Leukemia — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Leukemia is a group of cancers arising from abnormal proliferation of blood-forming cells in the bone marrow, causing an accumulation of immature or dysfunctional white blood cells (leukocytes) that crowd out normal blood cell production. There are four main types: Acute Myeloid Leukemia (AML), Acute Lymphoblastic Leukemia (ALL — most common childhood cancer), Chronic Myeloid Leukemia (CML), and Chronic Lymphocytic Leukemia (CLL — most common adult leukemia in Western countries). Globally, leukemia causes approximately 476,000 new cases and 311,000 deaths per year. Survival has dramatically improved with targeted therapies — CML now has near-normal life expectancy with tyrosine kinase inhibitors such as imatinib. Advances in molecular biology have transformed leukaemia from a largely fatal diagnosis to a manageable or even curable disease for many subtypes, though prognosis varies widely based on genetic risk stratification, cytogenetics, and early treatment response assessment at specific time points.

Most leukemia cases have no identifiable single cause. Established risk factors include ionizing radiation exposure (atomic bomb survivors, radiotherapy), benzene and other chemical exposures, prior chemotherapy (alkylating agents, topoisomerase II inhibitors increase risk of therapy-related AML), genetic conditions (Down syndrome has 10-20x increased AML/ALL risk; Fanconi anaemia; Li-Fraumeni syndrome), and viral infections (HTLV-1 causes adult T-cell leukaemia-lymphoma; EBV is associated with some lymphoid leukemias). CML is caused by the Philadelphia chromosome — translocation t(9;22) producing the BCR-ABL1 fusion oncogene, which drives uncontrolled myeloid proliferation. Smoking increases AML risk by 40%. Family history of leukemia slightly elevates risk. Epigenetic alterations — including aberrant DNA methylation and histone modification patterns — are increasingly recognised as co-drivers of leukaemia development alongside chromosomal abnormalities, and represent important emerging therapeutic targets in precision oncology.

Acute leukemias (AML, ALL) present over days to weeks with: fatigue and pallor (anaemia from bone marrow failure), easy bruising and petechiae (thrombocytopenia), recurrent severe infections (neutropenia — bacterial, fungal), bone and joint pain (especially in ALL — from bone marrow expansion), lymphadenopathy, splenomegaly and hepatomegaly, and fever. Blast crisis with very high white cell counts can cause leukostasis — hypoxia, visual disturbance, and neurological symptoms. Chronic leukemias (CML, CLL) often present insidiously: fatigue, weight loss, night sweats, abdominal fullness from massive splenomegaly (CML), or as an incidental finding of lymphocytosis on a blood count (CLL). CLL may cause recurrent infections from antibody deficiency.

Full blood count (FBC) typically shows anaemia, thrombocytopenia, and abnormal white cell count — markedly elevated (leukocytosis) with blasts in acute leukemia, or markedly elevated lymphocyte count in CLL. Peripheral blood film identifies blast cells, Auer rods (AML), and smear cells (CLL). Bone marrow aspirate and trephine biopsy is essential for definitive diagnosis and classification: >20% blasts in bone marrow confirms acute leukemia. Immunophenotyping by flow cytometry classifies the cell lineage (myeloid vs. lymphoid; B-cell vs. T-cell). Cytogenetics (karyotype) and molecular testing (PCR, FISH, next-generation sequencing) identify specific mutations and translocations guiding treatment and prognosis: t(15;17) in APL (AML-M3); t(9;22) BCR-ABL1 in CML and Ph+ ALL; FLT3-ITD, NPM1, IDH1/2 mutations in AML. Lumbar puncture assesses CNS involvement in ALL.

AML: intensive induction chemotherapy (7+3 regimen — cytarabine infusion for 7 days + daunorubicin for 3 days) aiming for complete remission; consolidation with high-dose cytarabine or allogeneic haematopoietic stem cell transplantation (allo-HSCT) in high-risk disease. Gemtuzumab ozogamicin (anti-CD33 antibody-drug conjugate) added for CD33-positive AML. Venetoclax + azacitidine for older/unfit patients. APL (AML-M3) is treated with ATRA (all-trans retinoic acid) + arsenic trioxide — a highly effective regimen achieving >95% cure rate. ALL: multi-agent induction (vincristine, dexamethasone, asparaginase, anthracycline); CNS prophylaxis with intrathecal chemotherapy; maintenance therapy for 2-3 years. Philadelphia-positive ALL adds tyrosine kinase inhibitor (imatinib, dasatinib, ponatinib). CML: imatinib (Gleevec/Glivec) 400mg daily — first-line; dasatinib, nilotinib, bosutinib as second-line TKIs; allo-HSCT for blast phase or TKI resistance. CLL: watch and wait for asymptomatic early disease; ibrutinib (BTK inhibitor), venetoclax (BCL-2 inhibitor) + obinutuzumab, or FCR chemo-immunotherapy for progressive disease.

Acute leukemias (AML, ALL) are rapidly fatal without treatment — progressive bone marrow failure causes life-threatening neutropenic infections (bacterial sepsis, invasive fungal infection), haemorrhage from severe thrombocytopenia, and profound anaemia. Median survival without treatment is weeks. Hyperleukocytosis (white cell count above 100 x10^9/L) causes leukostasis — microvascular occlusion in the lungs (respiratory failure) and brain (stroke, coma) — a haematological emergency requiring immediate leukapheresis and cytoreduction. Tumour lysis syndrome — rapid cell death releasing potassium, phosphate, and uric acid — causes acute kidney failure, life-threatening hyperkalaemia (cardiac arrhythmia), and hypocalcaemia-induced seizures, most commonly in ALL and Burkitt lymphoma. CML progresses from chronic phase through accelerated phase to blast crisis (resembling acute leukemia), typically within 3-5 years without treatment. CLL causes recurrent bacterial infections from antibody deficiency (hypogammaglobulinaemia), autoimmune haemolytic anaemia, and eventual Richter's transformation (5-10%) to aggressive large B-cell lymphoma.

Most leukemias cannot be prevented as causes are largely unknown. Minimize occupational benzene exposure (chemical and petroleum industries) — observe workplace safety standards and use protective equipment. Avoid unnecessary ionizing radiation exposure. Do not smoke — smoking raises AML risk by approximately 40%. For individuals with genetic predisposition syndromes (Down syndrome, Fanconi anaemia), regular haematology surveillance allows early detection. Patients in remission after leukemia treatment require regular follow-up: FBC monitoring for relapse, monitoring for late effects of chemotherapy (cardiotoxicity from anthracyclines, secondary myelodysplasia from alkylating agents), and management of long-term immunosuppression after allo-HSCT.

Seek urgent medical attention for unexplained bruising or petechiae (tiny red-purple spots), prolonged nosebleeds or bleeding gums that won't stop, rapidly progressive fatigue and pallor, recurrent fevers or infections that fail to resolve with antibiotics, or bone pain — especially in children. These can be presenting features of acute leukemia, which progresses rapidly and requires urgent diagnosis and treatment. Any suspicion of leukemia warrants same-day FBC. Known leukemia patients should attend the emergency department immediately for high fever (above 38°C on chemotherapy — neutropenic sepsis), unusual bleeding, severe breathlessness, or sudden neurological symptoms. Children and young adults with persistent unexplained lymphadenopathy (swollen lymph nodes lasting more than 2-3 weeks), particularly in combination with fatigue, pallor, and easy bruising, require urgent blood count assessment to exclude haematological malignancy without delay.