Which of these is the most important prognostic factor in ALL?
Ans. d. Response to steroids (Ref: Wintrobes Clinical Hematology 12/e p1892; Robbins 9/e p590-593, 8/e p627, 628: Nelson 18/e p2120)Three of the most important predictive factors are the age of the patient at the time of diagnosis, the initial leukocyte count, and the speed of response to treatment (i. e. how rapidly the blast cells can he cleared from the marrow or peripheral blood) Among these, response to the treatment with steroids is the most consistent prognostic marker."Prognosis. Pediatric ALL is one of the great success stories of oncology. With aggressive chemotherapy about 95% of children with ALL obtain a complete remission, and 75% to 85% are cured. Despite these achievements, however, ALL remains the leading cause of cancer deaths in children, and only 35% to 40% of adults are cured. Several factors are associated with a worse prognosis: (1) age younger than 2 years, largely because of the strong association of infantile ALL with translocations involving the MLL gene: (2) presentation in adolescence or adulthood; and(3) peripheral blood blast counts greater than 100,000, which probably reflects a high tumor burden. Favorable prognostic markers include (1) age between 2 and 10 years, (2) a low white cell count, (3) hyperdiploidy, (4) trisomy of chromosomes 4, 7, and 10, and (5) the presence of a t(l2;21). Notably, the molecular detection of residual disease after therapy is predictive of a worse outcome in both B- and T-ALL and is being used to guide new clinical trials. "-- Robbins 9/e p592Acute Lymphoblastic Leukemia (ALL)ALL is neoplasms of immature B (pre-B) or T (pre-T) cells, which are referred to as lymphoblastsB-ALLs (85%) typically manifest as childhood acute ''Leukemias"QT-ALLs tend to present in adolescent males as thymic "lymphomas"QEpidemiology:ALL: MC cancer of childrenQ; Peak Incidence: 3rd yearQ; Whites> blacks; Boys>girlsHighest incidence in HispanicsMature B-cell ALL is an uncommon type ALLQ (1-2% of ALL cases) in children.Pathology:T-ALLs have gain of function mutations in NOTCH-1QB-ALLs have loss of function mutations PAX5Q, E2AQ & EBFQ, or t(12;21)Q involving genes ETV6 & RUNX1, 2 genes that are needed in very early hematopoietic precursor.Mature B-cell ALL is associated with t(8;14) & over expression of the c-myc oncogeneT-ALL are aggressive lymphomasQIn T-ALL, cells are positive for markers of blasts like-Tdt,Q CD34 & T cell markers CD1, CD2, CD5, CD7QClassification of ALLImmunologic Subtype% of CasesFAB SubtypeCytogenetic AbnormalitiesPre-B ALL75L1, L2Qt(9;22),t(4;11), t(1;19)T-cell ALL20L1, L2Q14q11 or 7q34B-cell ALL5L3Qt(8;14), t(8;22), t(2;8)Clinical Features:Abrupt stormy onset; Symptoms related to depression of marrow functionFatigue due to anemia; Fever due to neutropenia & Bleeding due to thrombocytopeniaQMarrow expansion & infiltration of sub-periosteum: Sternal tendernessQGeneralized lymphadenopathy, hepatosplenomegaly & testicular enlargement due to neoplastic infiltrationCNS features: headache, vomiting & nerve palsies due to meningeal spreadT-ALL commonly presents with Mediastinal mass (Superior mediastinal syndrome)QDiagnosis:Hypercellular bone marrow with >20% lymphoblastsQCompared with myeloblasts, lymphoblasts have more condensed chromatin, less conspicuous nucleoli & scanty agranular cytoplasmQCytochemistry: Myeloperoxidase (MPO)-ve, Sudan Black B (SBB)-veQFAB (French American British) ClassificationALL-subtypeL1L2L3 (Mature B-cells)Morphology* Smalt homogenous blastsQ* Little cytoplasmQ* Regular nucleus* Small indistinct nucleoli* Large heterogeneous blasts* One or more nucleoli* Large homogenous blasts* Abundant basophilic cytoplasm* Prominent cytoplasmic vacuolation* Resemble Burkitt lymphomaQAge groupChildrenAdultsAdultsPrognosisGoodQIntermediateQPoorQCytochemistryPAS+PAS+PAS-, SBB+QBoth B-cell ALL & Burkitt lymphoma are characterized by FAB L3Q morphologyPrognostic Factors in ALLDeterminantsFavorableUnfavorableWBC counts<10 x 109/L (Low)Q>200 x 109/L (High)QAge3-7 yearsQ<1 year, >10 yearsGenderFemaleQMaleQEthnicityWhiteQBlackQNode, liver, spleen enlargementAbsentMassiveQTesticular enlargementAbsentPresentQCentral nervous systemAbsentOvert (blasts + pleocytosis)FAB morphologic features L1L1QL2QPloidyHyperdiploidyQHypodiploidy <45Cytogenetic markersTrisomies 4, 10 and/or 17t(12;21) (TEL-AML1)t(9;22) (BCR-ABL)t(4;11) (MLL-AF4)Time to remission<14 daysQ> 28 daysQDNA index>0.16Q< 0.16QImmunophenotypeEarly Pre-B cellT cell
Hyperploidy
Total leucocyte count greater than 50,000
Age
Response to steroids
Lukemia