αβ T Cell-Depleted Haploidentical Hematopoietic Stem Cell Transplantation without Antithymocyte Globulin in Children with Chemorefractory Acute Myelogenous Leukemia

Abstract

We evaluated the outcome of ab T cell-depleted haploidentical hematopoietic stem cell transplantation (HSCT) in a cohort of children with chemorefractory acute myelogenous leukemia (AML). Twenty-two patients with either primary refractory (n = 10) or relapsed refractory (n = 12) AML in active disease status received a transplant from haploidentical donors. The preparative regimen included cytoreduction with fludarabine and cytarabine and subsequent myeloablative conditioning with treosulfan and thiotepa. Antithymocyte globulin was substituted with tocilizumab in all patients and also with abatacept in 10 patients. Grafts were peripheral blood stem cells engineered by ab T cell and CD19 depletion. Post-transplantation prophylactic therapy included infusion of donor lymphocytes, composed of a CD45RA-depleted fraction with or without a hypomethylating agent. Complete remission was achieved in 21 patients (95%). The cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) was 18%, and the cumulative incidence of chronic GVHD was 23%. At 2 years, transplantation-related mortality was 9%, relapse rate was 42%, event-free survival was 49%, and overall survival was 53%. Our data suggest that ab T cell-depleted haploidentical HSCT provides a reasonable chance of long-term survival in a cohort of children with chemorefractory AML and creates a solid basis for further improvement.

“Ex‐vivo” T‐cell depletion in allogeneic hematopoietic stem cell transplantation: New clinical approaches for old challenges

“…A similar study conducted by another group reported an incidence of skin only, grade I‐II acute GvHD of 30%, no extensive chronic GvHD, 24% incidence of relapse, and NRM of 5%, comparable with patients who received an HLA‐matched donor transplant (NCT01810120) 40,47 . In a more recent report, using myeloablative conditioning with treosulfan and thiotepa and substituting tocilizumab or abatacept for ATG, an incidence of grade II‐IV acute GvHD of 18%, chronic GVHD of 23% and 2‐years relapse and OS of 42% and 53%, respectively, was experienced in children with refractory AML 49 . Transplantation with TCRαβ + /CD19 + depleted grafts has been associated with a high incidence of CMV and EBV viremias 50 .…”

Expression of NK Cell Receptor Ligands on Leukemic Cells Is Associated with the Outcome of Childhood Acute Leukemia

“…In fact, NK cells are the first lymphoid cell to recover after therapy [ 55 , 56 ] and could be involved in the elimination of cancer cells. In support of this hypothesis, numerous studies have shown that HSCT with the appropriate haploidentical donor may improve clinical outcomes [ 8 , 9 , 57 , 58 , 59 ]. The main effectors in haploidentical HSCT are NK cells, which trigger their antitumor activity in case of missing ligand in the leukemic cells [ 8 , 9 ].…”

The combination of clofarabine, etoposide, and cyclophosphamide shows limited efficacy as a bridge to transplant for children with refractory acute leukemia: Results of a monitored prospective study

“…8 Thus stem cell transplantation seems to be the most widely applied and proven curative procedure for children with refractory AL. [9][10][11][12] It is commonly accepted that the better the disease control before HSCT, [13][14][15][16] the better the expected outcome. Thus in r/r AL, the main focus is on effective reduction of blast cell load that can potentially bridge the patients to a salvage procedure: HSCT alone or cell therapy with or without subsequent HSCT.…”