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Pediatric & Adult Acute Lymphoblastic Leukemia

  • May 20,2022
  • 2 Min Read
Pediatric & Adult Acute Lymphoblastic Leukemia

SUBURBAN JOURNAL CLUB

A monthly precis of some of the best, most influential journal articles.

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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