~50%
of ALL cases occur
in adults 18 years old4

ALL in adult patients

~3000 adults patients are
diagnosed each year4,5


ALL develops from malignant cells within lymphocytes in the bone marrow3

  • Abnormal levels of T- or B-cell lymphoblasts accumulate in the bone marrow3
  • Diagnosis of ALL requires ≥20% of bone marrow to contain lymphoblasts1
Lymphocytes in the bone marrow Lymphocytes in the bone marrow

Pinch to zoom

Adapted from National Cancer Institute. Adult acute lymphoblastic
leukemia treatment (PDQ® )-health professional version3


While ALL originates in the bone marrow, it can migrate to the lymph nodes, liver, spleen, and central nervous system3

Patient demographics and symptoms Patient demographics and symptoms

Patient demographics

  • Median age among adults is 37 years2
  • More common in Hispanics and Whites5
  • ~30% more common in males5

Most patients present with cytopenia-related symptoms; additional signs and symptoms of ALL include1,3:

  • Weight loss
  • Fever
  • Night sweats
  • Bone or joint pain
  • Lymphadenopathy
  • Splenomegaly
  • Hepatomegaly
  • Difficulty breathing

Evaluations used for ALL diagnosis and risk assessment1

The NCCN recommends evaluation and treatment at specialized treatment centers with expertise in ALL management1

Diagnostic testing

Diagnostic testing1

  • Physical and labs
    • CBC, DIC panel, TLS panel, screen for infections, testicular exam, etc
  • Morphologic assessment of bone marrow
    • Hematopathology review to determine blast ratio
  • Immunophenotyping
    • Flow cytometry to identify ALL subtype
  • Cytogenetic analysis
    • Karyotyping to determine presence of high-risk features
  • Lumbar puncture
    • To determine presence of extramedullary disease
Pathological workup for risk stratification

Pathological workup for risk stratification1

  • Molecular characterization
    • FISH testing for genetic abnormalities, such as t(v;11q23.3)[KMT2A rearranged]
    • RT-PCR testing for BCR-ABL1 mutation
    • Next generation sequencing for gene fusions and pathogenic mutations
Minimal residual disease (MRD) testing and monitoring

Minimal residual disease (MRD) testing and monitoring1

  • MRD is the presence of leukemic cells below the detection threshold of ≥10-4 via conventional morphologic methods
  • Assess using bone marrow aspirate via flow cytometry, PCR, or next-generation sequencing (NGS)
  • An essential component of patient evaluation over the course of sequential therapy
  • NCCN recommended in patients with R/R disease after initial therapy, and at additional timepoints (dependent upon treatment regimen)

Classification of adult ALL is based on immunophenotype

Graph of T-cells and B-cells in adult cases Graph of T-cells and B-cells in adult cases

B-cells express the cell surface
antigen CD19 throughout their
maturation process1

Pinch to zoom


There are 4 key risk factors that affect the prognosis and management of B-cell precursor ALL in adults1,8,9

Age

Age8

Outcomes in adults with ALL worsen with increasing age

Cytogenetics

Cytogenetics1

Expression of certain cytogenetic abnormalities such as IKZF1, BCR-ABL, BCR-ABL1-like, and KMT2A are associated with worse outcomes

MRD Status

Minimal Residual Disease (MRD) status9

MRD positivity is associated with poor outcomes, including low survival rates and high risk of relapse

Time to relapse

Time to relapse1

Patients with early relapse (less than 18 months) have worse outcomes than patients with late relapse

Presence of these risk factors is often associated
with poor survival and higher risk of relapse1,8-10


ALL=acute lymphoblastic leukemia; BCR-ABL=breakpoint cluster region Abelson; CBC=complete blood count; CNS=central nervous system; DIC=disseminated intravascular coagulation; FISH=fluorescence in situ hybridization; IKZF1=Ikaros gene; KMT2A=lysine methyltransferase 2A; MLL=mixed lineage leukemia; MRD=minimal residual disease; NCCN=National Comprehensive Cancer Network; PCR=polymerase chain reaction; R/R=relapsed or refractory; RT PCR=reverse transcriptase-polymerase chain reaction; TLS=tumor lysis syndrome.

References: 1. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Lymphoblastic Leukemia V.2.2021 © National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed July 20, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. 2. Pulte A, Jansen L, Gondos A, et al. Survival of adults with acute lymphoblastic leukemia in Germany and the United States. PLoS One. 2014;9(1):e85554. doi:10.1371/journal.pone.0085554 3. National Cancer Institute. Adult acute lymphoblastic leukemia treatment (PDQ®)-health professional version. https://www.cancer.gov/types/leukemia/hp/adult-all-treatment-pdq. Updated January 13, 2021. Accessed July 7, 2021. 4. SEER*Explorer. Incidence and mortality comparison. National Cancer Institute. https://seer.cancer.gov/explorer/. Accessed June 10, 2021. 5. National Cancer Institute. Cancer stat facts: leukemia — acute lymphocytic leukemia (ALL). https://seer.cancer.gov/statfacts/. Accessed June 10, 2021. 6. Bassan R, Gatta G, Tondini C, Willemze R. Adult acute lymphoblastic leukaemia. Crit Rev Oncol Hematol. 2004;50(3):223-261. 7. Pui CH, Relling MV, Downing JR. Acute lymphoblastic leukemia. N Engl J Med. 2004;350(15):1535-1548. 8. SEER*Explorer. Survival. National Cancer Institute. https://seer.cancer.gov/explorer/. Accessed June 10, 2021. 9. Brüggemann M, Kotrova M. Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation. Blood Adv. 2017;1(25):2456-2466. 10. Saygin C, Papadantonakis N, Cassaday RD, et al. Prognostic impact of incomplete hematologic count recovery and minimal residual disease on outcome in adult acute lymphoblastic leukemia at the time of second complete response. Leuk Lymphoma. 2018;59(2):363-371.