Pediatric & Adult Acute Lymphoblastic Leukemia

May 20,2022
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SUBURBAN JOURNAL CLUB

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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
Patient age	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