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Key Points The incidence of acute cardiac toxicity remains low and manageable after matched allo-HCT in the era of PTCy prophylaxis.Older age, hypertension, arrhythmia, diabetes, and cardiac comorbidities increase this risk of cardiac toxicity but PTCy did not., Visual Abstract, Graft-versus-host disease (GVHD) is one of the leading causes of nonrelapse mortality (NRM) after allogeneic hematopoietic cell transplantation (allo-HCT). Posttransplant cyclophosphamide (PTCy) has shown promise in managing GVHD. However, cyclophosphamide has known cardiac toxicity, and few studies have evaluated the cardiac toxicities that arise after PTCy. We completed a retrospective analysis of patients who underwent matched-donor allo-HCT at our institution and who received PTCy- or non-PTCy–based GVHD prophylaxis, with the goal of determining the incidence of cardiac toxicities up to 100 days after allo-HCT. We included 585 patients in our analysis and found that 38 (6.5%) experienced cardiac toxicity after allo-HCT. The toxicities included arrhythmias (n = 21), heart failure (n = 14), pericardial effusion (n = 10), and myocardial infarction or ischemia (n = 7). Patients who received PTCy had a 7.4% incidence of cardiac toxicity, whereas non-PTCy recipients had an incidence of 5.8% (P = .4). We found that age >55 years (P = .02) and a history of hypertension (P = .01), arrhythmia (P = .003), diabetes (P = .04), and cardiac comorbidities (P < .001) were significant predictors of cardiac toxicity, whereas none of the preparative and GVHD prophylaxis regimens were predictive. From these findings, we proposed the use of a Cardiac Risk Stratification Score to quantify the risk of cardiac toxicity after allo-HCT. We found that a higher score correlated with an incidence of cardiac toxicity. Furthermore, the development of cardiac toxicity was associated with worse 1-year overall survival (OS) and NRM. The use of PTCy was associated with improvements in 1-year OS and NRM rates.

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their Food and Drug Adminsitration approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day (30-d) major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, four exacerbations of heart failure/cardiomyopathy, four cerebrovascular accidents, three myocardial infarctions, and one patient died due to myocardial infaction. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range, 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival or with overall survival. Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited follow-up, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

Donor-specific anti-HLA antibodies (DSAs) are a major cause of engraftment failure in patients receiving haploidentical stem cell transplantation (HaploSCT). Effective treatments are needed for these patients, who often have no other donor options and/or are in need to proceed urgently to transplantation. We studied a multimodality treatment with alternate-day plasma exchange (PE), rituximab, intravenous γ globulin (IVIg) and an irradiated donor buffy coat for patients with DSAs at 2 institutions. Thirty-seven patients with a median age of 51 years were treated with this desensitization protocol. Treatment outcomes were compared with a control group of HaploSCT patients without DSAs (n = 345). The majority of patients in the DSA group were female (83.8% vs 37.1% in controls, P < .001) and received stem cells from a child as the donor (67.6% vs 44.1%, P = .002). Mean DSA level before and after desensitization was 10 198 and 5937 mean fluorescence intensity (MFI), respectively, with mean differences of 4030 MFI. Fourteen of 30 tested patients (46.7%) had C1q positivity, while 8 of 29 tested patients (27.6%) remained positive after desensitization. In multivariable analysis, patients with initial DSA > 20 000 MFI and persistent positive C1q after desensitization had a significantly lower engraftment rate, which resulted in significantly higher non-relapse mortality and worse overall survival (OS) than controls, whereas graft outcome and survival of patients with initial DSA < 20 000 MFI and those with negative C1q after treatment were comparable with controls. In conclusion, treatment with PE, rituximab, IVIg, and donor buffy coat is effective in promoting engraftment in patients with DSAs ≤20 000 MFI.

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host disease (GVHD), all grade I-II. The cumulative incidence (CI) of chronic GVHD at five-year was 34%. The CI of non-relapse mortality at one-year was 29%. Progression-free survival (PFS) rates at two-year and five-year were 49% (95% CI = 22-71%) and 39% (95% CI = 14-64%), respectively. The two-year and five-year overall survival (OS) rates were 65% (95% CI = 38-82%) and 40% (95% CI = 12-68%), respectively. The five-year rate for both PFS and OS was 80% in CR1 patients versus 0% in patients not in CR1. In conclusion, allo-HCT provides long-lasting remissions in BPDCN patients, particularly when performed in CR1.

Purpose: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). Patients and Methods: We evaluated 194 patients with follicular lymphoma who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). Results: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT (P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively (P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27). Conclusions: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma.

Relapse after allogeneic hematopoietic cell transplantation (HCT) leads to poor survival in patients with acute myeloid leukemia (AML). A second HCT (HCT2) may achieve durable remission. To determine the outcomes of patients who received an HCT2 for relapsed AML and to evaluate the predictors of overall survival (OS) and progression-free survival (PFS). We retrospectively reviewed medical records of adult patients who underwent an HCT2 for relapsed AML at our institution during 2000 to 2019. Ninety-one patients were identified with a median age of 44 years (range 18-73) at HCT2. Donor types were HLA-identical sibling (n = 37 [41%]), HLA-matched–unrelated (n = 34 [37%]), haploidentical (n = 19 [21%]), and cord blood (n=1 [1%]). Donors were different at HCT2 in 53% of patients. The majority of patients received reduced intensity conditioning (n = 71 [78%]) and were in remission (n = 56 [61%]) at HCT2. The median remission duration after HCT1 was 8.4 months (range 1-70) and the median time between transplants was 14 months (range 3-73). The median follow-up of surviving patients after HCT2 was 66 months (range 2-171), with 32% alive at time of analysis. The most common cause of death was disease recurrence (n = 45 [73%]). At 2 years, the rates of OS, PFS, progression, and nonrelapse mortality were 36%, 27%, 42%, and 18%, respectively. The development of chronic graft-versus-host disease (GVHD) after first HCT and HCT comorbidity index (HCT-CI) ≥2 at HCT2 were associated with inferior PFS and OS after HCT2. A second HCT is feasible in selected patients with AML who have relapsed after HCT1. Long-term survival benefit is possible in patients without chronic GVHD after HCT1 and HCT-CI

Steroids remain the initial therapy for acute graft-vs.-host disease (AGVHD). Strategies to improve response and minimize steroid exposure are needed. We report results of a randomized, adaptive, Bayesian-designed, phase II trial of prednisone with or without extracorporeal photopheresis (ECP) as an initial therapy for patients with newly diagnosed AGVHD. The primary endpoint was success at day 56 defined as: alive, in remission, achieving AGVHD response without additional therapy, and on

This study investigated the efficacy and safety of azacitidine maintenance in the posttransplant setting based on the encouraging phase 1/2 reports for azacitidine maintenance in patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS). Between 2009 and 2017, a total of 187 patients aged 18 to 75 years were entered into a randomized controlled study of posttransplant azacitidine if they were in complete remission. Patients randomized to the treatment arm (n = 93) were scheduled to receive azacitidine, given as 32 mg/m2 per day subcutaneously for 5 days every 28 days for 12 cycles. The control arm (n = 94) had no intervention. Eighty-seven of the 93 patients started azacitidine maintenance. The median number of cycles received was 4; a total of 29 patients relapsed on study, and 23 patients withdrew from the study due to toxicity, patient’s preference, or logistical reasons. Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs 1.28 years in the control group (P = .43). There was also no significant difference for overall survival, with a median of 2.52 years vs 2.56 years in the azacitidine and control groups (P = .85), respectively. Multivariate Cox regression analysis revealed no improvement in RFS or overall survival with the use of azacitidine as maintenance compared with the control group (hazard ratios of 0.73 [95% confidence interval, 0.49-1.1; P = .14] and 0.84 [95% confidence interval, 0.55-1.29; P = .43]). This randomized trial with azacitidine maintenance showed that a prospective trial in the posttransplant setting was feasible and safe but challenging. Although RFS was comparable between the 2 arms, we believe the strategy of maintenance therapy merits further study with a goal to reduce the risk of relapse in patients with AML/MDS. This trial was registered at www.clinicaltrials.gov as #NCT00887068.

How to best use tyrosine kinase inhibitors (TKIs) of BCR-ABL after allogeneic stem cell transplantation for Philadelphia chromosome–positive acute lymphoblastic leukemia (ALL) is unknown but will almost certainly not be addressed by a definitive randomized trial. Saini and colleagues provide a large body of observational data to reinforce earlier circumstantial evidence favoring prophylactic use of TKIs for at least 2 years posttransplant.

Haploidentical donors are increasingly used for patients requiring hematopoietic stem cell transplantation (HSCT). Although several factors have been associated with transplant outcomes, the impact of HLA disparity in haploidentical HSCT (haplo-HSCT) remains unclear. We investigated the impact of HLA disparity quantified by mismatched eplets (ME) load of each HLA locus on the clinical outcome of 278 consecutive haploidentical transplants. Here, we demonstrated that the degree of HLA molecular mismatches, at individual HLA loci, may be relevant to clinical outcome in the haplo-HSCT. A significantly better overall survival was associated with higher ME load from HLA-A (hazard ratio [HR], 0.97; 95% confidence interval [CI], 0.95-0.99; P = .003) and class I loci (HR, 0.99; 95% CI, 0.97-0.99; P = .045) in the host-versus-graft direction. The apparent survival advantage of HLA-A ME was primarily attributed to reduced risk in relapse associated with an increase in HLA-A ME load (subdistribution HR, 0.95; 95% CI, 0.92-0.98; P = .004). Furthermore, we have identified an association between the risk of grade 3-4 acute graft-versus-host disease (GVHD) and a higher ME load at HLA-B and class I loci in graft-versus-host (GVH) direction. Additionally, GVH nonpermissive HLA-DPB1 mismatch defined by T-cell epitope grouping was significantly associated with relapse protection (subdistribution HR, 0.19; 95% CI, 0.06-0.59; P = .004) without a concurrent increase in GVHD. These findings indicate that alloreactivity generated by HLA disparity at certain HLA loci is associated with transplant outcomes, and ME analysis of individual HLA loci might assist donor selection and risk stratification in haplo-HSCT.

Fluid overload (FO) grade ≥2 (more than 10% weight gain from baseline) has recently been recognized as an important toxicity associated with a high rate of nonrelapse mortality in recipients of allogeneic hematopoietic cell transplantation (AHCT). The causes for FO remain unclear. We hypothesized that endothelial damage, possibly due to treatments received prior to AHCT, may be associated with this toxicity and sought to determine whether the Endothelial Activation and Stress Index (EASIX) (defined as lactate dehydrogenase [U/L] × creatinine [mg/dL]/platelets [109 cells/L]) correlates with grade ≥2 FO in 2 cohorts of recipients of AHCT at our institution. We tested our hypothesis in a cohort of 145 consecutive recipients (study cohort) of AHCT transplant from HLA-haploidentical donors and validated the findings in a cohort of 449 (validation cohort) recipients of AHCT from HLA-matched donors who underwent transplantation between 2010 and 2015. Predictors of grade ≥2 FO were evaluated using competing risks regression in univariate analysis and classification and regression tree (CART) analysis in multivariate analysis. The cumulative incidence of grade ≥2 FO was estimated considering death as a competing risk. EASIX scores were evaluated based on log2-transformed values. Optimal predictive EASIX cutoff values were determined based on receiver operating characteristics curve analysis. Grade ≥2 FO occurred in 21% and 6% of the study and validation cohorts, respectively, with the majority of these cases being diagnosed before the day of AHCT. Median log2 EASIX score at admission was 2.4 (interquartile range [IQR], 1.3, 3.7) and 2.5 (IQR, 1.4, 3.9) in the 2 respective cohorts. In univariate analysis, high EASIX at admission was a significant predictor of grade ≥2 FO in the study (cutoff: 4.4, hazard ratio [HR] = 4.8, P 60 years (HR = 9.6, P = .04) in the validation cohort. At admission, the prevalence of EASIX score of >4.3 (18% versus 17%, P = .9) was not different between the diabetics and nondiabetics. EASIX score at admission is a significant predictor of grade ≥2 FO in recipients of AHCT from HLA-haploidentical or HLA-matched donors. Independently of EASIX, older patients with low weight were associated with increased risk of grade ≥2 FO for recipients of HLA-haploidentical transplants. For the HLA-matched cohort, diabetes and older age were associated with increased FO risk. These findings require validation in external cohorts.

The optimal conditioning regimen for older patients with acute myeloid leukemia (AML) remains unclear. In this study, we compared outcomes of AML patients >60 years of age undergoing allogenic hematopoietic stem cell transplantation at our institution. All 404 consecutively treated patients received 1 of the following conditioning regimens: (1) fludarabine+melphalan 100 mg/m2 (FM100), (2) fludarabine+melphalan 140 mg/m2 (FM140), (3) fludarabine+IV busulfan AUC ≥ 5000/d × 4 d (Bu≥20000), and (4) fludarabine+IV busulfan AUC 4000/d × 4 d (Bu16000). A propensity score analysis (PSA) was used to compare outcomes between these 4 groups. Among the 4 conditioning regimens, the FM100 group had a significantly better long-term survival with 5-year progression-free survival of 49% vs 30%, 34%, and 23%, respectively. The benefit of the FM100 regimen resulted primarily from the lower nonrelapse mortality associated with this regimen, an effect more pronounced in patients with lower performance status. The PSA confirmed that FM100 was associated with better posttransplantation survival, whereas no significant differences were seen between the other regimen groups. In summary, older patients with AML benefited from a reduced-intensity conditioning regimen with lower melphalan doses (FM100), which was associated with better survival, even though it was primarily used in patients who could not receive a more intense conditioning regimen.

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic cell transplantation (allo-HCT). We conducted a retrospective study to determine the clinical and economic burden of pre-emptive therapy (PET) for CMV infection in 100 consecutive hospitalized adult CMV positive serostatus allo-HCT recipients and compared their hospitalization cost with allo-HCT recipients hospitalized with graft vs host disease without CMV infection (control group) and across 19 US cancer centers for hospitalized patients with CMV infection between 2012 and 2015 (Vizient database). A total of 192 CMV episodes of PET for CMV infection occurred within 1 year post-HCT. PET consisted of ganciclovir (41% of episodes), foscarnet (40%), and valganciclovir (38%) with the longest average length of stay in foscarnet-treated patients (41 days). The average direct cost per patient admitted for PET was $116 976 (range: $7866-$641 841) compared with $12 496 (range: $2004-$43 069) in the control group (P < .0001). The total direct cost per encounter was significantly higher in patients treated with foscarnet and had nephrotoxicity ($284 006) compared with those who did not ($112 195). The average cost amongst the 19 US cancer centers, including our institution, was $42 327 with major disparities in cost and clinical outcomes. PET for CMV infection is associated with high economic burden in allo-HCT recipients.

Although bortezomib and rituximab have synergistic activity in patients with lymphoma, and can both attenuate graft-versus-host disease (GVHD), the drugs have not been used together in patients undergoing allogeneic stem-cell transplantation (alloSCT). In this phase 1/2 trial, we assessed the safety and activity of bortezomib added to the rituximab (R) plus BEAM (carmustine, etoposide, cytarabine, melphalan) regimen in patients with relapsed lymphoma undergoing alloSCT. Primary GVHD prophylaxis consisted of tacrolimus and methotrexate. Bortezomib (1 – 1.3 mg/m(2) per dose) was administered intravenously on days −13, −6, −1, and +2. We performed inverse probability weighting analysis to compare GVHD and survival results to a historical control group that received R-BEAM without bortezomib. Thirty-nine patients were assessable for toxic effects and response. The median age was 54 years. The most common diagnosis was diffuse large B-cell lymphoma (41%). Twenty-two patients (56%) and 17 patients (44%) received their transplants from matched related and unrelated matched donors, respectively. The maximum tolerated bortezomib dose was 1 mg/m(2). The weighted cumulative incidences of grade II-IV and grade III or IV acute GVHD were 50% and 34%, respectively; these incidences and survival rates were not significantly different from those of the control group. Median survival has not been reached in patients age ≤50 years and who had a long follow-up time of 60.7 months. The R-BEAM regimen has a survival benefit in lymphoma patients age ≤50 years undergoing alloSCT. The addition of bortezomib has no impact on survival or incidence of GVHD.

Haplo-identical transplant with posttransplant cyclophosphamide (haplo) and umbilical cord blood transplant supported by third-party CD34 cells (haplo-cord) are competing approaches to alternative donor transplant. We compared, in adults younger than age 60 years, the outcomes of 170 haplo at 1 institution with that of 137 haplo-cord at 2 other institutions. All received reduced intensity conditioning with fludarabine and melphalan ± total body irradiation. GVHD prophylaxis for haplo consisted of cyclophosphamide, tacrolimus, and mycophenolate, whereas haplo-cord received antithymocyte globulin, tacrolimus, and mycophenolate. Haplo transplant used mostly bone marrow, and peripheral blood stem cells were used in haplo-cord transplants. Haplo-cord were older and had more advanced disease. Haplo-cord hastened median time to neutrophil (11 vs 18 days, P = .001) and platelet recovery (22 vs 25 days, P = .03). At 4 years, overall survival (OS) was 50% for haplo-cord vs 49% for haplo. Progression-free survival (PFS) was 40% for haplo-cord vs 45% for haplo. In multivariate analysis, the disease risk index was significant for OS (hazard ratio, 1.8; 95% confidence interval, 1.48-2.17; P = .00) and PFS. Total body irradiation was associated with decreased recurrence and improved PFS, age >40 with increased nonrelapse mortality. The type of transplant had no effect on OS, PFS, relapse, or nonrelapse mortality. Cumulative incidence of grade 2-4 acute graft-versus-host disease (GVHD) by day 100 was 16% after haplo-cord vs 33% after haplo (P < .0001), but grade 3-4 GVHD was similar. Chronic GVHD at 1 year was 4% after haplo-cord vs 16% after haplo (P < .0001). Haplo or haplo-cord results in similar and encouraging outcomes. Haplo-cord is associated with more rapid neutrophil and platelet recovery and lower acute and chronic GVHD. Institutional review board authorization for this retrospective study was obtained at each institution. Some patients participated in trials registered at www.clinicaltrials.gov as #NCT01810588 and NCT 01050946.

HLA-DPB1 mismatches between donor and recipient are commonly seen in allogeneic hematopoietic stem cell transplantation from an unrelated donor. HLA-DPB1 mismatch, conventionally determined by the similarity of the T-cell epitope (TCE), is associated with an increased risk of acute graft-versus-host disease (GVHD) and a decreased risk of disease relapse. We investigated the clinical impact of HLA-DPB1 molecular mismatch quantified by mismatched eplets (ME) and the Predicted Indirectly Recognizable HLA Epitopes Score (PS) in a cohort of 1,514 patients receiving hematopoietic stem cell transplants from unrelated donors matched at HLA-A, -B, -C, -DRB1/3/4/5, and - DQB1 loci. HLA-DPB1 alloimmunity in the graft-versus-host direction, determined by high graft-versus-host ME/PS, was associated with a reduced risk of relapse (hazard ratio [HR]=0.83, P=0.05 for ME) and increased risk of grade 2-4 acute GVHD (HR=1.44, P

The cell of origin (COO) classification into germinal center B cell (GCB) and non-GCB types has been shown to predict survival outcomes in newly diagnosed diffuse large B cell lymphoma (DLBCL). In the relapsed/refractory (R/R) setting, there is building evidence that COO does not predict prognosis after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT). The present analysis aimed to compare survival outcomes based on COO classification in R/R DLBCL patients who underwent auto-SCT. This retrospective study included adult patients with R/R DLBCL who underwent auto-SCT at MD Anderson Cancer Center between January 2007 and December 2016. The Hans algorithm using CD10, BCL6, and MUM1 markers was used to classify patients by COO. A total of 122 patients with DLBCL (71 GCB, 51 non-GCB) were included in the analysis. There were no significant differences in patient characteristics between the 2 groups, except for older median age in the GCB cohort (64 years versus 58 years; P.004). The median overall survival (OS) time was 68.5 (95% confidence interval [CI], 51.3 to not reached) months for the total population, 68.5 (95% CI, 44.8 to not reached) for GCB, and not reached for non-GCB. The 3-year OS rate was 0.659 (95% CI, 0.575 to 0.755) for the total population, 0.653 (95% CI, 0.547 to 0.779) for GCB, and 0.666 (95% CI, 0.537 to 0.824) for non-GCB. When adjusted for age and other factors of interest, no statistically significant associations for OS or progression-free survival were observed between the 2 cohorts. Our results confirm that COO loses its prognostic potential in patients with R/R DLBCL who receive high-dose chemotherapy followed by auto-SCT and both GCB and non-GCB types of DLBCL derive similar benefit from auto-SCT. Younger age, female sex, and pretransplantation disease status were associated with better OS.

Steroid-refractory (SR) lower gastrointestinal (LGI) acute graft-versus-host disease (aGVHD) has poor prognosis, and novel drugs are needed. We describe outcomes of patients with SR-LGI aGVHD treated with vedolizumab. The primary objective was to determine overall response rate (ORR) at days 14, 28, and 56. Secondary outcomes included overall survival (OS), non-relapse mortality and toxicities. Twenty patients, median age 46 years (range, 23-71), were included. All but 2 patients (90%) had grade 3 to 4 aGVHD (45% stage 4, 40% stage 3 LGI). Median time to vedolizumab was 21 days (range, 5-1031) and 13 days (range, 0-533) after diagnosis of LGI aGVHD and SR-LGI aGVHD, respectively. It was given as ≥3rd line (median 3; range 2-6) in 75% after failure of steroids, and additional treatments including ruxolitinib (n = 12) and others. Median follow-up was 17 months (range, 10-34). The days 14, 28 and 56 ORRs were 45% (9/20; complete response [CR] 25%), 35% (7/20; CR 20%), and 25% (5/20; CR 20%), respectively. Among ruxolitinib failures, it was 50% (6/12; CR 25%), 50% (6/12; CR 25%) and 25% (3/12; CR 16.7%), respectively. Fifteen patients died (14 GVHD, 1 leukemia relapse). The actuarial 6-month OS was 35% (95% confidence interval 16-55). No progressive multifocal leukoencephalopathy or infusion reaction occurred. Forty-four infection events (22 viral, 18 bacterial, and 4 fungal) were noted in 16 patients. Vedolizumab was well tolerated and demonstrated potential efficacy even after ruxolitinib failure for SR-LGI aGVHD. Yet the responses were suboptimal, and its use requires further investigation.

The long-term impact of Autologous hematopietic stem cell transplantation (ASCT) on renal function, and the impact of renal function on progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma are not known. We retrospectively reviewed the records of 885 patients at our institution. We used linear mixed effect models to study the change in estimated glomerular filtration rate (eGFR) and a joint model approach to assess associations between the eGFR, PFS and OS. Sensitivity analyses were conducted at days 0, 100, 180, and 365 post-SCT. eGFR post-ASCT was significantly lower than at day 0 but stabilized at approximately 80mL/min/1.73m(2). There was no association between eGFR and PFS or OS.; However, relapsed disease and ISS stage were associated with shorter PFS and OS. This data suggests that although there is a modest decline in eGFR post-ASCT, it is not associated with an adverse impact on PFS or OS

BACKGROUND BK polymavirus (BKPyV), a member of the family Polyomaviridae, is associated with increased morbidity and mortality in allogeneic stem cell transplant recipients. METHODS In our previous retrospective study of 2477 stem cell transplant patients, BKPyV replication independently predicted chronic kidney disease and poor survival. In this study, using the same cohort, we derived and validated a risk grading system to identify patients at risk of BKPyV replication after transplantation in a user-friendly modality. We used 3 baseline variables (conditioning regimen, HLA match status, and underlying cancer diagnosis) that significantly predicted BKPyV replication in our initial study in a subdistribution hazard model with death as a competing risk. We also developed a nomogram of the hazard model as a visual aid. The AUC of the ROC of the risk-score-only model was 0.65. We further stratified the patients on the basis of risk score into low-, moderate-, and high-risk groups. RESULTS The total risk score was significantly associated with BKPyV replication (P

BACKGROUND: Optimal conditioning regimen for older patients with myelofibrosis undergoing allogeneic hematopoietic cell transplantation (HCT) is not known. Likewise, role of dose intensity is not clear. METHODS: We conducted a non-randomized prospective phase II trial using low-dose, later escalated to high-dose (MAC) busulfan with fludarabine (Bu-Flu) in myelofibrosis patients up to 74 years. First 15 patients received intravenous busulfan 130 mg/m(2)/day on days −3 and −2 (“low dose”); 31 received high dose – either 100 mg/m(2)/day (days −5 to −2; n=4) or pharmacokinetic-guided area under the curve of 4,000 μmol.min (days −5 to −2; n=27). Primary endpoint was day 100 non-relapse mortality (NRM). FINDINGS: Median age was 58 years (interquartile range (IQR) 53–63). Dynamic international prognostic scoring system (DIPSS)-plus was intermediate (n=28) or high (n=18). Donors were related (n=19) or unrelated (n=27). Cumulative incidence of NRM was 9.7% (95% confidence interval (CI) 0-20.3) at day 100 and at 3 years in the high dose, while it was 0% in the low dose group at day 100, and increased to 20% (95% CI 0-41.9) at 3 years. With a median follow up of 5.1 years (IQR 3.8–6), 3-year relapse was 32.3% (95% CI 15.4-49.1) in high dose versus 53.3% (95% CI 26.6-80.1) in low dose; event-free survival was 58% (95% CI 43-78%) versus 27% (95% CI 12-62%), and overall survival was 74% (95% CI 60-91%) versus 60% (95% CI 40-91%) respectively. In multivariate analysis, high dose busulfan had a trend towards lower relapse (Hazard ratio (HR) 0.44, 95% CI, 0.18-1.07, p=0.07), with no impact on NRM. INTERPRETATION: Intensifying Bu-Flu regimen using pharmacokinetic-monitoring appears promising in reducing relapse without increasing non-relapse mortality. FUNDING: The study was supported partly by Otsuka pharmaceutical and partly by the Cancer Center Support Grant (NCI Grant P30 CA016672). TRIAL REGISTRATION: ClinicalTrials NCT00475020

With the availability of immunomodulatory imide drugs (IMiDs) and proteasome inhibitors (PI), most patients with immunoglobulin light chain amyloidosis (AL) receive induction therapy before autologous hematopoietic stem cell transplantation (auto-HCT). In this study we evaluated the type of induction therapy and its impact on the outcome of auto-HCT in AL. We identified 128 patients with AL who underwent high-dose chemotherapy and auto-HCT at our institution between 1997 and 2013. Patients were divided into 3 groups: no induction, conventional chemotherapy (CC)-based induction (melphalan, steroids), and IMiD/PI-based induction (thalidomide, lenalidomide, or bortezomib). The hematologic response (HR) and organ response were defined according to the established criteria. Median age at auto-HCT was 58 years (range, 35 to 75). Twenty patients (15.5%) received no induction, 25 (19.5%) received CC, and 83 (65%) received IMiDs/PIs. One, 2, or 3 or more organs were involved in 90 (70%), 20 (16%), and 18 (14%) patients, respectively. After auto-HCT 12 of 20 (60%), 15 of 24 (62%), and 72 of 83 (87%) assessable patients achieved HR at 100 days in no induction, CC, and IMiD/PI groups, respectively (P = .001). Organ response at 1 year after auto-HCT was seen in 7 of 18 (39%), 14 of 24 (58%), and 37 of 79 (47%) assessable patients in no induction, CC, and IMiD/PI groups, respectively (P = .3). Achieving a hematologic complete response was associated with a significantly higher probability of achieving an organ response (P = .02). After a median follow-up of 26 months, rates of 2-year progression-free survival were 67%, 56%, and 73% in no induction, CC, and IMiD/PI groups, respectively (P = .07; hazard ratio, .5; 95% confidence interval [CI], .3 to 1.1). Rates of 2-year overall survival were 73%, 76%, and 87% in no induction, CC, and IMiD/PI groups, respectively (P = .05; hazard ratio, .4; 95% CI, .2 to .9). On multivariate analysis a low β2-microglobulin (P = .01; hazard ratio, .3; 95% CI, .1 to .7) and induction therapy with IMiD/PI (P = .01; hazard ratio, .3; 95% CI, .1 to .7) were associated with a better overall survival. Induction therapy with either CC or IMiDs/PIs is safe and feasible in selected patients with AL. IMiD/PI-based induction is associated with a longer overall survival compared with patients who received no induction or CC before auto-HCT.

Allogeneic SCT for older patients remains challenging at least in part due to graft-versus-host disease (GVHD) and higher treatment-related mortality (TRM). We conducted a prospective pilot study primarily for older patients undergoing matched unrelated donor (MUD) SCT using a reduced-intensity (RIC) melphalan-based conditioning and post-transplant cyclophosphamide (PTCy)-based GVHD prophylaxis with tacrolimus and mycophenolate mofetil. Twenty-two patients (median age 64) underwent RIC MUD SCT for high-risk hematological malignancies including AML/MDS (73%), CML/MPD (18%), and other (10%). Two (9%) patients had early death; the rest (100%) engrafted. After a median follow-up of 17 months, 11 patients were alive and disease-free with an estimated 2-year progression-free (PFS) and overall (OS) survival of 48%. The cumulative incidences of grades 2-4 and 3-4 acute GVHD (aGVHD) at day +100 and 2-years post-SCT were 32% and 4%, and 59% and 24%, respectively. No cases of chronic GVHD (cGVHD) were noted. However, late acute GVHD was observed in 6 (27%) patients. In conclusion, RIC MUD SCT with melphalan-based conditioning and PTCy-based GVHD-based prophylaxis for older patients appears effective in controlling relapse. While cGVHD was not seen and early aGVHD appears controllable, a significant proportion developed late aGVHD responsible for higher TRM seen in these patients.

Outcomes after allogeneic stem-cell transplantation (AHSCT) are influenced by both disease- and patient-related factors. Here, we developed a novel prognostic model, hematopoietic cell transplant-composite risk (HCT-CR), by combining the refined disease risk index (DRI-R) and hematopoietic stem-cell transplant comorbidity/age index (HCT-CI/Age) to predict post-transplant survival for patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The analysis included 942 AML/MDS patients treated with AHSCT. Patients were stratified into 4 HCT-CR risk groups: Low-risk—patients with low/intermediate DRI-R and HCT-CI/Age ≤3 (N = 272); Intermediate-risk—patients with low/intermediate DRI-R and HCT-CI/Age >3 (N = 168); High-risk—patients with high/very high DRI-R and HCT-CI/Age ≤3 (N = 284); and Very high-risk—patients with high/very high DRI-R and HCT-CI/Age >3 (N = 184). Compared with the low-risk group, intermediate, high, and very high-risk groups had a significantly increased risk of death [adjusted HR of 1.37 (P

Introduction An HLA-matched unrelated donor (MUD) has been accepted as the next best option for patients who do not have a matched-related donor (MRD) available. However, identification of a MUD may be challenging due to donor availability for some populations. In addition, the MUD search and procurement of stem cell product usually takes much longer than that of a related donor, many patients may develop progressive disease or become medically unfit while waiting for a MUD transplant, which might have a negative impact on overall survival. Therefore, in this study we hypothesized that certain groups of patients may not benefit from performing a MUD search and sought to evaluate availability of a MUD donor, ability to proceed to transplant with a MUD, as well as transplant outcomes for all patients who had a MUD search started at our institution. Methods All consecutive patients with a diagnosis of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) who had a MUD search performed between 2013 and 2015 were included. All patients had high resolution HLA typing at HLA-A, -B, -C, -DRB1 and -DQB1 performed by DNA sequencing and had unrelated donor search by the NMDP. According to standard operating procedures, a MUD search was initiated when no MRD was available, or as soon as HLA typing was completed. If no 10/10 MUD was available, the choice between a 9/10 MUD, haploidentical or umbilical cord blood (UCB) was based on the treating physician's decision. Results The analysis included 242 patients with a median age of 58 years (range 9-80 years), 123 patients (51%) were male, 182 patients (75%) were Caucasian and 190 (79%) had common haplotypes. One hundred thirteen patients (47%), 35 (14%), 43 (18%) and 49 (20%) were in complete remission, primary induction failure (PIF), relapse/refractory and newly diagnosed, respectively. One hundred sixty (66%) patients had a 10/10 MUD identified. The majority of Caucasians (85%) had common haplotypes compared with only 58% of patients with other races (P Only 85 of 160 (53%) patients proceeded to MUD transplantation, while 66 (27%) patients received transplants from other donor types [9 (4%) 9/10 MUD, 20 (8%) haploidentical, 22 (9%) UCB and 15 (6%) MRD transplant], and 91 (38%) patients did not receive a transplant. The median time from MUD search to 10/10 MUD, MRD, haploidentical, 9/10 MUD and UCB transplant was 2.9, 2.3, 3.5, 4.6 3.2 months, respectively (P=0.002). Taken together, Caucasian race and having common haplotype were independently associated with 10/10 MUD identification with odds ratio (OR) of 6.8 (95%CI 3.1-14.9) and 39 (95%CI 13.9-110.4), respectively and with proceeding to MUD transplantation (OR 7.7, 95%CI 2.7-21.7 and OR 66, 95%CI 3.9->999), respectively. A multivariable analysis (MVA) for PFS of patients who received a transplant showed significant impact on transplant outcomes for disease status, cytogenetics and time from a MUD search to transplant, while donor type did not impact transplant PFS (Table 1). A second MVA for PFS was performed for all patients who had a MUD search. Patients who had intermediate/favorable cytogenetics, de novo AML, newly diagnosed/complete remission and received a transplant experienced significantly better PFS compared with their counterparts (Table 1, Figure 1). The highest percentages of 10/10 MUD identification, MUD transplant and PFS were observed for Caucasians who were newly diagnosed/complete remission with common haplotype (60% MUD identified, 69% MUD transplant, 3-year PFS rate of 46%), whereas the patient group with the lowest percentages was non-Caucasians with primary induction failure/relapsed/refractory and had uncommon haplotype (1% MUD identified, 0% MUD transplant, 3-year PFS rate of 0%). Conclusions Race, haplotype frequency and disease status at the time of MUD search influence probability to identify a MUD and receive a transplant. Patients with low likelihood to receive a MUD transplant may proceed to a haploidentical transplant as soon as indicated, as this approach does not appear to compromise transplant outcomes. Disclosures Konopleva: Stemline Therapeutics: Research Funding. Oran:AROG pharmaceuticals: Research Funding; Celgene: Consultancy, Research Funding; ASTEX: Research Funding. Champlin:Otsuka: Research Funding; Sanofi: Research Funding.

Purpose: Allogeneic hematopoietic stem cell transplantation (AHCT) outcomes depend on disease and patient characteristics. We previously developed a novel prognostic model, hematopoietic cell transplant composite-risk (HCT-CR) by incorporating the refined disease risk index (DRI-R) and hematopoietic cell transplant–comorbidity/age index (HCT-CI/Age) to predict post-transplant survival in patients with acute myeloid leukemia and myelodysplastic syndrome. Here we aimed to validate and prove the generalizability of the HCT-CR model in an independent cohort of patients with hematologic malignancies receiving AHCT. Experimental Design: Data of consecutive adult patients receiving AHCT for various hematologic malignancies were analyzed. Patients were stratified into four HCT-CR risk groups. The discrimination, calibration performance, and clinical net benefit of the HCT-CR model were tested. Results: The HCT-CR model stratified patients into four risk groups with significantly different overall survival (OS). Three-year OS was 67.4%, 50%, 37.5%, and 29.9% for low, intermediate, high, and very high-risk group, respectively (P < 0.001). The HCT-CR model had better discrimination on OS prediction when compared with the DRI-R and HCT-CI/Age (C-index was 0.69 vs. 0.59 and 0.56, respectively, P < 0.001). The decision curve analysis showed that HCT-CR model provided better clinical utility for patient selection for post-transplant clinical trial than the “treat all” or “treat none” strategy and the use of the DRI-R and HCT-CI/Age model separately. Conclusions: The HCT-CR can be effectively used to predict post-transplant survival in patients with various hematologic malignancies. This composite model can identify patients who will benefit the most from transplantation and helps physicians in making decisions regarding post-transplant therapy to improve outcomes.

We studied if the inclusion of early post–stem cell transplantation (SCT) minimal residual disease (MRD) assessments improved prognostication in patients with acute myeloid leukemia (AML). Two hundred sixty-nine AML patients in morphological complete remission (CR) who underwent a first SCT were included if they had evaluable pre-SCT MRD assessment by multiparametric flow cytometry. Post-SCT MRD assessments were performed at days +30, +100, and +180. The primary outcome was 1-year relapse incidence (RI). Of 269 patients in CR, 83 (30.8%) had detectable MRD pre-SCT. Post-SCT, during routine disease assessment time points, 9 of 241 evaluable patients (3.7%) at day +30, 6 of 191 evaluable patients (3.1%) at day +100, and 4 of 133 evaluable patients (3%) at day +180 were MRD positive while in CR. MRD positivity at day +30 predicted the highest risk of relapse at 1 year (group 1, 1-year RI 78%). Among MRD-negative patients at day +30, either adverse risk category by European Leukemia Net (ELN) or intermediate risk who were aged ≥60 years and/or pre-SCT MRD-positive represented the intermediate-risk group (group 2, 1-year RI 29%). The remaining patients represented the low-risk group (group 3, 1-year RI 5%). For patients in CR beyond day +30 post-SCT, detectable MRD at any time point predicted impending relapse within 2 months. Early post-SCT MRD assessment—combined with pre-SCT MRD assessment, ELN risk category, and age—improves risk stratification for relapse in AML patients post-transplant. Studies aimed at preventing impending relapse in this high-risk population are urgently needed.

TO THE EDITOR: Allogeneic hematopoietic stem-cell transplantation (ASCT) is curative treatment for patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), who otherwise have dismal outcomes.[1][1][⇓][2][⇓][3]-[4][4] The TP53 gene is located in the 17p13

In this study, we compared transplantation outcomes of allogeneic hematopoietic stem cell transplantation (HSCT) in patients with advanced myelodysplastic syndrome (MDS) who received a CD34+ cell-selected and those who received an unmodified allograft. This analysis initially included 181 patients, 60 who received a CD34+ cell-selected transplant and 121 who received an unmodified transplant. Owing to significant differences in disease characteristics, the analysis was limited to patients with

Cytomegalovirus (CMV) infection can increase the morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Because of a higher degree of immunosuppression, haploidentical transplant recipients may be at an increased risk of viral infections, particularly CMV. We retrospectively analyzed 86 haploidentical HCT recipients at our institution to determine whether a more intensified antiviral strategy would reduce the incidence of CMV reactivation compared with a traditional antiviral prophylaxis regimen. According to practice changes over time in antiviral prophylaxis at our institution, patients were divided into the following 3 groups: hybrid (n = 15), traditional (n = 26), and intermediate dose (n = 45). The hybrid group received valganciclovir from admission to day −2 followed by standard-dose valacyclovir. The traditional group received standard-dose valacyclovir starting on day −1. The intermediate-dose group received ganciclovir from admission through day −2, followed by intermediate-dose valacyclovir. The hybrid and intermediate-dose groups were combined into an intensified group for further analysis. We found the cumulative incidence (CI) of CMV reactivation within 100 days post-HCT was higher for patients receiving the traditional strategy compared with the hybrid and intermediate-dose strategy groups (81% versus 53% versus 71%, respectively; P = .08) and was significantly higher when the traditional group was compared against the intensified group (81% versus 67%, respectively; P = .032). Median time to CMV reactivation was also shorter in the traditional group versus the intensified group (31 versus 41 days, respectively). Moreover, the CI of CMV disease by day 100 was significantly worse for patients receiving the traditional prophylaxis strategy among the 3 groups (8% traditional versus 0% hybrid versus 0% intermediate dose; P = .032). Renal toxicity did not differ between the traditional and intensified group. In conclusion, an intensified approach to prevention of CMV reactivation was associated with lower incidence of CMV reactivation and less CMV disease without increased toxicity. Because the most benefit was observed in the intensified group, further studies are needed to assess which antiviral intervention is the most beneficial on lowering the rates of CMV viremia and disease.

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

Introduction: In patients undergoing allogeneic hematopoietic cell transplantation (HCT), venous thromboembolism (VTE) remains a serious complication that lacks validated risk assessment models to guide optimal timing and implementation of thromboprophylaxis. We recently derived the HIGH-2-LOW score that incorporated 7 simple clinical predictors assessed at day 30 post-transplant (Table 1, PMID 33570631). In this present study, we performed validation in two independent datasets. Methods: We selected consecutive patients undergoing first allogeneic HCT from Fred Hutchinson Cancer Research Center (FHCRC, 2015-2019) and MD Anderson Cancer Center (MDACC, 2016-2020). Patients who died, received therapeutic anticoagulation, or did not engraft platelets at day 30 were excluded (Table 2). Day 30 was chosen as the index date because most patients would be transfusion-dependent before that time. We used a combination of ICD9/10 codes and natural language processing (NLP) algorithms to identify possible cases of VTE, followed by confirmation via individual chart review. VTE was defined as radiology-confirmed pulmonary embolism (PE), lower-extremity deep venous thromboembolism (LE-DVT), or catheter-related DVT (CR-DVT). Covariates were captured and weighted according to the original model, except that grade 2-4 was used instead of grade 3-4 GVHD. Discrimination was assessed in each cohort by fitting logistic regression models with VTE and PE/LE-DVT outcomes at 100 days to estimate the c statistic, where a higher c statistic is desirable. Both continuous scores and categorical models were assessed. Kaplan Meier failure curves were plotted to compare the final risk stratification with high- vs. low/intermediate-risk groups. Results: The two cohorts (n=772 in FHCRC, n=1109 in MDACC) had similar characteristics in age, sex, race, weight, disease, and conditioning intensity. Key differences between the two cohorts included a higher number of umbilical cord transplants at FHCRC (vs. haploidentical at MDACC), higher numbers of acute GVHD at FHCRC (due to differences in grading criteria), fewer historical CR-DVT at FHCRC (4.0% vs. 6.8%), and more anticoagulation treatment at day 30 at FHCRC (9.0% vs. 3.5% - excluded). Incident VTE was 2.5% by 100 days and 7.8% by 365 days at FHCRC; incident VTE was 5.4% by 100 days and 9.4% by 365 days at MDACC (Table 2). Incident PE or LE-DVTs were similar in the two cohorts. When treated as a continuous score, every 1-point increase in the HIGH-2-LOW score was associated with odds ratio (OR) of 1.55 for VTE (1.06-2.27, c=0.64) and 2.50 (1.40-4.44, c=0.84) for PE/LE-DVT in the FHCRC cohort. The same increase was associated with OR of 1.93 (1.55-2.39, c=0.64) for VTE and 2.46 (1.61-3.76, c=0.79) for PE/LE-DVT in the MDACC cohort (Table 3). A total of 24% and 19% of patients were classified as high-risk (2+ points), respectively. High vs. low/intermediate-risk was associated with OR of 2.99 (1.20-7.49, c=0.62) for VTE and 19.93 (2.38-166.67, c=0.81) for PE/LE-DVT in the internal validation cohort. High vs. low/intermediate-risk was associated with OR of 4.58 (2.69-7.79, c=0.66) for VTE and 12.05 (3.17-45.81, c=0.77) for PE-LE-DVT in the external validation cohort. The VTE risk stratification separated early and persisted beyond 100 days (Figure 1). Conclusion: Despite differences in HCT and patient characteristics, the HIGH-2-LOW score identified ~20% of allogeneic HCT recipients at high-risk for VTE, particularly that of PE or LE-DVT, in both independent validation cohorts. The lower-than-expected absolute VTE incidence in the FHCRC cohort was likely driven by the increasing use of anticoagulation immediately post-transplant (exclusion criteria); however, the model retained similar OR with modest discrimination in both cohorts. In patients with prior history of PE/LE-DVT off anticoagulation, or those with prolonged admission and at least 1 additional risk factors from the HIGH-2-LOW score (2+ points), VTE prophylaxis should be considered upon platelet engraftment. Figure 1 Figure 1. Disclosures Lee: Kadmon: Research Funding; Syndax: Research Funding; Takeda: Research Funding; Pfizer: Research Funding; Novartis: Other: clinical trials, Research Funding; JANSSEN: Other; Incyte: Research Funding; AstraZeneca: Research Funding; Amgen: Research Funding; National Marrow Donor Program: Membership on an entity's Board of Directors or advisory committees. Shpall: Bayer HealthCare Pharmaceuticals: Honoraria; Novartis: Consultancy; Takeda: Patents & Royalties; Affimed: Patents & Royalties; Magenta: Honoraria; Magenta: Consultancy; Navan: Consultancy; Novartis: Honoraria; Axio: Consultancy; Adaptimmune: Consultancy.

Purpose/Objective(s) Craniospinal irradiation (CSI) improves local control of leukemia/lymphoma with central nervous system (CNS) involvement; however, for adult patients anticipating stem cell transplant (SCT), cumulative treatment toxicity is a major concern. We evaluated toxicities and outcomes for patients receiving proton or photon CSI before SCT. Methods and materials We identified 37 consecutive leukemia/lymphoma patients with CNS involvement who received CSI before SCT at our institution. Photon versus proton toxicities during CSI, transplant, and through 100 days posttransplant were compared using Fisher exact and Wilcoxon rank sum tests. Long-term neurotoxicity, disease response, and overall survival were analyzed. Results Thirty-seven patients (23 photon, 14 proton) underwent CSI for CNS involvement of acute lymphoblastic leukemia (49%), acute myeloblastic leukemia (22%), chronic lymphocytic leukemia (3%), chronic myelocytic leukemia (14%), lymphoma (11%), and myeloma (3%). CSI was used for consolidation (30 patients, 81%) and gross disease treatment (7 patients, 19%). Median radiation dose (interquartile range) was 24 Gy (23.4-24) for photons and 21.8 Gy (21.3-23.6) for protons ( P = .03). Proton CSI was associated with lower rates of Radiation Therapy Oncology Group grade 1-3 mucositis during CSI (7% vs 44%, P = .03): 1 grade 3 with protons versus 5 grade 1, 3 grade 2, and 2 grade 3 with photons. During CSI, other toxicities (infection, gastrointestinal symptoms) did not differ. Allogeneic stem cell transplant (SCT) was used in 95% of patients, with 53% of patients in remission before SCT. Myeloablative conditioning was used for 76%. During SCT admission and 100 days post-SCT, toxicities did not differ by CSI technique. Successful engraftment occurred in 95% of patients ( P = .67). Progression or death occurred for 47% of patients, with only 1 CNS relapse. Conclusion In our cohort, CSI offered excellent local control for CNS-involved hematologic malignancies in the pre-SCT setting. Acute mucositis occurred less frequently with proton CSI with comparable peritransplant/long-term toxicity profile, suggesting the need to further explore the benefit/toxicity profile of this technique.

Relapse has emerged as the most important cause of treatment failure after allogeneic hematopoietic stem cell transplantation (HSCT). To test the hypothesis that natural killer (NK) cells can decrease the risk of leukemia relapse, we initiated a phase 1 dose-escalation study of membrane-bound interleukin 21 (mbIL21) expanded donor NK cells infused before and after haploidentical HSCT for high-risk myeloid malignancies. The goals were to determine the safety, feasibility, and maximum tolerated dose. Patients received a melphalan-based reduced-intensity conditioning regimen and posttransplant cyclophosphamide-based graft-versus-host disease (GVHD) prophylaxis. NK cells were infused on days −2, +7, and +28 posttransplant. All NK expansions achieved the required cell number, and 11 of 13 patients enrolled received all 3 planned NK-cell doses (1 × 105/kg to 1 × 108/kg per dose). No infusional reactions or dose-limiting toxicities occurred. All patients engrafted with donor cells. Seven patients (54%) developed grade 1-2 acute GVHD (aGVHD), none developed grade 3-4 aGVHD or chronic GVHD, and a low incidence of viral complications was observed. One patient died of nonrelapse mortality; 1 patient relapsed. All others were alive and in remission at last follow-up (median, 14.7 months). NK-cell reconstitution was quantitatively, phenotypically, and functionally superior compared with a similar group of patients not receiving NK cells. In conclusion, this trial demonstrated production feasibility and safety of infusing high doses of ex vivo–expanded NK cells after haploidentical HSCT without adverse effects, increased GVHD, or higher mortality, and was associated with significantly improved NK-cell number and function, lower viral infections, and low relapse rate posttransplant.

High dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) are the standard of care for eligible patients with newly diagnosed myeloma [1]. Unfortunately, relapse rate...

BACKGROUND Data on the incidence of adverse liver outcomes are limited for cancer patients with chronic (hepatitis B surface antigen [HBsAg]–positive/hepatitis B core antibody [anti-HBc]–positive) or past (HBsAg-negative/anti-HBc–positive) hepatitis B virus (HBV) after chemotherapy. This study was aimed at determining the impact of test timing and anti-HBV therapy on adverse liver outcomes in these patients. METHODS Patients with solid or hematologic malignancies who received chemotherapy between 2004 and 2011 were retrospectively studied. HBV testing and anti-HBV therapy were defined as early at the initiation of cancer therapy and as late after initiation. Outcomes included hepatitis flares, hepatic impairment, liver failure, and death. Time-to-event analysis was used to determine incidence, and multivariate hazard models were used to determine predictors of outcomes. RESULTS There were 18,688 study patients (80.4% with solid tumors). The prevalence of chronic HBV was 1.1% (52 of 4905), and the prevalence of past HBV was 7.1% (350 of 4905). Among patients with solid tumors, late identification of chronic HBV was associated with a higher risk of hepatitis flare (hazard ratio [HR], 4.02; 95% confidence interval [CI], 1.26-12.86), hepatic impairment (HR, 8.48; 95% CI, 1.86-38.66), liver failure (HR, 9.38; 95% CI, 1.50-58.86), and death (HR, 3.90; 95% CI, 1.19-12.83) in comparison with early identification. Among patients with hematologic malignancies and chronic HBV, the risk of death was 7.8 (95% CI, 1.73-35.27) times higher for persons with late initiation of anti-HBV therapy versus early initiation. Patients with late identification of chronic HBV had late or no anti-HBV therapy. Chronic HBV predicted liver failure in patients with solid or hematologic malignancies, whereas male sex and late identification were predictors for patients with solid tumors. CONCLUSIONS Early identification correlates with early anti-HBV therapy and reduces the risk of liver failure and death in chronic HBV patients receiving chemotherapy. Cancer 2017. © 2017 American Cancer Society.

Donor type, in addition to transplantation in chronic phase and myeloablative conditioning, influence transplant survival for patients with advanced chronic myeloid leukemia in the era of tyrosine kinase inhibitors

In patients with AML with FMS-like tyrosine kinase 3 (FLT3) mutations, the significance of minimal residual disease (MRD) detected by PCR before allogeneic stem cell transplantation (SCT) on outcomes after transplant remains unclear. We identified 200 patients with FLT3-AML who underwent SCT at our institution. Disease status at transplant was: first or second complete remission (CR1/CR2, n=119), high-risk CR (third or subsequent CR, marrow hypoplasia, or incomplete count recovery) (CR-HR, n=31), and morphological evidence of active disease (AD, n=50). The median follow-up was 27 months, and the 2-year overall and progression-free survival were 43% and 41%, respectively. Relapse was highest in the AD group (85%) and the CR-HR FLT3 MRD positive group (72%), followed by CR-HR FLT3 MRD negative (58%), CR1/CR2 FLT3 MRD positive (39%), and lowest in the CR1/CR2 FLT3 MRD negative group (23%). On multivariate analysis, independent factors influencing the risk of relapse were detectable morphological disease and FLT3 MRD by PCR pre-transplant. Factors that did not influence the relapse risk included: age, graft type, graft source, type of FLT3 mutation, or conditioning intensity. Morphologic and molecular remission status at the time of transplant were key predictors of disease relapse and survival in patients with FLT3-AML. This article is protected by copyright. All rights reserved.

Haploidentical transplantation performed with post-transplantation cyclophosphamide (PTCy)–based graft-versus-host disease (GVHD) prophylaxis has been associated with favorable outcomes for patients with acute myeloid leukemia and lymphomas. However, it remains unclear if such approach is effective for patients with acute lymphoblastic leukemia (ALL). We analyzed outcomes of 109 consecutively treated ALL patients 18 years of age and older at 5 institutions. The median age was 32 years and the median follow-up for survivors was 13 months. Thirty-two patients were in first complete remission (CR1), while the rest were beyond CR1. Neutrophil engraftment occurred in 95% of the patients. The cumulative incidences of grades II to IV and III and IV acute GVHD at day 100 after transplantation were 32% and 11%, respectively, whereas chronic GVHD, nonrelapse mortality, relapse rate, and disease-free survival (DFS) at 1 year after transplantation were 32%, 21%, 27%, and 51%, respectively. Patients in CR1 had 52% DFS at 3 years. These results suggest that haploidentical transplants performed with PTCy-based GVHD prophylaxis provide a very suitable alternative to HLA-matched transplantations for patients with ALL.

We investigated the long-term safety and disease control data obtained with i.v. busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (HSCT). A total of 107 patients, median age 38 years (range, 19 to 64 years) received a matched sibling donor (n = 52) or matched unrelated donor (n = 55) transplant for ALL in first complete remission (n = 62), second complete remission (n = 28), or more advanced disease (n = 17). Nearly one-half of the patients had a high-risk cytogenetic profile as defined by the presence of t(9;22) (n = 34), t(4;11) (n = 4), or complex cytogenetics (n = 7). Clo 40 mg/m2 was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic cell infusion after 2 days of rest. The Bu dose was based on the drug clearance as determined by a test Bu dose of 32 mg/m2. The target daily area under the curve was 5500 µmol/min for patients aged 59 years. With a median follow-up of 3.3 years among surviving patients (range, 1 to 5.8 years), the 2-year progression-free survival (PFS) for patients undergoing HSCT in first complete remission (CR1), second complete remission (CR2), or more advanced disease was 62%, 34%, and 35%, respectively. The regimen was well tolerated, with nonrelapse mortality (NRM) of 10% at 100 days and 31% at 2 years post-HSCT. The incidence of grade II-IV and III-IV acute graft-versus-host disease (GVHD) was 35% and 10%, respectively; 18% patients developed extensive chronic GVHD. The 2-year overall survival (OS) for patients undergoing HSCT in CR1, CR2, or more advanced disease was 70%, 57%, and 35%, respectively. Among 11 patients aged >59 years treated with reduced-dose Bu in CR1 (n = 7) or CR2 (n = 4), 4 remain alive and disease-free, with a median follow-up of 2.6 years (range, 2 to 4.7 years). Only the presence of minimal residual disease at the time of transplantation was associated with significantly worse PFS and OS in multivariate analysis. Our data indicate that the Clo-Bu combination provides effective disease control while maintaining a favorable safety profile. OS and NRM rates compare favorably with those for traditional myeloablative total body irradiation-based conditioning regimens.

Background: Lower gastrointestinal (LGI) tract acute GVHD occurs in ~30% of patients after allogeneic hematopoietic cell transplantation (HCT). Failure to respond to first line treatment with corticosteroids (steroid-refractory (SR)-GVHD) has poor prognosis, with an overall response rate (ORR) of less than 50% and complete response (CR) rate Methods Patients ≥ 18 years with SR-LGI GVHD who were treated with vedolizumab between 03/2016 and 10/2019 were included. Other criteria were absence of liver GVHD, Karnofsky performance >30, any donor/graft and any conditioning. SR-GVHD was defined as failure to respond after 7 days of treatment with prednisone 2 mg/kg/day (or methylprednisolone equivalent), progression after 72 hours, or flare with steroid taper. Objectives were to determine LGI aGVHD response at day 14, 28 and 56 from start of vedolizumab, OS and non-relapse mortality at 6 month and toxicities from vedolizumab (any infection within 6 months of the last dose, hepatotoxicity, progressive multifocal leukoencephalopathy (PML) or infusion reactions). Vedolizumab 300 mg IV was given at 0, 2 and 6 weeks, and then every 8 weeks depending upon response. Acute GVHD was staged and graded as per the consensus criteria, and the standard definitions were used to assess response. Results: Median age was 46 years (range, 23-71). Majority (75%, n=15) received peripheral blood graft; 35% (n=7) had myeloablative conditioning. Two patients had prior allogeneic HCT. Donor was MUD (35%), MSD (30%), haplo (10%), cord (20%) or MMUD (5%). GVHD prophylaxis was PTCy/MMF +/-tacro (40%), tacro/MMF +/-ATG (35%) or tacro/methotrexate +/-ATG (25%). All but 2 patients (90%) had grade 3-4 GVHD (45% stage 4, 40% stage 3 LGI GVHD) at the time of vedolizumab. Median time to start of vedolizumab after LGI GVHD diagnosis was 21 days (range, 5-1031), and 13 days (range, 0-533) after diagnosis of SR-LGI GVHD. It was given as >/=3rd line (median 3; range 2-6) in 75% of patients after failure of steroids and additional treatments, that included ruxolitinib (n=12), photopheresis (n=9), sirolimus (n=3), or mesenchymal stromal cells (n=1). Median number of vedolizumab doses given was 2.5 (range 1-5). Median follow-up among survivors was 13.5 months (range, 10.4-33.3). Adverse events: No PML or infusion reactions occurred. Overall, 44 infection events (22 viral, 18 bacterial, and 4 fungal) were noted in 16 patients. Majority were grade 3 (n=24), followed by grade 1-2 (n=14) and grade 4 (n=6) [Table]. Biochemical liver abnormalities were noted in 5 patients; grade 1 (n=2), grade 2 (n=1), grade 3 (n=2) that peaked between 15-53 days after 1st dose of vedolizumab. Response: Day 14, 28 and 56 ORR were 45% (9/20; CR 25%), 35% (7/20; CR 20%) and 25% (5/20; CR 20%), respectively. Of 8 patients with no response (NR)/progression at day 14, 3 (37.5%) responded (1CR, 2PR) by day 28 with no additional therapy. Only 1/9 patients with NR/progression at day 28 responded (CR) by day 56 with no additional therapy. Among patients with prior ruxolitinib, day 14, 28 and 56 ORR were 50% (6/12; CR 25%), 50% (6/12; CR 25%) and 25% (3/12; CR 16.7%), respectively. Overall, 15 patients died (14 GVHD, 1 AML relapse). Actuarial OS was 35% (95% CI 16-55) at 6-month and 30% (95% CI 12-50) at 1 year, with a median OS of 2.2 months from start of vedolizumab [Figure]. Conclusion: Vedolizumab was well tolerated, and has potential efficacy even among those with prior ruxolitinib exposure for SR-LGI GVHD. The ORR noted in our series is suboptimal, which is likely a reflection of highly advanced LGI GVHD, and vedolizumab used as >/=3rd line therapy. Earlier use may lead to better outcomes, as seen with previous study [Floisand; BBMT 2019], and as seen with natalizumab for upfront management of LGI GVHD [Kekre Blood 2017]. Disclosures Mehta: CSL Behring: Research Funding; Kadmon: Research Funding; Incyte: Research Funding. Nieto:Affimed: Consultancy, Other: Grant Support; Astra Zeneca: Other: Grant Support; Novartis: Other: Grant Support; Secura Bio: Other: Grant Support. Oran:Arog Pharmaceuticals: Research Funding; Celgene: Consultancy; ASTEX: Research Funding. Qazilbash:Angiocrine: Research Funding; Bioclinica: Consultancy; Amgen: Research Funding; Bioline: Research Funding; Janssen: Research Funding. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding. Rezvani:Pharmacyclics: Other: Educational grant; Affimed: Other: Educational grant; Takeda: Other: Licensing agreement; Virogen: Membership on an entity's Board of Directors or advisory committees; Formula Pharma: Membership on an entity's Board of Directors or advisory committees; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; GemoAb: Membership on an entity's Board of Directors or advisory committees. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy; Kite: Other: Served on advisory board. Shpall:Takeda: Other: Licensing Agreement; Magenta: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees. Champlin:Genzyme: Speakers Bureau; Omeros: Consultancy; Johnson and Johnson: Consultancy; Cytonus: Consultancy; Takeda: Patents & Royalties; Actinium: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees. Alousi:Incyte: Honoraria, Research Funding; Alexion: Honoraria; Therakos: Research Funding. OffLabel Disclosure: Vedolizumab is FDA-approved for treatment of inflammatory bowel disease, but not for GI GVHD. This abstract summarizes our experience with Vedolizumab in the treatment of steroid-refractory GI GVHD.

Background: Fludarabine and melphalan (FM) reduced intensity conditioning regimen has been widely used for allogeneic stem cell transplantation (allo-SCT) in AML patients not eligible for more ablative regimens. In this study, we looked into a contemporary group of high risk AML patients treated with FM and updated their outcome expectation by donor type. Methods: We included 292 AML patients who had first allo-SCT between January 2010 and December 2019 if their donors were haploidential (haplo, n=142) or matched related sibling (MSD, n=49) or matched unrelated donor (MUD, n=101) and their conditioning regimen was intravenous melphalan given as 100 mg/m2 or 140 mg/m2 in addition to fludarabine. Graft versus host disease (GvHD) prophylaxis was either tacrolimus and methotrexate (n=91) or tacrolimus with post-transplant cyclophosphamide (PTCy) +/- Mycophenolate mofetil (n=201). The primary outcome was relapse-free survival (RFS) defined as time to relapse or death whichever happened first. Secondary outcomes was overall survival (OS). Results: The median age was younger in haplo transplants compared with MDS or MUDs (50 vs. 63)(Table 1). There were more patients in first or second complete remission with count recovery (CR1/2) in haplo group compared with MSD (29%) and MUD (37%) but that did not reach significance (p=0.22). High risk disease risk by European Leukemia Net (ELN), advance group, was also distributed similarly between donor groups (21% in MSD, 32% in MUD and 24% in haplo, p=0.5). Hematopoietic comorbidity index (HCT-CI) >2 was frequent in all donor groups (43% in MSD, 46% MUD and 36% haplo, p=0.4). Hematopoietic stem cell source and GvHD prophylaxis differed by donor as expected; all haplo patients but 15 had bone marrow (BM, 89%) while 2% of MSD and 26% of MUD had BM. GvHD prophylaxis was PTCy in all haplo patients but half of the MUD patients (49%) and some of the MSD also received PTCy (20%). The median follow-up of 143 survivors was 24 months (range, 1 to 102 months). RFS at 2 years was 41.6% (95% confidence interval (CI) 35.5%- 47.6%) and OS was 48.6% (95% CI=42.1%-54.7%). Outcome estimates by donor types are presented in table 2. Considering the haplo patients were younger, we also analyzed RFS for older patients aged >50 and >60 separately (Figure). Causes of death was mostly relapse in all donor types; 54.2% in MSD, 40.4% in MUD and 44.7% in haplo. Cox regression model for RFS revealed that CR1/2 or CR without count recovery (CRi/p) were favorable prognostic variables compared with advanced disease (hazard ratio (HR)=0.35, 95%CI=0.25-0.51, p2 (HR=1.62, 95%CI=1.17-2.23, p=0.003) were poor prognostic markers. Age >50 was not a prognostic factor for RFS. Conclusion: FM remains to be an effective conditioning regimen that is leading to similar RFS after transplant with different donor types. Despite smaller sample size, even older haploidentical patients had RFS that was not significantly different compared with older MSD and MUD patients. However, relapse remains to be the major reason of failure in patients with high risk features including disease status not in CR with count recovery at allo-SCT and/or adverse ELN risk. Innovative strategies either with more ablative regimens or post-transplant maintenance or integration of cellular therapy options are needed to improve outcomes for those AML patients. Disclosures Oran: Celgene: Consultancy; ASTEX: Research Funding; Arog Pharmaceuticals: Research Funding. Ciurea:Kiadis Pharma: Current equity holder in publicly-traded company, Research Funding. Mehta:Incyte: Research Funding; Kadmon: Research Funding; CSL Behring: Research Funding. Alousi:Incyte: Honoraria, Research Funding; Therakos: Research Funding; Alexion: Honoraria. Popat:Bayer: Research Funding; Novartis: Research Funding. Kebriaei:Pfizer: Other: Served on advisory board; Amgen: Other: Research Support; Ziopharm: Other: Research Support; Novartis: Other: Served on advisory board; Jazz: Consultancy; Kite: Other: Served on advisory board. Champlin:Actinium: Consultancy; Cytonus: Consultancy; Omeros: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Takeda: Patents & Royalties; Genzyme: Speakers Bureau; Johnson and Johnson: Consultancy.

Introduction. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are common adverse effects of chimeric antigen receptor (CAR) T-cell therapy. Elevated biomarkers, such as ferritin and LDH, have been shown to correlate with more severe toxicity. The endothelial activation and stress index (EASIX) is a surrogate of endothelial activation, and correlates to other biomarkers of endothelial dysfunction. In allogeneic hematopoietic cell transplantation (HCT), it is predictive of toxicity such as fluid overload, which is correlative with endothelial dysfunction, as well as sinusoidal obstruction syndrome, non relapse mortality and overall survival (Luft et al, BMT 2019, Varma et al, BBMT, 2020, Jiang et al, Haematologica, 2020). In this study we describe the correlation of EASIX to CAR T cell related CRS and ICANS. Methods. Retrospective data from consecutive patients treated with standard of care axi-cel for non-Hodgkin's lymphoma at MD Anderson Cancer Center between January 2018 and April 2020 were included in the study. CRS and ICANS were graded according to CARTOX criteria (Neelapu et al, Nat Rev Clin Oncol, 2018), and after 5/2019, according to the ASTCT criteria (Lee et al, BBMT, 2019). EASIX parameters were recorded prior to lymphodepletion (the latest value on days -12 to -6) and were available for all 171 patients. The score was defined as lactate dehydrogenase (U/L) × creatinine (mg/dL)/ thrombocytes (10^9 cells per L), with LDH adjusted to the upper limit of normal. Predictors of toxicity were evaluated using Fine and Grey regression analysis considering death before grade 2-4 toxicity as a competing risk. Results. 171 consecutive patients treated with commercial axi-cel for diffuse large B cell lymphoma (n=133), transformed follicular lymphoma (n=28) and primary mediastinal lymphoma (n=10) were included in the study. Median age was 59 years (range, 18-85), and 120 (70%) were male. 151 patients had an ECOG performance status ≤1, 45 patients (26%) had a previous autologous HCT, and 3 (1.8%) had a previous allogeneic HCT. Prior to lymphodepletion, 96 (56%) patients had a high IPI score (≥3) and 134 (78%) were refractory to the previous line of treatment. With a median follow-up of 259 days (range: 25-800) since infusion, ICANS of any grade was noted in 109 (64%) patients, with 84 (49%) having grades 2-4. CRS of any grade was observed in 160 (93%) patients, with 81 (47%) having grades 2-4 CRS. A total of 56 (33%) patients were diagnosed with grade 2-4 ICANS and CRS. The median EASIX score for the entire cohort was 2.1 (range: 0.3-283; inter-quartiles: 1.1 and 4.6). On univariate analysis, EASIX levels above the median were associated with higher cumulative incidence (CI) of grade 2-4 ICANS (% CI: 61 vs 31%; HR=2.4, p Multivariate analysis showed EASIX score to be an independent predictor of grade 2-4 ICANS (HR=2.3, p=0.001) or CRS (HR=2.3, p=0.001); female gender of ICANS (HR=1.7, p=0.03) and lack of prior autologous transplant of CRS (HR=1.9, p=0.02). The impact of IPI did not reach statistical significance for either ICANS (HR=1.3, p=0.3) or CRS (HR=1.2, p=0.4). Further multivariate analysis for other biomarkers and their incorporation into a revised biomarker score will be presented at the meeting. Conclusions. Our results suggest that the EASIX score prior to lymphodepletion predicts higher grade CRS and ICANS in patients receiving axi-cel. These results of routinely available clinical variables require further prospective studies for validation, however our study shows that this score may better stratify patient risk of toxicity, and possibly inform clinical decisions and prevention strategies for patients at higher risk. Disclosures Nieto: Secura Bio: Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Affimed: Consultancy, Other: Grant Support. Hosing:NKARTA Inc.: Consultancy. Westin:47: Research Funding; Amgen: Consultancy; Morphosys: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Kite: Consultancy, Research Funding; Curis: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding. Lee:Celgene: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Guidepoint Blogal: Consultancy; Aptitude Health: Speakers Bureau; Oncternal Therapeutics: Research Funding; Seattle Genetics: Research Funding; Takeda: Research Funding. Nastoupil:Celgene: Honoraria, Research Funding; Karus Therapeutics: Research Funding; Bayer: Honoraria; Genentech, Inc.: Honoraria, Research Funding; Gamida Cell: Honoraria; Gilead/KITE: Honoraria; Novartis: Honoraria, Research Funding; Merck: Research Funding; TG Therapeutics: Honoraria, Research Funding; LAM Therapeutics: Research Funding; Janssen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding. Parmar:Cellenkos Inc.: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties, Research Funding. Wang:Guidepoint Global: Consultancy; Dava Oncology: Honoraria; Verastem: Research Funding; Molecular Templates: Research Funding; Celgene: Consultancy, Other: Travel, accommodation, expenses, Research Funding; OMI: Honoraria, Other: Travel, accommodation, expenses; Nobel Insights: Consultancy; Lu Daopei Medical Group: Honoraria; Beijing Medical Award Foundation: Honoraria; Pharmacyclics: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; MoreHealth: Consultancy; AstraZeneca: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: Travel, accommodation, expenses, Research Funding; Oncternal: Consultancy, Research Funding; OncLive: Honoraria; InnoCare: Consultancy; Targeted Oncology: Honoraria; Loxo Oncology: Consultancy, Research Funding; Pulse Biosciences: Consultancy; Kite Pharma: Consultancy, Other: Travel, accommodation, expenses, Research Funding; Juno: Consultancy, Research Funding; BioInvent: Research Funding; VelosBio: Research Funding; Acerta Pharma: Research Funding. Flowers:AbbVie: Consultancy, Research Funding; Kite: Research Funding; Leukemia and Lymphoma Society: Membership on an entity's Board of Directors or advisory committees; V Foundation: Research Funding; Cancer Prevention and Research Institute of Texas: Research Funding; Bayer: Consultancy; National Cancer Institute: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Burroughs Wellcome Fund: Research Funding; TG Therapeutics: Research Funding; Millennium/Takeda: Consultancy, Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Pharmacyclics/Janssen: Consultancy; Karyopharm: Consultancy; OptumRx: Consultancy; Gilead: Consultancy, Research Funding; Genentech, Inc./F. Hoffmann-La Roche Ltd: Consultancy, Research Funding; Denovo Biopharma: Consultancy; Celgene: Consultancy, Research Funding; BeiGene: Consultancy. Hawkins:Kite: Membership on an entity's Board of Directors or advisory committees. Rezvani:GemoAb: Membership on an entity's Board of Directors or advisory committees; Affimed: Other: Educational grant; Adicet Bio: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Other: Educational grant; Virogen: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing agreement; Formula Pharma: Membership on an entity's Board of Directors or advisory committees. Champlin:Takeda: Patents & Royalties; DKMS America: Membership on an entity's Board of Directors or advisory committees; Genzyme: Speakers Bureau; Actinium: Consultancy; Johnson and Johnson: Consultancy; Omeros: Consultancy; Cytonus: Consultancy. Shpall:Magenta: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement; Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Zelluna: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees. Neelapu:Novartis: Other: personal fees; Bristol-Myers Squibb: Other: personal fees, Research Funding; Merck: Other: personal fees, Research Funding; Kite, a Gilead Company: Other: personal fees, Research Funding; Celgene: Other: personal fees, Research Funding; Pfizer: Other: personal fees; Allogene Therapeutics: Other: personal fees, Research Funding; Cell Medica/Kuur: Other: personal fees; Incyte: Other: personal fees; Precision Biosciences: Other: personal fees, Research Funding; Legend Biotech: Other; Adicet Bio: Other; Calibr: Other; Unum Therapeutics: Other, Research Funding; Poseida: Research Funding; Cellectis: Research Funding; Karus Therapeutics: Research Funding; Acerta: Research Funding; Takeda Pharmaceuticals: Patents & Royalties; N/A: Other. Kebriaei:Jazz: Consultancy; Novartis: Other: Served on advisory board; Kite: Other: Served on advisory board; Ziopharm: Other: Research Support; Pfizer: Other: Served on advisory board; Amgen: Other: Research Support.

Background Most PMBCL pts are cured with frontline chemoimmunotherapy ± RT. Data are scant regarding the role of HDC/ASCT for R/R PMBCL, and the benefit of RT administered peri-HDC/ASCT. Our institutional approach has focused on developing potentially more active HDC regimens, and on consideration of post-ASCT consolidation RT, especially for pts who had not achieved a CR at the time of HDC. Methods We retrospectively analyzed all patients (pts) with R/R PMBCL treated with HDC/ASCT at MDACC between 01/01/2000-12/31/2019. All pts underwent similar standard pre-SCT evaluation and met eligibility criteria as per our institutional guidelines. Response assessment differed over time and included CT and gallium scan (N=9) and PET/CT (N=49). Cox proportional hazards regression models evaluated the associations of the specific HDC regimen and clinical covariates of interest with EFS and OS. Results 58 pts received HDC/ASCT with BEAM-rituximab (N=36) or rituximab/gemcitabine/busulfan/melphalan ± vorinostat (R-GemBuMel) (n=22) (Table 1). The R-GemBuMel group included more pts pretreated with >2 lines of therapy than the R-BEAM group (55% vs. 28%, p=0.025), had fewer pts in CR (41% vs. 69%, P=0.01) and more pts in PD/SD at ASCT (32% vs. 3%, P=0.01). Prior RT at a median 44 (36-48) Gy was administered to 29 pts (20 R-BEAM, 9 R-GemBuMel, P=0.27). Nineteen pts (89% not in CR at SCT) who had not previously received full doses of RT received post-SCT RT (6 after BEAM, 13 after R-GemBuMel, P There were 2 treatment-related deaths in the R-BEAM arm, none in the R-GemBuMel arm. At median follow-up of 69.1 months (interquartile range, 36.5-85.2), the EFS rates were 57.6% (overall), 67.6% (R-GemBuMel) and 52.7% (R-BEAM) (Figure 1a). Their respective OS rates were 69.3%, 81.1% and 63.9% (Figure 1b). On multivariable Cox regression analyses, R-GemBuMel (vs. R-BEAM) (HR=0.29, p=0.05), and 1 organ involved (vs. >1) (HR 0.28, p=0.009) were associated with improved EFS, whereas older age (HR= 1.08 per year above median, p=0.005), refractory disease (SD/PD) at SCT (vs. CR/PR) (HR 5.44, p=0.01) correlated with worse EFS. Likewise, R-GemBuMel (HR= 0.16, p=0.03) and 1 organ involved (HR=0.17, p=0.004) significantly resulted in improved OS, whereas older age (HR= 1.11, p=0.002), and refractory (SD/PD) disease at SCT (HR= 21.27, p=0.001) correlated with worse OS. Neither sex nor disease status (primary refractory vs. relapse) nor No. prior lines (2 vs. >2) nor pre-SCT RT nor post-SCT RT correlated significantly with EFS or OS. Conclusions HDC/ASCT for R/R PMBCL pts, with post-SCT RT for pts with active disease at SCT, results in favorable long-term results. R-GemBuMel ± vorinostat seems to improve EFS and OS compared to R-BEAM. Disclosures Alousi: Incyte: Honoraria, Research Funding; Therakos: Research Funding; Alexion: Honoraria. Hosing:NKARTA Inc.: Consultancy. Kebriaei:Amgen: Other: Research Support; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Pfizer: Other: Served on advisory board; Jazz: Consultancy; Novartis: Other: Served on advisory board. Popat:Bayer: Research Funding; Novartis: Research Funding. Qazilbash:Angiocrine: Research Funding; Bioline: Research Funding; Janssen: Research Funding; Bioclinica: Consultancy; Amgen: Research Funding. Shpall:Zelluna: Membership on an entity's Board of Directors or advisory committees; Adaptimmune: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Magenta: Membership on an entity's Board of Directors or advisory committees; Takeda: Other: Licensing Agreement. Champlin:Takeda: Patents & Royalties; Genzyme: Speakers Bureau; Cytonus: Consultancy; Omeros: Consultancy; Actinium: Consultancy; Johnson and Johnson: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees. Nieto:Affimed: Consultancy, Other: Grant Support; Novartis: Other: Grant Support; Astra Zeneca: Other: Grant Support; Secura Bio: Other: Grant Support.

Background: Venetoclax has shown a promising benefit in patients (pts) with acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). There is paucity of information about the efficacy and risk of GVHD with alloSCT post venetoclax -based therapy. Methods: We conducted a retrospective analysis of 35 AML/ALL pts who received alloSCT following venetoclax-based therapies between 2013-2018 at MD Anderson Cancer Center. Results: Median age at alloSCT was 60 years and 23 (66%) pts had an age-adjusted HCT-CI score > 3. Disease diagnosis - AML (n=31; 89%), ALL (n=4; 11%). Disease status in pts with AML at study entry was CR1 (n=11; 35%), CR2/CR3 (n=6; 19%), Cri (n=2, 6%), hypoplastic marrow (n=2; 6%) or refractory disease (n=10; 32%). ALL pts were in CR1 (n=2) or CR2 (n=2). Sixteen (46%) pts were MRD-negative by flow cytometry on marrow samples pre-alloSCT, 7 (20%) were MRD-positive, and 10 (29%) had active disease; 2 pts had hypoplastic marrow. Median lines of prior therapies was 2 (range 1-7) and 6 (17%) pts had failed a prior alloSCT. Disease risk index was intermediate (n=18 of 34; 53%) or high/very-high (n=16 of 34; 47%). Venetoclax was provided in combination of hypomehylating (HMA) agents or other chemotherapies in 26 (74%) and 9 (26%) pts, respectively. Median duration of venetoclax-based treatment was 2.0 months (range 0.5- 4.6). Most pts (83%) continued their therapy as a bridge to alloSCT. Venetoclax was discontinued in 6 (17%) pts due to adverse events (n=4) or progression (n=2). Conditioning regimens were melphalan-based reduced intensity (n=26, 74%), or busulfan-fludarabine regimens (n=9; 26%). Donor source was matched unrelated (n=13, 37%), or related (n=9; 26%); haplo (n=12; 34%) and mismatched unrelated (n=1; 3%). Cell source was from peripheral blood (n=24; 69%) or bone marrow (n=11; 31%). GVHD prophylaxis consisted of tacrolimus with either post-transplant cyclophosphamide in 25 (71%) pts or methotrexate in 10 (29%) pts. Seven (20%) pts (3 with active disease, 2 MRD-positive and 2 were MRD-negative pre-alloSCT)) received maintenance therapy with agents other than venetoclax (Vidaza=2, Sorafenib =2, SGI =1, Ponatinib =1, Asparginase = 1) post alloSCT at a median of 3 months (range, 2-4 months). Median time to ANC >500 was 15.5 days (range, 10-24), and platelets counts >20 k was 22.5 days (range, 11-46). The cumulative incidence (CI) of acute 2-4 and 3-4 GVHD was 29% and 9%, respectively. Risks associated with 100 day-acute 2-4 GVHD were evaluated in univariate analyses. Factors evaluated were age, HCT-CI, # prior lines of therapies, prior alloSCT, type GVHD prophylaxis, donor type, cell source, female donor to male recipients, prior PD-1 therapy (n=3) , types of combination of venetoclax duration of treatment and timing of last venetoclax treatment to alloSCT. Only venetoclax timing to alloSCT was associated with significant risk. The CI of acute 2-4 GVHD in patients who discontinued venetoclax ≤ 2 weeks (n=11, 31%) vs > 2 weeks (n=24, 69%) was 55% vs 17% (P = 0.020; Figure 1), respectively [HR 0.24, 95% confidence interval 0.07-0.80; P = 0.020). . With a median follow up among surviving pts of 18.4 months (range 3.5-31.4), the 1-year rates of OS, PFS, and NRM were 72%, 57% and 12% respectively. Twelve patients died: 8 due to progression, 2 of GVHD, 1 of infection and 1 of unknown cause. Disease status was the only predictor of OS in univariate analysis. Pts who were MRD-negative pre-alloSCT had a 1-year OS of 92% while the 1-year OS in pts who were CR/MRD+ and those with active disease was 38% and 70%, respectively (Figure 2). No factor evaluated was significantly associated with NRM. Conclusions: Our data show that the use of venetoclax-based therapy as a bridge to alloSCT does not increase the risk of NRM or delayed engraftment. It does improve OS by inducing CR/MRD-negativity in high-risk acute leukemia. It may be prudent however to discontinue therapy > 2 weeks before alloSCT in order to avoid a higher risk of acute GVHD. Disclosures Jabbour: BMS: Other: Advisory role, Research Funding; Genentech: Other: Advisory role, Research Funding; Adaptive Biotechnologies: Other: Advisory role, Research Funding; AbbVie: Other: Advisory role, Research Funding; Pfizer: Other: Advisory role, Research Funding; Takeda: Other: Advisory role, Research Funding; Amgen: Other: Advisory role, Research Funding. Daver:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz: Consultancy, Membership on an entity's Board of Directors or advisory committees; Trillium: Consultancy, Membership on an entity's Board of Directors or advisory committees; Syndax: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; KITE: Consultancy, Membership on an entity's Board of Directors or advisory committees; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Research Funding; Servier: Research Funding; Genentech: Research Funding; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novimmune: Research Funding; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Trovagene: Research Funding; Fate Therapeutics: Research Funding; ImmunoGen: Research Funding; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Konopleva:Cellectis: Research Funding; Reata Pharmaceutical Inc.;: Patents & Royalties: patents and royalties with patent US 7,795,305 B2 on CDDO-compounds and combination therapies, licensed to Reata Pharmaceutical; F. Hoffmann La-Roche: Consultancy, Research Funding; AbbVie: Consultancy, Research Funding; Sanofi: Research Funding; Eli Lilly: Research Funding; Rafael Pharmaceutical: Research Funding; Ascentage: Research Funding; Agios: Research Funding; Amgen: Consultancy; Genentech: Consultancy, Research Funding; Kisoji: Consultancy; Ablynx: Research Funding; Stemline Therapeutics: Consultancy, Research Funding; AstraZeneca: Research Funding; Calithera: Research Funding; Forty-Seven: Consultancy, Research Funding. DiNardo:Novartis: Consultancy; AbbVie: Consultancy, Honoraria, Research Funding; ImmuneOnc: Honoraria; Notable Labs: Membership on an entity's Board of Directors or advisory committees; Syros: Honoraria; Calithera: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; MedImmune: Honoraria; Jazz: Honoraria; Agios: Consultancy, Honoraria, Research Funding; Daiichi Sankyo: Consultancy, Honoraria, Research Funding. Ravandi:Orsenix: Consultancy, Honoraria, Research Funding; Jazz Pharmaceuticals: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Astellas: Consultancy, Honoraria, Research Funding; Macrogenics: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Xencor: Consultancy, Honoraria, Research Funding. Kadia:Pulmotec: Research Funding; Astra Zeneca: Research Funding; Genentech: Honoraria, Research Funding; Cellenkos: Research Funding; Celgene: Research Funding; Amgen: Research Funding; Ascentage: Research Funding; Novartis: Honoraria; Incyte: Research Funding; JAZZ: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Astellas: Research Funding; Cyclacel: Research Funding; Pfizer: Honoraria, Research Funding. Alousi:Incyte: Honoraria, Research Funding; Alexion: Honoraria; Therakos: Research Funding. Oran:Arog Pharmaceuticals: Research Funding; Celgene: Consultancy; ASTEX: Research Funding. Kebriaei:Amgen: Other: Research Support; Pfizer: Other: Served on advisory board; Ziopharm: Other: Research Support; Kite: Other: Served on advisory board; Novartis: Other: Served on advisory board; Jazz: Consultancy. Popat:Bayer: Research Funding; Novartis: Research Funding. Kantarjian:Aptitute Health: Honoraria; BioAscend: Honoraria; Adaptive biotechnologies: Honoraria; Novartis: Honoraria, Research Funding; Actinium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Research Funding; Oxford Biomedical: Honoraria; Immunogen: Research Funding; BMS: Research Funding; Ascentage: Research Funding; Amgen: Honoraria, Research Funding; Pfizer: Honoraria, Research Funding; Jazz: Research Funding; Janssen: Honoraria; Delta Fly: Honoraria; Daiichi-Sankyo: Honoraria, Research Funding; Abbvie: Honoraria, Research Funding. Champlin:Omeros: Consultancy; Actinium: Consultancy; DKMS America: Membership on an entity's Board of Directors or advisory committees; Cytonus: Consultancy; Genzyme: Speakers Bureau; Takeda: Patents & Royalties; Johnson and Johnson: Consultancy. Khouri:Bristol Myers Squibb: Research Funding; Pfizer: Research Funding.