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Participation of women and early-career faculty in hematology and medical oncology board review lecture series has not been studied previously. We aimed to evaluate gender and early-career faculty disparities in hematology and medical oncology board review lecture series. Speakers at major hematology and/or oncology board review lecture series meetings in the United States were analyzed in this cross-sectional study during a 5-year period from the years 2017 through 2021. Data about the lecture topic, field, speaker’s gender, years of experience, and the frequency at which the lecture was given by the speaker were collected. Of 386 speakers participating, 315 (81.6%) were ABIM (American Board of Internal Medicine)-certified. A total of 1,224 board review lectures were given in the studied period, of which 1,016 (83%) were given by an ABIM-certified speaker. Women constituted 37.7% of all speakers, with less than 50% representation in five out of six courses. Lectures discussing malignant hematology topics had the lowest proportion of women presenters (24.8%), followed by solid tumors (38.9%) and benign hematology lectures (44.1%). Faculty with more than 15 years since initial certification presented more than 50% of lectures. The median time from initial hematology or medical oncology certification to lecture presentation was 12.5 years and 14 years, respectively. A positive trend in the participation of women was found at all board review conferences across the studied period. Our data suggest that women and early-career faculty participation in hematology and oncology board review series is inadequate.

The first ‘advanced course on biomarkers in molecular and immuno-oncology’ in the Middle East took place in Beirut, Lebanon, as a hybrid meeting on 11 December 2020. The aim of this seminar was to discuss biomarker development, implications and detection modalities and to highlight advances in molecular technologies as well as the clinical applicability of biomarkers in oncology. The seminar consisted of five sessions, each discussing a special topic in the biomarker field. It also included a competition in the form of a quiz following each session. This was followed by a plenary session presented by well-known national and international speakers, highlighting various aspects of biomarkers in immuno-oncology.

CD19-targeted chimeric antigen receptor (CAR) T cell therapy has shown high efficacy in patients with refractory B-cell malignancies such as non-Hodgkin lymphoma and acute lymphoblastic leukemia. Despite promising results, responses are not durable in most patients. In addition, patients receiving CD19 CAR T cell therapy are at risk of developing severe, potentially life-threatening, adverse events including cytokine release syndrome and immune effector-cell associated neurotoxicity syndrome. Many combinatorial approaches are currently being investigated to improve CAR T cell in vivo function, antitumor effects, and mitigate toxicities. In this review, we discuss the use of ibrutinib and immune checkpoint inhibitors in combination with CAR T cell therapy in patients with lymphoid B-cell malignancies.

This perspective article discusses the various practices classified as complementary and alternative medicine (CAM) and reviews the benefits and uncertainties with respect to nutritional supplements in patients with hematological disease. It considers the high prevalence of CAM use especially among cancer survivors, particularly patients with hematologic malignancies and allogeneic stem cell transplant survivors, many of whom believe (because of extensive advertising) that supplements are anticancer/antitoxic agents, despite the paucity of evidence to support any benefit and the enormous cost to the individual. CAM constitutes various practices and nutritional behaviors including prayers, relaxation, spiritual healing, nutritional supplements, meditation, religious counseling, massage, and support groups. We highlighted the current literature regarding CAM practices and focused our discussion on the omnipresent nutritional supplements in particular to further expound on their benefits and adverse effects. As the number of survivors after HSCT increases over the next several years along with prevalence of CAM use, it becomes imperative to ascertain any beneficial potential, as well as toxicities associated with CAM use in this population.

Chimeric antigen receptor T-cell (CAR T) therapy has been proven effective in the third-line (and beyond) setting in patients with large B-cell lymphoma (LBCL). Until recently, high-dose chemotherapy followed by autologous hematopoietic cell transplantation (auto-HCT) was considered the standard of care in the second-line setting in patients demonstrating an objective response before the procedure. The ZUMA-7 and TRANSFORM studies showed the benefit of axicabtagene ciloleucel and lisocabtagene maraleucel, respectively, in patients refractory to or relapsing within 12 months of first-line anthracycline-based chemoimmunotherapy. However, a third trial (BELINDA study) using tisagenlecleucel failed to show a benefit in the same setting compared to standard salvage chemoimmunotherapy followed by auto-HCT. Several differences exist between these trials, including trial designs, patient population, crossover permissibility, bridging therapy, and end-point definitions. In this review, we summarize the current evidence for the treatment of patients with LBCL in the third line and beyond and standard treatment in the second line before CAR T therapy approval and interpret outcomes of the three trials examining the role of CAR T therapy in the second line and their impact in reshaping future practice.

Chimeric antigen receptor (CAR) T cell therapy represents a significant advancement in the treatment of patients with relapsed/refractory B cell lymphoid malignancies. Cytokine release syndrome and immune effector cell-associated neurotoxicity represent the most acute serious adverse events post CAR T cell therapy but the occurrence and persistence of cytopenias post CAR T cell therapy represent a significant adverse event and a management challenge. While most patients typically recover blood counts by 30 days, a significant subset of patients have persistent or late cytopenias beyond 30 days. Patients receiving CAR T cell are heavily pre-treated and the impact of prior therapies on late cytopenias is not well understood. In this study, we found an association between increased number of rituximab infusions and/or cumulative rituximab dose received prior to CAR T cell infusion and persistent anemia and thrombocytopenia at 90 and 180 days afterwards. An overall increased number of prior lines of therapy was also associated with persistent lymphopenia and anemia at 90 days while receiving a prior autologous hematopoietic cell transplant was associated with a greater risk of neutropenia and lymphopenia.

Background Graft-versus-host disease (GVHD) is a major cause of mortality after allogeneic stem-cell transplantation. Posttransplantation cyclophosphamide (PT/CY) has become standard prophylaxis of GVHD in T-replete haploidentical transplantation. The question is whether adding antithymocyte globulin (ATG) to PT/CY may further reduce the incidence of GVHD compared to PT/CY only. Patients and Methods We retrospectively studied 268 patients undergoing myeloablative haploidentical transplantation with thiotepa, busulfan, and fludarabine (TBF) conditioning. Sixty-nine patients (26%) received ATG. Results In the ATG group, 3% died due to GVHD versus 8% in the no ATG group. The 100-day and 1-year nonrelapse mortality (NRM) was 0% and 19%, respectively, in the whole cohort. On univariate analysis, the 1-year NRM was 8% versus 23% in patients receiving ATG and no ATG, respectively (P = .005). The no ATG group had a higher incidence of acute GVHD at 12 months compared to the ATG group (22% vs. 12%, respectively, P = .029). The ATG group had better overall survival at 12 months compared to the no ATG group (79% vs. 69%, P = .029). On multivariate analysis, adding ATG to PT/CY had no significant impact on any of the outcomes. A low disease risk index was associated with better overall survival and lower NRM, while Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) score ≥ 3 was associated with higher NRM. Conclusion ATG can be safely used as part of the pretransplantation conditioning and does not increase the incidence of relapse or complications after transplantation.

Chimeric antigen receptors (CARs) are synthetic engineered receptors with an antigen recognition domain derived from a high-specificity monoclonal antibody that can target surface molecules on tumor cells. T cells are genetically engineered to express CARs, thereby harnessing the antigen-recognition ability of antibodies and effector function of T cells. Target surface molecule selection is crucial for manufacturing CARs. Ideally, a target surface molecule should be restricted to tumor cells and minimally expressed or absent on normal tissues. Different CD19-targeted CAR-T cell therapies have been approved for the treatment of B-cell lymphoid malignancies that are refractory to other therapies, including indolent and aggressive B-cell non-Hodgkin lymphomas (NHL) and B-cell acute lymphoblastic leukemia (B-ALL). Despite impressive results, many patients with aggressive and refractory B-cell malignancies do not respond to or relapse after CD19 CAR-T cell therapies. Thus, several additional strategies are currently being evaluated to overcome these limitations. This review discusses studies on other promising CAR-T cell targets, including CD20, CD22, BAFF-R, ROR1, CD70, BCR complex, kappa/lambda light chains, multitargeted CAR-T cells, and combinations of CAR-T cell therapy with different drugs.

Lebanon is a relatively small country located on the eastern coast of the Mediterranean Sea. It includes one of the most developed healthcare systems and world-renowned healthcare workers in the region. Cancer cases are steadily increasing in Lebanon reaching 11,589 new cases in 2020. Preventions and screenings programs are conducted to decrease cancer incidence and aim for early cancer detection. Cancer treatment is provided in public and private hospitals and financial coverage is assured through the Ministry of Public Health (MOPH) and third-party payers. All Lebanese cancer patients have access to treatment through universal cancer drug coverage by the MOPH. Recently, economic, financial, and political constraints have increased the burden on the healthcare system. Further improvements are needed to keep the healthcare system resilient enough to face these difficulties.

Methemoglobinemia is a rare disorder associated with oxidization of divalent ferro-iron of hemoglobin (Hb) to ferri-iron of methemoglobin (MetHb). Methemoglobinemia can result from either inherited or acquired processes. Acquired forms are the most common, mainly due to the exposure to substances that cause oxidation of the Hb both directly or indirectly. Inherited forms are due either to autosomal recessive variants in the CYB5R3 gene or to autosomal dominant variants in the globin genes, collectively known as HbM disease. Our recommendations are based on a systematic literature search. A series of questions regarding the key signs and symptoms, the methods for diagnosis, the clinical management in neonatal/childhood/adulthood period, and the therapeutic approach of methemoglobinemia were formulated and the relative recommendations were produced. An agreement was obtained using a Delphi-like approach and the experts panel reached a final consensus >75% of agreement for all the questions.

Hodgkin lymphoma is a highly curable disease. Although most patients achieve complete response following frontline therapy, key unmet clinical needs remain including relapsed/refractory disease, treatment-related morbidity, impaired quality of life and poor outcome in patients older than 60 years. The incorporation of novel therapies, including check point inhibitors and antibody–drug conjugates, into the frontline setting, sequential approaches, and further individualized treatment intensity may address these needs. We summarize the current treatment options for patients with classical Hodgkin lymphoma from frontline therapy to allogeneic hematopoietic stem cell transplantation and describe novel trials in the field.

Background Post-transplant cyclophosphamide (PT-Cy) has become a standard of care in haploidentical hematopoietic stem cell transplantation (HSCT) to reduce the risk of graft-versus-host disease. However, data on cardiac events associated with PT-Cy are scarce. Objectives This study sought to assess the incidence and clinical features of cardiac events associated with PT-Cy. Methods The study compared clinical outcomes between patients who received PT-Cy (n = 136) and patients who did not (n = 195), with a focus on early cardiac events (ECE) occurring within the first 100 days after HSCT. All patients had the same systematic cardiac monitoring. Results The cumulative incidence of ECE was 19% in the PT-Cy group and 6% in the no–PT-Cy group (p < 0.001). The main ECE occurring after PT-Cy were left ventricular systolic dysfunction (13%), acute pulmonary edema (7%), pericarditis (4%), arrhythmia (3%), and acute coronary syndrome (2%). Cardiovascular risk factors were not associated with ECE. In multivariable analysis, the use of PT-Cy was associated with ECE (hazard ratio: 2.7; 95% confidence interval: 1.4 to 4.9; p = 0.002]. Older age, sequential conditioning regimen, and Cy exposure before HSCT were also associated with a higher incidence of ECE. Finally, a history of cardiac events before HSCT and ECE had a detrimental impact on overall survival. Conclusions PT-Cy is associated with a higher incidence of ECE occurring within the first 100 days after HSCT. Patients who have a cardiac event after HSCT have lower overall survival. These results may help to improve the selection of patients who are eligible to undergo HSCT with PT-Cy, especially older adult patients and patients with previous exposure to Cy., Central Illustration

OBJECTIVES CYP3A5 and ABCB1 are highly implicated in the pharmacokinetics and pharmacodynamics of immunosuppressive agents, such as calcineurin inhibitors and mammalian target of rapamycin inhibitors. The polymorphisms of their coding genes play important roles in the interindividual and intraindividual differences of bioavailability of these drugs. In this study, our objective was to investigate, in a Lebanese population,the frequency of ABCB1C3435T (rs1045642) and CYP3A5*3 (rs776746) polymorphisms and to compare the results to preexisting data from other populations. MATERIALS AND METHODS We determined the frequencies of the allelic variants of interest for 1824 Lebanese participants, and we compared these results with those from other major ethnic groups. RESULTS The allelic frequencies were 91.4% (C) and 8.6% (T) for CYP3A5*3 and 50.8% (T) and 49.2% (C) for ABCB1 C3435T. Our results were significantly different from most other world populations, except the European population. CONCLUSIONS The frequencies of gene variants of interest in our Lebanese population were similar to those found in European populations. Most of our study population were CYP3A5*3 carriers, and more than half may have a lower P-glycoprotein efflux pump. These characteristics might render Lebanese transplant recipients more prone to the development of drug toxicity and in need of lower drug doses.

Patients receiving allogeneic hematopoietic cell transplantation (alloHCT) were previously shown to display a bacterial gut dysbiosis; however, limited data are available regarding the role of fungal microbiota in these patients. We evaluated the bacterial and fungal composition of the fecal microbiota at day 0 of alloHCT. Higher bacterial diversity was associated with an improved overall survival (OS) and disease-free survival (DFS). While fungal diversity had no impact on patient outcomes, we observed that high versus low relative abundance of Candida albicans in alloHCT patients at day 0 was associated with a significantly lower OS, DFS and graft-versus-host-free, relapse-free survival (GRFS) (p = 0.0008, p = 0.0064 and p = 0.026, respectively). While these results are limited by low patient numbers and low fungal read counts in some samples, they suggest a potentially important role for C albicans in alloHCT.

Myelofibrosis (MF) is a clonal stem cell neoplasm with heterogeneous clinical phenotypes and well-established molecular drivers. Allogeneic haematopoietic stem cell transplantation (HSCT) offers an important curative treatment option for primary MF and post-essential thrombocythaemia/polycythaemia vera MF or secondary MF. With a disease course that varies from indolent to highly progressive, we are now able to stratify risk of mortality through various tools including patient-related clinical characteristics as well as molecular genetic profile. Owing to the high risk of mortality and morbidity associated with HSCT for patients with myelofibrosis, it is important to improve patient selection for transplant. Our primary goal is to comprehensively define our understanding of current practices including the role of Janus Kinase (JAK) inhibitors, to present the data behind transplantation before and after leukaemic transformation, and to introduce novel personalization of MF treatment with a proposed clinical-molecular prognostic model to help elucidate a timepoint optimal for consideration of HSCT.

e18709 Background: The mortality rate of cancer patients diagnosed with COVID-19 infection has reached 25%. The time from symptom onset to admission to the intensive care unit (ICU) was on average 10 days, with approximately 26% of patients requiring ICU admission. A higher mortality attributed to COVID-19 was seen in older patients, patients with certain cancer types, and patients with a higher Charslon comorbidity score. Moreover, male sex and leukopenia at diagnosis were associated with an increased risk of worse clinical outcomes. Furthermore, a study done at Memorial Sloan Kettering showed that patients with hematological malignancies had a worse prognosis than those with solid tumors. Our aim is to identify the predictive factors for ICU admission in the setting of positive COVID-19 infection in cancer patients. Differences in prognosis were compared between cancer and non-cancer patients admitted to the ICU due to COVID-19 infection. We also compared the overall outcome between patients with solid cancers and hematologic malignancies. Methods: This is a single institution retrospective study based on chart review analysis conducted at the American University of Beirut Medical Center (AUBMC). 248 patients were diagnosed with COVID-19 from 1 January 2020 to 31 December 2021. The patient groups were (1) all cancer patients admitted to the COVID unit, (2) all cancer patients admitted to ICU, and (3) all other patients without cancer admitted to the ICU. The main outcomes were ICU admission and mortality. Results: 173 cancer patients were admitted to our institution for the management of COVID-19 with a mean age of 63 years. 52 patients (30%) required ICU admission and 50 patients (29%) died during hospital stay or 1 month following discharge. The time from symptom onset to ICU admission and death were 12.8 and 35 days, respectively. Patients admitted to the ICU were more likely to have anemia (Hb < 8 g/dL) and thrombocytopenia (< 50,000/mm3) on admission (p = 0.001). Age, male sex and history of smoking, diabetes or cardiopulmonary diseases were not associated with greater risk of ICU admission or death. Among cancer patients, those with uncontrolled disease at the onset of COVID-19 had greater risk of death from COVID-19 (p = 0.001). Cancer type, number of lines of treatment, history of radiation to the chest, recent cytotoxic therapy, and neutropenia were not associated with ICU admission or death from COVID-19. There was no statistical significance in mortality or disease progression between patients with solid or hematologic malignancies. Conclusions: Our data reaffirms previously reported findings of high mortality in cancer patients who contract COVID-19. In particular, patients with anemia, thrombocytopenia, and uncontrolled disease at diagnosis had unfavorable outcomes. Contrary to the literature, age, male sex, cancer type, and neutropenia were not predictive factors for mortality in cancer patients in the setting of COVID-19 infections.

e19049 Background: Prognosis of COVID-19 is poor in the setting of immunosuppression. Casirivimab/imdevimab (REGEN-COV), bamlanivimab, and sotrovimab are investigational monoclonal antibodies (MoAbs) authorized for treatment of mild/moderate COVID-19 for patients (pts) 12 years or older and who are at high-risk for progression to severe COVID-19. These neutralizing antibodies, against SARS-CoV-2 spike proteins, have been shown to decrease risk of progression to severe disease. Recipients of allogeneic stem cell transplants (allo-SCT) or chimeric antigen T cell therapy (CAR T cell) represent a high risk population. However, treatment outcomes with these MoAbs in these pts are not well described. Methods: This retrospective study included 33 consecutive adult pts who developed mild/moderate COVID-19 and received anti-spike SARS-CoV-2 MoAbs between December 2020 and November 2021. Allo-SCT (N=27) or CAR T cell (N=6) recipients were included, and outcomes were analyzed separately. Pts received REGEN-COV (N=19), bamlanivimab (N=11), or sotrovimab (N=1), missing (N=2). Results: In the allo-SCT cohort (N=27), median age at time of COVID-19 was 55 (23-76) years. Median time from allo-SCT to COVID-19 was 31 (22-64) months. Two pts received CAR T-cell therapy prior to allo-SCT. Diagnoses included leukemia or myeloid diseases (82%), lymphoma (11%), or myeloma (7%). Transplant characteristics are summarized (Table). Thirteen pts were vaccinated against SARS-CoV-2 prior to breakthrough COVID-19. Events considered included hospitalization due to COVID-19, disease progression, or death from any cause. The 6-month event-free and overall survivals were 81% and 91%, respectively. In the CAR T cell recipients cohort (N=6), 4 pts received axicabtagene ciloleucel for diffuse large B-cell or follicular lymphoma and 2 received brexucabtagene autoleucel for mantle cell lymphoma. The median follow-up was 8 (1-11) months. Two pts received autologous SCT prior to COVID-19. Median time from CAR T cell therapy to COVID-19 was 10 (3-24) months. Three pts were vaccinated prior to COVID-19. Only 1 pt was hospitalized due to severe COVID-19 requiring mechanical ventilation leading to death. Conclusions: These results show a potential benefit of MoAbs in high-risk pts, namely allo-SCT or CAR T cell recipients. Future studies should evaluate the role of prophylactic use MoAbs in these populations. A comparative analysis with a matched control cohort (who did not receive MoAbs) will be provided at the meeting. [Table: see text]

11060 Background: Studies show that women and early career faculty members have less access to career development opportunities and leadership positions. These disparities slow the process of change and may affect leadership roles, promotions, and career advancements in academic medicine. Here, we provide the first analysis of speakers’ gender and early faculty disparities in hematology and medical oncology board review series. Methods: We performed a cross-sectional analysis of speakers at all major hematology and/or oncology board review series meetings, which were held in the United States between January 2017 and December 2021. Six major board review series were involved: Baylor/M.D. Anderson Cancer Center, the Brigham and Dana-Farber, George Washington School of Medicine and Health Sciences, Memorial Sloan Kettering Cancer Center, Seattle Cancer Care Alliance, and the American Society of Hematology. Details of the lectures were acquired via accessing brochures available on the institutions’ official websites. Data on board certification and maintenance of certificate (MOC) were obtained from the American Board of Internal Medicine (ABIM) website. We extracted the number of publications from the PubMed website (MEDLINE). Results: Our analysis included 1224 board review lectures presented by 386 speakers. Of which, 315 (81.6%) were American Board of Internal Medicine (ABIM) certified, and MOC was active in 56.1% of speakers. Females accounted for 37.7% of all speakers, with a representation of less than 50% in 5 out of 6 board review series. The least proportion of female participation was among lectures discussing malignant hematology topics (24.8%), followed by solid tumors (38.9%), and benign hematology topics (44.1%). Faculty members with more than 15 years of experience since initial certification presented more than half of the lectures. The median time from initial hematology or medical oncology certification to lecture presentation was 12.5 years and 14 years, respectively, which varied significantly among different series (p < 0.001). Speakers’ median number of publications was 84. We also investigated how frequently the same speaker gave lectures. Thirteen male speakers conducted more than or equal to 10 lectures across all board review series, compared to only two female speakers who did the same. An upward trend of improvement in females participation was found at all board review conference meetings across the years. Conclusions: Our data suggest that women and early career faculty members are underrepresented in hematology and oncology board review series. Therefore, efforts should be made to ensure equal participation of them in such important activities needed to advance academic careers.

Context Autologous hematopoietic stem cell transplant (ASCT) has become the mainstay treatment for many hematological malignancies and solid tumors. An adequate number of stem cells must be collected for better ASCT outcomes, which is challenging in 5%–30% of patients. To improve mobilization, plerixafor is used, along with granulocyte colony-stimulating factor. Objective To evaluate the real-life efficacy of plerixafor and to identify factors associated with poor mobilization. Design and Setting This is a retrospective, single-center study involving patients who received plerixafor pre-ASCT between January 2013 and December 2020 at a tertiary care center in Lebanon. Patients We identified a total of 72 consecutive adult patients. Patients who received plerixafor were divided into two groups: poor mobilizers with pre-emptive use before first apheresis for those with peripheral CD34+ stem cells (PSC) 20 cells/µL. Main Outcome Measures The main endpoints were to evaluate characteristics of poor mobilizers, stem cell yields pre- and post-plerixafor, as well as the time to neutrophil and platelet engraftment. Results The median age at diagnosis was 54 years (12–73). 60% were males. 50 (70%) patients had multiple myeloma (MM), 12 (15%) had non-Hodgkin lymphoma, 7 (10%) had Hodgkin lymphoma, and 3 (4%) had solid tumors and Waldenstrom macroglobulinemia. The median follow-up was 9 months (1–59). 59 (82%) patients had low PSCs, requiring pre-emptive plerixafor prior to apheresis. 62% of MM and 54.5% of non-MM patients needed >1 collection. 97% of all patients collected CD34+ >2×106cells/kg post-plerixafor. The median collected final CD34+ cells post-plerixafor was 4.4×106/kg (1.84–18.62). Factors associated with poor mobilization were male gender, age at diagnosis >55 years, MM, and bone marrow involvement (p=0.041, p=0.031, p=0.04, and p=0.012, respectively). Median times to absolute neutrophil count (ANC) and platelet engraftment were 11 (4–26) and 17 (4–28) days, respectively. A longer ANC engraftment (>2 weeks) was observed in patients who were infused Conclusion These results can guide us to use plerixafor early in selected patients who are predicted to fail mobilization.

Therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for patients with EGFR-mutated non-small cell lung cancer (NSCLC) has been shown to have superior outcomes when compared to chemotherapy. First-generation EGFR TKI, including gefitinib and erlotinib, and second-generation EGFR TKI, including afatinib and dacomitinib, proved to be effective in patients with NSCLC harboring EGFR-sensitizing mutation. Later, resistance mutations were identified. Consequently, osimertinib, a third-generation EGFR TKI, was studied and demonstrated activity against EGFR-sensitizing and resistant mutations. Osimertinib moved recently to the first-line setting with the positive results of the FLAURA (AZD9291 Versus Gefitinib or Erlotinib in Patients With Locally Advanced or Metastatic Non-small Cell Lung Cancer) trial. The use of these drugs is limited by their cost and availability mainly in middle- to low-income countries.

We report results of a thiotepa-based conditioning in haploidentical stem cell transplantation (haplo-SCT) with posttransplant cyclophosphamide (PT-CY) and antithymocyte globulin (ATG), for unmanipulated peripheral blood stem cell (PBSC) transplants, in 80 patients with hematological malignancies. Patients in complete remission (CR) received a thiotepa-busulfan-fludarabine (TBF) regimen, while patients with relapsed/refractory (R/R) malignancies received a sequential regimen consisting of thiotepa-etoposide-cyclophosphamide (TEC) and reduced-intensity conditioning (RIC). The median age was 52 (range, 17-72) years, 44% patients had R/R disease at transplant, and the median follow-up was 417 (range, 180-1595) days. The median days to neutrophil engraftment was 17 (range, 12-34). The cumulative incidences (CI) of acute graft-versus-host disease (GVHD) grade III to IV, severe chronic GVHD, nonrelapse mortality (NRM), and relapse were 16%, 16%, 26, and 26%, respectively. The 2-year overall survival (OS) and disease-free survival (DFS) were 53% and 47%, respectively. There were no significant differences between the patients in CR and R/R patients in terms of engraftment, GVHD, NRM, relapse, OS, or DFS. We conclude that thiotepa-based regimen with PT-CY can be modified with PBSC and ATG, still providing low toxicity, protection against GVHD, and low relapse incidence. Particularly encouraging are the results with the modification to sequential regimen in R/R patients.

Isocitrate dehydrogenase (IDH) 1 and 2 mutations occur in 20% of acute myeloid leukemia (AML). Patients with AML carrying IDH1-2 mutations have a similar prognosis compared to patients without these mutations (DiNardo et al, AM J H, 2015). However, the impact of IDH1-2 mutations on patients with AML undergoing allogeneic hematopoietic stem cell transplantation (allo-HCT) is not well known. In this study, we investigate the prognostic impact of IDH1-2 mutational status on AML patients undergoing alloHCT in complete remission (CR). In this retrospective registry-based analysis, we identified 710 consecutive adult patients (46.2% female; median age: 58.5 years [range, 18-78]) with AML undergoing allo-HCT in CR between 2015 and 2019 at 85 EBMT participating centers. Cord blood, ex-vivo graft manipulated transplants, and patients with favorable cytogenetics were excluded. Median follow-up was 15 months [95% CI 13.4-16.6]. Patients were categorized based on IDH1-2 mutational status, with 300 (42%) mutated and 410 (58%) wild type. Six hundred and fifty-two (92%) and 58 (8%) patients had de novo and secondary AML, respectively, and 141 (20%) patients had poor-risk cytogenetics. IDH1-2 mutation was positively correlated with NPM1 mutation (40% in IDH1-2 mutated vs 27% in wild type, p=0.0001) and more frequently encountered in middle-aged patients (p=0.01). No correlation was noted between IDH1-2 and FLT3 mutation or other patient characteristics. Minimal residual disease (MRD) data was available for 344 patients, 53% of which were MRD-negative at transplant in both groups. Six hundred and twenty-three (88%) and 87 (12%) patients were in first and second CR at time of transplant, respectively. Patients received grafts from a matched sibling (24%), unrelated (62%), or haploidentical (14%) donor, and myeloablative conditioning (MAC) was used in 42%. Ninety-three percent of the patients received peripheral blood as the stem cell source. At day 180, the cumulative incidence of grade II-IV acute graft-versus-host disease (aGVHD) was significantly lower in IDH1-2 mutated compared to wild-type patients (22% vs 33%, p=0.002). No differences in chronic GVHD rates were noted between the 2 groups (39% vs 40%, p=0.87). The 2-year cumulative relapse incidence (RI) was significantly lower and the GVHD-free, relapse-free survival (GRFS) was also improved in IDH1-2 mutated compared to wild-type patients (14.4% vs 27%, p=0.001 and 47% vs 39%, p=0.006, respectively). This led to an improved leukemia-free survival (LFS) in IDH1-2 patients (69% vs 59%, p=0.01), however, it did not translate into an overall survival (OS) difference. No significant difference was noted in non-relapse mortality (NRM) between the 2 groups (17% vs 14.2%, p=0.26). These findings were confirmed in multivariate analysis. In fact, IDH1-2 mutation was associated with significant improvement in RI (hazard ratio [HR]=0.4 [95%CI 0.25-0.64], p=0.0001), LFS (HR=0.7 [95%CI 0.51-0.95], p=0.022), aGVHD II-IV (HR=0.63 [95%CI 0.45-0.87], p=0.005) and GRFS (HR=0.69 [95%CI 0.54-0.89], p=0.004). Conversely, the presence of adverse cytogenetics and undergoing allo-SCT in second CR increased the RI (HR=2.29 [95%CI 1.46-3.61], p=0.0003 and HR=2.84 [95%CI 1.64-4.91], p=0.0002, respectively) and were associated with a shorter LFS (HR=1.67 [95%CI 1.18-2.36], p=0.004 and HR=1.61 [95%CI 1.06-2.44], p=0.025) while reduced intensity (RIC) conditioning had a worse impact on OS compared to MAC (HR=1.56 [95%CI 1.07-2.29], p=0.022). Additionally, in the subgroup of patients with available MRD data, MRD positivity at transplant significantly increased RI (HR=2.15 [95%CI 1.09-4.23], p=0.027) with no impact on survival. In conclusion, our data suggest that the presence of IDH1-2 mutations acts as an independent prognostic factor and is associated with improved outcome in patients with AML in CR undergoing allo-HCT. Indeed, patients with IDH1-2 mutations had significantly lower rates of RI and aGVHD, which translated into improved LFS and GRFS. Nevertheless, patients with MRD positivity at time of transplant had significantly increased RI. Further studies investigating allo-HCT outcomes in IDH1-2 mutated patients with AML in the era of IDH inhibitors (both in the pre- and post-transplant setting) would help to further define the impact of these mutations in this setting and thus optimize an individualized treatment approach. Disclosures Labopin: Jazz Pharmaceuticals: Honoraria. Esteve: Abbvie: Consultancy; Pfizer: Consultancy; Astellas: Consultancy; Novartis: Research Funding; Novartis: Consultancy, Research Funding; Bristol Myers Squibb/Celgene: Consultancy; Jazz: Consultancy. Kröger: Novartis: Research Funding; Riemser: Honoraria, Research Funding; Sanofi: Honoraria; Neovii: Honoraria, Research Funding; Jazz: Honoraria, Research Funding; Gilead/Kite: Honoraria; Celgene: Honoraria, Research Funding; AOP Pharma: Honoraria. Blaise: Jazz Pharmaceuticals: Honoraria. Socie: Alexion: Research Funding. Ganser: Jazz Pharmaceuticals: Honoraria; Novartis: Honoraria; Celgene: Honoraria. Yakoub-Agha: Jazz Pharmaceuticals: Honoraria. Bazarbachi: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Hikma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astra Zeneca: Membership on an entity's Board of Directors or advisory committees.

Despite advances in the treatment of acute myeloid leukemia (AML), cytotoxic chemotherapy remains the standard induction regimen.In this single center retrospective study, we assessed outcomes of 99 consecutive adult AML patients treated with a risk-adapted strategy with a median follow-up of 35.5 months.We identified 24 (24 %), 55 (56 %) and 20 (20 %) patients classified as favorable-, intermediate-, and adverse- risk group respectively, according to the European LeukemiaNet (ELN) 2017 classification. Patients either received idarubicin and cytarabine induction chemotherapy with or without FLT3 inhibitors or hypomethylating agents based on age and comorbidity. The complete response (CR) rate was 76 % (82 % and 61 % in patients aged60 and ≥ 60, respectively). For the whole cohort, the 3-year overall survival (OS) was 53 %, being 62 % and 30 % in patients aged60 and ≥ 60, respectively. The 3-year leukemia-free survival (LFS) was 54 %, with 56 % and 45 % in patients aged60 and ≥ 60, respectively. The 3-year LFS were 58 %, 62 % and 25 % for patients within ELN favorable-, intermediate-, and adverse-risk groups respectively. Twenty-seven (36 %) out of 75 patients with intermediate- and adverse-risk disease underwent allogeneic hematopoietic cell transplantation (allo-HCT) in first CR with 92 % of them receiving post-transplant maintenance consisting of azacitidine in 19 (76 %) patients or sorafenib in 6 (24 %) patients. Of these patients younger than 60 years, the 3-year OS and LFS were 85 % and 69 %, respectively.These results indicate an improved OS for AML patients especially in intermediate-risk category who were treated with a total therapy consisting of induction chemotherapy followed by allo-HCT and post-transplant maintenance.

Context Outcomes of haplo-identical hematopoietic stem cell transplantation (haploSCT) have recently improved due to better control of allo-reactive reactions related to the major HLA mismatch between the recipient and the donor. Presence of pretransplant donor-specific anti-HLA antibodies (DSA) is associated with higher risk of graft failure. However, little is known regarding the association between the presence of these antibodies and platelet transfusion refractoriness (PTR) post-haploSCT that could predict poor transplant outcomes. Objective The aim of this study is to evaluate the association between DSA status of the recipient and the corrected platelet count increment (CCI) from day 0-100 post-haploSCT as an objective measure of PTR. Design This is a retrospective study that comprises chart review of patients who underwent haplo-SCT between June 2015 and January 2020 at the American University of Beirut medical center in Lebanon. Main outcome measures Pretransplant panel reactive antibodies (PRA) and DSA status at the time of transplant were collected, and the 24-hour CCI was calculated for every platelet donor transfusion. Results We identified 69 patients with a median age of 36 years (range: 16-77). 44 patients (64%) were males and 52 patients (75%) had myelodysplastic syndrome or acute leukemia. Median time from diagnosis to transplant was 13.8 months (range: 2.5-91.7), and 43 patients (62%) were in complete remission at transplant. Of all patients, only 6 patients (8.7%) were DSA+ at time of transplant, 14 (20.3%) were PRA+/DSA-, and the remaining 49 (71%) were PRA-. All 6 patients with DSAs underwent desensitization with a median MFI decrease of 375 (range: -541-1603). One of these 6 did not reach platelet nor leukocyte engraftment. Patients with persistent DSAs had lower mean CCI (9.27, range: 4.58-12.37) compared to those without DSAs (mean CCI: 11.93, range: 1.34-29.71; p=0.017). Statistical significance was maintained upon comparing PRA+DSA+ patients to PRA+DSA- and to PRA- patients with mean CCI of 14.04 (range: 1.39-29.71; p=0.005) and 11.38 (range: 1.34-28.00, p=0.024), respectively. Conclusions Presence of anti-HLA DSAs in haploSCT recipients, even at MFI lower than 1500, was associated with increased PTR. Larger number of patients is needed to evaluate its impact on survival outcomes.

Alterations of gut bacterial microbiota composition have been associated with outcome after allogeneic hematopoietic cell transplantation (alloHCT), including overall survival (OS), graft versus host disease (GVHD) and relapse incidence . Furthermore, the role of eukaryotic gut virome in GVHD was recently shown (Legoff et al., Nature Medicine, 2017). In contrast, the impact of gut fungal microbiota (mycobiota) is still unknown in the alloHCT setting. Earlier studies in patients with inflammatory bowel diseases or primary sclerosing cholangitis, suggested that gut mycobiota composition and diversity contribute to disease severity. With this background, we examined the role of fecal mycobiota in patients undergoing alloHCT with the aim of identifying fungi factors associated with patients' outcome. Fecal specimens were collected at day 0 of alloHCT (before graft infusion). The fecal mycobioat was characterized by ITS2 sequencing using the MiSeq (illumine) technology. Phylogenetic classification was obtained using the UNITE ITS database (version 12_11). Association of fungal microbiota with clinical predictors and outcomes were assessed using multivariate modeling. In all, we analyzed 52 patients (28 males and 24 females). Median age was 60 (range, 22-74) years. Disease risk index was low-intermediate in 29 patients, high-very high in 20 patients (not assessed in 3 patients with aplastic anemia). Fourty three patients received a myeloablative reduced toxicity conditioning regimen, while 9 patients received a reduced intensity conditioning regimen. Ten patients received their graft from a matched sibling donor, 11 from a haploidentical donor, and 26 from a matched or mismatched unrelated donor. All patients received anti-thymocyte globulin as part of their conditioning regimen, and patients undergoing alloHCT from a haploidentical donor also received post-transplant cyclophosphamide. Overall we found a low fungal diversity score of the fungal microbiota at day 0 in all patients from this cohort, with little variations. Therefore, it proved difficult to establish any statistically significant correlations between fungal diversity and patients outcome. However, in multivariate Cox hazard analysis including the most important parameters associated with patients' outcome, we found that an increased proportion (>median) of Candida albicans and Malassezia genera was associated with a lower OS [Hazard ratio (HR)= 7.12, p=0.02 and HR=14.99, p=0.007, respectively]. We did not find any parameter with a significant impact on progression free survival in multivariate analysis. When investigating acute GVHD, a hight amount of Candida glabrata (>median) was the only parameter associated with grade II-IV acute GVHD in multivariate analysis (HR=4.49, p=0.009). The day 180 cumulative incidence of grade II-IV acute GVHD was 24% in patients with low Candida glabrata colonization (below the median) versus 80% (p=0.0005) in patients with high Candida glabrata colonization (above the median). In conclusion, we found an important disruption of the fecal mycobiota in patients undergoing alloHCT, as evidenced by the low fungal diversity observed at day 0 . Furthermore, increased amount of Candida albicans and Malassezia genera at the time of alloHCT were independent predictors of mortality. Finally fecal mycobiota might also contribute to acute GVHD as evidenced by the higher incidence of grade II-IV acute GVHD in patients colonized with higher amount of Candida glabrata . These results indicate that, in addition to bacterial and viral microbiota, the mycobiota might be an important factor influencing outcome after alloHCT. Disclosures Malard: Therakos/Mallinckrodt: Honoraria; Janssen: Honoraria; Keocyte: Honoraria; Sanofi: Honoraria; JAZZ pharmaceutical: Honoraria; Astellas: Honoraria. Duléry:Keocyt: Honoraria. Mohty:Jazz Pharmaceuticals: Honoraria, Research Funding.

Several studies have shown that alteration of the microbiota, particularly in the gastrointestinal tract, can be associated with graft-versus-host disease (GvHD). Patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) usually get exposed to antibiotics (ATB), mainly in the peri-transplant period. Moreover, ATB, specifically those that target anaerobic bacteria, can alter the microbiota in a variety of body organs. This, in turn, renders several organs vulnerable to injury making them more prone to developing diseases such as GvHD. In this study, we evaluate whether the use of ATB, characterized by duration, timing and type, in the peri-transplant period, is associated with an increased incidence of acute GvHD (aGvHD) and aGvHD-related mortality. In this retrospective study, we included 318 consecutive patients who underwent allo-SCT including haploidentical and cord blood transplantation between December 2012 and June 2018 at a single center. ATB exposure was collected and classified into 3 groups according to the date of initiation of ATB: from the start of conditioning to day - 1 of allo-SCT (early ATB exposure), from day 0 to neutrophil engraftment (late ATB exposure) and a third group of patients who did not receive ATB (no ATB exposure). ATB were only initiated if a patient develop fever or show signs of infection. Patients did not receive any prophylactic ATB. Exposure was further categorized as primary or adjunct. Primary exposure included the use of 4 classes of ATB: carbapenems, anti-pseudomonal penicillin, 4thand 5thgeneration cephalosporins and fluoroquinolones. Adjunct ATB comprised other ATB and was further divided into 2 groups according to anaerobic coverage. The median age at transplant was 55 years. The stem cell source was peripheral blood in 85%, bone marrow in 10% and cord blood in 5% of the patients. Ninety-nine percent of the patients received cyclosporine A as GvHD prophylaxis and 80% and 7% of the patients received (along with cyclosporine A), mycophenolate mofetil and methotrexate, respectively. In addition, 35% and 89% of the patients received post-transplant cyclophosphamide and anti-thymocyte globulin, respectively, as GvHD prophylaxis. The median time to neutrophil engraftment was 16 days post-transplant. The median follow-up was 85 months. 93.7% of the patients received ATB in the peri-transplant period with 64.5% of them in the early ATB exposure group, and 29.2% of them in the late ATB exposure group. The 2-year overall survival and progression free survival were 74.3% and 63.6% in patients with early ATB exposure, compared to 79.5% and 70.8% in patients with late ATB exposure (p=0.11 and p=0.07 respectively). The 2-year cumulative incidence of non-relapse mortality was 16.5% in patients with early ATB exposure, compared to 15.1% in patients with late ATB exposure (p=0.63). The 180-days cumulative incidence of grade 2-4 and 3-4 aGvHD were 23.8% and 12.2% in patients with early ATB exposure, compared to 27.2% and 5.4% in patients with late ATB exposure (p=0.64 and p=0.06 respectively). In multivariate analysis, including the most important parameters associated with GvHD (stem cell source and donors, conditioning regimen, sex mismatch and patients age), early ATB initiation was the only parameter associated with a significantly higher risk of severe grade 3-4 aGvHD [HR 0.51 (0.28-0.90); p=0.02]. In conclusion, in the absence of any ATB prophylaxis, early initiation of ATB, before graft infusion,is associated with a significantly higher risk of severe grade 3-4 aGvHD. Weighing risk of morbidity and mortality associated with infections versus later on risk of developing aGvHD is essential. Hence, new strategies should be developed to risk stratify patients with fever and thus to avoid early non necessary ATB exposure especially in those who develop fever during anti-thymocyte globulin infusion. Studies evaluating such strategies will be necessary in the next years. Disclosures Mohty: Jazz Pharmaceuticals: Honoraria, Research Funding. Malard:Astellas: Honoraria; JAZZ pharmaceutical: Honoraria; Sanofi: Honoraria; Keocyte: Honoraria; Janssen: Honoraria; Therakos/Mallinckrodt: Honoraria.

In this "real-life" retrospective study, we assessed outcome after a "personalized" treatment strategy for patients with acute myeloid leukemia (AML) in a tertiary care center. Our strategy consisted of induction therapy adjusted to age, comorbidities and molecular abnormalities, as well as allogeneic stem cell transplantation (allo-SCT) in first complete remission (CR1), whenever possible, for patients with European Leukemia Net 2017 (ELN) intermediate or high-risk patients. Allo-SCT was followed by post-transplant maintenance consisting of 5-azacytidine (AZA) for most patients, or sorafenib for patients with FLT-3 ITD. We included 99 consecutive patients (65% male). The median age at diagnosis was 49 years (range, 18-88) with 28 patients older than 60. Karyotype was normal in 59 patients. Molecular analysis revealed core binding factor (CBF) mutation in 13 patients (13%), NPM1 mutation in 26 patients (26%), FLT3-ITD and FLT3-TKD mutation in 15 (15%) and 1 (1%) patient, respectively. According to the ELN 2017 classification, 24, 48 and 27 patients belonged to the low, intermediate and high-risk groups, respectively. Patients aged 60. Of those 26 transplanted patients, 24 received post-allo-SCT maintenance consisting of AZA in 18 patients (69%) or sorafenib in 6 patients (23%). Allo-SCT was performed in 20 additional patients at time of relapsed and/or refractory disease, with 14 of them receiving post-transplant maintenance. The median follow-up for alive patients was 35 months. For the whole cohort, the 3-year overall survival (OS) was 54%. In patients aged These results indicate an improved outcome for AML patients who receive a treatment strategy tailored to age, comorbidities, and disease risk with an overall 76% CR rate and a relatively low rate of mortality during induction (7%). The use of allo-SCT in CR1 followed by post-transplant maintenance significantly improved outcome of young patients ( Disclosures No relevant conflicts of interest to declare.

Introduction: Haploidentical stem cell transplantation (Haplo-SCT) using post-transplant cyclophosphamide is widely used for the treatment of patients with hematologic malignancies especially in patients who lack related or unrelated donors. Several factors were shown to affect hematopoietic recovery after allogeneic hematopoietic stem cell transplantation, including age at transplant, initial diagnosis, stem-cell source, CD34 count in the graft, conditioning regimen intensity, infections, etc. The aim of this study was to evaluate immune reconstitution, neutrophils and platelets recovery, transfusion needs and main transplant outcomes after Haplo-SCT and to identify factors correlated with improved or worsened recovery. Methods: This study included 72 consecutive patients who underwent haploidentical stem cell transplantation between December 2012 and March 2018, in a single center. Graft was either bone marrow (n=21) or peripheral blood stem cells (n=51). Patients were given PT-Cy (50mg/kg/d) for one (n=20) or two days (n=52), cyclosporine, mycophenolate mofetil and ATG for GvHD prophylaxis. Conditioning regimen was reduced toxicity one (RIC) in 69% (n=50) of patients, and a myeloablative one (MAC) in 31% (n=22) of cases . Main transplant outcomes, neutrophil and platelets recovery, and needs for transfusion were evaluated at day +30, day +60 and day +90 after Haplo-SCT. Results: The median CD34+ cells infused was 10.62 x106/kg (range, 1.02-15.06). The median time to neutrophil recovery (>500/µL) was 16 days post-transplant (range, 5-29). The median time to neutrophil count >1000/µL was 17 days post-transplant (range, 5-32). Platelets recovery (>20.000/µL) was observed at a median of 13 days post-transplant (range, 10-193). Platelets recovery (>50.000/µL) was documented at a median of 60 days post-transplant (range, 10-193). Forty-five (63%) and 49 (68%) patients had a platelets count >50.000/µL at days +30 and +60 post-transplant respectively. At day +90 post-transplant, 61 patients were assessable with 56 (92%) of them having a platelets count >50.000/µL. In this series, 61 patients (85%) needed platelets transfusion with a median number of 13 units (range, 2-60), transfused for a median of 26 days (range, 5-198) post-transplant. Similarly, 59 patients (82%) needed RBCs transfusion and received a median of 6 RBCs packs (range, 1-60) for a median duration of 31 days (range, 5-147) post-transplant. 23 patients (32%) had anemia and/or thrombocytopenia requiring the administration of growth factors, either erythropoietin in 14 patients (19%) (Epoetin, n=8 or Darbepoetin, n=6) and/or Thrombopoietin in 15 patients (20%) (Romiplostim, n=13 or Eltrombopag, n=2). In all, 6 patients received unmanipulated CD34+ donor stem cell ("boost" procedure), 5 of them for poor graft function and 1 patient as a consolidation after immunosuppressive therapy for relapse after Haplo-SCT. Such boost proved to be successful in 4 patients while 2patients had an incomplete response with persistent anemia and/or thrombocytopenia. In the multivariable analysis, donor age (>40 years) and CMV reactivation within the first 3 months were shown to meaningfully affect day +90 platelets recovery >100 x109/L (HR 4.86, 95%CI 1.08-21.80, p=0.04 and HR 5.15, 95% CI, 1.22-21.7, p=0.03). Number of CD34, conditioning regimen, stem cell source, donor age and disease status at transplant have no impact on platelet recovery at day +90. Conclusion: In conclusion, our data show that Haplo-SCT is associated with a fast hematopoietic recovery with an acceptable rate of transfusions. While the adverse impact of CMV reactivation on platelet recovery was expected, the relation between donor age (>40 years) and platelets recovery is new. This finding should guide in selection of potential donors for Haplo-SCT. Disclosures Mohty: Celgene: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria; Takeda: Honoraria, Speakers Bureau; Janssen: Honoraria, Research Funding, Speakers Bureau; Servier: Consultancy; MaaT Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Molmed: Consultancy; Bristol Myers: Consultancy, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau.

Background: Allogeneic hematopoietic stem cell transplantation using a related haploidentical donor (Haplo-HCT) using post-transplant high-dose cyclophosphamide (PTCy) is increasingly used for patients lacking a matched related or unrelated donor. However, use ofperipheral blood stem cell graft (PBSC) is associated with an increased risk of acute GvHD (aGvHD) compared to bone-marrow graft. Therefore, while cyclosporine A (CsA) and mycophenolate mofetil (MMF) are traditionally initiated after completion of PT-Cy at day +5, we decided to initiate them at day -3 before transplant and to add a low dose of ATG to reinforce GvHD prophylaxis in those patients. With this background, we analyze retrospectively the impact of early initiation of CsA and of CsA concentration on patients' outcome in all patients who underwent Haplo-HCT with PBSC grafts and PTCy. Patients and Methods: Sixty-one consecutive patients who underwent Haplo-HCT for hematological malignancies between October 2013 and August 2017 were included in this retrospective single-center study. All patients received G-CSF mobilized PBSC as grafts and post-transplantation immunosuppression with CsA and MMF. CsA was administered at a dose of 3mg/kg by continuous intravenous infusion starting from D -3 and changed to twice daily oral dosing as soon as tolerated.MMF was administered at a fixed oral dose of 2g per day starting from day 6 without adjustment. In the absence of GvHD, MMF and CsA were tapered over 4 weeks starting from day 30 and day 60, respectively. CsA blood trough concentrations were monitored 3 times per week during the intravenous treatment and at least once per week after switch to oral dosing. CsA doses were adjusted to achieve blood levels between 200 and 300 ng/mL and to prevent renal dysfunction. The primary endpoint was to determine the impact of the CsA concentration on the risk of grade II-IV and III-IV aGvHD. Results: Median age was 53 (range, 15-72) years, with 16 male patients (26%) receiving a graft from a female donor. Diagnoses were myeloid (64%) or lymphoid malignancies (36%). According to the Disease Risk Index, patients were considered as low-risk, intermediate-risk, high-risk or very-high-risk (respectively 8%, 56%, 31% and 5%). Twenty-five patients (41%) with refractory disease received a sequential conditioning regimen while the remaining (n=36, 59%) received a RIC/RTC regimen based on fludarabine, busulfan and thiotepa. 51 patients (83%) received ATG (2.5-5 mg/Kg total dose) as part of the conditioning regimen. All patients received standard PTCy, nine at D+3 (15%) and 52 at D+3 and D+5 (85%). All patients engrafted at a median of 18 (range: 13-35) days after Haplo-HCT and the median follow-up among surviving patients was 21 (range: 13-53) months. The median concentrations of CsA at 1, 2, 3, and 4 weeks after Haplo-HCT were 272 (range: 114-911), 296 (range: 132-516), 251 (range: 111-485), and 246 (range: 36-375) ng/mL, respectively. At d180, the cumulative incidences (CIs) of grade II-IV and grade III-IV aGvHD were 39% and 18%, respectively. The CIs of chronic GvHD (cGvHD), extensive cGvHD and relapse were 41%, 19% and 35% at 18 months after Haplo-HCT, respectively. At 18 months after the transplant, the OS, PFS and GPFS rates were respectively 60%, 55% and 48%. In univariate analysis, patients having the lowest CsA concentration in the first week after Haplo-HCT had a significantly higher risk of grade II-IV aGvHD (49% vs 18%; P= .02), severe grade III-IV aGvHD (26% vs 0%; P = .03), cGvHD (P= .02) and extensive cGvHD (P= .04). We do not find statistically significant correlation between CsA concentration and relapse incidence, NRM, PFS, GPFS or OS. In multivariate logistic regression analysis, higher CsA concentration (> 301 ng/ mL; the cut-off value defined by ROC analysis) during the first week following Haplo-HCT was the only independent parameter significantly associated with a reduced risk of grade II-IV and grade III-IV aGvHD (respectively P = .04; RR .11; 95% CI, 0.05-0.94; and P < .0001; RR < .001; 95% CI, 0.000007-0.00006). There was no association with extensive cGvHD (P = .14; RR .11; 95% CI, 0.06-1.48). Conclusion: We conclude that achievement of high concentration of CsA early after Haplo-HCT using PBSC graft is associated with a low incidence of aGvHD and that CsA should be initiated at time of transplant with adequate monitoring during the engraftment period to reduce the risk of grade II-IV aGvHD. Disclosures Mohty: MaaT Pharma: Consultancy, Honoraria.