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Pediatric & Adult Acute Lymphoblastic Leukemia

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Journal Article: Association Of Minimal Residual Disease With Clinical Outcome In Pediatric & Adult Acute Lymphoblastic Leukemia: A Meta-analysis

Journal: JAMA Oncology, Volume 3, 2017

DOI: 10.1001/jamaoncol.2017.0580

Introduction:

  • Minimal residual disease (MRD) refers to the presence of disease in cases deemed to be in complete remission by conventional pathologic analysis.
  • Detecting MRD in various hematological malignant diseases has been associated with higher relapse rates – these include chronic myeloid leukemia (CML), acute myeloid leukemia (AML), acute and chronic lymphoblastic leukemia (ALL and CLL), and multiple myeloma.
  • Minimal residual disease in patients with ALL can be measured in several ways, including by multiparametric flow cytometry (MFC), by polymerase chain reaction (PCR) of the IgH VDJ and/or TCR gene rearrangements, and by leukemia specific fusion transcripts (eg, BCR-ABL).
  • The authors identified 39 studies with 13,637 patients to assess the association of MRD with clinical outcome in ALL.

Results:

Clinical outcomes MRD-negative patients MRD-positive patients
Pediatric Patients
Disease-free after 10 years 77% 32%
Alive after 10 years 84% 55%
Adult Patients
Disease-free after 10 years 64% 21%
Alive after 10 years 60% 15%
Patient age Hazard ratios
EFS (Event-Free Survival) OS (Overall Survival)
Pediatric patients 0.23 0.28
Adult patients 0.28 0.28

On MRD status, hazards are much higher for adult patients than for pediatric patients in the first 3 years. Hazards for adults were comparable or possibly even lower than for pediatric patients in subsequent years.

Also, the relationship between MRD and EFS can be exploited for the following:

  • In clinical practice, assigning patients who have MRD to alternative therapy, perhaps an allograft or a clinical trial.
  • As a research tool for better defining patients at high risk for recurrence and eligibility for clinical trials.
  • Assigning the highest priority for definitive evaluation in phase 3 trials for therapies that achieve the lowest rates of MRD.
  • Providing supportive data in regulatory decisions based primarily on complete response rates with incomplete hematological recovery (as in the approval of blinatumomab).
  • Extrapolating from disease types where therapy has a known effect on other hematological malignant diseases where it shows a benefit on MRD.

The full article can be accessed at: https://jamanetwork.com/journals/jamaoncology/fullarticle/2626509

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