仲宗根 秀樹

Choosing an optimal alternative donor is an important clinical concern in allogeneic hematopoietic cell transplantation (HCT). In Japan, single-unit umbilical cord blood transplantation (UCBT) has been widely used in the last two decades, whereas HCT from HLA-haploidentical related donors (haplo-HCT) has been increasingly used following the advent of posttransplant cyclophosphamide (PTCY) for graft-versus-host disease (GVHD) prophylaxis. This registry-based study aimed to compare outcomes between single-unit UCBT (n = 848) and PTCY-based haplo-HCT (n = 241) performed during first complete remission in patients with acute myeloid leukemia. UCBT was associated with a lower likelihood of engraftment (P < 0.001), a higher risk of grade 2-4 and grade 3-4 acute GVHD (P = 0.003 each), and a lower risk of extensive chronic GVHD (P = 0.048). The UCBT and haplo-HCT groups did not significantly differ in 3-year probabilities of overall survival (68% versus 69%, P = 0.686), GVHD/relapse-free survival (55% versus 54%, P = 0.866), relapse (14% versus 16%, P = 0.463), and non-relapse mortality (21% versus 19%, P = 0.403), respectively, which were confirmed with multivariate analysis. These results indicate that both procedures should be considered viable options for patients lacking a matched donor.

In this Japanese registry-based analysis of 9105 adult patients with acute leukemia undergoing allogeneic hematopoietic stem cell transplantation, a marked difference in survival was observed based on platelet levels: ≤ 20 × 109/L, 20-50 × 109/L, and > 50 × 109/L. The number of patients with thrombocytopenia receiving cord blood (CB, 39%) was significantly larger than those receiving unrelated bone marrow (uBM, 17%) on Day 50 (p < 0.001); however, this difference disappeared on Day 100 posttransplantation (both 11%, p = 0.4).

Pre-engraftment syndrome (PES) is a unique complication of cord blood transplantation (CBT) whose risk factors and impact on transplant outcomes remain controversial. Using a nationwide database in Japan, we analyzed a total of 3734 patients who underwent single-unit CBT. PES occurred in 18.3% of patients, and risk factors for PES included a higher hematopoietic cell transplantation-specific comorbidity index, first transplantation, myeloablative conditioning (MAC), lower total nucleated cell (TNC) dose, and graft-versus-host disease (GVHD) prophylaxis regimens excluding tacrolimus with methotrexate. Patients who developed PES had significantly higher incidences of grade II-IV acute GVHD (53.1% vs. 31.3%, p < 0.001) and chronic GVHD (27.2% vs. 21.7%, p = 0.002) compared to those without PES. Landmark analysis with multivariable adjustment revealed that PES was independently associated with increased non-relapse mortality (NRM, hazard ratio [HR] 1.46; 95% CI 1.22-1.75; p < 0.001), reduced relapse incidence (HR 0.78; 95% CI 0.63-0.96; p = 0.020), and a trend toward inferior overall survival (OS, HR 1.13; 95% CI 0.98-1.30; p = 0.088). Moreover, patients who experienced both PES and acute GVHD had the highest 2-year NRM (31.7%; 95% CI 26.0%-37.6%) and the lowest 2-year OS (55.9%; 95% CI 50.0%-62.4%), compared with those who experienced either PES (NRM 20.7%; OS 65.0%) or acute GVHD (NRM 19.5%; OS 62.8%) (p < 0.001), highlighting the combined effects of these complications. This study, the largest to date on PES, demonstrates its clinical significance as an early complication with lasting effects on transplant outcomes.

BACKGROUND: The hematopoietic cell transplantation comorbidity index (HCT-CI) assigns a score of 2 to Rheumatologic (RD), reflecting its presumed association with increased nonrelapse mortality (NRM) based on data from earlier transplant eras, when disease control and immunosuppressive management were inadequate. Given recent advances in transplant-related supportive care and RD treatment, reassessment of the prognostic impact of preexisting RD in contemporary risk models is warranted. OBJECTIVES: We assessed the impact of preexisting RDs on outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). STUDY DESIGN: In this retrospective cohort study, using Japan's nationwide Transplant Registry Unified Management Program database, we analyzed the data of adults (≥16 yr) who underwent first allo-HSCT for hematologic malignancies between 2006 and 2018. Patients with a prior diagnosis of RD at the time of transplantation were compared with those without. To minimize confounders, we performed 1:4 (RD:control) propensity score matching (PSM) based on 14 transplant-related variables. RESULTS: Overall, the data of 216 patients with RD and 864 matched controls were analyzed. The standardized mean difference for all variables except HSCT year was below the threshold of .1. The 3-yr overall survival (OS) was 41.1% (95% CI: 33.9-48.1) in the RD group versus 44.7% (95% CI: 41.2-48.2) in the control group. NRM was 31.8% (95% CI: 25.2-38.5) versus 26.0% (95% CI: 23.0-29.0), and CIR was 31.8% (95% CI: 25.4-38.4) versus 34.3% (95% CI: 31.0-37.5), without significance differences. Rates of grade II-IV acute graft versus host disease (GVHD) were comparable between the RD (33.2%, 95% CI: 27.0-39.6) and control (32.7%, 95% CI: 29.6-35.9) groups, as were chronic GVHD rates (22.9%, 95% CI: 17.3-29.0 versus 24.3%, 95% CI: 21.3-27.3). Day-30 neutrophil engraftment occurred in 89.8% (95% CI: 84.9-93.2) of patients with RD and 87.0% (95% CI: 84.6-89.1) of controls. In univariate Cox regression, RD was not a significant predictor for OS, NRM, or relapse. Subgroup analyses stratified by donor type and conditioning regimen showed consistent findings, with no excess mortality or GVHD attributable to RD history. To assess the applicability of our findings to older or more comorbid patients, we conducted a subgroup analysis of those aged >59 yr and those with HCT-CI >0 (excluding the RD component) in the prematching cohort. The 3-yr OS was 38.0% (95% CI, 23.6-52.3) in the RD group and 33.6% (95% CI, 31.9-35.3) in the control group (P = .71), and the 3-yr NRM was 37.4% (95% CI, 22.7-52.1) and 34.7% (95% CI, 33.0-36.4), respectively (P = .79). Thus, a history of RD had little effect on OS or NRM even in these higher-risk subgroups. CONCLUSIONS: In the contemporary allo-HSCT era, the unfavorable impact of preexisting RD on survival and NRM appears insignificant. Further studies incorporating detailed information on RD type and treatment history are warranted to refine comorbidity risk models and to reassess if RD should be weighted in the HCT-CI.