Post-transplant cyclophosphamide versus anti-thymocyte globulin as graft- versus -host disease prophylaxis in haploidentical transplant

Abstract

Severe graft-versus-host disease is a major barrier for non-T-celldepleted haploidentical stem cell transplantation. There is no consensus on the optimal graft-versus-host disease prophylaxis. This study compared the two most commonly used graft-versus-host disease prophylaxis regimens (post-transplant cyclophosphamide-based vs. the anti-thymocyte globulin-based) in adults with acute myeloid leukemia reported to the European Society for Blood and Bone Marrow Transplantation. A total of 308 patients were analyzed; 193 received posttransplant cyclophosphamide-based regimen and 115 anti-thymocyte globulin-based regimen as anti-graft-versus-host disease prophylaxis. The post-transplant cyclophosphamide-based regimen was more likely to be associated to bone marrow as graft source (60% vs. 40%; P=0.01). Patients in the post-transplant cyclophosphamide-based regimen group had significantly less grade 3-4 acute graft-versus-host disease than those in the anti-thymocyte globulin-based group (5% vs. 12%, respectively; P=0.01), comparable to chronic graft-versus-host disease. Multivariate analysis showed that non-relapse mortality was lower in the post-transplant cyclophosphamide-based regimen group [22% vs. 30%, Hazard ratio (HR) 1.77(95%CI: 1.09-2.86); P=0.02] with no difference in relapse incidence. Patients receiving post-transplant cyclophosphamide-based regimen had better graft-versus-host disease-free, relapse-free survival [HR 1.45

Haploidentical hematopoietic stem cell transplantation with post‐transplant high‐dose cyclophosphamide in high‐risk children: A single‐center study

“…However, we have not found such an effect in our study. In addition, Ruggeri et al reported that a Post‐Cy‐without ATG‐based regimen can achieve a lower incidence of GVHD than an ATG‐without Post‐Cy regimen in adult patients with AML, suggesting that any effect on GVHD rates seen in our study is linked to Post‐Cy administration regardless of ATG usage.…”

The impact of HLA matching on outcomes of unmanipulated haploidentical HSCT is modulated by GVHD prophylaxis

“…It should be noted that the population included in this study partially overlaps with the recently published data by Ruggeri et al, 27 in which haplo-HSCT using PTCy was compared with ATG platforms, showing significantly better LFS, lower incidence of GVHD, and nonrelapse mortality of the former regimen compared with the latter in patients with AML in complete remission. In the study by Ruggeri et al, 27 the incidence of aGVHD was not influenced by the stem cell source or intensity of conditioning regimens in multivariate analysis adjusting for the adopted GVHD prophylaxis.…”

“…In the study by Ruggeri et al, 27 the incidence of aGVHD was not influenced by the stem cell source or intensity of conditioning regimens in multivariate analysis adjusting for the adopted GVHD prophylaxis. We hypothesize that the inclusion of advanced status diseases and ALL patients in our cohort could partly explain these results.…”

“…Despite this, over recent years, clinical protocols for unmanipulated T-cell-replete haplo-HSCT have been successfully developed, using either posttransplant cyclophosphamide (PTCy) or antithymocyte globulin (ATG) as alternative platforms to harness alloreactivity to the mismatched HLA haplotype. [21][22][23][24][25][26][27] Although haploidentical donors are referred to as HLA-haplotypemismatched, some recipients who share an HLA haplotype with their donor are also matched for 1 or more HLA antigens on the unshared haplotype. Until now, scarce evidence existed on the relative role of optimal HLA mismatching on the unshared haplotype in haplo-HSCT.…”

Novel strategies for improving hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation or intensive chemotherapy

“…Initial approaches aimed at expanding UCB with various cytokine cocktails met with little successes [12,13]. Fortunately, novel strategies aimed at increasing the number of hematopoietic stem and progenitor cells (HSPCs) transplanted for UCBT or at increasing their ability to home to their bone marrow niches have been much more encouraging and might lead in the future to a regrowth of adult UCBT in Europe, a transplant approach currently challenged by the development of T-cell repleted HLA-haploidentical stem cell transplantation [42][43][44]. These strategies have consisted of double UCBT with or without expansion of one of the 2 UCB units, cotransplanting a single UCB unit with HLA-haploidentical CD34+ cells (haplo-cord transplantation), or increasing UCB HSC homing to marrow niches via direct intrabone UCB administration, pulse treatment with dmPGE2 or enforced fucosylation [13,45] (Table 2).…”