Using data from a nationwide Japanese registry, we evaluated the impact of the total body irradiation (TBI) dose in reduced-intensity conditioning (RIC) for allogeneic hematopoietic cell transplantation (allo-HCT) in patients with acute myeloid leukemia (AML). Adults undergoing their first allo-HCT with RIC between 2010 and 2021 were classified into three groups: non-TBI, low-TBI (2 to < 4 Gy), or moderate-TBI (4-8 Gy). Outcomes were analyzed separately for patients in complete remission (CR, n = 1949) and those in the non-CR group (n = 1484). Non-TBI was associated with higher overall mortality than low-TBI (hazard ratio [HR], 1.27; 95% confidence interval [CI], 1.03-1.56 in CR; HR, 1.19; 95% CI, 1.00-1.42 in non-CR). Moderate-TBI showed no significant difference in overall mortality compared to low-TBI (HR, 0.96; 95% CI, 0.80-1.15 in CR; HR, 0.89; 95% CI, 0.77-1.05 in non-CR). Among patients in the CR group with matched sibling donors, moderate-TBI reduced overall mortality (HR, 0.33; 95% CI, 0.17-0.64) and relapse (HR, 0.29; 95% CI, 0.12-0.69). In cord blood transplantation, non-TBI increased relapse in CR (HR, 2.73; 95% CI, 1.48-5.06) and overall mortality in non-CR (HR, 1.62; 95% CI, 1.19-2.19). In haploidentical transplants, non-TBI increased relapse (HR, 5.52; 95% CI, 1.72-17.72 in CR; HR, 1.54; 95% CI, 1.04-2.30 in non-CR). The incidence of secondary primary malignancies did not differ according to the use or dose of TBI. In conclusion, adding low- or moderate-TBI to RIC may improve disease control and survival without increasing non-relapse mortality.

Comparative data on alternative donor platforms in adolescent and young adult (AYA) allogeneic hematopoietic cell transplantation (HCT) are limited. We conducted a nationwide retrospective registry study in Japan comparing unrelated umbilical cord blood transplantation (UCBT), haploidentical transplantation without post-transplant cyclophosphamide (non-PTCy-haplo), and PTCy-based haploidentical transplantation (PTCy-haplo). The study included 458 patients aged 16-25 years (UCBT, n = 101; non-PTCy-haplo, n = 132; PTCy-haplo, n = 225). The main endpoints were overall survival (OS) and relapse-free survival (RFS); relapse, non-relapse mortality (NRM), graft-versus-host disease (GVHD), and engraftment were also evaluated. UCBT showed the most favorable survival. In multivariable analyses, non-PTCy-haplo was associated with inferior OS and RFS, higher NRM, and a higher incidence of grade II-IV acute GVHD than UCBT. PTCy-haplo was associated with inferior OS versus UCBT but showed no significant differences in RFS, relapse, NRM, acute GVHD, or chronic GVHD. Both haploidentical platforms showed faster neutrophil engraftment than UCBT, and PTCy-haplo also showed faster platelet engraftment. Sensitivity analyses restricted to malignant disease and stratified by conditioning intensity supported these findings. In this AYA cohort, UCBT was associated with the most favorable survival, non-PTCy-haplo showed consistently inferior outcomes, and PTCy-haplo remained a practical alternative when rapid donor availability and early hematopoietic recovery are prioritized.

Despite recent advances, data on allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients aged ≥70 years remain limited. We identified prognostic factors and developed a risk score to guide transplant eligibility. Using the Japanese Transplant Registry Unified Management Program, we retrospectively analyzed 929 patients aged ≥70 years who underwent their first allo-HSCT for hematologic malignancies between 2000 and 2022. Prognostic factors were identified by multivariate Cox regression to construct a scoring system. The median patient age was 71 years (range, 70-88), with acute myeloid leukemia being the most common disease. The 2-year overall survival (OS) rate was 34.2%. Multivariate analysis identified age ≥75 years, ATL, lymphoma, high disease risk, hematopoietic cell transplant-specific comorbidity index ≥5, and performance status ≥2 as adverse factors. Using the hazard ratio-based scoring system derived from multivariate analysis, patients were stratified into low- (0), intermediate-1- (1), intermediate-2- (2-3), and high-risk (4-5) groups, with 2-year OS rates of 57.1%, 35.0%, 18.3%, and 2.5%, respectively (p < 0.01). We identified prognostic factors and developed a scoring system stratifying survival in patients aged ≥70 years, potentially facilitating the selection of older candidates most likely to benefit from allo-HSCT.

CD34+ cell dose is believed to impact the outcomes of allogeneic peripheral blood stem cell transplantation (PBSCT), yet the optimal dose remains unclear. We retrospectively reviewed 2407 adult patients with acute myeloid leukaemia who underwent their first related PBSCT between 2000 and 2019. The median infused CD34+ cell dose was 3.67 × 106/kg. Patients were divided into three groups based on infused CD34+ cell dose: low (1.0-2.0 × 106/kg), intermediate (2.0-4.0 × 106/kg) and high (4.0-10.0 × 106/kg) groups. The 5-year overall survival rates were 37.2%, 40.2% and 37.4% in the low, intermediate and high groups respectively (p = 0.176). Although the high-group patients experienced faster neutrophil engraftment, cumulative incidences of infection and primary engraftment failure were comparable across groups. Platelet engraftment was significantly delayed in the low group, with 21.7% failing to engraft at day 100, compared to 14.6% and 13.4% in the intermediate and high groups (p < 0.001). Furthermore, the incidence of secondary graft failure was significantly higher in the low group. In conclusion, a CD34+ cell dose >2.0 × 106/kg improves platelet engraftment and reduces the risk of secondary graft failure but does not confer additional long-term benefits.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is usually performed as a curative treatment for adult T-cell leukemia/lymphoma (ATL), following first-line chemotherapy. We conducted a nationwide retrospective study to examine the prognostic impact of donor sources based on transplantation application timings: human leukocyte antigen (HLA)-matched related donor (MRD; n = 253), unrelated donor (URD; n = 656), unrelated cord blood (U-CB; n = 599), and HLA-haploidentical related donor with post-transplant cyclophosphamide (PT-CY; n = 166). In patients with the early application of allo-HSCT (< 100 days from diagnosis), the multivariate analysis showed no significant difference in overall mortality (OM) among all donor sources. Regarding the middle timing of allo-HSCT (100-179 days), the U-CB group showed higher OM than the MRD group (hazard ratio [HR], 1.37; p = 0.013), while the URD and PT-CY groups showed no significant difference in OM with the MRD group. Concerning the late timing of allo-HSCT (180-270 days), the U-CB (HR, 1.88; p = 0.005) and PT-CY groups (HR, 1.90; p = 0.043) showed higher OM than the MRD group, whereas the URD group exhibited comparable OM to the MRD group. The present study demonstrated the differential impact of the graft source based on the timing of allo-HSCT for ATL; therefore, it is important to select an optimal alternative donor based on application timing.

Abstract: Expression levels of HLA are associated with susceptibility to various diseases and outcomes after allogeneic hematopoietic cell transplantation (HCT). However, there has been no comprehensive analysis of the effect of the expression levels of the HLA-A, -B, -C, and -DRB1 alleles in unrelated HCT (UR-HCT). Using the capture RNA-sequencing method, we analyzed the gene expression of HLA alleles in 443 healthy donors and determined allele-specific transcription (AST) levels. We assigned median AST (M-AST) levels to HLA typing data of patients who received a transplant from unrelated donors matched for HLA-A, -B, -C, and -DRB1 alleles, using transplant registry data. All 6084 patients were divided into low, middle, and high tertile groups according to the distribution of the sum of the 2 alleles of the M-AST level for each HLA locus and the sum of the 8 alleles of the M-AST level for all 4 loci. The risk of grade 2 to 4 acute graft-versus-host disease was significantly higher in the middle group (hazard ratio [HR], 1.11; P = .044) and high group (HR, 1.20; P < .001) than in the low group for the sum of the HLA-A, -B, -C, and -DRB1 loci. Similar results were observed at the HLA-A, -B, -C, and -DRB1 loci. Higher transcription levels were also associated with a lower risk of relapse at the HLA-B, -C, and -DRB1 loci. Our data suggest that high transcription levels of patient and/or donor HLA may evoke strong alloimmune responses and affect UR-HCT outcomes.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers potentially curative outcomes for adult T-cell leukaemia/lymphoma (ATL), but post-transplant refractory/relapsed (R/R) ATL is associated with poor outcomes. Advances have been made in transplant modalities, novel targeted agents and supportive care; however, it remains unclear whether these advances have improved survival outcomes of post-transplant R/R ATL. To clarify changes in survival after post-transplant R/R, we evaluated the survival outcomes in 1146 patients over a 24-year period, using a nationwide database. The period was divided into three groups: 1999-2010 (early period, as reference), 2011-2016 (middle period) and 2017-2022 (late period). In patients with refractory ATL, multivariate analyses showed no significant difference in overall mortality (OM) after post-transplant refractory in the early and middle periods, but a significantly lower OM in the late period than in the early period (hazard ratio [HR], 0.73 [95% confidence interval, 0.55-0.96]). In patients with relapsed ATL, OM after post-transplant relapse was significantly lower in the middle (HR 0.62 [0.48-0.80]) and late periods (HR 0.68 [0.52-0.90]) than in the early period. Thus, recent advances appear to have contributed to increased opportunities for therapeutic interventions, leading to improved survival outcomes in patients with post-transplant R/R ATL.

OBJECTIVES:Bacteraemia and cytomegalovirus (CMV) infection are major infectious complications after allogeneic haematopoietic cell transplantation (HCT). However, their bidirectional relationship, particularly in the setting of letermovir (LTV) prophylaxis, remains unclear. We investigated the bidirectional associations between bacteraemia and CMV infection and their impact on transplantation outcomes. We also evaluated the effect of LTV prophylaxis on these associations. METHODS:Using a nationwide Japanese transplant registry database, we analysed 23,841 patients who underwent their first allogeneic HCT between 2008 and 2022. Multivariable Cox proportional hazards models with time-dependent covariates were used to evaluate bidirectional associations between bacteraemia and clinically significant CMV infection (csCMVi). RESULTS:csCMVi was associated with an increased risk of subsequent bacteraemia (adjusted hazard ratio [aHR], 1.48; 95% CI, 1.33-1.64), with a stronger association among patients in the LTV group (aHR, 2.59; 95% CI, 1.87-3.60) than among those in the no-LTV group (aHR, 1.30; 95% CI, 1.16-1.46). Conversely, bacteraemia was modestly associated with an increased risk of csCMVi overall (aHR, 1.06; 95% CI, 1.01-1.11), but this association was observed only in the LTV group (aHR, 1.61; 95% CI, 1.40-1.85). These bidirectional associations were consistent in the LTV era and in patients without grade II-IV acute graft-versus-host disease. The findings were robust in sensitivity analyses, including landmark and propensity score-matched analyses. In propensity score-matched cohorts, both bacteraemia and csCMVi were associated with higher nonrelapse mortality (NRM; defined as death without relapse of the underlying malignancy) and inferior overall survival (OS), regardless of LTV use. CONCLUSIONS:Bacteraemia and csCMVi were bidirectionally associated after allogeneic HCT, particularly in the LTV group. Both bacteraemia and csCMVi were consistently associated with higher NRM and inferior OS, regardless of LTV prophylaxis. These findings highlight the need for integrated infection management strategies, particularly in the LTV era.

Outcomes of allogeneic hematopoietic stem cell transplantation are significantly influenced by conditioning regimens and graft-versus-host disease (GVHD) prophylaxis. Previous studies comparing matched-related donor (MRD) and umbilical cord blood (UCB) transplantation included patients with heterogeneous conditioning regimens and GVHD prophylaxis, potentially obscuring the true effects of donor type. We retrospectively compared outcomes of MRD (n = 1335) and UCB (n = 1097) transplantation performed with conditioning regimens and GVHD prophylaxis considered appropriate for cyclophosphamide/total body irradiation-based transplantation. Multivariable analysis revealed better relapse-free survival (RFS) for UCB than MRD in acute myeloid leukemia (hazard ratio [HR]: 0.80; 95

Donor selection in allogeneic haematopoietic stem cell transplantation (allo-HSCT) requires balancing donor safety and recipient survival. We aimed to identify dual-association donor factors (DADFs)-donor characteristics associated with both increased serious adverse events (SAEs) and inferior patient survival-using umbilical cord blood (UCB) as a donor-safety benchmark. This nationwide retrospective cohort study analysed Japanese registry data (2013-2022) including 22 892 donors and 29 559 recipients. Logistic regression identified donor SAE risk factors, while patient outcomes were evaluated using inverse probability of treatment weighting (IPTW)-adjusted Cox models with UCB as reference. Propensity score matching (PSM) compared UCB with older donor haploidentical transplantation using post-transplant cyclophosphamide (OD-PTCy-Haplo). Among donors, 93 (0.41%) experienced an SAE. Older donor age and female sex were independent risk factors for SAE. In IPTW-adjusted analyses, allo-HSCT from older haploidentical donors was associated with inferior overall survival (OS) and relapse-free survival (RFS) compared with UCB. In PSM analyses of elderly high-risk recipients, OD-PTCy-Haplo resulted in significantly worse OS and RFS than UCB. Older donor age emerged as a donor characteristic associated with increased donor SAE risk and inferior patient survival, particularly in haploidentical transplantation. UCB may offer a more favourable balance between donor safety and patient outcomes in selected high-risk settings.

This study examined changes in practice patterns and outcomes of allogeneic hematopoietic cell transplantation (HCT) over the past 20 years. Data were analyzed from a Japanese nationwide registry of consecutive adult patients with acute myeloid leukemia who underwent allogeneic HCT between 2001 and 2020. The study population included 17,553 patients, of whom 6653 underwent allogeneic HCT in 2001–2010 and 10,900 in 2011–2020. Patients in the later period were older, were more likely to be in first complete remission, and more frequently received umbilical cord blood transplantation. After adjusting for major covariates, the 2011–2020 cohort had lower risks of overall mortality (hazard ratio [HR], 0.84; 95

Post-transplant cyclophosphamide (PTCy) is now being increasingly applied to HLA-matched donor (MD) transplantation. Prior studies in Western countries have demonstrated that allogeneic hematopoietic cell transplantation (allo-HCT) employing PTCy yields better outcomes with HLA-matched donors (MDs) than with haploidentical donors (HIDs). However, the effect of HLA mismatch may differ among racial groups. We retrospectively analyzed adult patients with hematological malignancies who underwent their first allo-HCT with PTCy from MDs or HIDs registered to the Japanese registry database between 2013 and 2021. Among 63 (related, n = 33; unrelated, n = 30) and 1261 patients who received MD and HID allo-HCT with PTCy, 50 (related, n = 30; unrelated, n = 20) and 100 patients were assigned to MD and HID groups by 1:2 propensity score matching (PSM). The results showed that MD recipients had better neutrophil recovery (hazard ratio [HR], 1.48; 95

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) offers a curative potential for myelodysplastic syndrome (MDS) and myelodysplastic/myeloproliferative neoplasm (MDS/MPN). We examined survival trends using a nationwide database of 7175 patients who underwent their first allo-HSCT between 1998 and 2022. Overall mortality decreased over time in patients with early MDS (hazard ratio [HR] 0.79, 95% confidence interval [CI] 0.65-0.97, p = 0.026 in 2013-2017; HR 0.54, 95% CI 0.42-0.70, p < 0.001 in 2018-2022), advanced MDS (HR 0.80, 95% CI 0.71-0.90, p < 0.001 in 2013-2017; HR 0.74, 95% CI 0.65-0.85, p < 0.001 in 2018-2022), chronic myelomonocytic leukaemia (HR 0.45, 95% CI 0.32-0.64, p < 0.001 in 2013-2017; HR 0.53, 95% CI 0.37-0.74, p < 0.001 in 2018-2022) and atypical chronic myeloid leukaemia (HR 0.32, 95% CI 0.13-0.80, p = 0.016 in 2013-2017; HR 0.26, 95% CI 0.10-0.68, p = 0.006 in 2018-2022). These decreases in overall mortality were mainly attributable to reductions in non-relapse mortality. Meanwhile, no significant difference in overall mortality was observed in patients with MDS/MPN-unclassified and therapy-related myeloid neoplasm. Across all disease subtypes, relapse incidence did not significantly decrease over time, highlighting persistent challenges in reducing the risk of post-transplant relapse.

The Disease Risk Index (DRI) is a widely used prognostic tool following hematopoietic stem cell transplantation (HSCT), based on disease classification and status. However, the refined DRI (rDRI) does not fully account for regional variations in disease distribution and treatment practices. To refine the rDRI by accounting for underrepresented disease entities in the rDRI and by considering regional differences in HSCT treatment strategies, and to identify the most suitable donor selection strategy based on the newly developed disease risk criteria. We analyzed 7720 patients with hematologic malignancies who underwent their first allogeneic HSCT between 2014 and 2016 and developed a region-adjusted DRI (raDRI) using the Japanese registry database. We then validated predictive performance in 5108 patients transplanted between 2017 and 2018. The raDRI demonstrated superior accuracy compared with the rDRI (time-dependent AUC: .705 versus .670; integrated calibration index: .016 versus .017). In patients with low to intermediate raDRI, matched related donors (MRD) were associated with improved overall survival compared with matched unrelated bone marrow donors (bone marrow (BM): hazard ratio (HR) .50, 95% CI: .26 to .96; peripheral blood (PB): HR .54, 95% CI: .36 to .83), whereas no differences were seen in patients with high to very high raDRI (MRD-BM: HR: 1.03, 95% CI: .69 to 1.54, MRD-PB: 1.15, 95% CI: .89 to 1.49). Our findings underscore that prognostic indices such as the DRI are inherently shaped by the populations and clinical practices from which they are derived. Regional differences in disease prevalence, treatment strategies, and donor-source utilization can substantially influence risk stratification and transplant outcomes.

ABSTRACT:Cord blood transplantation (CBT) is a curative option for patients with high-risk acute myeloid leukemia (AML), including therapy-related AML (t-AML). However, the optimal prophylaxis for graft-versus-host disease (GVHD) remains unclear. We conducted a nationwide, retrospective cohort study including 3222 adults with high-risk AML (t-AML and non-t-AML) who underwent their first CBT in Japan between 2010 and 2023. GVHD prophylaxis consisted of cyclosporine or tacrolimus combined with mycophenolate mofetil (CSP/TAC + MMF) or methotrexate (CSP/TAC + MTX). MMF regimens were associated with faster neutrophil engraftment than MTX regimens (P < .001). However, CSP/TAC + MMF showed significantly higher incidences of grades 2 to 4 acute GVHD (P < .001) and chronic GVHD (P < .001). Two-year transplant-related mortality and relapse rates were 26 to 38% and 41 to 46%, respectively. Overall survival and disease-free survival at 2 years were higher with MTX than with MMF (P < .001 and P = .003, respectively), indicating a modest survival advantage for MTX. Multivariable analysis identified older age (≥55 years), male sex, Karnofsky performance status <80, higher hematopoietic cell transplantation-specific comorbidity index, and no remission at transplantation as adverse prognostic factors. Notably, MMF use was associated with an increased risk of human herpesvirus 6 encephalitis. Both CSP/TAC + MMF and CSP/TAC + MTX regimens support successful CBT in high-risk AML. Although MMF accelerates engraftment, this benefit is offset by greater GVHD and viral complications. These real-world, nationwide data highlight the need to individualize GVHD prophylaxis based on patient and transplant characteristics and provide essential benchmarks for future multicenter prospective studies.

Post-transplant cyclophosphamide-based haploidentical transplantation (PTCy-haplo) and umbilical cord blood transplantation (uCBT) have the potential to mitigate the adverse impact of pretransplant measurable residual disease (MRD) on post-transplant survival of patients with acute myeloid leukemia (AML). To compare outcomes between PTCy-haplo and uCBT in patients with MRD-positive AML, we retrospectively analyzed MRD-positive AML patients aged ≥16 years enrolled in the Japanese nationwide registry from 2015 to 2023 who underwent PTCy-haplo (n = 94) or single uCBT (n = 275) as first transplantation. MRD was evaluated by polymerase chain reaction for chimeric genes (n = 139) or Wilms' tumor 1 expression (n = 230). In multivariable analyses, the PTCy-haplo and uCBT groups showed comparable relapse-free survival (RFS) (hazard ratio [HR], 1.06; 95% confidence interval [CI], 0.67‒1.67; P = 0.809), overall survival (HR, 0.92; 95% CI, 0.57‒1.49; P = 0.735), graft-versus-host disease (GVHD)-free RFS (HR, 0.89; 95% CI, 0.61‒1.31; P = 0.560), chronic GVHD (cGVHD)-free RFS (HR, 1.20; 95% CI, 0.81‒1.78; P = 0.368), relapse (HR, 0.78; 95% CI, 0.39-1.57; P = 0.490) and nonrelapse mortality (HR, 1.48; 95% CI, 0.79-2.79; P = 0.230). Compared to the uCBT group, the PTCy-haplo group showed lower incidences of grade II‒IV (HR, 0.60; 95% CI, 0.39-0.92; P = 0.020) and III‒IV acute GVHD (aGVHD) (HR, 0.28; 95% CI, 0.10-0.79; P = 0.016), but a higher incidence of extensive cGVHD (HR, 2.23; 95% CI, 1.16-4.29; P = 0.017). Furthermore, higher likelihoods of neutrophil (HR, 2.12; 95% CI, 1.61-2.80; P < 0.001) and platelet engraftment (HR, 1.96; 95% CI, 1.39-2.76; P < 0.001) were observed in the PTCy-haplo group. In subgroup analysis, uCBT was associated with improved RFS in AML with poor cytogenetic risk (HR for PTCy-haplo versus uCBT, 2.49; 95% CI, 1.04-5.97; P for interaction = 0.032). In conclusion, survival outcomes were comparable between PTCy-haplo and uCBT in patients with MRD-positive AML. PTCy-haplo was associated with a lower risk of aGVHD, a higher risk of cGVHD and superior hematopoietic engraftment. In the subgroup of patients with poor cytogenetic risk, uCBT was associated with improved RFS.

Background In adult patients with Philadelphia chromosome–negative B-cell acute lymphoblastic leukemia (Ph– B-ALL), treatment strategies must balance long-term survival with the mitigation of therapy-related toxicity. The introduction of the bispecific T-cell engager blinatumomab (Blina) has emerged as a promising approach, particularly for measurable residual disease (MRD)-positive patients. However, the optimal timing of Blina administration and its role in modulating chemotherapy intensity remain to be fully elucidated. We conducted a comparative analysis of two prospective clinical trials: ALL/MRD2019, which added Blina only for patients with post-intensive chemotherapy MRD positivity, and ALL/MRD2023, which implemented upfront Blina in all patients following early consolidation with reduced-intensity chemotherapy. Methods Both protocols consisted of induction therapy (Treatment A) followed by consolidation using cytarabine (Treatment B) and methotrexate (Treatment C). MRD was evaluated by allele-specific oligonucleotide quantitative PCR targeting rearranged TCR and IG genes. In the ALL/MRD2019 protocol, patients who were MRD-negative after Treatment C-1 received additional cycles of A, B, and C, followed by maintenance. MRD-positive patients received one additional A course, omitted additional B and C, and received 4 cycles of Blina. In the ALL/MRD2023 protocol, all patients received 4 cycles of Blina after Treatment C-1, regardless of MRD status. In both protocols, patients with MRD positivity after C-1 or with relapse during therapy were recommended for allogeneic stem cell transplantation if feasible; non-transplant candidates received 2 years of maintenance. ALL/MRD2023 omitted Treatment B-2 and C-2 (thus reducing chemotherapy intensity) but increased intrathecal prophylaxis from 7 to 12 doses. As both studies are ongoing, the primary endpoints of this interim analysis were 2-year overall survival (OS) and leukemia-free survival (LFS). Results As of June 2025, 137 patients had been enrolled in the ALL/MRD2023 study and 121 in the ALL/MRD2019 study (total 258 patients). The MRD negativity rate after induction (Treatment A-1) was 53.3% in ALL/MRD2023 vs 45.5% in ALL/MRD2019 (p=0.21). In the ALL/MRD2019 cohort, 26.4% were MRD-positive after Treatment C-1 and received Blina accordingly. The 2-year OS and LFS were 98.9% (95%CI: 92.5 to 99.8) and 85.6% (95%CI: 71.9 to 92.9) in ALL/MRD2023, compared to 89.6% (95%CI: 82.0 to 94.1) and 74.1% (95%CI: 64.7 to 81.3) in ALL/MRD2019, respectively (OS: p=0.07, LFS: p=0.69). Age-stratified analyses showed consistently superior 2-year OS and LFS in ALL/MRD2023 across all age groups (16–35, 36–55, 56–65 years), with OS: 100% (95%CI: not reached to not reached) vs 91.4% (95%CI: 78.7 to 96.7), 97.3% (95%CI: 82.3 to 99.6) vs 88.5% (95%CI: 72.2 to 85.5), and 100% (95%CI: not reached to not reached) vs 87.5% (95%CI: 65.8 to 95.9); and LFS: 87.3% (95%CI: 71.9 to 94.6) vs 71.3% (95%CI: 56.3 to 81.9), 90.9% (95%CI: 77.4 to 96.5) vs 73.6% (95%CI: 55.4 to 85.3), and 93.3% (95%CI: 61.3 to 99.0) vs 80.3% (95%CI: 58.8 to 91.4), respectively. Among MRD-negative patients after Treatment C-1, 2-year OS and LFS were 98.6% (95%CI: 90.4 to 99.8) and 92.0% (95%CI: 82.7 to 96.4) in ALL/MRD2023 vs 91.1% (95%CI: 82.3 to 95.7) and 76.8% (95%CI: 65.6 to 84.7) in ALL/MRD2019 (OS: p=0.13, LFS: p=0.57). Among MRD-positive patients after Treatment C-1, ALL/MRD2023 showed 2-year OS and LFS of 100% (95%CI: not reached to not reached) and 72.2% (95%CI: 41.6 to 88.6) compared to ALL/MRD2019 [85.3% (95%CI: 65.4 to 19.9) and 67.2% (95%CI: 65.4 to 94.2)] (OS: p=0.22, LFS: p=0.93). Conclusion Although the follow-up period remains relatively short and statistical significance has not yet been demonstrated, preliminary data suggest that the ALL/MRD2023 protocol with upfront blinatumomab administration and reduced-intensity chemotherapy may offer improved OS and LFS compared to the conventional intensive chemotherapy approach of ALL/MRD2019. Given the numerically superior outcomes observed across multiple age groups and MRD strata, the ALL/MRD2023 regimen represents a promising treatment strategy that warrants further validation through longer follow-up and mature outcome analyses. These findings support the potential of upfront Blina to enhance survival while minimizing chemotherapy-related toxicity in adult Ph– B-ALL.

The SARS-CoV-2 pandemic disrupted healthcare systems worldwide, particularly affecting hematopoietic stem cell transplantation (HSCT) activities. Understanding the impact of the SARS-CoV-2 pandemic on transplant practices, especially in Japan, where cord blood transplantation (CBT) is prevalent, is crucial. A total of 40,444 allogeneic HSCT cases in Japan between 2011 and 2021 were examined using an interrupted time series analysis to assess the impact of COVID-19 on CBT utilization. Following the SARS-CoV-2 pandemic, CBT cases demonstrated a significant increase (11.06 [95% confidence interval (CI): 1.87 to 20.25] cases per month), whereas bone marrow transplantation cases decreased, by 10.74 cases per month (95% CI, −19.84 to −1.63 cases per month). Total HSCT cases remained stable with a level change of 5.47 cases per month (95% CI, −10.07 to 21.01 cases per month) and a trend change of −1.11 cases per month (95% CI, −2.22 to 0.004 cases per month). The interrupted time series analysis showed significantly increased CBT cases in Japan, highlighting its crucial role as an alternative transplant source during the pandemic. CBT offset the impact of the decrease in bone marrow transplantation and contributed to the maintenance of HSCT activity in Japan during the unprecedented crisis.