Abstract Graft-versus-host disease (GVHD) is a major risk factor for transplant-associated thrombotic microangiopathy (TA-TMA), and the 2 conditions often co-occur; therefore, we evaluated the biomarkers of endothelial injury to clarify their relationship. Our prospective Microangiopathy, Endothelial Damage in Adults Undergoing Stem Cell Transplantation cohort study of 368 adult (aged ≥18 years) patients measured biomarkers before and after their first allogeneic hematopoietic cell transplantation (HCT). We found that posttransplant cyclophosphamide significantly reduced acute GVHD incidence but had no impact on the reduction of TA-TMA incidence. Severe TA-TMA occurred in the absence of acute GVHD but also occurred more frequently with higher grades of acute GVHD. Pretransplant serum creatinine and detectable placental growth factor were associated with post-HCT TA-TMA. In sex-stratified multivariable models, a 1 mg/dL increase in pretransplant creatinine conferred a ∼40-fold higher TA-TMA risk in females vs approximately fivefold in males. Both landmark and association analyses identified day +28 creatinine and suppression of tumorigenicity 2 (ST2) as significant TA-TMA risk factors. Our study phenotyped TA-TMA and GVHD concurrently, and we show that ST2, previously linked to GVHD treatment response and nonrelapse mortality (NRM), also predicted TA-TMA. Day +28 levels of ST2, soluble FLT-1, and epidermal growth factor were associated with NRM and overall survival (OS), whereas baseline or day +28 soluble C5b-9 was not associated with TA-TMA. Post hoc analyses of Endothelial Activation and Stress Index composite score at day +28 after HCT found significant associations with severe TA-TMA, acute GVHD, NRM, and OS. Overall, our data highlight distinct risk factors and biomarker profiles for TA-TMA and GVHD and also identify differences between adults and reported biomarkers of TA-TMA in children.

INTRODUCTION: Severe transplant-associated thrombotic microangiopathy (TMA) is a serious complication of allogeneic hematopoietic cell transplantation (HCT), which is frequently linked with acute GVHD. The association between serum biomarkers predictive of acute GVHD and TMA remains understudied in adult HCT patients. METHODS: Established and novel biomarkers of both acute GVHD and TMA were selected including serum concentrations of ST2, ANG-2 (angiopoietin-2), EGF (epidermal growth factor), VEGFR2, sFLT-1 (soluble fms-like tyrosine kinase-1), PlGF (placental growth factor), cystatin-C, VDBP (vitamin D binding protein), sC5b-9, NETs (neutrophil extracellular traps), and F-actin measured pre-HCT in a centralized laboratory using enzyme-linked immunosorbent assay. ST2 and sC5b-9 were analyzed as log-transformed variables. TMA was adjudicated by a blinded three-member panel. Time to event multivariable analyses were performed for severe TMA, grade III-IV acute GVHD, NRM and OS using a predictive approach including pre-HCT variables significant (P<0.01) in the univariable analysis with backward elimination. RESULTS: 368 HCT patients had prospectively collected biospecimens for serum biomarker evaluation from 3 participating centers of the MIDAS (Microangiopathy, endothelial Damage in Adults undergoing Stem cell transplantation) consortium. At time of HCT, median age was 61 years (range 19-78), ~60% were male, 88% were non-Hispanic White, 42% had HCT comorbidity index >/=3, myeloid malignancies were the most common (82%) indication, ~60% were in CR, 72% received RIC regimens, and peripheral blood was the predominant (96%) graft source. Most frequent donor type was 10/10 HLA matched unrelated donor (MUD, 56.5%), with <10/10 HLA-mismatched unrelated (MMUD, 16.6%), haploidentical (14.4%) and HLA-matched related donor (12.5%) less frequently used. GVHD prophylaxis was tacrolimus (Tac) and methotrexate (MTX) based regimen in 44% and post-HCT cyclophosphamide (PTCy) based regimen in 54% (35% with Tac and 19% with sirolimus). Median follow up of survivors was 9.6 months (range, 1.0-12.9). The incidence of severe TMA by day + 100 was 18.5%, about half of which occurred before onset of acute GVHD and half occurred after acute GVHD onset. Acute GVHD grade III-IV was less frequent in PTCy-based prophylaxis compared to MTX-based prophylaxis (11.5% vs 20.5%), however severe TMA occurred in a similar proportion of patients with PTCy-based prophylaxis (22% vs. 19%). In addition, severe TMA occurred in 12% of patients with a maximum grade of 0-I and 18% of patients with grade II acute GVHD demonstrating that severe TMA occurs in ~10-20% of patients without severe grade III-IV acute GVHD and in those receiving PTCy-based prophylaxis. In multivariable analysis of severe TMA, we discovered effect modification between pre-HCT creatinine and sex, therefore stratified models are presented. In males, severe TMA risk was increased 6-fold with each unit (1 mg/dL) increase of pre-HCT creatinine (HR=6.34, 95% CI 2.55-15.72; p<0.001). In females, severe TMA risk was increased 36-fold with each one-unit increase in pre-HCT creatinine (HR=36.34, 95% CI 13.91-94.91; p<0.0001) and was increased with detectable PlGF (HR=2.84, 95% CI 1.39-5.81, P=0.004). In multivariable analysis, grade III-IV acute GVHD was significantly reduced in PTCy-sirolimus compared to MTX-based regimens (HR=0.23, 95% CI 0.07-0.73; p=0.01), significantly higher with increasing pre-HCT serum creatinine (HR=2.66, 95% CI 1.22-5.80; p=0.01) and soluble C5b-9 (HR=1.72, 95% CI 1.09-2.71; p=0.02). NRM increased with elevated pre-HCT serum creatinine (HR=4.17, 95% CI 2.13-8.16; p<0.001) and detectable PlGF (HR=1.94, 95% CI 1.05-3.61; p=0.035). In stratified models, overall mortality was significantly higher with increasing pre-HCT serum creatinine in males (HR=4.41, 95% CI 1.43-13.61; p=0.01), and females (HR=8.3, 95% CI 1.68-40.97; p=0.009). CONCLUSIONS: In this prospective study, we show that distinct biomarkers measured pre-HCT are associated with severe TMA, acute GVHD, NRM and OS. Pre-HCT serum creatinine was the strongest factor associated with all 4 outcomes. Severe TMA incidence was similar between PTCy and MTX prophylaxis, despite a significant reduction in acute GVHD with PTCy. Additional analyses of biomarkers measured post-HCT are ongoing and our results are worthy of further validation.

No prospective study has evaluated the incidence of transplant-associated thrombotic microangiopathy (TA-TMA) in adult allogeneic hematopoietic cell transplant (HCT) recipients. The MIDAS (microangiopathy, endothelial damage in adults undergoing stem cell transplantation) Consortium conducted, to our knowledge, the first multicenter study to prospectively screen for TA-TMA. Longitudinal blood samples and detailed clinical data were collected weekly through day +100 and at months 5, 6, 9, and 12 from first allogeneic HCT recipients at 3 sites (The Ohio State University, Moffitt Cancer Center, and Roswell Park Comprehensive Cancer Center). Adjudication of TA-TMA diagnosis was reviewed in real time by 3 blinded independent reviewers. Incidence of TA-TMA was scored using 6 published criteria, as well as the center-reported diagnosis and MIDAS adjudication categorized as none, nonsevere, or severe TA-TMA. Incidence of severe TATMA by day +100 was similar across the 3 centers at 21.8%, with a median onset of 14.5 days in 239 patients. Incidence of nonrelapse mortality was 42% in severe compared with 8.4% in nonsevere and 5.8% in no-TMA groups (P < .001). Rise in serum creatinine as early as day +7 and occurrence of hypertension by day +14 after HCT were early indicators of severe TA-TMA. Our prospective study of systematic screening for TA-TMA identifies a higher incidence of a clinically impactful phenotype of TA-TMA than previously reported in adult HCT recipients. Our natural history study provides an essential foundation for urgently needed studies of TA-TMA prophylaxis and treatment in adults and suggests clinical value in our inexpensive screening strategy.

Transplant-associated thrombotic microangiopathy (TA-TMA) can be associated with significant morbidity and mortality but is under-studied in adults. An expert consensus panel recently published Modified Jodele Criteria (MJC) to define TA-TMA with the intent for adoption across transplant registries and centers (PMID: 36442770).We performed the first study in adults applying MJC criteria for TA-TMA in a prospective cohort with weekly biospecimen and data collection through day+100 after allogeneic HCT. The MIDAS Consortium consists of 3 adult HCT centers, with a plan to enroll 1000 first allo HCT patients. Herein we report on the first 101 patients who have reached 1-year post-HCT (Table). TA-TMA was adjudicated using the MJC definition by a 3-member panel who were blinded to each other and to the HCT center's reporting of TA-TMA.We defined severe TA-TMA as meeting the MJC definition while also having end-organ damage (new hypertension, neurologic manifestations, renal dysfunction, proteinuria) OR high transfusion requirements. Median follow up in the first 101 patients was 344.5 days post-HCT.At day+100 post-HCT, the cumulative incidence of TA-TMA by MJC was 46.8% (95% CI 36.8-56.2%) and severe TA-TMA was 17% (95% CI 10.4-24.9%), neither of which significantly differed by center. TA-TMA defined by MJC was significantly associated with 1-year overall survival (OS) and non-relapse mortality (NRM, Figure 1A, 1B). OS and NRM were significantly affected by severe TA-TMA but not by not-severe TA-TMA. (Figure 1C, 1D).The proportion of patients with severe TA-TMA increased with increasing severity of acute GVHD (Figure 2). TA-TMA preceded GVHD in patients with grade I or II acute GVHD, while most patients with grade III-IV acute GVHD were diagnosed concurrently with severe TA-TMA.Concordance of TA-TMA diagnosis between the MIDAS panel and HCT center was low. Of 17 patients adjudicated as severe TA-TMA by MIDAS, 10 were reported as having TA-TMA by the center, with 8 receiving TA-TMA-directed therapy (6 eculizumab, 2 other) and only 2 of 8 survived (both received eculizumab). Of 23 patients adjudicated as MJC-defined TA-TMA that was not severe, 5 were reported as TA-TMA by the center, with 5 receiving TA-TMA-directed therapy (2 eculizumab, 3 other). All 5 of these patients remain alive at last follow-up. Both MJC defined and severe TA-TMA were under-reported by the centers.TA-TMA as defined by MJC is frequent in adults after allogeneic HCT, but not all TA-TMA is actionable. Actionable cases of severe TA-TMA can be identified by end-organ damage and high transfusion requirements. Weekly biospecimens have been collected up to day+100 and will be analyzed for biomarkers associated with development and prognosis of TA-TMA.

Introduction-Chronic graft-versus-host disease (cGVHD) poses as a major late complication of hematopoietic stem cell transplantation. The role of cGVHD as a determinant in transplant-related morbidity and mortality, infectious complications, prolonged immune suppression, and impaired patient-reported quality of life has been extensively studied. Nonetheless, numerous advances in allogeneic hematopoietic stem cell transplant (allo-SCT) in recent years have expanded the indications for allo-SCT to a broader range of patients, including previously excluded older patients. However, long-term health status of older transplant recipients is poorly studied. Notably, the incidence of cGVHD may increase with age. Therefore, the development of cGVHD and the use of immunosuppressive therapy may lead to a higher degree of non-relapse mortality (NRM) in older patients. The objective of this study was to compare the NRM in both younger and older transplant recipients with and without cGVHD. Methods-We performed a retrospective cohort study of patients that underwent allo-SCT at the Ohio State University from 1999 to 2018. Data was analyzed from 1194 patients who survived or have been followed up with by at least day (d) 180 post-transplantation, among which 373 patients had developed cGVHD. Patients were grouped based on their age into a younger and older population. The older population was defined as ≥60 (N=373, 31%) with the younger population defined as <60 (N=821, 69%) years (yr) of age. NRM was defined as death unrelated to relapse, with relapsed mortality as a competing risk. A landmark analysis approach was used to study the association between the age groups to NRM, stratified by whether or not patients had developed cGVHD by d180. Fine and Gray competing risk model was used to build the multivariable regression model controlling for confounding variables, such as gender, donor type, donor source, conditioning regimen, and diagnosis. Results-The median age at allo-SCT was 53.0 yr (range: 18-76) and 61.1% were male. Acute myeloid leukemia accounted for 36.7% of transplants, followed by non-Hodgkin's lymphoma (14.8%), acute lymphoid leukemia (12.7%), and myelodysplastic syndrome (11.0%). Additionally, 58.0% received reduced-intensity conditioning regimen. The majority of stem cell donor types were match unrelated (45.3%) and match related (39.8%). Patients who had developed cGVHD by d180, regardless of age, were at higher risk of NRM compared to patients with no cGVHD (hazard ratio [HR]: 1.52, 95% confidence interval [CI]: 1.16-1.99; p=0.002). To examine the influence of age with NRM, we stratified the analysis by cGVHD status by d180. Among patients developed cGVHD by d180, in both univariable (HR 1.22, 95% CI 0.79-1.9, p=0.373) and multivariable analysis (HR: 1.17, 95% CI: 0.74-1.87; p=0.501), there was no statistically significant difference in NRM between patients ≥60 and <60 yr of age. Among patients without cGVHD by day 180, age ≥60 yr was a significant factor for increased NRM in both univariable (HR: 1.52, 95% CI 1.08-2.15; p=0.017) and multivariable (HR: 1.55, 95% CI: 1.04-2.30; p=0.031) analysis. Conclusion-This study showed that patients with cGVHD by day 180 were at higher risk for higher NRM compared to patients without cGVHD. Among cGVHD patients, there was no difference on the outcome of older patients (≥60 years old) compared to younger ones (<60 years old). This suggests that cGVHD therapy is equally tolerable among different age groups. Disclosures Chaudhry: Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees. Bumma:Sanofi: Speakers Bureau; Amgen: Speakers Bureau. Khan:Amgen: Consultancy; Janssen: Consultancy. Devarakonda:Janssen: Consultancy. Vasu:Kiadis Inc: Other: Kiadis has obtained exclusive licensing requirements from The OHio State University; Janssen: Membership on an entity's Board of Directors or advisory committees; Omeros: Membership on an entity's Board of Directors or advisory committees. Jaglowski:Novartis: Consultancy, Research Funding; Juno: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; CRISPR: Consultancy. William:Celgene: Consultancy, Honoraria; Dova: Research Funding; Guidepoint Global: Consultancy; Merck: Research Funding; Kyowa Kirin: Consultancy, Honoraria; Seattle Genetics: Research Funding; Incyte: Research Funding. Mims:Syndax Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Other: Data Safety Monitoring Board; Abbvie: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Leukemia and Lymphoma Society: Other: Senior Medical Director for Beat AML Study; Novartis: Speakers Bureau; Agios: Consultancy. Brammer:Bristol-Myers Squibb: Research Funding; Celgene: Research Funding; Seattle Genetics: Honoraria, Speakers Bureau; Kymera: Honoraria; Verastem Oncology: Other: Travel. Saad:Magenta Therapeutics: Other: Personal Fees; Incyte Pharmaceuticals: Other: Personal Fees; Amgen: Other: research support; Kadmon: Other: research support; Orcabio: Other: research support. Efebera:Takeda: Honoraria, Speakers Bureau; Pharmacyclics: Research Funding; Celgene: Research Funding; Ohio State University: Current Employment.

Background Allogeneic stem cell transplant (allo-SCT) plays a key role in the treatment of patients with both acute myeloid leukemia (AML) and myelodysplastic (MDS). Outcomes of allo-SCT have improved with optimization of transplant practices. We sought to evaluate trends in survival in AML and MDS patients undergoing allo-SCT at our institution from 1984 to 2018. Methods A retrospective analysis of 900 consecutive AML and MDS patients undergoing allo-SCT was performed. Patients were divided by year of transplant for analysis. Primary endpoints were progression free survival (PFS) and overall survival (OS). Secondary endpoints included non-relapse mortality (NRM), graft-versus-host disease (GVHD), GVHD-free relapse free survival (GRFS), and transplant complications. Results We found a significant improvement in survival from 1984 to 2018 with 5-year PFS and OS improving from 17% to 49% and 17% to 53%, respectively (statistically significant difference since 2004; p<0.001). There was a significant difference in rates of grade II-IV aGVHD (p<0.001) and chronic GVHD at day +365 with cumulative incidence of both highest from 2014-2018, however, NRM improved across the years with 5- year NRM decreasing from 45% to 21%. Rates of pulmonary infections, hemorrhagic cystitis, veno-occlusive disease, and fungal infections also decreased across the years (p<0.001). Conclusions We found a significant improvement in survival of AML and MDS patients undergoing allo-HCT over the past several decades. This likely reflects improvements in transplant practices and general supportive care. Post-transplant relapse remains the leading cause of transplant failure in this group.

The standard preparative regimen for autologous stem cell transplant (ASCT) in multiple myeloma (MM) is 200 mg/m(2) of intravenous melphalan; however, a dose of 140 mg/m(2) is often used when concerns exist related to patient age, performance status, organ function, and other factors. It is unclear whether a lower dose of melphalan impacts post-transplant survival outcomes. We performed a retrospective review of 930 patients with MM who underwent ASCT with 200 mg/m(2) versus 140 mg/m(2) melphalan. On univariable analysis, no difference in progression-free survival (PFS) was observed, however, an overall survival (OS) benefit was observed in patients receiving 200 mg/m(2) melphalan (p = 0.04). Multivariable analyses showed patients receiving 140 mg/m(2) faired no worse than those receiving 200 mg/m(2). While a subset of younger patients with normal renal function may achieve superior OS with a standard dose of 200 mg/m(2) melphalan, these findings suggest an opportunity to individualize the ASCT preparative regimen to optimize outcomes.

IgD multiple myeloma is uncommon. Patients generally present at a younger age and have shorter progression free and overall survivals (OSs). Its rarity has inhibited development of a specific risk stratification system or informed best treatment protocols. We present interphase fluorescence in situ hybridization results from a group of 29 cases. These showed evidence of a decreased male to female ratio, decreased OS in patients aged 70 and over, better outcomes in those with kappa light chain restriction, and CD56 positive patients had longer survivals than those lacking CD56. We discuss the biology of IgD multiple myeloma, the need for prospective studies, and challenges for improvements in diagnosis and treatment. We suggest an International Register to accelerate development of best practice guidelines for diagnosis, risk stratification, and treatment.

BackgroundAllogeneic hematopoietic stem cell transplant (allo-HCT) is a potential curative therapy for a variety of hematologic disorders. However, it requires highly specialized care that is only available at select centers across the country. Thus, minority populations are at risk for healthcare disparities in access to and outcomes of allo-HCT. Our study aimed to assess the impact of race and location of residence on outcomes of allo-HCT. MethodsWe performed a retrospective analysis of all patients who underwent allo-HCT at the Ohio State University from 1984 to 2018. Patients were divided by race (Caucasian, African American, and other) and grouped by zip code into rural, suburban, and urban groups. Primary endpoints included progression-free survival (PFS) and overall survival (OS). ResultsOf the 1,943 patients included in the study, 94.3% self-identified as Caucasian, 4.6% African American, and 1.1% other. In total, 63.4% lived in rural areas, 22.9% suburban, and 13.8% urban. There was no significant difference in OS or PFS by race (p = 0.15, 0.21) or place of residence (p = 0.39, 0.17). In addition, no difference in nonrelapse mortality, acute and chronic graft-versus-host disease (GVHD), and GVHD-free relapse-free survival (GRFS) was seen among the race or place of residence. ConclusionOur study suggests that when appropriate access to HCT is given, there is no difference in outcomes based on race, ethnicity or place of primary residence. Further research is needed to further evaluate barriers for these patients to undergo transplant and help mitigate these barriers.

•Peripheral blood CD38 bright CD8+TEM cell expansion did not predict acute GVHD.•Markers of T-cell activation were not different in patients with and without acute GVHD.•Markers of cytotoxic potential or proliferative state were not different in patients with and without acute GVHD.

Anti-CD19 chimeric antigen receptor T cell therapy (CAR19) represents a critical treatment modality for patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, the majority of patients subsequently experience disease progression following CAR19, and data are limited on assessing the best salvage regimen for these patients. This study aimed to evaluate outcomes in R/R DLBCL patients with progressive disease post-CAR19 and to assess variables that predict response to salvage therapy. We performed a retrospective analysis of all patients with DLBCL who received CAR19 at our institution between January 2018 and February 2021, collecting data on demographic characteristics, disease characteristics, best response to CAR19, date of relapse or progression, and first salvage therapy and response to salvage. We analyzed patients according to whether they responded to CAR19 (responders) or did not (nonresponders). Salvage regimens were classified into 6 groups for analysis. Primary endpoints included overall survival (OS) and progression-free survival (PFS), calculated using the Kaplan-Meier method. Cox models were fit to evaluate the effect of prognostic factors. Among the 120 patients who received CAR19 during the analysis period were 69 responders who achieved a complete or partial response to CAR19 and 51 nonresponders, including 44 with stable or progressive disease and 7 who died before assessment. Thirty responders relapsed and 26 received salvage therapy, and 24 nonresponders received salvage therapy. The primary salvage regimens included lenalidomide-based regimens (n = 17; 34%), BTKi (n = 10; 20%), checkpoint inhibitor-based (n = 7; 14%), chemo-immunotherapy (n = 5; 10%), allogeneic hematopoietic stem cell transplantation (n = 5; 10%), and others (n = 6; 12%). There was no significant difference in OS based on salvage regimen (P = .4545). Responders who received salvage therapy had significantly longer OS than nonresponders (median OS not reached versus 10.9 months; P = .0187), and response to CAR19 and elevated lactate dehydrogenase level at time of salvage treatment were the only two statistically significant prognostic factors after accounting for other variables. Responders to CAR19 had significantly better outcomes with salvage therapy compared with nonresponders to CAR19. There was no significant difference in outcomes based on salvage regimen. Future research is needed to assess the best salvage regimen post-CAR19 failure. (c) 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

The United States Food and Drug Administration has approved several oral, targeted therapies for the treatment of Acute Myeloid Leukemia (AML) in recent years. These agents are approved in patients with relapsed/refractory disease or as frontline therapy in patients who are ineligible for intensive chemotherapy based on age, performance status, or comorbidities. They are also being increasingly utilized frontline in patients of all ages and fitness levels through clinical trials and off label prescribing, but comparative treatment outcomes associated with intensive versus targeted therapy have not been extensively studied. We conducted a single center, retrospective analysis to address the impact of treatment intensity on survival in patients with AML aged 60-75 at diagnosis. This study included 127 patients, 73 of whom received high intensity chemotherapy at any point during treatment (any HiC) and 54 of whom received only low intensity targeted therapy (LITT only). Overall survival (OS) from treatment initiation did not differ significantly between the any HiC and LITT only groups (hazard ratio (HR) for death, 0.67; 95% CI, 0.41 to 1.09; P=0.11). The only three variables that were independently associated with superior OS were lower European Leukemia Net (ELN) risk classification, TP53 unmutated status, and receipt of transplant. Our data suggest that baseline genomic features and receipt of transplant are more important than treatment intensity in predicting survival in this patient population. They also highlight the vital role of transplant in older patients with AML regardless of treatment intensity utilized for remission induction. Larger studies are needed to further address this question, including prospective randomized trials.

Allogeneic hematopoietic stem cell transplantation (allo-SCT) is a potentially curative treatment for many hematological disorders, but is often complicated by relapse of the underlying disease, graft-versus-host disease (GVHD), and infectious complications. We conducted a retrospective analysis on patients undergoing allo-SCT from 1984 to 2018 to better understand how survival has changed longitudinally with therapeutic advancements made to mitigate these complications. Method: We analyzed data from 1943 consecutive patients who received allo-SCT. Patients were divided into groups (gps) based on the year (yr) of transplant. Primary endpoints were overall survival (OS), progression free survival (PFS), and GVHD-free relapse-free survival (GRFS). Secondary endpoints were the cumulative incidences of grade II–IV and grade III–IV acute GVHD (aGVHD), chronic GVHD (cGVHD), and non-relapse mortality (NRM). Results: Our study found statistically significant improvements in OS, PFS, and GRFS. Five-year PFS among the groups increased from 24% to 48% over the years. Five-year OS increased from 25% to 53%. Five-year GRFS significantly increased from 6% to 14%, but remained relatively unchanged from 2004 to 2018. Cumulative incidences of grade II–IV aGVHD increased since 2009 (p < 0.001). However, cumulative incidence of NRM decreased since 2004 (p < 0.001). Conclusions: Our data show improved OS, PFS, and GRFS post allo-SCT over decades. This may be attributed to advances in supportive care and treatments focused on mitigation of GVHD and relapse.

Multiple myeloma (MM) represents 1.8% of all new cancer cases in the U.S. While not curable, advances in treatment, including autologous stem cell transplant (ASCT) and maintenance therapy, have dramatically improved progression-free survival (PFS) and overall survival (OS). We performed a retrospective survival analysis on newly diagnosed MM (NDMM) patients receiving ASCT from 1992–2016 at the Ohio State University. A total of 1001 consecutive NDMM patients were eligible. Patients were split into five groups based on historic changes in novel agents for the treatment of MM. Across the years (1992–2016), there was a statistically significant improvement in both PFS (p < 0.01) and OS (p < 0.01). Significant improvements in both PFS and OS were seen in patients ≤65 years (p < 0.001 and p = 0.002) and >65 years old (p < 0.001 and p = 0.001), respectively. Improved PFS and OS were seen in both standard-risk (p < 0.001 and p < 0.001) and high-risk patients (p < 0.001 and p = 0.019). The post-transplant response showed statistically significant improvement across the years (p < 0.01). Survival rates for NDMM patients have significantly improved primarily due to the inclusion of novel therapies and post-ASCT maintenance.