CD3+ graft cell count influence on chronic GVHD in haploidentical allogeneic transplantation using post-transplant cyclophosphamide

Abstract

The effects of graft or donor characteristics in haploidentical hematopoietic cell transplantation (HCT) using post-transplant cyclophosphamide (PT-Cy) are largely unknown. In this multicenter retrospective study we analyzed the correlations between graft cell composition (CD34+, CD3+) and donor features on transplant outcomes in 234 patients who underwent HCT between 2010 and 2016. On multivariate analysis, the use of peripheral blood stem cells (PBSC) was associated with an increased incidence of grade 2-4 acute GVHD [HR 1.94, 95% confidence Interval (CI) = 1.01-3.98, p = 0.05]. An elevated CD3+ graft content was associated with an increased incidence of all-grade chronic GVHD [HR 1.36 (95% CI = 1.06-1.74), p = 0.01]. This effect was confirmed only for the PBSC graft group. A higher CD34+ graft content had a protective role on non-relapse mortality [HR 0.78 (95% CI = 0.62-0.96), p = 0.02] but this was confirmed only for the bone marrow (BM)-derived graft cohort. Donor characteristics did not influence any outcomes. GVHD prophylaxis should be modulated accordingly to CD3+ graft content, especially when a PBSC graft is used. These results need further validation in prospective trials.

Coronavirus disease 2019 pandemic and allogeneic hematopoietic stem cell transplantation: a single center reappraisal

“…Multiple reasons can account for this finding. Before the pandemic, we used to perform transplants from haploidentical donors using BM as a stem cell source, due to the concern of the higher incidence of acute and chronic GVHD reported in PBSC haploidentical transplants [13] , [14] , [15] . Nevertheless, at the onset of the pandemic our hospital was designed as a dedicated COVID -19 center in Rome, leading to the rearrangement of many departments and the establishment of COVID-19 dedicated pathways, including surgery rooms.…”

Impact of T Cell Dose on Outcome of T Cell-Replete HLA-Matched Allogeneic Peripheral Blood Stem Cell Transplantation

“…In addition, in the current era of post-transplantation cyclophosphamide (PTCy) for prevention of GVHD, it may be imperative to assess the impact of these T cell subsets in haploidentical and HLA-matched HCT. Interestingly, a multicenter study has indeed indicated an increased risk of cGVHD of all severity with an elevated CD3 + T cell dose with haploidentical PBSC HCT using PTCy [41]. CD3 + T cell dose has also been shown to be predictive of graft failure with TCD allogeneic HCT [42].…”

Allogeneic Stem Cell Transplantation Platforms With Ex Vivo and In Vivo Immune Manipulations: Count and Adjust

“…The surplus of αβT cells per body weight seems to mainly result in increased incidences of both acute and chronic GVHD, without improving GVL effects or engraftment. 4 , 5 Within this context, approximately 25% of all individuals in T cell repleted allo-SCT with matched unrelated donors (MUDs) 4 and 50% from haploidentical donors would benefit from infusing fewer donor cells 5 (Figure 1 ). This observation emphasizes that grafts differ substantially in immune compositions, and these variations need to be taken into consideration when treating patients.…”

“…Limiting T cell numbers rarely interferes with stem cell numbers needed for a sufficient engraftment. 4 , 5 In addition to qualitative and quantitative variations of cell types in the stem cell product, chemotherapeutic drugs used during conditioning can also impact complications and efficacy after allo-SCT. This is a consequence of the fact that concentration of a defined drug, for example, in the blood stream, cannot be precisely predicted based on body weight, body surface area, or kidney or liver function.…”

“…We illustrate different T cell dosage within the context of 2 key studies. 4 , 5 Haplo = haploidentical donor; MUD = matched unrelated donor; PBMC = peripheral mononuclear cells; PTCy = post-transplantation cyclophosphamide; SCT = stem cell transplantation; SIB = sibling.…”