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BACKGROUND High-dose chemotherapy (HDCT) plus peripheral blood stem cell transplantation (PBSCT) is effective salvage therapy for relapsed metastatic germ cell tumors (GCTs) but has potential toxicity. Historically, an age of ≥40 years has been associated with greater toxicity and worse outcomes. METHODS This is a retrospective analysis of 445 consecutive patients with relapsed GCT treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen. Kaplan-Meier methods and log-rank tests were used for progression-free survival (PFS) and overall survival (OS) analysis. RESULTS A total of 329 patients were

Post-transplant cyclophosphamide (PTCy) has significantly increased the successful use of haploidentical donors with a relatively low incidence of graft-versus-host disease (GVHD). Given its increasing use, we sought to determine risk factors for GVHD after haploidentical hematopoietic cell transplantation (haplo-HCT) using PTCy. Data from the Center for International Blood and Marrow Transplant Research on adult patients with acute myeloid leukemia, acute lymphoblastic leukemia, myelodysplastic syndrome, or chronic myeloid leukemia who underwent PTCy-based haplo-HCT (2013 to 2016) were analyzed and categorized into 4 groups based on myeloablative (MA) or reduced-intensity conditioning (RIC) and bone marrow (BM) or peripheral blood (PB) graft source. In total, 646 patients were identified (MA-BM = 79, MA-PB = 183, RIC-BM = 192, RIC-PB = 192). The incidence of grade 2 to 4 acute GVHD at 6 months was highest in MA-PB (44%), followed by RIC-PB (36%), MA-BM (36%), and RIC-BM (30%) (P = .002). The incidence of chronic GVHD at 1 year was 40%, 34%, 24%, and 20%, respectively (P < .001). In multivariable analysis, there was no impact of stem cell source or conditioning regimen on grade 2 to 4 acute GVHD; however, older donor age (30 to 49 versus

There is a lack of large comparative study on the outcomes of reduced intensity conditioning (RIC) in acute myeloid leukemia (AML) transplantation using fludarabine/busulfan (FB) and fludarabine/melphalan (FM) regimens. Adult AML patients from Center for International Blood and Marrow Transplant Research who received first RIC allo-transplant between 2001 and 2015 were studied. Patients were excluded if they received cord blood or identical twin transplant, total body irradiation in conditioning, or graft-versus-host disease (GVHD) prophylaxis with in vitro T-cell depletion. Primary outcome was overall survival (OS), secondary end points were leukemia-free survival (LFS), nonrelapse mortality (NRM), relapse, and GVHD. Multivariate survival model was used with adjustment for patient, leukemia, and transplant-related factors. A total of 622 patients received FM and 791 received FB RIC. Compared with FB, the FM group had fewer transplant in complete remission (CR), fewer matched sibling donors, and less usage of anti-thymocyte globulin or alemtuzumab. More patients in the FM group received marrow grafts and had transplantation before 2005. OS was significantly lower within the first 3 months posttransplant in the FM group (hazard ratio [HR] = 1.82, P < .001), but was marginally superior beyond 3 months (HR = 0.87, P = .05). LFS was better with FM compared with FB (HR = 0.89, P = .05). NRM was significantly increased in the FM group during the first 3 months of posttransplant (HR = 3.85, P < .001). Long-term relapse was lower with FM (HR = 0.65, P < .001). Analysis restricted to patients with CR showed comparable results. In conclusion, compared with FB, the FM RIC showed a marginally superior long-term OS and LFS and a lower relapse rate. A lower OS early posttransplant within 3 months was largely the result of a higher early NRM.

Transplant-associated thrombotic microangiopathy (TA-TMA) is a complication of allogeneic transplantation (allo-HCT). The incidence and risk factors associated with TA-TMA are not well known. A retrospective analysis from the Center for International Blood and Marrow Transplant Research (CIBMTR) was conducted including patients receiving allo-HCT between 2008 and 2016, with the primary objective of evaluating the incidence of TA-TMA. Secondary objectives included identification of risk factors associated with TA-TMA, and the impact of TA-TMA on overall survival and the need for renal replacement therapy (RRT). Among 23,665 allo-HCT recipients, the 3-year cumulative incidence of TA-TMA was 3%. Variables independently-associated with increased incidence of TA-TMA included female sex, prior autologous transplant, primary disease (acute lymphoblastic leukaemia and severe aplastic anaemia), donor type (mismatched or unrelated donor), conditioning intensity (myeloablative), GVHD prophylaxis (sirolimus + calcineurin inhibitor), pre-transplant kidney dysfunction and acute GVHD (time-varying effect). TA-TMA was associated with higher mortality (HR = 3·1, 95% Confidence Interval [CI] = 2·8-16·3) and RRT requirement (HR = 7·1, 95% CI = 5·7-311·6). This study provides epidemiologic data on TA-TMA and its impact on transplant outcomes. Increased awareness of the risk factors will enable providers to be vigilant of this uncommon but serious transplant complication. The results will also provide benchmarking for future study designs and comparisons.

Background : Male-specific late effects after hematopoietic cell transplantation (HCT) include genital chronic graft-versus-host disease (GvHD), hypogonadism, sexual dysfunction, infertility, and subsequent malignancies, such as prostate, penile, and testicular cancer. They may be closely intertwined and cause prolonged morbidity and decreased quality of life after HCT. Objective : Here, we provide a systematic review of male-specific late effects in a collaboration between transplant physicians, endocrinologists, urologists, dermatologists, and sexual health professionals through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research, and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Study Design : We utilized systematic review methodology to summarize incidence, risk factors, screening, prevention and treatment of these complications and provide consensus evidence-based recommendations for clinical practice and future research. Results : Most of the evidence regarding male GvHD is still based on limited data, precluding strong therapeutic recommendations. We therefore recommend to systematically screen for male genital GvHD regularly and report it to large registries to allow for a better understanding. Future research should also address treatment since little published evidence is available to date. Male-specific endocrine consequences of HCT include hypogonadism which may also affect bone health. Since the evidence is scarce, current recommendations for hormone substitution and/or bone health treatment are based on similar principles as for the general population. Following HCT, sexual health decreases and this topic should be addressed at regular intervals. Future studies should focus on interventional strategies to address sexual dysfunction. Infertility remains prevalent in patients having undergone myeloablative conditioning, which warrants offering sperm preservation in all HCT candidates. Most studies on fertility rely on descriptive registry analysis and surveys, hence the importance of reporting post-HCT conception data to large registries. Although the quality of evidence is low, the development of cancer in male genital organs does not seem more prevalent than in the general population; however, subsequent malignancies in general seem to be more prevalent in males than females, and special attention should be given to skin and oral mucosa. Conclusion : Male-specific late effects, probably more under-reported than female-specific complications, should be systematically considered during the regular follow-up visits of male survivors who have undergone HCT. Care of patients with male-specific late effects warrants close collaboration between transplant physicians and specialists from other involved disciplines. Future research should be directed towards better data collection on male-specific late effects and on studies about the interrelationship between these late effects, to allow the development of evidence based effective management practices.

Key Points CIBMTR prognostic score predicts PFS and OS of patients with DLBCL receiving axicabtagene ciloleucel treatment after a prior autoHCT failure.CIBMTR high/very high-risk score marks an adverse risk cohort where novel immunotherapy or relapse prevention approaches are warranted., Visual Abstract, Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR)-T cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto)HCT. Although the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis, we report outcomes of patients with DLBCL (≥18 years) undergoing a reduced intensity alloHCT or CAR-T therapy with axicabtagene ciloleucel during 2012 to 2019 after a prior auto-HCT failure and apply the CIBMTR prognostic model to CAR-T recipients. A total of 584 patients were included. The 1-year relapse, nonrelapse mortality, overall survival (OS), and progression-free survival for CAR-T treatment after autoHCT failure were 39.5%, 4.8%, 73.4%, and 55.7%, respectively. The corresponding rates in the alloHCT cohort were 26.2%, 20.0%, 65.6%, and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3%, respectively (P = .002). The corresponding rates for low-, intermediate-, and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (P < .001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in a subset of patients with DLBCL relapsing after a prior autoHCT. The simple CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high-risk patients.

BACKGROUND: Bortezomib-based triplet regimens, specifically bortezomib, lenalidomide and dexamethasone (VRD) and bortezomib, cyclophosphamide and dexamethasone (VCD) are the two most common induction regimens used in transplant-eligible patients with NDMM, with conflicting data on comparative efficacy and outcomes in this population. OBJECTIVES: We compared long-term outcomes of multiple myeloma (MM) patients receiving VRD vs. VCD induction prior to autologous stem cell transplant (ASCT). STUDY DESIGN: Patients registered with Center for International Blood and Marrow Transplant Registry were included if they underwent ASCT for MM from 01/2013 to 12/2018 within 6 months of diagnosis, received VRD or VCD induction and achieved pre-transplant ≥ partial response. Of 1,135 patients, 914 received VRD and 221 received VCD. RESULTS: Patients receiving VCD were more likely to have renal impairment and ISS stage III disease and less likely to receive full dose melphalan (200 mg/m(2)) conditioning (69% vs 80%, p

Reduced-intensity conditioning (RIC) regimens developed to extend the use of allogeneic hematopoietic stem cell transplantation (HSCT) to older patients have resulted in encouraging outcomes. We aimed to compare the 2 most commonly used RIC regimens, i.v. fludarabine with busulfan (FluBu) and fludarabine with melphalan (FluMel), in patients with myelodysplastic syndrome (MDS). Through the Center for International Blood and Marrow Transplant Research (CIBMTR), we identified 1045 MDS patients age >= 60 years who underwent first HSCT with a matched related or matched (8/8) unrelated donor using an RIC regimen. The CIBMTR's definition of RIC was used: a regimen that incorporated an i.v. busulfan total dose

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care.

We analyzed late fatal infections (LFIs) in allogeneic stem cell transplantation (HCT) recipients reported to the Center for International Blood and Marrow Transplant Research. We analyzed the incidence, infection types, and risk factors contributing to LFI in 10,336 adult and 5088 pediatric subjects surviving for ≥2 years after first HCT without relapse. Among 2245 adult and 377 pediatric patients who died, infections were a primary or contributory cause of death in 687 (31%) and 110 (29%), respectively. At 12 years post-HCT, the cumulative incidence of LFIs was 6.4% (95% confidence interval [CI], 5.8% to 7.0%) in adults, compared with 1.8% (95% CI, 1.4% to 2.3%) in pediatric subjects; P < .001). In adults, the 2 most significant risks for developing LFI were increasing age (20 to 39, 40 to 54, and ≥55 years versus 18 to 19 years) with hazard ratios (HRs) of 3.12 (95% CI, 1.33 to 7.32), 3.86 (95% CI, 1.66 to 8.95), and 5.49 (95% CI, 2.32 to 12.99) and a history of chronic graft-versus-host disease GVHD (cGVHD) with ongoing immunosuppression at 2 years post-HCT compared with no history of GVHD with (HR, 3.87; 95% CI, 2.59 to 5.78). In pediatric subjects, the 3 most significant risks for developing LFI were a history of cGVHD with ongoing immunosuppression (HR, 9.49; 95% CI, 4.39 to 20.51) or without ongoing immunosuppression (HR, 2.7; 95% CI, 1.05 to 7.43) at 2 years post-HCT compared with no history of GVHD, diagnosis of inherited abnormalities of erythrocyte function compared with diagnosis of acute myelogenous leukemia (HR, 2.30; 95% CI, 1.19 to 4.42), and age >10 years (HR, 1.92; 95% CI, 1.15 to 3.2). This study emphasizes the importance of continued vigilance for late infections after HCT and institution of support strategies aimed at decreasing the risk of cGVHD. ispartof: BIOLOGY OF BLOOD AND MARROW TRANSPLANTATION vol:25 issue:2 pages:362-368 ispartof: location:United States status: published

Patients who develop therapy-related myeloid neoplasm, either myelodysplastic syndrome (t-MDS) or acute myelogenous leukemia (t-AML), have a poor prognosis. An earlier Center for International Blood and Marrow Transplant Research (CIBMTR) analysis of 868 allogeneic hematopoietic cell transplantations (allo-HCTs) performed between 1990 and 2004 showed a 5-year overall survival (OS) and disease-free survival (DFS) of 22% and 21%, respectively. Modern supportive care, graft-versus-host disease prophylaxis, and reduced-intensity conditioning (RIC) regimens have led to improved outcomes. Therefore, the CIBMTR analyzed 1531 allo-HCTs performed in adults with t-MDS (n = 759) or t-AML (n = 772) between and 2000 and 2014. The median age was 59 years (range, 18 to 74 years) for the patients with t-MDS and 52 years (range, 18 to 77 years) for those with tAML. Twenty-four percent of patients with t-MDS and 11% of those with t-AML had undergone a previous autologous (auto-) HCT. A myeloablative conditioning (MAC) regimen was used in 49% of patients with t-MDS and 61% of patients with t-AML. Nonrelapse mortality at 5 years was 34% (95% confidence interval [CI], 30% to 37%) for patients with t-MDS and 34% (95% CI, 30% to 37%) for those with t-AML. Relapse rates at 5 years in the 2 groups were 46% (95% CI, 43% to 50%) and 43% (95% CI, 40% to 47%). Five-year OS and DFS were 27% (95% CI, 23% to 31%) and 19% (95% CI, 16% to 23%), respectively, for patients with t-MDS and 25% (95% CI, 22% to 28%) and 23% (95% CI, 20% to 26%), respectively, for those with t-AML. In multivariate analysis, OS and DFS were significantly better in young patients with low-risk t-MDS and those with t-AML undergoing HCT with MAC while in first complete remission, but worse for those with previous auto-HCT, higher-risk cytogenetics or Revised International Prognostic Scoring System score, and a partially matched unrelated donor. Relapse remains the major cause of treatment failure, with little improvement seen over the past 2 decades. These data mandate caution when recommending allo-HCT in these conditions and indicate the need for more effective antineoplastic approaches before and after allo-HCT. (C) 2021 Published by Elsevier Inc. on behalf of The American Society for Transplantation and Cellular Therapy.

We examined the risk of subsequent neoplasms (SNs) and late mortality in children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) for nonmalignant diseases (NMDs). We included 6028 patients (median age, 6 years; interquartile range, 1-11; range

BACKGROUND Upfront autologous hematopoietic stem cell transplantation (AHCT) remains an important therapy in the management of patients with multiple myeloma (MM), a disease of older adults. METHODS The authors investigated the outcomes of AHCT in patients with MM who were aged ≥70 years. The Center for International Blood and Marrow Transplant Research (CIBMTR) database registered 15,999 patients with MM in the United States within 12 months of diagnosis during 2013 through 2017; a total of 2092 patients were aged ≥70 years. Nonrecurrence mortality (NRM), disease recurrence and/or progression (relapse; REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models with age at transplantation as the main effect. Because of the large sample size, a P value

Histoplasma capsulatum infection is a rare complication in the allogeneic stem cell transplant patients. Minimal guidance exists on how to appropriately manage histoplasmosis in these patients. We report a patient who developed Histoplasma pneumonia while receiving voriconazole prophylaxis at a therapeutic trough level. The patient experienced significant clinical improvement after initiation of itraconazole pharmacotherapy. We recommend a lower threshold for evaluation for histoplasmosis in allogeneic hematopoietic stem cell transplant recipients who live in endemic regions, regardless of their antifungal prophylactic regimen.

Allogeneic hematopoietic cell transplantation (HCT) is the only curative therapy for myelofibrosis (MF). In this large multicenter retrospective study, overall survival (OS) in MF patients treated with allogeneic HCT (551 patients) and without HCT (non-HCT) (1377 patients) was analyzed with Cox proportional hazards model. Survival analysis stratified by the Dynamic International Prognostic Scoring System (DIPSS) revealed that the first year of treatment arm assignment, due to upfront risk of transplant-related mortality (TRM), HCT was associated with inferior OS compared with non-HCT (non-HCT vs HCT: DIPSS intermediate 1 [Int-1]: hazard ratio [HR] = 0.26, P < .0001; DIPSS-Int-2 and higher: HR, 0.39, P < .0001). Similarly, in the DIPSS low-risk MF group, due to upfront TRM risk, OS was superior with non-HCT therapies compared with HCT in the first-year post treatment arm assignment (HR, 0.16, P = .006). However, after 1 year, OS was not significantly different (HR, 1.38, P = .451). Beyond 1 year of treatment arm assignment, an OS advantage with HCT therapy in Int-1 and higher DIPSS score patients was observed (non-HCT vs HCT: DIPSS-Int-1: HR, 2.64, P < .0001; DIPSS-Int-2 and higher: HR, 2.55, P < .0001). In conclusion, long-term OS advantage with HCT was observed for patients with Int-1 or higher risk MF, but at the cost of early TRM. The magnitude of OS benefit with HCT increased as DIPSS risk score increased and became apparent with longer follow-up.

T-cell acute lymphoblastic leukemia (T-ALL) is an uncommon, yet aggressive leukemia that accounts for approximately one-fourth of acute lymphoblastic leukemia (ALL) cases. CDKN2A/CDKN2B and NOTCH1 are the most common mutated genes in T-ALL. Children and young adults are treated with pediatric intensive regimens and have superior outcomes compared to older adults. In children and young adults, Nelarabine added to frontline chemotherapy improves outcomes and end of consolidation measurable residual disease has emerged as the most valuable prognostic marker. While outcomes for de-novo disease are steadily improving, patients with relapsed and refractory T-ALL fare poorly. Newer targeted therapies are being studied in large clinical trials and have the potential to further improve outcomes. The role of allogeneic stem cell transplant (HSCT) is evolving due to the increased use of pediatric-inspired regimens and MRD monitoring. In this review we will discuss the biology, treatment, and outcomes in pediatric and adult T-ALL.

Relapsed or refractory acute myeloid leukemia (R/R AML) has a poor prognosis and is best treated with salvage chemotherapy as a bridge to allogeneic stem cell transplant (alloSCT). However, the optimal salvage therapy remains unknown. Here we compared two salvage regimens; mitoxantrone, etoposide, and cytarabine (MEC) and mitoxantrone and high-dose Ara-C (Ara-C couplets). We analyzed 155 patients treated at three academic institutions between 1998 and 2017; 87 patients received MEC and 68 received Ara-C couplets. The primary endpoint was overall response (OR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and nonhematologic toxicities, and success in proceeding to alloSCT. Baseline characteristics of the cohorts were well matched, though patients receiving Ara-C couplets had more co-morbidities (48.5% vs 33%; P = .07). OR was achieved in 43.7% of MEC and 54.4% of Ara-C couplets patients (P = .10). Ara-C couplets patients also trended towards a longer OS and PFS, more frequently proceeded to alloSCT (31% vs 54.4%; P = .003), and experienced less febrile neutropenia (94% vs 72%; P < .001) and grade 3/4 gastrointestinal toxicities (17.2% vs 2.94%; P = .005). No significant differences in other toxicities or median duration of hospitalization were noted. This is the first multi-institutional study directly comparing these regimens in a racially diverse population of R/R AML patients. Although these regimens have equivalent efficacy in terms of achieving OR, Ara-C couplets use is associated with significant reductions in toxicities, suggesting it should be used more frequently in these patients.

We evaluated for the first time, to our knowledge, adverse health outcomes (AHOs) among US testicular cancer survivors (TCS) given chemotherapy (n = 381) vs surgery-only patients (n = 98) managed at a single institution, accounting for non-treatment-related risk factors to delineate chemotherapy’s impact. Chemotherapy consisted largely of bleomycin-etoposide-cisplatin (BEP) administered in three or four cycles (BEPx3, n = 235; BEPx4, n = 82). Incidence of at least 3 AHOs was lowest in surgery-only TCS and increased with BEPx3, BEPx4, and other cisplatin-based regimens (12.2%, 40.8%, 52.5%, 54.8%; P

The curative potential of autologous hematopoietic cell transplantation (autoHCT) for male germ cell tumors (GCTs) is well established. The optimal timing and number (single transplant [ST] versus tandem transplants [TT] versus triple transplants) of autoHCT are controversial, with wide practice variations. We examined survival trends among 2395 recipients of autoHCT for male GCTs between 1990 and 2015 reported to the Center for International Blood and Marrow Transplant Research. Trends and outcomes were analyzed by year of transplantation for intervals 1990 to 1994 (N = 288), 1995 to 1999 (N = 351), 2000 to 2004 (N = 376), 2005 to 2009 (N = 509), and 2010 to 2015 (N = 871). Multivariate analysis was restricted to the subset from 2000 to 2015 with research-level data (n = 267). The median duration of follow-up was 51 months. The median age at autoHCT was 31 years; 633 patients (26%) had primary extragonadal GCT, and 1167 (49%) underwent TT. The 3-year progression-free (PFS) and overall survival (OS) improved from 24% (95% confidence interval [CI], 18% to 31%) and 35% (95% CI, 29% to 40%), respectively, in 1990 to 1994 to 47% (95% CI, 43% to 50%) and 54% (95% CI, 50% to 57%), respectively, in 2010 to 2015 (P < .0001). TT recipients were more likely than ST recipients to undergo autoHCT as first salvage treatment. The proportion of TTs increased from 38% of all autoHCTs in 2000 to 2004 to 77% in 2010 to 2015. Nonseminoma histology, residual disease at autoHCT, >1 line of pretransplantation chemotherapy, and ST versus TT were associated with inferior PFS and OS. Post-transplantation survival has improved significantly over time for relapsed/refractory male GCT and is associated with the increased use of TTs (compared with STs) and performance of autoHCT earlier in the disease course.

Opana ER (oxymorphone) is an opioid drug available throughout the United States, and intravenous abuse of the crushed oral formulation has been associated with drug-induced thrombotic microangiopathy. In this abstract, we describe two young patients who lived together and used Opana ER intravenously. Both presented with microangiopathic hemolytic anemia that mimicked thrombotic thrombocytopenic purpura (TTP). Treating this condition poses a clinical challenge, as it is difficult to distinguish it from TTP. The role for plasma exchange is not clear but can be used while awaiting the results of the ADAMTS-13 activity, but ultimately supportive care with drug discontinuation is the recommended therapy of choice. Patients should be counseled against Opana ER’s intravenous use, and users should be offered drug rehabilitation therapy.

e17054 Background: HDCT plus PBSCT is effective salvage therapy for relapsed mGCT but has potential toxicity. Historically, age ≥ 40 years has been associated with greater toxicity and worse outcomes. Methods: 445 consecutive pts with relapsed mGCT were treated with HDCT and PBSCT with tandem cycles at Indiana University from between 2004-2017 per our institutional regimen ( N Engl J Med 2007; 357:340-8). Kaplan-Meier methods and log-rank tests were used for progression free survival (PFS) analysis. Results: 329 pts were age < 40 while 116 pts were age≥40 and HDCT was being used as 2nd line in 85% and 79%, respectively. Median follow-up time was 42.5 months (range 0.3-173.4). Pulmonary metastasis was more frequent in the age < 40 group (66% vs. 41%, P < 0.001). Patients age≥40 were more likely to have seminoma (45% vs. 14%, P < 0.001), were more likely not platinum refractory (80% vs. 63%, P = 0.0010), and were less likely to complete 2 planned tandem cycles of HDCT (86% vs. 93%, P = 0.03). Grade 3 or higher toxicities were similar between either cohort, except for greater pulmonary toxicity in age≥40 group (8% vs. 2%, P = 0.02). Treatment-related mortality was similar between both age groups: 10 patients (3%) in age < 40 and 4 patients (3.5%) in age≥40 group died from complications of HDCT. 2-year PFS for age < 40 vs. age ≥ 40 was 58.7% vs. 59.6% (P = 0.76) and 2-year OS was 63.9% vs. 61.5% (P = 0.93). When evaluating patients with pure seminoma: 2- year OS for age < 40 vs. 40-50 vs. ≥ 50 was 100% vs 90.3%, vs 81.4%, respectively (P = 0.09). For patients with non-seminoma: 2-year OS was 58.1% vs. 37.1% vs. 54.2%, respectively (P = 0.01). In multivariable analysis for PFS: significant factors predicting worse outcomes included platinum refractory disease (HR = 1.55, P = 0.03), primary mediastinal non-seminoma (HR = 2.41, P = 0.03), not completing 2 cycles of HDCT (HR = 2.47, P = 0.01), and hCG > 1000 at initiation of HDCT (HR = 1.92, P < 0.001). Age was not a significant factor predicting worse outcomes. Conclusions: HDCT plus PBSCT is effective salvage therapy in pts age≥40 with relapsed mGCT. Patients age > 40 experience similar rates of toxicity and treatment-related mortality as those < 40 years of age.

e17061 Background: About 40% of patients with relapsed GCT will progress after HDCT and PBSCT and are generally incurable with further standard dose chemotherapy. We previously evaluated standard dose cisplatin combination chemotherapy in 15 patients following progression from HDCT and observed only a single brief PR ( JCO 18(6), 1181-1186.). We report results of non-platinum standard-dose chemotherapy regimens in refractory mGCT. Methods: Pts with mGCT who progressed after HDCT+PBSCT at Indiana University from 2004-2019 were evaluated. Kaplan-Meier methods and log-rank tests were used to analyze PFS and OS for the regimen directly following HDCT. Results: 78 pts with refractory mGCT were reviewed. 64 pts. (82%) received paclitaxel+gemcitabine (TG), 10 pts. (13%) received daily oral etoposide (E), and 4 pts. (5%) received oxaliplatin-based (O) regimens (oxaliplatin+gemcitabine or oxaliplatin+bevacizumab). Median age was 29 (range, 16-57). Primary site was testis in 62, retroperitoneum in 6, mediastinum in 9. Metastatic sites included retroperitoneal LNs (62), pulmonary (58), liver (23), bone (6), and brain (21). IGCCCG risk was good in 16, intermediate in 5, and poor in 57. HDCT was utilized as 2nd line setting in 72 pts, and ≥3rd line in 6 pts. Median time from HDCT to progression was 4 months (upper limit 16.6 months). PS and OS data is shown in the table, with superior outcomes in TG compared to O and E (p < 0.001). Maintenance oral etoposide after HDCT was administered in 44% (n = 28) of all patients who later progressed and received TG. Among 12 patients (19%) with 12-month PFS on TG, the median overall PFS was 18.3 months with 2 patients alive at the time of last follow-up. The primary site was testis in 11 patients, 67% (n = 8) were platinum refractory, and 83% (n = 10) were IGCCCG poor risk. 10 patients achieved a PR to TG, and two patients achieved CR. Conclusions: Salvage standard-dose chemotherapy with paclitaxel+gemcitabine after progression on HDCT is superior to oral etoposide or oxaliplatin-based regimens and should be the preferred regimen in patients with refractory mGCT. [Table: see text]

The Revised International Staging System (R-ISS) and the International Myeloma Working Group 2014 (IMWG 2014) are newer staging systems used to prognosticate multiple myeloma (MM) outcomes. We hypothesized that these would provide better prognostic differentiation for newly diagnosed multiple myeloma (MM) compared with ISS. We analyzed the Center for International Blood and Marrow Transplant Research database from 2008 to 2014 to compare the 3 systems (N = 628) among newly diagnosed MM patients undergoing upfront autologous hematopoietic cell transplantation (AHCT). The median follow-up of survivors was 48 (range, 3 to 99) months. The R-ISS provided the greatest differentiation between survival curves for each stage (for overall survival [OS], the differentiation was 1.74 using the R-ISS, 1.58 using ISS, and 1.60 using the IMWG 2014) . Univariate analyses at 3 years for OS showed R-ISS I at 88% (95% confidence interval [CI], 83% to 93%), II at 75% (95% CI, 70% to 80%), and III at 56% (95% CI, 3% to 69%; P < .001). An integrated Brier score function demonstrated the R-ISS had the best prediction for PFS, though all systems had similar prediction for OS. Among available systems, the R-ISS is the most optimal among available prognostic tools for newly diagnosed MM undergoing AHCT. We recommend that serum lactate dehydrogenase and cytogenetic data be performed on every MM patient at diagnosis to allow accurate prognostication.

Ocular graft-versus-host disease (GVHD) occurs in more than half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity, which affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplant physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD, regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed in this review. Ocular GVHD has at least three biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have found several novel pathogenic mechanisms, including renin angiotensin system and endoplasmic reticulum stress signaling that can be targeted by therapeutic agents. Many studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. Efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important for all health professionals taking care of HCT recipients to have adequate knowledge of ocular GVHD for optimal care.

Non-graft-versus-host disease (GVHD) ocular complications are generally uncommon after hematopoietic cell transplantation (HCT) but can cause prolonged morbidity affecting activities of daily living and quality of life. Here we provide an expert review of non-GVHD ocular complications in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Complications discussed in this review include cataracts, glaucoma, ocular infections, ocular involvement with malignancy, ischemic microvascular retinopathy, central retinal vein occlusion, retinal hemorrhage, retinal detachment and ocular toxicities associated with medications. We summarize the incidence, risk factors, screening, prevention, and treatment of individual complications and generate evidence-based recommendations. Baseline ocular evaluation before HCT should be considered in all patients who undergo HCT. Follow-up evaluations should be considered according to clinical signs and symptoms and risk factors. Better preventive strategies and treatments remain to be investigated for individual ocular complications after HCT. Both transplantation physicians and ophthalmologists should be knowledgeable about non-GVHD ocular complications and provide comprehensive collaborative team care.

Ocular graft-versus-host disease (GVHD) occurs in more than one-half of patients who develop chronic GVHD after allogeneic hematopoietic cell transplantation (HCT), causing prolonged morbidity that affects activities of daily living and quality of life. Here we provide an expert review of ocular GVHD in a collaboration between transplantation physicians and ophthalmologists through the Late Effects and Quality of Life Working Committee of the Center for International Blood and Marrow Transplant Research and the Transplant Complications Working Party of the European Society of Blood and Marrow Transplantation. Recent updates in ocular GVHD regarding pathophysiology, preclinical models, risk factors, prevention, screening, diagnosis, response criteria, evaluation measures, and treatment are discussed. Ocular GVHD involves at least 3 biological processes: lacrimal gland dysfunction, meibomian gland dysfunction, and corneoconjunctival inflammation. Preclinical models have identified several novel pathogenic mechanisms, including the renin angiotensin system and endoplasmic reticulum stress signaling, which can be targeted by therapeutic agents. Numerous studies have identified reliable tests for establishing diagnosis and response assessment of ocular GVHD. The efficacy of systemic and topical treatment for ocular GVHD is summarized. It is important that all health professionals caring for HCT recipients have adequate knowledge of ocular GVHD to provide optimal care. ispartof: Biol Blood Marrow Transplant vol:25 issue:2 pages:e46-e54 ispartof: location:United States status: published

Early treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high-risk group of patients with an expected 5-year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.This study compared autologous hematopoietic stem cell transplantation (auto-HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo-HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto-HCT or allo-HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression-free survival, relapse, and nonrelapse mortality (NRM).Four hundred forty FL patients had ETF (auto-HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow-up of 69 to 73 months, the adjusted probability of 5-year OS was significantly higher after auto-HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5-year adjusted probability of NRM was significantly lower for auto-HCT (5%) versus MSD (17%) or MUD HCT (33%; P .0001). The 5-year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto-HCT (58%; P .0001).Patients with high-risk FL, as defined by ETF, undergoing auto-HCT for FL have low NRM and a promising 5-year OS rate (70%). MSD HCT has lower relapse rates than auto-HCT but similar OS. Cancer 2018;124:2541-51. © 2018 American Cancer Society.

Background: HIV infection is the strongest of all known risk factors for the development of tuberculosis. Tuberculosis is the most common opportunistic infection and the number one cause of death in HIV/AIDS patients in developing countries. Materials and Methods: The aim of this study is to assess and compare the outcome of pulmonary tuberculosis in HIV-seropositive and HIV-seronegative patients. This was cross-sectional, observational and prospective study conducted at tertiary care center in western Maharashtra from May 2010 to April 2012. A total 50, HIV-seronegative patients and 50 HIV-seropositive patients of both genders, with pulmonary tuberculosis fulfilling inclusion criterion (age > 18 years, newly detected pulmonary tuberculosis) were included in present cross-sectional, observational, prospective and comparative study. Results: Of the total 50 HIV-seropositive patients, 36 (72%) males were newly detected pulmonary tuberculosis (PTB) with mean age of 40.61 ± 8.74 years and 14 (28%) were females with mean age 37.72 ± 9.54 years. Of total 50 patients amongst HIV seronegative-group patients with PTB, 29 (58%) were males with mean age of 42.44 ± 5.79 years and 21 (42%) were females with mean age of 38.9 ± 7.91 years. A total 10/50 (20%) patients in HIV-seropositive group and 3/50 (6%) HIV-seronegative group had evidence of jaundice. There was a statistical difference between development of jaundices in HIV and HIV-seronegative group ['P' = 0.037]. Total 9/36 (25%) male patients and 2/14 (14.28%) females patients died in HIV-seropositive group with no death recorded amongst in HIV-seronegative groups with high mortality in HIV-seropositive group ['P' < 0.0001]. Total 4 male and 4 female patients had inflammatory response syndrome (IRIS). Total 40/50 (80%) patients were sputum negative at the end of 6 th month (2 nd follow-up) among HIV-seropositive group. Total 49/50 (98%) become a sputum negative at the end of 2 nd follow-up, 6 month among HIV-seronegative group there was a statistically significant difference between two group ['P' = 0.021]. Total 10/50 (20%) and 1/50 (2%) patients were diagnosed with multidrug resistant tuberculosis (MDR-TB) among HIV-seropositive group and HIV-seronegative group, respectively ['P' = 0.002]. There was high prevalence of middle and lower lobe lesions and bilateral extensive pulmonary tuberculosis (BEPT) in patients with HIV-seropositive group patients and upper lobe, miliary shadow and cavitary lesions in HIV-seronegative group patients ['P' < 0.02]. The cavitary lesions were significantly low in HIV-seropositive group with low CD+4 counts. Duration of stay was significantly more in HIV-seropositive group compared with HIV seronegative- seropositive group ['P' < 0.01]. Conclusions: We found high prevalence of MDR-TB pulmonary tuberculosis in HIV-seropositive patients. Mortality was significantly high in HIV-seropositive patients than HIV-seronegative patients. Jaundice was more prevalent in HIV-seropositive patients than HIV-seronegative patients. There was high prevalence of middle and lower lobe lesions and BEPT in patients with HIV-seropositive group patients and upper lobe, miliary shadow and cavitary lesions in HIV-seronegative group patients. The cavitary lesions were significantly low in HIV-seropositive group with low CD+4 counts. Duration of stay was significantly more in HIV-seropositive group compared with HIV-seronegative group. Success rate of directly observed treatment short-course was less (80%) in HIV-seropositive group.

Background: Non-communicable diseases like DM2, cardiac diseases, chronic respiratory disorders, brain disorders like stroke have created a havoc in developing countries, especially India which harbors 2nd largest population in the world. The present study was planned in this area to capture the data regarding epidemiology, risk factors of DM2, and use this information to plan health program to formulate effective preventive measures, including raising general awareness about the disease in that geographical area.Methods: The present cross sectional study was carried out in population of Karad area of Satara district in Maharashtra state. The study duration was of 1 year, from 1st February 2018 to 1st February 2019.Results: Out of total 1100 study population in the present study, 99 (9%) were diagnosed as diabetics (DM2) while 1001 were normal/non-diabetics. Majority of the diabetic patients were of the age group 41 to 50 years. Females (47%) showed slightly more prevalence of diabetes as compared to males (53%). Majority of the diabetic patients were having sedentary lifestyle, which consisted of 69 patients (70%), which was statistically significant, as compared to non-diabetic group.Conclusion: Thus, findings of the present study amply clarifies that DM2 is on longer a disease of urban population. Its prevalence is increasing in rural population, as well. Lack of awareness, sedentary lifestyle, faulty dietary habits, etc. are some of the reasons for such high prevalence.

Background: Venomous snake bite is a common and frequently devastating environmental and occupational disease, especially in rural areas of Maharashtra India. Aims & Objectives: To determine the clinical profi le and outcome of snakebite cases in rural western Maharashtra. Material & Methods: This was a retrospective study conducted over one year period (January 2009 to December 2009) at a tertiary health care centre in Maharashtra. Results: Out of 167 admitted snakebite 103 (61.67%) were complicated snake bites. Total 88 (85.43%) patients were with vasculo-toxic snake bite. Total 15 (14.56%) patients were with neuroparalytic snakebite. Total 35 (39.77%) patients out of 88 with vasculotoxic snakebite developed local cellulitis requiring fasciotomy and or debridement, 17 (19.31%) patients had clinical and laboratory parameters favoring DIC. Total 12 (13.63%) patients had ARF, one developed AMI and one developed cortical venous sinus thrombosis (CVT). Out of 88 patients with vasculotoxic snakebite 2 died with case fatality rate of 2.27% (2/88). Out of 15 patients with neuroparalytic snake bite 13 (86.66%) required artifi cial ventilatory support and one patient developed delayed peripheral neuropathy. Overall mortality was 1.94% (2/103). The needle to ASV time was positively correlated with duration of hospital admission, complications and mortality ('p' < 0.02). Conclusions: Snakebite is a common life-threatening emergency in the study area. Delay in hospitalization is associated with poor prognosis and increased mortality rate due to consumptive coagulopathy, renal failure and respiratory failure. Unusual complications like AMI, CVT and delayed peripheral neuropathy were observed in present study.

Background: Relapsed or refractory acute myeloid leukemia (R/R AML) portends a poor prognosis, thus salvage chemotherapy is commonly used as a bridge to HSCT, however the optimal salvage regimen remains unknown. For decades cytarabine (Ara-C) has served as the backbone of regimens frequently used in the R/R setting. MEC is among the most studied regimens for R/R AML; up to 66% of patients achieve complete remission (CR), with a median survival of 36 weeks (Arcese et al., J Clin Oncol. 1991). The Ara-C couplets regimen was shown to have a similar overall response rate (ORR) of 55%, in a single study (Larson et al., Leukemia & Lymphoma. 2012). Currently, there are no studies directly comparing these regimens. Here, in a multi-institution retrospective analysis we assessed the efficacy and toxicity of MEC and Ara-C couplets therapy. Methods: We analyzed the records of 136 patients treated between 1998 and 2017. There were 87 patients (15 from University of Illinois and 72 from Indiana University) treated with MEC (mitoxantrone 8 mg/m2 IV, etoposide 80 mg/m2 IV and Ara-C 1 g/m2 x 5 days) and 49 patients (36 from University of Illinois and 13 from University of Chicago) treated with Ara-C couplets (mitoxantrone 30 mg/m2 daily and Ara-C dosed at 2 g/m2 twice daily or 3 g/m2 daily; both drugs given on days 1 and 5). The primary endpoint was comparison of response rates. Secondary endpoints included progression free survival (PFS), overall survival (OS), duration of hospitalization, hematologic and non-hematologic toxicities, and success in proceeding to HCT. Results: The median age of the MEC group was 52 years (yr) (range: 20-75 yr) vs 55 yr (22-75 yr) in the Ara-C couplets group. There were significantly more white patients in the MEC group (72% vs 41%; p = 0.004). The incidence of unfavorable cytogenetics was similar between groups; 32 in the MEC group (36.8%) and 19 in the Ara-C couplets group (38.7%). High-risk patients, as defined by Charlson Comorbidity Index (CCI) ≥4, comprised 29 of 87 (33.3%) of MEC, and 26 of 49 (53.1%) of Ara-C couplets patients (p = 0.03). Time from initial diagnosis to diagnosis of R/R AML was similar between groups, 303 days (MEC) and 306 days, respectively (p = 0.10). CR or CRi (ORR) was achieved in 44% of MEC, and 55% of the Ara-C couplets patients. OS was 159 days and 186 days, respectively (p = 0.055). PFS was 66 days in the MEC group and 113 days in the Ara-C couplets group (p = 0.56). In total, 27 (31%) of the MEC patients and 24 (49%) Ara-C couplets patients underwent HCT (p = 0.04). Within the MEC group, the median number of days to ANC and platelet recovery was 34 days and 35 days, respectively. ANC and platelet recovery was slightly longer within the Ara-C couplets group, at 41 days and 55 days, respectively (p = 0.02 for platelet recovery). The median duration of hospitalization was similar, 29 days for MEC and 30 days for Ara-C couplets. The most common adverse event was febrile neutropenia (FN), occurring in 93% of the MEC and 78% of the Ara-C couplets patients (p = 0.01). Notably, grade 3/4 GI toxicity occurred in 15 MEC (17.2%) and one (2.0%) of the Ara-C couplets patients (p = 0.01). There were no significant differences between groups in terms of pulmonary, liver, renal, cardiac or neurologic toxicities. Conclusions: This is the first large multi-institutional retrospective study directly comparing salvage regimens in a racially diverse population of R/R AML patients. While matched for a number of variables (including the incidence of unfavorable cytogenetics), patients receiving Ara-C couplets did have a significantly higher CCI. Despite this, use of the Ara-C couplets regimen resulted in improved ORR, significantly improved efficacy as a bridge to HCT, and led to a significant comparative decrease in the incidence of FN and grade 3/4 GI toxicities. Our retrospective analysis suggests that this regimen should be considered as an effective, safe salvage regimen in this population. Disclosures Patel: Janssen: Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Khan:Teva: Speakers Bureau. Stock:Jazz Pharmaceuticals: Consultancy. Odenike:ABBVIE: Honoraria, Research Funding; Pfizer: 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; CTI/Baxalta: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Dava Oncology: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Oncotherapy Science: Research Funding; Agios: Research Funding; Celgene: Research Funding; NS Pharma: Research Funding; Janssen: Research Funding; Astex: Research Funding; Gilead Sciences: Research Funding.

Background: The optimal setting to treat AYA patients remains a complex decision involving access to different treatment regimens, clinical trial availability, and appropriate psychosocial support. There are data to support that AYA patients with acute lymphoblastic leukemia (ALL) have better outcomes and improved overall survival when treated on pediatric inspired treatment protocols. However, limited data exist for similar patients with AML. We, therefore, sought to assess the variation in outcomes between AML patients within the AYA population treated in our pediatric setting versus adult setting. Methods: A retrospective review of patients with newly diagnosed AML aged 17-25 years old (n=33) treated at either the Indiana University Simon Cancer Center (n=20) or Riley Hospital for Children at Indiana University Health (n=13) between 2006 and 2018 was completed. All patients in the adult setting received standard induction therapy with the 7+3 (standard-dose cytarabine, anthracycline) regimen, while patients in the pediatric setting received an ADE (daunorubicin, cytarabine, etoposide) backbone +/- investigational agents per clinical trial protocols. Data were analyzed with t-tests using IBM SPSS v25 software. This study was approved by the Indiana University Institutional Review Board. Results: Median age was 23 years in patients treated in the adult setting (range 19-25) compared with 17 years (range 17-20) in the pediatric setting. As per the most recent NCCN risk classification for AML, patients in the adult setting were classified as 55% poor risk, 35% intermediate risk, and 10% favorable risk; in the pediatric setting, risk classification was 15% poor risk, 62% intermediate risk, and 23% favorable risk. The incidence of FLT3 mutations was n=4 (20%) in the adult setting and none in the pediatric setting. Clinical trial enrollment was markedly lower in the adult setting with no patients enrolled compared with 54% (7/13) enrolled in the pediatric setting. Complete response (CR) was achieved in 85% of patients treated in the adult setting, but only 62% of patients treated in the pediatric setting. Relapse post induction was higher in the pediatric setting (n=6, 46%) compared to the adult setting (n=5, 40%), and median time to relapse was shorter in the pediatric setting (275 days vs. 344 days). During induction, no statistically significant differences in toxicities were found as measured by ICU interventions (dialysis, mechanical ventilation/NIPPV, and/or use of vasopressors) and identified infections (bacteremia, pneumonia, and/or clostridium difficile). Clostridium difficile infections were increased in the adult setting (15% vs. 0%), but identified bacteremia was higher in the pediatric setting (38% vs. 20%). The median time to allogeneic stem cell transplantation in the adult setting was 117.5 days compared to a median of 223 days seen in the pediatric setting. Incidence of relapse post stem cell transplantation was higher in the adult setting (36% vs. 17%). Proportion of overall survival was 50% (n=10) in the adult setting and 28% (n=8) in the pediatric setting. The highest mortality was seen in poor-risk patients (90%) in the adult setting and intermediate risk patients (62.5%) in the pediatric setting. A trend was seen towards improved overall survival in the adult setting with median overall survival of 739.5 days in the adult setting compared to 415 days in the pediatric setting (p=0.11). In both settings, patients that proceeded to stem cell transplantation had conferred survival benefit: median 1128 vs. 414.5 days in the adult setting and median 530.5 vs. 486.5 days in the pediatric setting. Conclusion: Despite having a higher risk population and lower clinical trial enrollment, we found a trend towards higher complete response rate after induction, reduced relapse rate after induction, shorter time to transplant, longer time to relapse post-transplant, improved survival in the transplant population, and improved median overall survival without a clear increase in toxicity in patients treated in our adult setting. This is in contrast to data in ALL, which suggests improved patient outcomes in AYA patients treated with pediatric based regimens. Our data is limited by a small sample size and a single institution experience. Larger, multicenter studies are needed to understand the optimal AML treatment strategy in the AYA population. Table. Table. Disclosures No relevant conflicts of interest to declare.

Pericardial effusion is frequently found in patients with hypothyroidism, but it is rarely associated with cardiac tamponade. Hypothyroidism complicated by cardiac tamponade is rarely referenced in the medical literature. Here we report an unusual case of a 45-year-old female, who presented with breathlessness and was found to have hypothyroidism with large pericardial effusion with cardiac tamponade. Treatment included an emergency pericardiocentesis followed by thyroxine hormone replacement.

e19035Background: 90Y-Ibritumomab tiuxetan (90Y-IT) as radioimmunotherapy in the treatment of B-cell non-Hodgkin lymphoma (NHL) has been approved for consolidation and salvage treatment of follicul...

Background: Leptospirosis is an emerging spirochetal zoonosis world wide. Leptospirosis is common zoonosis that is under reported and under diagnosed in India. The aim of this study was to study the clinical profile outcome and prognostic factors in human leptospirosis at tertiary care centre. Settings and Design: This was a retrospective study of leptospira positive patients who were admitted in tertiary care centre. The study was conducted in 2010, over a period of 6 month from July to December. Materials and Methods: All patients who presented with clinical features and tested IgM positive for leptospirosis were taken into the study and analyzed based on modified Faine's criteria. Results: Out of total 23 patients there were 21 males and 2 females, with mean age was 32 years. Maximum incidence of cases was found in month of July and August. Out of total 23 patients, 18 (78.26%) were farmers and 5 (21.73%) were laborers. Predominant complaints were fever, jaundice, myalgia, and headache. All 23 had positive results for IgM against leptospira. Liver function tests were deranged in 16 (69.56%) and renal functions were deranged in 12 (52.17%). Total 7 (30.43%) patients had Weil's syndrome and 7 (30.43%) had acute respiratory distress syndrome (ARDS). Total 7 (30.43%) patients had neuroleptospirosis, out of which 5 (21.73%) had aseptic meningitis, one had paraparesis secondary to lumbar radiculopathy and one had meningoencephalitis. Hyperkalemia was present in 6 (26.08%) patients, 7 (30.43%) patients had hypokalemia. Total 11 (47.82%) patients had metabolic acidosis (pH Conclusions: Leptospirosis was unexpectedly found to be positive in many of our patients who were having pyrexia with multiorgan dysfunction during the monsoons. Hepatic dysfunction, acute renal failure, ARDS, and neuroleptospirosis in decreasing frequency were the commonest complication. Daily dialysis, ventilatory support and intensive care management has definitely reduced morbidity and mortality associated with leptospirosis with multi-organ failure.