Quality of the hematopoietic stem cell graft affects the clinical outcome of allogeneic stem cell transplantation

Abstract

BACKGROUND In approximately two‐thirds of patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) no suitable related donor can be identified but an unrelated HLA‐matched donor can be found through international donor registries. HSCT grafts from unrelated donors are commonly collected at distant sites. Therefore, graft storage and transportation becomes crucial in the HSCT process. We aimed to study the impact of graft quality on clinical outcome and identify factors affecting graft quality. STUDY DESIGN AND METHODS We investigated the influence of graft quality on the clinical outcome in 144 HSCT patients. Graft quality was assessed by determining the viability (7‐aminoactinomycin D [7AAD]) on a frozen‐thawed sample from the peripheral blood stem cell (PBSC) graft. RESULTS Patients receiving PBSCs with inferior quality (i.e., viability < 64% in the frozen‐thawed sample) more frequently developed acute graft‐versus‐host disease (aGVHD) Grades I to IV than patients receiving grafts with better quality (p = 0.025). The transplant‐related mortality (TRM) was higher in the group receiving grafts with lower viability (p = 0.03). The viability of the frozen‐thawed samples was highly variable (median, 64%; range, 24%‐96%). No correlation could be observed when comparing the viability in newly arrived PBSC grafts to frozen‐thawed vials. Grafts with white blood cell (WBC) count of more than 300 × 109/L had lower viability than those with lower WBC counts (p < 0.001). CONCLUSION Graft quality affects clinical outcome. Patients receiving grafts with inferior quality had more aGVHD and higher TRM. There is a need for better analyses for assessing graft quality in routine HSCT care; analysis using 7AAD on fresh PBSC grafts is not sufficient.

The importance of graft cell composition in outcome after allogeneic stem cell transplantation in patients with malignant disease

“…34 Other than the pivotal role of graft CD34 + cell number, the optimal cellular composition of other graft cell components remains to be determined. 19 In this retrospective study, we hypothesized that donor grafts flow cytometry data were associated to outcome ie, GVHD, relapse, TRM and TA B L E 2 Median cell dose in sibling and unrelated donors overall survival. 19 In this retrospective study, we hypothesized that donor grafts flow cytometry data were associated to outcome ie, GVHD, relapse, TRM and TA B L E 2 Median cell dose in sibling and unrelated donors overall survival.…”

“…High donor graft B-cells (CD19 + ) in sib-HSCT was associated to more acute GVHD. 19 This could contribute to inter-center differences in outcomes and results. 17 A recent meta-analysis has shown that high levels of donor T-regulatory cells improve overall survival.…”

Graft Composition and Post-Thawing Cell Viability Influence the Hematopoietic Recovery in Autologous Hematopoietic Stem Cell Transplantation

“…Data gathered in both allogeneic and autologous hematopoietic stem cell transplantation, suggest that low post-thawing cell viability predicts delayed neutrophil engraftment [2,7,12]. Indeed, we investigated this issue in our series of patients.…”

“…An adequate number of total nucleated and CD34+ cells in the graft plays a pivotal role to achieve sustained engraftment and good survival. However, recent evidences in the allogeneic HSCT setting suggest that additional factors, from cellular graft composition to freezing and storage procedure, determine the graft quality and, ultimately, influence the outcome of patients [1,2]. In the field of Autologous Stem Cell Transplantation (ASCT), the attention has mainly focused on the amount of transplanted cells: it is widely acknowledged that a clear relationship exists between dose of CD34+ cells infused and engraftment [3][4][5][6].…”

Change of apheresis device decreased the incidence of severe acute graft‐versus‐host disease among patients after allogeneic stem cell transplantation with sibling donors

“…Graft composition influences the risk of GvHD, time to engraftment, and relapse risk . CD34+ cells per kilogram recipient have often been used as marker for graft quality, but there are no clear limitations/recommendations on other lymphocyte populations in the graft .…”