Acute lymphoblastic leukemia /lymphoma

1. ALL Risk Stratification
Yahya mulikandathil

2. Agenda
Definition
Pathogenesis
Classification
Risk stratification
Summary
`Risk stratification ALL NCCCR fellow activity 2

3. o Which one of the ALL has poor risk
Presentation title 3
I. High Hyper diploidy
II. WBC < 100 in T-ALL, WBC < 30 IN B ALL
III. ETV 6- RUN X ,t (12-21) ( p13-22)
IV. Trisomy 4, 10 , 17
V. None of these

4. Introduction
Acute lymphoblastic leukemia/lymphoma : 2nd most common acute
leukemia in adult population
Is abnormal proliferation of lymphoid progenitor cells in BM , blood ,
extramedullary site
More common in children
Devastating disease when occurs in adult
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5. • In ALL Bone marrow LYMPHOBLAST exceeding 20 % called leukemia
Less than 20 lymphoblast lymphoma
• WHO 2017 ,reclassified as LBL lymphoblastic leukemia/lymphoma
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6. Epidemiology
 1-5 cases per 100000 population
 More common in males than females
 Peak age , 6 year and 2nd peak in >60 ages
 B ALL more common T ALL
 Previous name s pro B lymphoblastic leukemia ,precursor B
lymphoblastic leukemia , common precursor lymphoblastic leukemia
/lymphoma
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7. Classification
 B cell lymphoblastic leukemia/lymphoma (B cell ALL/LBL)
 T cell lymphoblastic leukemia/lymphoma (T cell ALL/LBL)
Based on cell involvement
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8. Classification
 L1
 L2
 L3
Based on cell size, cytoplasm, nucleoli, vacuolation and basophilia
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9. Classification
 B lymphoblastic
 T lymphoblastic
 Burkitt-cell Leukemia
Based on morphology and cytogenetic profile of the leukemic blasts,
B-lymphoblastic leukemia was divided into two subtypes: B-ALL with
recurrent genetic abnormalities and B-ALL not otherwise specified.
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10. Presentation title 10
WHO CLASSIFICATION 2022

11. Risk factor
 Ionizing radiation
 Pesticides, certain solvents or viruses such as Epstein-Barr Virus and
Human Immunodeficiency Virus
 Idiopathic
 Genetics
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12. Diagnostic work up
• Peripheral smear
• BM Biopsy –Morphology ,Immunophenotype ,Genetic aberration
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13. Peripheral smear
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14. BM aspirate
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15. BM biopsy
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16. Immunophenotype
• Distinguish B-ALL ,T-ALL or Mature Lymphoid Neoplasm
• T-ALL –CD 3+ ,TDT+ ,CD 7 + weak
• B-ALL 2 of CD19, cCD79a, or CD22 ,TDT+
• Mature lymphoblastic lymphoma : TDT (negative),strong expression of
CD 20
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17. Presentation title 17

18. Risk stratification
 Allows initial treatment and plan for Allo-HSCT
 Historically High WBC , Age at time of diagnosis
Ages > 60-year, long term survival ~10 -15 %
 Philadelphia chromosome positive, hypodiploidy and complex
karyotype
Presentation title

19. Trial MRC UKALL XII/ECOG E2993
 Largest prospective trial to determine optimal treatment
 >30 × 10 9 for B-ALL or >100 x 109 for T-ALL, was an independent
prognostic factor for DFS and OS
 Ph negative categorized (ages >35 ,high WBC)
 low risk – NO risk factor
 Intermediate either ages >35 or high wbc
 High- both ages and wbc
 5-year OS ~55, 34 , 5 %
Presentation title 19

20.  Cytogenetic abnormities important prognostic factor for os and
treatment
 Historically Ph Positive( t 9-22) 1 year survival ~10 %
 TKI has improved survival in Ph positive ALL
 Prevalence of Ph positive ~ranges 15-50 % , also increases with ages
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21. • Race
• CNS involvement
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22. Another risky cytogenetics
 t(4;11)
 KMT2A translocation
 t(8;14)
 complex karyotype (⩾ 5 chromosomal abnormalities)
 Low hypodiploidy (30–39 chromosomes)/near triploidy (60–78
chromosomes)
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23.  Hyperdiploidy and del(9p) had a significantly better outcome in This
trial
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24.  Southwest Oncology Group (SWOG) showed that among the 200 study
patients, cytogenetic profile was a more important prognostic factor
than age or WBC count
 a subset of high-risk ALL without t(9;22) has been identified with a
genetic profile similar to that of Ph-positive ALL. This so called, Ph-like
ALL has been associated with poor response to induction
chemotherapy, elevated minimal residual disease and poor survival.
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25.  Historically, treatment response was evaluated morphologically.
 Recently, it has become standard practice to evaluate patients for
minimal residual disease (MRD) using molecular techniques such as
flow cytometry and PCR
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26.  Several studies have shown the importance of MRD in assigning risk
 Re-stratified standard-risk patients to low risk, intermediate risk and high risk with
relapse rates of 0%, 47% and 94%, respectively, based on the persistence of
elevated MRD, defined as >10 − 4
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27.  In a multivariate analysis of 326 adolescent and adult patients with
high-risk Ph-negative ALL treated in The Programa Espanol de
Tratamientos en Hematologia (PETHEMA ALL-AR-03), Ribera et al.35
showed that poor MRD clearance, defined as levels >1 × 10 − 3 after
induction and levels >5 × 10 − 4 after early consolidation by flow
cytometry, was the only significant prognostic factor for disease-free
and overall survival
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29. National Comprehensive Cancer Network (NCCN)
 Based on what is known about prognostic factors in adult ALL, the National
Comprehensive Cancer Network (NCCN) has developed recommendations to
approach risk stratification
 The National Cancer Institutes defines adolescent and young adults (AYA) to be
those aged 15–39 years.
 The NCCN recognizes that AYA may benefit from treatment with pediatric-inspired
regimens and thus are considered separately from adults >40 years.
 Both age groups are then stratified into high-risk Ph-positive and standard-risk Ph-
negative subgroups.
 The Ph-negative subgroup can further be categorized as high-risk based on the
presence of MRD, elevated WBC (defined above) or unfavorable cytogenetics
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30. Presentation title 30

31. o Which one of the ALL has poor risk
Presentation title 31
I. High Hyper diploidy
II. WBC < 100 in T-ALL, WBC < 30 in B ALL
III. ETV 6- RUN X ,t (12-21) ( p13-22)
IV. Trisomy 4, 10 , 17
V. None of these

32. Summary
o Age less than 35 , wbc less than 30 in B-ALL , less than 100 in T-
ALL has favorable risk factor
o MRD clearance favors good outcome
o Genetics: hypoploidy ,Ph +ve , Ph like +ve, KMT2A ,t(v 14-
q32/IgH), complex cytogenetic carrier poor out come
Presentation title 32

33. Thank you
Yahya mulikandathil
NCCCR

34. Reference
• Upto date
• ASH SAP 8 th edition
• Acute lymphoblastic leukemia: a comprehensive review and 2017
update Citation: Blood Cancer Journal (2017) 7, e577;
doi:10.1038/bcj.2017.53 www.nature.com/bcj
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35. Presentation title 35