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Haploidentical hematopoietic-cell transplantation using post-transplant cyclophosphamide(Haplo-PTCy) is a feasible procedure in children with haematologic malignancies. However, data of a large series of children with acute leukaemia(AL) in this setting is missing. We analysed 144 AL Haplo-PTCy paediatric recipients; median age was 10 years. Patients had acute lymphoblastic(ALL; n = 86) or myeloblastic leukaemia(AML; n = 58) and were transplanted in remission(CR1: n = 40; CR2: n = 57; CR3+: n = 27) or relapse (n = 20). Bone marrow was the graft source in 57%; donors were father (54%), mother (35%), or sibling (11%). Myeloablative conditioning was used in 87%. Median follow-up was 31 months. At day +100, cumulative incidence (CI) of neutrophil recovery and acute GVHD (II-IV) were 94% and 40%, respectively. At 2-years, CI of chronic GVHD and relapse, were 31%, 40%, and estimated 2-year overall survival (OS), leukaemia-free survival (LFS) and graft-versus-host-relapse-free survival (GRFS) were 52%, 44% and 34% respectively. For patients transplanted in remission, positive measurable residual disease (MRD) prior to transplant was associated with decreased LFS (p = 0.05) and GRFS (p = 0.003) and increased risk of relapse (p = 0.02). Mother donor was associated with increased risk of chronic GVHD (p = 0.001), decreased OS (p = 0.03) and GRFS (p = 0.004). Use of PBSC was associated with increased risk of chronic GVHD (p = 0.04). In conclusion, achieving MRD negativity pre-transplant, avoiding use of mother donors and PBSC as graft source may improve outcomes of Haplo-PTCy in children with AL.

Background: Fibromyalgia (FM) is a chronic condition related to dysfunctional central pain processing mechanisms, which affects 3-6% of the world population, leading to widespread pain, stiffness, and tenderness of the muscles, tendons, and joints, as well as restless sleep, fatigue, depression, and anxiety. Exercise is the most effective way of reducing pain and improving global well-being in people with FM, but such patients present an important limitation to exercise adherence. Objective: We aim to evaluate whether a home-based gamification strategy will improve the Fibromyalgia Impact Questionnaire Revised (FIQR) scores in female patients aged 18-60 years old as an alternative to traditional exercise. Methods: The proposed trial is a multicenter, phase II, open-label, parallel, randomized, superiority trial. Female patients ranging from 18 to 60 years old with a diagnosis of FM will be randomized to the intervention group, designed to play the Nintendo Switch Ring Fit Adventure game on three home-based weekly sessions, or to the control group, which will receive general educational guidance through videos and pamphlets provided by the study staff for a total of 12 weeks. The primary outcome will be the mean change in FIQR score results. Discussion: The development of new strategies to increase exercise adherence can enhance the control of symptoms such as pain, depression, low quality of sleep, and physical limitation in FM patients, thereby improving their quality of life. We believe that gamification strategies such as the one used here can make physical activity more playful, accessible, and dynamic, motivating patients and increasing their physical function compared to those seeking center-based or conventional exercises.

Background: Relapsed and refractory large B cell lymphomas (RR-LBCL) have a poor prognosis. Chimeric antigen receptor (CAR) T-cell therapies have shown considerably high response rates even in RR-LBCL patients who fail to achieve remission after multiple chemotherapy lines. Currently, three CAR T-cell treatments - axicabtagene ciloleucel (Yescarta), tisagenlecleucel (Kymriah), and lisocabtagene maraleucel (Breyanzi) - have been approved for adults with RR-LBCL by regulatory agencies. Non-pivotal clinical trials have independently examined different types of CAR T-cells and have demonstrated remarkable clinical benefit and safety. Yet, no comparison of the experimental and approved CAR T-cells has been conducted. Objectives: To address this limitation, we aim to: (1) Identify comparative efficacy and safety of experimental CAR T-cells to the approved CAR T-cells, and (2) Identify how observed differences vary by different CAR T-cell types and regimens differences in CAR T-cell administration. Methodology: This protocol proposes a matching-adjusted indirect comparison (MAIC) of experimental CAR T-cell trials based on individual patient data (IPD) vs. three existing pivotal trials (comparator trials). The MAIC approach is appropriate given that CAR T-cells have solely been assessed in single-arm trials consisting of heterogeneous patient populations and the lack of IPD for the existing pivotal trials (active comparator trials), which hampers the traditional network meta-analysis approach. Conclusion: Knowledge of the relative value of experimental CAR T-cell products compared to the currently approved ones may provide insights for patients, clinicians, and CAR T-cell developers to advance and optimize the balance of potency and toxicity of these targeted immunotherapies.

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

THE BRAZILIAN SOCIETY FOR BLOOD AND MARROW TRANSPLANTATION (SBTMO) PRESENTS THE BRAZILIAN GUIDELINES ON HEMATOPOIETIC STEM CELL TRANSPLANTATION

Objectives The aim of this study was to analyze the outcomes of children with Diamond-Blackfan anemia (DBA) treated in Brazil with hematopoietic cell transplantation (HCT). Methods We performed a retrospective analysis of 44 pediatrics patients transplanted between 1990 and 2018. The median age of patients was 5 years, and 57% were male. Twenty-five received their first HCT from an HLA-matched sibling donor (MSD), 12 from a HLA matched unrelated bone marrow donor (MUD 10/10, n = 12) and 7 other HLA mismatched donors (MMD). Results After a median follow-up of 4 years, estimate 5-year overall survival (OS) for the entire cohort was 70%, 80% for MSD group, 73% for MUD, and 29% for MMD. Thirty-eight out of the 44 evaluable patients engrafted successfully. Primary and secondary graft failure was observed in five and three patients, respectively. Rates of grade II-IV and III-IV acute graft-versus-host disease (aGVHD) were 25% and 18%, respectively. Nine patients developed chronic GVHD (cGVHD). Conclusion Overall survival rates observed after HLA matched donors transplant for DBA were comparable to those reported from higher-income countries and international registries.

In this 2022 Update of Version 2020 of the VI Consensus of the Brazilian Society of Bone Marrow Transplantation (SBTMO) for Graft-versus-Host-Disease (GVHD), we seek to provide evidence-based guidance on all the novel and clinically relevant advancements in both prophylaxis and therapy of Graft-versus-Host Disease for all of those who delve into the field of Hematopoietic Stem Cell Transplantation.

Chronic Myeloproliferative Neoplasms are an important indication of allogeneic hematopoietic cell transplant. This consensus summarizes the indications and management of these onco-hematological diseases.

Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.NOVELTY AND IMPACTAlthough currently approved CAR T-cells demonstrated unprecedently high response in relapsed / refractory LBCL in the salvage setting, lack of outcome durability and toxicity remain. We delineated the relative clinical benefit of the innovative experimental CAR T-cell approaches to Yescarta for insights into the ongoing efforts to address these inadequacies. Tandem CAR T-cells may provide higher efficacy and safer profile than Yescarta. Toxicity attenuated CAR T-cells present remarkable safety but no Progression-Free Survival (PFS) benefit.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach to children and adolescents with high-risk acute lymphoblastic leukemia (ALL) at diagnosis or relapsed disease. Nonetheless, despite the graft versus leukemia (GVL) effect, treatment-related morbidity and mortality remains a major challenge. Moreover, the significant heterogeneity of the available data on the selection of patients, type of conditioning regimen, and type of donor hampers any definitive conclusions in the pediatric population. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) and the Brazilian Society for Pediatric Oncology (SOBOPE) convened a task force to provide general guidance on HSCT for childhood ALL to providing evidence-based guidance for the appropriate management of this disease.

Hematopoietic stem cell transplantation (HSCT) offers the opportunity for cure to patients with malignant and non-malignant diseases. Given the myriad advances in the past few decades, coupled with the rising numbers of transplants worldwide, the number of long-term survivors, many of whom are free of the disease for which they were transplanted, is constantly increasing. Despite the improved prognosis observed overall, long-term outcome may be undermined by transplant-associated morbidity and mortality. Long-term survivors may present a variety of complications, comprising physical, psychological, social, and economic arenas, with a deep impact on quality of life. Therefore, drawing greater attention to and raising awareness of the potential long-term effects of HSCT is key to providing a tailored approach to pretransplant counseling and to devising appropriate recommendations for post-transplant screening, prevention, and timely treatment of secondary events. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the long- term follow-up of pediatric patients undergoing HSCT, the results of which are presented here.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a potentially curative approach to children and adolescents with high-risk acute lymphoblastic leukemia (ALL) at diagnosis or relapsed disease. Nonetheless, despite the graft versus leukemia (GVL) effect, treatment-related morbidity and mortality remains a major challenge. Moreover, the significant heterogeneity of the available data on the selection of patients, type of conditioning regimen, and type of donor hampers any definitive conclusions in the pediatric population. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society of Bone Marrow Transplantation and Cellular Therapy (SBTMO) and the Brazilian Society for Pediatric Oncology (SOBOPE) convened a task force to provide general guidance on HSCT for childhood ALL to providing evidence-based guidance for the appropriate management of this disease.

Graft-versus-host disease (GVHD), either in its acute or chronic form, is the main contributory factor for morbidity and non-relapse mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Recent advancements in the classification of this disease, with better applicability and reproducibility of standardized criteria, coupled with improvements in the management of steroid-refractory or resistant cases, have led to promising results. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide updated, evidence-based guidance for the diagnosis, classification, staging, prophylaxis, and treatment of GVHD, with a focus on the pediatric population, the results of which are presented here.

Chronic myeloid leukemia (CML) accounts for approximately 2 to 3% of all pediatric leukemias. Compared to adults, children tend to present with more aggressive features, such as higher leukocyte counts and massive splenomegaly, and are more likely to be diagnosed with advanced stage disease. Before the advent of tyrosine kinase inhibitors, a couple of decades ago, allogeneic hematopoietic stem cell transplantation (allo-HSCT) was the mainstay of treatment for this disease. This, however, was associated with considerable treatment-related morbidity and mortality. Even so, despite its secondary and somewhat limited indication today, allo-HSCT remains an important alternative and the only curative treatment for CML. In 2020, the Brazilian Group for Pediatric Bone Marrow Transplantation of the Brazilian Society for Blood and Marrow Transplantation and Cellular Therapy (SBTMO) convened a task force to provide evidence-based guidance on the use of allo-HSCT for the appropriate management of childhood CML, the results of which are presented here.

Despite favorable results of CAR T-cell therapy for relapsed/refractory large B-cell lymphoma (R/R LBCL), several challenges remain, including incomplete response, immune-mediated toxicity, and antigen-loss relapse. We delineated the relative clinical benefit of the novel approaches compared to the currently approved CAR T-cell therapies. In the absence of head-to-head comparisons and randomized controlled trials, we performed Matching Adjusted Indirect Comparisons to quantify the relative efficacy and safety of experimental CARs against Axicabtagene ciloleucel (Yescarta), the first FDA-approved CAR. A total of 182 R/R LBCL patients from 15 clinical trials with individual patient data (IPD) were pooled into eight populations by their CAR T-cell constructs and +/- ASCT status. The study endpoints were Progression-Free Survival (PFS), grade ≥ 3 cytokine release syndrome (CRS), and grade ≥ 3 neurotoxicity (NT). Tandem CD19.CD20.4-1BBζ CARs indicated favorable efficacy and safety, whereas the co-infusion of CD19 & CD20 with 4-1BBζ showed no clinical benefit compared to Yescarta. Third generation CD19. CD28. 4-1BBζ, and sequential administration of autologous stem cell transplantation (ASCT) and CD19. CARs presented statistically insignificant yet improved PFS and safety except for ASCT combined intervention which had suggestively higher NT risk than Yescarta. CARs with modified co-stimulatory domains to reduce toxicity (Hu19. CD8.28Zζ and CD19. BBz.86ζ) presented remarkable safety with no severe adverse events; however, both presented worse PFS than Yescarta. Third-generation CARs demonstrated statistically significantly lower NT than Yescarta. CD20. 4-1BBζ data suggested targeting CD20 antigen alone lacks clinical or safety benefit compared to Yescarta. Further comparisons with other FDA-approved CARs are needed.

This study aimed at evaluating the use of immunophenotyping (IMP) in the identification of blast cells in the cerebrospinal fluid (CSF) of children and adolescents with acute lymphoblastic leukemia (ALL). Sixty-seven patients aged 18 years or younger were included. Fifty-five CSF samples were analyzed at initial diagnosis and 17 at the time of relapse. A cytological analysis (CA) was performed in all 72 samples, while IMP was done in 63. Blasts were identified in only three samples by CA, whereas all three samples were found negative by IMP, one of which had no isolation of nucleated cells after centrifugation. Among the samples analyzed by IMP, 11 showed a positive blast count, two of which had been inconclusive using CA. No equivalence was found between CA and IMP results (p = 0.55). CSF IMP positivity was not associated with other risk factors for ALL relapse. Among the 55 patients included at the time of diagnosis of ALL, eight relapsed during follow-up. Considering the cases of central nervous system (CNS) relapse, one of the patients belonged to the CSF IMP-positive group (11%) at diagnosis, and the other two cases, to the IMP-negative (5%) group. Detection of CSF blast cells using IMP was associated with a worse overall (p0.0001) and event-free survival (p0.0001). These results show that CSF IMP may be a useful additional method to conventional CA in the diagnosis of CNS involvement in ALL, and for the identification of high-risk subgroups that would benefit from an intensified therapy.

This is an overview of the current COVID-19 pandemic in the Hematopoietic Stem Cell Transplantation Scenario in Brazil.

Introduction The Acute Leukemia-European Society for Blood and Marrow Transplantation (AL-EBMT) risk score was recently developed and validated by Shouval et al. Objective To assess the ability of this score in predicting the 2-year overall survival (OS-2), leukemia-free survival (LFS-2) and transplant-related mortality (TRM) in acute leukemia (AL) adult patients undergoing a first allogeneic hematopoietic stem cell transplant (HSCT) at a transplant center in Brazil. Methods In this prospective, cohort study, we used the formula published by Shouval et al. to calculate the AL-EBMT score and stratify patients into three risk categories. Results A total of 79 patients transplanted between 2008 and 2018 were analyzed. The median age was 38 years. Acute myeloid leukemia was the most common diagnosis (68%). Almost a quarter of the cases were at an advanced stage. All hematopoietic stem cell transplantations (HSCTs) were human leukocyte antigen-matched (HLA-matched) and the majority used familial donors (77%). Myeloablative conditioning was used in 92% of the cases. Stratification according to the AL-EBMT score into low-, intermediate- and high-risk groups yielded the following results: 40%, 12% and 47% of the cases, respectively. The high scoring group was associated with a hazard ratio of 2.1 (p = 0.007), 2.1 (p = 0.009) and 2.47 (p = 0.01) for the 2-year OS, LFS and TRM, respectively. Conclusion This study supports the ability of the AL-EBMT score to reasonably predict the 2-year post-transplant OS, LFS and TRM and to discriminate between risk categories in adult patients with AL, thus confirming its usefulness in clinical decision-making in this setting. Larger, multicenter studies may further help confirm these findings.

Background: Cancer is the second leading cause of death globally. Up to 86% of advanced cancer patients experience significant pain, while 10-20% live in chronic pain. Besides, increasing prescription of opioids resulted in 33,000 deaths in the US in 2015. Both reduce patients’ functional status and quality of life. While cancer survival rates are increasing, therapeutic options for chronic opioid refractory pain are still limited. Esketamine is the s-enantiomer of ketamine, with superior analgesic effect and less psychotomimetic side effects. Intranasal esketamine was approved by the FDA for treatment-resistant depression. However, its use in chronic cancer pain has never been tested. Therefore, we propose a phase II, randomized, placebo-controlled trial to evaluate the efficacy and safety of intranasal esketamine in chronic opioid refractory cancer pain. Methods and analysis: We will recruit 120 subjects with chronic opioid refractory pain, defined as pain lasting more than 3 months despite optimal therapy with high dose opioids (>60 mg morphine equivalent dose/day) and optimal adjuvant therapy. Subjects will be randomized into two groups: intranasal esketamine (56mg) and placebo. Treatment will be administered twice a week for four consecutive weeks. The primary outcome is defined as reduction in the Numeric Pain Rating Scale (NPRS) after first application. Secondary outcomes include NPRS reduction after four weeks, the number of daily morphine rescue doses, functional status and satisfaction, and depression. Conclusion: This study may extend therapeutic options in patients with chronic pain, thus improving their quality of life and reducing opioid use. Trial registration: Clinical Trials.gov, NCT04666623. Registered on 14 December 2020

In this study, we report on major MRD or URD BMT outcomes in pediatric patients with SAA in Brazil. This was a retrospective study, which included 106 patients ≤18 years old who received a first BMT for SAA. All patients received bone marrow as graft source from an MRD (n = 69) or a URD (n = 37). Conditioning regimen was non-myeloablative in 73.6% of cases, and GVHD prophylaxis comprised a calcineurin inhibitor plus methotrexate in 89.6% of patients. After a median follow-up of 4.5 years after BMT, 81 patients are alive, with a 4-year OS of 77% and no statistically significant difference between the MRD and URD groups (82% vs. 69%, respectively; P = .08). Grade III-IV aGVHD at 6 months and cGVHD at 2 years were observed in 8% and 14% of cases, respectively, and were not statistically different between the groups. Twenty-five (23%) patients died at a median of 2.9 months after BMT. Our study showed that 4-year OS after BMT was not statistically different between MRD and URD recipients. This study shows that the outcomes of pediatric patients transplanted for SAA with a URD in Brazil are approaching those of MRD transplants. In contrast, OS after MRD BMT was lower than we would expect based on previous reports. The wide range of preparatory regimens used by the study centers highlights the need for standardized protocols for these children. Our findings provide a benchmark for future studies focused on improving BMT outcomes in this setting in Brazil.

Objective Describe the profile of reported Healthcare-Associated Infections (HAIs) in pediatric patients submitted to hematopoietic stem cell transplantation (HSCT) at a reference center. Methods Retrospective cohort of pediatric patients who were submitted to HSCT from 2008 to 2016. The criteria for HAI were based on those established by the National Healthcare Safety Network. Data were collected by active surveillance performed daily by professionals. This study was approved by the Institutional Research Ethics Committee. Results A total of 86 HSCTs were performed in 81 patients younger than 18 years of age (median, 10 years). Of these, 69 (85%) were males. Aplastic anemia and leukemia were the main diagnoses. A total of 140 HAIs were diagnosed with an incidence density of 28.2 infections/1.000 patient-days. The most common HAI was Laboratory Confirmed Bloodstream Infection (46), the majority of which was reported to be central venous catheter-associated (43). Gram-negative bacteria were the most prevalent microorganisms (58.5%). Almost all the infections occurred until 30 days after transplantation, and 17 deaths were observed within 180 days after the procedure. Conclusion Active surveillance of HAIs in HSCT children allowed the evaluation of the incidence and profile of HAIs, which is essential for the healthcare of these patients. This article is protected by copyright. All rights reserved.

In this prospective, observational study, we sought to investigate the incidence, risk factors, and outcomes of central venous catheter-associated infection in 56 patients admitted for hematopoietic stem cell transplantation. In multivariate analysis, we found a 7-fold higher risk of central line-associated bloodstream infection with central venous catheter insertion in the internal jugular vein as compared with the subclavian access. Patients with central line-associated bloodstream infection had a higher incidence of acute renal failure.

Although the application of Hematopoietic Cell Transplantation-specific Comorbidity Index (HCT-CI) has enabled better prediction of transplant-related mortality (TRM) in allogeneic hematopoietic stem cell transplants (AHSCT), data from developing countries are scarce. This study prospectively evaluated the HCT-CI and the Adult Comorbidity Evaluation (ACE-27), in its original and in a modified version, as predictors of post-transplant complications in adults undergoing a first related or unrelated AHSCT in Brazil. Both bone marrow (BM) and peripheral blood stem cells (PBSC) as graft sources were included. We analyzed the cumulative incidence of granulocyte and platelet recovery, sinusoidal obstructive syndrome, acute and chronic graft-versus-host disease, relapse and transplant-related mortality, and rates of event-free survival and overall survival. Ninety-nine patients were assessed. Median age was 38 years (18–65 years); HCT-CI ≥ 3 accounted for only 8% of cases; hematologic malignancies comprised 75.8% of the indications for AHSCT. There was no association between the HCT-CI or the original or modified ACE-27 with TRM or any other studied outcomes after AHSCT. These results show that, in the population studied, none of the comorbidity indexes seem to be associated with AHSCT outcomes. A significantly low frequency of high-risk (HCT-CI ≥ 3) in this Brazilian population might justify these results.

We describe a case of hemophagocytic lymphohistiocytosis related to visceral leishmaniasis in late adulthood. Because clinical features of visceral leishmaniasis can mimic those of hemophagocytic lymphohistiocytosis, diagnosing leishmaniasis as the underlying etiology can be quite challenging. In our case, treatment with amphotericin B resulted in a dramatic resolution of clinical abnormalities.

BACKGROUND AND OBJECTIVES: Disease evolution depends in part on the source of transplanted cells. Therefore, we compared outcomes after allogeneic bone marrow (BM) and peripheral blood stem cell (PBSC) transplantation in patients who underwent transplant at Hospital das Clinicas of the Federal University of Minas Gerais, Brazil. PATIENTS AND METHODS: We studied 364 patients who received allogeneic BM (n=142) or PBSC transplantation (n=222) between July 1995 and May 2005. The median age of the patients was 31 years (range, 3.1-58 years). Chronic myeloid leukemia was the predominant diagnosis (41.2%). A conditioning regimen with cyclosphosphamide and busulfan was used in 79.4% (n=289) and graft-versus-host disease (GVHD) prophylaxis was cyclosporine/methotrexate in 95.9% (n=349) of cases. RESULTS: The patients in the PBSC group had faster neutrophil (P

Imatinib mesylate (IM) is now first-line treatment for CML. To study the results of treatment with IM after IFN failure/intolerance versus allogeneic BMT (allo-BMT), we retrospectively analyzed 264 patients treated for CML in first chronic phase in three different institutions. Over a 6-year period (2001–2006), 174 patients received IM after failure of or intolerance to IFN. During the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). The IM group was older (41 versus 33 years, P

Abstract 3198 Poster Board III-135 Introduction Cyclophosphamide (Cy) with/without antithymocyte globulin (ATG) as conditioning regimen for allogeneic hematopoietic stem cell transplantation (AlloHSCT) is the treatment of choice for young patients with severe aplastic anemia (SAA). In developing countries, and particularly in Brazil, ATG costs limit its use in AlloHSCT for SAA patients. Alternative low-cost regiments, like busulfan (BU) with Cy as conditioning regimen is still associated with a significant rate of rejection, especially in heavily transfused patients, and long-term infertility. Alemtuzumab (Cam) was reported as an alternative to ATG for SAA patients, with similar activity and a lower cost. Material and Methods In order to study the effect of the combination of Cy and Cam, we reviewed all AlloHSCT performed for SAA using this conditioning regimen. Between April 2007 and Mai 2009, fifteen patients with SAA (defined by Camitta criteria) underwent an AlloHSCT in our institution. Median age at transplantation was 25 (range 5-42) years. All but one patient had positive CMV serology. Median number of transfusions was 20 (range 10-67). One patient received a second AlloHSCT due to a late (> 4 years) graft rejection. Patients received an unmanipulated bone marrow (n=11) or peripheral blood (n=4) graft as stem cell source and all but one patient were transplanted with an HLA-identical sibling. Median number of nucleated cell infused was 2.86 (range 1.65-6.50)x10 8/kg. Cyclosporin alone (n=10) or in combination with methotrexate (n=5) was used as GVHD prophylaxis. Results Thirteen out of 15 patients presented neutrophil recovery with a median time to > 0.5×10 9 neutrophil/L of 23 (range 13-30) days. Platelet recovery (> 20×10 9 platelets/L) occurred in thirteen patients with a median time of 16.5 (range 9-45) days. Acute graft versus host disease (GVHD) was observed in just one patient (grade II). None of 12 patients alive 100-days after AlloHSCT presented chronic GVHD. Seven patients presented CMV reactivation. One patient did not engrafted and other presented a late (14 months) rejection. One patient became pregnant after alloHSCT and gave birth to a healthy child. With a median follow-up of 315(range 4-782) days, two patients died and the estimate 1-year overall survival rate is 87%. One patient died due to complications of a CNS bleeding that occurred hours before marrow infusion and the other of GI infection while still on neutropenia. Conclusion Use of cyclophosphamide and alemtuzumab as conditioning regimen is a valid option in SAA patients undertaking AlloHSCT, with significant lower rates of acute and chronic GVHD. Nevertheless, a longer follow-up is required to properly evaluate rejection incidence. Disclosures Off Label Use: Drug: Alemtuzumab Off-label Use: Aplastic Anemia.

Imatinib has profoundly change indication of allogeneic bone marrow transplantation (alloBMT) worldwide for CML and is now the first line of treatment in most countries. However, in Brazil, Imatinib for CML in first chronic phase is provided by Federal Health Agency only for patients refractory/intolerant to interferon (IFN). In order to study results of treatment with imatinib and alloBMT in this particular scenario we retrospectively analyzed 266 patients treated for CML in first chronic phase (less than 60 years-old) in three different institutions in Brazil. End points were event free survival (EFS = absence of hematological response, lost of hematological/cytogenetic response, relapse in accelerated phase/blast crisis or death) and overall survival (OS). From jan/2001 to dec/2006, 176 patients received imatinib 400 mg after failure or intolerance to IFN. Median time from diagnosis to imatinib treatment was 19 months (range: 2 to 205). At the same period of time, 90 patients received an allo-BMT from an HLA-matched sibling (n=83) or an unrelated donor (n=7). Patients receiving peripheral blood stem cell or umbilical cord blood were excluded. Eighty-two patients received busulfan+cyclophsphamide as conditioning regimen and all patients received cyclosporin+methotrexate±steroids as GVHD prophylaxis. Median time from diagnosis to allo-BMT was 16 (range: 5 to 104) months. Gender distribution was similar between groups. Imatinib group had a higher median age (40.7 vs. 32.8 years, P