Our study includes 278 patients aged between 40 and 50 years from 29 centers who received allogeneic hematopoietic stem cell transplantation (allo-HSCT) from matched sibling donors (MSDs) (n = 106) and haploidentical donors (HIDs) (n = 172) over the last decade. Univariate analysis revealed that HID recipients was associated with more serious disease severity, a delayed allo-HSCT after diagnosis, a higher pretransplant transfusion burden and poor performance status pre-transplant than MSD recipients in clinical settings. After these pretransplant clinical factors were well balanced following propensity score-matching (PSM), 80 matched pairs were selected for further analysis. Following PSM, the cumulative incidences of neutrophil were comparable between two matched groups (P = 0.14), while the 100-day engraftment rates of platelet were significant lower in HID-HCT (P < 0.001); The HID cohort showed higher cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) compared with MSD group (P = 0.04). In contrast, the incidence of severe (grade III-IV) acute GVHD and chronic GVHD were not statistically significant (severe acute GVHD P = 0.10; chronic GVHD P = 0.28). Our study observed comparable overall survival (OS) (P = 0.14); failure free survival (FFS) (P = 0.23); GVHD-free/relapse-free survival (GRFS) (P = 0.26) between matched HID and MSD recipients. In conclusion, our data indicates that allo-HSCT from an HID could be considered for SAA patients between 40 and 50 years old who do not have an MSD.

Real-world data on blinatumomab (BLI) and inotuzumab ozogamicin (INO) for relapsed or refractory B-acute lymphoblastic leukemia (RR-ALL) before hematopoietic stem cell transplantation (HCT) are limited. To compare the efficacy of salvage therapy with BLI and/or INO and conventional chemotherapy as a bridge to HCT, we retrospectively evaluated patients with RR-ALL who underwent first HCT at our institute between 2004 and 2023. Based on whether they had received salvage therapy with BLI and/or INO, 70 recipients were divided into a BLI/INO (n = 22) and a control group (n = 48). The complete remission (CR) rate before HCT was higher in the BLI/INO group than in the control group (77.3 % vs. 35.4 %, p = 0.002). Two years after the first HCT, the overall survival (OS) and disease-free survival (DFS) were significantly higher in the BLI/INO group than in the control group (OS, 63.0 % vs. 31.2 %, p = 0.022; DFS 49.6 % vs. 22.9 %, p = 0.049), with comparable cumulative incidence of relapse (CIR, 41.3 % vs. 47.9 %; p = 0.767) and lower tendency of non-relapse mortality (NRM, 9.1 % vs. 29.2 %; p = 0.057). Multivariate analysis revealed that non-CR status before HCT was the only factor associated with poor OS (hazard ratio [HR], 4.263; p < 0.001) and higher CIR (HR, 2.250; p = 0.048). In patients in CR at HCT, there was no difference in HCT outcomes at 2 years (OS, 82.4 % vs. 58.8 %; p = 0.324; DFS, 64.2 % vs. 47.1 %; p = 0.496; CIR, 24.1 % vs. 41.2 %; p = 0.375; NRM, 11.8 % vs. 11.8 %; p = 0.950). BLI and/or INO therapy for RR-ALL was associated with better survival after HCT, probably due to the higher CR rate.

Allogeneic hematopoietic stem cell transplantation is recommended for TP53-mutant acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) despite a high relapse rate and poor survival. To understand TP53 alterations on a molecular level and define stratified prognostic outcomes following transplantation, we performed targeted next-generation sequencing on 63 patients who underwent transplantation for TP53-mutant AML/MDS and profiled their molecular spectrum. Sixty-eight TP53 mutations were detected, with a median variant allele frequency of 46.8%. Copy number alterations at the TP53 locus were present in 19 patients (30%). Complex karyotype was detected in 48 patients (76%) and was significantly associated with larger TP53 clone size, bi-allelic status, and the absence of concurrent mutations, reflecting the high TP53 mutational burden. Specifically, 51 patients (81%) with the dominant TP53 clone greatly overlapped with those with the complex karyotype. Multivariable overall survival (OS) analysis identified AML (hazard ratio [HR], 2.51; P = 0.03) and TP53 clonal dominance (HR, 5.30; P = 0.002) as prognostic factors. One-year OS was worse in AML with the dominant TP53 clone than in others (13% vs 61%; P < 0.001). Our results underscore the utility of mutational profile-guided risk stratification in patients with TP53-mutant AML/MDS, and could aid in transplantation-related decision-making.

Fluid retention presenting as effusions in body cavities is sometimes encountered following allogeneic stem cell transplantation (allo-HSCT). It is unclear whether cavity effusions at independent sites may serve as cumulative correlates of fluid overload and whether a higher number of effusion sites are associated with a worse prognosis. Here, we comprehensively reviewed pleural, peritoneal, and pericardial effusions in 178 first allo-HSCT recipients retrospectively. A total of 123 (69.1%) patients developed effusions in any cavity. New pleural, peritoneal, and pericardial effusions were found after allo-HSCT in 106, 88, and 53 patients, at a median of 38.0 (range, 2-2950), 22.5 (range, 2-1324), and 40 (range, 2-945) days, respectively. The cumulative incidence at day 100 was 41.0%, 40.4%, and 20.8%, respectively. Of the 92 patients who presented with effusions by day 100, 28 patients presented with effusion in a single cavity, 39 in two cavities, and 25 in all three cavities. The 2-year overall survival rates of patients with effusions in zero, one, two, and three cavities by day 100 were 86.1%, 60.0%, 59.6%, and 18.8%, respectively, showing an additive adverse association with outcome. Prospective studies to further characterize fluid dynamics following allo-HSCT are warranted.

Hematopoietic stem cell transplantation (HCT) is a potentially curative treatment for children with hematological or immunological disorders. However, treatment-related morbidity and mortality remain concerning. Various comorbidity indices are currently used to assess the risk of complications following pediatric HCT.

We compared four comorbidity indices to determine which can most accurately estimate the risk of morbidity and mortality in pediatric nonmalignant HCT. We analyzed 308 pediatric allogeneic nonmalignant HCTs performed between January 2010 and December 2022. Four indices were evaluated: hematopoietic stem cell transplantation-specific comorbidity index (HCT-CI), youth nonmalignant hematopoietic stem cell transplantation comorbidity index (ynHCT-CI), simplified ynHCT-CI, and simplified comorbidity index (SCI). The primary outcome was overall survival (OS). The secondary outcome was graft-versus-host disease (GvHD)-free event-free survival (EFS), defined as acute GvHD Grade 3 or 4, extensive chronic GvHD, retransplantation, or death. The area under the receiver operator characteristic curve (AUC) was calculated per index and outcome at 100 days, 1 year, and 2 years post-HCT.

For OS, AUC values ranged from 0.611 to 0.755. The simplified ynHCT-CI and ynHCT-CI generally had superior discriminative abilities for OS, although no significant difference was found. For EFS, AUC values were between 0.539 and 0.632. The ynHCT-CI performed best for EFS, with AUC values of the simplified ynHCT-CI marginally lower. The ynHCT-CI significantly outperformed the HCT-CI at 100 days post transplantation (p = 0.045).

The ynHCT-CI most accurately predicted outcomes after pediatric nonmalignant HCT. We propose the use of ynHCT-CI in future clinical management guidelines in this cohort.

Diffuse large B cell lymphoma, not otherwise specified (DLBCL-NOS) is the most common aggressive lymphoma and can be cured with CHOP-R immunochemotherapy in 60% of cases. The second-line therapy includes salvage regimens followed by autologous stem cell transplantation (ASCT), which offers a cure to a minority of patients due to limitations in efficacy and eligibility. These data present the unmet need in the field, and this review article focuses on how second-generation chimeric antigen receptor T (CAR T) cell therapy targeting CD19 antigen may improve the outcomes with relapsed/refractory DLBCL. In heavily pretreated patients, who have dismal outcomes with conventional therapy, all three approved products-tisangenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), and lisocabtagene maraleucel (liso-cel) have shown durable, unprecedented complete responses with the potential for cure. When compared to salvage regimens and ASCT as the standard of care, axi-cel and liso-cel, unlike tisa-cel, have demonstrated superiority in long-term control. In ASCT-ineligible r/r DLBCL, liso-cel has shown a favourable benefit-risk ratio. Regarding safety, two adverse events of interest have emerged: cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, both of which are manageable. Real-world evidence reflects the results of pivotal trials while favouring axi-cel in heavily pretreated patients, albeit with higher toxicity. The main barrier to the implementation of this treatment modality is the cost associated with the process of CAR T therapy, along with complications and reimbursement issues. However, the barriers can be overcome, and CAR T therapy has the potential to become the standard of care in relapsed/refractory DLBCL. Furthermore, with advances in the scientific engineering of CAR products and the understanding of novel treatment modalities currently being tested in clinical trials, we believe that targeted cellular therapy will become the future of relapsed/refractory DLBCL treatment.

Older adults (OA) with DLBCL are a heterogenous population with suboptimal outcomes. In this review, we identify and address the unique challenges encountered in the care of OA with DLBCL. We elaborate on the role and limitations of current geriatric assessment (GA) tools and ways to incorporate fitness in therapeutic decision making. We suggest best practices to implement GA in routine practice and clinical trials. The most widely used tool is simplified GA (sGA) which categorizes patients into fit, unfit and frail groups. Patients who are fit benefit from full dose/curative approach, whereas consideration should be made to reduce the intensity of chemotherapy for unfit patients. Frail patients with DLBCL are a major unmet need without any satisfactory treatment options. Ongoing investigations combining novel therapies into chemotherapy-free regimens are underway with promising early results. In the relapsed/refractory (R/R) setting, anti-CD19 CAR-T cell therapy (CART) is now the standard of care for primary refractory disease or relapse within 12 months of completing therapy. Autologous stem cell transplant is still a consideration for fit OA with relapse >12 months after completing therapy. The recent approval of bispecific antibodies is a welcome advance that will greatly benefit OA not eligible for CART. Other regimens available for patients ineligible for CART or for those who experience progression post-CART include polatuzumab-rituximab±bendamustine, tafasitamab-lenalidomide, loncastuximab or chemotherapy-based approaches such as rituximab-gemcitabine-oxaliplatin. We discuss the changing paradigm in R/R DLBCL and spotlight emerging data from recent congresses that can improve outcomes in this vulnerable population.

Double-unit cord blood transplantation (dCBT) has been associated with high rates of progression-free survival (PFS) in adults with hematologic malignancies but also with relatively high rates of acute graft-versus-host disease (aGVHD). We conducted a single-arm, phase 2 clinical trial that investigated the addition of tocilizumab, an interleukin-6 receptor blocker, to cyclosporine-A (CSA) and mycophenolate mofetil (MMF) for aGVHD prophylaxis after intermediate-intensity dCBT. A total of 45 patients (median age, 47 years; range, 27-60 years; 80% acute leukemia; median hematopoietic cell transplant-comorbidity index, 2) were enrolled from March 2018 to March 2021. Transplant outcomes were compared with 39 previous CSA and MMF dCBT controls with similar inclusion criteria. Tocilizumab recipients had less pre-engraftment syndrome (38%; 95% confidence interval [CI], 24-52 vs 72%; 95% CI, 54-84; P < .001) but inferior day 45 neutrophil engraftment (93%; median, 25.5 days vs 97%; median, 22 days; P = .009]. The primary end point of day 100 grade 2 to 4 aGVHD was no different between groups (71%; 95% CI, 55-82 with tocilizumab vs 82%; 95% CI, 65-91; P = .11). However, there was a trend toward a lower day 100 incidence of stage 1 to 4 lower gastrointestinal aGVHD with tocilizumab (16%; 95% CI, 7-28 vs 33%; 95% CI, 19-48; P = .059). There were no significant differences in the 3-year incidences of relapse, transplant-related mortality, PFS, or overall survival between the groups. Tocilizumab recipients exhibited a distinct pattern of gut microbiome disruption. In summary, tocilizumab-based GVHD prophylaxis delayed neutrophil recovery without a significant reduction in aGVHD and had no survival benefit after dCBT. Investigation of alternative strategies to prevent severe aGVHD after dCBT is warranted. This trial was registered at www.clinicaltrials.gov as #NCT03434730.

High-dose posttransplantation cyclophosphamide (HD-PTCy), given at 50 mg/kg/day on days +3/+4, is a standard-of-care graft-versus-host disease (GVHD) prophylaxis for allogeneic hematopoietic cell transplantation (HCT). Our murine MHC-haploidentical HCT studies suggested intermediate-dose PTCy produces superior GVHD control compared with HD-PTCy and PTCy is maximally effective on day +4. We conducted a single-institutional prospective phase 1/2 trial to reduce PTCy dosing to 25 mg/kg/day on days +3/+4 or on day +4 only for myeloablative HLA-haploidentical bone marrow HCT using PTCy, sirolimus, and mycophenolate mofetil. Among 35 patients, 89% were ethnic/racial minorities, 46% had high/very-high-risk disease, and median comorbidity score was 3. The phase 1 dose-limiting-toxicity, grade III-IV acute GVHD, was not observed after either reduced-PTCy dose level. PTCy 25 mg/kg/day on days +3/+4 (intermediate-dose (ID)-PTCy; n = 23), the phase 2 dose, resulted in no grade II-IV acute GVHD; 2-year cumulative incidences of chronic GVHD requiring systemic immunosuppression, nonrelapse mortality, and relapse were 13%, 17%, and 22%, and 2-year overall survival, disease-free survival, and GVHD-free/relapse-free survival were 61%, 61%, and 52%. In exploratory analysis compared with HD-PTCy (n = 5), ID-PTCy resulted in significantly faster engraftment and T-cell reconstitution, fewer transfusions, less mucositis, and reduced severity of BK-virus-associated cystitis/urethritis; area-under-the-curve exposure of 4-hydroxycyclophosphamide (4HCY), a key cyclophosphamide metabolite, correlated with these outcomes but not with chronic GVHD occurrence. Ideal-body-weight-based PTCy dosing best approximated 4HCY exposure. ID-PTCy is effective and has apparent clinical benefits compared with HD-PTCy. Before broader implementation, further studies are needed to confirm these findings and define optimal PTCy dosing across various donor/graft types. This trial was registered at www.clinicaltrials.gov as #NCT03983850.

Prophylactic, diagnostic, and treatment strategies for acute graft-versus-host disease (aGVHD) may vary across medical centers and physicians. We aimed to investigate the relationship between center volume and the incidence and outcomes of aGVHD. This retrospective study included 28,786 patients who underwent their first hematopoietic stem cell transplantation (HSCT) (entire cohort) and 9498 patients who developed grade II-IV aGVHD (aGVHD cohort). Data were categorized into quartiles (very low, low, high, and very high) based on the number of HSCTs the treating center performed during the study period. We assessed the incidence of aGVHD using the entire cohort and overall survival (OS) using the aGVHD cohort. Higher center volume was associated with a higher incidence of grade II-IV aGVHD than very low center volume, with an adjusted hazard ratio of 1.07-1.11. Conversely, center volume was not associated with the incidence of grade III-IV aGVHD. OS after development of aGVHD was better in the higher center volume group than the very low-volume group, with an adjusted hazard ratio of 0.81-0.89. A very low-volume center was associated with a lower incidence of grade II-IV aGVHD in patients with allogeneic HSCT and poor survival in patients with aGVHD.

Few reports exist on the transplant outcomes of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH). This nationwide survey evaluated the clinical outcomes of pediatric patients with EBV-HLH who underwent allogeneic HCT.

Data from 32 pediatric patients with EBV-HLH who underwent their first allogeneic HCT between 2000 and 2020 were reviewed retrospectively.

Of the 32 patients, 12 had a performance status of 3-4 and 8 had multiple organ dysfunction. The cumulative incidence of engraftment on day 30 was 53.1% (95% confidence interval [CI] 34.1-68.9). The 1-year overall survival (OS) rate of the entire cohort was 56.2% (37.6-71.3). Univariate analysis revealed that poor ECOG-PS at HCT and a reduced-intensity conditioning regimen were significant risk factors for OS. Furthermore, multivariate analysis revealed that only ECOG-PS was a significant risk factor for OS. Sixteen of the 32 (50.0%) patients died after HCT, and the main causes of death were HLH progression (n = 12) and infection (n = 2). Most notably, 12 of the 13 patients with primary graft failure died of HLH.

Good general condition prior to HCT, which is typically achieved through optimal disease control, is essential for stable engraftment and long-term survival following allogeneic HCT.

Upfront autologous hematopoietic cell transplantation (autoHCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (MM). Comorbidities are routinely evaluated to determine eligibility and estimate mortality after autoHCT, including the history of prior solid tumor (PST). While PST is considered high-risk for worse survival based on widely used risk indices, its independent impact on transplant outcomes in MM remains unclear.

To elucidate the prognostic impact of PST in patients with MM undergoing upfront autoHCT.

We conducted a single-center retrospective analysis of consecutive MM patients who underwent upfront autoHCT between 1997 and 2021, categorizing them into those with (PST+) and without (PST-) prior solid organ malignancy. Primary endpoints were progression-free survival (PFS) and overall survival (OS).

Among 2853 patients included in this analysis, 274 (10%) were PST+ and 2579 (90%) were PST-. The PST+ patients were older (67 vs. 60 years; p<0.001), predominantly male (66% vs. 58%; p=0.010), were more often transplanted in the year 2010 or later (78% vs. 69%; p=0.003) and were more likely to have high-risk cytogenetic abnormalities (30% vs. 24%; p=0.06). There was no significant difference in pre-transplant hematologic response (p=0.33), day-100 post-transplant (p=0.35) or the best post-transplant response (p=0.27) between the PST+ and PST- groups. Similarly, there were no differences in pre-transplant (p=0.34) or best post-transplant (p=0.44) MRD status between the two groups. After a median follow-up of 53.8 months (range 0.2 - 262), the median PFS was comparable (36.7 months in PST+ vs. 39.9 months in PST-, p=0.31), yet the median OS was significantly shorter in the PST+ group (81.3 months vs. 104.0 months, p=0.020). Multivariable analysis confirmed PST as an independent predictor of inferior OS (HR 1.34, p=0.011).

MM patients undergoing upfront autoHCT with PST had worse OS compared to those without PST, despite similar response rates and PFS.

Post-transplant cyclophosphamide (PTCy) for graft-versus-host disease (GVHD) prophylaxis is now being used beyond haploidentical (HID) allogeneic hematopoietic cell transplant (alloHCT). However, the kinetics of chimerism in patients receiving PTCy and its impact on post-transplant relapse is unknown. In this study we describe the kinetics of donor chimerism in patients receiving PTCy, factors predisposing to mixed donor chimerism, and the associated survival outcomes.

Patients undergoing alloHCT at Mayo Clinic, Rochester, from January 2018 to June 2023 were included in the study. Full donor chimerism was defined as donor cell fraction ≥95%, and mixed chimerism as donor cell fraction <95%. Analysis of covariance was used to assess the trend of tacrolimus levels in patients with mixed vs. full donor CD3 chimerism. Relapse-free survival (RFS) and overall survival (OS) from transplant were determined using the Kaplan-Meier method. Mixed donor chimerism was considered a time-dependent covariate in multivariate analysis.

A total of 500 patients were evaluated. A total of 189 (37.8%) patients received myeloablative conditioning (MAC); 27 (14.3%) of whom received PTCy and 162 (85.7%) received methotrexate (MTX) for GVHD prophylaxis. Among patients receiving PTCy, HID and mismatched donor transplants were significantly associated with a lower risk of mixed CD3 chimerism. In patients receiving PTCy, myeloablative busulfan/fludarabine (BuFlu), compared to non-busulfan MAC regimens, was associated with an increased risk of day +90 mixed chimerism (OR 10.47, P=0.02). However, reduced intensity (RIC) BuFlu was not associated with an increased risk of mixed CD3 chimerism (OR 0.71, P=0.7). Among patients receiving MAC and PTCy, those with high tacrolimus levels (≥11 mcg/ml) beyond the 2nd week post-transplant period were more likely to have mixed CD3 chimerism (F1,145 = 4.15, P=0.043). In patients receiving MAC and PTCy, day +90 mixed CD3 chimerism was associated with an inferior RFS (1-year RFS: 89.16% vs. 40.0%, P = 0.009). Multivariate analysis showed that mixed donor CD3 chimerism was associated with an inferior RFS in patients receiving MAC and PTCy (HR 6.53, 95% CI 1.18 - 36.15, P=0.032).

Among patients receiving MAC and PTCy, detection of mixed donor CD3 chimerism at any timepoint after transplant portends an inferior RFS. A high tacrolimus level beyond 2nd week of transplant in this subset of patients was associated with mixed CD3 chimerism. The detection of mixed CD3 chimerism provides an opportunity to implement strategies that may help in decreasing the risk of relapse in this subset of patients.

While donor age significantly impacts allogeneic hematopoietic cell transplantation (HCT) outcomes, the effect of donor cytomegalovirus (CMV) serostatus, particularly in CMV-seronegative recipients, remains a critical consideration. Donor CMV seropositivity is linked to increased CMV viremia and non-relapse mortality (NRM) in these recipients. Given the limited scope of novel antiviral prophylaxis drugs, eg, letermovir solely for CMV-seropositive recipients and the association of post-transplant cyclophosphamide (PTCy) with increased CMV reactivation, this study investigates the impact of donor CMV serostatus on outcomes in CMV-seronegative acute myeloid leukemia (AML) patients undergoing HLA-matched or mismatched unrelated donor HCT with PTCy. We retrospectively analyzed data from the Center for International Blood and Marrow Transplant Research, including adult CMV-seronegative AML patients who underwent unrelated donor HCT with PTCy between 2017 and 2021. Primary outcome was overall survival (OS). Secondary outcomes included relapse, NRM, and acute/chronic graft-versus-host disease. Donor age was dichotomized at ≤32 and >32 years. Multivariable Cox proportional hazards models, stratified by donor age, and Restricted Mean Survival Time (RMST) and Restricted Mean Time Lost (RMTL) analyses were performed. Of 408 CMV-seronegative recipients, 127 received transplants from CMV-seropositive donors. Baseline characteristics were well-balanced between groups. Multivariable analysis demonstrated that recipients of CMV-seropositive donors had a significantly higher hazard of mortality (hazard ratios [HR] 1.51, 95% confidence interval [CI] 1.07 to 2.14, P = .019). Donor age and donor type did not significantly impact OS in this CMV seronegative patient population. RMST analysis showed that recipients with CMV-seronegative donors lived on average 2.95 months longer (P = .045), while RMTL ratio was 1.34 (P = .037), indicating that recipients of CMV-seropositive donors experienced a 34% higher risk of loss of survival time. The difference in OS was primarily driven by a trend toward increased relapse risk in the CMV-seropositive donor group (HR 1.42, 95% CI: 0.95 to 2.08, P = .06) rather than NRM (HR 1.19, 95% CI: 0.66 to 2.13, P = .56). In CMV-seronegative adult AML patients undergoing unrelated donor HCT with PTCy, CMV-seropositive donors are associated with worse OS than CMV-seronegative donors, likely linked to higher relapse risk. These findings underscore the importance of considering donor CMV serostatus in donor selection for CMV-seronegative recipients undergoing HCT with PTCy. Further investigation is necessary to optimize donor selection strategies and improve outcomes in this patient population.

Oral bacteria influence bloodstream infections in hematopoietic stem cell transplantation (HSCT). We investigated the effects of oral health management and its relationship with medical care delivery systems.

Patients aged >16 years who underwent HSCT, discharged from Japanese acute care hospitals between April 2018 and March 2022, were categorized into autologous and allogeneic HSCT groups. Multivariable analysis assessed the impact of peri-HSCT oral management on antibiotic use, narcotic injections, and mortality rates.

We included 12,248 patients, 5936 autologous and 6312 allogeneic HSCT patients, across 298 hospitals. The defined daily dose (DDD) of antibiotic use within 14 days post-transplantation in the oral and nonoral management groups for allogeneic HSCT patients was 34.10 (standard deviation [SD] 20.35) vs 36.37 (SD 21.33); broad-spectrum antibiotics use was 23.87 (SD 15.82) vs 24.45 (SD 15.76). Within 30 days post-transplantation, the DDD of antibiotic use was 69.13 (SD 40.18) vs 75.16 (SD 43.47) was 45.70 (SD 29.63) vs 47.95 (SD 30.48), respectively. In allogeneic HSCT patients, oral management resulted in lower DDD of antibiotic use by 2.66 within 14 days and 6.74 within 30 days post-transplantation, after adjustment for relevant factors. Broad-spectrum antibiotic use within 30 days post-transplantation showed a lower DDD by 2.79 (P < .01). Narcotic use led to a 0.34 lower DDD (P < .01) within 14 days and 0.70 lower DDD (P < .01) within 30 days. In autologous HSCT patients, oral management did not affect the outcomes. The certification standard for unrelated HSCT, categorized into four classes (no certification and certification levels 1-3), was associated with an 8.41 point increase in hospital oral management implementation per class.

Ensuring an appropriate oral environment for allogeneic HSCT patients helps preventing infection, extending life expectancy, and alleviating pain.

Coordinated care between dental and medical teams is essential to deliver safe, personalized, and high-quality patient outcomes during HSCT.

Cytomegalovirus (CMV) reactivation following allogeneic hematopoietic cell transplantation (HCT) is a significant complication; however, its impact on relapse remains controversial.

This study aimed to evaluate the clinical impact of CMV reactivation on relapse and survival after HCT in patients with acute leukemia.

We conducted a retrospective analysis of 1258 patients diagnosed with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) who underwent their first HCT between 2000 and 2020.

Our cohort included 871 patients with AML and 387 patients with ALL. Among all patients, 751 (61.6%) experienced CMV reactivation within one year post-HCT. CMV reactivation was associated with HCT from unrelated donors, anti-thymocyte globulin use, and the occurrence of acute graft-versus-host disease. Notably, CMV reactivation was associated with a lower risk of relapse (HR, 0.713; P = .001) and improved event-free survival (HR, 0.743; P = .001) in both AML and ALL patients. However, there was no significant difference in non-relapse mortality or overall survival according to CMV reactivation.

These results suggest that CMV reactivation may prevent post-HCT relapse and enhance event-free survival in AML and ALL patients. Therefore, a CMV prophylaxis strategy is warranted to establish a safe range of CMV reactivation titers that can yield beneficial effects.

BackgroundThe medication regimen complexity index (MRCI) quantifies patient-level regimen complexity, and higher scores are associated with adverse clinical outcomes. Characterization of regimens using the MRCI for allogeneic hematopoietic cell transplant (allo-HCT) recipients remains unexplored. Regimens may include letermovir which is used for cytomegalovirus prophylaxis and may prevent the need for addition of complex preemptive therapies. However, quantification of complexity in patients receiving letermovir has not been described.ObjectiveThis study aimed to compare MRCI scores over a one-year period in allo-HCT recipients who received letermovir prophylaxis versus those who did not.MethodsA retrospective analysis included adults who underwent allo-HCT from January 1, 2016 to October 31, 2021. MRCI scores were calculated at admission, discharge, day +100, 6 months, and 1-year post-transplant.ResultsA total of 218 patients were included, with 67 receiving letermovir and 151 not receiving letermovir. Median MRCI scores were comparable at discharge post allo-HCT (23 [10-39] vs 22 [12-37], p = 0.97). However, at day +100, patients in the letermovir group exhibited significantly higher median scores compared to the non-letermovir group (59 [46-74] vs 50 [37-67], p = 0.009). By 1-year post allo-HCT, no significant difference in scores was observed between groups (47 [30-68] vs 41 [27-61], p = 0.12).Conclusion and RelevanceThis study revealed increased MRCI scores up to one year after transplantation in allo-HCT recipients receiving letermovir. The nonrandomized study design and potential patient differences between groups complicate the interpretation of the findings. Future analyses should aim to account for these differences.

To validate the ability of the haematopoietic cell transplantation comorbidity index (HCT-CI) to predict the outcomes of patients with severe aplastic anaemia (SAA) receiving haploidentical haematopoietic stem cell transplantation (haplo-HSCT), we conducted a retrospective study including 530 SAA patients. Patients were stratified based on their HCT-CI scores into three distinct risk categories: low-risk (HCT-CI scores of 0, n = 343), intermediate-risk (HCT-CI scores of 1, n = 126), and high-risk groups (HCT-CI scores ≥ 2, n = 61). The 100-day platelet engraftment rate was significantly higher in the low-risk group compared to the intermediate-risk and high-risk groups (92.1% vs. 86.5% vs. 83.6%, P = 0.014). In addition, compared with the intermediate-risk and high-risk groups, the low-risk group demonstrated superior 5-year overall survival (OS, 91.8% vs. 83.3% vs. 70.1%, P < 0.001) and graft-versus-host disease-free/graft failure-free survival (GFFS, 80.1% vs. 71.3% vs. 63.6%, P = 0.009). Multivariate analysis revealed that elevated HCT-CI scores and previous antithymocyte globulin treatment were independent risk factors for OS, whereas elevated HCT-CI scores and donor age ≥ 40 years were correlated with worse GFFS. Consequently, the HCT-CI is associated with the clinical outcomes of SAA patients following haplo-HSCT, and it is imperative to closely monitor patients with a high comorbidity burden.

The primary aim of this study is to evaluate the impact of diagnostic procedures and treatment interventions performed at our medical institution on the final outcomes and survival rates of patients with iatrogenic and traumatic pharyngeal perforation (PP).

We reviewed the medical records of 36 patients with iatrogenic and trauma-induced PP who were treated at the Quaternary Medical Center of Otorhinolaryngology between 2010 and 2020. Comorbidities were classified according to the Age-adjusted Charlson Comorbidity Index (ACCI) scoring system, and postoperative complications were classified according to the Clavien and Dindo scoring system.

Of the 36 patients, 15 (41.7%) were male and 21 (58.3%) were female. The median age was 73 years, and PP was typically diagnosed within one day. Notably, the perforation site was identified in the hypopharynx in 29 (80.5%) patients. The median ACCI score was 4, with the most frequent ACCI score observed being 5. During the treatment course, 17 patients (47.2%) experienced complications, with 9 of these patients experiencing grade IV complications according to the Clavien and Dindo classification.

Our study showed that patients with hypopharyngeal perforations have an almost 42-fold higher risk of mortality during hospitalization compared to those with epipharyngeal or oropharyngeal perforations, though results are limited by the small sample size and the variable dates. Additionally, neurosurgery of the cervical spine, transesophageal echocardiography, and diverticular surgery emerged as procedures carrying the highest risk for pharyngeal perforations. Within our patient cohort, 4 patients (11.11%, all female) died during the treatment course.

Cord blood transplantation (CBT) is a valuable donor source for patients without human leukocyte antigen (HLA)-matched donors. While CBT has a lower risk of graft-versus-host disease and requires less stringent histocompatibility, it is associated with a higher transplantation-related mortality (TRM) compared to other donor sources. We hypothesized that assessing the immunogenicity of mismatched HLA could reveal non-permissive mismatches contributing to increased TRM. We retrospectively analysed 1498 single-unit CBT cases from 2000 to 2018 across eight Japanese institutions, evaluating the immunogenicity of mismatched HLA using the PIRCHE algorithm to examine binding affinities of HLA-derived epitopes to donor or recipient HLA. Results indicated that Class I epitopes from mismatched recipient HLA-B were significantly associated with poor outcomes due to higher TRM and lower neutrophil engraftment, particularly when presented on matched HLA class I. Notably, epitopes from HLA-B exon 1 showed stronger prognostic significance, with HLA-B alleles carrying M-type leader peptides exhibiting higher affinity for these epitopes. Patients with a matched M-type HLA-B and Class I epitopes derived from mismatched HLA-B exon 1 had worse outcomes. These findings suggest that immunogenicity-informed donor selection could improve CBT outcomes.

Autologous stem cell Transplant (ASCT)-related mortality (TRM) in AL amyloidosis remains elevated. AL amyloidosis patients (n = 1718) from 9 centers, transplanted 2003-2020 were included. Pre-ASCT variables of interest were assessed for association with day-100 all-cause mortality. A random forest (RF) classifier with 10-fold cross-validation assisted in variable selection. The final model was fitted using logistic regression. The median age at ASCT was 58 years. Day-100 TRM occurred in 75 patients (4.4%) with the predominant causes being shock, high-grade arrhythmia, and organ failure. Ten factors were associated with day-100 TRM on univariate analysis. RF classifier using these variables generated a model with an area under the curve (AUC) of 0.72 ± 0.12. To refine the model selection using importance hierarchy function, a 4-variable model [NT-proBNP/BNP, serum albumin, ECOG performance status (PS), and systolic blood pressure] was built with an AUC of 0.70 ± 0.12. Based on logistic regression coefficients, ECOG PS 2/3 was assigned two points while other adverse predictors 1-point each. The model score range was 0-5, with a day-100 TRM of 0.46%, 3.2%, 5.8%, and 14.5% for 0, 1, 2, and ≥3 points, respectively. This model to predict day-100 TRM in AL amyloidosis allows better-informed decision-making in this heterogeneous disease.

Although the hematopoietic cell transplantation (HCT)-comorbidity index (HCT-CI) score is associated with an increased risk of mortality after allogeneic HCT, it remains unclear how pre-HCT liver dysfunction affects clinical outcomes. We retrospectively compared clinical HCT outcomes among four groups stratified according to the presence of HCT-CI liver and other organ scores, using a Japan transplant registry database between 2010 and 2020. Of the 14235 recipients, 1527 tested positive for an HCT-CI liver score including HBV or HCV hepatitis (n = 503). The 5-year overall survival (OS) was significantly lower in the HCT-CI liver(+) other(+) and HCT-CI liver(-) other(+) groups compared to the HCT-CI liver(+) other(-) and HCT-CI liver(-) other(-) groups [49.9% vs. 59% vs. 66.5% vs. 68.3%, p < 0.001]. A multivariate analysis showed that both the HCT-CI liver(+) other(+) [HR 1.62, p < 0.001] and HCT-CI liver(-) other(+) groups [HR 1.21, p < 0.001] were significantly associated with inferior OS. Similarly, both the HCT-CI liver(+) other(+) [HR 1.89, p < 0.001] and liver(-) other(+) groups [HR 1.26, p < 0.001] were significantly associated with an increased risk of NRM. On the other hand, the HCT-CI liver(+) other(-) group was not associated with either OS or NRM. Separately analyzing the subcohorts with or without HCT-CI other scores, the presence of an HCT-CI liver score alone did not affect survival, while the co-presence of pretransplant liver dysfunction seemed to synergistically increase the adverse impact on OS and NRM among recipients with other organ comorbidities. Further studies will be needed to identify optimal strategies for recipients with pretransplant liver dysfunction.

Several studies have shown that the telomere length of engrafted donor cells affects the clinical outcomes in patients with hematologic diseases after allogeneic stem-cell transplantation (allo-SCT). However, the relationship between donor telomere length and clinical outcomes after umbilical-cord blood transplantation (UCBT) remains unknown. The study aim was to assess the relationship between donor telomere length and transplantation outcomes.

We measured donor-derived relative telomere length (RTL) in 75 patients after single-unit UCBT and evaluated the association between telomere length and transplantation outcomes.

Compared with patients with shorter RTL, patients with longer RTL had a higher risk of bacterial and bloodstream infections [hazard ratio (HR), 4.79; 95% confidence interval (CI), 1.70-13.46; P = 0.003 and HR, 3.43; 95% CI, 1.19-9.82; P = 0.022, respectively] and was possibly associated with reduced relapse (HR 0.44, 95% CI 0.15-1.27, P = 0.13) by multivariate analysis.

Patients after UCBT who received engrafted donor cells with longer RTL had a higher risk of bacterial and bloodstream infections. The measured donor-derived RTL at engraftment after UCBT may predict clinical outcomes.

For patients with myelodysplastic neoplasm/syndrome (MDS), allogeneic hematopoietic cell transplantation (allo-HCT) represents the only potentially curative treatment, capable of eradicating disease-related mutant hematopoietic cells and establishing normal donor hematopoiesis. Biologic-assignment clinical trials have indicated that in eligible patients, allo-HCT is associated with superior clinical outcomes compared with nontransplant therapy. However, this therapeutic option is only available to a subset of patients, and the outcome is influenced by multiple factors inherent to the patient, the MDS subtype, and the allo-HCT procedure itself. In 2017, the European Society for Blood and Marrow Transplantation (EBMT) published recommendations for allo-HCT in MDS to guide practical decision making. In the contemporary era, genomic profiling has become routine clinical practice in many centers, and the most recent classification systems include MDS entities that are defined by genetic abnormalities. In particular, the molecular International Prognostic Scoring System offers more precise prognostication across all clinical end points and currently represents the standard tool for estimating patient survival in the absence of disease-modifying treatment. Evidence from multiple sources increasingly indicates that allo-HCT should be considered at the time of diagnosis in all eligible patients with MDS. Therefore, genomic profiling for somatic mutations and testing for germ line predisposition variants are integral to determining a patient's eligibility for transplantation. Although all patients with higher-risk MDS are potential candidates for immediate transplantation, a subset of those with lower-risk MDS may also derive benefit from this procedure at an earlier disease stage. Comprehensive recommendations on behalf of an expert international panel for clinical practice and future clinical studies of relevance are presented.

Prognostic scores are an important tool in medical statistics. In chronic myeloid leukaemia (CML), prognostic models have existed for many years, enabling the classification of patients into groups that can be clearly differentiated in terms of their prognosis. However, over time, the focus of these models has shifted from solely survival outcomes to a broader range of diverse endpoints. This review explores the development and applications of these scores, offering recommendations for their use, and looks ahead to potential future advancements in the field. As the landscape of CML treatment evolves with newer therapeutic options, it is crucial to adapt prognostic models to reflect not only survival rates but also other important clinical milestones such as molecular remission, progression-free survival, and CML-related survival. The continued refinement of these tools, alongside international validation efforts, will be essential in providing clinicians with more accurate and individualized patient prognostication, ultimately improving therapeutic decision-making and patient outcomes.

Allogeneic hematopoietic stem transplantation (allo-HSCT) constitutes a curative treatment for various hematological malignancies. However, various complications limit the therapeutic efficacy of this approach, increasing the morbidity and decreasing the overall survival of allo-HSCT recipients. In everyday clinical practice, various laboratory and clinical biomarkers and scorning systems have been developed and implemented focusing on the recognition of high-risk patients for organ dysfunction-related complications and those who might experience low overall survival. However, the predictive accuracy of developed scores has been reported deficient in some studies. The aim of the current retrospective study is to develop a machine learning (ML) model to predict the long-term survivorship of patients who receive allo-HSCT based on clinical pre- and post-allo-HSCT variables, and on transplantation-related characteristics.

For this purpose, a database of 564 allo-HSCT recipients incorporating 16 clinical and laboratory variables and the survivorship status of the patients during follow-up (Alive, Dead, Alive but follow-up less than 24 months) was used. An ML model was developed and tested, based on the previously published Data Ensemble Refinement Greedy Algorithm (DEGRA) algorithm.

A predictive ML model was built with 92.02 % accuracy. The eight parameters included in the algorithm were the following: CD34+ cells infused, patients' age and gender, conditioning regimen toxicity, disease risk index (DRI), graft source, and platelet and neutrophil engraftment.

To our knowledge, this is the first AI model incorporating post-HSCT variables for the prediction of mortality in adult HSCT recipients. In the era of precision medicine, the recognition of patients who undergo allo-HSCT and face a great risk for mortality and morbidity, with high-accuracy algorithms is crucial.