Impact of CD34/CD3 Ratio in Graft on the Outcome of Ptcy-Haplo PBSCT

Introduction：

Haploidentical peripheral blood stem cell transplantation with posttransplant cyclophosphamide (PTCY-haplo-PBSCT) is a rapidly increasing therapeutic option for patients lacking HLA-matched donors. In Japan, even though the results of PTCY-haplo-PBSCT for hematological malignancies are comparable to those of HLA-matched unrelated donor HSCT, analyzing various prognostic factors is important to further improve outcomes. Although the CD34+ cell dose in grafts has been reported to be a favorable factor in the outcome of PTCY-haplo-PBSCT, an excess CD3+ cell dose may increase the risk of GVHD. We examined the impact of CD34 (×10⁶ /kg)/CD3 (×10⁸ /kg) ratio and CD4/8 ratios in the graft on the outcome of PTCY-haplo-PBSCT.

Methods：

We retrospectively analyzed 45 patients (20 with AML, 13 with ALL, six with MDS, two with MF, three with malignant lymphoma/LPD, and one with AA). Twenty-seven patients were in complete response (CR) and 18 were in non-CR at transplantation. years who underwent PTCY-haplo-PBSCT at our hospital between 2014 and 2024. The median patient age was 43 years (range:18-66). The conditioning regimen was 25 (56%) in MAC (Flu+BU4) in 20 (44%) patients and RIC (Flu+BU2). Total body irradiation (TBI) was performed in 19 cases (3 Gy/fr in 18 cases, 12 Gy/6fr in one case). GVHD prophylaxis was MMF+FK506+CY (40-50 mg/kg/day on day3-4) in all patients. The donor relationship was a sibling in 38%, parent in 24%, and child in 38% of the cases. The median observation period was 352 [32-3249] days. The number of CD34+cells, CD3+cells, and CD4/8 ratio in the graft were measured by FCM. Cumulative incidence of relapse (CIR), overall survival (OS), GVHD-free survival (GRFS), and non-relapse mortality (NRM) were assessed. GRFS was defined as the absence of grades III-IV acute GVHD or chronic GVHD requiring systemic treatment, relapse, or death.

Results：

The median dose of CD34+ cells and CD3+cells, CD34/CD3, and CD4/8 ratio were 9.37 (×10⁶ /kg) and 2.38 (×10⁸ /kg), 3.85 and 1.31 respectively.

In comparison among the 3 groups (CD34+cell dose <7.0 (Low), 7.0 to 12.0 (Int), >12.0 (High) ), the 3-year OS rate in the Int group were significantly higher than those in the Low and High group (100%, 37.5%, 41.7%, respectively, p=0.03).

CIR did not show significant differences when comparing the doses of CD34+cells, CD3+cells, and CD4/8 ratios, but did show differences when comparing CD34/3 ratios. i.e., <2.5 vs. >2.5, 3-year CIR rates were 19.2% and 75.0% (p=0.002).

When the CD34/CD3 ratio was compared between the two groups (< 2.5 vs. > 2.5), the 1-year GRFS rates were 12.5% and 78.0%, respectively (p=0.002). The cumulative incidence of Grade II-IV aGVHD at day + 100 for CD3+cells >3.5 group was 60.0% compared with 8.5% for the CD3+cells <3.5 group (p < 0.01). Similarly, the cumulative incidence of Grade III-IV aGVHD at day + 100 for the > 2.5% CD3 + cells group was 25.4% compared with 0% for the CD3+cells group (p < 0.05). The CD4/8 ratio (> 1.0) group had a lower incidence of Grade III-IV aGVHD than the <1.0 group (p < 0.05).

In multivariate analysis adjusted for CR status (CR/non-CR), HCT-CI (>2), conditioning (MAC/RIC), and CD34/CD3 ratio >2.5 was independent favorable factors for GRFS (HR:0.16, 95%CI:0.035-0.748, p=0.02).

Conclusion：

A CD34/CD3 ratio > 2.5 can improve 1-year GFRS on PTCY-haplo-PBSCT.

Takizawa:Janssen: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Chugai: Honoraria, Research Funding; Kyowa Kirin: Honoraria, Research Funding; Nippon Kayaku: Honoraria, Research Funding; Mitsubishi Tanabe: Research Funding; Eli Lilly: Research Funding; Asahi Kasei: Research Funding.