Blood Cancer — Leukaemia, Lymphoma & Myeloma Guide — Symptoms, Causes & Treatment | MyMedicPlus

Blood cancers (haematological malignancies) are a heterogeneous group of malignancies that originate in the blood, bone marrow, or lymphatic system — affecting the production, function, or lifespan of haematopoietic cells (blood-forming cells). They are classified into three principal categories based on the cell of origin: leukaemia — cancer arising from haematopoietic precursor cells in the bone marrow, causing malignant cells to flood the bloodstream and displace normal haematopoiesis; further classified as acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), chronic myeloid leukaemia (CML), and chronic lymphocytic leukaemia (CLL). Lymphoma — malignancy of lymphocytes (B-cells, T-cells, or NK-cells) presenting as solid tumour masses in lymph nodes, spleen, and other lymphoid tissue; divided into Hodgkin lymphoma (HL — characterised by Reed-Sternberg cells, accounting for approximately 10% of all lymphomas) and non-Hodgkin lymphoma (NHL — a broad category of over 60 B- and T-cell lymphoma subtypes, with diffuse large B-cell lymphoma/DLBCL being the most common aggressive form). Multiple myeloma — cancer of plasma cells (antibody-secreting B-cell derivatives) in the bone marrow, causing M-protein production, bone destruction, renal failure, and immune paresis. Together, blood cancers account for over 1.2 million new diagnoses and approximately 720,000 deaths annually worldwide — approximately 6-7% of all cancer diagnoses. Haematological malignancies collectively include over 80 distinct disease entities spanning a spectrum from very indolent conditions (CLL, follicular lymphoma) to rapidly fatal acute leukaemias. Outcomes have been dramatically transformed over the past two decades by targeted therapies (imatinib for CML, ibrutinib for CLL), immunotherapy (daratumumab for myeloma), anti-CD20 monoclonal antibodies (rituximab for NHL), and CAR-T cell therapy (tisagenlecleucel, axicabtagene ciloleucel for relapsed/refractory DLBCL and ALL).

Blood cancers arise from acquired somatic mutations in haematopoietic stem cells or lymphoid precursor cells that confer survival and proliferative advantage, disrupting normal differentiation and haematopoiesis. The specific genetic event determines the biological behaviour: chromosomal translocations (Philadelphia chromosome t(9;22) BCR-ABL1 — hallmark of CML; t(14;18) BCL-2 — follicular lymphoma; t(8;14) MYC — Burkitt lymphoma; t(15;17) PML-RARα — APL); gene mutations (FLT3-ITD and NPM1 — AML prognostic markers; KRAS; IDH1/IDH2 — targetable in AML); and chromosomal deletions (del(17p) in CLL — worst prognosis). Established risk factors: ionising radiation — atomic bomb survivors had 10-20-fold increased leukaemia risk; prior radiotherapy (secondary leukaemia and lymphoma 5-15 years after treatment); previous alkylating agent chemotherapy (cyclophosphamide, melphalan, chlorambucil — therapy-related AML); benzene and chemical carcinogens (occupational exposure in petrol workers, shoe makers, rubber industry — causes AML and MDS); viral infections — EBV (Epstein-Barr virus) causes endemic Burkitt lymphoma (in children in tropical Africa — associated with malaria co-infection) and contributes to Hodgkin lymphoma and post-transplant lymphoproliferative disorder (PTLD); HTLV-1 (Human T-lymphotropic virus type 1) causes adult T-cell leukaemia/lymphoma (ATLL — endemic in Japan, Caribbean, and parts of Africa); HIV/AIDS increases risk of high-grade NHL (Burkitt, DLBCL) and Hodgkin lymphoma; hepatitis C virus infection (marginal zone lymphoma); Helicobacter pylori (MALT lymphoma of the stomach — eradication of H. pylori can cure early-stage gastric MALT lymphoma). Congenital and genetic risk: Down syndrome (trisomy 21) — 20-fold increased risk of ALL and AML in children; Klinefelter syndrome (XXY); Fanconi anaemia and dyskeratosis congenita (bone marrow failure syndromes progressing to MDS/AML); familial CLL predisposition. Advancing age is the strongest risk factor for most blood cancers — AML, CLL, and myeloma are predominantly diseases of older adults. Immunosuppression (transplant recipients, autoimmune disease patients) increases lymphoma risk. Most blood cancers arise sporadically without an identifiable single cause.

Clinical presentation varies substantially by disease type, but common haematological malignancy symptoms reflect bone marrow failure (from displacement by malignant cells) and systemic tumour effects. Symptoms of bone marrow failure — present in acute leukaemia and advanced chronic disease: fatigue, pallor, and dyspnoea on exertion from anaemia (Hb below 10 g/dL — bone marrow replaced by leukaemic blasts cannot produce adequate red cells); recurrent and severe infections (bacterial, fungal, viral) from neutropenia (ANC below 0.5 × 10⁹/L — granulocyte maturation arrested); easy bruising, petechiae, purpura, mucosal bleeding, and epistaxis from thrombocytopenia (platelets below 50 × 10⁹/L). Lymphoma-specific: painless progressive lymphadenopathy — most commonly cervical (neck), axillary (armpit), or inguinal (groin) lymph node enlargement, initially rubbery and mobile; 'B symptoms' (defined as a specific prognostic group in lymphoma staging): drenching night sweats requiring change of bedclothes (not normal sweating), unexplained fever above 38°C recurring, and unexplained loss of more than 10% body weight in 6 months — their presence denotes a worse prognosis and affects treatment intensity. Splenomegaly (left upper quadrant fullness and discomfort), hepatomegaly, and bulky mediastinal mass (superior vena cava obstruction — facial swelling, arm oedema, stridor in aggressive lymphoma). Myeloma-specific: bone pain — characteristically in the spine (vertebral pathological fractures), ribs, and pelvis; hypercalcaemia (anorexia, nausea, confusion, thirst, constipation); renal impairment from light chain deposition ('myeloma kidney'); recurrent serious infections from immune paresis (reduced normal immunoglobulin production); neuropathy from amyloid deposition or nerve compression; 'CRAB' criteria for myeloma end-organ damage: hyperCalcaemia, Renal failure, Anaemia, Bone lesions. Acute leukaemia: dramatic acute onset over days to weeks — severe life-threatening pancytopenia, fever, bruising, DIC (acute promyelocytic leukaemia/APL — presenting with DIC and life-threatening haemorrhage). CML: often asymptomatic chronic phase, discovered on routine FBC (markedly elevated white cell count with granulocyte differential); constitutional symptoms; massive splenomegaly. CLL: typically discovered incidentally on FBC (lymphocytosis); progresses insidiously to lymphadenopathy, splenomegaly, and marrow failure.

Full blood count (FBC) with differential is the critical first screening test: blast cells in blood (circulating immature myeloid or lymphoid cells — greater than 20% blasts defines acute leukaemia by WHO criteria); lymphocytosis above 5 × 10⁹/L with mature small lymphocytes (CLL — 'smudge cells' on blood film); elevated total WBC with full granulocyte differential including promyelocytes, myelocytes, metamyelocytes, and eosinophilia/basophilia (CML); pancytopenia (AML, ALL — marrow replacement); anaemia and thrombocytopenia. Peripheral blood film: morphological description of abnormal cells (blast characteristics in AML — Auer rods — pathognomonic of myeloid lineage; hypersegmented neutrophils in megaloblastic anaemia/MDS). Bone marrow aspirate and trephine biopsy: mandatory for definitive diagnosis of leukaemia and myeloma — aspirate provides cells for morphology, flow cytometry, cytogenetics, and molecular testing; trephine (core biopsy) provides architectural information including cellularity, fibrosis, and infiltration pattern. Immunophenotyping (multi-parameter flow cytometry): identifies characteristic surface antigen expression patterns defining specific haematological malignancies (e.g., CD5+/CD23+/CD19+ for CLL; CD34+/MPO+ for AML; surface light chain restriction for B-cell lymphoma). Cytogenetics and molecular pathology: conventional karyotyping (G-banding) detects chromosomal abnormalities; FISH for specific translocations (BCR-ABL1 for CML/ALL, PML-RARα for APL); RT-PCR for fusion transcripts and MRD (minimal residual disease) monitoring; next-generation sequencing (NGS) panels for actionable mutations (FLT3-ITD/TKD, NPM1, IDH1/2, TP53, DNMT3A in AML; IGHV somatic hypermutation status, TP53, del(17p), del(11q) in CLL prognostication). Lymphoma staging: CT-PET (18F-FDG PET-CT) is the gold standard for staging FDG-avid lymphomas (HL, DLBCL) — Ann Arbor/Lugano staging I-IV; lymph node biopsy (excisional preferred over core needle for adequate tissue) for histological classification. Myeloma diagnosis: serum protein electrophoresis (SPE — M-protein spike), serum immunofixation (characterises M-protein type — IgG, IgA, IgM, light chain only), serum free light chain assay (kappa/lambda ratio), 24-hour urine protein electrophoresis (Bence-Jones protein — light chain in urine); whole-body low-dose CT or PET-CT for bone lesions (replacing skeletal survey); bone marrow biopsy (above 10% clonal plasma cells defines myeloma in context of CRAB/SLiM criteria); serum calcium, creatinine/eGFR, LDH, beta-2 microglobulin, and albumin for ISS staging (International Staging System).

Treatment is highly disease-specific and based on histological subtype, molecular features, stage, and patient fitness. Acute Myeloid Leukaemia (AML): intensive induction chemotherapy — '7+3' (cytarabine 7 days + anthracycline 3 days; e.g., daunorubicin or idarubicin) induces remission in 60-80% of younger fit patients; followed by consolidation chemotherapy or allogeneic stem cell transplant (allo-SCT) for high-risk disease (based on ELN risk stratification — adverse risk: TP53 mutation, monosomal karyotype, del(5q), del(7q)); CPX-351 (liposomal cytarabine+daunorubicin) for therapy-related AML or AML with myelodysplasia-related changes; targeted therapy — midostaurin (FLT3 inhibitor) added to induction for FLT3-mutated AML (RATIFY trial — survival benefit); gilteritinib (FLT3 inhibitor) for relapsed/refractory FLT3-mutated AML; enasidenib and ivosidenib (IDH1/IDH2 inhibitors) for IDH-mutated AML; venetoclax + azacitidine (hypomethylating agent — HMA) for older/unfit patients — now standard of care for elderly AML (VIALE-A trial). Acute promyelocytic leukaemia (APL/AML-M3): ATRA (all-trans retinoic acid) + arsenic trioxide — curative in 85-90%+ without conventional chemotherapy. Acute Lymphoblastic Leukaemia (ALL): paediatric-inspired regimens (UKALL2011, BFM protocols) with prolonged maintenance; tyrosine kinase inhibitors (imatinib, dasatinib) for Philadelphia chromosome-positive ALL (t(9;22)-positive — accounts for 25-30% of adult ALL); blinatumomab (bispecific T-cell engager — CD3 × CD19) for relapsed/refractory B-ALL; inotuzumab ozogamicin (anti-CD22 ADC); CAR-T therapy (tisagenlecleucel — Kymriah) for relapsed/refractory B-ALL in children and young adults (complete remission 81% — ELIANA trial). CML: imatinib (first-generation TKI) achieves major molecular response in 80-90% — transforming CML from a disease with median survival of 3-5 years to near-normal life expectancy; dasatinib, nilotinib (second-generation), or asciminib (STAMP inhibitor — third-generation) for imatinib-resistant or intolerant disease. Hodgkin Lymphoma: ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine) for stages I-II (interim PET-CT guided deescalation); BrECADD or BEACOPP for advanced stages III-IV; excellent 5-year OS above 85-90%; PET-guided therapy reduces toxicity; brentuximab vedotin (anti-CD30 ADC) + AVD for stage III-IV; pembrolizumab/nivolumab (PD-1 blockade) for relapsed/refractory. Diffuse Large B-Cell Lymphoma (DLBCL): R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone) — 6-8 cycles; 60-70% cured; polatuzumab vedotin + R-CHP for high-risk DLBCL; CAR-T (axicabtagene ciloleucel — axi-cel; tisagenlecleucel) for relapsed/refractory DLBCL after 2+ prior lines — superior to salvage chemo+ASCT in early relapse (ZUMA-7 trial). CLL: watch-and-wait for early-stage asymptomatic; ibrutinib (BTK inhibitor) or acalabrutinib for high-risk; venetoclax + obinutuzumab (fixed-duration, MRD-guided) for fit or unfit patients. Multiple Myeloma: transplant-eligible — VRd induction (bortezomib + lenalidomide + dexamethasone) × 4 cycles + autologous SCT + maintenance lenalidomide; transplant-ineligible — Dara-VRd (daratumumab + VRd); isatuximab, carfilzomib for relapsed disease; belantamab mafodotin (BCMA-targeted ADC); CART therapies (idecabtagene vicleucel — ide-cel, ciltacabtagene autoleucel — cilta-cel) for heavily pre-treated myeloma.

Acute leukaemia (AML/ALL) is rapidly fatal without treatment — median survival is weeks to months without chemotherapy, due to severe bone marrow failure causing life-threatening infections, haemorrhage, and anaemia. CML untreated transforms from chronic to accelerated then blast crisis phase — mimicking acute leukaemia. Aggressive lymphomas are fatal within months without treatment. Myeloma causes severe bone destruction, kidney failure, recurrent infections from immune paresis, and spinal cord compression from vertebral disease. Even for more indolent blood cancers, untreated disease eventually leads to bone marrow failure.

No specific lifestyle measures prevent most blood cancers. Avoid unnecessary radiation exposure (X-rays, CT scans should only be ordered when clinically indicated). Minimise occupational exposure to benzene, formaldehyde, and other chemical carcinogens. HIV prevention and treatment (antiretroviral therapy) reduces HIV-associated lymphoma risk. Vaccination against EBV, HPV, and hepatitis B may reduce specific lymphoma risks. For patients in treatment or remission: maintain nutrition, manage infection risk (neutropenic precautions during chemotherapy), regular follow-up, and promptly report new symptoms. Survivor care addresses long-term effects of chemotherapy and radiation.

See your GP urgently — ideally within a week — for any of the following: persistent unexplained fatigue not improving with rest; recurrent or unusual infections; unexplained bruising or bleeding; painless, persistent swelling of lymph nodes in the neck, armpit, or groin lasting more than 2-4 weeks; drenching night sweats requiring a change of clothes; unexplained weight loss of more than 10% in 6 months; persistent fever without obvious infection; or bone pain without injury history. Any routine blood test showing abnormal blood counts (high or very low white cells, low platelets, unexplained anaemia) warrants urgent GP review and possible same-week haematology referral. Do not wait and see — blood cancers are most treatable when detected early. Children with any of these symptoms warrant same-day urgent GP assessment. If you are in treatment for blood cancer, seek emergency care immediately for fever above 38.5°C (neutropenic sepsis — a life-threatening emergency that requires immediate IV antibiotics and hospital admission).