Feasibility of Treating Post-Transplantation Minimal Residual Disease in Children with Acute Leukemia

Abstract

Outcomes for patients with hematologic malignancies who experience overt relapse after allogeneic hematopoietic stem cell transplantation (HCT) are poor. There are limited data on outcomes of post-transplant minimal residual disease (MRD). In this single institution, retrospective cohort analysis of children with acute leukemia and myelodysplastic syndrome we document the pattern of relapse with a primary focus on outcomes of post-transplant MRD. Forty of 93 (43%) patients who underwent a first allogeneic HCT and who all had systematic pre and post-transplant MRD evaluations at +30, +60, +90, +180 days and at +1 and +2 years post-transplant, experienced relapse. The median time to relapse was 4.8 months post-transplant with a median survival of 4 months post-relapse. Despite frequent, systematic, routine post-HCT disease restaging evaluation, 31 patients (78%) presented with overt disease at the time of relapse. 7 patients with acute leukemia who had post-transplant MRD, presented at a median of 1 month post-transplant. Due to rapid disease progression or treatment-related mortality (TRM), there was no improvement in survival for those patients whose leukemia was detected in a state of MRD post-transplant. Our results suggest that early intervention strategies targeting post-transplant MRD for relapse prevention in acute leukemia may not be feasible.

Persistent Multiyear Control of Relapsed T‐Cell Acute Lymphoblastic Leukemia With Successive Donor Lymphocyte Infusions: A Case Report

“…[5] The indolent course of disease in this particular patient is in marked contrast to the usual rapid progression among hematologic malignancy HSCT patients who relapse. [15] It may be that the indolent course of recurrence in this case (with first MRD recurrence >1 year after transplant, and only very slowly rising MRD after detection) is itself an indicator of significantly but not completely effective GVL in the original graft that would be most likely to be amenable to a boost with DLI. Alternatively, it is possible that GVL was sufficient such that the de-tectable MRD might have spontaneously resolved even had DLI been deferred, or that the single cyclophosphamide dose alone was sufficient to reinduce remission.…”

“…The indolent course of disease in this particular patient is in marked contrast to the usual rapid progression among hematologic malignancy HSCT patients who relapse . It may be that the indolent course of recurrence in this case (with first MRD recurrence >1 year after transplant, and only very slowly rising MRD after detection) is itself an indicator of significantly but not completely effective GVL in the original graft that would be most likely to be amenable to a boost with DLI.…”

Prophylaxis and treatment of acute lymphoblastic leukemia relapse after allogeneic hematopoietic stem cell transplantation

“…A recent retrospective cohort analysis of children with acute leukemia after transplantation by Shah et al 31 suggested that there was no improved survival in those patients whose leukemia was detected in a state of MRD post transplantation. This indicates that the relationship between MRD and ALL relapse might be more complex than we thought, and other significant factors may need to be investigated before drawing conclusions regarding the exclusivity of using MRD alone as a metric for prediction of post-allo-HSCT relapse.…”

Future of Allogeneic Hematopoietic Stem Cell Transplantation for Chemotherapy-Resistant Pediatric Acute Leukemia: Potential Advances

“…This is especially important given that the tempo of pediatric post-HCT relapse is typically rapid, generally making preemptive management when persistent or recurrent disease is detected after HCT either impossible or ineffective [2]. With the advent of new highly sensitive tools for MRD monitoring the feasibility of identifying post-HCT MRD with sufficient lead time to effectively intervene may improve [22].…”

“…Unfortunately, relatively little reduction has been achieved in relapse rates, making relapse now the most frequent cause of failure of HCT for leukemia [1]. Relapse occurs in 10-30% of HCTs performed for pediatric leukemia in remission and has a dismal prognosis: the median survival of children with post-HCT relapse is 4 months [2]. In order to further improve overall survival after allogeneic HCT for pediatric leukemia, novel strategies to address post-HCT leukemia relapse are crucial.…”