Loading....
Coupon Accepted Successfully!

 

Acute Leukemia

 
Markers for various lineage
Lymphoid Lineage Myeloid lineage
B lineage T lineage Meyloid lineage
CD79a
cyt IgM
cyt CD22
CD19 – Pan B marker
CD10
CD20
 
TdT
CD24
CD3 (m/eyt) – Pan T marker
Anti-TCR a/b
Anti- TCR g/d
CD2
CD5
CD8
CD10
TdT
CD7
CD1a
Anti-MPO (monoclonal)
MPO cytochemistry
CD 117
CD 13
CD33
CD65s
Anti-MPO (polyclonal)
CD14
CD15
CD64
 
Important T cell Markers
Pan Tcell markers Subset markers
Markers that are common to all cells of a given type Pan T cell markers include
CD2
CD3
CD5
CD7
Markers that are present only on a subset of population of cells in a given lineage
Subset T cell markers include
CD4
CD8
 
CD Marker T cell
CD 45 RA
CD 45 RB
CD45 RC
CD45 RO
Subset T, medullary thymocytes “naïve” T cell
All leukocytes
Subset T, medullary thymocytes, “naïve” T cells
Subset T, cortical thymocytes, “memory” T cells

B-cell CD markers
Marker Status  
Type CD5 CD10 CD19 CD20 CD21 CD22 CD23 CD43 CD79a sIg cIg
Follicular 1 3 4 4   4 2 1 4 4 0
Nodal marginal zone 1 1 4 4   4 1 2 4 M4, D1 2
MALT 1 1 4 4   4 1 2 4 M4 2
Splenic Marginal zone 1 1 4 4   4 1 0 4 M4 2
CLL/SLL 4 0 4 4   4 4 4 4 D3 2
Lymphoplasmacytic
Waldenström’s
1 1 4 4   4 0 3 4 M4, D2 4
Mantle Cell 4 1 4 4   4 1 4 4 M&D 4 0
Precursor B-cell
(lymphoblastic)
4 3 4 4   4 0 0 4 0 0
Diffuse large B-cell 2 2 4 4   4 0 1 4    
Mediastinal large cell 2                    
Burkitt's 1 4                  
Intravascular B-cell                      
Footnote: 0 = negative, 1 = <10% positive, 2 10-50% positivity, 3 = 50-90% positivity and 4 = >90% positive
 
T-cell CD markers
Marker Status
Type CD3 CD5 CD7 CD4 CD8 CD30 NK16/56
T-prolymphocytic leukaemia + - + +(-) -(+) - -
T-large granular lymphoproliferative + - + - + - +(-)
Mycosis Fungoides + + + - -(+) -(+) -
Cutaneous ALCL + +(-) +(-) +(-) - ++ -(+)/-(+)
Primary systemic ALCL +(-) +(-) +(-) -(+) -(+) ++ -
Peripheral T-cell lymphoma, unspecified +(-) +(-) -(+) +(-) -(+) -(+) -(+)/-(+)
Subcutaneous panniculitis-like T-cell + + + -(+) +(-) -(+) -/-(+)
Hepatosplenic T-cell lymphoma + - + - - - +/+(-)
Angioimmunoblastic T-cell lymphoma + + - +(-) -(+) - -
Extranodal NK/Tcell lymphoma S -, C + - -(+) -(+) - - -/+
Enteropathy-associated T-cell lymphoma + + + -(+) +(-) +(-) -
Adult T-cell leukaemia/lymphoma + + - +(-) -(+) +(-) -
Footnote: + = >90% positive: +(-) = >50% positive; -(+) = <50% positive; - = <10% positive.
ALCL-Anaplastic large cell lymphoma; C=Cytoplasmic; S-Surface.


Acute Lymphoblastic leukemia (ALL) may be associated with t(4;11), t(9;22) or t(8; 14) but association with t(9:20) is not seen.
Type of Leukemia Translocation Deletion (-) / Trisomy (+)
CML   t(9; 22)1 Philadelphia      chromosome  -
AML  t(8; 21), t(9;22)  +8, 7-, 5-, 7q, 5q-
AML  t(9; 11), t(1l; 23)  -
Acute Promyelocytic leukemia (M3)  t(15; 17)  
ALL  t(4; II), t(9; 22), t(8; 14)  20q-
CLL  -  +12
Erythroleukemia  -  7q-,5q-
PCV -  20q-
Burkitt lymphoma T(8:14) -

Leukemias

Leukemias are malignant neoplasms of the hematopoietic stem cells, arising in the bone marrow, that flood the circulating blood or other organs.
 
Acute Lymphocytic Leukemia (ALL)
ALL (Working Classification)
L1     Small round blasts with scanty cytoplasm
L2     Pleomorphic larger blasts with more cytoplasm and prominent nucleoli
L3     Vacuolated cytoplasm with vesicular nuclei.

 
Clinical Features
  1. ALL is common in children
  2. AML in young and middle – aged.
  3. Onset is abrupt and stormy, and patients present within 3 months of the onset of symptoms.
  4. Fatigue, anemia, fever (due to infection), bleeding episodes (petechiae, ecchymoses, epistaxis, gum bleeding, fundal hemorrhage) secondary to thrombocytopenia;
  5. Bone pain and tenderness due to marrow involvement and subperiosteal bone infiltration are seen.
  6. CNS involvement is due to leukemic infiltration of the meninges, resulting in headache, vomiting, papilledema, cranial nerve palsies etc.
  7. ALL presents with hepatosplenomegaly and lymphadenopathy.
  8. Patients are prone to super impose infection by bacteria, HZV, CMV, measles, candidiasis, pneumocystic carinii   
Important Points:: - Pathology of ALL
  1. ALL blasts do not contain azurophilic granules  
  2. ALL blast contain PAS positive material.             
  3. Terminal deoxy transferase (TdT) is present in 95% cases.
Classification of Acute lymphoid leukemia (ALL) 
Immunologic Subtype % of Cases FAB Subtype Cytogenetic Abnormalities
Pre-B ALL 75 L1, L2 t(9;22), t( 4, 11), t(1; 19)
T Cell ALL 20 L1, L2 14q 11 or 7q34
B Cell ALL 5 L3 t(8; 14), t(8; 22), t(2;8)


Immunophenotypic Classification for ALL
FAB
classification
Immunologic
classification
Phenotype
Pre-B Cell Early Pre-B CDI9, CD20-/+, CDIO, CD34, TdT
Pre-B CDl9, CD20+/-, CDI0, CD34-, clgM, Tdt+/-
B cell B cell CDl9, CD20, CD22, CD10+/-, CD34-, Tdt-, sIg
T cell T cell CD1, CD2, CD3, CD5, CD7, CD10+/-, CD34-/+, Tdt, dual CD4/CD8
Pre B-cell ALL are the commonest types of Acute Lymphoblastic leukemias and account for upto 75% of all ALL Characteristic Features of T cell ALL (20% of ALL)
  1. Occurrence in older children (adolescents) and adult
  2. Predilection for males                               
  3. Presence of anterior mediastinal mass in upto half of the cases at presentation (thymic mass)
  4. Early CNS involvement (Early dissemination to meninges and testes)
  5. High WBC count often greater than 100,000/mm3
The presence of a mediastinal mass in a young adolescent male suggests the diagnosis of precursor T cell ALL. Precursor T cell ALL is phenotypically characterized by an immature T cell phenotype and is positive for TDT and CD7 and may be positive for CD34.

Investigations

  1. Anemia (normal or raised MCV)
  2. WBC count: 50,000 – 100,000/mL
  3. Blood film: Shows blast cells and other primitive cells
  4. Bone marrow examination: Hypercellular bone marrow with blasts replacing normal cells to varying degrees (30% or more)
  5. Presence of larger blasts, lower nuclear – cytoplasmic ratio and Auer rods in the cytoplasm of blast cells indicate a myeloblastic type of leukemia
  6. Thrombocytopenia and spontaneous bleeding, especially with platelet count (20,000/mL)

Management of ALL

ALL
Remission induction CNS prophylaxis
Prednisolone
Vincristine
Daunorubicin
L- Asparaginase
Methotrexate
Intrathecal methotrexate (or cytarabine)
Cranial irradiation
Consolidation Maintenance
Cyclophosphamide
Vincristine
Cytarabine
6-Mercaptopurine
Prednisolone
Vincristine
Daunorubicin
L – Asparaginase
Methotrexate
6-MP

Combination of intrathecal methotrexate and cranial irradiation for CNS involvement.
Agents used for intrathecal chemotherapy
a. Methotrexate                   b. Cytarabine                        c. Thiotepa

Poor Prognostic Factors

  1. High white cell count at presentation (> 100,000/mL)
  2. Male sex
  3. Age <2 or > 10 years
  4. Chromosomal abnormalities
    Philadelphia chromosome (15% of adults) – poor prognosis
    Ph chromosome is most commonly found in non – T, non – B – cell ALL, and is nerve found in T – cell ALL and hence there is a better prognosis in the latter variety
  5. Pre – B – cell ALL with t(1: 19) translocation – poor prognosis
  6. Mature B – cell ALL with t(8 : 14) translocation – very poor prognosis
  7. CNS involvement
  8. L2 and L3 stages.
Good prognostic factors. (LQ 2012)
  1. Low WBC count <50,000/mL                 
  2. Age 2 -10 yrs (LQ 2012)                                               
  3. Female sex      
  4. No dissemination                                    
  5. Hyperdiploidy (LQ 2012)                             
  6. DNA index >.16
  7. Early pre B cell stage (LQ 2012)           
  8. 70% of patients survive for 5 years when they have good prognostic indices (curable)
Hematological evidence of remission.
1. No evidence of leukemia in blood or bone marrow.             
2. BM blast cell < 5%.




Test Your Skills Now!
Take a Quiz now
Reviewer Name