Leukaemia Flashcards
(15 cards)
What is the peak incidence of ALL?
2-3 years
Is ALL homogenous or a heterogenous group of malignancies?
ALL is a heterogenous group of malignancies with a number of distinctive genetic abnormalities -> varying clinical behaviours and responses to Tx
What chromosomal abnormalities is ALL associated with?
Down syndrome
Bloom syndrome
Ataxia-telangiectasia
Fanconi anaemia
How is ALL classified and what is the most common type?
WHO classification of leukaemias is the current system used
o B-lymphoblastic leukaemia
- Previously termed precursor B-ALL or Pre-B-ALL
- ~85% of cases
o T-lymphoblastic leukaemia
- ~15% of cases
o Burkitt leukaemia
- Derived from mature B cells
- ~1% of casesDoes patients with ALL on initial presentation usually have a raised WCC?
No; many pts present with WCC of <10,000/microL
What is found on the peripheral blood film of a patient presenting with ALL?
Pancytopenia
Blasts present on the film
May have elevated WCC
What are the Ddx of ALL?
• With only pancytopenia -> aplastic anaemia, myelofibrosis, familial haemophagocytic lymphohistiocytosis
• Failure of a single cell line -> transient erythroblastopenia of childhood, immune thrombocytopenia, congenital or acquired neutropenia
• High index of suspicion required to differentiate ALL from
- Infectious mononucleosis in pts with acute onset of fever and lymphadenopathy
- JIA in pts with fever, bone pain but often no tenderness, and joint swelling
• Other malignant that invade bone marrow and can have clinical and laboratory findings similar to ALL -> AML, neuroblastoma, rhabdomyosarcoma, Ewing sarcoma, retinoblastoma
What is diagnostic of ALL?
Bone marrow evaluation demonstrating >25% of the bone marrow cells as a homogeneous population of lymphoblasts
What is the most important prognostic factor in ALL?
Response to treatment
What risk factors does risk-directed Tx take into account?
- Age at Dx (standard risk is 1-10yr)
- Initial WCC (standard risk is <50,000/microL)
- Immunophenotypic and cytogenetic characteristics of blast populations
- Rapidity of early Tx response (i.e. clearance rate of leukaemic cells from the marrow or peripheral blood)
- Assessment of MRD (minimal residual disease) at the end of induction therapy (>0.01% of the marrow on day 29 of induction a significant risk factor for shorter event-free survival compared with pts with negative MRD)
When is imatinib used in ALL?
Imatinib is added to intensive chemotherapy regimen for Philadelphia chromosome-positive ALL with t(9;22), inhibiting the BCR-ABL kinase resulting from the translocation
What are the phases in treatment for ALL and what chemotherapeutic agents are used in each?
Remission induction - designed to eradicate the leukaemic cells from the bone marrow, with Tx for 4/52 with dexamethasone or prednisone, weekly vincristine, a single dose of pegylated asparaginase, IT chemotherapy at start and at least once more during induction and in higher-risk pts weekly daunomycin
Consolidation - intensive CNS Tx in combination with continued intensive systemic therapy in an effort to prevent later CNS relapses
Intensification
- 14-28/52 of Tx with medications and schedules varying based on risk group of the pt
- Includes phases of delayed intensification (aggressive Tx) and interim maintenance (relatively non-toxic phases of Tx)
- Includes cytarabine, methotrexate, asparaginase and vincristine to eradicate residual disease
Maintenance
- Lasts for 2-3yr, depending on protocol
- Daily mercaptopurine and weekly oral MTX, usually with intermittent doses of vincristine and a corticosteroid
What are the major side effects of common chemotherapeutic agents?
Remember chemo man!!!
What five main features of supportive care are required during treatment with aggressive chemotherapeutic programmes?
- Monitoring for/preventing tumour lysis syndrome
- Preventing/treating renal failure secondary to high levels of serum uric acid with allopurinol or urate oxidase (Rasburicase)
- PRBC and platelet transfusion for severe myelosuppression secondary to chemotherapy
- Aggressive empirical antimicrobial thearpy for sepsis in febrile neutropenia
- Prophylaxis for Pneumocystis jiroveci pneumonia
Describe acute vs. chronic leukaemia
Acute leukemias are characterized by abnormal cells that are less mature, develop quickly, and leave the bone marrow as dysfunctional cells called “blasts.” These blasts crowd out healthy cells in the bone marrow, causing the rapid onset of symptoms. Blasts normally make up 1% to 5% of marrow cells, and having more than 20% blasts in the bone marrow is required for a diagnosis of acute leukemia.
In contrast, chronic leukemias develop slowly and may take years to develop symptoms. They are composed primarily of more mature and functional cells, and there are generally not elevated numbers of blasts.
