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Impact of CD34+ cell dose on patient outcomes after haplo-PBSCT with PTCy

Apr 12, 2024
Learning objective: After reading this article, learners will be able to cite a new clinical development in graft-versus-host disease.

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After receiving haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) some patients may also receive posttransplant cyclophosphamide (PTCy) as a graft-versus-host disease (GvHD) prophylaxis. However, it remains uncertain how patients who receive haplo-PBSCT and PTCy are impacted by CD34+ cell dose from their donor graft.

Here, we summarize an article by Maruyama et al.1 published in Blood Cells, Molecules and Diseases evaluating how CD34+ cell dose impacts patient outcomes after haplo-PBSCT with PTCy treatment.


  • A retrospective, single-center study of patients with hematological malignancies who received haplo-PBSCT or matched PBSCT from a human leukocyte antigen-matched related donor at the University of Tsukuba Hospital, Tsukuba, Japan, between May 2011 and May 2022.
  • Transplantations were performed using T cell-replete PBSC grafts
    • Doses of CD34+ cells and total nucleated cells were defined as the number of cells per recipient body weight, and were measured after graft harvesting
  • Patients who underwent haplo-PBSCT received:
    • PTCy (50 mg/kg/day) on Days +3 and +5;
    • cyclosporine A was administered on Day –1 at a target blood concentration of 500 ng/mL, and tapering began at ~Day +56; and
    • mycophenolate mofetil (2,000 mg/day) was administered from Day –1 to Day +30.
  • Outcomes measured included:
    • median time to neutrophil and platelet count recovery;
    • GvHD severity;
    • overall survival (OS) at 3 years;
    • progression-free survival (PFS) at 3 years;
    • GvHD-free relapse-free survival (GRFS) at 3 years;
    • cumulative incidence of relapse;
    • non-relapse mortality (NRM); and
    • complete remission (CR).
  • GvHD severity was defined using the Mount Sinai Acute GvHD International Consortium (MAGIC) report and National Institutes of Health classification.
  • The receiver operating characteristic (ROC) curve analysis was used to determine the cutoff CD34+ cell dose.

Key findings1

  • In total, 111 patients were included in this study.
    • 54 patients, with a median age of 47, received matched PBSCT.
    • 57 patients, with a median age of 51, received haplo-PBSCT.
  • Using the area under the ROC curve, a moderate cutoff value for CD34+ cell dose was established as 3.9 × 106/kg (sensitivity, 66.7%; specificity, 88.1%).
    • Patients who received haplo-PBSCT were then divided into two groups to analyze the impact of CD34+ cell dosage which included a haplo-low group (<4.0 × 106/kg CD34+ cells, n = 15) and a haplo-high group (≥4.0 × 106/ kg CD34+ cells, n = 42).
  • There were no significant differences observed between the haplo-low and haplo-high groups in patient characteristics, median dose of total nucleated cells, refined disease risk index (p = 0.761), CR status (p = 0.358), or hematopoietic cell transplant comorbidity index score (p = 0.371).
  • Patients in the haplo-high group had greater survival outcomes compared with those in the haplo-low group (Figure 1).

Figure 1.  Survival outcomes at 3 years after haplo-PBSCT* 

GRFS, graft-versus-host disease-free relapse-free survival; haplo-PBSCT, haploidentical peripheral blood stem cell transplantation; OS, overall survival; PFS, progression-free survival.
*Data from Maruyama, et al.1


  • In the haplo-high group, the cumulative incidence of relapse was lower compared with the haplo-low group, 24.1% vs 73.3%, respectively (p = 0.001).
  • Table 1 compares additional endpoint data between the haplo-low and haplo-high groups.
    • There were no significant differences in the incidence of Grade 2─4 acute GvHD or moderate and severe chronic GvHD.

Table 1. Outcomes of both groups after haplo-PBSCT*


(<4.0 × 106/kg CD34+ cells)

(≥4.0 × 106/ kg CD34+ cells)

p value

Median time to achieve an absolute neutrophil count of ≥0.5 × 109/L

17 days

17 days

p = 0.832

Median time to achieve a platelet count of ≥50 × 109/L

33 days

29 days

p = 0.466

NRM (95% CI), %



p = 0.075

Cumulative incidence of Grade 2-4 aGvHD (95% Cl), %



p = 0.058

Cumulative incidence of moderate-to-severe cGvHD (95% CI), %



p = 0.720

aGvHD, acute graft-versus-host disease; cGvHD, chronic graft-versus-host disease; CI, confidence interval; haplo-PBSCT, haploidentical peripheral blood stem cell transplantation; NRM, non-relapse mortality.
*Adapted from Maruyama, et al.1

  • In both univariate and multivariate analysis, disease status and CD34+ cell dose were prognostic for outcomes including OS, PFS, and relapse.
    • In multivariate analysis:
      • a lower dose of CD34+ cells (<4.0 x 106/kg) correlated with disease relapse (hazard ratio [HR], 4.51; 95% confidence interval [CI], 1.66─12.2; p = 0.003); and
      • a non-CR correlated with shorter OS (HR, 2.63; 95% CI 1.13─6.14; p = 0.025), shorter PFS (HR, 2.63; 95% CI 1.23─5.63; p = 0.013), and a higher relapse rate (HR, 2.97; 95% CI, 1.37─6.43; p = 0.006).

Key learnings

  • In this study, improved survival outcomes and reduced disease relapse were observed in patients who received a higher dose of CD34+ cells (≥4.0 × 106/kg dose) during haplo-PBSCT and were then treated with PTCy for GvHD prophylaxis.
  • Receiving a higher dose of CD34+ cells did not significantly increase the incidence of GvHD in patients undergoing haplo-PBST with PTCy.
  • Optimizing CD34+ cell dose based on donor type may be beneficial for patients who receive PBSCT.

  1. Maruyama Y, Nishiki H, Kurita N, et al. Impact of CD34 positive cell dose in donor graft on the outcomes after haploidentical peripheral blood stem cell transplantation with post-transplant cyclophosphamide – a retrospective single-center study with a Japanese cohort. Blood Cells Mol Dis. 2024;105:102820. DOI: 1016/j.bcmd.2023.102820


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