Auro Viswabandya

Background: Belumosudil has demonstrated clinical activity in chronic graft‐versus‐host disease (cGvHD), but its impact on patient‐reported symptom burden in routine practice remains incompletely characterized. Objective: To evaluate longitudinal changes in cGvHD‐related symptom burden during belumosudil‐containing therapy, using the modified Lee symptom score (mLSS). Methods: This retrospective, multicenter study included 87 heavily pretreated patients with cGvHD from four Canadian centers. We scored the mLSS at baseline and 3, 6, and 12 months after belumosudil initiation. Clinically meaningful improvement (CMI) was a ≥ 6‐point reduction in the overall mLSS. We analyzed longitudinal changes using a linear mixed‐effects model. Results: Item‐level data were available for 48 patients (55%). Mean ± standard error mLSS decreased from 25.4 ± 1.8 at baseline to 16.5 ± 2.3 ( n = 25), 14.6 ± 3.0 ( n = 14), and 15.6 ± 4.5 ( n = 8) at 3, 6, and 12 months ( p < 0.001). CMI occurred in 52%, 64%, and 50% of evaluable patients, but in 15%, 10%, and 5% of all 87 treated patients. Best CMI was 65% ( n = 17/26) of evaluable patients and 20% of all treated patients, and best overall response rate was 41% ( n = 32/78). Conclusions: Belumosudil‐containing therapy was associated with reduced symptom burden among patients with evaluable item‐level data. Declining data capture limits conclusions about durability and generalizability; prospective studies with systematic symptom burden capture are needed.

Objectives: To evaluate whether Hematopoietic Cell Transplantation Frailty Scale (HCT‐FS)‐defined frailty predicts overall survival (OS), nonrelapse mortality (NRM), and relapse across diverse hematologic diagnoses undergoing allogeneic hematopoietic cell transplantation (alloHCT), including nonmalignant disorders. Methods: We conducted a multicenter retrospective cohort study of 992 adults undergoing alloHCT at 16 centers in Canada and Spain (2018–2023). Frailty was assessed at consultation using the HCT‐FS (fit, prefrail, frail). OS was estimated by Kaplan–Meier, competing‐risks methods by cumulative incidence. Multivariable models assessed associations with OS and NRM. Results: Frailty was assessed across six diagnostic categories, including nonmalignant disorders (4.8%). At consultation, 32.1% were fit, 54.7% prefrail, and 13.2% frail. Increasing frailty was associated with progressively lower 2‐year OS (78.9%, 66.0%, 51.7%; p < 0.001) and higher 2‐year NRM (10.5%, 18.9%, 33.2%; p < 0.001; HR 1.77 [95% CI 1.21–2.60] prefrail and 3.65 [2.36–5.65] frail vs. fit), while 2‐year relapse incidence did not differ (19.0%, 23.5%, 22.3%; p = 0.229). Disease‐specific estimates were exploratory and limited by small subgroup sizes. Conclusions: HCT‐FS‐defined frailty is associated with OS and NRM but not relapse in this multicenter alloHCT cohort. Larger disease‐specific studies are needed to establish its prognostic value in less represented indications.

PURPOSE: Post-transplant cyclophosphamide (PTCy) is increasingly used for graft-versus-host disease (GVHD) prophylaxis, but long-term outcomes remain incompletely defined. PATIENTS AND METHODS: We analyzed 874 relapse-free survivors at 2 years from 2,046 patients who underwent allogeneic hematopoietic stem-cell transplantation (HSCT) for hematologic malignancies between 2010 and 2022. GVHD prophylaxis included PTCy plus rabbit antithymocyte globulin (ATG) and a calcineurin inhibitor (CnI; Group I, n = 429) or alternative regimens (Group II, n = 445). RESULTS: With an overall follow-up of 5,275 person-years after HSCT, overall survival (OS) 3 years after the landmark was 88.7% (95% CI, 86 to 91). Patients receiving ATG-PTCy-CnI had improved outcomes compared with those receiving alternative regimens, with OS of 93.2% versus 85.0% ( P < .001), and lower nonrelapse mortality (NRM; 3.4% v 10.8%; P < .001). On multivariable analysis, ATG-PTCy-CnI was independently associated with improved OS (hazard ratio [HR], 0.41; 95% CI, 0.21 to 0.79; P = .007) and lower NRM (HR, 0.34; 95% CI, 0.17 to 0.74; P = .006). Chronic GVHD remained the leading cause of late mortality; deaths from GVHD, infections, treatment-related toxicity, and second primary malignancies were all reduced with ATG-PTCy-CnI. The cumulative incidence of relapse was similar between groups. Standardized mortality ratios were 1.32 for ATG-PTCy-CnI and 2.06 for other regimens, corresponding to a 1.6-fold higher excess mortality with alternative prophylaxis ( P = .036). CONCLUSION: Among patients alive and relapse-free at least 2 years after HSCT, long-term outcomes were excellent. The use of ATG-PTCy-CnI prophylaxis was associated with further improvements in survival through reductions in GVHD-related mortality and late complications.

Background/Objectives: Smoking is linked to an increased risk of pulmonary complications and adverse outcomes following allogeneic hematopoietic cell transplantation (Allo-HCT). Unfortunately, data is rarely correlated with the incidence of GVHD and does not show whether smoking has a negative impact independent from underlying pulmonary comorbidities. Methods: We retrospectively analyzed 407 patients who underwent Allo-HCT between January 2019 and May 2021 and evaluated the impact of smoking history and pre-transplant pulmonary comorbidities on the risk of outcomes including graft-versus-host disease (GVHD), overall survival (OS), and non-relapse mortality (NRM). Results: Patients were divided into the following groups: Group A: smokers with pre-transplant pulmonary comorbidity, 40 pts (9.8%); Group B: non-smokers with pre-transplant pulmonary comorbidity, 71 pts (17.4%); Group C: smokers without pre-transplant pulmonary comorbidity, 105 pts (25.8%); and Group D: non-smokers without pre-transplant pulmonary comorbidity, 191 pts (46.9%). Smokers were also grouped by their smoking history (25 pack-years (35 pts)) and by smoking recency: Recent (until Allo-HCT), Former (quit > 1 year ago), and Remote smokers (quit > 10 years ago). Our results showed that Group A demonstrated increased chronic lung GVHD compared to the other groups (p = 0.01). The 3-year OS was lowest in Group A at 45.0%, compared to 70.4%, 62.4%, and 69.4% (p = 0.006), and the NRM was highest at 37.5%, compared to 15.5%, 18.2%, and 14.7% in Groups B, C, and D, respectively (p = 0.001). Smoking recency and higher pack-year dose were associated with worse outcomes. Conclusions: Our study demonstrated the negative synergistic effect of smoking history and pre-transplant pulmonary comorbidities on the incidence of lung GVHD, OS, and NRM.

Chronic graft-versus-host disease (cGvHD) remains one of the common causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Belumosudil (BEL), a selective ROCK2 inhibitor, has immunomodulatory and anti-fibrotic properties, offering a new therapeutic option. Real-world data (RWD) in heavily pretreated patients remain limited, particularly for combination of BEL with ruxolitinib (RUX). We conducted a multicenter, real-world study in 46 patients treated for refractory cGvHD with BEL under a Canadian compassionate program. Treatment outcomes were assessed using the NIH consensus response criteria for overall response rate (ORR), failure-free (FFS), overall survival (OS), and safety. Forty-six patients were included with a median follow-up of 11.4 months; the best ORR was 52% ( n = 20/38). The FFS and OS rates at 12 months were 64.3% and 91.1%, respectively. Steroids were discontinued in 73% at 12 months. BEL combination therapy with RUX exhibited equivalent treatment outcomes to BEL monotherapy, although patients treated with drug combination presented with more advanced form of GvHD and mostly failed RUX therapy. A prognostic risk model based on prior acute GvHD and involvement of ≥ 4 organs effectively stratified FFS at 12 months: 100% with no risk factors, 75.8% with one, and 30% with two risk factors (HR 3.91, 95% CI 1.58–9.67, p = 0.003). BEL demonstrated durable efficacy and acceptable safety in heavily pretreated cGvHD. BEL treatment was associated with a high probability of corticosteroid withdrawal. Risk stratification by disease burden and prior aGvHD identified distinct prognostic groups, informing patient selection and future therapeutic strategies.

Allogeneic hematopoietic stem-cell transplantation (allo-HCT) is a potentially curative treatment for hematological diseases, but the prolonged length of stay (LOS) post-transplant remains a significant challenge. This retrospective cohort study analyzed 977 patients undergoing allo-HCT at Princess Margaret Cancer Centre between 2017 and 2022 to identify predictors of prolonged LOS and their impact on overall survival (OS) and non-relapse mortality (NRM). The median LOS within the first year was 37 days (range: 15–340). Pre-transplant predictors of prolonged LOS included HLA-mismatched donors (HR = 1.11, P < 0.001), Karnofsky Performance Scale (KPS) < 90 (HR = 1.09, P = 0.007), age >65 (HR = 1.15, P < 0.001), hematopoietic cell transplantation comorbidity index ≥3 (HR = 1.07, P = 0.04), and high disease risk index (DRI) (HR = 1.09, P < 0.01). Patients without these risk factors had a 1-year OS of 82.9%, compared to 41.9% in those with four or five factors. Post-transplant complications associated with prolonged LOS included grade III-IV acute graft-versus-host disease (HR = 1.40, P < 0.001), graft failure (HR = 1.20, P < 0.001), hemorrhagic cystitis (HR = 1.18, P < 0.001), bloodstream infections (HR = 1.19, P < 0.001), and cytomegalovirus reactivation (HR = 1.10, P < 0.001). Despite advancements in transplant protocols, age>65, mismatched donors, KPS < 90, HCT-CI ≥ 3, and high DRI remain associated with prolonged LOS and worse OS. Personalized strategies are needed to mitigate risks, reduce LOS, and improve outcomes.

Introduction: Myeloablative conditioning (MAC) for acute myeloid leukemia (AML) improves disease control by reducing relapse risk but is associated with higher non‐relapse mortality (NRM). Reduced‐intensity conditioning (RIC) aims to minimize toxicity but raises concerns about higher relapse rates. This study evaluates the impact of RIC versus MAC in AML patients under 65 years receiving GVHD prophylaxis with antithymocyte globulin, post‐transplant cyclophosphamide, and cyclosporine.Methods: We retrospectively analyzed 322 AML patients undergoing allogeneic HCT with uniform GVHD prophylaxis. Propensity score matching (PSM) was applied to adjust for baseline differences.Results: In the matched cohort, 2‐year overall survival (OS) did not differ significantly between RIC and MAC recipients (64.4% vs. 66.9%, p = 0.56). Relapse‐free survival (RFS) at 2 years was 65.0% for MAC and 52.7% for RIC (p = 0.20). Two‐year NRM was 19.4% for MAC and 19.1% for RIC (p = 0.84). Improved RFS was associated with non‐high‐risk DRI (HR: 0.39, p = 0.008), whereas conditioning intensity had no significant effect (HR: 0.98, p = 0.97). NRM was higher among patients with KPS < 90 (HR: 3.63, p = 0.01), with no significant impact observed from conditioning intensity (HR: 1.44, p = 0.43).Conclusion: In a relatively younger cohort, conditioning intensity did not significantly impact survival, and MAC was not associated with increased NRM.

Background: Clinical outcome disparities among racial and ethnic groups have been described following allogeneic hematopoietic cell transplantation (HCT). This study investigated the impact of race and ethnicity on HCT outcomes in a multi-ethnic single-center population. Methods: We analyzed outcomes of 709 allogeneic HCT patients, stratified by racial and ethnic groups, who underwent allogeneic HCT between January 2018 and April 2022. Outcomes examined included overall survival (OS), cumulative incidence of relapse (CIR), non-relapse mortality (NRM), and graft-versus-host disease/relapse-free survival (GRFS). Results: No significant differences in OS, CIR, NRM, GRFS, acute GVHD (aGVHD), or chronic GVHD (cGVHD) were observed. Significant differences in age, use of human leukocyte antigen-mismatched donors (HLA-MM), and HCT-CI comorbidity scores ≥ 3 across racial and ethnic groups were observed. Overall mean age was 58 years, with Black patients having the youngest mean age of 43 (range 22–73) and White patients the highest mean age of 59 (range 18–76) (p < 0.001). HCT-CI score ≥ 3 was seen in 35.9% of the entire cohort, varying by race and ethnicity: 60.5% in Black, 41.4% in South Asian, 31.5% in White, and 29.0% in East Asian patients (p < 0.001). Utilization of HLA-MM donors (including haploidentical) was 29.2% overall, with highest frequencies in Black (65.1%) and East Asian (45%) patients, and lowest in White patients (20.4%) (p < 0.001). Conclusions: Statistically significant differences were observed across self-identified racial and ethnic groups regarding age, HCT-CI ≥ 3, and the use of HLA-MM donors. However, post-allogeneic HCT outcomes did not differ significantly by race or ethnicity. Larger prospective trials are warranted to validate our findings.

Posttransplant cyclophosphamide (PTCy) is a promising graft-versus-host disease (GVHD) prophylaxis in haploidentical and matched unrelated donor hematopoietic stem cell transplantation (HSCT), but its role in matched sibling donor (MSD) transplants remains unclear. We conducted a retrospective study of 413 MSD-HSCT patients receiving peripheral blood stem cell (PBSC) grafts from January 2010 to January 2023. Patients were categorized into 4 groups: group I (calcineurin inhibitor [CNI] + methotrexate [MTX] or mycophenolate mofetil [MMF]), group II (CNI + MTX or MMF + antithymocyte globulin [ATG]), group III (PTCy + ATG + CNI), and group IV (PTCy + CNI + MMF). PTCy was associated with a significant reduction in grade 2- 4 and grade 3-4 acute GVHD and moderate-to-severe chronic GVHD compared with CNI + MTX (or MMF)–containing regimens. PTCy did not increase relapse risk; PTCy reduced nonrelapse mortality, leading to improved GVHD-free/relapse-free survival (GRFS; Hazard Ratio, 0.4; P < .001). PTCy was also associated with improved overall survival. Bloodstream infections were increased with PTCy. The addition of ATG to PTCy did not further improve GRFS and was associated with a higher incidence of clinically significant cytomegalovirus (csCMV) and Epstein-Barr virus (csEBV) reactivation and a numerical increase in NRM. PTCy significantly appeared to improve GRFS in the MSD setting using PBSC grafts. The addition of ATG to PTCy increases csCMV and csEBV reactivation without further improving GRFS. Prospective trials and PTCy dose optimization are warranted.