Outcome of children who experience disease relapse following allogeneic hematopoietic SCT for hematologic malignancies

Abstract

Relapse after allogeneic hematopoietic SCT (HSCT) carries a poor prognosis and is a common cause of death. Outcomes of children who relapse post HSCT are not well known. In this retrospective multicenter study we included 532 patients who underwent allogeneic HSCT and examined the outcomes of 160 patients (30%) who relapsed. Treatment options after relapse included (i) palliative therapy with non-curative intent (n ¼ 43), (ii) salvage chemotherapy (without a second HSCT, n ¼ 55) or (iii) salvage chemotherapy followed by a second HSCT (n ¼ 62). Sixty two patients underwent a second HSCT. The 1-year disease-free survival (DFS) for those given palliative therapy, chemotherapy alone and who underwent a second transplant was o1%, 9% and 50% (P ¼ o0.0001), respectively. The DFS at 1 and 2 year was 50% and 35%, respectively, among the patients who received a second transplant versus 9% and 2% in those who did not (P ¼ o0.0001). In multivariable analysis longer time to relapse (P ¼ 0.04) and undergoing a second HSCT (Po0.001) were associated with improved outcome. Withdrawal of immunosuppressive therapy, followed by curative intent chemotherapy should be offered to all patients who relapse after an allogeneic HSCT. A second HSCT should be considered, especially in patients who respond to salvage chemotherapy. INTRODUCTIONRelapse of the primary malignancy after HSCT is a common cause of transplant failure. According to the Center for International Blood and Marrow Transplantation and Research data, relapse accounts for 41% of deaths after matched-sibling donor HSCT and 34% of deaths after unrelated-donor HSCT. 1 In the recent European Bone Marrow transplantation report on behalf of the acute leukemia working party, the 5-year OS was 8 ± 1% for adults who experience relapse post-transplant. 2 Similarly, patients who experience relapse after reduced intensity conditioning (RIC) HSCT, have a 2-year OS of 29%. 3 Second allogeneic HSCT has always been considered a potential treatment option for patients who relapse following their first transplant. In a retrospective study of 150 adult patients who underwent a second HSCT, the reported 5-year OS and disease-free survival (DFS) were 32% and 30%, respectively; the risks of relapse and a non-relapse mortality (NRM) were 44% and 45%, respectively. 4 Kurosawa et al. 5 from Japan reported that the 1-year OS after post-transplant relapse was significantly better at 58% in patients who had a second HSCT as compared with 14% in the cohorts who got chemotherapy or no intervention with curative intent. They concluded that for patients who relapse after transplant, successful re-induction chemotherapy and a second HSCT may be effective for prolonging survival without excessive NRM. While the overall prognosis of patients relapsing after a RIC HSCT is poor, interventions such as the combined use of immunotherapy and chemotherapy can improve patient

Relapse post hematopoietic SCT remains the Achilles heel for the field

“…Unlike what has been observed in adult patients, pediatric patients who received a second HSCT had a significantly improved survival compared to those who were treated with salvage therapy without HSCT (35% vs 2%). 8 It is also clear from our data that there is no consistent approach regarding the preparative regimen, intensity or timing of the second HSCT. A report from the CIBMTR on the outcome following second allogeneic HSCT in patients with acute and chronic leukemia found that patients younger than 20 years and those who relapse 46 months from the first HSCT have improved survival.…”

“…[8][9][10][11][12][13] In a study by the Seattle group the authors reported on the outcome of 307 adult patients who relapsed following HSCT. The 2-year survival was 3-19% depending on the time from transplant to relapse, with those experiencing relapse 4200 days having the best outcome.…”

“…One hundred and seventeen patients received salvage therapy and, interestingly, among the 78 patients with available detailed re-induction therapy 25 different regimens were used. 8 The number of regimens used in those patients underscores the lack of uniform therapy for children who relapse following allogeneic HSCT. Unlike what has been observed in adult patients, pediatric patients who received a second HSCT had a significantly improved survival compared to those who were treated with salvage therapy without HSCT (35% vs 2%).…”

Open access? Widening access to chimeric antigen receptor (CAR) therapy for ALL

“…Within relapsed patients, high risk groups are identifiable by timing and site of relapse and have a long term event free survival of 30% or less even with allogeneic stem cell transplantation (allo-sct) 3,5,6 . The outcomes of those relapsing following allo-sct are dismal, with long term survival of only 10-20% in those undergoing second transplantation procedures [7][8][9] , which was also associated with significant adverse toxicity. For these groups, novel therapies were urgently needed, and access to CAR T cell therapy has been a "game-changer" in terms of outcomes.…”

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

“…(3, 4, 6) However, with frequent post-transplant surveillance and more sensitive measures of detection, disease recurrence could, in theory, be detected both earlier and at a state of lower disease burden that may be more amenable to treatment, potentially leading to improved outcomes. (10–12) Certainly, preemptive immunotherapy in the setting of mixed chimerism has shown promise in relapse prevention.…”