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Introduction Blinatumomab (Blina) and inotuzumab ozogamicin (Ino) have shown remarkable responses in relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL), however, a significant number of patients (pts) relapse. Prior reports suggest that allogeneic hematopoietic stem cell transplantation (SCT) consolidation after Blina/Ino may be associated with increased transplant related complications. To address this issue, we assembled a large retrospective multi-center cohort of RR ALL pts who received SCT after Blina/Ino. Methods Medical records of RR ALL pts who received SCT after Blina or Ino at 11 academic transplant centers across USA were reviewed. These pts were evaluated for response and toxicity after SCT. Results From December 2014 to May 2019, 223 and 86 pts who received Blina and Ino, respectively, for RR ALL outside clinical trials were identified. Among them 85 (38%) pts in the Blina group (gp) and 21 (25%) pts in the Ino gp who achieved remission and underwent SCT were included in this analysis. Median age of pts in the Blina and Ino gp was 59 (range [R], 18-72) and 43 (R, 20-75) years, respectively. Median number (no.) of therapies (Rx) prior to SCT in Blina and Ino gp was 2, ranging from 2-5 and 2-6, respectively. Five (6%) and 2 (5%) pts in the Blina and Ino gp, respectively, received second SCT. Median time from remission to SCT in Blina gp was 1.7 months (mo) (R, 0.20 to 13.2) and in Ino gp was 4.3 mo (R, 1-13.3). In the Blina and Ino gp: 36.5% vs. 38%, 42% vs. 42%, 15% vs. 9.5% and 6% vs. 9.5% had matched related donor (MRD), matched unrelated donor (MUD), haploidentical and cord blood SCT, respectively. Acute graft versus host disease (aGVHD), chronic (c) GVHD, veno-occlusive disease (VOD) and infectious complications post SCT were observed in 28 (33%), 14 (16.5%), 2 (2%) and 12 (14%) pts, respectively, in the Blina gp. While in the Ino gp, 8 (38%), 1 (5%), 3 (14%) and 4 (19%) pts had these complications, respectively. Six (7%) and 2 (9%) pts had TRM within 100 days of SCT in Blina and Ino gp, respectively. The median PFS and OS in Blina gp was not reached (NR); 66% were progression free and 62% were alive at 2 yrs (Fig 1 A & B). Similarly, median PFS and OS in the Ino gp was NR; 53% were progression free at 6 mo and 53% were alive at 1 yr mark (Fig 1 C & D). In the Blina gp, history of CRS (p= 0.41), no. of prior Rx (p= 0.5), time from response to SCT (p=0.48), and type of donor (p= 0.7) were not significantly associated with GVHD. Similarly, in the Ino gp, no. of prior Rx (p= 0.6), time from response to SCT (p=0.84), type of donor (p= 0.9) were not significantly associated with GVHD. Occurrence of VOD in the Ino gp was not significantly associated with type of donor (p= 0.3), second SCT (p= 0.1), no. of prior Rx (p= 0.6), myeloablative conditioning (p> 0.9) or time from response to SCT (p= 0.5). Conclusion Our real-world analysis suggests that SCT is feasible and effective after Blina or Ino in pts with RR ALL.

Background The molecular events that drive the transformation from myelodysplastic syndromes (MDS) to acute myeloid leukemia (AML) have yet to be fully characterized. We hypothesized that detection of these mutations at the time of transformation from MDS to AML may lead to poorer outcomes. Methods We analyzed 102 MDS patients who were admitted to our institution between 2004 and 2013, had wild-type (wt) FLT3-ITD and RAS at diagnosis, progressed to AML, and had serial mutation testing at both the MDS and AML stages. Results We detected FLT3-ITD and/or RAS mutations in twenty-seven (26%) patients at the time of transformation to AML. Twenty-two patients (81%) had RAS mutations and five (19%) had FLT3-ITD mutations. The median survival after leukemia transformation in patients who had detectable RAS and/or FLT3-ITD mutations was 2.4 months compared to 7.5 months in patients who retained wt RAS and FLT3-ITD (hazard ratio [HR]: 3.08, 95% confidence interval [CI]: 1.9–5.0, p FLT3-ITD and RAS mutations had independent prognostic significance for poor outcome.

Background Autologous stem cell transplant (ASCT) is frequently used as a consolidative therapy option after induction treatment in fit patients with mantle cell lymphoma (MCL) with the goal of prolonging the initial response duration. Despite recent advances there remains a subset of patients who experience early disease relapse after ASCT. We examined predictors of shortened progression-free survival (PFS) and post-relapse overall survival (OS) in a cohort of patients completing ASCT in first remission. Methods We evaluated MCL patients treated at 10 US academic medical centers. Eligible patients were treated from 2000 through 2017, and we collected information on demographic, clinical, and treatment-related variables of interest. Patients were then categorized into three post-ASCT PFS groups: 0-2 years, 2-5 years, and > 5 years, with PFS determined from the date of ASCT until progression or death from any cause. Patients followed for at least 5 years post-ASCT who were relapse free were included in the > 5 sub group. Associations were examined between groups and collected characteristics using chi-squared tests for categorical patient characteristics and ANOVA for numeric patient characteristics. The Kaplan-Meier method was used to estimate overall survival (OS) for each group, using time of relapse after ASCT as the starting point. Results Of 968 total MCL patients, 242 patients completed ASCT in first remission and either had a PFS event or were relapse-free for at least 5 years post-ASCT. Patients were 80% male, and the median age was 59 (Range: 29-83). The patients were divided into groups of post-ASCT PFS 0-2 years (n=74), 2-5 years (n=75), and more than 5 years (n=93). Post-ASCT PFS was shorter in patients with stage 4 disease (p=0.022), splenomegaly at baseline (p=0.005), and a lymph node size > 5 centimeters at baseline (p=0.043). Other variables were not significantly associated with PFS, including time to transplant and use of intensive therapy. Patients with 0-2 year PFS had a shorter median OS (22.1 months, 95% CI: 13.1- 38.1 months) in comparison to 2-5 year PFS (132 months, 95% CI: 36-132 months) and 5+ year PFS not reached (95% CI: 41.2 – N.A; Figure). Conclusion Patients with higher tumor burden at baseline have a shorter post-ASCT PFS and are more likely to relapse within 2 years. As has been seen in other lymphoma subtypes, early relapse is associated with shorter OS. This represents a patient group requiring improved therapies and perhaps are the best candidates for post-ASCT maintenance or consolidation approaches. Further studies integrating minimal residual disease and molecular risk-stratification may better identify patients at high risk for early progression.

Background Engraftment syndrome (ES) is a complication of autologous hematopoietic stem cell transplantation (auto-HCT), often characterized by non-infectious fever, rash, diarrhea, hepatic or renal dysfunction and non-cardiogenic pulmonary edema at the time of neutrophil recovery. Based on our experience observing increased incidence of ES in recent years, we conducted single center study and evaluated incidence of ES in patients (pts) with light chain amyloidosis (AL). Methods We reviewed data of 72 AL pts who underwent auto-HCT at our center between 1999 and 2017. We reviewed data regarding incidence of ES, feature of ES and evaluated it effects on outcome post auto-HCT. Engraftment syndrome was defined according to Maiolino criteria (Bone Marrow Transplant 2003; 31(5):393-7). Results Baseline characteristics are summarized in the figure 1. The median age of pts at auto-HCT was 58 years (range, 30-75). Twenty-two (31%) pts developed ES, two patients died before neutrophil engraftment. Most common symptoms observed with ES were fever (77%), diarrhea (73%), rash (68%), weight gain (56%), non-cardiogenic pulmonary edema (23%), and acute kidney injury (9%), as shown in figure 2. All patients with ES were treated with steroids. One patient with ES required hemodialysis and management in intensive care unit. In univariate analysis, age (p= 0.23), AL stage (p= 0.24), number of organs involved (p= 0.30), cytoreductive therapy prior to auto-HCT (p= 0.5), method of stem cell mobilization (G vs P+G; p= 0.16) and dose of melphalan used (p= 0.19) were not predictive of ES, as shown in figure 3. Similarly, day 100 post auto-HCT hematological response (19.5% vs 14%, p= 0.7), best organ response (23% vs 36%, p= 0.24) and median length of hospital stay after auto-HCT (20 vs 19 days, p= 0.5) were not significantly different between patients who did not or develop ES, respectively. Overall survival censored at day 180 post auto-HCT to focus on short term outcome, 100% and 80% were alive with or without ES, respectively (p= 0.3; Fig. 3). Conclusion In this single center series, we report a relatively high rate of ES among recipients of auto-HCT for AL compared with previous reports in AL (8%) (Irazabel MV et al. AJH 2012;87[1]:51–54) or with auto-HCT for MM at our center (21%) (Cornell, RF et al. Biol Blood Marrow Transplant. 2013;19[9]:1368-73). Although higher morbidity (ICU stay/ peri engraftment weight change) appeared to be associated with ES, statistically significant predictors or sequelae could not be identified. A larger series with multicenter collaboration is needed to better identify the risk factors associated with ES in AL pts.

Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome.

Introduction The outcomes for DLBCL patients who relapse following auto-HCT have been historically poor. Using data from four transplant centers, we studied the outcomes of DLBCL patients who relapsed following auto-HCT and evaluated whether survival improved in the most recent time period with the advent of novel agents. Methods Eligibility criteria included adult (≥18 years) patients with DLBCL experiencing disease relapse following auto-HCT performed during 2006-2015. The time-period was stratified into two eras (era-1: 2006-2010 and era-2: 2011-2015). The primary endpoint was to determine post-relapse overall survival (PR-OS). Secondary endpoints included a comparison of PR-OS based on the timing of relapse post auto-HCT (early [≤1 year] vs late [>1 year]) and era of transplant (era-1 vs era-2). PR-OS was measured from the date of relapse following auto-HCT to date of death or last follow-up. Results Of the total 700 patients with DLBCL undergoing auto-HCT, 250 patients (36%) (n=113 from era-1 and n=137 from era-2) relapsed following auto-HCT between 2006 and 2015. Patient characteristics are shown in Table with a breakdown between the two eras. The median age was 59 years with male predominance. 92% were chemosensitive (n=230) at the time of auto-HCT. The median time to relapse post auto-HCT was 5.6 months (range: 0.8–96.6 months). Median lines of therapy for post auto-HCT relapse were 1 (range: 0-9), with the most common treatments being allogeneic HCT (21%), lenalidomide (18%) and on clinical trials (17%). Median follow-up of survivors post auto-HCT relapse was 39 months (range: 1-116 months). At 5-year post auto-HCT relapse, the PR-OS for the entire population was 25%, with a median PR-OS of 8.5 months (95% CI=6.3-11.5). Median PR-OS (in months) was significantly better for patients who had late relapse vs early relapse (56.4 [95% CI=23.7-∞] vs 5.5 [95% CI=4.1-7.2], respectively, p Conclusion In DLBCL patients who relapse following auto-HCT, there has been no significant improvement in PR-OS despite the advent of novel agents in the most recent era. More importantly, the outcomes are dismal for patients who relapse within 1 year of auto-HCT representing an urgent unmet need.