Nonmyeloablative, HLA-haploidentical bone marrow transplantation with high dose, post-transplantation cyclophosphamide

Ashley Munchel, Chimen Kesserwan, Heather J Symons, Leo Luznik, Yvette L Kasamon, Richard J Jones, Ephraim J Fuchs, Ashley Munchel, Chimen Kesserwan, Heather J Symons, Leo Luznik, Yvette L Kasamon, Richard J Jones, Ephraim J Fuchs

Abstract

Allogeneic stem cell transplantation (SCT) from an HLA-haploidentical relative provides a potentially curative treatment option for hematologic malignancies patients who lack a suitably HLA-matched donor. The greatest challenge to performing HLA-haploidentical SCT has been high rates of graft failure and severe graft-versus-host disease (GVHD). Our group has been exploring high dose, post-transplantation cyclophosphamide (Cy) as prophylaxis of GVHD after nonmyeloablative, HLA-haploidentical bone marrow transplantation, or mini-haploBMT. Among 210 recipients of mini-haploBMT, 87% of patients have experienced sustained donor cell engraftment. The cumulative incidences of grades II-IV acute GVHD and chronic GVHD are 27% and 13%, respectively. Five-year cumulative incidence of non-relapse mortality is 18%, relapse is 55%, and actuarial overall survival and event-free survivals are 35% and 27%, respectively. These outcomes suggest that mini-haploBMT with post-transplantation Cy is associated with acceptably low toxicities and can provide longterm survival, if not cure, for many patients with advanced hematologic malignancies.

Keywords: HLA-haploidentical bone marrow transplantation.

Conflict of interest statement

Conflict of interest: The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Treatment schema for nonmyeloablative conditioning regimine in HLA-haploidentical transplantation with post-transplantation cyclophosphamide. MMF=mycophenolate mofetil; TBI=total body irradiation; Cy=cyclophosphamide; G-CSF=granulocyte colony stimulating factor.
Figure 2
Figure 2
Cumulative incidence of acute (A) and chronic (B) GVHD after nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide. n=210
Figure 3
Figure 3
Cumulative incidence of relapse and nonrelapse mortality after nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide.
Figure 4
Figure 4
Actuarial curves of (A) overall survival (OS) and event-free survival (EFS) in all patients undergoing nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide; (B) overall survival in patients with acute lymphocytic leukemia (ALL), acute myelocytic leukemia (AML) or myelodysplastic syndrome (MDS) or myeloproliferative disorder (MPD); (C) overall survival in patients with Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL) and chronic lymphocytic lymphoma (CLL).
Figure 5
Figure 5
Event-free survival (EFS) of patients undergoing nonmyeloablative haploidentical stem cell transplantation with post-transplantation cyclophosphamide according to number of nismatched HLA-antigens in any direction (GVH or HVG).

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