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For acute lymphoblastic leukemia (ALL) patients, total body irradiation (TBI)- based conditioning regimens are the first choice specially in young population. However, several studies have shown an equivalence in clinical outcomes with thiotepa-based conditioning regimen. We performed a retrospective study to evaluate the outcome of adult ALL patients who received allogeneic hematopoietic stem cell transplantation (allo-HCT) with a thiotepa-busulfan-fludarabine (TBF) myeloablative conditioning regimen with reduced toxicity. Fifty-five patients received a TBF regimen. The median age of the patients was 51 years (range, 17 to 72.4). Most patients had a diagnosis of B-ALL (93%) with 7% having T-ALL. Two - and 5-year overall survival was 73.2% and 64%, respectively. At 2 years, leukemia-free survival and GVHD-free, relapse-free survival were 59.5% and 57.6%, and at 5 years, 53.4% and 51.8%, respectively. The 5-year non-relapse mortality was 15%. The day 180 cumulative incidence (CI) of grade II-IV acute GVHD and grade III-IV acute GVHD were 38.2% and 5.5%, respectively. At 2 years, the CI of chronic GVHD and extensive chronic GVHD was 16.9% and 1.9%, respectively. Our study results do suggest that using TBF as the conditioning regimen in adult ALL patients is a promising option with acceptable toxicity.

We assessed the outcomes associated with thiotepa, busulfan and fludarabine (TBF) conditioning regimen in a cohort of 29 consecutive patients allografted for myelofibrosis (MF). The median age was 56 (range 42-70) years. According to the refined Dynamic International Prognostic Scoring System (DIPSS-plus), 15 (52%) patients were classified as high risk. Graft source was peripheral blood stem cells in 27 patients. Donor type was HLA-matched related (

Background: Pre- and post-transplant pulmonary function tests (PFT) have been previously analyzed in patients who underwent allogeneic hematopoietic stem cell transplantation (HSCT). A deterioration in pulmonary function could be observed in this setting and accounts for higher morbidity and mortality. Haploidentical allogeneic stem cell transplantation (HAPLO) with post-transplant cyclophosphamide (PTCY) is increasingly used. Limited data exists on evaluation of PFT after HAPLO and the number of patients who underwent HAPLO in previously published studies is negligible. We report the evolution of PFT as well as pre-transplant characteristics and outcomes after HAPLO in the adult setting. Methods: We retrospectively analyzed 80 HAPLO performed in a single center between 2013 and 2019. All patients with available pre- and post-transplant PFT results were included in the study. The Friedman test was used for comparing PFT at baseline, 100 days and 1 year after HAPLO. Results: The median follow up was 32 (range: 12-74) months. CMV serology was positive in 45% and 65% of patients were male. The median age was 58 (range: 16-73) years. The proportion of surviving patients with available PFT at 3 months and 1 year were 86% and 68%, respectively. Diagnosis was acute myeloid leukemia in 51% and disease risk index was intermediate-low in 75% of the cases. Disease status before HAPLO was complete remission in 61%. Graft source was peripheral blood stem cells in 91% of the cases. Conditioning regimen was reduced intensity in 40% and the most frequent chemotherapy regimen was thiotepa, busulfan and fludarabine. Graft-versus- host disease (GvHD) prophylaxis consisted of Cyclosporine A (CsA) and mycophenolate mofetil in all but one patient who received methotrexate and CsA. All patients received PTCY, 64 (80%) at days 3 and 5 after HAPLO, 7 (9%) at days 3 and 4, and 9 (11%) at day 3 only. Seventy-three (91%) patients received anti-thymocyte globulin. In total, 24% of the patients had previously smoked, 8% had type 2 diabetes, and 23% suffered from hypertension. Three patients had a lung infection at baseline, of which one was bacterial and two were possibly aspergillosis. At screening for HAPLO, five (6%) patients had restrictive lung disease, nine (11%) met the criteria for obstructive lung disease, and diffusing capacity for carbon monoxide (DLCO) corrected for hemoglobin was impaired in 74% of the patients. The median forced expiratory volume in the first second (FEV1) was 100 (range: 58-146) before HAPLO, 93 (range: 42-10) at 100 days after HAPLO and 99 (range: 32-144) at 1 year. The median forced vital capacity (FVC) was 106 (range: 57-153), 98 (range: 44-148) and 106 (range: 31-153) at pre HSCT, 100 days and 1 year after HAPLO, respectively. FEV1 and FVC were significantly different over time during the 1 year follow up (p=0.01 and p=0.001, respectively). The median FEV1/FVC was 80 (range 51-105) before HAPLO, 77 (range: 54-103) after 3 months, and 75 (range: 43-100) after 1 year. FEV1/FVC, residual volume, and total lung capacity (TLC) remained stable from baseline to 1 year (p=0.27, p=0.84 and p=0.21, respectively). In contrast, DLCO remained impaired during the follow-up period (p Twenty-nine patients had an infectious respiratory complication during the follow-up period. Of these, 19 were bacterial, three were viral, two were fungal and five had no microbial documentation. During the 1-year follow-up period, four patients met the criteria for bronchiolitis obliterans syndrome and two for interstitial lung disease. Of these, only one had died at last follow-up. The cumulative incidence of grade II-IV acute GvHD was 21% (95% CI 14-33%). At 1 year, the cumulative incidence of chronic GvHD was 26% (95% CI 18-39%). Non-relapse mortality was 9% (95% CI 4-18%) at 100 days and 14% (95% CI 8-24%) at 1 year. Relapse incidence was 3% (95% CI 1-10%) and 14% (95% CI 8-24%) at 100 days and 1 year, respectively. Overall survival was 73% (95% CI 62-82%). In all, 22 patients died. Cause of death was relapse of hematological disease in 7 (35%), infection in 7 (35%), GvHD in 2 (9%), multi organ failure in 4 (20%) and other causes in 2. Conclusion: We observed a significantly impaired DLCO at baseline, which remained impaired at 3 months and 1 year after HAPLO, but with a substantial stable pulmonary function at 1 year. Disclosures Malard: Theralos/Mallinckrodt: Honoraria; Sanofi: Honoraria; Keocyt: Honoraria; Astellas: Honoraria; JAZZ pharmaceutical: Honoraria; Biocodex: Honoraria; Janssen: Honoraria.

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

International audience; Background aims: Corticosteroids are the standard first-line treatment for acute graft-versus-host disease (aGVHD), but they are associated with many complications, and less than half of patients have a sustained response.Methods: To improve outcomes, we performed a retrospective study to analyze the efficacy of the addition of extracorporeal photopheresis (ECP) to low-dose corticosteroids in 37 adult patients (median age, 57 years) with skin-predominant aGVHD (grade I, n = 17; grade II, n = 18; and grade III, n = 2). All patients received ECP in combination with 1 mg/kg prednisone (n = 26) or topical steroids (n = 11).Results: Overall response rate was 81% after a median of three ECP procedures (range, 2–8), including 22 complete responses (CR, 59%) and eight very good partial responses (VGPR, 22%). The 11 patients treated with topical corticosteroids achieved CR. Furthermore, 16 (62%) patients reached prednisone withdrawal at a median of 100 days (range, 42–174 days) after its initiation. Eighteen patients developed chronic GVHD (cGVHD); 11 of them (who were in CR of aGVHD) had a new-onset cGVHD, and seven experienced progressive cGVHD (five non-responding and two VGPR patients). A second-line immunosuppressive treatment was initiated in only five (14%) non-responding patients. With a median follow-up of 31 months (range, 6–57 months) 2-year overall survival and non-relapse mortality were 74% and 11%, respectively.Conclusions: Overall, the combination of low-dose corticosteroids and ECP appear to be safe and effective for first-line treatment of skin predominant aGVHD.

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.

Background T-cell-depleted, haploidentical transplantations (haplos) are commonly offered to patients who have high-risk, acute leukemia in the absence of a human leukocyte antigen (HLA) full-matched donor. Methods To determine the effect of transplantation period, the authors divided 308 adults with de novo, acute leukemia who underwent T-cell-depleted haplo from 2005 to 2015 into 2 groups, according the year in which they underwent transplantation (2005-2011 [n = 191] and 2012-2015 [n = 117]). Results The median age was 41 years in patients who underwent transplantation before 2012 and 46 years in those who underwent transplantation after 2012 (P = .04). Most patients had acute myeloid leukemia (75% vs 69%; P = .26) and were in first complete remission (CR1) (55% vs 64%; P = .12) at the time of transplantation. The cumulative incidence of grade 2, 3, and 4 acute graft-versus-host disease (GvHD) and chronic GvHD were not different between the 2 groups (acute GvHD: 20% vs 22% cumulative incidence in patients who underwent haplo before and after 2012, respectively [P = .67]; chronic GvHD: 19% vs 11% cumulative incidence, respectively; P = .12]. The 2-year relapse incidence was 20%, the nonrelapse mortality (NRM) rate was 48%, and no difference was observed over time (21% vs 19% [P = .72] and 54% vs 38% [P = .11] for patients who underwent haplo before and after 2012, respectively). The main cause of NRM was infection. Haplo after 2012 (hazard ratio [HR], 0.57; P = .01), younger age (HR, 0.82; P = .02), and receipt of a reduced-intensity conditioning (RIC) regimen (HR, 0.53; P = .01) were independently associated with lower NRM. The 2-year overall survival rate was 36% and improved after 2012 (29% vs 47% before 2012; P = .02); and it was higher for patients who underwent transplantation in CR1 (41% vs 29%; P = .01). In multivariate analysis, haplo after 2012 (HR, 0.54; P = .003) and receipt of a RIC regimen (HR, 0.54; P = .005) were independently associated with better overall survival. Similarly, leukemia-free survival and GvHD-free/relapse-free survival (GRFS) improved over time: the leukemia-free survival rate was 31% (25% vs 43% in the groups who underwent transplantation before and after 2012, respectively; P = .05), and the GRFS rate was 24% (19% vs 34%, respectively; P = .09). In addition, leukemia-free survival and GRFS improved among patients who received a RIC regimen. Conclusions The outcome of patients with acute leukemia who underwent T-cell-depleted haplo has improved over time. Cancer 2018;124:2142-50. © 2018 American Cancer Society.

Introduction/Background Azacytidine (AZA) has been used as a promising treatment for relapse after allogeneic transplantation. A clear benefit has been demonstrated when treating patients with a reduced disease burden, thus a prophylactic and preemptive approach to these patients has emerged. Materials and Methods We retrospectively analyzed patients with myeloid malignancies treated with azacytidine in the posttransplantation setting between September 2013 and April 2018 in a single tertiary care hospital. Of 32 patients analyzed, 21 were treated for prophylactic use and 11 preemptively, with a median follow-up of 20 months. Prophylactic treatment consisted of AZA at 32 mg/m2 for 5 days every 28 days, and preemptive treatment of AZA 75 mg/m2 for 5 or 7 days per cycle. In addition, 10 patients received one or more donor lymphocyte infusions (DLIs). Two patients presented with infectious complications demanding hospitalization, and 13 patients (10 in the prophylactic group and 3 in the preemptive group) presented graft-versus-host disease (GvHD). Of patients who had GvHD, 3 needed treatment discontinuation. Overall, 12 patients suspended treatment, 8 for disease progression and 1 due to patient request. Results In the prophylactic group, all patients are alive at 1 year with an event-free survival (EFS) of 95%, as only 1 patient relapsed. In the preemptive group, 1-year EFS was 54% and 1-year overall survival was 82%. Conclusion Low-dose AZA in posttransplantation patients with myeloid neoplasms is a well-tolerated therapy with the potential to prevent relapse and maintain stable remissions. Randomized prospective trials are needed to determine patient selection and dosage, timing, and duration of treatment.

We report the outcomes of 51 patients who underwent unmanipulated haploidentical hematopoietic stem cell transplantation (haplo-HSCT) with post-transplantation cyclophosphamide (PT-Cy) and antithymocyte globulin (ATG), from peripheral blood stem cells (PBSCs) or bone marrow, after receipt of a TBF (thiotepa, busulfan, and fludarabine) conditioning regimen. Their median age was 55 years (range, 16 to 72 years). Hematologic diagnoses included acute leukemias (n = 31), lymphoid neoplasm (n = 12), myeloproliferative neoplasm (n = 5), and myelodysplastic syndromes (n = 3). Thirty-seven patients (73%) were in complete remission. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate for all patients, associated with ATG in 39 patients (76.5%). The median time to neutrophil engraftment was 17 days (range, 12 to 34 days). The cumulative incidences of grade II-IV and grade III-IV acute GVHD were 27.5% and 14%, respectively. In patients receiving a PBSC graft and ATG prophylaxis, grade II-IV aGVHD occurred in 16% of patients. The use of ATG and a lower thiotepa dose (5 mg/kg versus 10 mg/kg) were associated with a reduced cumulative incidence of grade II-IV acute GVHD (P = .03 and .005, respectively). The 2-year cumulative incidence of chronic GVHD was 29% and was significantly reduced to 13% with the lower thiotepa dose (P = .002). After a median follow-up of 25 months (range, 12 to 62 months), the cumulative incidences of nonrelapse mortality, relapse, overall survival (OS), disease-free survival (DFS), and GVHD-free, relapse-free survival (GFRFS) were 20%, 22.5%, 67%, 58%, and 51%, respectively. Pretransplantation disease status (complete remission versus others) was the main factor associated with OS, DFS, and GFRFS. In conclusion, the TBF conditioning regimen is an appealing platform in the haplo-HSCT setting with PT-Cy in terms of engraftment rate, toxicity, and disease control. We found no benefit of a thiotepa dose of 10 mg/kg compared with a dose of 5 mg/kg. ATG reduced the risk of acute GVHD without comprising outcomes.

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.

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.