Myelogenous Leukemia (CML and AML): Symptoms, Diagnosis and Treatment — Overview, Diagnosis & Treatment Options | MyMedicPlus

Myelogenous leukemia encompasses two major malignancies of the myeloid cell lineage. Chronic myeloid leukemia (CML) is a clonal stem cell disorder defined by the Philadelphia chromosome — the t(9;22) reciprocal translocation that produces the BCR-ABL1 fusion oncogene — and is characterized by a chronic phase with granulocytic proliferation, progressing through an accelerated phase to blast crisis if untreated. CML accounts for approximately 15% of all leukemias, with an annual incidence of 1–2 per 100,000. The discovery of imatinib (Gleevec) — the first BCR-ABL1 tyrosine kinase inhibitor (TKI) — transformed CML from a uniformly fatal disease into a chronic, manageable condition with near-normal life expectancy for most patients. Acute myeloid leukemia (AML) is a rapidly progressive clonal proliferation of immature myeloid progenitors (blasts) in the bone marrow and blood, defined by ≥20% blasts in the marrow. AML accounts for 80% of adult acute leukemia, with an annual incidence of approximately 4 per 100,000, rising sharply after age 60. AML is molecularly heterogeneous, with prognostic significance of cytogenetics (ELN 2022 classification: favorable, intermediate, adverse) and somatic mutations (NPM1, FLT3, CEBPA, IDH1/2, TP53).

CML is caused by the t(9;22)(q34;q11.2) translocation — acquired somatically in a hematopoietic stem cell — producing the BCR-ABL1 fusion protein with constitutively active tyrosine kinase activity that drives uncontrolled myeloid proliferation and resistance to apoptosis. The etiology of the translocation is unknown in most cases; ionizing radiation exposure (survivors of atomic bomb detonations, prior radiotherapy) is the only established environmental risk factor for CML. AML etiology is more diverse: prior chemotherapy (alkylating agents, topoisomerase II inhibitors) causes therapy-related AML (t-AML) with typically poor prognosis; myelodysplastic syndrome (MDS) and other clonal hematopoietic disorders evolve to AML; inherited predispositions include Down syndrome (21-fold risk of AML under age 4), Fanconi's anemia, Diamond-Blackfan anemia, RUNX1, CEBPA, GATA2 germline mutations; benzene and pesticide exposure; and prior radiotherapy. Older age is the strongest non-modifiable risk factor for AML.

CML chronic phase: most patients (~40%) are asymptomatic at diagnosis, detected on routine blood count (massive leukocytosis with left shift, basophilia, thrombocytosis). Symptomatic patients report fatigue, left upper quadrant discomfort or fullness from massive splenomegaly (hallmark of CML), weight loss, and night sweats. Hyperuricaemia and gout from rapid cell turnover may occur. Blast crisis mimics acute leukemia with fever, bleeding, and pallor. AML presents acutely with cytopenias: anaemia (fatigue, dyspnoea, pallor), neutropenia (recurrent fever and infections, particularly gram-negative bacteremia, fungal infections), and thrombocytopenia (mucosal bleeding, petechiae, ecchymoses, gum bleeding — particularly prominent in acute promyelocytic leukemia, APL/AML-M3, which causes severe DIC). Leukostasis — in patients with very high blast counts (>100×10⁹/L) — causes CNS symptoms (confusion, blurred vision, headache), respiratory failure, and priapism; it is a medical emergency.

CML: Full blood count shows leukocytosis (typically 50–300×10⁹/L) with left shift (metamyelocytes, myelocytes, promyelocytes), basophilia (>2%), and thrombocytosis. Philadelphia chromosome is confirmed by conventional cytogenetics (karyotype), FISH (BCR-ABL1 fusion), or RT-PCR (quantitative BCR-ABL1/ABL1 ratio — used for monitoring treatment response). AML: peripheral blood film and bone marrow aspirate show ≥20% myeloblasts (or <20% in specific genetic subtypes: t(8;21), inv(16), t(15;17)). Immunophenotyping by flow cytometry defines the blast lineage. Cytogenetics (karyotype and FISH) and comprehensive molecular profiling (NPM1, FLT3-ITD/D835, CEBPA, IDH1/IDH2, TP53, RUNX1, ASXL1, SF3B1 by NGS) are essential for ELN 2022 risk stratification and treatment selection. Lumbar puncture is performed if CNS involvement is suspected. PML-RARA fusion FISH or RT-PCR diagnoses APL urgently — ATRA must be started immediately on suspicion.

CML treatment: First-line TKI therapy — imatinib 400 mg/day (generic available), nilotinib 300 mg BID, or dasatinib 100 mg/day — achieves major molecular response (BCR-ABL1/ABL1 <0.1% IS) in 85–90% of patients within 12–18 months. Second-generation TKIs (nilotinib, dasatinib) achieve faster and deeper responses than imatinib. Asciminib (STAMP inhibitor targeting ABL myristoyl pocket) is highly effective for TKI-resistant/intolerant CML. Treatment-free remission (TFR) — stopping TKI in patients achieving sustained deep molecular response (MR4.5, ≥2 years) — is achievable in 40–60% of patients who reach eligibility criteria. Allogeneic SCT is reserved for blast crisis or advanced accelerated phase. AML treatment: Induction chemotherapy: '7+3' regimen (cytarabine continuous infusion 7 days + anthracycline [idarubicin or daunorubicin] 3 days) achieves CR in 60–80% of younger patients. Age ≥75 or unfit patients receive hypomethylating agent (azacitidine) + venetoclax (BCL-2 inhibitor) — VIALE-A trial: CR rate 66% vs 28% with azacitidine alone. Targeted additions: midostaurin (FLT3 inhibitor) to 7+3 for FLT3-mutated AML (RATIFY trial); enasidenib/ivosidenib for IDH2/IDH1-mutated AML. Post-remission consolidation: allogeneic SCT for intermediate/adverse risk; high-dose cytarabine or daunorubicin/cytarabine for favorable risk (NPM1+ without FLT3-ITD, biallelic CEBPA). APL: ATRA + arsenic trioxide (ATO) — the dual differentiation therapy — is curative in >95% of patients with low/intermediate-risk APL without conventional chemotherapy.

CML prognosis has been transformed by TKI therapy. In chronic-phase CML treated with imatinib, 10-year overall survival exceeds 80–85%, approaching that of the age-matched general population — a remarkable achievement for a disease that was previously uniformly fatal within 3–5 years. Second-generation TKIs (nilotinib, dasatinib) achieve deeper and faster molecular responses — 5-year major molecular response rates of 77–87%. Treatment-free remission (TFR), achieved in 40–60% of patients reaching sustained deep molecular response (MR4.5 for ≥2 years), represents a functional cure for many patients. Blast crisis CML has poor prognosis: median survival is 6–12 months even with TKI plus chemotherapy. AML prognosis varies dramatically by cytogenetic and molecular risk. Favorable-risk AML (CBF leukemia t(8;21), inv(16), NPM1+ without FLT3-ITD, biallelic CEBPA) achieves 5-year OS of 60–70% with chemotherapy consolidation. Intermediate-risk AML achieves 40–60% 5-year OS with allogeneic SCT. Adverse-risk AML (TP53 mutation, complex karyotype, monosomal karyotype) has 5-year OS of 10–20% despite aggressive treatment. APL treated with ATRA+ATO achieves complete remission in >95% and 5-year OS approaching 90% — the most favorable AML subtype. Overall, 5-year OS for AML across all patients is approximately 30%. MRD negativity (NPM1 PCR or flow cytometry after induction) predicts durable remission and is the key monitoring endpoint.

CML: No modifiable preventive strategy exists for sporadic CML. Patients treated with curative intent (e.g., occupational radiation exposure) should minimize ionizing radiation exposure. BCR-ABL1 PCR monitoring every 3 months on TKI therapy guides treatment response assessment and early identification of resistance (per ELN 2020 response milestones). Patients achieving Treatment-Free Remission require monthly BCR-ABL1 PCR for the first year off therapy; reinstitution of TKI is recommended promptly on molecular relapse. AML: Avoid known AML risk factors (alkylating agent chemotherapy minimized where possible with alternative regimens for solid tumors; benzene/pesticide occupational exposure minimization; MDS surveillance in patients with clonal cytopenia). Therapy-related AML is diagnosed early with regular CBC monitoring in long-term cancer survivors receiving alkylating agents or topoisomerase inhibitors. Germline predisposition syndromes (RUNX1, GATA2) require regular haematological monitoring.

AML is a haematological emergency: any patient with rapidly progressive pallor, unexplained fever, new mucosal bleeding, petechiae, or severe fatigue requires a same-day full blood count and urgent haematology review. A peripheral blood film showing blasts requires immediate haematology admission — do not wait for bone marrow results before initiating supportive care and diagnosis. Febrile neutropenia in an AML patient on chemotherapy requires empirical broad-spectrum antibiotics (piperacillin-tazobactam or cefepime) within 1 hour of presentation. Suspected leukostasis (confusion, dyspnoea with blast count >100×10⁹/L) is an emergency requiring leukapheresis and immediate chemotherapy. For CML patients on TKI: report any new bone pain, fever, or accelerated splenomegaly — these may indicate transformation to accelerated phase or blast crisis. Loss of haematological or cytogenetic response on treatment requires urgent BCR-ABL1 mutation testing for TKI resistance mutations.