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

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.

Method¹

• 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).

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*

	Haplo-low (<4.0 × 106/kg CD34+ cells)	Haplo-high (≥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), %	0.0 (0.0─0.0)	19 (8.9─36.9)	p = 0.075
Cumulative incidence of Grade 2-4 aGvHD (95% Cl), %	40.0 (15.6─63.6)	16.7 (7.2─29.5)	p = 0.058
Cumulative incidence of moderate-to-severe cGvHD (95% CI), %	13.3 (1.8─36.4)	17.6 (6.8─32.4)	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.