Citations

Objectives: The Ice Hockey Summit III provided updated scientific evidence on concussions in hockey to inform these 5 objectives: (1) describe sport related concussion (SRC) epidemiology; (2) classify prevention strategies; (3) define objective, diagnostic tests; (4) identify treatment; and (5) integrate science and clinical care into prioritized action plans and policy. Methods: Our action plan evolved from 40 scientific presentations. The 155 attendees (physicians, athletic trainers, physical therapists, nurses, neuropsychologists, scientists, engineers, coaches, and officials) voted to prioritize these action items in the final Summit session. Results: To (1) establish a national and international hockey database for SRCs at all levels; (2) eliminate body checking in Bantam youth hockey games; (3) expand a behavior modification program (Fair Play) to all youth hockey levels; (4) enforce game ejection penalties for fighting in Junior A and professional hockey leagues; (5) establish objective tests to diagnose concussion at point of care; and (6) mandate baseline testing to improve concussion diagnosis for all age groups. Conclusions: Expedient implementation of the Summit III prioritized action items is necessary to reduce the risk, severity, and consequences of concussion in the sport of ice hockey.

Background: There are limited data comparing the outcomes of similarly matched patients with a medial meniscus posterior root tear (MMPRT) treated with nonoperative management, partial meniscectomy, or repair. Purpose/Hypothesis: The purpose was to compare treatment failure, clinical outcome scores, and radiographic findings for a matched cohort of patients who underwent either nonoperative management, partial meniscectomy, or transtibial pull-through repair for an MMPRT. We hypothesized that patients who underwent meniscus root repair will have lower rates of progression to arthroplasty than patients who were treated with nonoperative management or partial meniscectomy. Study Design: Cohort study; Level of evidence, 3. Methods: Patients who underwent transtibial medial meniscus posterior horn root repair were matched by meniscal laterality, age, sex, and Kellgren-Lawrence (K-L) grades to patients treated nonoperatively or with a partial meniscectomy. Progression to arthroplasty rates, International Knee Documentation Committee and Tegner scores, and radiographic outcomes were analyzed between groups. Results: Forty-five patients were included in this study (15 nonoperative, 15 partial meniscectomy, 15 root repair). Progression to arthroplasty demonstrated significant differences among treatment groups at a mean of 74 months (nonoperative, 4/15; partial meniscectomy, 9/15; meniscal repair, 0/15; P = .0003). The meniscus root repair group had significantly less arthritic progression, as measured by change in K-L grade from pre- to postoperatively (nonoperative, 1.0; partial meniscectomy, 1.1; meniscal repair, 0.1; P = .001). Conclusion: Meniscus root repair leads to significantly less arthritis progression and subsequent knee arthroplasty compared with nonoperative management and partial meniscectomy in a matched cohort based on patient characteristics.

Background: Patients ≥55 years of age with rel/ref AML who have failed to achieve complete remission (CR) after standard induction & salvage therapies do not routinely undergo allogeneic hematopoietic cell transplantation (HCT) due to inability to receive myeloablative conditioning and lack of efficacy. With the advent of recently approved targeted therapies (e.g. venetoclax, IDH inhibitors) more patients achieve CR, however durable responses in heavily pre-treated patient populations remain unsatisfactory with very few patients being transplanted. The SIERRA (Study of Iomab-B in Elderly Relapsed or Refractory AML) trial is a prospective, randomized, phase 3 trial designed to address this unmet need. We present the preliminary analysis of the first 50% of patients and analyze the proportion of patients who fail standard chemo and targeted therapies that can then successfully undergo HCT with Iomab-B-based conditioning. Study continues to enroll (N=150), primary end-point durable CR of ≥180 days. Methods: Eligible patients are ≥ 55 years with rel/ref AML (≥5% blasts), adequate organ function, and related/unrelated 8/8 HLA-matched donors. Patients are randomized (1:1) to receive Iomab-B followed 12-14 days later by reduced intensity conditioning (fludarabine(FLU)/TBI) and HCT, or to conventional care (CC). CC patients may receive investigator's choice of salvage therapy, including newly approved targeted agents such as venetoclax, IDH Inhibitors and may proceed to standard HCT if they achieve CR. If patients do not achieve CR, the study allows cross-over (CO) to Iomab-B with HCT. Results: Preliminary data are available from the first 75 patients enrolled on the SIERRA trial. Median age of 64 years (range: 55-77). All patients had active measurable disease (Table 1). Patients in this trial were heavily pretreated with 85% failing ≥2 induction therapies and 33% failing targeted therapies. Molecular and cytogenetics was 68% adverse risk. (NCCN, v1.2018) Following therapeutic dose of Iomab-B as a single agent, there was significant reduction of circulating blasts by day 3 (99%, p<0.0001), and peripheral blasts became undetectable by day 8 prior to FLU. All patients transplanted on the Iomab-B arm with data available showed median days to engraftment of ANC at 14 (range: 9-22) and platelets at 16 (range: 4-30) (Table 1). After randomization, 82% (31/38) patients in the CC arm failed salvage therapy and did not proceed to standard HCT. Significantly, 32% (12/38) of these patients received targeted therapy. 73% (8/11) of the patients receiving venetoclax with HMA or cytarabine did not adequately respond and did not proceed to standard HCT, 45% (5/11) crossed over to Iomab-B and received HCT. Following standard chemotherapies, 85% (22/26) were evaluated for CO. In total, 63% (19/30) received Iomab-B and HCT. The most common reason preventing crossover was disease progression. All crossover (Iomab-B) patients showed similar engraftment (Table 1). CC patients showed increased incidence of febrile neutropenia with grade 3 prior to CO evaluation or HCT, compared to Iomab-B patients prior to HCT (CC: 34%, Iomab-B: 8%). Iomab-B administration was generally well-tolerated with no grade 4 and 1 grade 3 infusion reaction. There were no Iomab-B-related deaths or 100 day non-relapse transplant related mortality deaths in patients on the Iomab-B arm (Table 1). Conclusion: 100% of the patients receiving HCT on the Iomab-B arm engrafted, despite a median of 29% BM blasts pre-Iomab-B. 82% of the patients on the CC arm failed to be eligible for standard of care transplant, including a high percentage of those receiving targeted therapies. On the CC arm, 63% of eligible patients crossed over to Iomab-B/HCT with robust engraftment despite a median of 35% BM blasts pre-Iomab-B. The incidence of grade 3 febrile neutropenia was higher in patients treated on the conventional care arm with salvage therapy vs. those treated on the Iomab-B arm prior to HCT. In conclusion, despite advanced age, active disease and heavily pre-treated patients, 68% (50/74) of all patients enrolled in the SIERRA trial were able to undergo HCT after reinduction and targeted conditioning with Iomab-B. These results show significant improvements in the current rates of transplantation in this patient population. This SIERRA trial is currently enrolling. For full study details see www.sierratrial.com or clinicaltrials.gov (NCT02665065). Disclosures Gyurkocza: Actinium Pharmaceuticals: Research Funding. Nath:Astellas: Consultancy; Actinium: Consultancy; Daiichi Sankyo: Consultancy. Stiff:Amgen: Research Funding; Gamida-Cell: Research Funding; Incyte: Research Funding; Unum: Research Funding; Cellectar: Research Funding; Gilead/Kite Pharma: Consultancy, Honoraria, Research Funding. Tomlinson:Actinium Pharmaceuticals, Inc: Other: Travel Support. Abhyankar:Incyte: Speakers Bureau; Therakos: Other: Consulting, Speakers Bureau. Hari:AbbVie: Consultancy, Honoraria; Cell Vault: Equity Ownership; Sanofi: Honoraria, Research Funding; Spectrum: Consultancy, Research Funding; Amgen: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Janssen: Consultancy, Honoraria; Kite: Consultancy, Honoraria. Al-Kadhimi:Seattle Genetics: Other: Stocks; Celldex Biotech: Other: Stocks. Foran:Agios: Honoraria, Research Funding. Orozco:Actinium Pharmaceuticals: Research Funding. Van Besien:Miltenyi Biotec: Research Funding. Sabloff:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Astellas Pharma Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; ASTX: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jazz Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Actinium Pharmaceuticals, Inc: Membership on an entity's Board of Directors or advisory committees; Novartis Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer Canada: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi Canada: Research Funding. Kebriaei:Pfizer: Honoraria; Kite: Honoraria; Jazz: Consultancy; Amgen: Research Funding; Pfizer: Honoraria; Kite: Honoraria; Jazz: Consultancy; Amgen: Research Funding. Levy:Takeda (Millennium Pharmaceuticals): Consultancy. Lazarus:Adaptive Biotechnologies: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria, Speakers Bureau; Actinium Pharmaceuticals: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva Pharmaceuticals: Speakers Bureau; Biosight: Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; AstraZeneca: Honoraria, Speakers Bureau; Bristol Myers Squibb: Honoraria, Speakers Bureau; Pluristem Therapeutics, Inc: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Consultancy; Genentech: Speakers Bureau. Giralt:Novartis: Consultancy; Actinium: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy; Amgen: Consultancy, Research Funding; Kite: Consultancy; Miltenyi: Research Funding; Takeda: Consultancy, Research Funding; Johnson & Johnson: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy. Berger:Actinium Pharmaceuticals, Inc: Employment, Equity Ownership. Reddy:Actinium Pharmaceuticals: Employment. Pagel:Pharmacyclics: Consultancy; AstraZeneca: Consultancy; Gilead Sciences: Consultancy.

Abstract Glioblastomas (GBMs) are known to be complex tumors comprising multiple subpopulations of genetically-distinct cancer cells; it is thought that this genetic variation is a major factor in the lack of observed survival benefit of treatment regimes that target one of these subpopulations. The field of radiogenomics seeks to study correlations between MRI patterns and genetic features of GBM tumors. Spatial radiogenomic maps produced using machine-learning (ML) methods that are trained against information from image-localized patient biopsies identify regions where particular cancer sub-populations are predicted to occur within a GBM, thus non-invasively characterizing the regional genetic variability of these tumors. These tumor subpopulations may also interact with one another, in ways which may be of a competitive or cooperative nature to varying degrees. It is important to ascertain the nature of these interactions, as they may have implications for treatment response to targeted therapies, and characterization of the spatio-temporal dynamics of these co-evolving sub-populations will shed light on why some therapies fail. Here we combine mathematical modeling techniques and spatially-resolved radiogenomic maps to study the nature of these interactions between molecularly-distinct GBM subpopulations. We model the interactions between cell populations using a partial differential equation based formalism. The model is parameterized using radiogenomic ML maps from which we infer the nature of interactions between subpopulations. Furthermore, using maps as inputs, the model turns static maps into dynamic information, thus providing insight into how these subpopulations composing the tumor change over time and the effect this has on observed treatment response for individual patients.

Accurate antemortem diagnosis of parkinsonism is primarily based on clinical evaluation with limited biomarkers. We evaluated the diagnostic utility of quantitative rapid eye movement (REM) sleep without atonia analysis in the submentalis and anterior tibialis muscles in parkinsonian patients (53 synucleinopathy, 24 tauopathy). Receiver operating characteristic curves determined REM sleep without atonia cutoffs distinguishing synucleinopathies from tauopathies. Elevated submentalis muscle activity was highly sensitive (70–77%) and specific (95–100%) in distinguishing synucleinopathy from tauopathy. In contrast, anterior tibialis synucleinopathy discrimination was poor. Our results suggest that elevated submentalis REM sleep without atonia appears to be a potentially useful biomarker for presumed synucleinopathy etiologies in parkinsonism. ANN NEUROL 2019;86:969–974

Objective This study aims to (1) determine and validate living cartilage allograft transplantation as a novel source for viable osteochondral allograft (OCA) tissues and (2) perform histologic and viability comparisons of living donor cartilage tissues to currently available clinical-grade standard processed grafts. Design Using healthy cartilage from well-preserved contralateral compartments in 27 patients undergoing total knee arthroplasty (TKA) and 10 clinical-grade OCA specimens obtained immediately following operative implantation, standard and living donor OCA quality was evaluated at the time of harvest and following up to 3 weeks of storage on the basis of macroscopic International Cartilage Repair Society grade, histology, and viability. Results Osteochondral samples demonstrated a consistent decrease in viability and histologic quality over the first 3 weeks of storage at 37°C, supporting the utility of an OCA paradigm shift toward early implantation, as was the clinical standard up until recent adoption of transplantation at 14 to 35 days following donor procurement. Samples from the 10 clinical-grade OCAs, implanted at an average of 23 days following graft harvest demonstrated a mean viable cell density of 45.6% at implantation, significantly lower ( P < 0.01) than the 93.6% viability observed in living donor allograft tissues. Conclusions Osteochondral tissue viability and histologic quality progressively decreases with ex vivo storage, even when kept at physiologic temperatures. Currently available clinical OCAs are stored for 2 to 5 weeks prior to implantation and demonstrate inferior viability to that of fresh osteochondral tissues that can be made available through the use of a living donor cartilage program.

Abstract Background: Patients ≥55 years of age with active, relapsed or refractory acute myeloid leukemia (R/R AML) who have failed standard induction therapies most often receive salvage therapy with a wide variety of agents, but very few achieve remission. These patients do not routinely undergo allogeneic hematopoietic cell transplantation (HCT) due to lack of efficacy using a standard HCT approach. The SIERRA trial is a prospective, randomized, phase 3, open-label, ongoing multicenter trial designed to address this significant unmet need in R/R AML. This trial compares Iomab-B, an 131I-radiolabeled anti-CD45 antibody as targeted conditioning prior to HCT against standard conventional care therapies with an accrual goal of 150 patients. We have performed a preliminary safety analysis, validating the initial feasibility of this multi-center trial. Methods: Eligible patients are ≥ 55 years of age with active, R/R AML, adequate organ function, and related/unrelated matched donor. Patients are randomized (1:1 ratio) to receive dosimetry directed Iomab-B followed 12 days later by HCT with fludarabine 30 mg/m2 x 3 days and 2 Gy of total body irradiation as transplant conditioning, or to a Conventional Care (CC) arm. Patients randomized to CC, may receive investigator's choice of salvage induction chemotherapy including approved targeted agents as well as Venetoclax (in combination with a hypomethylating agent) and proceed to standard HCT if they achieve complete remission (CR). If patients do not achieve CR, the study allows optional cross-over to the Iomab-B arm, evaluated between days 28-42 after CC therapy. The primary efficacy endpoint for the study is durable complete remission (dCR) of 6 months. The secondary efficacy objective is to evaluate overall survival at 1 year. Results: Forty patients have been enrolled to date and data are available for 38 patients (19 = Iomab-B, 19 = CC) as of July 5th, 2018. The median age was 63 years (range: 55-76). All patients had active disease at the time of enrollment with median bone marrow (BM) blasts of 30% in the Iomab-B arm and 47% in the crossover arm prior to receiving Iomab-B (Table 1). Of the patients in the CC arm, 88% did not achieve a CR and 65% of those crossed-over to receive Iomab-B. The most common reason preventing crossover was declining performance status. Time to HCT was not increased in the crossover patients receiving Iomab-B compared to those that underwent a standard of care transplant after achieving CR (median 65 vs 75 days), while the Iomab-B arm patients were transplanted at a median of 27 days after randomization. Iomab-B therapy was well-tolerated with no grade 3 or 4 infusion-related reactions reported. The median activity of Iomab-B was 626 mCi (range: 397-1027). All patients randomized to Iomab-B (N=13) engrafted, with median days to engraftment of ANC at 13 (range: 9-22) and platelets at 17 (range: 13-26). All patients who received Iomab-B after crossover (N=9) also engrafted with time to engraftment similar to patients initially randomized to the Iomab-B arm (Table 1). Donor chimerism (≥95%), within 100 days after HCT, was found in 9 of 10 patients in the Iomab-B arm and 8 of 9 patients in those that crossed over to receive Iomab-B, with two patient exceptions having mixed donor chimerism at day 28. A preliminary safety analysis for all randomized patients on either study arm showed the most frequent non-hematologic adverse events ≥ grade 3 occurring in >10% patients were febrile neutropenia (34.2%), stomatitis (15.8%), malnutrition (13.2%), epistaxis, sepsis, hypotension, hypobilirubinemia and fatigue (all 10.5%). There were no Iomab-B-related deaths. Interpretation: Preliminary safety analysis demonstrates the feasibility of delivering targeted conditioning with Iomab- B for HCT in R/R AML patients who have active disease and a high BM blast burden (median: ≥ 30%) prior to transplantation. All patients who received Iomab-B, including those crossed over after failing to achieve CR on CC salvage therapy, engrafted ANC within 13 days, despite active disease prior to transplant. In addition, the time to HCT from randomization was not increased in patients receiving Iomab-B after cross-over compared to those who underwent standard of care HCT after achieving CR on the CC arm. This study is currently enrolling and for full study details see www.sierratrial.com or clinicaltrials.gov (NCT02665065). Disclosures Tomlinson: Foundation Medicine: Consultancy. Foran:Xencor, Inc.: Research Funding; Agios: Research Funding. Chen:Bellicum Pharmaceuticals: Research Funding. Levy:Takeda (Millennium Pharmaceuticals, Inc.): Consultancy. Lazarus:Pluristem Ltd.: Consultancy. Berger:Actinium Pharmaceuticals: Employment, Equity Ownership. Reddy:Actinium Pharmaceuticals: Employment, Equity Ownership; Pharmacyclics: Employment. Pagel:Pharmacyclics, an AbbVie Company: Consultancy; Gilead: Consultancy.

Abstract Abstract 2859 Introduction: Patients with chronic lymphocytic leukemia who relapse following purine-analog or bendamustine-based treatments have a poor prognosis. These patients have limited therapeutic options and novel agents with alternative mechanisms of action are needed. In phase 1 and 2 trials, escalating dose regimens of the immunomodulatory agent lenalidomide demonstrated promising activity with relapsed/refractory CLL. Of interest, the data indicate that superior efficacy might be achieved by a starting dose above 2.5 mg daily lenalidomide. A phase 2 trial (CLL-009 study) was developed to investigate the safety of different starting doses of lenalidomide followed by a step-wise dose escalation as tolerated in relapsed/refractory CLL. Methods: In this ongoing trial, eligible subjects with relapsed/refractory CLL who have received at least 1 prior treatment regimen are being enrolled. Subjects are randomized 1 :1 :1 to receive a double-blinded starting dose of 5 mg, 10 mg, or 15 mg oral lenalidomide on days 1–28 of each 28-day cycle. The primary objectives are to determine the safety and efficacy of the different lenalidomide starting doses of 5 mg, 10 mg or 15 mg daily, followed by an intra-patient escalation up to a maximum of 25 mg daily using a Bayesian approach. Based on individual patient tolerability, the daily lenalidomide dose can be escalated every 28 days by 5 mg increments. Dose reductions also occur in 5 mg increments; however, dose levels below 5 mg sequentially include 2.5 mg and 1.25 mg daily. Tumor lysis syndrome (TLS) prophylaxis, comprised of oral hydration and allopurinol 300 mg/day is initiated at least 3 days prior to starting study drug and for a minimum of the first 3 treatment cycles. This adaptive design trial is considering joint efficacy and toxicity outcomes to stop randomization of less promising arms. Accrual to a starting dose arm will be stopped if unacceptable toxicities and/or high progression rate are observed in that arm. A total of 90 subjects will be enrolled in the study. Results: To date, 51 subjects with a median age of 63 years (range 39–78) have been enrolled. Subjects to date are primarily male (65%) and Caucasian (84%), and slightly more than half (53%) are ≥ 65 years old. Cytogenetic data is available for 42 subjects; 10 have del(11q), 8 have del(17p), and 24 have del(13q). Overall, 31 subjects had at least one cytogenetic deletion. Based on the Binet and Rai staging systems: 3 (6%), 10 (20%) and 15 (29%) of subjects are stage A, B and C, respectively; and, 6 (12%), 7 (14%) and 7 (14%) subjects are low, intermediate or high-risk disease, respectively. For 3 (6%) subjects the Binet/Rai staging is currently unknown. The most common hematological grade 3/4 adverse events (AEs) thus far include neutropenia (41% of patients) and thrombocytopenia (24%). The most common non-hematological grade 3/4 AEs include fatigue (12%) and tumor flare (12%). Only 1 subject (2%) experienced tumor lysis syndrome of grade 1. Over half of the subjects (53%) remain on therapy; 24 (47%) subjects have discontinued treatment. The longest subject has completed 17 cycles, and remains on study medication. The most common reasons for study discontinuation include disease progression (n = 8) and AEs (n = 10). To date, 20 subjects (54% of eligible patients) have successfully dose escalated above their respective starting double blinded dose level, including 3, 3, 2 and 12 subjects undergoing 4, 3, 2, and 1 dose escalations, respectively. As 14 patients are still in the first cycle of the study, a total of 20 subjects have had no dose level reduction or escalations. The average duration of treatment is 4.34 cycles, and the median number of cycles is 3. Efficacy evaluations are completed monthly after 3 months of study drug treatment. By investigator assessment, 34 subjects have been evaluated to date, including 1 (3%) complete response, 12 (35%) partial response, 7 (21%) stable disease, 10 (29%) progressive disease and 4 (12%) not evaluable. Conclusion: The independent Data Monitoring Committee, as of March 24, 2011 (N=41), recommended that accrual into all three treatment arms should continue as planned, suggesting all three starting doses were tolerated. To date, the ORR is 38% (13/34 evaluable subjects), and 54% of subjects (20/37) have dose escalated at least once. In this relapsed/refractory CLL population lenalidomide appears active, and completion of accrual will hopefully demonstrate the appropriate starting dose. Disclosures: Wendtner: Celgene: Consultancy, Honoraria, Research Funding. Off Label Use: lenalidomide in cll. Goldberg:Celgene: Honoraria, Research Funding, Speakers Bureau. Bloor:Celgene: Honoraria, Research Funding. Stilgenbauer:Celgene: Consultancy, Honoraria, Research Funding. Cymbalista:Roche: Research Funding; Mundipharma: Honoraria; Genzyme: Honoraria. Kipps:Celgene: Consultancy, Research Funding; Abbott Industries: Research Funding; Genentech: Research Funding; Gilead Sciences: Consultancy, Research Funding; Igenica: Membership on an entity's Board of Directors or advisory committees. Purse:Celgene: Employment, Equity Ownership. Zhang:Celgene: Employment, Equity Ownership. Mei:Celgene: Employment.

Abstract Systemic mastocytosis (SM) is a rare hematologic neoplasm characterized by abnormal growth and accumulation of tissue mast cells (MC) in various organ systems, including bone marrow (BM). Indolent and advanced forms of SM have been described. Whereas patients with ISM have a normal or near normal life-expectancy, patients with advanced SM, including those suffering from mast cell leukemia (MCL) have a poor prognosis. In these patients, neoplastic MC are usually resistant against conventional drugs and various targeted drugs. In rapidly progressive aggressive SM (ASM) and MCL, polychemotherapy followed by allogeneic hematopoietic stem cell transplantation (alloHCT) has been proposed. However, outcome of alloHCT in advanced SM is unknown, and it also remains uncertain whether clinically relevant graft-versus-SM (GVSM) effects may occur in these patients, as only sporadic case reports have been published. We performed a retrospective multi-center analysis to evaluate the outcome of alloHCT in patients with advanced SM. Fifty-four advanced SM patients receiving SCT in 32 transplantation centers in Europe and America were identified between 1990 and 2013. The median patient age was 45 years. Donors were: HLA identical siblings (31), unrelated donors (URD) (15), umbilical cord blood donors (UCB) (2), and haploidentical donors (1). In 5 patients, stem cell source was not defined (5). Thirty-four patients received myeloablative conditioning (MAC) and 18 received reduced intensity conditioning regimens (RIC). In 2 patients, conditioning regimen was not specified. Indications for alloHCT were SM with an associated clonal hematologic non-mast cell lineage disease (SM-AHNMD) (n=32), MCL (n=13, including one with MCL-AHNMD), 8 with ASM and 1 with myelomastocytic leukemia (MML). The most prevalent AHNMD was acute myeloid leukemia (AML, n=16). With follow-up of 35-6180 (median 365) days, SM responses (defined as ≥50% decrease in BM mast cells ± decrease in serum tryptase ± regression of other organ manifestations) were observed in 39 patients (72%), including complete responses (CR) documented in 12 patients (22%). Eleven patients had stable disease, whereas 4 patients (7%) progressed immediately after alloHCT (primary resistance). In addition, 10 patients progressed (5 of them within 100 days) after an initial response. Progression was most frequently seen in MCL patients (n=6, 50%). In the AHNMD group, only 8 patients relapsed/progressed (25%). The overall survival (OS) and SM progression-free survival (PFS) at 1 year were 63% and 50% for all patients, 77% and 68% for SM-AHNMD, 63% and 50% for ASM, and 25% and 17% for MCL, respectively. The strongest predictive variable associated with inferior survival was a diagnosis of MCL. Other factors associated with poor outcome were: Karnofsky performance status ≤70%, ≥2 SM regimens given before alloHCT (e.g., steroids, cladribine, chemotherapy, tyrosine kinase inhibitor), donor source (alternative donors-UCB and haploidentical compared to sibling or URD), SM progression within the first 100 days, normal cytogenetics (compared to t(8;21) (q22;q22), and RIC (compared to MAC). The following variables were not associated with poor outcome: patient and donor age, recipient-donor sex match status, graft source (BM vs. peripheral stem cells), BM mast cell percentage at time of alloHCT, and CR status of AML or SM response at time of alloHCT. This largest multi-center analysis of results in advanced SM provides evidence for clinical efficacy of alloHCT, presumably because of a GVSM effect of alloHCT (achieving CR, and response to donor-lymphocyte infusions and RIC alloHCT). However, responses varied among different SM categories: while patients with SM-AHNMD enjoyed excellent outcomes, the OS for MCL patients in general, was poor. Nevertheless it is remarkable that 3 of 13 patients with MCL – an otherwise fatal disease with a median survival of &lt;12 months – became long-term survivors after alloHCT. In summary, our results support development of a prospective alloHCT study, with the aim to optimize therapy and to improve overall outcome in advanced SM. Based on our pilot study, alloHCT should also be considered in practice for eligible and fit patients with SM-AHNMD (if treatment of AHNMD component needs alloHCT or SM component is aggressive), rapidly progressing ASM, MCL and MML when a suitable HLA-matched sibling donor or URD is available. Disclosures: Vercellotti: Sangart Inc.: Research Funding; Seattle Genetics: Research Funding. Akin:Novartis: Consultancy. Valent:Novartis: Consultancy, Honoraria, Research Funding.