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

Abstract

Relapse of acute lymphoblastic leukemia remains a major cause of death in patients following allogeneic hematopoietic stem cell transplantation. Several factors may affect the concurrence and outcome of relapse, which include graft-versus-host disease, minimal residual disease or intrinsic factors of the disease, and transplantation characteristics. The mainstay of relapse prevention and treatment is donor leukocyte infusions, targeted therapies, second transplantation, and other novel therapies. In this review, we mainly focus on addressing the impact of graft-versus-host disease on relapse and the prophylaxis and treatment of acute lymphoblastic leukemia relapse following allogeneic hematopoietic stem cell transplantation. We also make recommendations for critical strategies to prevent relapse after transplantation and challenges that must be addressed to ensure success.

TcRαβ-depleted haploidentical transplantation results in adult acute leukemia patients

“…Relapse-related death rates were higher among ALL patients. In general, the main cause of mortality was relapsing among ALL patients after allogeneic stem cell transplantations [18]. In our cohort, frequency of relapse rates in post-transplant ALL patients might be due to the general opinion of weak graft-versus-malignancy effect, but also [19] it might be due to early relapsing of patients before development of graft-versus-leukemia effect.…”

Haploidentical transplantation compared with matched sibling and unrelated donor transplantation for adults with standard‐risk acute lymphoblastic leukaemia in first complete remission

“…However, Solomon et al (2016) reported that the relapse rate was not different between ALL and AML after allo-HSCT. It has been reported by other studies that ALL could benefit from the GVL effect by DLI intervention (Yan et al, 2012;Chen et al, 2015), including patients with ALL relapse post-transplantation (Terwey et al, 2013;Yan et al, 2016).…”

“…We also analysed GRFS, and found that the 1year and 3-year GRFS of HID transplants was equivalent to those of the MSD and MUD transplants. It has been reported by other studies that ALL could benefit from the GVL effect by DLI intervention (Yan et al, 2012;Chen et al, 2015), including patients with ALL relapse post-transplantation (Terwey et al, 2013;Yan et al, 2016). Increasingly, improvements have been made in prophylaxis for GVHD, such as the use of T-cell depletion in vivo by means of Cy or ATG (Bashey et al, 2013;Luo et al, 2014;Chang et al, 2016b).…”

Hematopoietic Stem Cell Transplantation for Adult Acute Lymphoblastic Leukemia in the Era of Novel Agents and Targeted Therapies

“…However, allogeneic HSCT offers the best and may be the only chance for cure in adult patients with relapsed ALL [103][104][105]. GVHD, MRD, intrinsic factors of the disease and transplantation characteristics affect the occurrence as well as the outcome of ALL relapse after HSCT [106]. Unfortunately, the prognosis of patients with ALL who relapse after HSCT and those who are refractory to chemotherapy is extremely poor with ˂ 10% long-term survival [23,78,107].…”

“…Management of ALL relapse post-HSCT includes: tapering of immunosuppressive therapy; salvage chemotherapy followed by second allogeneic HSCT; pre-emptive immunotherapy in the form of DLI with frequent MRD monitoring; post-transplantation maintenance therapy; the use of novel and targeted therapies in post-HSCT to prevent further relapses; and enrollment in clinical trials [106][107][108].…”