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Posttransplant minimal residual disease may predict relapse for childhood ALL
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Minimal residual disease after allogeneic stem cell transplantation may be prognostic for relapse in children with acute lymphoblastic leukemia, according to study findings.
“Allogeneic stem cell transplantation (allo-SCT) is the only curative treatment option for the great majority of children and adolescents with ALL who relapsed after a having achieved a first remission induced by multimodal chemotherapy,” Peter Bader, MD, of the department for stem cell transplantation and immunology at University Hospital for Children and Adolescents in Frankfurt, Germany, told HemOnc Today. “However, even after allo-SCT, relapse remains the major cause for treatment failure in these patients.”
In a prior study, Bader and colleagues confirmed that the risk for ALL relapse in children was strongly dependent on the minimal residual disease (MRD) level at the time of stem cell transplantation.
In the current prospective study, Bader and colleagues aimed to further elucidate the impact of posttransplant MRD for the prediction of relapse after allogeneic transplantation.
The researchers identified 113 children with relapsed ALL who underwent allo-SCT.
MRD was assessed in the bone marrow on days 30, 60, 90, 180 and 365 after transplantation.
The follow-up time was considered from the point of transplantation to the last observation in continuous complete remission. Median follow-up was 5.1 years (range, 3.4-6.5).
Researchers divided patients into three groups: those with undetectable MRD loads (MRD-negative), those with detectable loads less than 10-4 leukemic cells (MRD-low), and those with detectable loads greater than 10-4 leukemic cells (MRD-high).
Among all patients, 3-year probability of EFS was 55%. The cumulative rate of relapse was 32%, and the rate of treatment-related mortality was 12%. The probability of 3-year EFS was 60% for patients who received their transplantations in their second complete remission, 50% for patients who received stem cell transplants in their third or greater complete remission, and 0% for patients who were not in remission (P = .015).
MRD prior to transplantation was inversely correlated with EFS (P = .009) and positively correlated to the incidence of non-relapse mortality (P = .039). However, it showed no correlation with cumulative incidence of relapse.
MRD after transplantation was inversely correlated with EFS (P = .004) and positively correlated with cumulative incidence of relapse (P < .01).
MRD-high status consistently correlated with an inferior EFS (P < .003).
Among patients in the MRD-low group, the probability of 3-year EFS increased with the time interval from the date of their transplant. Those who were MRD-negative at 30-days post-transplantation had a 61% (± 6%) probability of 3-year EFS, and those who were MRD-negative at 365 days post-transplantation had a 93% (± 5%) probability of 3-year EFS. However, all patients in whom MRD was not eliminated by day 365 eventually experienced relapse.
The cumulative incidence of relapse declined with time among patients who were MRD-negative, declining from 27% (± 5%) among those who were MRD-negative at 30 days post-transplantation to 7% (± 5%) among those who were MRD-negative at 365 days post-transplantation.
Researchers observed a similar trend in the MRD-low group. Cumulative incidence of relapse was 58% (± 15%) among those classified as MRD-low at 30 days post-transplantation and declined to 29% (± 13%) among those who were MRD-low at 180 days post-transplantation.
“We could show that all patients who develop MRD after transplantation and achieve a level of residual disease of greater than 10-4 will finally relapse,” Bader said. “These are patients in whom, we believe, pre-emptive treatment will be justified. For current, evolving, new and leukemia-specific cellular treatment options (eg, CAR-modified anti-CD19 T cells) or CD19-directed antibodies, this patient group will be the target treatment population. Based on this, we believe that our manuscript will serve as the platform for further therapy trials assessing the value of new treatment options.” – by Anthony SanFilippo
For more information:
Peter Bader, MD, can be reached at peter.bader@kgu.de.
Disclosure: The researchers report financial or other relationships with Amgen, AOP Orphan, Amomed, Astellas Pharma, Bayer, BB Biotech, CSL Behring, EUSA Pharma, Fresenius Biotech, Gentium, Genzyme, Gilead Sciences, Medac, Miltenyi, MSD, Neovii, Novartis, Pfizer, Pierre Fabre, Riemser and Therakos.
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