Haema 2017; 8(2): 200-211
by Ioannis Baltadakis, Ioannis Konstantellos
Department of Hematology and Bone Marrow Transplantation Unit, Evangelismos Hospital, Athens
Abstract
AML is the most frequent indication for allogeneic hematopoietic stem cell transplantation (alloHSCT). The decision to perform a transplant is dependent on the assessment of the risk-benefit ratio, namely nonrelapse mortality (NRM) versus reduction of relapse risk by transplantation. The choice to proceed to transplant in first complete remission is based primarily on the genetic risk stratification according to ELN (European LeukemiaNet). AlloHSCT is not generally indicated in favorable-risk AML, whereas it is the preferred post-remission treatment for adverse-risk AML. In intermediate-risk disease, alloHSCT is clearly superior to conventional chemotherapy, albeit autologous HSCT remains a therapeutic option. Monitoring of minimal residual disease (MRD) becomes increasingly important for considering transplantation during first complete remission. AlloHSCT is invariably indicated in primary refractory or relapsed AML offering the possibility of cure in 20-40% of such cases. Access of patients to alloHSCT has considerably improved over the last several years. Apart from HLA identical siblings, alternative stem cell donors (volunteer unrelated, umbilical cord blood, as well as haploidentical family donors) are now available for practically every patient who needs an allotransplant. Hence, the decision on transplantation is not as much influenced by the availability of a donor as by the fitness of a patient for the procedure. Patients should not be precluded from transplantation solely based on age, and transplant evaluation must rely on the presence of significant comorbidities and geriatric assessment. Of note, NRM is reliably predicted by the hematopoietic cell transplantation comorbidity index (HCT-CI). AlloHSCT has become feasible in older or medically infirm patients with the advent of reduced-intensity conditioning (RIC) regimens. However, the intensity of the conditioning regimen is strongly associated with the risk of disease relapse. Therefore, myeloablative regimens remain the standard of care for fit patients with AML. Prognosis for patients relapsing after alloHSCT is extremely poor. Treatment options for post-transplant relapse include chemotherapy followed by donor lymphocyte infusions (DLI) or a second transplant. Of greater interest is the prevention of relapse, which is currently pursued by enhancement of the antileukemic activity of conditioning regimens, by maintenance or preemptive therapy with hypomethylating agents or FLT3 inhibitors, as well as by novel methods of immunotherapy in the context of stem cell transplantation.