Second allogeneic hematopoietic SCT for relapsed ALL in children

Abstract

A second SCT is generally accepted as the only potentially curative approach for ALL patients that relapse after SCT, but the role of second SCT for pediatric ALL is not fully understood. We performed a retrospective analysis of 171 pediatric patients who received a second allo-SCT for relapsed ALL after allo-SCT. OS at 2 years was 29.4 ± 3.7%, the cumulative incidence of relapse was 44.1±4.0% and non-relapse mortality was 18.8±3.5%. Relapse occurred faster after the second SCT than after the first SCT (117 days vs 164 days, P ¼ 0.04). Younger age (9 years or less), late relapse (180 days or more after first SCT), CR at the second SCT, and myeloablative conditioning were found to be related to longer survival. Neither acute GVHD nor the type of donor influenced the outcome of second SCT. Multivariate analysis showed that younger age and late relapse were associated with better outcomes. Our analysis suggests that second SCT for relapsed pediatric ALL is an appropriate treatment option for patients that have achieved CR, which is associated with late relapse after the first SCT. Keywords: second transplantation; relapse; ALL; children INTRODUCTION SCT is the most effective treatment for high-risk and refractory leukemia, but relapse is still a major event of allo-SCT. It is generally accepted that a second SCT is the only potentially curative approach for patients who relapse after allo-SCT, but only some patients are eligible for a second SCT because of the high mortality and morbidity associated with repeated allo-SCT. In addition, high relapse rates occur because of the resistance of leukemic cells that have not been eliminated by the first SCT. Some previous studies have examined the role of second SCT, 1 --10 but because of the small number of patients in these studies, the efficacy and safety of second allo-SCT for pediatric ALL patients that have relapsed after SCT remains unclear.In this study, to investigate the prognostic factors of second SCT and identify subgroups for whom second SCT is effective, we performed a retrospective analysis of 171 patients who received a second SCT for relapsed ALL after allo-SCT.

Pediatric posttransplant relapsed/refractory B-precursor acute lymphoblastic leukemia shows durable remission by therapy with the T-cell engaging bispecific antibody blinatumomab

“…Therefore, blinatumomab can facilitate long-term survival by inducing complete remission for subsequent HSCT. 6 At a median observation time of 398 days, the event-free survival in our cohort of patients is 30%. Three of 9 patients remain in ongoing complete remission.…”

“…When blinatumomab was started the blast load was 97% in the bone marrow. After the 1 st cycle of treatment, the patient reached the MRD level of 1x10 6 and after the 2 nd cycle there was no longer any detectable MRD (<1x10 6 ). The figure shows the effect of blinatumomab on the absolute counts of CD3 + , CD4 + , CD8 + and CD19 + cells as well as the course of the MRD level (PCR) displayed on the secondary axis.…”

“…1,2 Despite several advances over the last decade which led to significantly reduced transplantrelated mortality, relapse rates are still high and represent the major cause of death in these patient cohorts. [3][4][5][6] Level of pre-transplant minimal residual disease (MRD) has been shown to be an important adverse prognostic parameter for estimating the risk of relapse; MRD, therefore, influences long-term event-free survival after allogeneic stem cell transplantation. [7][8][9][10][11][12] In particular, patients who relapsed posttransplant have an extremely poor prognosis and need to achieve another hematologic remission or an even more advantageous very low or negative MRD level before proceeding to a subsequent SCT.…”

“…[7][8][9][10][11][12] In particular, patients who relapsed posttransplant have an extremely poor prognosis and need to achieve another hematologic remission or an even more advantageous very low or negative MRD level before proceeding to a subsequent SCT. 6 Additional chemotherapy will often be of limited benefit and may be associated with high toxicity. 7,8 Moreover, with duration and progression of relapsed ALL, treatment faces multi-drug resistance which constitutes an unsolved problem.…”

Successful Treatment With Third Stem Cell Transplant From an Allogeneic Donor for a Patient With Relapsed Diffuse Large B-Cell Lymphoma

“…14,15 In our patient, a favorable outcome was achieved, probably because recurrence occurred 4 years after the first allo-SCT and because HCT-CI at second allo-SCT remained good. There are no confirmatory data about an advantage for the selection of a different donor for the second SCT, 16 although there are reports about this selection, including a study showing that different donor has a trend toward better outcome. 15 In conclusion, we treated a patient with DLBCL recurring after autologous transplant and allo-SCT who underwent second allo-SCT and achieved a good therapeutic effect.…”