Leukaemia

Also known as: Leukemia

Malignant clonal proliferation of hematopoietic stem/progenitor cells, causing bone marrow infiltration and impaired normal hematopoiesis, with variable peripheral blood and extramedullary involvement.

Classified by cell lineage and acuity:

Acute lymphoblastic leukemia (ALL): predominantly pediatric (peak 2-5 years), but occurs in adults with worse prognosis; lymphoblast proliferation
Acute myeloid leukemia (AML): predominantly adult (median age ~65-70), myeloblast proliferation; subtyped by WHO classification (genetic/molecular abnormalities increasingly define subtype and prognosis, e.g., APL with PML-RARA translocation)
Chronic lymphocytic leukemia (CLL): most common leukemia in Western adults, indolent, elderly predominant, mature B-lymphocyte clonal proliferation
Chronic myeloid leukemia (CML): defined by BCR-ABL1 fusion gene (Philadelphia chromosome, t(9;22)), triphasic course (chronic → accelerated → blast crisis)

Bone marrow failure symptoms (common to acute leukemias, from crowding out of normal hematopoiesis):
Anemia: fatigue, pallor, dyspnea
Thrombocytopenia: easy bruising, petechiae, mucosal bleeding (epistaxis, gum bleeding), menorrhagia
Neutropenia: recurrent/severe infections, fever
Bone pain (marrow expansion, especially in children with ALL)
Lymphadenopathy, hepatosplenomegaly (more prominent in ALL, CLL, CML)
Gum hypertrophy, skin infiltration (leukemia cutis) — more characteristic of certain AML subtypes (monocytic)
CNS involvement: headache, cranial nerve palsies (more common in ALL, especially at relapse)
AML-specific: DIC risk especially in acute promyelocytic leukemia (APL) — life-threatening bleeding, requires urgent recognition
CLL: often asymptomatic, found incidentally on routine FBC (lymphocytosis); B-symptoms (fever, night sweats, weight loss) in more advanced disease; autoimmune hemolytic anemia/thrombocytopenia can complicate
CML: often insidious, fatigue, splenomegaly (can be massive, causing early satiety/left upper quadrant discomfort), night sweats, weight loss; blast crisis presents like acute leukemia
B-symptoms across chronic leukemias/lymphomas: fever, drenching night sweats, unintentional weight loss (>10% in 6 months)

FBC: leukocytosis (or leukopenia), anemia, thrombocytopenia; blast cells on differential in acute leukemia
Peripheral blood film: blasts (acute), Auer rods (pathognomonic for AML, especially APL), smudge cells (CLL characteristic)
Bone marrow aspirate and trephine biopsy: definitive diagnosis — blast percentage (≥20% defines acute leukemia per WHO), morphology, cellularity
Immunophenotyping (flow cytometry): lineage determination (myeloid vs. lymphoid markers), essential for classification and treatment planning
Cytogenetics/molecular testing: essential for prognosis and targeted therapy selection
AML: FLT3, NPM1, CEBPA mutations; core-binding factor abnormalities; PML-RARA (APL) — urgent test given specific treatment implications
ALL: BCR-ABL1 (Philadelphia-positive ALL — different treatment pathway), other fusion genes
CML: BCR-ABL1 confirmatory (defines diagnosis)
CLL: FISH panel (del17p, del11q — high-risk features), IGHV mutation status (prognostic)
Lumbar puncture with CSF cytology: CNS involvement assessment, particularly in ALL (routine) and high-risk AML
Coagulation studies: essential in AML, especially APL (DIC screen — PT, APTT, fibrinogen, D-dimer)
Imaging (CT/PET): staging for lymphadenopathy/organomegaly, particularly CLL

Differentials: reactive leukocytosis (infection, especially in children with high WCC — leukemoid reaction), infectious mononucleosis (atypical lymphocytosis), other bone marrow failure syndromes (aplastic anemia, myelodysplastic syndrome), lymphoma with marrow involvement.

Acute lymphoblastic leukemia (ALL):

Multi-agent chemotherapy in phases: induction (vincristine, corticosteroids, asparaginase, ± anthracycline) → consolidation → maintenance (often 2 years, including methotrexate/mercaptopurine)
CNS prophylaxis: intrathecal chemotherapy (methotrexate) — essential given CNS relapse risk, ± cranial irradiation in high-risk cases
Philadelphia-positive ALL: add tyrosine kinase inhibitor (imatinib, dasatinib) to chemotherapy backbone
Targeted immunotherapy for relapsed/refractory disease: blinatumomab (bispecific T-cell engager), CAR-T cell therapy (tisagenlecleucel), inotuzumab ozogamicin
Allogeneic stem cell transplant: for high-risk features, poor response to induction, or relapsed disease

Acute myeloid leukemia (AML):

Standard induction: "7+3" regimen — cytarabine (7 days continuous infusion) + anthracycline (daunorubicin, 3 days)
Acute promyelocytic leukemia (APL) — distinct urgent treatment pathway: all-trans retinoic acid (ATRA) + arsenic trioxide (± chemotherapy in high-risk) — differentiation syndrome risk (fever, dyspnea, pulmonary infiltrates, requires prompt steroids); aggressive management of coagulopathy/DIC critical (high early mortality from bleeding if untreated urgently)
Targeted therapy per molecular profile: FLT3 inhibitors (midostaurin, gilteritinib) for FLT3-mutated AML; IDH1/2 inhibitors for IDH-mutated disease; venetoclax (BCL-2 inhibitor) + hypomethylating agent for older/unfit patients
Consolidation: high-dose cytarabine, or allogeneic stem cell transplant for intermediate/high-risk cytogenetics

Chronic lymphocytic leukemia (CLL):

Early-stage asymptomatic: "watch and wait" — no survival benefit to early treatment
Treatment indicated for: symptomatic disease, cytopenias, bulky/progressive lymphadenopathy, B-symptoms, autoimmune complications
Targeted therapy (preferred over chemoimmunotherapy in most): BTK inhibitors (ibrutinib, acalabrutinib), BCL-2 inhibitor (venetoclax) ± anti-CD20 monoclonal antibody (rituximab, obinutuzumab)
High-risk cytogenetics (del17p, TP53 mutation): poor response to chemotherapy, targeted agents preferred

Chronic myeloid leukemia (CML):

Tyrosine kinase inhibitors (TKIs) — revolutionary, most patients achieve near-normal life expectancy: imatinib 400mg od first-line, or second-generation TKIs (dasatinib, nilotinib) for higher-risk disease or intolerance
Monitor BCR-ABL1 transcript levels (PCR) — molecular response milestones guide treatment adjustments
Treatment-free remission possible in select patients with sustained deep molecular response
Blast crisis: treated as acute leukemia (lymphoid or myeloid blast phenotype-directed) with TKI continuation

Supportive care (across all leukemias):

Transfusion support: packed red cells, platelets (irradiated/leukodepleted products in transplant candidates)
Infection prophylaxis/management: neutropenic sepsis protocol (empirical broad-spectrum antibiotics within 1 hour of fever in neutropenic patient — e.g., piperacillin-tazobactam), antifungal/antiviral prophylaxis during intensive chemotherapy
Tumor lysis syndrome prevention: aggressive hydration, allopurinol or rasburicase (high tumor burden, high-risk AML/ALL) before/during induction
Fertility preservation counseling before treatment where feasible

Referral: all suspected leukemia requires urgent hematology/oncology referral — same-day/emergency referral for suspected acute leukemia given risk of rapid deterioration (bleeding, infection, tumor lysis).

Clinical toolsCalculators

BMI GCS EDD Parkland Formula

Corrected Sodium Corrected Calcium Anion Gap Creatinine Clearance Insulin Calculations qSOFA Wells PE Wells DVT CHA₂DS₂-VASc HAS-BLED CURB-65 Centor/McIsaac

Tumour Lysis Syndrome

Also known as: TLS, Tumor lysis syndrome

Tumour lysis syndrome is an oncological emergency caused by rapid release of intracellular contents from dying tumour cells, producing the characteristic tetrad of hyperkalaemia, hyperphosphataemia, hyperuricaemia and hypocalcaemia, with consequent acute kidney injury, arrhythmia, seizures and death.

It occurs most often shortly after starting cytotoxic chemotherapy, but can follow radiotherapy, corticosteroids or targeted agents, and can occur spontaneously in highly proliferative disease before any treatment is given.

The highest-risk settings are Burkitt lymphoma, acute lymphoblastic leukaemia, acute myeloid leukaemia with high white cell counts, and high-grade lymphomas, particularly with bulky disease, raised baseline LDH, pre-existing renal impairment or volume depletion.

Venetoclax in chronic lymphocytic leukaemia is a specific modern risk requiring structured ramp-up and monitoring.

It is far more effectively prevented than treated, which is why risk stratification before treatment is the central clinical task.

Cairo-Bishop criteria are used, distinguishing laboratory from clinical tumour lysis syndrome.

Laboratory TLS — two or more of the following within 3 days before to 7 days after starting treatment:

Uric acid raised, or a 25% increase from baseline
Potassium raised, or a 25% increase
Phosphate raised, or a 25% increase
Calcium reduced, or a 25% decrease

Clinical TLS — laboratory TLS plus one or more of: acute kidney injury (creatinine rise), cardiac arrhythmia or sudden death, or seizure.

Investigations:

Baseline before treatment: potassium, phosphate, calcium, uric acid, LDH, renal function, and urine output — establishing the baseline is what makes the 25% change criteria usable
Frequent monitoring during the at-risk period: every 4–8 hours in high-risk patients for the first 24–72 hours, and at least daily in intermediate-risk patients
ECG and cardiac monitoring for hyperkalaemia and hypocalcaemia
Strict fluid balance and urine output monitoring
LDH and white cell count as markers of tumour burden and proliferation rate

Prevention, which is where the greatest benefit lies:

Risk-stratify every patient before starting treatment, based on tumour type, bulk, LDH, white cell count and baseline renal function
Aggressive intravenous hydration is the single most important preventive measure, typically 2–3 L/m²/day started before treatment, maintaining a high urine output. This dilutes and clears the released solutes
Allopurinol for low and intermediate risk, started 24–48 hours before treatment; it blocks xanthine oxidase and prevents further uric acid formation, but does not remove uric acid already present, which is why it is preventive rather than a rescue treatment
Rasburicase for high-risk patients and for established tumour lysis syndrome; it converts uric acid to allantoin and lowers uric acid within hours. It is contraindicated in G6PD deficiency, where it causes severe haemolysis and methaemoglobinaemia, so G6PD status must be considered before use in at-risk populations
Urinary alkalinisation is no longer recommended: it increases uric acid solubility but promotes calcium phosphate precipitation, and the balance of harm has moved against it
Avoid nephrotoxins and potassium- or phosphate-containing fluids and supplements

Established tumour lysis syndrome:

Continue aggressive hydration with close attention to fluid balance
Hyperkalaemia is the most immediately life-threatening component and is managed as in the hyperkalaemia entry: calcium for cardiac protection, insulin-glucose and salbutamol to shift, and binders or dialysis to remove
Hyperphosphataemia: phosphate binders, and dialysis where severe
Hypocalcaemia: treat only if symptomatic, since giving calcium in the presence of high phosphate promotes calcium phosphate precipitation and worsens renal injury. This is a deliberate departure from the usual approach to hypocalcaemia
Rasburicase for hyperuricaemia
Renal replacement therapy for refractory hyperkalaemia, severe hyperphosphataemia, fluid overload, or established acute kidney injury; the threshold for dialysis is lower than in other settings given the rate at which derangement can progress

Referral: haematology or oncology, with critical care and nephrology involvement early in high-risk or established cases.

Leukaemia

Overview

Clinical Features

Diagnosis

Management

Overview

Diagnosis

Management