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Quality of the data was assessed as high. Background: Autologous haematopoietic stem cell transplantation AHSCT is a promising strategy for Multiple Sclerosis MS patients that do not respond to conventional treatments, but the mechanisms enabling clinical improvement of MS in transplant recipients are not fully understood.

We hypothesised that AHSCT induces a rebooting of thymic function, resulting in the re-development of a functional, tolerant immune system. A multicolour flow cytometry panel to optimally identify RTE's was performed on 10 patient samples at 0, 6, 12, 24 and 36 month timepoints, allowing us to track changes in thymic output longitudinally following AHSCT.

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DNA markers of thymic function - Sj:b TREC ratio was performed in the same cohort of patients, on the same bio-banked sample to enhance the validity of observed changes. Statistical analysis was performed with GraphPad Prism.

In patients where similar analysis was able to be performed at 36 months a trend to increased markers of thymic output was observed. Greater thymic output as determined by Sj:b TREC was observed at all timepoints in patients who had evidence of sustained disease remission as opposed to patients who experienced disease relapse. Previous studies have only demonstrated thymic activity at 12 months but this study confirms that thymic activity remains prominent at 24 and even 36 months.

This retrospective study assessed long-term outcomes of this strategy in patients treated for severe autoimmune diseases ADsreported to the EBMT registry. Methods: Among the total patients who received allogeneic HSCT betweenwe received detailed questionnaires on long-term outcomes from 64 patients.

The median age of patients at HSCT was All patients were refractory to previous immunosuppressive therapies median of 4 lines of treatments, rangeand eight of them received a previous autologous transplant. Serotherapy with ATG was given in 16 patients, while 30 patients received alemtuzumab. Results: Median follow-up was 67 months range 7. Toxicity profile was similar to allogeneic HSCT in other contexts. Cumulative incidence of chronic GvHD was Overall graft rejection rate was 4.

Seven secondary AD and one case of new malignancy lymphoma occurred. Seven cases of invasive fungal infection were reported one rgillosis and three candidiasis. Ten bacterial infections only 4 patients developed infection from Gram-negative bacteria and four pneumonia were observed.

At the last follow-up complete clinical response was obtained in Relapse incidence RI was Post-HSCT autoimmune disease specific treatment was required for 12 patients. In subgroup analysis among different diseases, the OS rates were similar between immune cytopenia and other ADs. Outcomes have improved in recent years.

Background: Systemic sclerosis SSc is a chronic autoimmune disease characterized by skin thickening and visceral involvement, leading to impairment of physical function, daily life activities and quality of life. Severe cases usually have poor prognosis, despite conventional immunosuppressive treatment. Autologous hematopoietic stem cell transplantation AHSCT has been investigated as treatment for patients with severe and rapidly progressive SSc and promotes reduction of skin thickening and at least stabilization of pulmonary involvement.

The aim of this study was to evaluate the impact of AHSCT on skin involvement, pulmonary function, functional capacity and quality of life QoL of SSc patients, and to evaluate if pulmonary function measurements correlate with the other evaluated variables.

Results: Twenty-seven patients were evaluated before and at 6 months after transplant, 22 of which were additionally evaluated at 12 months. No changes were observed in FVC after treatment. No significant correlation was observed between pulmonary function and the other evaluated variables mRSS, respiratory muscle strength, physical capacity and quality of life.

Although the pulmonary function remained stable after AHSCT, there was significant increase in the physical capacity and quality of life of patients. It is required to improve the results by analysis of long-term follow-up and late effects.

Several challenges identified in multidisciplinary collaboration for successful treatment as well as a problem of switching these patients to the adult healthcare. We aimed to create a model of organization of help for children with severe refractory multiple sclerosis based on multidisciplinary and multicenter approach.

Gender: females - 11, males - 4. All patients had severe refractory MS treated with corticosteroids, interferons, plasmapheresis and mitoxantron with negative results.

These patients presented signs of neuroinflammation. Mean baseline EDSS before the start of mobilization was 4. We analysed the incidence and nature of late effects in patients with at least one year of follow-up based on the standard protocol for late effects. Fertility preservation proposed for patients.

Technology of transfer patients to adult center for post-transplant observation was identified. Results: All patients survived.

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Eleven patients experienced culture negative fever, one patient - cystitis, and one patient had CMV reactivation within days of the transplant. Mean improvement of EDSS was 2. In-time transplanted patients improved better. Improvement confirmed by immunological data increasing of immune regulation index and T-regs in comparison with the baseline. Median follow-up period was 48 months months.

Four patients No onsets of secondary autoimmune disease and malignancies was seen. Cardiocascular late effects were seen in 6 patients and endocrine - in 3 patients all females. All these late effects were successfully treated. Patients after the age of 18 years old were transferred to partnering adult center. This center uses the same protocol for HSCT in adults and post-transplant observation.

Detailed scheme of transfer developed. Most of the patients did not experienced exacerbations. Late effects found in patients were successfully treated. We provide a best care for these patients in both childhood and adulthood by transferring them to adult center. Thus, a unique multicenter and multidisciplinary model of care for children with severe refractory MS was found. Background: Neuromyelitis optica spectrum disorder NMOSD is an inflammatory central nervous system disorder characterized, despite immunotherapy treatments, by life-long, severe, and disabling attacks of optic neuritis and myelitis.

The aim is to determine if autologous non-myeloablative hematopoietic stem cell transplantation could be an alternative treatment option. Unselected peripheral blood stem cells were infused on day 0. Cell killing activity was measured using a flow cytometry based complement assay.

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Ten patients are more than five years post-transplant. The SF quality of life total score improved from mean AQP4-IgG serostatus converted to negative in nine patients and complement activating and cell killing ability of patient serum was switched off. Conclusions: Prolonged drug-free remission with AQP4-IgG seroconversion to negative following non-myeloablative autologous HSCT warrants further investigation in larger randomized controlled trial.

The auto immune haemolytic anaemia AIHA is the most frequent of these complications in paediatrics and is difficult to treat. So far, there has been no nationwide post transplantation AIHA study. Data concerning patient, primary diagnosis, HSCT procedure, pre-transplant viral status, blood group compatibility, characteristics of cytopenia, delay transplant-cytopenia, graft vs host reaction.

Laboratory characteristics and therapies were analyzed as well as the response to first, second or third line treatments. The median age at HSCT was 4,9 years old 0,8. Average delay between transplantation and AIC was days The median follow-up after transplant was 35,8 months It's a rare but severe complication with multiple risk factors associated with a high mortality rate and no standardized therapy at this time. Further studies would allow us to understand the disease better in order to prevent its occurrence and treat it more efficiently.

In the last decade, several chimeric antigen receptor anti-CD19 CAR19 constructs have been developed. Methods: The first academic pilot clinical trial clinicaltrials. The primary objective of the study was safety, and secondary objectives were response rate and its duration progression-free survival.

Here we report an ated analysis of this trial. Of these, we performed lymphoapheresis to 34 and we processed the cells of 33, although for the moment we have only infused to 25 of them. These deaths were due to CRS 2 and pseudomembranous colitis 1and all happened in cohort 1. We had no cases of severe neurotoxicity, and grade II neurotoxicity was only seen in 2 patients. Of the 14 patients with active ALL at inclusion, 11 had enough follow-up for efficacy analysis, and all of them achieved a CR 9 of them with negative MRD.

With a median follow-up of 8. One NHL patient has not been evaluated yet and the other 2 patients did not respond and have died due to their lymphoma.

Conclusions: Treatment with ARI cells is effective with a response rate of Still, longer median follow-up and further patient inclusions are needed. Previous studies indicated higher CAR-T cell expansion in vivo achieved better remission. Results: As of the data cut-off date Nov 28th,17 patients, median age Patients had a median of 14 prior regimens range 4 to 24 Figure 1A. All the 17 patients were eligible for initial evaluation of early clinical response with a median observation period of 12 0.

Partial response 1 PR, 5. The disease progressed in 1 patient from PR by week 5 Figure 1B. One patient died of severe infection by Day 9. Expansion peaks were found between Day 6 to Day Cytokine release syndrome CRS was reported in all the 17 patients, including 2 with Grade 1, 4 with Grade 2 and 11 with Grade 3. No patient died of CRS complication.

These initial data provide strong evidence to support the further development of this anti-myeloma cellular immunotherapy. Here we hypothesized that antigen receptor engineering of hematopoietic stem cells would fundamentally impact lymphoid progenitor cell fate and as a consequence biological properties thereby allowing to generate an ubiquitously available lymphoid cell product for targeted immunotherapy across MHC barriers.

Methods: Murine hematopoietic stem cells were transduced with a broad panel of 1 st and 2 nd generation murine CARs containing different costimulatory domains and numbers of active immune receptor-based activation motifs ITAMs against CD19 in a lentiviral backbone and consecutively differentiated into lymphoid progenitors using the OP9-DL1 feeder layer system.

Resulting products were comparatively assessed in vitro and in vivo FACS, functional assays, microarray gene transcript analysis, western blotting, timely controlled transgene expression, leukemia challenge experiments, in vivo lymphoid depletion experiments upon co-transplantation into a MHC-mismatched myeloablative transplantation model for relapsed leukemia.

Results: CAR expression on early ex vivo generated lymphoid progenitors suppresses Bcl11b Figure 1B and leads to decreased T cell-associated gene expression. Concomitantly, suppressed Bcl11b permits lymphoid progenitors to acquire NK cell-like properties Figure 1A and upon adoptive transfer into hematopoietic stem cell transplant recipients they differentiate into CAR-induced killer cells CARiK that mediate potent antigen-directed antileukemic activity across MHC barriers Figure 1C,D.

Disclosure: M. All remaining authors have no conflict of interest. Numbers of NK1. Statistics was performed by using Students t-test two-tailed. D CAR-lymphoid progenitor-co-transplanted mice were treated with weekly i.

All mice received 1. Survival curves were compared using Mantel-Cox log-rank test. Therefore, targeting HLA-DPB1 mismatched antigens by donor T cells seems to be an attractive strategy to enhance graft-versus-leukemia effect. However, our data also indicate that finding of the most suitable TCR candidate is challenging. We initiated a prospective trial to directly test the efficiency of this approach. We report here an interim result of a prospective, randomized, single-centre trial NCT Median age at HSCT was 8.

Neither anti-thymocyte globulin nor calcineurin inhibitors were used. Results: Median follow-up for survivors was 1 year 0, WBC and platelets engrafted at a median of 11 days and 14 days, respectively.

Causes of death were pre-engraftment bloodstream infection and disseminated adenovirus infection. Incidence of CMV viremia]. Outcomes of interest were complete response CRoverall survival OS. To less extent, disease burden prior to treatment with conditioning chemotherapy and CAR T cells impacted response. Conclusions: In this preliminary analysis we demonstrate that dose intensity of conditioning chemotherapy positively correlated with response and overall survival for patients treated with CAR T cells and confirms, to a lesser extent, pre-treatment disease burden impacts both response and overall survival.

Disclosure: The authors acknowledge William Lawrence and Blanche Hughes Foundation provided funding for the conduct of this study with Juno Therapeutics providing funding for an extension cohort of patients. The most common adverse events reported are cytokine-release syndrome CRS and neurotoxicity. Here we study and profile of hematologic toxicity of patients following locally produced CAR T cells.

Results: Between July and March38 patients were enrolled on the trial, and 35 patients who received CAR-T cells and survived more than 21 days were included in this analysis. To further study potential causes of late events in patients who were in remission, and in absence of signs of hemophagocytosis, patients' serum was analyzed for chemokine panel at different time points.

As expected, serum thrombopoietin levels were correlated with the platelet count. Late neutropenia events which occurred later than expected recovery from conditioning chemotherapy and following resolution of CRS, were correlated with serum SDF1 levels, similar to prior observations with late onset neutropenia related to rituximab Dunleavy, Blood As CAR T cell products are entering standard of care for relapsed patients, detection and proper management of hematologic toxicities is warranted.

It has been highlighted the role of immune system for the control of AML and new therapeutic strategies have been developed. In this setting, the use of alloreactive Natural Killer NK cells could play a key role not only in the context of hematopoietic stem cell transplantation HSCT but also as adoptive immunotherapy in patients with minimal residual disease.

In this project we proposed including the cellular therapy with haploidentical activated and expanded NK cells as adjuvant therapy in pediatric patients affected by AML in complete remission and without indication of HSCT. Methods: It is a multicentre, open, prospective and no randomized phase II clinical trial, to evaluate the efficacy and safety of allogenic NK cells infusion from haploidentical donor after a lympho- ablative chemotherapy in pediatric patients affected by low and intermediate risk AML in first complete cytological remission.

NK cells were obtained from ml of peripheral blood from haploidentical donors selected based on alloreactivity of KIR inhibitors and KIR activators receptors. NK cells were activated and expanded for 3 weeks trough co-culture with the cellular line Kmbilbbl suitable for clinical use in humans Good Manufacturing Practices, GMP. One product was rejected for quality criteria.

A mean of Median age of the patients were 7 years Treatment and infusions were well tolerated. The main adverse event was neutropenic fever in one patient. After a median follow up of days all the 7 patients are alive. Conclusions: The preliminary results of this trial suggest that NK cells infusion as consolidative strategy in pediatric patients with AML, is feasible and secure.

The therapeutic effect should be confirmed in a larger cohort of patients. Both cell types are not restricted by MHC molecules which makes them unlikely to elicit graft versus host disease GvHD even in mismatched SCT and therefore are suited also for cell-based posttransplant immunotherapy.

Incubation with cytokines strongly enhances their spontaneous and antibody dependent cellular cytotoxicity ADCC. The results for CDa assays are in line with the cytotoxicity approaches. A median number of Side effects were treatable cytokine release syndrome in 3 patients; no GvHD occurred. Infused cells could be tracked by CD69 expression for up to 26 days in peripheral blood. Further investigations are needed to evaluate the role of this cellular therapy.

CAR-T cell based activity in Europe is still at early stages. Few European academic and pharma-sponsored clinical trials are currently opened to inclusions, and access to the two EMA-approved autologous CAR-T products remains limited for the majority of European centers, since they must undergo a tedious and non-harmonized qualification process imposed by the manufacturer as part of the drug label.

Using monkey survey, the survey was sent to EBMT-centers. Results: centers replied to the survey. Most patients were treated in the setting of academic clinical trials This first results confirms active and growing involvement and high quality standards of European centers having CAR-T cell program.

The expanding use of these complex ATMP approaches could be facilitated through harmonization of the clinical practice, shared analysis of good quality data, and by a centralized European clinical trial office.

The cellular therapy CAR-T form is readily available to capture in more detail safety and efficacy of this intervention and will allow sharing in a transparent process registry data with stakeholders.

But there are still lots of uncertainties pending research. The primary outcome measure is incidence of adverse events AEs especially clinical events, including CRS, neurotoxicity and coagulopathy, et al. Results: 19 patients median age of 61, range 41 to 71 with RRMM have received treatment.

As of data cut-off Dec 1,CRS grade occurred in 8 patients, grade occurred in Surprisingly, not a few patients developed coagulation disfunction, manifesting elevated D-dimer, prolonged APTT, PT, TT, and decreased fibrinogen, with 0 case of organ bleeding. AEs of coagulation were observed. Given extensive cross-talk between inflammation and coagulation, coagulation-related indictors are more convenient for monitoring CRS.

Also, our study suggests the importance in diagnosis and early management for coagulopathy to avoid CRS-related mortality. The predominant manufacturing model is a centralized industrial-type production process.

An alternative approach to CAR-T cell production and delivery to the patient is via a point-of care manufacturing process. Eight patients received previous blinatumomab infusion.

Results: All production cycles were successful. Median expansion of T cells was 36 fold Grade I neurotoxicity had 2 pts, grade II - 1 pt, grade V - 1 pt. Four patients were admitted to the intensive care unit ICU. Three patients died until day 28 2 due to sepsis, 1 due to fatal brain edema and sepsis, on autopsy in the brain vessels of this patient were found Klebsiella pneumoniae emboli.

Twelve patients were evaluable for response at day Three pts had persistent leukemia, without evidence of CAR-T expansion. MRD-negative responses were achieved in 8 cases among 11 evaluable cases with bone marrow involvement. CD19 - relapse after initial response was registered in 1 case at day.

Robustness and consistency of this approach provides a solid basis for multi-center academic trials in the field of adoptive cell therapy. Furthermore, the prognostic relevance of mutation profile resulted in a mutation-enhanced system MIPSS70 in transplant-age PMF patients 70 years or younger. While all scoring systems were developed in non-transplant populations and may be useful in decision finding regarding transplantation, uncertainty remains regarding usefulness of these systems to predict posttransplant outcome and thus counseling patients whether to proceed to transplant.

Methods: Bone marrow or peripheral blood samples were obtained before transplantation and mutations were detected using next-generation sequencing. Cytogenetic analysis and reporting were performed according to the International System for Human Cytogenetic Nomenclature criteria using standardized techniques. A training cohort of patients was used to create a clinical-molecular transplant scoring system MTSS predicting survival from Cox models, internally validated by use of bootstrap and cross-validation.

Model discrimination was measured by the concordance index C. The final MTSS was externally validated in a cohort of patients and was furthermore applied to posttransplant non-relapse mortality as a secondary objective. The uncorrected concordance index for the final survival model was 0. Conclusions: We show here that this internally and externally validated MTSS accurately discriminated different risk for death and may improve counseling patients with respect to transplant compared with currently existing systems, as well as facilitate design of clinical trials in the transplant setting.

Background: JMML is a chemotherapy-resistant neoplasia of early childhood. Relapse is the major cause of treatment failure, with chemotherapy prior to HSCT being notably unsuccessful. Novel therapies controlling the disorder prior to HSCT are urgently needed. Methods: We conducted a phase 2, multicenter, open-label study to evaluate pharmacodynamics, safety, and antileukemic activity of azacitidine monotherapy prior to HSCT in patients with newly diagnosed JMML.

The primary endpoint was the number of patients with clinical complete remission or clinical partial remission cPR at Cycle 3 Day 28 C3D28 ; secondary endpoints included overall survival following HSCT.

Median range WBC, platelet count and spleen size were: DNA methylation class Lipka et al. Sixteen patients completed 3 cycles of therapy and 5 of them completed 6 cycles. Two patients discontinued treatment before completing 3 cycles due to disease progression. Importantly, 8 of the 15 patients who needed platelet transfusions before or shortly after treatment initiation did not require transfusions at the time of HSCT. Palpable spleen size decreased in 11 responders by a median of 3.

Thirteen transplanted patients were leukemia-free at median follow-up of Two children both high methylation class given HSCT relapsed after the allograft. Sixteen of the 18 patients were alive at a median follow-up of One patient who discontinued treatment before cycle 3 died from disease progression, and 1 non-responder died from graft failure. Conclusions: This study shows azacitidine monotherapy was well tolerated in children with newly diagnosed JMML.

Although the long-term advantage of azacitidine therapy remains to be fully assessed, both the decrease in spleen size and significant platelet responses observed demonstrate that the drug was effective in JMML and provided clinical benefit to JMML patients in this study.

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Disclosure: Charlotte Niemeyer is a member of a board of directors or advisory committee and provides consultancy for Celgene. Retrospective studies show that ruxolitinib has been used in patients before HSCT with apparent good tolerance. Patients had to start ruxolitinib after inclusion and were transplanted in case a donor has been identified within 4 months.

Primary aim was progression-free survival at one year after HSCT. Results: 76 patients could be included. Median follow-up was 31 months. Three renal failures secondary to tumor lysis syndrome were declared just after conditioning regimen initiation. Conclusions: OS was very good in patients with HLA matched related donor and significantly better than in patients with an unrelated donor.

More analyses are currently ongoing to determinate the potential role of cytokine release in peri-transplantation time, as well as specific myelofibrosis and quality of life questionnaires assessing the impact of ruxolitinib in patients. Figure 1. Background: While cytogenetics may influence outcome in primary myelofibrosis PMF from diagnosis which lead to several prognostic systems incorporating different cytogenetic risk classifications, its definitive role specific after allogeneic stem cell transplantation is still unclear.

Methods: In this multicenter retrospective study, we examined PMF patients undergoing allogeneic stem cell transplantation.

Results: The median follow-up period of all PMF patients was 56 months and the median time from diagnosis to transplant was 26 months. Conclusions: Current cytogenetic risk stratifications do not predict outcome in PMF after allogeneic stem cell transplantation.

Background: The aim of this study was to assess the outcome of patients with Myelofibrosis allografted before and afterin two transplant Centers Genova San Martino and Rome Gemelli. Results: Outcome. Predictive factors. The following factors predicted survival in multivariate Cox analysis: high risk transplant score HR 2. Molecular analysis, today available for all the affected patients, allows the physicians to correlate mutational status with prognosis, potentially representing a powerful tool to guide the clinical management.

No data are available about the outcome of transplantation in the specific MPL-mutated group. Median age was 59 years min 43, max Prognostic risk assessed according to the international DIPSS system was high in 6 cases, intermediate-2 in 7 cases, intermediate 1 in 5 cases. One patient was previously splenectomised, 8 patients received ruxolitinib before the transplantation, 7 were transfusion-dependent. Six patients received a fully myeloablative schema, 12 reduced-intensity conditioning.

Only one patient received conditioning with TBI. Relapse occurred in only 1 case. NRM incidence was With a median follow up of 55 months, 5-year overall survival was Conclusions: These retrospective data suggest that the particular group of MPL-mutated myelofibrosis may have a good outcome after stem cells transplantation.

In particular, our data revealed very low rate of disease relapse 5. This retrospective study may be helpful to support future guidelines. One patient had missing data at the time to transplant. TKI therapy was re started in all patients after a median time from transplant of 4. After a median time from TKI discontinuation of However, such approach in patients who transform to advanced phases before allo-HSCT remains a matter of concerns given the high incidence of post allo-HSCT relapse.

OS according to pre-transplant status]. Patient's characteristics]. Background: Allogeneic stem-cell transplantation allo-SCT is a well-established treatment modality for high-risk hematopoietic malignancies. However, the optimal intensity of myeloablation with a reduced-toxicity conditioning regimen to decrease relapse rate after allo-SCT without increasing TRM has not been well established. Thiotepa is an alkylating compound with antineoplastic activity and immunosuppressive properties, as well as the ability to penetrate the blood brain barrier.

Thiotepa has become an integral part of the Thiotepa, Busulfan iv Busilvexand fludarabine TBF conditioning regimen, which is being used with increasing frequency, particularly for Haploidentical and cord-blood transplants.

However, few studies have focused on analyzing the effect of Thiotepa dose in the TBF conditioning. Results: We identified AML patients allotransplanted between January and June from matched related or unrelated donors or T replete haplo-identical donors. Median follow-up was 20 months IQR: Outcomes are summarized in the table 1.

With the limitation of the retrospective nature of registry data, these results suggest that a lower dose-intensity of Thiotepa and Busilvex in the TBF regimen in general may yield better results in AML patients transplanted in complete remission. Background: TheThiotepa-Busulfan-Fludarabine TBF based conditioning regimen is widely used in T-cell repleted haploidentical transplantation Haplo with post-transplant cyclophosphamide. However, the use of Anti-thymocyte globulin ATG has not been well established.

It decreases the incidence of graft versus host disease however some claim that it's at the cost of increased relapse. We conducted this multi centric study to compare the outcomes of patients who underwent Haplo with TBF conditioning regimen with ATG to those without.

Methods: This is a multicentric retrospective study. We included all consecutive adult patients who underwent Haplo with TBF conditioning. Patients who received ATG received a dose of 2. Patients who received ATG had a younger median age compared to the second group without ATG group 1 53 and 58 years respectively; p value 0.

At a median follow-up of ATG also resulted in higher progression and overall survival at 24 months, which was not statistically significant Background: High-risk leukemia is associated with poor prognosis and inferior outcome. In elderly or comorbid patients allogeneic SCT with myeloablativ conditioning regimen as the most effective treatment option is not available.

Sequential regimen combining cytoreductive therapy with RIC has shown high antileukemic activity for high-risk patients with acceptable toxicity profile. This study is based on the observation that antileukemic effects have been described previously for the nucleoside analogue clofarabine.

Secondary objectives were overall and relapse-free survival, mortality rate, safety profiles and cardiac toxicity. Mean time to event was The treatment arms were well-balanced at study baseline for relevant covariates. Consistently hazard ratios for event free survival, overall survival and relapse-free survival were in favor of the control group with FLAMSA treatment. No differences were found regarding cardiac toxicity, rate of engraftment, or chimerism.

Regarding general safety parameters, no relevant differences between the two treatment strategies were found. Disclosure: Conflict of interest: Nothing to declare. Background: Currently, there is no direct evidence to recommend specific conditioning intensities in myelofibrosis undergoing allogeneic stem cell transplantation. Moreover, recent risk stratifications for diagnosed myelofibrosis MF included specific mutation profiles as prognostic factors.

Using clinical-molecular data from four different centers from Germany and France, we sought to determine whether molecular genetics have an impact on outcome after reduced intensity RIC and myeloablative conditioning MAC stem cell transplantation in MF. Methods: Previously published methods were used to sequence myelofibrosis-associated genes i.

Risk ratios RR were obtained for subgroup analysis. Various modifications of this protocol have been developed in recent years see table 1. Patients were grouped according to the type of SR used as shown in table1. The primary endpoint was leukemia-free survival LFS. Multivariate analysis was done using Cox regression. Median follow-up was 41 months IQR Median age was Table 1 Groups of Sequential Regimens]. Background: Bendamustine-based conditioning regimens have been extensively used prior to autologous stem cell transplantation ASCT for lymphoma.

Matched criteria were age at transplant, gender, stage at diagnosis, number of prior lines of chemotherapy, disease status at transplant and year of transplant. Hazard ratios for OS and LFS were estimated using Cox regression models stratified on the matched sets, to account for the matched-cohort design. Results: Patients' characteristics are detailed in Table 1. The higher relapse rate following BeEAM requires further evaluation.

A prospective randomized study will be required to confirm the equivalence of the two regimens. Table 1: Patient Characteristics]. Each patient with IBD was matched with 3 controls according to following factors: patient sex, patient age, disease, intensity of conditioning, donor type and HLA disparity, cell source and year of transplant.

Group comparisons were done using log-rank test or Gray test for competing risks outcomes. The cohort comprised 94 males and 81 females, with a median age of 53 years range, 18 to 69 years at the time of transplantation. However, IBD patients have a higher risk for developing severe forms of chronic GVHD, which could considerably impair their long-term quality of life.

Results: Median age was With a median follow up of 4. The 1 and 3-year NRM were The 1-year cumulative incidence of gradeand acute GVHD was CDselected pts were 1. Endothelial damage is an important contributor to poorer outcomes after alloHCT and EASIX formula provides an easy complimentary tool to predict outcomes in these patients.

Table 1. Univariate analysis]. Figure 1]. Background: Subsequent malignant neoplasms SMNs are one of the most important complications of hematopoietic stem cell transplantation HSCT and result in considerable morbidity and mortality. Methods: All HSCT patients age years at time of transplant who survived at least 2-years after HSCT in the province of Ontario, Canada between and were identified from 3 transplant centers.

Clinical data were linked to provincial administrative databases and the Ontario Cancer Registry that identifies cancer cases based on pathology reports and electronic patient records. Several patients developed more than 1 SMN. Ten other types of SMNs were found including sarcoma, melanoma, nerve sheath tumor and breast cancer. Nine survivors died at a median of 7.

Careful observation in the survivorship period is required for potential early detection. Background: Allogeneic haematopoietic cell transplantation HCT is potentially curative for a variety of benign and malignant haematological disorders. Numerous long-term conditions and complications can arise as a result of the transplant that may decrease survival and quality of life.

The purpose of the present study is to review the comorbidities of a single-centre cohort of allogeneic HCT recipients that survived twenty years post-transplant. Methods: We retrospectively investigated patients that underwent allogeneic HCT at the Princess Margaret Cancer Centre Toronto, Canada between and and who survived at least 20 years post-HCT while continuing follow-up at our centre.

We documented performance status, comorbidities, number of medications and occurrence of secondary malignancies at 20 years, as well as survival following the year time-point. At the 20 year mark, median Karnofsky Performance Status was range At the time of the year post-HCT follow-up, the median number of medications patients were taking was 2 range Median follow-up of survivors after the year mark was 59 months range months.

Conclusions: Long-term allogeneic HCT recipients may develop a number of long-term comorbidities that negatively influence survival even past the year mark. These findings warrant the continuous long-term medical follow-up of allogeneic transplant patients, regardless of age or time that has lapsed post-HCT.

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Overal Survival of 20 year HCT-survivors after 20 years]. Results were validated in an independent cohort of adult alloSCT recipients from another single institution transplanted between and Disclosure: The authors thank Jazz Pharmaceuticals for providing financial support that was used for data collection. Background: Endothelial dysfunction is a risk factor for early mortality after allogeneic stem cell transplantation alloSCT and is linked to transplant-associated thrombotic microangiopathy TAM.

Early hyperbilirubinaemia occurs frequently after alloSCT. Methods: In two independent cohorts of and patients, serum bilirubin levels before alloSCT and on days 0, 3, 5, 7, 14, 21 and 28 were retrospectively retrieved.

Endothelial protection with statins and ursodeoxycholic acid was associated with reduced incidence of and reduced NRM after early hyperbilirubinaemia. The endothelial relationship of this condition is underlined by the observation that Angiopoietin-2, EASIX-pre and EASIX-d0 but not markers of liver damage associate with the incidence of early hyperbilirubinaemia.

Therapeutic strategies aiming at normalization of endothelial dysfunction after alloSCT are attractive. As a first example, our data demonstrate reduced incidence of early hyperbilirubinaemia and reduced NRM thereafter in alloSCT recipients prophylactically treated with statins and ursodeoxycholic acid in the peri-transplant period. Background: Accumulating evidence has suggested complement activation in transplant-associated thrombotic microangiopathy TA-TMAmainly in the pediatric setting.

To further understand its pathogenesis in adults, we hypothesized that both complement and neutrophils are activated in TA-TMA as previously observed in distinct thrombotic disorders. Full donor chimerism was evident in all patients. No significant difference in transplant characteristics was observed among groups, except for the significantly lower GVHD rate in the control group. In the receiver-operating characteristic curve, we found a significantly high area under the curve 0.

Values higher than Lastly, we studied changes of complement and neutrophil activation in 3 patients that received complement inhibition by eculizumab. Despite delayed initiation in the first two patients 28 and 18 days post TA-TMA diagnosis respectivelywe observed laboratory response including evidence of reduced hemolysis, schistocytosis and transfusion needs.

However, all patients succumbed to complications of end-stage renal disease and infections after a median of 3 doses of eculizumab. Conclusions: Our findings demonstrate for the first time a crosstalk between complement and neutrophils in adult TA-TMA. In addition, we were able to set a cut-off C5b-9 value for distinguishing complement activation in unselected patients diagnosed with the IWG criteria.

Although complement inhibition by eculizumab seems to hinder this pathophysiological process, further studies are needed to clarify changes and identify optimal therapeutic targets in this complex setting. Disclosure: E. The remaining authors declare no competing financial interest.

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In the T-IND, patients discontinued treatment due to CR median time to discontinuation, 22 days after initiation of defibrotide; range,with 57 patients Disclosure: Paul G. Richardson has served on advisory committees and as a consultant, and has received research funding from Jazz Pharmaceuticals.

Nancy A. Kernan received grants from Gentium during the conduct of the study, and her research was supported by The National Cancer Institute of the National Institutes of Health under award number P30 CA; the content is solely the responsibility of the author and does not necessarily represent the official views of the National Institutes of Health.

She has a research grant from Jazz Pharmaceuticals. Stephan A. Grupp has served on a steering committee and as a consultant to Jazz Pharmaceuticals.

Background: Little is known about the long-term effects of pediatric HSCT on the male reproductive axis. We investigated sperm counts and prevalence of testosterone substitution twenty years after pediatric HSCT and aimed at identifying risk factors for azoospermia and testosterone substitution.

The study included medical history; physical examination including testicular volume and screening for chronic graft-versus-host-disease cGvHD ; sex hormones and a semen sample. Results of semen and sex hormone analyses are listed in table 1. Cumulative CED adjusted for testicular irradiation was not a risk factor for azoospermia or testosterone substitution, nor was cGvHD.

Pre-pubertal stage at HSCT increases the risk for later testosterone substitution supporting the hypothesis that pre-pubertal Leydig cells are more sensitive to irradiation than more mature ones. Additionally, the risk of testosterone substitution increased with time from transplantation indicating a potential early androgen insufficiency in male HSCT recipients. Thus, close follow-up and focus on cumulative irradiation doses are needed. Background: Hematopoietic stem cell transplantation HSCT has become a standard component of therapy for several malignant indications.

As HSCT may improve survival for some cancers, the risk for late complications is of increasing concern. The frequency of hospitalizations can serve as a proxy measure of severe morbidity.

However, knowledge regarding late hospitalizations is limited. We also described intensive-care unit admissions. The study population included Ontario residents with cancer age years who underwent HSCT between andwho survived more than 2 years from transplant index date. Hospitalizations were described from the index date until Dec or death.

Results: The cohort consisted of survivors who were followed for a median of Of these, There were a total of hospitalizations, resulting in a hospitalization rate of 0. Average length of hospital stay was 6.

A total of 97 intensive-care unit admissions were documented among 57 At 10 years following HSCT, the proportion of patients hospitalized was In the follow-up period, 73 Careful observation in the survivorship period is required for potential prevention of hospitalization.

Background: Engraftment syndrome ES is a clinical complication characterized by inflammatory signs and symptoms occurring during neutrophil recovery after stem cell transplantation SCT. Its incidence varies depending on the clinical criteria used.

The objective of this study was to analyze the incidence, clinical characteristics, risk factors and clinical outcomes of ES after haploidentical-SCT with post-transplant cyclophosphamide HaploSCT in a single center. Methods: consecutive Haplo-SCT performed between in our center were retrospectively reviewed.

Results: Characteristics of the 94 transplant included are shown in Table 1. The ES incidence was There were other 5 cases of fever and skin rash during the peri-engraftment period with a final diagnosis of GVHD considering clinical outcome. There were no deaths secondary to ES. No other risk factors were identified.

No association was noted with acute or chronic GVHD. SCT characteristics]. To our knowledge, this is the largest study including only haploidentical SCT.

Most cases of ES had a self-limited course or good response to corticosteroids, and there were no associated mortality. However ES can progress to multi-organ dysfunction with need of intensive supportive care.

In our analysis, incidence of ES was higher with the use of sibling haplo-donors, and further studies are needed to confirm these results. Specific biomarkers may contribute to an early identification of this entity in order to install therapeutic measures.

Thus, we compared clinical outcomes between patients who received PT-Cy and patients who did not in a cohort study including all consecutive patients allografted in our center. Prior to transplant, patients Median age was 55 years range, and Results: In univariate analysis, cumulative incidence of ECE was Cardiovascular risk factors and the cumulative doses of anthracycline were not significantly associated with the incidence of ECE.

After a median follow-up of At last-follow-up, patients have died. In elderly patients or with a history of pre-transplant cardiac event, an alternative to PT-Cy should be considered to prevent ECE. In this analysis, we wanted to check if IO affected adversely to the long-term outcome of our series de patients.

Among the pts consecutively transplanted between June and Julypts signed the informed consent and underwent a pre-HSCT MRI to assess the hepatic iron load.

Results: 64 pts were male, and 36 were female. Median age was 54 years range: Stem cell source was PB in 96, and BM in 4 cases. As shown in table 1, majority of patients with severe iron overload had been heavily transfused, and had a high pre-HCST ferritin level. The aim of this study was to analyze the incidence, characteristics, risk factors and outcomes of patients developing NCs after allo-HSCT.

We collected data on neurological symptoms, diagnostic methods, time of onset and cause. NC was defined as any neurological event that occurred after starting the conditioning regimen and before relapse. NC due to central nervous system CNS infections o neoplastic infiltration were excluded. Median follow-up of surviving patients was 71 months range, Median time to NC was 78 days range, Neurologic complications according to post-transplant period].

Multivariable analyses identified alternative donors hazard risk[HR],1. NCs were more frequent in recipients allografted from alternative donors, recipients older than 40 years, and in those developing GvHD. Background: Non myeloablative allogeneic stem cell transplantation HSCT by limiting toxicity, can be proposed to elderly patients.

However, acute renal injuries related to anti-calcineurin, which are frequent in this population, can negatively impact the outcome. Currently, the exposure indexes to follow and the target to use are not consensually established.

However, using the area under the curve AUC for therapeutic drug monitoring TDM is theoretically the best method to describe the patient's exposure. The primary objective of this study was to determine an AUC target for ciclosporin associated to the occurrence of acute kidney injury in HSCT patients. Methods: We retrospectively studied all consecutive patients who received a non-myeloablative allogeneic stem cell transplantation at Limoges University Hospital from June to December GvH prophylaxis consisted in rabbit anti-lymphocyte serum at the dose of 2.

Mycophenolate mofetil was added for patients with HLA-matched or mismatched unrelated donors. TDM of ciclosporin was done based on trough concentration C0 twice a week with concomitant renal evaluation using creatininemia. Ciclosporin's AUC was evaluated at day 1, day 14 and day 28 after allograft using bayesian estimation from a limited sampling strategy and a population pharmacokinetics model previously published. The association between ciclosporin AUC and acute kidney injury was investigated using a joint model.

Results: We included 79 patients, with a median [min-max] age of 60 years. New evaluations of AUC in prospective studies are needed to better define the relevance of this marker in clinical practice.

Background: Human cord blood CB provides an attractive source of hematopoietic stem cells for allogeneic transplantation of patients with a variety of diseases. Results: In total, we detected a median of Clonal patterns in blood early after transplant differed markedly from those at later time points, and became increasingly deterministic over time. The majority of clones displayed multilineage output, yet clones with bias towards lymphoid or myeloid lineages were also present.

Similar to recent data on murine HSC clones, human CB clones were distributed asymmetrically across different bone marrow sites. Future research will be aimed at identifying the underlying mechanisms guiding HSC behavior upon transplantation and expanding our findings to human HSCT recipients.

Background: Chronic Granulomatous Disease CGD is a rare genetic immune disorder that leaves patients susceptible to life-threatening infections, chronic inflammation and often long hospital stays. Allogeneic hematopoietic stem cell transplant HSCT has been a potentially curative approach for X-CGD patients, but is often complicated by lack of HLA-matched donors and risks of graft versus host disease, graft rejection, and procedure-related fatality.

Previous attempts at autologous ex vivo gene therapy for X-CGD using gammaretroviral vectors have met with limited efficacy due to transient engraftment of gene corrected cells, gene silencing, and mutagenic activation leading to myelodysplasia.

Here we report on 9 patients with a history of severe X-CGD-related complications, who received autologous ex vivo gene therapy GT using a novel self-inactivating lentiviral vector G1XCGD LV designed to limit the risk of mutagenesis through preferential expression of the missing g91phox subunit in mature myeloid cells. All patients had histories of severe, persistent infections, and inflammatory disease. Freshly prepared or cryopreserved quality-tested gene-modified cells, manufactured on-site, were administered intravenously.

Primary endpoints were efficacy, as determined by percent of oxidase positive granulocytes by dihydrorhodamine [DHR] flow cytometry, and safety at 12 months. Results: We report results for 7 patients years with GT was well-tolerated, only one serious adverse reaction a systemic inflammatory process at engraftment of functional neutrophils was reported as possibly related to GT.

Patients experienced typical conditioning-related transient neutropenia, thrombocytopenia and mucositis. There has been no molecular evidence for clonal dysregulation or gene silencing through CpG dinucleotide methylation. Patients have been well, without new X-CGD-related infections, and 4 are successfully weaned off prophylactic antibiotics.

Conclusions: These results are the first demonstration of effective autologous lentiviral GT at 12 months in severely affected X-CGD patients without evidence of genotoxicity. Gene therapy has the potential to be an effective treatment option for patients with TDT, but without some of these limitations. Patients received myeloablative conditioning with single-agent busulfan before DP infusion. Patients are followed for 2 years and offered participation in a long-term follow-up study.

Statistics are presented as median min-max.

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Patients received a cell dose of 7. Baseline liver iron content LIC was 6. Outcomes by age and baseline LIC will be reported. Times to neutrophil and platelet engraftment were 19 and At last study visit, total Hb in these 10 patients was One treated patient had no RBC transfusions for 11 months, then re-initiated transfusions due to low Hb.

One grade 3 event of serious prolonged thrombocytopenia after platelet engraftment was considered possibly related to LentiGlobin. The three grade 4 serious VOD events were attributed to myeloablative conditioning Table 1. Not Rated min Action, Drama, Fantasy. A bike stuntman recalls his previous life as a warrior, and pursues his love's reincarnation. A sinister figure from their shared past threatens to separate them forever. Votes: 17, Not Rated min Action, Crime.

Surya arrives in Mumbai to revive the mafia and ends up making enemies who threaten his life. Votes: 9, Not Rated min Action, Comedy, Romance. Krishna Nani is a coward who is in love with Mahalakshmi Mehreen Pirzada and they have kept it a secret. Mahalakshmi is sister of Ramaraju, who in turn is a henchmen of Rajayya.

At the Arvind Nani who came to the city from a rural area, is a naive employee in a company. He cannot tolerate corruption, bribery, breaking rules, lavishness and the urban culture of youth in Votes: A fast-paced socially relevant political drama that revolves around the struggles of an ordinary citizen against crime and political corruption. The scion of a powerful family is tasked with retrieving an estranged family member. Votes: 7, Not Rated min Comedy, Drama, Fantasy.

Through reincarnation, family members are able to cross generations and meddle in each others' lives. Director: Vikram K. He turns as a cop and gets posted to his Votes: 5, Not Rated min Action. Vikram Rathod, a policeman, joins with a small time thief Satthi Babu who looks identical to him to avenge his own destruction. A man returns to his parents' village to claim his land. Along the way, he befriends a charming young woman.

Unbeknownst to him, her family has a long-standing feud with his family. Votes: 6, Before he can marry his sweetheart, a wealthy city boy from England is challenged to prove his work ethic on a farm in rural India. A young man realizes that he has to push back against his domineering father if he wants to find true happiness and love.

Daya, a corrupt police officer, finds his life changing when he takes on a case of gang rape. Director: Puri Jagannadh Stars: N. A happy-go-lucky man with wit and an instinct to kill teams up with a timid cop after being pursued by the criminal whose plans to rob a bank he foiled.

Votes: 4, A well educated idealist, who is a son of Political leader in power wants to correct the rigged political system of favors and corruption. However, this soon becomes a game of power. Impressed by his carefree attitude, Vikram, a quadriplegic multi-billionaire, hires a convict out on parole as his caretaker.

What follows is a string of life lessons they learn from each other. Naa Bangaaru Talli explores the consequences of sex trafficking, testing the vulnerability of trust in human relations. Karthikeya Nikhil who loves to solve mysteries goes to Subramanyapuram for a medical camp where the villagers are frightened by a deadly snake in the temple.

How Karthikeya will solve the mystery is the crux of the story. A small time crook faces a big time challenge: he must fight to retrieve a priceless article and win the heart of his love. The film story revolves around a young man Surya Nikhil Siddharth who suffers with a heriditary disorder Porphyria, that prevents him from going outside during the day and enjoying the The film tells the story of an NRI from America who is on the verge of bankruptcy.

He finds out that he owns a Sign In. Copy from this list Export Report this list. Refine See titles to watch instantly, titles you haven't rated, etc. Feature Film IMDb user rating average 1 1.

Error: please try again. Baahubali Not Rated min Action, Drama 8.

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