Use of tyrosine kinase inhibitors to prevent relapse after allogeneic hematopoietic stem cell transplantation for patients with Philadelphia chromosome–positive acute lymphoblastic leukemia: A position statement of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation

Abstract

Allogeneic hematopoietic stem cell transplantation (alloHSCT) is a standard of care for patients with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL). The introduction of tyrosine kinase inhibitors (TKIs) to first-line therapy has improved overall outcomes; however, a significant proportion of patients still relapse after alloHSCT. Posttransplant TKI maintenance was demonstrated to reduce the risk of relapse in a large retrospective study and, therefore, should be considered a valuable option. This consensus paper, written on behalf of the Acute Leukemia Working Party of the European Society for Blood and Marrow Transplantation, presents an overview of clinical studies on the use of TKIs after alloHSCT and proposes practical recommendations regarding the choice of TKI, treatment timing, and dosage. It is hoped that these recommendations will become the state of art in this field and, more importantly, lead to a reduction of Ph-positive ALL relapse after alloHSCT. Cancer 2016;122:2941-2951. © 2016 American Cancer Society.

Unmanipulated haploidentical stem cell transplantation in adults with acute lymphoblastic leukemia: a study on behalf of the Acute Leukemia Working Party of the EBMT

“…In particular, treatment protocols differ for patients with Ph-positive and Ph-negative disease. Tyrosine kinase inhibitors are widely implemented in up-front treatment of Ph-positive ALL, but their use is also recommended in post-allo-SCT prophylaxis, which may influence the final outcome [42]. The retrospective nature of our study did not allow including this variable in the analysis.…”

The Persistence of Minimal Residual Disease in Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: We Know It's Bad, Now What?

“…The question remains, however, should novel therapies be introduced prior to transplant to reduce the risk of relapse or should patients who enter transplant with measurable MRD be started on a TKI after transplant? The use of post-transplant TKIs has been evaluated in a number of retrospective studies as well as in several prospective studies, and has been summarized in a position statement from the European Society for Blood and Marrow Transplantation [11]. Almost universally, studies have reported a reduction in the risk of relapse with post-transplant TKI usage.…”

“…While treatment interruptions and dose reductions were commonly reported, drug related complications were not the primary reason for drug discontinuation in these studies. Although many issues need to be clarified including which TKI to use, what dose is most appropriate, whether therapy should be given prophylactically (to all patients) or pre-emptively (to only those who have a molecular relapse), and duration of treatment, there is a strong body of evidence to show that post-transplant TKI administration to patients that are MRD positive reduces the risk of relapse and extends overall survival [11].…”

Closing the gap: Novel therapies in treating acute lymphoblastic leukemia in adolescents and young adults

“…However, now with the utilization of TKIs throughout therapy, outcomes have greatly improved with two-year OS of~60%, although long-term outcomes remain inadequate due to relapse [44][45][46]. Several studies that have included TKIs in maintenance therapy have shown lower rates of late relapse [47]. While patients often are referred for allogeneic HSCT, pediatric studies suggest that transplant does not provide an additional survival benefit for patients whose disease are rendered MRD negative [48].…”