Haematological malignancy

Classification

• Bone marrow based
  • Leukaemia
    • Myeloid vs. Lymphocytic
    • Acute – Usually blastic in appearance with rapidly fatal outcome w/o therapy
    • Chronic – More differentiated cells and indolent course
  • Multiple myeloma
• Peripheral lymphoid tissue
  • Hodgkin’s (nodal and extranodal)
  • Non-Hodgkin’s

Myeloid neoplasms

• Derived from bone marrow progenitors that develop into erythrocytes, granulocytes (neutrophils, basophils, eosinophils), monocytes and megakaryocytes
• Exception is CML where cell of origin is pluripotent 
• Divided into:
  • AML
    • Blasts >20% of marrow aspirate
  • Myeloproliferative disorders (may transform into AML)
    • CML
    • Polycythaemia vera
    • Essential thrombocythaemia
    • Primary myelofibrosis
  • Myelodysplastic syndromes (may transform into AML)
    • Bone marrow cellularity increased but may be normocellular. Percentage of blasts is <20% in marrow aspirate

Lymphoid neoplasms

• Derived from cells that develop into T cells, B cells
• Divided into lymphoblastic (lymphoid precursor derived) and mature lymphocyte or plasma cell cancers
• Historically leukaemic (blood and marrow) vs. lymphoma (mass) but overlap is tremendous as almost all can present with either
• Precursor B lymphoblastic leukaemia/lymphoma
• Precursor T lymphoblastic leukaemia/lymphoma
• Mature B cell neoplasms
  • CLL, Hairy cell leukaemia, Waldenstrom macroglobulinaemia, MGUS, mu/gamma/alpha heavy chain disease, follicular lymphoma, mantle cell lymphoma, DLBCL (most common non-Hodgkins lymphoma), Burkitt lymphoma
• Mature T and NK cell neoplasms
  • T cell prolymphocytic leukaemia, adult T cell leukaemia/lymphoma
• Hodgkin’s lymphoma
  • Nodular lymphocyte predominant
  • Classic
    • Nodular sclerosis
    • Lymphocyte-rich
    • Mixed cellularity
    • Lymphocyte-depleted

Lymphoid neoplasms

• Historically divided into the following:
  • Indolent: 40% of NHL. Follicular, CLL, mantle cell
  • Aggressive: 50% of NHL. DLBCL, peripheral T cell lymphoma
  • Highly aggressive: 5% of NHL. B or T cells
  • Hodgkin’s: Excellent prognosis

Hodgkin’s lymphoma

• Unique cellular composition with minority of neoplastic cells (Reed-Sternberg cells) in an inflammatory background
• Germinal or post-germinal B cell origin
• Two major subtypes:
  • Nodular lymphocyte-predominant HL
  • Classical
• One peak in young adults (20) and one in older adults (65)
• Classic presentation is painless lymphadenopathy in cervical region or mass in chest +- B symptoms
• Usually diagnosed by lymph node biopsy with Reed-Sternberg cells on inflammatory background

Multiple myeloma

• Presentation
  • Bone pain with lytic lesions
  • Increased total serum protein or monoclonal protein in urine or serum
    • May be normal total serum protein if light chain disease (as need huge amounts to affect total serum protein)
  • B symptoms – Normocytic normochromic anaemia very common, fatigue, weight loss
  • Hypercalcaemia (28% of patients at diagnosis)
  • Acute renal failure
    • Light chain cast nephropathy + hypercalcaemia + light chain amyloidosis
  • Spinal cord compression
  • Immunosuppression with subsequent infection
• Median age of diagnosis 66yo

Multiple myeloma

• 97% have monoclonal protein production detected by protein electrophoresis of serum or urine
  • Mostly IgG (52%), IgA (21%), light chain kappa/lambda (Bence-Jones) 16%
  • Renal failure much more common in light chain myeloma
• Of the 3% without detectable monoclonal protein production, can measure kappa/lambda ratio to detect most abnormalities
• Peripheral blood smears
  • Anaemia
  • Rouleaux formation
  • Leukopaenia
  • Thrombocytopaenia
  • Monoclonal plasma cells are rarely seen

General notes

• AML
  • Mostly present with marrow failure
  • Acute promyelocytic leukaemia
    • Unique subtype of AML that presents with DIC requiring expert haematological management
• ALL
  • Most common in children
• Myelodysplastic syndromes
  • Main feature is bone marrow dysplasia
  • Potentially malignant haematological disorders that may progress to classic leukaemoid states or behave as slowly evolving marrow failure syndromes
  • Usually occur in the elderly

complications

• Metabolic disturbances
  • At presentation, haematological malignancy can be associated with hyperuricaemia, hypercalcaemia and/or tumor lysis syndrome
  • Multiple myeloma may be complicated by renal failure hypercalcaemia, hyperviscosity and hyperuricaemia
• ARDS
  • May be a consequence of hyperleukocytosis, TRALI, CMV, DIC, post-marrow transplant and sometimes following chemo/radiotherapy

complications

• Side effects of chemotherapy
  • Bone marrow failure
    • Neutropaenia
      • Absolute count, rate of fall, duration of neutropaenia and nadir are all crucial
      • Often infectious agent not identified and patient marrow recovers with resolution of fevers
      • May not show same clinical picture due to lack of neutrophils
      • Rigors, hypotension and shock suggest Gram-negative sepsis
      • IVIG for agammaglobulinaemia
      • G-CSF may play a role in neutropaenia (but does not prevent it)
      • Lung infiltrates have high risk of treatment failure. Empirical antifungal therapy in selected high-risk patients may improve outcomes. Always consider pulmonary haemorrhage as a cause also.

Haematopoietic stem cell transplant

• Allogenic stem cell transplant has been used in acute leukaemia with impressive long-term cure rates
• Stem cells can be obtained from aspirated marrow or from peripheral blood by apheresis following stimulation with haematopoietic growth factors +- cytotoxic chemotherapy
• Complications
  • Respiratory failure
    • Most common cause of death following haematopoietic stem cell transplant
    • CMV-induced interstitial pneumonitis (can be treated with ganciclovir) and idiopathic pneumonia syndrome (almost universally fatal)
    • Aspergillus also frequently seen

Stem cell continued

• GVHD
  • Major complication, especially with unrelated and mismatched donors
  • Target previously thought to be host MHC antigens by donor antibodies but self-antigens are now known to exist
  • Rash, liver, GI dysfunction
  • Systemic corticosteroids for low-grade GVHD and more intense immunosuppression for more severe cases
  • Low-grade GVHD may be beneficial for malignancy clearance
• Veno-occlusive disease of the liver
  • Mostly seen with allogeneic stem cell transplants
  • Thrombotic occlusion of small hepatic vessels, probably due to chemo-induced endothelial damage
  • Weight gain, hepatomegaly, jaundice +- liver failure
  • Heparin prophylaxis can be of benefit with supportive therapy

Last Updated on October 2, 2020 by Andrew Crofton