BACKGROUND:Bronchiolitis obliterans syndrome (BOS) is a severe manifestation of pulmonary chronic graft vs host disease (cGvHD) that occurs in around 10% of allogeneic hematopoietic cell transplant (HCT) recipients and confers poor prognosis, with survival rates at 5 years of < 50%. Posttransplant cyclophosphamide (PTCy) has emerged as an effective GvHD prophylaxis that reduces overall cGvHD incidence, but its specific impact on BOS risk remains unclear. RESEARCH QUESTION:How does PTCy affect the rate of BOS among patients undergoing allogeneic HCT? STUDY DESIGN AND METHODS:We conducted a retrospective multicenter cohort study across 3 US centers between 2015 and 2023 comparing BOS incidence between patients receiving PTCy vs non-PTCy GvHD prophylaxis. BOS was defined as either meeting strict National Institutes of Health criteria (4 of 4) or meeting 3 of 4 criteria with clinical BOS diagnosis. We used competing risk regression accounting for death and performed mediation analysis to evaluate whether cGvHD reduction mediates PTCy's protective effect. RESULTS:Among 900 patients (276 with PTCy, 624 without PTCy), PTCy was associated with a 75% reduction in BOS risk (adjusted hazard ratio [HR], 0.25; 95% CI, 0.09-0.74; P = .012) when adjusted for age, immunologic matching status, and baseline FEV1 and stratified by conditioning strategy. Mediation analysis demonstrated that when cGvHD was added to the model, the PTCy HR attenuated from 0.26 to 0.41 (57% attenuation toward the null; P = .108), indicating that cGvHD prevention mediates PTCy's protective effect. Results remained robust after excluding haploidentical transplants (HR, 0.24; 95% CI, 0.07-0.77; P = .016). INTERPRETATION:Our results show that PTCy significantly reduces BOS risk through prevention of cGvHD, expanding current evidence of PTCy's benefits beyond overall cGvHD reduction to include protection against this often fatal pulmonary complication. These findings support consideration of PTCy-based regimens for patients at high risk of BOS and may inform risk stratification strategies in posttransplant monitoring.

Measurable residual disease (MRD) has established prognostic significance in patients with myeloid disorders; however, there is limited data regarding its prognostic and predictive value and the optimal technique for measurement in the setting of post allogeneic hematopoietic cell transplantation (allo-HCT). A multi-gene next generation sequencing (NGS) panel can overcome the limitations of conventional techniques for measurement of MRD and can shed light onto the longitudinal evolution and genomic complexity of patients undergoing allo-HCT for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). In this study, patients with AML or MDS who underwent their first allo-HCT and completed NGS testing at day +100 and were in a state of morphological remission were identified from the transplant registry of Mayo Clinic in Florida. The primary aim was to evaluate the prognostic impact of somatic variants detected via NGS at day +100 post allo-HCT on long-term outcomes. In total, 105 patients who underwent allo-HCT for AML and MDS and completed NGS testing on day +100 were included in the study population. Seventeen patients were found to have detectable variants, and 88 patients were without a detectable variant. At a median follow up of 1.4 years (0.1–5.5), presence of any variant at day +100 was associated with inferior 4-year overall survival (OS) (32% vs. 69%, P < 0.001), decreased progression free survival (PFS) (34% vs. 61%, P < 0.001), and a higher incidence of relapse (64% vs. 23%, P < 0.001). In univariate models, a lower Karnofsky performance score and presence of variants post allo-HCT remained significantly associated with inferior OS, higher relapse incidence, and a decreased PFS. The presence of variants at day +100 post allo-HCT remained significant in multivariate models for relapse (P = 0.002) but not for OS (P = 0.06) and PFS (P = 0.08). These results indicate that the presence of detectable somatic variants at day +100 is associated with poor long-term outcomes and are predictive of a higher incidence of relapse.

Background Allogeneic hematopoietic cell transplantation (Allo-HCT) is associated with replacement of the immune system of the host. The response of autoimmune disorders (AIDs) to Allo-HCT remains unclear. This study aimed to evaluate disease-related outcomes of underlying autoimmune disorders on patients undergoing allogeneic bone marrow transplantation for hematologic malignancies. Methods We retrospectively evaluated Allo-HCT records across three Mayo Clinic sites (Jacksonville, Rochester, and Arizona) between July 2015 and July 2025. Adult patients diagnosed with autoimmune disorders prior to bone marrow transplantation were included in the study. Exclusion criteria were initial diagnosis of AID after bone marrow transplantation and non-confirmed AIDs. Results A total of 61 patients were included in the study. The median age was 37.9 years (range, 27-74). Female patients comprised 54.9% of the cohort, and 93.4% were White Americans. Inflammatory bowel disorders were the most common AIDs in patients who underwent Allo-HCT (44.2%). There were 24 (39.3%) patients diagnosed with rheumatological disorders and 9 patients (14.7%) with neurological conditions. A total of 46 (75.4%) patients were receiving treatment for AIDs before transplantation. Chemotherapy agents were used in 19 patients (31.1%). The AIDs were active in 39.3% (n=24) of patients. The median number of total lines of therapy for AIDs prior to BMT were 2 (range, 0-12). The median age at Allo-HCT was 57 years (range, 27-75). The mean HCT-CI score was 3.5 (range, 0-10). The median day of neutrophil engraftment was 15 (range, 11-37), and the median day of platelet engraftment was 19 (range, 9-65). Acute GvHD was seen in 36 (59%) patients and chronic GvHD was observed in 11 (18%) patients. Only 3 (4.9%) patients required treatment for the underlying AIDs after transplantation, and relapse of the AIDs was observed in only 2 (3.8%) patients. Conclusion Allo-HCT induces durable remissions in the vast majority of patients with AIDs, with low rates of post-transplantation relapses and treatment requirements. These findings suggest a potential therapeutic role for Allo-HCT in severe, refractory AIDs. Further prospective studies with larger cohorts are needed to confirm these observations and establish optimal patient selection criteria.

OBJECTIVE:Systemic sclerosis (SSc) is an autoimmune disease marked by immune dysregulation, leading to progressive fibrosis and multiorgan dysfunction. Autologous hematopoietic cell transplantation (autoHCT) has demonstrated superiority over conventional immunosuppression in randomized trials yet remains underused in the United States. We report outcomes following implementation of autoHCT as a standard-of-care strategy at our institution. METHODS:We performed a retrospective analysis of consecutive patients with severe SSc undergoing autoHCT between April 1, 2020, and December 31, 2023. Eligibility required progressive disease despite standard immunosuppressive therapy. Primary endpoints were overall survival (OS) and event free survival (EFS). Secondary endpoints included cumulative incidence of relapse and nonrelapse mortality (NRM), organ-specific outcomes, and transplant-related complications. RESULTS:Twenty-five patients underwent autoHCT. Median age was 46 years; 80% were female. At a median follow-up of 23 (interquartile range 16.4-31.9) months, two-year OS was 91.67% (95% confidence interval [CI] 81.25-100.0) and EFS was 74.51% (95% CI 58.78-94.45). Two-year cumulative incidence of relapse was 23.93% (95% CI 4.27 -43.59), and NRM was 8.33% (95% CI 2.97-19.64). Significant improvement in Modified Rodnan Skin Score was observed at day +90 and +180 (P < 0.05), whereas pulmonary function stabilized. Infectious complications occurred in 56% of patients, primarily viral reactivations. CONCLUSION:Implementation of autoHCT for severe SSc in a multidisciplinary care model was associated with favorable survival and meaningful improvement in skin disease, with acceptable toxicity. Earlier referral and optimization of conditioning strategies may further reduce relapse and treatment-related morbidity.

INTRODUCTION:The efficacy of donor lymphocyte infusions (DLIs) among various myeloid malignancies (particularly genetic subtypes) and the optimal timing of DLI initiation remains unclear. METHODS:This was a retrospective study of 62 patients with myeloid malignancies treated with alloHSCT and DLI from years 2001 to 2022. DLI indications were therapeutic 55 (89%), preemptive 6 (10%), and prophylactic in 1 (2%) patients with complete remission (CR/CRi) in 20 patients; diagnoses included 9 (45%) acute myeloid leukemia, 6 (30%) myelodysplastic syndromes, and 3 (15%) chronic myelomonocytic leukemia among others. RESULTS:Among patients who received therapeutic DLI (n = 55), the best response was CR/CRi in 16 (29%) patients. At a median follow-up from the date of DLI of 75 (95% CI 35-121) months, there were 49 (79%) deaths with a median OS of 6 (95% CI 4-14) months, higher in patients in CR/CRi versus no CR/CRi (median 51 versus 4 months, p = 0.008). Presence of cytogenetic abnormalities such as complex karyotype, deletions in chromosome 5, 7, and 17p, and mutations in TP53, KRAS, NRAS, RUNX1, or JAK2 were associated with adverse outcomes. CONCLUSION:DLI is an effective treatment strategy for post-transplant relapse across myeloid malignancies, with specific genetic subtypes showing poorer outcomes and survival.

Abstract Solitary bone plasmacytoma (SBP) and SBP with minimal marrow involvement (SBPmm) are treated similarly with definitive radiation therapy (RT) followed by observation. However, differences in the natural disease course after RT between the two, are not well described. We performed a multicenter study assessing outcomes after RT in 141 patients with SBP and 102 with SBPmm diagnosed between January 2010 and December 2024. About 92% of patients with SBPmm progressed to multiple myeloma (MM) vs 76% of those with SBP (P = .01). Among patients with SBP, 21% progressed with a second solitary bone lesion vs 4% with SBPmm (P< .01). Patients with longer time to progression (TTP) after initial RT could achieve durable responses with RT to a second solitary plasmacytoma in the absence of other myeloma-defining events (MDE). Multifocal lytic bone lesions were the most common MDE, occurring in 89% and 81% of patients with SBPmm and SBP, respectively. Patients with SBPmm had a median TTP of 15 months (95% confidence interval [CI], 14-21) compared to 43 months (95% CI, 34-55) for those with SBP (P< .0001); 67% with SBPmm progressed within 2 years of diagnosis. Del(17p) and 1q+ (gain or amplification) were associated with shorter TTP to MM in SBPmm, with 2-year progression rates of 100% and 82%, respectively. We report significant differences in risk and modes of progression between SBP and SBPmm. Patients with SBPmm are at particularly high risk for early progression to MM, with most developing bone disease as the MDE. These findings support prospective studies incorporating frontline systemic therapy for SBPmm.

BACKGROUND:Proteasome inhibitors, immunomodulatory drugs, and monoclonal antibodies form the backbone of initial treatment for myeloma and play an important role in the treatment of relapsed disease. However, global access to many novel therapies is limited and alkylating agents remain relevant in certain clinical settings. Ixazomib is an oral PI that enables development of all oral regimens. PATIENTS:We designed this open-label, multi-arm phase 2 study to evaluate the safety and efficacy of weekly oral ixazomib in various combinations for patients with relapsed MM. Herein, we discuss the results of Arms D (ixazomib, cyclophosphamide, and dexamethasone-ICd, n=33) and E (Daratumumab-ICd, n=24) that examined the ixazomib and dexamethasone in combination with cyclophosphamide or cyclophosphamide and daratumumab, respectively. RESULTS:The overall response rate was 73% and 75% and ≥VGPR rate was 45% and 54% in the Arms D and E, respectively. After the median follow-up of 27 months for Arm D and 41 months for Arm E, the median progression free survival was 27.1 months (95% confidence interval [CI]: 17.8-38.6) and 37.7 months (95% CI: 17.9-NA) for the arms D and E, respectively. The median overall survival was not reached for either arm. A grade 3 or higher hematological adverse event considered at least possibly related, occurred in approximately 75% of patients. CONCLUSIONS:The results of this phase 2 trial demonstrate clinically meaningful efficacy of ICd (±) daratumumab in the relapsed setting, with the indirect comparison suggesting a deeper response and longer PFS with adding daratumumab.

The 100 days following allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a critical period despite advancements in transplant-related care. Post-transplant cyclophosphamide (PTCy) has been implemented as an effective strategy for GVHD prevention across various donor types. This study aimed to evaluate causes of early mortality and prognostic factors for non-relapse mortality (NRM), disease-related mortality (DRM), and overall survival (OS). This was a single institution, retrospective study including adult patients who received their first allo-HCT from 2009 to 2023. Patient- and transplant- related variables were compared between patients who died and those who were alive at 100 days post-allo-HCT. A total of 536 patients were evaluated, including 285 men (53%). Median age at time of allo-HCT was 59 years (range 19-75), and most were White/Caucasian (n = 232; 86%). The predominant diagnosis included acute myeloid leukemia (AML) (n = 195, 36%), myelodysplastic syndrome (MDS) (n = 95, 18%), and myelofibrosis (MF) (n = 57, 11%). Eighty patients (15%) died within 100 days following allo-HCT, with NRM accounting for most early deaths (N = 61; 76%). Primary causes of death were acute GVHD (n = 23), disease relapse/progression (n = 19), and infections (n = 18). On multivariate analysis, earlier transplant year was the only independent predictor of increased 100-day DRM (HR 1.15; P = .049). Male gender (HR 1.78; P = .035), non-acute leukemia diagnoses (HR 2.38; P = .003), and non-PTCy prophylaxis (HR 2.2; P = .032) were independently associated with higher 100-day NRM. PTCy-based GVHD prophylaxis was the only modifiable factor associated with lower early NRM, through reduced GVHD-related deaths without increased infection or DRM.

Background: Allogeneic hematopoietic cell transplantation (allo-HCT) is the only curative option for myelofibrosis (MF) but carries significant non-relapse mortality (NRM). Splenomegaly in MF patients undergoing allo-HCT is linked to delayed engraftment, poor graft function, and worse overall survival (OS). Strategies to reduce spleen size pre-HCT have been explored. Splenic irradiation (SI) offers a non-invasive approach for rapid spleen size reduction, though data on transplant outcomes are limited. Retrospective studies suggest SI just before HCT may reduce relapse and effectively shrink spleens with acceptable toxicity. Methods: We conducted a single-center observational study on MF patients with splenomegaly undergoing allo-HCT between 2022–2024. SI (100 cGy in 5 fractions) was delivered within 6 weeks pre-HCT. Primary endpoints: engraftment kinetics (including primary engraftment failure), time to neutrophil/platelet engraftment, and transfusion independence. Secondary endpoints: OS, progression-free survival (PFS), relapse, NRM, and rates of acute/chronic GVHD. Kaplan–Meier methods were used for OS/PFS; cumulative incidence functions with competing risks were used for relapse/NRM. Results: Thirteen patients were analyzed. Median age was 63 (range 40–74) years, and 54% were male. Eight (62%) patients had primary MF, 3 (23%) post-essential thrombocytosis, and 2 (17%) post-polycythemia vera. Eleven (94.6%) patients had prior Ruxolitinib therapy, and 10 (76.9%) harbored a JAK2 mutation with a median variant allele frequency of 51% (range 34%–94%). DIPSS risk at transplant was low in 1 (7.7%), intermediate-1 in 8 (61.5%), and intermediate-2 in 4 (30.8%) patients. Median pretransplant spleen size was 22.4 (range 14.5–28) cm. Two patients had a history of thrombosis, including 1 with portal vein thrombosis. The median interval between SI and stem cell infusion was 14 (range 10–43) days. The median HCT-CI score was 2 (range 0–6), and the median KPS was 80% (range 80–100%). Most patients (76.9%) received a HLA-matched unrelated donor transplantation, while 3 (23.1%) received haploidentical donor grafts. All grafts used peripheral blood stem cells. Reduced-intensity conditioning (RIC) was used in 11 (84.6%) patients, while 2 (15.4%) received myeloablative conditioning (MAC). Five (38.5%) patients received total body irradiation (TBI) as part of conditioning, with all receiving a TBI dose of 200 cGy. All patients received post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis. With a median follow-up of 17.1 months, median neutrophil engraftment occurred at 18 (range 14–45) days, platelet engraftment at 30 (range 15–434) days, red blood cell transfusion independence at 35 (range 11–341) days, and platelet transfusion independence at 24 (range 10–312) days. Median hospital stay was 26 (range 14–86) days. Primary engraftment failure occurred in 1 (8.3%) patient. One (7.7%) patient developed veno-occlusive disease. Four (33.3%) patients experienced CMV reactivation, and 3 developed CMV disease requiring systemic therapy. Median post-transplant spleen size was 16.6 (range 12.2–25.2) cm, and 30% of patients achieved >50% spleen size reduction, with a median time of 114 (range 45–212) days, with none having a normal spleen at day 30 post-transplant but 2 (15%) patients having a normal spleen at day 100 post-transplant. At 1 year, OS was 73.3% (95%CI, 51.5–100%), and PFS was 66% (95%CI, 44%–100%). The 1-year cumulative incidence of relapse was 7.6%, while 1-year NRM was 25.7%. Seven (53%) patients developed acute GVHD, with 1 patient experiencing grade III acute GVHD that progressed to sepsis and death at day 248 post-transplant. Two additional deaths occurred (graft failure=1, multiorgan failure=1). Two (15%) patients developed moderate chronic GVHD Conclusion: In this single-center cohort, SI pre-allo-HCT was feasible, tolerated, and associated with promising OS and PFS. Engraftment occurred in >90%, with one case of primary engraftment failure and most achieving transfusion independence within reasonable time frames. SI reduced spleen size in >30%, though acute GVHD was frequent. It remains uncertain whether the incidence and severity of GVHD may be influenced using TBI as part of the conditioning regimen (albeit reduced in intensity) in addition to splenic irradiation. Larger prospective studies are needed to clarify SI's impact on engraftment, transfusion dependence, GVHD, and outcomes in MF patients.

Background: MM is the second most common hematologic malignancy, which despite significant therapeutic advancements, remains incurable. The complexity of MM and its intricate management creates substantial informational demands for patients navigating their care. Methods: A cross-sectional survey study (Mayo Clinic IRB # 25-004671) was conducted to assess MM patients’ awareness about disease basics. A voluntary English language survey (47 questions) encompassing multiple domains of patient MM awareness was administered (REDCap) via the patient EMR portal (Mayo Clinic) and MM support groups nationally. Responses were analyzed using descriptive and inferential statistics (R; Bluesky Statistics, V 10.3.4). Multiple model logistic regression was used for multivariate analysis using age (≤70 or >70 yrs), gender, education (high school or less vs bachelor's and above), income (≤$74999 vs ≥$75000) and insurance status (private vs public). Results: The survey was completed by 2353 patients (pts) with 2177 MM (83.4% active, 16.6% smoldering) and 176 MGUS. Among MM pts median age was 63 yrs with 52.5% males, 91.5% white and 95.7% non-Hispanic. 17.5% had a prior diagnosis of MGUS and 20.2% of smoldering MM prior to MM, and 79.5% were not aware of MM prior to their own diagnosis. Majority (77%) depended most on their doctors to gain MM information but 24.3% reported not having sufficient discussion about MM at diagnosis. 31.2% were not sure what type of MM they had, 22.9% could not correctly report the cell of MM origin (plasma cell), 40.6% did not receive MM stage information at diagnosis, 45.4% were either unsure or reported wrong risk factors for MM and 22% were unsure or mistaken about MM symptoms. Majority (62.9%) did not understand genetic risk categories of MM, 32.3% did not report adequate understanding of MM tests and 31.9% did not understand the difference between response and remission. 57.5% reported not understanding about MRD status and 57.1% never had MRD testing. Majority (86.8%) felt they got adequate opportunity to participate in treatment decisions but only 54.2% felt confident in managing MM with their current knowledge and 28.2% had not discussed their prognosis although 77.7% wanted to know about it. Majority (64.4%) felt they had knowledge gaps about MM and its management. Multivariate analysis showed that females were less likely (OR 0.67) while those with public insurance were more likely (OR 1.35) to report receiving adequate information at diagnosis. Older pts (OR 0.55), males (OR 0.43), with lower education (OR 0.5), lower income (OR 0.5) and public insurance (OR 0.72) were less likely to identify the cell of MM origin correctly. These same groups were significantly less likely to be aware of types of MM as well. Older pts (OR 0.73), with lower education (OR 0.6), lower income (OR 0.77) and public insurance (OR 0.76) were less likely to be aware of MM genetic risk categories. Females (OR 0.81), with lower education (OR 0.68) and lower income (OR 0.63) were less likely to understand MM lab tests. Females and those with lower income were significantly less likely to report receiving adequate information about treatment options. Females reported that they did not get adequate opportunities to participate in treatment decisions (OR 0.65). Older pts, and those with lower income, lower education or public insurance were less likely to understand minimal residual disease (MRD) and all these groups were less likely to have had MRD testing. Those with lower income (OR 0.75) and lesser education (OR 0.72) felt less confident in managing MM with current knowledge. Older pts, females and those with lesser education, lower income and public insurance were also significantly less likely to have discussed about MM prognosis. Conclusion: This study demonstrates substantial basic knowledge deficits integral to managing and prognosticating MM among patients. Patients from unfavorable sociodemographic-economic groups were more likely to have awareness gaps and report lack of information which is integral to having adequate understanding of MM being provided to them. These findings highlight the critical need for structured, comprehensive educational interventions that address fundamental disease concepts to empower pts, overcome healthcare disparities, and engage pts in shared decision-making.

Background In patients with myelofibrosis (MF) undergoing allogeneic hematopoietic cell transplantation (allo-HCT), graft-versus-host disease (GVHD) prophylaxis has traditionally included a calcineurin inhibitor (CNI) plus methotrexate (MTX). We conducted a retrospective study comparing the safety and efficacy of post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis to CNI-based regimens. Methods This study was approved by the Mayo Clinic IRB. Patients with myelofibrosis who underwent allo-HCT after 2016 at Mayo Clinic in Arizona and Florida were included. Categorical variables were compared using Chi-square or Fisher's exact tests. Overall survival (OS) was defined from transplant to death, and progression-free survival (PFS) from transplant to relapse or death. OS and PFS were estimated using Kaplan-Meier methods; univariate differences were assessed with log-rank tests. The cumulative incidence of acute and chronic GVHD and time to neutrophil and platelet engraftment were analyzed using competing risk models, with death as a competing event; differences were tested using Gray's test. Cox proportional hazards models were used to estimate adjusted hazard ratios (HRs). Results A total of 110 patients were included. 53 patients received PTCy-based prophylaxis (43 PTCy/Tac/MMF, 1 PTCy/CSA/MMF, 9 PTCy/Siro/MMF), while 57 received non-PTCy regimens (54 Tac/MTX +/- 39 T-cell depletion, 2 CSA/MMF, 1 Tac/MMF). Median age at transplant was 63 (range: PTCy 40-76; others 38-74) years in both groups; 59 were male (58.5% PTCy vs 49.1% others). Median Karnofsky Performance Status (KPS) and HCT–Comorbidity Index (HCT-CI) in patients receiving PTCy vs non-PTCy were 90 vs 80 and 1 vs 3, respectively. Conditioning intensity was similar: 22.6% myeloablative vs 21.7%, and 77.4% reduced-intensity vs 76.7% in PTCy and non-PTCy, respectively (p=1.000). Stem cell source was peripheral blood in all patients except one in the non-PTCy group who received bone marrow. 58 patients had primary MF (54.7% PTCy vs 50.9% others), and 52 had secondary MF (45.3% PTCy vs 49.1% others), including essential thrombocythemia (28.3% PTCy vs 31.6% others), polycythemia vera (17.0% vs 15.8%), and MPN-NOS (0% vs 1.8%). Median follow-up was 26.2 months (95% CI: 20.7-52.7) in the PTCy and 60.6 months (95% CI: 53.1-70.6) in the non-PTCy cohort. CD3 and CD33 donor chimerism ≥95% at day +100 was 66.7% and 86.7% in PTCy vs 63.6% and 92.7% in others, respectively (p=0.50); day +100 driver molecular mutations were present in 32.1% of PTCy and 32.0% of others (p>0.99). Rates of acute GVHD grades ≥2 and ≥3 were not statistically significant, in the PTCy group (37.7% vs 49.1% p=0.229 and 17.0% vs 22.8% p=0.445, respectively). Chronic GVHD (any grade) occurred in 42.3% of PTCy vs 38.2% of others (p=0.664), while moderate-to-severe cGVHD was lower with PTCy (21.2% vs 27.3% p=0.461). Platelet engraftment was significantly delayed in the PTCy group (median 33 vs 21 days, p=0.030). Median time to neutrophil engraftment was also delayed in the PTCy group (20 vs 17 days, adjusted p=0.025). Age-adjusted HR for time to platelet engraftment was 0.60 (95% CI: 0.41–0.90; p=0.014), and for neutrophil engraftment 0.65 (95% CI: 0.44–0.95; p=0.025), indicating significantly delayed hematopoietic recovery with PTCy. Graft failure occurred in 9.4% vs 5.3% (p = 0.48); primary 7.5% vs 3.5%, secondary 1.9% vs 1.8% in PTCy vs non-PTCy groups, respectively. Relapse or progression occurred in 11.3% of PTCy vs 17.5% of others (p=0.355); four patients in the non-PTCy group progressed to AML post-transplant, versus none in the PTCy group (p=0.119). 1-year TRM was 22.6% in the PTCy group and 14.0% in the non-PTCy group, p = 0.324. Median OS was 72.8 months in the PTCy group (95% CI: 49.9 months, upper limit not estimable [NE]) and 93.4 months in the non-PTCy group (95% CI: 48.5 months, upper limit NE), although the difference was not statistically significant (p=0.739). After adjusting for age and HCT-CI, there were no significant differences in PFS (adjusted HR 1.37; 95% CI: 0.73–2.56; p=0.331) or OS (adjusted HR 1.27; 95% CI: 0.64–2.51; p=0.498). Conclusions In myelofibrosis patients undergoing allo-HCT, PTCy-based GVHD prophylaxis showed similar rates of grade ≥2 acute and moderate-severe chronic GVHD compared to non-PTCy regimens. Engraftment was significantly delayed, while OS and PFS were comparable. PTCy appears to be a safe and viable alternative to CNI-based prophylaxis.

Introduction Survival following allogeneic hematopoietic cell transplantation (allo-HCT) has improved over the last several decades. Implementation of reduced-intensity conditioning and improvement in graft selection, graft vs. host disease (GVHD) prophylaxis and treatment, and infection disease management, among others, have contributed to reducing non-relapse mortality (NRM). The use of post-transplant cyclophosphamide (PTCy) for GVHD prophylaxis, in particular, has been associated with reduced incidence of acute and chronic GVHD in both HLA-matched related and matched unrelated donor allografts. In this study, we aim to determine prognostic factors for NRM (including early NRM defined as within 100 days post-transplantation), disease-related mortality (DRM), and overall survival (OS) in a large cohort of patients following allo-HCT. Methods Patients who received consecutive allo-HCT at our institution from 2009-2023 were included. Clinical data were collected from retrospective reviews of the electronic medical records. Patient- and transplant-related variables were compared between patients who died and those who were alive at 100 days post allo-HCT. Univariate and multivariate Cox proportional hazard models were used to identify prognostic associations between risk factors and OS. Kaplan-Meier method was used to evaluate OS. Log-rank test was used to compare OS between groups. Statistical significance was set to < 0.05. Results A total of 536 patients (male=285, 53%) were included. Median age at time of allo-HCT was 59 (range, 19-75) years. Most patients were White/Caucasian (n=232, 86%). The most common diagnoses included acute myeloid leukemia (AML) (n=110, 41%), myelodysplastic syndrome (n=52, 19.2%), myelofibrosis (n=23, 9%), B-cell acute lymphoblastic leukemia (B-ALL) (n=22, 8.1%), non-Hodgkin lymphoma (n=21, 8%), and chronic myeloid leukemia (n=10, 4%). The median follow-up for survivors was 4.2 (range, 1.1-14.4) years. A total of 80 (14.9%) patients died within 100 days with most deaths attributed to NRM (n=61, 76%). Specific causes of death included infection/sepsis in 22 (27.5%) patients, GVHD in 10 (12.5%), respiratory failure in 9 (11.2%), multiorgan failure in 5 (6.3%), graft failure in 5 (6.3%), and other causes in 10 (12.5%). Progressive disease was the cause of death in 19 (23.8%) patients. Male gender (HR=1.92; p= 0.006), remission status other than CR1 or CR2 for acute leukemia patients (HR=8.44; p<0.0001), non- PTCy strategies (HR=2.4; p= 0.0006), and earlier year of transplantation (HR=1.12; p=< 0.001) were associated with increased risk of mortality at 100 days on univariate analysis. Only use of TBI (HR=2.56, p=0.048) and earlier year of transplantation (HR=1.2; p=0.001) were associated with increased risk of DRM at 100 days post-allografting on univariate analysis. Pertaining to risk of NRM at 100 days, male gender (HR=1.89; p=0.02), diagnosis other than acute leukemia (HR=2.27; p=0.004), non-PTCy strategies (HR=2.44; p=0.003), and earlier year of transplantation (HR=1.1; p=0.004) were adversely associated with NRM. On multivariate analysis, only earlier year of transplantation was found to be associated with increased risk of DRM at 100 days (HR 1.15; p=0.049). Male gender (HR=1.78; p=0.035), diagnosis other than acute leukemia (HR=2.38; p=0.003), and non-PTCy strategies (HR=2.2; p=0.032), were associated with increased risk of NRM at 100 days. Conclusion Non-relapse mortality (NRM) accounted for most deaths within the first 100 days of allo-HCT, primarily due to infection/sepsis and GVHD. Factors associated with increased NRM included male gender and diagnoses other than acute leukemia. Significantly, post-transplantation cyclophosphamide (PTCy) was the only treatment strategy modification that decreased 100-day NRM and improved survival, independent of the transplantation year.