Haematological MalignancyKim Gibson, F1January 2015

Objectives

• Leukaemias – ALL, CLL, AML, CML.

• Lymphomas– Hodgkin’s vs Non-Hodgkin’s

• Myeloma

Blood Components

Blood Cell Components

• Lymphocytes form in marrow – T cells mature in the thymus. B and T cells are deposited in lymph organs (e.g. spleen) and circulate in lymphatic system.

• Myeloid cells include all other haematological cell types, which form in bone marrow before release into vascular space.

Leukaemia

• Leukaemic cells (cancerous WBC) infiltrate bone marrow, affecting normal function, i.e. There is inadequate haematopoeisis.

• Aetiology mostly unknown, but viruses/chemicals/drugs/radiation all implicated

Leukaemia

Leukaemia: Signs & Symptoms• Mostly seen in acute leukaemia, late

chronic.

• Due to bone marrow failure – red marrow in central skeleton and proximal long bones

Leukaemia: Investigations

• FBC – Hb low, WBC usually high

• Blood film – shows precursor lymphoblast cells

• Bone Marrow aspirate – increased cellularity, reduced erythropoeisis, reduced megakaryocytes - replaced by blasts

• CXR – why?

• LP for CSF examination in ALL

Leukaemia: Treatment

• Without treatment, acute leukaemia is invariably fatal within months.

• ALL in the young has best chance of cure, AML good chance of cure but secondary AML poorest prognosis.

• Curative treatment carries both morbidity and mortality – Risk vs Benefit

Leukaemia: Treatment

• All need supportive treatment:– Transfusions of red cells and platelets and necessary,

prevention of infection, treatment of infection with antibiotic/antifungal agents as soon as fever develops

• Curative Intent:– Try to return marrow to normal – complete remission

(CR). ‘Induction chemo’ not specific to cancerous cells – major infection risk. Followed by specific ‘consolidation’ regimen – ESSENTIAL or remission will certainly occur.

Acute Myeloid Leukaemia

• Treatment with curative intent if <60

• Risk and prognosis based on bone marrow result

• Bone marrow transplant in some higher risk patients, or if fail 2 cycles chemo

• 75% achieve CR, 50% of those are ‘cured’ (1/3 overall)

Acute Lymphocytic Leukaemia

• ALL commonest childhood malignancy, but can be any age

• CR and consolitation achieved with different agents than in AML

• Early transplant if high risk (older pts, high WCC, >3-4 weeks to achieve CR)

• Major difference is need to treat CNS as soon as CR achieved – intrathecal chemo

• Very high risk may need cranial radiotherapy

• Maintenance Tx for at least 2 years

Acute Leukaemias

• ALL in childhood good prognosis – 80% alive at 5 years

• Overall cure rate for ALL 30%

• In both AML and ALL recurrence usually within 3 years – poor prognosis. Transplant usually considered, despite the risks.

Chronic Myeloid Leukaemia• Peak age 40-60 years.

• Slow, progressive disease. If untreated acute phase (blast crisis) leads to death rapidly.

• Often no symptoms in chronic phase. Symptoms often suggest blast crisis is occurring.

• Philadelphia chromosome associated with 95% cases

• Fluoroscein-in-situ-Hybridisation and reverse-transcriptase PCR helps diagnosis and monitoring response to Tx

CML: Treatment

• Supportive treatment as necessary

• Imatinib is therapy of choice in chronic phase – complete response in 95%, well tolerated, can continue indefinitely

• Acute phase treated in similar way to acute leukaemias to try and return to second chronic phase.

• Stem cell transplant cures 75% where imatinib fails

Chronic Lymphocytic Leukaemia

• Commonest leukaemia, presents mostly >65 years

• Mostly asymptomatic incidental finding

• Median survival approx 10 years

• Diagnosis depends on lymphocyte count >5x 109/L

• Clinical course is variable, difficult to determine prognosis

CLL: Management• Major decision is when to treat – 1/3 never need intervention

• Rai and Binet systems use presence of symptoms and results of investigations to stage – helps determine when to treat

• Treatment (intermittent chemo) can help the symptoms and signs, effect on life expectancy uncertain.

• Supportive treatments as above are important

• Stem cell transplant benefits under Ix in younger patients

• CLL can undergo lymphomatous (Richter’s) transformation (7%) – survival is short.

Lymphomas

• Commoner than leukaemias

• Abnormal proliferation of lymphoid tissue – can occur anywhere lymph tissue found (LNs, spleen, thymus, GI tract...)

• Classifed as Hodgkin’s or Non-Hodgkin’s depending on histology

Hodgkin’s Lymphoma

• Rare, M:F = 1.3:1, 90% in over 16s. Peak incidence in 20s

• Mostly involves LNs

• Definition of HL is presence of Reed-Sternberg cells in lymph tissue on biopsy.

Hodgkin’s Lymphoma: Classification

• Classical HL:– Nodular sclerosing (70%): fibrotic bands and

nodules, usually affects young adults– Lymphocyte-rich HL (5%): infiltration of many

small lymphocytes and R-S cells, peripheral nodes, older age.

– Mixed Cellularity HL (25%): M>F, associated with B symptoms

– Lymphocyte-depleted HL: rare. Numerous R-S cells, advanced B symptoms, associated with HIV.

HL: Signs & Symptoms

• Lymph node enlargement (usually cervical) – painless and rubbery.

• Enlarged spleen/liver

• Others include pruritis, fatigue, anorexia, alcohol-induced pain at affected LNs.

HL: Investigations & Treatment• LN biopsy.

• FBC – Hb can be normal or low. High lymphocytes. ESR raised, abnormal LFTs.

• CXR and CT, ? PET scan

• Staging by Ann Arbor classification based on number/spread affected nodes and presence of B symptoms which carry a worse prognosis. Fever, drenching night sweats, >10% weight loss in 6/12

• Treatment – curative intent. Chemo and site-specific radiation. Recurrence uncommon, but 2nd/3rd remissions achievable

Non-Hodgkin’s Lymphoma• 70% B cell, 30% T cell

• Viruses including HBV, herpesvirus 8, HIV all implicated

• Malignant proliferation of lymphocytes

• Signs and Symptoms: painless superficial LN enlargement, systemic B symptoms. Extra-nodal involvement inc GIT, lung, brain, testes, thyroid, skin...

• Ix – FBC to look for bone marrow infiltration, ESR raised, U&Es (big nodes obstruct ureters), LFTs, CXR, CT, Bone Marrow Bx, trephine Bx, LN Bx

NHL: Types• Follicular Lymphoma: painless lymphadenopathy.

Remitting/relapsing over ~10 years. Treatment: chemo-immunotherapy, radiotherapy and occasioanlly stem cell transplant. High risk transformation to diffuse large B cell lymphoma

• Lymphoplasmacytic lymphoma: uncommon. Extensive marrow infiltration. Management can be expectant, supportive or chemotx. Survival ~4 years

• Diffuse large B cell lymphoma: commonest. Without Tx fatal in months. >50% younger pts cured. Rapid infiltration of other organs, treated with chemoimmunotherapy.

• Burkitt’s lymphoma – endemic to Africa. Rapid progression. 30% have meningitis at presentation. 60% cure with chemo.

Multiple Myeloma

• Malignancy of plasma (B!) cells within bone marrow

• Clonal expansion of abnormal proliferative plasma cells paraproteinaemia and excretion of light chains in urine (Bence Jones protein)

• Disease of elderly, commoner in men

Multiple Myeloma Features

• Bone destruction (vertebral or long bones, can cord compression). Pain and/or pathological fractures

• Hypercalcaemia

• Bone marrow infiltration (anaemia, neutropenia, thrombocytopenia)

• Renal impairment from light chain deposition in tubules

• Recurrent infections (healthy immunoglobulins reduced)

C alcium

R enal failure

A naemia

B one problemsIf you see back pain and renal failure, think MYELOMA

Multiple Myeloma: Investigations• FBC – suggestive of marrow infiltration

• ESR and CRP possibly raised

• U&Es (renal failure) and uric acid

• Blood film

• Serum calcium

• Serum free light chain assay

• Urinary Bence-Jones protein

• Bone Marrow aspirate

• Skeletal Survey

AKA: MYELOMA SCREEN

Multiple Myeloma: Treatment

• Survival is 5-10 years if treatment of complications is successful. Chemo and steroids

• There is no ‘cure’ for multiple myeloma

• Supportive therapy as before

• Orthopaedic involvement in pathological fractures

Conclusion

• Haematological malignancies are COMPLICATED

• Lots of overlap

• Symptoms are non-specific and often insidious

• Easier to learn if you break it down into different classifications

ANY QUESTIONS?

THANK YOU!