神田 善伸

BACKGROUND: The advent of novel therapeutic agents has improved the prognosis of multiple myeloma (MM). However, autologous stem cell transplantation (ASCT) remains a key treatment option for eligible patients. While stem cell mobilization using cyclophosphamide and granulocyte colony-stimulating factor (G-CSF) has long been the standard approach, the introduction of plerixafor (PLER) has led to broader adoption of G-CSF±PLER-based mobilization, offering improved scheduling flexibility. Nevertheless, real-world data on current mobilization practices and their effects on post-ASCT outcomes remain limited. METHODS: We evaluated mobilization strategies and their associations with clinical outcomes in MM patients who underwent ASCT between 2019 and 2022. A total of 3,319 patients were analyzed, including 743 patients mobilized with cyclophosphamide and 2,576 mobilized with G-CSF±PLER. The primary endpoint was 2-year overall survival (OS). Multivariate analysis and propensity score matching were performed to identify factors associated with superior OS. RESULTS: The 2-year OS rates were 89.7% (95% CI: 87.0-91.8) and 93.2% (95% CI: 91.8-94.3) in the cyclophosphamide and G-CSF groups, respectively. Multivariate analysis showed that age <65 years (P < 0.001), lower ISS stage (P < 0.001), good performance status (P < 0.001), G-CSF mobilization (P = 0.005), and deep response pre-ASCT (P < 0.001) were independent predictors of superior OS. Propensity score matching analysis demonstrated significantly better OS in the G-CSF group than in the cyclophosphamide group (P = 0.041). Among patients achieving complete or very good partial response (CR/VGPR) pre-ASCT, OS did not differ between the groups; however, among patients who did not reach CR or VGPR pre-ASCT, the G-CSF group showed significantly better OS than the cyclophosphamide group. CONCLUSIONS: G-CSF‒based mobilization may offer prognostic advantages after ASCT, particularly in patients with suboptimal pre-ASCT response.

BACKGROUND: Previous reports have suggested an association between cytomegalovirus (CMV) infection and bacterial or fungal infections after allogeneic hematopoietic cell transplantation (HCT). This study aimed to examine the relationship between letermovir (LTV) prophylaxis and the incidence of bacteremia and invasive fungal infections. METHODS: Using a Japanese transplant registry database, we analyzed 19,531 patients who underwent their first allogeneic HCT from 2011 to 2022. Patients who initiated LTV prophylaxis within the first week post-transplantation were classified as the LTV group. RESULTS: A total of 4915 patients in the LTV group and 14,616 in the No LTV group were analyzed. The incidence of bacteremia by day 100 was significantly lower in the LTV group compared to the No LTV group (17.4 % vs. 21.7 %, P < 0.001). In the multivariate analysis, LTV prophylaxis (HR 0.75, 95 %CI: 0.69-0.81) was found to be significantly associated with a reduced risk of bacteremia, along with neutrophil engraftment. Age >50 years, male, non-remission status, alternative donors, higher values of the hematopoietic cell transplantation-comorbidity index, poor performance status, and grade II-IV acute graft-versus-host disease were associated with an increased risk of bacteremia. LTV was associated with a reduced risk of bacteremia both within 30 days (HR 0.74, 95 %CI: 0.68-0.81) and beyond 30 days (HR 0.76, 95 %CI: 0.66-0.89) after HCT. Conversely, it was not associated with the risk of invasive aspergillosis or candidemia. CONCLUSIONS: LTV prophylaxis significantly reduced the risk of bacteremia. However, it was not associated with the risk of invasive fungal infections.

Despite the increasing number of cancer survivors, the impact of prior solid tumors and their treatment modality on outcomes after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This multi-center retrospective study compared transplant outcomes in allo-HSCT recipients with and without a history of solid tumors. Of 5,850 adult patients who underwent first allo-HSCT, 303 (5.2%) had a prior solid tumor. After propensity score matching, overall survival (OS) and cumulative incidences of relapse, non-relapse mortality (NRM), and acute and chronic graft-versus-host diseases were almost comparable between the two groups. Progression or recurrence of solid tumors after allo-HSCT occurred in only eight cases (2.8%). Importantly, patients who received both chemotherapy and radiation therapy (Chemo + RT) for prior solid tumors had significantly worse OS (35.3% vs. 54.1% [P < 0.001] vs. 56.8% [P < 0.001] at 2 years) and higher NRM (36.2% vs. 18.7% [P = 0.002] vs. 19.3% [P = 0.001] at 2 years) compared to patients who received other treatment modalities for prior solid tumors or patients without prior solid tumors. These findings highlight the feasibility of allo-HSCT in selected patients with prior solid tumors, while demonstrating the negative impact of Chemo + RT on outcomes after allo-HSCT.

HLA class I allele loss in acquired aplastic anemia (AA) represents an immune escape from the T cell-mediated pathogenesis. We investigated the impact of loss-prone HLA alleles on the hematopoietic cell transplantation (HCT) outcomes using registry data of 875 Japanese patients with acquired AA. HLA associations were evident exclusively among 399 patients who received HCT within 1 year of the diagnosis, consistent with the predominance of HLA loss in this group. A set of five HLA alleles with the highest propensity for loss (HLA-A*02:01, HLA-A*02:06, HLA-A*31:01, HLA-B*40:02, and HLA-B*54:01) was the strongest predictor of post-transplant survival among all possible allele combinations (5-year survival, 80.3% vs. 54.4%; p < 0.0001), partly due to improved engraftment and pre-transplant conditions. Another set (HLA-A*33:03, HLA-B*07:02, HLA-B*44:03, HLA-B*52:01, and HLA-B*54:01)-less frequently lost in AA and underrepresented in Epstein-Barr virus (EBV)-related diseases outside AA-was associated with an increased risk of post-transplant lymphoproliferative disorders (5-year incidence, 10.2% vs. 1.8%; p = 0.00019), suggesting that the loss of protective alleles against EBV during AA pathogenesis may predispose to EBV-driven lymphoproliferations. These associations were determined by recipient, not donor, HLA. Therefore, specific HLA class I alleles and their potential loss significantly influence the HCT outcomes in acquired AA.