Low CD34 Dose Is Associated with Poor Survival after Reduced-Intensity Conditioning Allogeneic Transplantation for Acute Myeloid Leukemia and Myelodysplastic Syndrome

Abstract

Reduced intensity conditioning/non-myeloablative conditioning regimens are increasingly used in allogeneic hematopoietic cell transplantation (HCT). Reports have shown CD34+ dose to be important for transplant-outcome using myeloablative conditioning. The role of CD34+ dose of peripheral blood progenitor cells (PBPC) has not been previously analyzed in a large population undergoing reduced intensity conditioning/non-myeloablative HCT. We studied 1,054 patients aged 45–75 years, with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) transplanted between 2002 and 2011. Results of multivariate analysis showed that PBPC from HLA-matched siblings containing <4 × 106 CD34+/kg were associated with higher non-relapse mortality (HR 2.03, p=0.001), overall mortality (HR 1.48, p=0.008), and lower neutrophil (OR 0.76, p=0.03) and platelet (OR 0.76, p=0.03) recovery. PBPC from unrelated donors with CD34+ dose <6 × 106 CD34+/kg were also associated with higher non-relapse (HR 1.38, p=0.02) and overall mortality (HR 1.20, p=0.05). In contrast to reports after myeloablative HCT, CD34+ dose did not affect relapse or graft-versus-host disease with either donor type. An upper cell dose limit was not associated with adverse outcomes. These data suggest that PBPC CD34+ dose >4 × 106 CD34+/kg and >6 × 106 CD34+/kg are optimal for HLA-matched sibling and unrelated donor HCT, respectively.

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

“…Regarding the effects of CD3+ on NRM and acute GVHD incidence, it is possible that our study is not powered enough to evaluate this effect (234 vs. 340 patients). Finally, we confirmed a protective role of CD34+ graft content on NRM as previously reported in the HLAidentical setting [37,38], probably due to a reduction in the number of infection-related deaths. However, a subgroup analysis showed that this protective effect was evident only when a BM graft was used at doses of >2 × 10 6 CD34+/kg.…”

Prediction of hematopoietic stem cell yield after mobilization with granulocyte–colony‐stimulating factor in healthy unrelated donors

“…The use of our prediction model might then be attractive. Notably, a recent publication suggested that the target CD34+ cell dose for PBSCs from unrelated donors should be increased to more than 6 × 10 6 CD34+ cells/kg recipient body weight . When such recommendations are adopted, many donors will fail to mobilize enough stem cells within a 1‐day apheresis session and a relevant percentage of donors will fail to collect enough PBSCs even after multiple apheresis sessions.…”

Targeted recruitment of male donors for allogeneic haematopoietic cell transplantation: A review of the evidence

“…Today, peripheral blood stem cells (PBSC) are the most commonly collected source of CD34+ haematopoietic stem cells used in transplantation. Although the minimum dose of CD34+ cells to ensure engraftment remains an area of debate, higher doses have been shown to result in more rapid engraftment, decreased transplant‐related mortality and improved overall survival .…”