Impact of CD34+ cell dose on reduced intensity conditioning regimen haploidentical hematopoietic stem cell transplantation

Abstract

Objectives Haploidentical hematopoietic stem cell transplant (haplo‐SCT) has been associated with higher rates of graft rejection, and a higher dose of CD34+ cell dose is frequently requested. We aim to explore the impact of CD34+ cell dose in peripheral blood stem cell (PBSC) grafts using reduced intensity conditioning (RIC) in haplo‐SCT. Methods Sixty‐eight consecutive haplo‐SCT in adult patients were included. Graft‐vs‐host disease (GVHD) prophylaxis consisted on ATG, PTCy, and CsA. The cohort was divided in two groups using CD34+ dose of ≥ 9 × 106 CD34+/Kg as cutoff point. Median follow‐up was 8.9 months. Results Median cell dose infused was 9.32 × 106 CD34+/Kg. Forty (58.8%) recipients received grafts with CD34+ cells ≥9 × 106/kg. The infusion ≥ 9 × 106 CD34+/Kg cell dose had a negative impact in overall survival (P = .03) after adjusting for age at transplant. The cumulative incidence of acute GVHD and graft failure were not significantly influenced per CD34+ cell dose. Only four recipients had grade III aGVHD, and all of them received grafts with a CD34+ cell dose ≥ 9 × 106. Conclusion In RIC haplo‐SCT, recipients may not benefit from PBSC grafts with a CD34+/kg cell dose higher than 9 × 106 cells/kg, as it can have an adverse impact in post‐transplant outcome.

Non-Clinical Cell Therapy Development Using the NCG Mouse Model as a Test System

“…As an example, mice are lymphocyte predominant amongst the total leukocyte population while humans have a higher population of polymorphonuclear cells. 61 In humans, studies have investigated varying doses of CD34 + cells in multiple contexts and patient populations 62-64 with variable results, ultimately demonstrating that the optimal cell dose is heavily dependent on the donor and the stem cell source. 62…”

“…As an example, mice are lymphocyte predominant amongst the total leukocyte population while humans have a higher population of polymorphonuclear cells. 61 In humans, studies have investigated varying doses of CD34 + cells in multiple contexts and patient populations [62][63][64] with variable results, ultimately demonstrating that the optimal cell dose is heavily dependent on the donor and the stem cell source. 62 Rather than informing future dose levels in humans, the pertinence of murine toxicology studies is mostly related to identifying the interaction of gene edited human cells in various organs and confirming that malignancies do not develop over the observation period.…”

Effect of pre‐transplant JAK1/2 inhibitors and CD34 dose on transplant outcomes in myelofibrosis

“…Our results highlight the favorable effect of higher CD34 dose on post-transplant survival in MF, and the impact of pre-transplant JAKi of our knowledge on this aspect specifically in the MF transplant setting. [28][29][30] For RFS a significant interaction between the effects of CD34 cell dose and GVHD prophylaxis regimen (use of ATG-PTCy) was found on UVA (P =.04) and MVA (Table 3). The association of CD34 dose on RFS was seen mainly in patients who had received ATG/PTCy for GVHD prophylaxis.…”

Effects of CD34+ cell dose on haematopoietic recovery in acute lymphoblastic leukaemia patients with positive pretransplant measurable residual disease

“…Haematopoietic reconstitution is a key issue for successful allo‐HSCT 1 . A number of studies reported by others and have delineated the association of a higher CD34 + cell dose in allografts with faster haematopoietic recovery 2–6 and better survival, 7–12 although a few researchers failed to demonstrate this association 13,14 . The above‐mentioned controversy might be related to the differences in underlying disease, conditioning regimen, and graft‐versus‐host disease (GVHD) prophylaxis of these studies.…”

“…1 A number of studies reported by others and have delineated the association of a higher CD34 + cell dose in allografts with faster haematopoietic recovery [2][3][4][5][6] and better survival, [7][8][9][10][11][12] although a few researchers failed to demonstrate this association. 13,14 The abovementioned controversy might be related to the differences in underlying disease, conditioning regimen, and graft-versus-host disease (GVHD) prophylaxis of these studies. Thus, further studies are needed to elucidate the effects of CD34 + cell dose in patients with homogeneous underlying disease and other clinical characteristics.…”