藤原 慎一郎

BACKGROUND: For peripheral blood stem cell (PBSC) collection of unrelated donors, the Japan Marrow Donor Program (JMDP) sets the target CD34+ cell dose as the minimum of 2 × 106 cells/kg of recipient body weight (RBW) and recommends a processing blood volume (PBV) as high as 200 mL/kg of donor body weight (DBW) with ≤250 mL/kg per day within two consecutive days. Here, we retrospectively reviewed this guideline. STUDY DESIGN AND METHODS: We analyzed 1656 unrelated donor PBSC collections between January 2012 and November 2022 from the JMDP database. RESULTS: The target CD34+ cell dose was achieved within 2 days in all but 40 cases (2.4%), suggesting that the current JMDP guideline largely meets its objectives. The distribution of PBV per DBW showed three peaks. The most prominent peak, consisting of 834 (50.4%) cases, occurred around the recommended PBV (180-220 mL/kg of DBW), whereas 659 (39.8%) cases were in the lower PBV range (<180 mL/kg), and, notably, there was no significant difference between these groups in the collected CD34+ cells/kg RBW. On the other hand, among the 163 (9.8%) cases in the higher PBV group (>220 mL/kg), the number of collected CD34+ cells/kg of RBW was significantly lower than in the other two groups. DISCUSSION: These results suggest that the target PBV in the lower and higher PBV groups was determined using CD34+ enumeration before or during apheresis procedure. CD34+ enumeration may help reduce the burden on donors, although further investigations are needed to confirm.

Previous studies have shown that the pre-transplant C-reactive protein (CRP)/platelet ratio (CP ratio) is a predictor of survival. The aim of this multicenter retrospective study was to evaluate the clinical significance of CP ratio in patients with malignant lymphoma (ML) who underwent allogeneic hematopoietic stem cell transplantation (alloHCT). The cohort included patients with ML who underwent first alloHCT from 2007 to 2021. CP ratio was defined as CRP [mg/dL]/platelet [104/μL] and evaluated prior to alloHCT. The cutoff value for CP ratio was set at 0.05 based on previous studies. A total of 311 cases were analyzed, of which 134 were mature B cell lymphoma, 177 were T/NK cell lymphoma (including 70 cases of adult T-cell leukemia/lymphoma), and 17 were Hodgkin's lymphoma. The median age was 53 years (range: 17-69 years). High CP ratio was associated with status of disease, presence of infections, poor performance status at alloHCT, and high transfusion volume received prior to alloHCT. Overall survival (OS) at 2 years according to CP ratio (low vs. high) was 61.1% versus 30.1% (p < 0.001), non-relapse mortality (NRM) was 21.4% versus 40.7% (p = 0.001), and the relapse rate was 23.7% versus 32.6% (p = 0.061), respectively. In multivariate analysis, the high CP ratio group was associated with poor OS (HR = 2.20, 95% CI: 1.61-3.02, p < 0.001) and higher NRM (HR = 1.90, 95% CI: 1.28-2.81, p = 0.0014). High CP ratio was found to be associated with poor post-transplant OS and NRM, and was a suitable prognostic biomarker for stratifying the risk of patients with ML who are candidates for alloHCT.

Allogeneic hematopoietic stem cell transplantation (HSCT) from HLA-matched donors is the gold standard. However, haploidentical stem cell transplantation using posttransplant cyclophosphamide (PTCY-haplo) and cord blood transplants (CBTs) are alternatives when HLA-matched donors are not available. Using Japanese registry data, we evaluated the impact of haploidentical donor age on posttransplant outcomes by comparing PTCY-haplo and CBT. We analyzed data for 5161 patients aged 16 to 70 years who received their first HSCT for acute leukemia, myelodysplastic syndrome, or chronic myeloid leukemia. Haploidentical donors were categorized as "younger" (aged <40 years) or "older" (aged ≥40 years), and the patients were divided into younger (aged <50 years) and older (aged ≥50 years) cohorts. In the older cohort, PTCY-haplo from younger donors had better overall survival (OS; 55.5% vs 50.8%, P = .006), lower nonrelapse mortality (NRM; 17.3% vs 28.6%, P < .001), and higher relapse rates (33.0% vs 24.9%, P = .017) than with CBT. PTCY-haplo from older donors had comparable OS (44.1% vs 50.8%, P = 1.00), NRM (27.3% vs 28.6%, P = 1.00), and relapse (29.2% vs 24.9%, P = .90) to that with CBT. In the younger cohort, PTCY-haplo from younger and older donors showed OS, NRM, and relapse comparable with CBT. In the older cohort, cumulative incidence of acute graft-versus-host disease (GVHD) was higher with CBT than with PTCY-haplo, regardless of donor age. However, in the younger cohort, acute GVHD was lower in PTCY-haplo from younger donors than with CBT. PTCY-haplo from younger donors to older patients offers better clinical outcomes than CBT.