinely.

Living with a TKI: side effects

Figure 10. Side-effect map (ELN 2025, Table 8, expert opinion from mainly first-line studies; UpToDate chronic phase review). Dot size = relative frequency, not a percentage.

Early effects are mild and usually settle: nausea (less with food for imatinib and bosutinib), cramps (about half on imatinib; correct electrolytes), rash, oedema, diarrhoea (check for lactose intolerance), fatigue (check thyroid, sleep, mood). Report even grade 1–2 effects early: persistent low-grade effects drive non-adherence.
Cytopenias in the first weeks are mostly the leukaemia clearing: continue if mild; hold or reduce for severe ones; avoid erythropoietin-stimulating agents (thrombosis, no benefit); growth factors occasionally, with the TKI continued.
Drug holidays and dose reduction: a 5–7-day break often resolves a low-grade effect. In patients with at least MMR, dose reduction keeps the response in most: in DESTINY 20–30% lost MMR on half dose, and all regained it on full dose (Clark 2017^[20]). Avoid long interruptions.
Other effects: hypophosphataemia (nilotinib, imatinib), gynaecomastia with low free testosterone (imatinib), skin hypopigmentation (reported in Indian patients), gastric antral vascular ectasia (rare). No excess of second cancers (1445 patients followed a median of 107 months).

Figure 11. Cardiovascular and lung toxicity (UpToDate chronic phase and after-failure reviews; ELN 2025, Table 9; Jain 2019; Cortes 2018 PACE; Cortes 2021 OPTIC).

Cardiovascular risk is highest with ponatinib and nilotinib, slightly raised with dasatinib, lower with imatinib and bosutinib; older age, hypertension, diabetes, high lipids and smoking add risk whatever the TKI, especially in the early years (Jain 2019^[21]).
QTc: ECG at baseline and 1–2 weeks after starting nilotinib or dasatinib, after dose changes and with new QT-prolonging drugs; correct potassium and magnesium.
Pancreas and liver: lipase (and amylase) monthly in the first months on nilotinib, bosutinib or asciminib, or as clinically indicated (ELN 2025); reduce, hold or switch for clinically significant rises. Liver enzymes rise most with bosutinib, imatinib and nilotinib; avoid alcohol and hepatotoxic drugs.

Monitoring and molecular milestones

Figure 12. Milestones (ELN 2025, Table 4; UpToDate overview and chronic phase reviews; Lauseker 2023).

Schedule: CBC every 2 weeks until complete haematological response (weekly in month 1 in UpToDate's algorithm); BCR::ABL1 (IS) at least every 3 months until MMR is achieved and confirmed, then every 4–6 months (ELN 2025) or 3–6 months (UpToDate); more often if values fluctuate or rise, and around treatment-free remission. Cytogenetic monitoring is no longer routine.
Achieving MMR within a year predicts CML-specific survival close to 100%; a deep response (MR4 or deeper) is what treatment-free remission needs.
New ELN 2025 wording: favourable, warning and unfavourable replace optimal, warning and failure, to stress that a switch depends on the trend, adherence, comorbidity and goals. In CML Study IV, patients who missed the 3-, 6- or 12-month milestones still had about 80% 10-year survival, but only 55% if BCR::ABL1 was still >10% at 12 months (Lauseker 2023^[22]). Without early molecular response, switching to dasatinib (DASCERN) deepened responses (MMR 77% vs 44%) without a survival difference.
Fit or younger patients seeking treatment-free remission may switch to a more potent TKI; older or comorbid patients may continue with close monitoring. A confirmed rise without explanation needs karyotype, mutation testing and a switch.

Resistance and intolerance: second line and beyond

Figure 13. Second line (UpToDate after-failure and overview reviews; ELN 2025).

Intolerance has no consensus definition: persistent or recurrent grade ≥3 non-haematological effects despite management, or lower-grade effects the patient cannot live with. Choose the next TKI by toxicity profile and comorbidity.
Resistance: confirm with repeat PCR, ask about adherence and interacting drugs, then marrow (blasts, karyotype) and kinase-domain mutation testing. ELN 2025 reports unfavourable responses in 15–20% on first line and up to 50% in later lines.
After imatinib: dasatinib, nilotinib, bosutinib or asciminib by mutation and comorbidity; no TKI has proved superior. Dasatinib (7-year data), nilotinib (4-year OS 78%) and bosutinib (2-year OS 91%) all work (Shah 2016^[23]; Giles 2013^[24]; Gambacorti-Passerini 2014^[25]). Dasatinib beat high-dose imatinib (START-R^[26]); imatinib dose escalation is a fallback where nothing else is affordable.
After a 2G TKI: another 2G TKI rarely works; ponatinib or asciminib. ASCEMBL (after ≥2 TKIs): MMR at 96 weeks 37.6% with asciminib vs 15.8% with bosutinib, with fewer discontinuations for side effects (Réa 2021^[27]; Hochhaus 2023^[28]).
T315I resists imatinib, dasatinib, nilotinib and bosutinib: ponatinib or asciminib (asciminib at a higher dose than for other mutations), with a parallel donor search. In a registry comparison, ponatinib gave better 48-month survival than transplant (73% vs 56%) (Nicolini 2017^[29]). Omacetaxine is no longer manufactured; olverembatinib is approved only in China.
Ponatinib: PACE (chronic phase, resistant or intolerant to dasatinib/nilotinib): major cytogenetic response 60%, MMR 40%, 5-year OS 73%, but vascular events in 31% (PACE^[30]; Cortes 2018^[31]). OPTIC: starting higher and reducing once BCR::ABL1 <1% balanced response (44%, 29%, 23% under 1% at 12 months by starting dose) against arterial events (10%, 5%, 3%) (OPTIC^[32]).
Asciminib in heavily pretreated patients: MMR at 12 months in 48% of evaluable patients and 28% of those with T315I, including some after ponatinib (Hughes 2019^[33]).
After ≥2 TKIs: a third-line TKI or allogeneic HCT, decided with the patient; donor search should begin at resistance to the first 2G TKI, and transplant referral at resistance to ponatinib and/or asciminib (ELN 2025^[2]).

Figure 14. Mutation-guided choice (ELN 2025, Table 5; UpToDate after-failure, accelerated and blast phase reviews). ✓ = recommended option; — = not recommended. In vitro data, not trials.

Treatment-free remission

Figure 15. TFR (ELN 2025, Table 6; UpToDate chronic phase and overview reviews; Saussele 2018; Clark 2019; de Bruijn, STOP IMAPED).

A reasonable goal for most young and middle-aged patients, especially women planning pregnancy and those with troublesome side effects; some, especially older patients, prefer to stay on treatment. Discuss the data and the withdrawal syndrome first.
Results: 40–50% of eligible patients remain off treatment. EURO-SKI (755 patients): MMR kept by 61% at 6 and 46% at 12 months (EURO-SKI^[34]). LAST: 77% at 6 and 71% at 12 months, with less fatigue, depression, diarrhoea and sleep disturbance (LAST^[35]). Similar after nilotinib and dasatinib (ENESTfreedom^[36], DASFREE^[37]). No asciminib data yet.
DESTINY: halving the dose for 12 months before stopping gave 72% TFR in those with MR4 or deeper, and allows restarting at the reduced dose (DESTINY^[38]).
Monitoring is the safety net: more than 80% of molecular relapses occur in the first 6–8 months; late loss of MMR in up to 14% after 2 years (Rousselot 2020^[39]). Loss of MMR triggers restarting (one result is enough per ELN 2025); mutation testing is not needed; 90–95% regain their response. Sudden blast phase after stopping is very rare (≤0.1%).
Not for: accelerated or blast phase (no data), patients without reliable fast IS-standardised PCR, and children outside expert centres (see section 08).

Pregnancy and fertility

Figure 16. Parenting (ELN 2025, Table 7; UpToDate chronic phase review; Pye 2008; Cortes 2015; Chelysheva 2024; Kondo 2025). No doses.

Women: all TKIs are potentially teratogenic; risk is assumed from implantation (about 15 days after fertilisation) until organogenesis is complete (around week 16). Imatinib and nilotinib cross the placenta poorly; dasatinib reached 75% of maternal levels in the one case measured. Of 180 imatinib-exposed pregnancies, half with known outcome were normal and about 10% had fetal abnormalities (Pye 2008^[40]); dasatinib-exposed pregnancies also had high loss and abnormality rates (Cortes 2015^[41]).
ELN 2025 parenting guidance: plan from diagnosis; with MR4 or deeper, stop as for TFR; with MMR, stop and watch, or (for women with regular cycles and access to tests) continue until the first positive pregnancy test; without MMR, deepen the response first (IVF with a planned TKI interruption is an option in older women). During pregnancy: no TKI to week 16; interferon (including pegylated forms) at any time for count control; imatinib or nilotinib after week 16 if CHR is lost or PCR rises fast; avoid dasatinib throughout; PCR and CBC every 6–8 weeks; early and regular fetal scans; no TKI while breastfeeding.
Diagnosed in pregnancy: of 87 women in the ELN registry, 66 (76%) had a normal childbirth with no excess of malformations; treatment was mostly interferon and, after week 16, imatinib (Chelysheva 2024^[42]). With WBC <100,000/µL, low or intermediate ELTS and no extra chromosomes, watchful waiting is reasonable; leukapheresis and/or interferon for symptomatic or high counts; aspirin and/or LMW heparin for thrombocytosis. In advanced phase, treatment cannot wait and termination should be discussed with the woman and her family.
Planned pregnancies take time: in a Japanese series of 70 pregnancies, planned pregnancies (during TFR or on interferon) came a median 10.6 years after diagnosis vs 4.1 years for unplanned ones (Kondo 2025^[43]).
Men: no convincing effect of TKIs on fertility or on their children; in 428 pregnancies of partners of men on TKIs, live births were 93.5% and congenital abnormalities 2.5%. Men should continue the TKI when trying to conceive (ELN 2025^[2]).

Accelerated and blast phase

Figure 17. Advanced phases (UpToDate accelerated and blast phase reviews; Ohanian 2014; Saxena 2021; Strati 2014; Thota 2014 via Ganesan 2016).

De novo accelerated phase: a 2G TKI rather than imatinib, ponatinib or upfront transplant; 90% complete cytogenetic response in 21 patients on dasatinib or nilotinib (Ohanian 2014^[44]). Continue indefinitely; no TFR attempts. BCR::ABL1 <10% at 3 months predicted better survival.
Transformed accelerated phase: adherence, mutation test, switch TKI; transplant-eligible patients proceed to allogeneic HCT once disease is controlled. Dasatinib in imatinib-resistant AP: complete haematological response 50%, complete cytogenetic response 32% (Kantarjian 2009^[45]).
Myeloid blast phase: TKI plus AML-type induction (intensive, or a hypomethylating agent ± venetoclax in older patients), then HCT. In 104 patients, 5-year OS was 30% with TKI + intensive chemotherapy, 28% with TKI + HMA, 13% with TKI alone and 0% with chemotherapy alone (Saxena 2021^[46]). Ponatinib + FLAG-IDA bridged two-thirds back to chronic phase (MATCHPOINT^[47]). Dasatinib alone: short remissions (Saglio 2010^[48]).
Lymphoid blast phase (one-third): TKI plus a Ph+ ALL regimen (hyper-CVAD best studied; TKI + steroid or lower intensity if frail; TKI + blinatumomab or inotuzumab emerging); lumbar puncture. With hyper-CVAD + TKI, median OS was 93 months with transplant vs 9 months without (Strati 2014^[49]). See the ALL module (Ph+ ALL).
TKI in blast phase: chosen by prior TKIs and mutation, not lineage; avoid imatinib; T315I → ponatinib. Continue the TKI during induction and keep the dose despite cytopenias in responding patients (support with transfusion). After remission monitor PCR every 3 months for 2 years.
Relapsed or refractory blast phase: very poor outlook; repeat mutation testing, clinical trial, donor lymphocytes or second HCT after transplant, otherwise palliation.

Allogeneic transplant

Figure 18. Transplant (UpToDate overview, after-failure, accelerated and blast phase reviews; Kebriaei 2007; Lübking 2019; ELN 2025).

Indications: blast phase once back in chronic phase or remission; transformed accelerated phase; chronic phase failing ponatinib and/or asciminib or intolerant of all TKIs. Transplant of resistant blast phase outside a study is not recommended (ELN 2025^[2]).
Outcomes: up to 80% 5-year survival after TKI failure in chronic phase, with 10–20% early mortality; advanced phase 37–59% in small series; reduced-intensity in advanced CML 33% 5-year OS with 39% transplant-related mortality at 2 years (Kebriaei 2007^[50]). In a Swedish population series, outcomes in the TKI era were reported by phase (Lübking 2019^[51]).
After transplant: PCR at least every 3 months early, then 6-monthly for life; TKI and/or escalating donor lymphocyte infusions for molecular relapse; TKI given before transplant in advanced phase is restarted once engraftment is secure.

India: check availability and cost before planning

Generic imatinib is widely available and inexpensive; patient-assistance programmes (GIPAP, Max Foundation) and generics made it reachable for most patients, and at Tata Memorial generic imatinib gave the same responses as the innovator (Parikh 2013^[52]). ELN 2025 puts generic imatinib at as little as US$200–500 a year.
Dasatinib and nilotinib have been available in India, including generics (Ganesan 2016^[3]); check current price and supply.
Bosutinib, asciminib and ponatinib: current Indian availability and cost were not verified for this page; check with the pharmacy before planning second- or third-line treatment.
Testing: IS-standardised BCR::ABL1 PCR, NGS mutation testing and a laboratory that confirms MR4.5 with a two-week turnaround (needed for TFR) are not available everywhere; few Indian laboratories reported on the International Scale (Balasubramanian 2012^[53]).
Pregnancy and transplant: confirm access to interferon (including pegylated forms) and to allogeneic HCT, including haploidentical donors.

Quick reference: tests, settings, options, problems

Table A. Diagnosis, staging and baseline tests, and what they change

Test	When	What it changes	Pitfalls
CBC + blood film	Every suspected case; every 2 weeks until CHR	Left-shifted granulocytes, basophils, blasts; phase clues	Leukemoid reaction looks similar: BCR::ABL1 decides
Qualitative PCR (transcript type) + quantitative PCR (IS)	At diagnosis, blood	Confirms CML; sets the baseline for all later monitoring	Routine kits detect p210 and p190 only: p230 and rarer types need FISH or a personalised assay
Marrow: morphology + karyotype (≥20 metaphases)	At diagnosis; at resistance or progression	Phase (blasts, basophils, fibrosis); extra chromosomes (ACA)	FISH alone misses ACA; not needed for routine follow-up
FISH for BCR::ABL1	No Ph on karyotype; atypical transcripts	Finds variant or cryptic fusions	Interphase FISH ≥200 nuclei can document CCyR
Flow cytometry	Blasts raised	Myeloid vs lymphoid blast phase → AML-type vs ALL-type induction	Any lymphoblasts should raise suspicion of lymphoid BP
ELTS score	Before any treatment	High risk → 2G TKI or asciminib; ELN "warning"	Spleen in cm below the costal margin; values after hydroxyurea are not valid
ECG (QTc), BP, lipids, HbA1c	Baseline; lipids/HbA1c every 6–12 months on nilotinib or ponatinib	Avoid nilotinib with high CV risk; QT drugs	Repeat ECG 1–2 weeks after starting nilotinib or dasatinib
Hepatitis B serology; liver, kidney tests; lipase as indicated	Baseline	Reactivation risk; bosutinib dose; pancreatitis	Lipase may rise without pancreatitis
Kinase-domain mutation (NGS or Sanger)	Warning or unfavourable response, progression, blast phase; not at diagnosis in CP	Which TKI can still work (mutation figure, section 06)	Not needed after loss of MMR during TFR
HLA typing (patient and siblings)	Blast phase, transformed AP, resistance to a 2G TKI	Early donor search	Haploidentical donors widen access

Table B. Treatment by setting

Setting	Usual approach	Alternatives	Key points
Chronic phase, ELTS low or intermediate	Imatinib (generic), a 2G TKI or asciminib	—	Same long-term survival; 2G/asciminib reach deep responses faster
Chronic phase, ELTS high	A 2G TKI or asciminib	Imatinib if nothing else is affordable	Fewer early progressions than imatinib
Very high count or painful spleen before confirmation	Hydroxyurea for days	Leukapheresis only for leukostasis	Start the TKI as soon as BCR::ABL1 is confirmed
Warning at a milestone	Check adherence and interactions; repeat PCR in 1–2 months	Switch TKI if the trend does not fall	Late responders may stay on the same TKI
Unfavourable / resistant after imatinib	Mutation test; a 2G TKI or asciminib	Higher-dose imatinib if no other option	Choice by mutation, comorbidity and cost
Resistant after a 2G TKI	Ponatinib or asciminib	Another 2G TKI rarely works	Start donor search now
T315I	Ponatinib or asciminib	Allogeneic HCT if inadequate response	Asciminib for T315I needs a higher dose than usual
Intolerance with a good response	Dose reduction with close monitoring	Switch by side-effect profile	Some toxicities always need a switch
Stable deep response	TFR attempt if ELN criteria met	Dose halving for a year first (DESTINY)	Monitor every 6–8 weeks for 6 months
Planning pregnancy (woman)	Deep response, then stop as for TFR	Stop at first positive test (MMR, regular cycles)	Interferon if counts need control; TKI only after week 16
De novo accelerated phase	A 2G TKI	—	No TFR attempts
Transformed accelerated phase	TKI by mutation, then allogeneic HCT	TKI alone if not eligible	Adherence and mutation test first
Myeloid blast phase	TKI + AML-type induction (intensive or HMA ± venetoclax), then HCT	TKI alone (palliative)	See the AML module
Lymphoid blast phase	TKI + Ph+ ALL regimen (or TKI + blinatumomab/inotuzumab), then HCT	TKI + steroid if frail	Lumbar puncture; see the ALL module

Table C. Treatment options: evidence and best fit

Option	Best fit	Evidence	Watch for
Imatinib (generic)	Lower-risk CP; cost-limited care; CV disease	IRIS^[12], IRIS 10-year^[13]; generic = innovator in India	Cramps, periorbital oedema, fluid retention, nausea, diarrhoea
Dasatinib	High-risk CP; second line; pancreatitis history	CA180-034^[23]	Effusions, pulmonary hypertension, bleeding, QTc; avoid in lung disease
Nilotinib	High-risk CP without CV risk; second line	ENESTnd^[15]	Arterial events, glucose and lipids, QTc, pancreatitis; twice daily, food rules
Bosutinib	CV disease; second line	Gambacorti-Passerini 2014^[25]	Early diarrhoea, liver enzymes; avoid in GI, liver or kidney disease
Asciminib	First line (FDA); after ≥2 TKIs; T315I	ASC4FIRST^[16], ASCEMBL^[27]	Lipase, hypertension; take without food; myristoyl-pocket mutations resist
Ponatinib	T315I; failure of a 2G TKI; blast phase	PACE^[31], OPTIC^[32]	Arterial occlusion, hypertension, liver; reduce the dose once BCR::ABL1 <1%
Interferon alfa	Pregnancy (any trimester)	Chelysheva 2024^[42]	Slow count control; molecular response not assured
Hydroxyurea	Short cytoreduction before confirmation	Kockerols 2022^[19]	Does not change milestones; teratogenic in animals
Allogeneic HCT	Blast phase, transformed AP, failure of ponatinib/asciminib	Lübking 2019^[51], Nicolini 2017^[29]	Early mortality 10–20%; GVHD; lifelong PCR after

Table D. Managing problems during treatment

Problem	First steps	Then	Points
Nausea, cramps, rash, oedema, diarrhoea, fatigue (early)	Symptomatic care; take imatinib and bosutinib with food; correct electrolytes	Brief interruption (5–7 days) or dose adjustment	Usually settle; ask about lactose intolerance with diarrhoea
Low counts in the first weeks	Continue if mild: it is the leukaemia clearing	Hold or reduce for severe cytopenias; growth factors rarely	Avoid ESAs; transfusion for symptomatic anaemia
Breathless or coughing on dasatinib	Chest X-ray; look for effusion, pneumonitis, infection, heart failure	Interrupt or reduce; drain if large	Recurrent effusions or pulmonary hypertension: switch for good
Chest pain, claudication, TIA on nilotinib or ponatinib	Urgent CV assessment	Stop that TKI; switch (imatinib, bosutinib or TFR if eligible)	Control BP, glucose, lipids, smoking from the start
QTc prolongation	Correct potassium and magnesium; stop QT-prolonging drugs	Dose adjustment or switch	ECG 1–2 weeks after starting nilotinib or dasatinib
Raised lipase or abdominal pain	Check lipase; image if symptomatic	Reduce or hold; switch if it persists	Nilotinib, bosutinib, asciminib, ponatinib
Bleeding or bruising on dasatinib	Platelet count; review antiplatelets and anticoagulants	Drug holiday usually enough	Qualitative platelet defect with normal counts
Aches after stopping the TKI	Simple analgesia or an NSAID	Short steroid course occasionally	Withdrawal syndrome in 20–30%; usually self-limiting
Missed doses, cost or travel problems	Ask at every visit; involve family; patient-assistance programmes	Simplify the schedule; generic options	Adherence ≤80%: no MMR (Marin 2010)
New medicine or herb	Check CYP3A4 interactions and QT effect	Choose an alternative	PPIs reduce dasatinib and nilotinib absorption (special formulations exist)

07 Management algorithms

Six decision paths pull together sections 02–06.

Algorithm 1Suspected CML: from a high white count to a phase and a plan

Leukocytosis with myelocytes and basophils, often a big spleen → blood film; blood BCR::ABL1 (qualitative + quantitative PCR) or FISH; spleen size in cm before any hydroxyurea

Confirm

BCR::ABL1 positive → CML

PCR negative, suspicion high → FISH (rare transcript, cryptic fusion)

Negative → leukemoid reaction, aCML, CMML, CNL, other MPN

Very high count or symptoms → hydroxyurea for days; leukostasis: AML module

Stage (marrow)

Morphology, karyotype ≥20 metaphases

Blasts <10%, no AP features → chronic phase

10–19%, basophils ≥20%, high-risk ACA → accelerated (ICC)

≥20%, myeloid sarcoma, lymphoblasts → blast phase

Blasts raised → flow cytometry (myeloid or lymphoid)

Prepare

ELTS; ECG; BP, lipids, HbA1c; HBV; full drug list

Pregnancy or fatherhood plans

Chronic phase → Algorithm 2

Accelerated or blast → Algorithm 6

Explain: daily tablets, PCR every 3 months, adherence

Before treatment: transcript type recorded · one IS-standardised laboratory for every PCR · drug access arranged (generic or assistance programme).

Algorithm 2Chronic phase: choosing the first TKI

Chronic phase confirmed → ELTS risk, comorbidities, interacting drugs, goals (stopping, pregnancy), cost

ELTS low or intermediate

Imatinib (generic), a 2G TKI or asciminib

Same long-term survival

Wants TFR or pregnancy → a faster TKI may help

Cost limits → generic imatinib

Asciminib first line: FDA, not EMA

ELTS high or high-risk ACA

A 2G TKI or asciminib

Fewer early progressions than imatinib

Closer monitoring (ELN "warning")

Imatinib if nothing else is accessible

Comorbidity filter

Vascular disease, diabetes → not nilotinib

Lung disease, effusion risk → not dasatinib

Pancreatitis → not nilotinib, bosutinib, asciminib

Bowel, liver, kidney disease → not bosutinib

Long-term PPI → avoid dasatinib and nilotinib

All: CBC every 2 weeks until CHR · BCR::ABL1 (IS) at 3, 6 and 12 months (Algorithm 3) · ECG 1–2 weeks after starting nilotinib or dasatinib · treat cardiovascular risk factors.

Algorithm 3Monitoring: what to do with each BCR::ABL1 result

BCR::ABL1 (IS) at 3, 6 and 12 months, then every 3–6 months in MMR → compare with ELN 2025 milestones; look at the trend

Favourable

3 m ≤10% · 6 m ≤1% · 12 m ≤0.1%

Continue the same TKI

Stable MR4 or deeper → TFR? (Algorithm 5)

Side effects with ≥MMR → dose reduction, not a switch

Warning

3 m >10% · 6 m >1–10% · 12 m >0.1–1%

Adherence, interactions; repeat in 1–2 months

Falling → continue, monitor closely

Flat or rising → mutation test, consider a switch

Older, comorbid late responders: continuing is reasonable

Unfavourable

>10% confirmed at 3 m · >10% at 6 m · >1% at 12 m

Loss of response, mutation, high-risk ACA

Marrow, karyotype, mutation test

Switch TKI → Algorithm 4

Same milestones for 2nd and 3rd line · a rising PCR without explanation is resistance until proved otherwise · confirm results near a threshold before acting.

Algorithm 4Resistance or intolerance in chronic phase

Off track or intolerant → confirm with repeat PCR; adherence, interactions; marrow and kinase-domain mutation if resistant

Intolerance

Good response (≥MMR) → dose reduction

Otherwise switch by toxicity and comorbidity

Always switch: recurrent effusion, PAH, arterial or venous occlusion, enterocolitis

Resistance, no T315I

Mutation-guided TKI (mutation figure, section 06)

After imatinib → a 2G TKI or asciminib

After a 2G TKI → ponatinib or asciminib

Start the donor search at 2G TKI resistance

T315I or ≥2 TKIs failed

T315I → ponatinib or asciminib

Milestones missed → allogeneic HCT if eligible

After ≥2 TKIs → third-line TKI or HCT

Phase change → Algorithm 6

Response targets on 2nd and 3rd line are the same as first line · ASCEMBL: asciminib beat bosutinib after ≥2 TKIs · India: check access to ponatinib and asciminib early.

Algorithm 5Stopping treatment (TFR) and planning a pregnancy

Stable deep response, or a wish for pregnancy → ELN 2025 criteria; reliable IS PCR with fast results; an informed patient

TFR

First CP; TKI >5 y (>4 y if 2G); MR4 >2 y

Stop (or halve the dose for a year first)

PCR every 6–8 wk to 6 m, 2-monthly to 12 m, then 3–6-monthly

MMR lost → restart the same TKI; 90–95% regain

Woman planning pregnancy

MR4 or deeper → stop as for TFR

MMR only → stop and watch, or stop at first positive test

No MMR → deepen first; IVF route if older

In pregnancy: interferon; TKI only after week 16; never dasatinib

Man planning fatherhood

Continue the TKI

428 partner pregnancies: 93.5% live births, 2.5% anomalies

As in the general population

No TKI while breastfeeding · aches after stopping in 20–30% · children: stopping succeeds less often (STOP IMAPED: 28.6% at 6 months).

Algorithm 6Accelerated and blast phase

Accelerated or blast phase (new or on a TKI) → marrow with flow cytometry and karyotype; kinase-domain mutation (NGS); fitness; HLA typing now

Accelerated phase

De novo → a 2G TKI

Transformed → TKI by mutation

Transformed and eligible → allogeneic HCT

No TFR attempt in accelerated phase

Myeloid blast phase

TKI + AML-type induction

Intensive, or HMA ± venetoclax if older

Remission → allogeneic HCT

Not fit: TKI ± consolidation; TKI alone is palliative

Lymphoid blast phase

TKI + Ph+ ALL regimen

Or TKI + blinatumomab or inotuzumab

Lumbar puncture; CNS therapy

Remission → HCT; not fit: TKI + maintenance

TKI by prior TKI and mutation, not lineage · avoid imatinib · T315I → ponatinib · leukostasis, tumour lysis, infection: AML module · Ph+ ALL regimens: ALL module.

08 Survivorship, follow-up & late effects

Lifelong follow-up: PCR as in Algorithm 3 for as long as the TKI is taken, and lifelong after stopping or after transplant; blood pressure, glucose, lipids and symptoms of vascular disease at visits.
Quality of life: patients over 60 on imatinib reported quality of life similar to their peers, but younger patients reported worse; one-third to one-half have symptoms that affect mood or daily life. Ask about fatigue, cramps, diarrhoea and mood; dose reduction in deep responders and treatment-free remission can help.
Adherence is treatment: with ≥90% adherence 95% reached MMR at 6 years vs 28% below that, and none with ≤80% (Marin 2010^[54]). In India non-adherence affects up to one-third and shortens event-free survival (Ganesan 2011^[55]). Ask kindly and specifically; involve family; link to assistance programmes.
Long-term issues: cardiovascular disease (nilotinib, ponatinib); hypophosphataemia and bone changes; gynaecomastia; thyroid (ponatinib); fertility and pregnancy planning; no excess of second cancers.
Children and adolescents need growth, puberty, thyroid and bone surveillance and endocrinology input when growth falls (figure below; Millot 2025^[56]).

Figure 19. Children vs adults (UpToDate chronic phase review; Millot 2025 and 2026; Stiehler 2024; Shima 2024 (JPLSG); COG CML Working Group 2019; Bansal 2012; Indian adult ages from Bansal 2013). Childhood CML belongs to the future Pediatric Oncology card.

09 Landmark trials

Figure 20. How to read a survival curve (illustrative). Use the absolute gap at a fixed time and overall survival, not the median or PFS alone, when weighing benefit against toxicity and cost.

Figure 21. Landmark results (UpToDate chronic phase and after-failure reviews: O'Brien 2003, Cortes 2026, Hochhaus 2023, Nicolini 2017, Saussele 2018, Marin 2010; DASCERN as reported in ELN 2025).

IRIS (1106 patients): imatinib vs interferon + cytarabine; 18-month PFS 97% vs 92%; 10-year OS 84% (O'Brien 2003^[12]).
ENESTnd (846): nilotinib vs imatinib; 33 progressions on imatinib vs 12 and 9 on the two nilotinib arms; more cardiovascular events on nilotinib (Hochhaus 2016^[15]).
ASC4FIRST (405): asciminib vs investigator-chosen TKI; MMR at 96 weeks 74.1% vs 52.0%; fewer grade ≥3 events and discontinuations (Cortes 2026^[16]).
ASCEMBL: after ≥2 TKIs, asciminib vs bosutinib; MMR 37.6% vs 15.8% at 96 weeks (Hochhaus 2023^[28]).
PACE and OPTIC: ponatinib works after 2G TKI failure and for T315I; response-based dose reduction lowers arterial risk (PACE^[31]; OPTIC^[32]).
EURO-SKI, LAST, DESTINY: stopping is safe with monitoring; about half stay off treatment (EURO-SKI^[34]; LAST^[35]; DESTINY^[38]).
India: Tata Memorial (972 patients, median age 36): OS 86% at a median follow-up of 51 months, equal responses on generic and innovator imatinib (Parikh 2013^[52]).

Figure 22. Indian data (Bansal 2013 and the 2016 South Asian J Cancer summary of the IJMPO 2013 centre reports; Parikh 2013; Ganesan 2011 and 2016; ELN 2025). Hospital series, different eras: not comparable with population registries.

10 Practice pearls & pitfalls

"Resistance" is often missed tablets. Ask at every visit, kindly and specifically, before ordering a mutation test.
Measure the spleen before hydroxyurea. ELTS needs untreated values.
One laboratory, one scale. Trends mean nothing if the laboratory or method changes.
Know the transcript. p230 and rare transcripts are invisible to routine PCR: monitor with FISH or a personalised assay.
Never switch on one result. Trend, adherence, interactions and the patient's goals come first.
After a 2G TKI fails, go to ponatinib or asciminib (or transplant), not to another 2G TKI.
Lymphoblasts in a "chronic phase" patient mean lymphoid blast phase until proved otherwise: flow cytometry and a lumbar puncture.
Unexplained falling platelets on treatment can mean progression: marrow and karyotype.
Check every new prescription: azoles, macrolides, PPIs and QT-prolonging drugs interact with dasatinib and nilotinib.
Talk about pregnancy at diagnosis with every woman of child-bearing age; men can continue their TKI.
Loss of MMR after stopping: restart. No mutation test is needed.
Generic imatinib is a legitimate first choice: same long-term survival as newer TKIs at a fraction of the cost.

11 Case vignettes: lines of management

Nine cases from the clinic.

Case 1Chronic phase · low ELTS · generic imatinib

A routine count before a hernia operation

34 years, manWBC 86,000/µLSpleen 4 cm

A 34-year-old shop owner from Nellore has a blood count before a hernia repair: WBC 86,000/µL with myelocytes, metamyelocytes and 6% basophils, 1% blasts; haemoglobin 12.1 g/dL; platelets 410,000/µL. He feels well; the spleen is 4 cm below the costal margin.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Confirm and stage
Blood qualitative PCR: e14a2 (p210); baseline quantitative PCR on the International Scale. Marrow: chronic phase, 2% blasts; karyotype 46,XY,t(9;22) in 20 of 20 metaphases, no extra chromosomes.
Risk and baseline
ELTS low. ECG, BP, lipids and HbA1c normal; hepatitis B negative; no interacting medicines. Surgery can wait until counts are controlled.
Choose
Lower risk: imatinib, a 2G TKI or asciminib are all acceptable. He pays himself: generic imatinib with food, and a written plan for missed doses.
Follow
CBC every 2 weeks to complete haematological response; BCR::ABL1 4% at 3 months, 0.6% at 6 and 0.07% at 12: favourable each time. PCR every 3–6 months; discuss stopping once criteria are met.

Teaching points

Measure the spleen before any hydroxyurea: ELTS needs untreated values.
Any first-line TKI gives the same long-term survival; generic imatinib costs least.
Record the transcript type: monitoring depends on it.

See: Sections 03 and 06, Algorithms 1–3.

Case 2High ELTS · diabetes · TKI choice

A big spleen and high sugars

56 years, womanSpleen 14 cmHbA1c 8.4%

A 56-year-old teacher from Ongole has had abdominal fullness and weight loss for 3 months. WBC 214,000/µL, 3% blasts, 8% basophils, platelets 780,000/µL; spleen 14 cm. She has diabetes (HbA1c 8.4%) and hypertension.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Stage
Marrow: chronic phase (blasts <10%, basophils <20%, no extra chromosomes); transcript e13a2. ELTS high.
First TKI
High risk favours a 2G TKI or asciminib. Diabetes and hypertension argue against nilotinib; with no lung disease, dasatinib is reasonable, bosutinib an alternative.
Before starting
Hydroxyurea for a few days after samples and spleen measurement; ECG; correct potassium and magnesium; ECG again 1–2 weeks after starting dasatinib.
Look after the vessels
Glucose and blood pressure to target with her physician; lipids every 6–12 months; ask about chest pain and claudication at every visit.

Teaching points

High ELTS: fewer early progressions with a 2G TKI or asciminib, same overall survival.
Comorbidity chooses among the 2G TKIs.
Cardiovascular risk factors matter whatever the TKI.

See: Section 06 (first TKI, side effects), Algorithm 2.

Case 3Warning at 3 months · adherence

The tablets ran out

29 years, manBCR::ABL1 18% at 3 monthsGeneric imatinib

A 29-year-old construction worker from Gudur started generic imatinib for chronic phase CML (ELTS low). At 3 months BCR::ABL1 is 18% (IS). He admits stopping for 3 weeks while working in another town, where he could not refill his prescription.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Classify
BCR::ABL1 >10% at 3 months = warning (ELN 2025); unfavourable only if confirmed within 1–3 months.
Find the cause
Missed doses explain it. Ask about side effects, cost, travel, alcohol, other medicines and herbs; involve his family; enrol him in an assistance programme with a pharmacy near his work.
Repeat
PCR in the same laboratory after 4–6 weeks of regular tablets: 6%. At 6 months 0.8%: favourable.
If it had not fallen
Marrow karyotype, kinase-domain mutation test and a switch to a 2G TKI or asciminib by the result.

Teaching points

Check adherence before declaring resistance.
One result never decides a switch: follow the trend.
Up to one-third of Indian patients miss doses, and it worsens outcome.

See: Section 06 (monitoring), section 08, Algorithm 3.

Case 4Resistance · T315I

A rising PCR after two good years

44 years, manBCR::ABL1 0.9% → 2.4%Imatinib, then dasatinib

A 44-year-old auto-rickshaw driver from Kavali reached MMR on imatinib and lost it after 3 years; no mutation was found and he switched to dasatinib. Over 6 months his BCR::ABL1 has risen from 0.9% to 2.4% despite regular tablets.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Confirm and test
Repeat PCR confirms the rise. Marrow: chronic phase, no new extra chromosomes. NGS: T315I.
Choose
T315I resists imatinib, dasatinib, nilotinib and bosutinib: ponatinib or asciminib (asciminib at a higher dose than usual). No vascular disease, so either is reasonable.
Access
Availability and cost may be the barrier in India: involve the pharmacy and assistance programmes early, and record a fallback plan.
Prepare transplant
HLA-type him and his siblings now; if milestones are missed on ponatinib or asciminib, proceed to allogeneic HCT.

Teaching points

After a 2G TKI fails, another 2G TKI rarely works.
Begin the donor search at resistance to the first 2G TKI.
For T315I, ponatinib gave better 48-month survival than transplant in a registry comparison (73% vs 56%).

See: Section 06 (resistance and mutation figure), Algorithm 4.

Case 5Dasatinib · pleural effusion

Breathless on dasatinib

61 years, womanMMR on dasatinibRight effusion

A 61-year-old woman from Nellore, in MMR after 2 years of dasatinib, has had breathlessness and a dry cough for 3 weeks. Chest X-ray: a moderate right pleural effusion. No fever; echocardiography is normal.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Exclude other causes
Infection, heart failure, kidney disease, progression: counts normal, still in MMR.
Treat
Interrupt dasatinib; drain because she is breathless. Restart at a reduced dose once it settles; she stays in MMR.
If it recurs
Recurrent effusion despite dose reduction → switch (imatinib, nilotinib, bosutinib or asciminib, chosen by comorbidity).
Watch for PAH
Breathlessness without effusion on dasatinib → echocardiography for pulmonary arterial hypertension; if confirmed, stop dasatinib permanently.

Teaching points

Up to one-third develop effusions on dasatinib; lower doses reduce the risk.
In responders, reduce the dose before switching.
Pulmonary arterial hypertension means stopping dasatinib for good.

See: Section 06 (side effects), Table D.

Case 6Treatment-free remission

Can I stop the tablets?

48 years, manMR4.5 for 4 yearsImatinib for 7 years

A 48-year-old bank officer from Nellore has taken imatinib for 7 years; BCR::ABL1 has been undetectable at MR4.5 sensitivity in the same IS laboratory for 4 years. He asks to stop.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Eligible?
First chronic phase, e14a2, no resistance, more than 5 years of TKI, MR4.5 for more than 2 years: meets the ELN 2025 optimal criteria; results come back within 2 weeks.
Counsel
About half stay off treatment; most relapses come in the first 6–8 months; restarting works in 90–95%; aches in 20–30%.
Monitor
PCR every 6–8 weeks for 6 months, every 2 months to 12 months, then every 3–6 months for life.
Outcome
At 5 months BCR::ABL1 0.15% (MMR lost): imatinib restarted; MR4 again by 4 months. A second attempt later is possible but less likely to succeed.

Teaching points

Loss of MMR, not of MR4, triggers restarting.
No mutation test is needed after loss of MMR in TFR.
Aches after stopping are a withdrawal syndrome, not relapse.

See: Section 06 (treatment-free remission), Algorithm 5.

Case 7Pregnancy

Diagnosed at 10 weeks of pregnancy

25 years, woman10 weeks pregnantWBC 64,000/µL

A 25-year-old woman from Kavali, 10 weeks into her first pregnancy, has WBC 64,000/µL with myelocytes and basophils, platelets 520,000/µL and a spleen 3 cm below the costal margin. BCR::ABL1 is positive (e13a2). She feels well.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Stage and risk
Marrow: chronic phase, no extra chromosomes; ELTS low.
Plan
WBC <100,000/µL, low ELTS, no extra chromosomes: watchful waiting with counts and obstetric scans; no TKI in the first trimester.
If counts rise
Interferon (usable throughout pregnancy) and/or leukapheresis; aspirin and/or LMW heparin if platelets climb. After week 16 imatinib (or nilotinib) can be started if needed; never dasatinib.
After delivery
Start a TKI after delivery; discuss breastfeeding versus starting treatment, since TKIs pass into breast milk.

Teaching points

76% of women diagnosed in pregnancy had a normal childbirth in the ELN registry.
Organogenesis runs to about week 16: no TKI before then.
No TKI while breastfeeding.

See: Section 06 (pregnancy and fertility), Algorithm 5.

Case 8Lymphoid blast phase

Bone pain and lymphoblasts on imatinib

22 years, manBlasts 46%TdT+, CD19+

A 22-year-old student from Gudur, on imatinib for 2 years with irregular follow-up, presents with bone pain and fever. WBC 58,000/µL with 46% blasts; platelets 31,000/µL.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Diagnose
Flow cytometry: TdT+, CD19+, CD10+ blasts = lymphoid blast phase; BCR::ABL1 also in mature granulocytes (CML, not de novo Ph+ ALL). Karyotype: extra Ph, i(17q). NGS: no T315I.
Stabilise
Tumour lysis precautions, transfusion and infection care as for acute leukaemia (AML module, emergencies).
Induce
A TKI chosen by prior TKI and mutation (not imatinib) plus a Ph+ ALL-type induction; lumbar puncture with CNS-directed therapy.
Consolidate
HLA typing at diagnosis; allogeneic HCT in remission (median OS 93 vs 9 months with vs without transplant in one series); TKI restarted after engraftment.

Teaching points

One-third of blast crises are lymphoid; they have more treatment options than myeloid ones.
Choose the TKI by prior TKIs and mutation, not by lineage.
Treat as Ph+ ALL: see the ALL module.

See: Section 06 (accelerated and blast phase), Algorithm 6, ALL module (Ph+ ALL).

Case 9Child · contrast

A 12-year-old who stopped growing

12 years, boyImatinib 2 yearsHeight falling

A 12-year-old boy from Ongole with chronic phase CML (WBC 310,000/µL and a 15 cm spleen at diagnosis) is in MMR after 2 years of imatinib, but his height has fallen from the 50th to the 15th centile.

Before you open the answer: what is the likely diagnosis, what must be done before treatment, and what is the plan?

Show the line of management

Recognise
Growth slowing on imatinib is common before and during puberty (German cohort: median height fell 0.76 SD by 24 months).
Assess
Paediatric endocrinology: growth velocity, puberty staging, thyroid function, bone health.
Decide with a paediatric CML centre
TKI choice per the 2025 international paediatric recommendations; transplant is not first line.
Long view
Stopping can be considered after a sustained deep response but succeeds less often than in adults; growth improved in some children during TKI breaks.

Teaching points

Children present with bulkier disease than adults.
Height, puberty, thyroid and bone must be followed in every child on a TKI.
Childhood CML is shown here only as a contrast.

See: Section 08 (contrast figure).

12 References & guidelines

European LeukemiaNet 2025 recommendations for CML; NCCN Guidelines: Chronic Myeloid Leukemia (current version); International Consensus Classification and WHO 5th edition (2022); international pediatric CML expert panel recommendations (chronic phase 2025, blast phase 2023).
Cross-checked in October 2026 against 6 UpToDate topic reviews: chronic myeloid leukemia: pathogenesis, clinical manifestations, and diagnosis; overview of the treatment of chronic myeloid leukemia; chronic myeloid leukemia in chronic phase: initial treatment; treatment of chronic phase chronic myeloid leukemia after failure of the initial tyrosine kinase inhibitor; accelerated phase chronic myeloid leukemia: diagnosis and treatment; and chronic myeloid leukemia-blast phase: diagnosis and treatment. Trial citations come from the reference lists of these reviews, except the ELN 2025 recommendations (full text read), the pregnancy and paediatric papers and the Indian papers found and verified by web search on 17 October 2026, and the Indian series cited from the reference list of Ganesan and Kumar (2016).
Reviewed and approved by Dr. Haritha Chiramana, 18 October 2026.

Core trials and papers cited on this page (72)

Journal, year, volume and first page (or DOI); each links to PubMed.

Numbered in order of first citation in the text

Indian CML data, 22 centres (Bansal 2013): Bansal S, Prabhash K, Parikh P. Chronic myeloid leukemia data from India. Indian J Med Paediatr Oncol 34:154. 2013. doi:10.4103/0971-5851.123711. PubMed India
ELN 2025 CML (Apperley 2025): Apperley JF, Milojkovic D, Cross NCP, et al. 2025 European LeukemiaNet recommendations for the management of chronic myeloid leukemia. Leukemia 2025;39:1797. PubMed Guidelines and classification
CML in India: review (Ganesan 2016): Ganesan P, Kumar L. Chronic myeloid leukemia in India. J Glob Oncol 3:64 (Cancer Institute, Chennai, and AIIMS, New Delhi). 2016. doi:10.1200/JGO.2015.002667. PubMed India
ICC 2022 (Arber 2022): Arber DA, Orazi A, Hasserjian RP, et al. International Consensus Classification of myeloid neoplasms and acute leukemias. Blood 2022;140:1200. PubMed Guidelines and classification
WHO 5th edition, myeloid (Khoury 2022): Khoury JD, Solary E, Abla O, et al. The 5th edition of the WHO classification of haematolymphoid tumours: myeloid and histiocytic/dendritic neoplasms. Leukemia 2022;36:1703. PubMed Guidelines and classification
ELTS score (Pfirrmann 2016): Pfirrmann M, Baccarani M, Saussele S, et al. Prognosis of long-term survival considering disease-specific death in patients with CML. Leukemia 2016;30:48. PubMed Diagnosis, risk and prognosis
ELTS vs Sokal (Pfirrmann 2020): Pfirrmann M, Clark RE, Prejzner W, et al. The EUTOS long-term survival (ELTS) score is superior to the Sokal score for predicting survival in CML. Leukemia 2020;34:2138. PubMed Diagnosis, risk and prognosis
Comorbidity and survival, CML Study IV (Saussele 2015): Saussele S, Krauss MP, Hehlmann R, et al. Impact of comorbidities on overall survival in patients with CML. Blood 2015;126:42. PubMed Diagnosis, risk and prognosis
ACA at diagnosis, CML Study IV (Fabarius 2011): Fabarius A, Leitner A, Hochhaus A, et al. Impact of additional cytogenetic aberrations at diagnosis on prognosis of CML (CML Study IV). Blood 2011;118:6760. PubMed Diagnosis, risk and prognosis
ACA risk groups (Wang 2016): Wang W, Cortes JE, Tang G, et al. Risk stratification of chromosomal abnormalities in CML in the era of TKI therapy. Blood 2016;127:2742. PubMed Diagnosis, risk and prognosis
Molecular response definitions (Cross 2012): Cross NC, White HE, Müller MC, et al. Standardized definitions of molecular response in chronic myeloid leukemia. Leukemia 2012;26:2172. PubMed Guidelines and classification
IRIS (O'Brien 2003): O'Brien SG, Guilhot F, Larson RA, et al. Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase CML. N Engl J Med 2003;348:994. PubMed First-line treatment, monitoring and toxicity
IRIS long-term (Hochhaus 2017): Hochhaus A, Larson RA, Guilhot F, et al. Long-term outcomes of imatinib treatment for CML. N Engl J Med 2017;376:917. PubMed First-line treatment, monitoring and toxicity
Life expectancy with CML (Bower 2016): Bower H, Björkholm M, Dickman PW, et al. Life expectancy of patients with CML approaches the life expectancy of the general population. J Clin Oncol 2016;34:2851. PubMed Diagnosis, risk and prognosis
ENESTnd 5-year (Hochhaus 2016): Hochhaus A, Saglio G, Hughes TP, et al. Long-term benefits and risks of frontline nilotinib vs imatinib for CML in chronic phase: 5-year update of ENESTnd. Leukemia 2016;30:1044. PubMed First-line treatment, monitoring and toxicity
ASC4FIRST (Cortes 2026): Cortes JE, Hughes TP, Wang J, et al. Asciminib demonstrates superior efficacy and safety in newly diagnosed CML in the ASC4FIRST trial. Blood 2026;147:1433. PubMed First-line treatment, monitoring and toxicity
First-line TKI meta-analysis (Yun 2016): Yun S, Vincelette ND, Segar JM, et al. Comparative effectiveness of newer TKIs versus imatinib in first-line treatment of chronic-phase CML: meta-analysis of eight randomized trials. Clin Lymphoma Myeloma Leuk 2016;16:e85. PubMed First-line treatment, monitoring and toxicity
JALSG CML212 (Matsumura 2024): Matsumura I, Ohtake S, Atsuta Y, et al. Nilotinib vs dasatinib in achieving MR4.5 for de novo CML: the randomized JALSG CML212 study. Blood Adv 2024;8:5237. PubMed First-line treatment, monitoring and toxicity
Hydroxyurea before a TKI (Kockerols 2022): Kockerols CCB, Geelen I, Levin MD, et al. The use of hydroxyurea pretreatment in CML in the current TKI era. Haematologica 2022;107:1940. PubMed First-line treatment, monitoring and toxicity
DESTINY dose halving (Clark 2017): Clark RE, Polydoros F, Apperley JF, et al. De-escalation of TKI dose in CML with stable major molecular response (DESTINY): interim analysis. Lancet Haematol 2017;4:e310. PubMed First-line treatment, monitoring and toxicity
Cardiovascular events on frontline TKIs (Jain 2019): Jain P, Kantarjian H, Boddu PC, et al. Analysis of cardiovascular and arteriothrombotic adverse events in chronic-phase CML patients after frontline TKIs. Blood Adv 2019;3:851. PubMed First-line treatment, monitoring and toxicity
Survival after missed milestones (Lauseker 2023): Lauseker M, Hehlmann R, Hochhaus A, Saußele S. Survival with chronic myeloid leukaemia after failing milestones. Leukemia 2023;37:2231. PubMed First-line treatment, monitoring and toxicity
Dasatinib second line, 7 years (Shah 2016): Shah NP, Rousselot P, Schiffer C, et al. Dasatinib in imatinib-resistant or -intolerant chronic-phase CML: 7-year follow-up of study CA180-034. Am J Hematol 2016;91:869. PubMed Resistance and later lines
Nilotinib second line, 48 months (Giles 2013): Giles FJ, le Coutre PD, Pinilla-Ibarz J, et al. Nilotinib in imatinib-resistant or imatinib-intolerant patients with CML in chronic phase: 48-month follow-up. Leukemia 2013;27:107. PubMed Resistance and later lines
Bosutinib second line (Gambacorti-Passerini 2014): Gambacorti-Passerini C, Brümmendorf TH, Kim DW, et al. Bosutinib efficacy and safety in chronic phase CML after imatinib resistance or intolerance. Am J Hematol 2014;89:732. PubMed Resistance and later lines
START-R (Kantarjian 2009): Kantarjian H, Pasquini R, Lévy V, et al. Dasatinib or high-dose imatinib for chronic-phase CML resistant to imatinib: two-year follow-up of a randomized phase 2 study (START-R). Cancer 2009;115:4136. PubMed Resistance and later lines
ASCEMBL (Réa 2021): Réa D, Mauro MJ, Boquimpani C, et al. A phase 3 randomized study of asciminib vs bosutinib in CML after 2 or more prior TKIs. Blood 2021;138:2031. PubMed Resistance and later lines
ASCEMBL 96 weeks (Hochhaus 2023): Hochhaus A, Réa D, Boquimpani C, et al. Asciminib vs bosutinib in chronic-phase CML previously treated with at least two TKIs: longer-term follow-up of ASCEMBL. Leukemia 2023;37:617. PubMed Resistance and later lines
Ponatinib vs transplant for T315I (Nicolini 2017): Nicolini FE, Basak GW, Kim DW, et al. Overall survival with ponatinib versus allogeneic stem cell transplantation in Ph+ leukemias with the T315I mutation. Cancer 2017;123:2875. PubMed Resistance and later lines
PACE (Cortes 2013): Cortes JE, Kim DW, Pinilla-Ibarz J, et al. A phase 2 trial of ponatinib in Philadelphia chromosome-positive leukemias. N Engl J Med 2013;369:1783. PubMed Resistance and later lines
PACE 5-year (Cortes 2018): Cortes JE, Kim DW, Pinilla-Ibarz J, et al. Ponatinib efficacy and safety in Ph+ leukemia: final 5-year results of the phase 2 PACE trial. Blood 2018;132:393. PubMed Resistance and later lines
OPTIC (Cortes 2021): Cortes J, Apperley J, Lomaia E, et al. Ponatinib dose-ranging study in chronic-phase CML: a randomized, open-label phase 2 clinical trial. Blood 2021;138:2042. PubMed Resistance and later lines
Asciminib phase 1 (Hughes 2019): Hughes TP, Mauro MJ, Cortes JE, et al. Asciminib in chronic myeloid leukemia after ABL kinase inhibitor failure. N Engl J Med 2019;381:2315. PubMed Resistance and later lines
EURO-SKI (Saussele 2018): Saussele S, Richter J, Guilhot J, et al. Discontinuation of TKI therapy in CML (EURO-SKI): a prespecified interim analysis. Lancet Oncol 2018;19:747. PubMed Treatment-free remission
LAST (Atallah 2021): Atallah E, Schiffer CA, Radich JP, et al. Assessment of outcomes after stopping TKIs among patients with CML: a nonrandomized clinical trial. JAMA Oncol 2021;7:42. PubMed Treatment-free remission
ENESTfreedom 5-year (Radich 2021): Radich JP, Hochhaus A, Masszi T, et al. Treatment-free remission following frontline nilotinib in chronic phase CML: 5-year update of ENESTfreedom. Leukemia 2021;35:1344. PubMed Treatment-free remission
DASFREE 5-year (Shah 2023): Shah NP, García-Gutiérrez V, Jiménez-Velasco A, et al. Treatment-free remission after dasatinib in chronic phase CML with deep molecular response: final 5-year analysis of DASFREE. Br J Haematol 2023;202:942. PubMed Treatment-free remission
DESTINY (Clark 2019): Clark RE, Polydoros F, Apperley JF, et al. De-escalation of TKI therapy before complete treatment discontinuation in CML (DESTINY): a phase 2 trial. Lancet Haematol 2019;6:e375. PubMed Treatment-free remission
Late recurrence after stopping (Rousselot 2020): Rousselot P, Loiseau C, Delord M, et al. Late molecular recurrences in patients with CML experiencing treatment-free remission. Blood Adv 2020;4:3034. PubMed Treatment-free remission
Imatinib exposure in pregnancy (Pye 2008): Pye SM, Cortes J, Ault P, et al. The effects of imatinib on pregnancy outcome. Blood 2008;111:5505. PubMed Pregnancy and fertility
Dasatinib exposure in pregnancy (Cortes 2015): Cortes JE, Abruzzese E, Chelysheva E, et al. The impact of dasatinib on pregnancy outcomes. Am J Hematol 2015;90:1111. PubMed Pregnancy and fertility
CML diagnosed in pregnancy, ELN registry (Chelysheva 2024): Chelysheva E, Apperley J, Turkina A, et al. CML diagnosed in pregnancy: management and outcome of 87 patients reported to the ELN international registry. Leukemia 2024;38:788. PubMed Pregnancy and fertility
Pregnancy in CML, Japan (Kondo 2025): Kondo T, et al. Outcomes of pregnancy in patients with chronic myeloid leukemia in the era of tyrosine kinase inhibitors. Cancer 131:e35611. 2025. doi:10.1002/cncr.35611. PubMed Pregnancy and fertility
TKI in de novo accelerated phase (Ohanian 2014): Ohanian M, Kantarjian HM, Quintas-Cardama A, et al. TKIs as initial therapy for CML in accelerated phase. Clin Lymphoma Myeloma Leuk 2014;14:155. PubMed Accelerated phase, blast phase and transplant
Dasatinib in accelerated phase (Kantarjian 2009): Kantarjian H, Cortes J, Kim DW, et al. Phase 3 study of dasatinib 140 mg once daily versus 70 mg twice daily in accelerated-phase CML resistant or intolerant to imatinib. Blood 2009;113:6322. PubMed Accelerated phase, blast phase and transplant
Myeloid blast phase: frontline approach (Saxena 2021): Saxena K, Jabbour E, Issa G, et al. Impact of frontline treatment approach on outcomes of myeloid blast phase CML. J Hematol Oncol 2021;14:94. PubMed Accelerated phase, blast phase and transplant
MATCHPOINT (Copland 2022): Copland M, Slade D, McIlroy G, et al. Ponatinib with FLAG-IDA for blast-phase CML (MATCHPOINT): a phase 1/2 trial. Lancet Haematol 2022;9:e121. PubMed Accelerated phase, blast phase and transplant
Dasatinib in blast phase (Saglio 2010): Saglio G, Hochhaus A, Goh YT, et al. Dasatinib in imatinib-resistant or -intolerant CML in blast phase after 2 years of follow-up in a phase 3 study. Cancer 2010;116:3852. PubMed Accelerated phase, blast phase and transplant
Hyper-CVAD + TKI in lymphoid blast phase (Strati 2014): Strati P, Kantarjian H, Thomas D, et al. HCVAD plus imatinib or dasatinib in lymphoid blastic phase CML. Cancer 2014;120:373. PubMed Accelerated phase, blast phase and transplant
RIC transplant in advanced CML (Kebriaei 2007): Kebriaei P, Detry MA, Giralt S, et al. Long-term follow-up of allogeneic HCT with reduced-intensity conditioning for CML. Blood 2007;110:3456. PubMed Accelerated phase, blast phase and transplant
Transplant in the TKI era, Sweden (Lübking 2019): Lübking A, Dreimane A, Sandin F, et al. Allogeneic stem cell transplantation for CML in the TKI era: population-based data from the Swedish CML registry. Bone Marrow Transplant 2019;54:1764. PubMed Accelerated phase, blast phase and transplant
Tata Memorial chronic phase series (Parikh 2013): Parikh P. Report of CML in chronic phase from Tata Memorial Hospital, Mumbai, 2002–2008. Indian J Med Paediatr Oncol 34:164. 2013. doi:10.4103/0971-5851.123716. PubMed India
International Scale reporting in India (Balasubramanian 2012): Balasubramanian P, Chendamarai E, Markose P, et al. International reporting scale of BCR-ABL1 fusion transcript in CML: first report from India. Acta Haematol 2012;127:135. PubMed India
Adherence and molecular response (Marin 2010): Marin D, Bazeos A, Mahon FX, et al. Adherence is the critical factor for achieving molecular responses in CML patients with complete cytogenetic responses on imatinib. J Clin Oncol 2010;28:2381. PubMed First-line treatment, monitoring and toxicity
Non-adherence to imatinib, Chennai (Ganesan 2011): Ganesan P, Sagar TG, Dubashi B, et al. Nonadherence to imatinib adversely affects event free survival in chronic phase CML. Am J Hematol 2011;86:471. PubMed India
Paediatric CML chronic phase recommendations (Millot 2025): Millot F, Ampatzidou M, Moulik NR, et al. Management of children and adolescents with CML in chronic phase: international pediatric CML expert panel recommendations. Leukemia 2025;39:779. PubMed Children (contrast only)

Further reading (not cited in the text above)

ELN 2020 CML (Hochhaus 2020): Hochhaus A, Baccarani M, Silver RT, et al. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia. Leukemia 2020;34:966. PubMed Guidelines and classification
Presenting features of 430 patients (Savage 1997): Savage DG, Szydlo RM, Goldman JM. Clinical features at diagnosis in 430 patients with chronic myeloid leukaemia. Br J Haematol 1997;96:111. PubMed Diagnosis, risk and prognosis
Sokal score (Sokal 1984): Sokal JE, Cox EB, Baccarani M, et al. Prognostic discrimination in "good-risk" chronic granulocytic leukemia. Blood 1984;63:789. PubMed Diagnosis, risk and prognosis
Paediatric CML blast phase recommendations (Sembill 2023): Sembill S, Ampatzidou M, Chaudhury S, et al. Management of children and adolescents with CML in blast phase: international pediatric CML expert panel recommendations. Leukemia 2023;37:505. PubMed Children (contrast only)
International Registry of Childhood CML (Millot 2026): Millot F, de Keizer J, Metzler M, et al. Children with chronic-phase CML: characteristics and outcomes from the International Registry of Childhood CML. Haematologica 2026;111:1280. PubMed Children (contrast only)
COG CML Working Group recommendations (2019): Management of CML in children and adolescents: recommendations from the Children's Oncology Group CML Working Group. Pediatr Blood Cancer 66:e27827. Pediatr Blood Cancer 2019;66:e27827. PubMed Children (contrast only)
Imatinib and growth, CML-PAED II (Stiehler 2024): Stiehler S, Sembill S, Schleicher O, et al. Imatinib treatment and longitudinal growth in pediatric patients with CML (German CML-PAED cohort). Haematologica 2024;109:2555. PubMed Children (contrast only)
Imatinib in children, French phase IV (Millot 2011): Millot F, Baruchel A, Guilhot J, et al. Imatinib is effective in children with previously untreated CML in early chronic phase. J Clin Oncol 2011;29:2827. PubMed Children (contrast only)
STOP IMAPED (de Bruijn): de Bruijn CMA, Millot F, Suttorp M, et al. Discontinuation of imatinib in children with CML in sustained deep molecular remission: results of the STOP IMAPED study (Br J Haematol). PubMed Children (contrast only)
TKI discontinuation in children, Japan (Shima 2022): Shima H, Kada A, Tanizawa A, et al. Discontinuation of TKIs in pediatric CML. Pediatr Blood Cancer 2022;69:e29699. PubMed Children (contrast only)
Growth and adult height, JPLSG CML-08 (Shima 2024): Shima H, et al. Growth retardation and adult height in pediatric patients with chronic-phase CML treated with TKIs (Leukemia; ASH 2024 abstract 4537). 2024. PubMed Children (contrast only)
Summary of Indian CML data (South Asian J Cancer 2016): Summary of the published Indian data on chronic myeloid leukemia. South Asian J Cancer 5:162. 2016. doi:10.4103/2278-330X.187593. PubMed India
Imatinib in AP/BP, Hyderabad (Thota 2014): Thota NK, Gundeti S, Linga VG, et al. Imatinib mesylate as first-line therapy in CML in accelerated phase and blast phase: a retrospective analysis. Indian J Cancer 2014;51:5. PubMed India
Imatinib and growth in Indian children (Bansal 2012): Bansal D, Shava U, Varma N, et al. Imatinib has adverse effect on growth in children with CML. Pediatr Blood Cancer 2012;59:481. PubMed India
Paediatric CML at AIIMS (Ganguly 2020): Ganguly S, Pushpam D, Mian A, et al. Real-world experience of imatinib in pediatric chronic phase CML: a single-center experience from India. Clin Lymphoma Myeloma Leuk 2020;20:e437. PubMed India
Paediatric CML in Chennai (Kesana 2021): Kesana S, et al. Real-world experience of treating pediatric CML: retrospective study from a cancer center in southern India. Indian J Med Paediatr Oncol 42:561. 2021. doi:10.1055/s-0041-1740951. PubMed India

How to cite this page

VancouverChiramana H. Chronic Myeloid Leukaemia: a mini review for clinicians. Oncology Knowledge Hub [Internet]. Nellore (India): drharitha.co.in; 2026 [updated 2026 Oct 17; cited year month day]. Available from: https://drharitha.co.in/professionals/chronic-myeloid-leukaemia

APA 7Chiramana, H. (2026, October 17). Chronic Myeloid Leukaemia: A mini review for clinicians. Oncology Knowledge Hub. Retrieved Month Day, Year, from https://drharitha.co.in/professionals/chronic-myeloid-leukaemia

Free to use and share for education with attribution; please do not alter or use commercially (CC BY-NC-ND 4.0). Replace the italic parts with the date you accessed the page.

Educational summary for health professionals, written in our own words from current guidelines and primary trials. No drug doses are given. Hodgkin, aggressive B-cell, indolent B-cell, T-cell and cutaneous lymphomas are parts 1–5, multiple myeloma is part 6, acute myeloid leukaemia part 7 and acute lymphoblastic leukaemia part 8; CLL is covered in the indolent B-cell module; other myeloproliferative neoplasms appear here only as differentials, and childhood CML only as a contrast. Verify current guidelines, Indian regulatory approvals and individual patient factors before treatment decisions.

Written by Dr. Haritha ChiramanaSenior Medical Oncologist & Hemato-Oncologist · MD, DM (Medical Oncology) · C.R. Reddy Cancer Center, Nellore, Andhra Pradesh, India

Medically reviewed by Dr. Haritha Chiramana on 18 October 2026. This page is general education and cannot replace an individual consultation.