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  • 1
    Publication Date: 2016-12-02
    Description: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely used in the treatment of a variety of hematologic diseases. However, allo-HSCT can be associated with many complications, including poor graft function early after transplant requiring long-lasting supportive care. In the literature, the incidence of poor graft function post allo-HSCT has been reported to range from 4 to 27%. Here, we retrospectively studied 10 patients (male/female: 4/6, median age: 45 years, range 19 to 67) who received a boost of CD34+ selected cells for poor graft function after allo-HSCT (of whom 4 cases of haplo-identical allo-HSCT with post-Cy prophylaxis), between January 2014 and January 2016. Patients' disease and transplant characteristics are summarized in the below table. Patients were selected for the CD34+ cells "boost" therapy after eliminating other causes that could explain a poor graft function (eg. drug toxicity, infections, disease relapse, etc.) The same original allo-HSCT donor was used to collect the CD34+ cells after mobilization with G-CSF and positive selection. The patients did not receive any prior conditioning therapy prior to CD34+ cells boost infusion. At time of the boost, all patients were in full donor chimerism. The number of infused CD34+ cells differed from one patient to another ranging from 2.91 to 7.99 x106 cells/kg recipient body weight. The median day of infusion post- allo-HSCT was 120 (range, 76-352). Among these 10 patients, 7 patients had full counts recovery at a median of 15 days (range, 7-30) post-infusion, while 3 patients had an incomplete response with persistent anemia and/or thrombocytopenia. None of the patients experienced clinically significant GVHD symptoms after the boost. At last follow-up, 7 patients were alive whereas 3 patients died of severe infections after 1, 6 and 13 months post-boost. Based on these results, we concluded that boost therapy can be used in the treatment of poor graft function post-allogeneic HSCT, including in those patients who received a haplo-transplant. Disclosures No relevant conflicts of interest to declare.
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  • 2
    Publication Date: 2018-11-29
    Description: 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.
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  • 3
    Publication Date: 2018-11-29
    Description: 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.
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  • 4
    Publication Date: 2018-11-29
    Description: Background: Allogeneic hematopoietic stem cell transplantation (allo-HCT) using a haploidentical donor (haplo-HCT) using post-transplant high-dose cyclophosphamide (PTCy) is increasingly used for patients lacking a matched related or unrelated donor. We recently noticed a relatively high incidence of infectious complications, especially Epstein-Barr virus (EBV) reactivation after haplo-HCT. However, the mechanisms underlying the increased incidence of this complication in the haplo-HCT setting are unknown. We hypothesized that the use of PTCy may be associated with a deficit in innate-like effector T cells essential for preventing EBV reactivation.This study aimed to analyze immune reconstitution following haplo-HCT using peripheral blood stem cells (PBSC) grafts and to evaluate the correlations with EBV reactivation and outcomes. Patients and Methods: One hundred and twenty-three consecutive patients who underwent allo-HCT for hematological malignancies between 2013 and 2016 were included in this single-center retrospective study. All patients received G-CSF mobilized PBSC grafts and ATG 2.5-5 mg/Kg total dose. All patients received a combination of cyclosporine A and mycophenolate mofetil for GvHD prophylaxis, except for patients with a matched related donor (MRD) who received cyclosporine A alone and patients with an haploidentical donor who received PTCy (50mg/kg/d at d3+/-d5). α/β T cells (CD3+, CD4+ and CD8+), γ/δ T cells (pan γ/δ and Vδ2+), mucosal-associated T cells wich express a highly restricted TCR comprising a semi-variant Vα7.2-Jα33 (MAIT), invariant NK T cells, NK cells, B cells, Tregs, monocytes subsets and dendritic cells (myeloid DC, plasmacytoid DC and Slan-DC) were analyzed by multi-color flow cytometry at months (M) 1, 3, 6 and 12 following allo-HCT. Clinical data [acute GvHD (aGvHD), relapse incidence, chronic GvHD (cGvHD), viral reactivations, bacterial and fungal infections, non-relapse mortality (NRM), progression-free survival (PFS), refined GvHD-free and progression-free survival (GPFS), overall survival (OS)] were assessed together with sequential quantitative evaluation of immune subsets. Results: Median age was 55 (range, 17-70) years, with 32 male patients (26%) receiving a graft from a female donor. Diagnoses were myeloid malignancies (66%) or lymphoid malignancies (34%). Thirty-three patients (27%) received a graft from a MRD, 65 from an unrelated donor (MUD, 53%), and 25 from a haplo-identical donor (20%). Thirty patients (24%) with refractory disease received a sequential conditioning regimen while the remaining (n=93, 76%) received a RIC/RTC regimen based on fludarabine, busulfan +/- thiotepa. At d180, the cumulative incidences (CIs) of grade II-IV and grade III-IV aGvHD were 34% and 5%, respectively. The 2 years CIs of cGvHD, extensive cGvHD and relapse were 23%, 8% and 17%, respectively. At 2 years, NRM was 7%, PFS was 77%, GPFS was 66% and OS was 83%. The rate of EBV reactivation was significantly increased in haplo-HCT recipients as compared to fully-matched donor recipients (respectively, 68% versus 26%, P〈 .001). At one month after allo-HCT, the median counts of all immune cells subsets (except monocytes) was significantly lower in haplo-HCT recipients as compared to MRD or MUD recipients. At 3 months, α/β T cells, iNK T cells, NK cells, B cells, Tregs and Slan-DC reached similar median counts in haplo-HCT recipients as compared to MRD or MUD recipients. In contrast, Vδ2+ T cells and MAIT cells median counts remained significantly lower at 3, 6 and 12 months in haplo-HCT recipients compared to MRD or MUD recipients (at M1, M3, M6, M12, the median Vδ2+ T cells counts were 0.05/µL, 0.24/µL, 1.38/µL and 2.97/µL, and MAIT cells were 0.07/µL, 0.70/µL, 1.00/µL and 1.21/µL, respectively). Lower Vδ2+ T-cells and MAIT cells counts at one month was associated with a significantly increased CI of EBV reactivation (respectively, P=.04 and P
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  • 5
    Publication Date: 2019-11-13
    Description: 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.
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  • 6
    Publication Date: 2019-11-13
    Description: 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
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  • 7
    Publication Date: 2019-11-13
    Description: 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.
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  • 8
    Publication Date: 2017-12-07
    Description: Introduction. Haploidentical stem cell transplantation (Haplo-SCT) using post-transplant cyclophosphamide (PT-Cy) is being increasingly used in patients who lack a matched related or unrelated donor. It provides the opportunity for nearly all patients to benefit from hematopoietic stem cell transplantation when a matched donor is unavailable. However, while the use of PT-Cy has proven to be very effective to prevent graft-versus-host disease (GVHD) in the haplo setting, this effect may be associated with an enhanced and prolonged immunosuppression leading to a higher infectious related morbidity and mortality in those patients. Therefore, we performed this retrospective study to evaluate comprehensively the incidence and features of infectious complications in adult patients receiving PT-Cy haplo-SCT. Patients and Methods. Seventy-two consecutive adult patients who underwent haplo-SCT with PT-Cy between December 2012 and December 2016, in Saint-Antoine Hospital, Paris, France were included in this study. Graft was either bone marrow (BM, n=21) or peripheral blood stem cell (PBSC, n=51). All patients received PT-Cy 50 mg/Kg/d, either one (BM, n=20; PBSC, n=1) or two days (BM=1, PBSC, n=50), for GVHD prophylaxis. In addition all patients received cyclosporine A and mycophenolate mofetil and 60 patients (83%) received antithymocyte globuline. Conditioning regimens were reduced in 23 patients (32%), sequential in 27 (38%) and myeloablative (reduced toxicity) in 22 (30%). 42 recipients (58%) and 48 donors were CMV positive, whereas 66 donors and recipients (92%) were EBV positive. The HSCT comorbidity index (Sorror Score) was 0 in 29 patients (40%), 1 or 2 in patients 29 (40%) and ≥3 patientsin 14 (%20). Main transplant outcomes and cumulative incidence (CI) of bacterial, fungal and viral were evaluated. Results. Median age at transplantation was 48 (range, 15-72) years. 44 patients (61%) had myeloid malignancies and 28 patients (39%) had lymphoid malignancies. Disease risk index was low/intermediate in 42 patients (59%) and high/very-high in 30 patients (41%). Median dose of total nucleated cells was 3.61´108 (range, 1.16-11.86) cells/kg. Median follow-up was 23.3 (range, 4.7-48.9) months. The 2-years overall survival and progression free survival were respectively 60% and 40%. The 2-years CI of relapse was 18%. The CI of NRM was 16% at day 100, 31% at one year and 33% at 2-years. Neutrophil recovery was achieved at a median time of 17 (range: 12-88) days after haplo-SCT. The days CI of grade II-IV and grade 180III-IV acute GVHD were, respectively, 28% and 15%. The 2-years, CI of overall .and extensive chronic GVHD were, respectively, 31% and 12% The CI of bacterial infections was 43% at day 100, 46% at one year and 48% at 2-years. 8 patients were admitted to intensive care unit for bacterial infections. The CI of fungal infections was 24% at day 100, 28% at one year and 28% at 2-years. Although the CI of cytomegalovirus (CMV) reactivation was 56% at day 100 and 60% at one and 2-years, only one patient presents a CMV disease (CMV retinitis). With a CI of Epstein Barr Virus (EBV) reactivation was 54% at day 100, 68% at one year and 72% at 2-years, only 2 patients developed an EBV related post-transplant lymphoproliferative disease (PTLD, 2-years CI: 2.8%). The CI of BK virus and severe BK virus cystitis were respectively 31% and 24% at day 100, and 33% and 25% at one and 2-years. Concerning Human Herpes Virus 6 reactivation, the CI was 65% at day 100, 67% at one year and 69% at 2-years. Finally, the CI of infectious-related mortality (IRM) was 13% at day 100, and 20% at one year and 2-years. Of note, type of graft and dose of Cy have no impact on IRM and CI of infections. Conclusion. In conclusion, this data shows that haplo-SCT is associated with a high incidence of infections, in particular viral reactivation, and that these complications occur mainly within the first 100 days after allo-SCT. However, beside BK virus cystitis, these complications remain manageable as highlighted by the low incidence of CMV disease and PTLD. The high incidence of severe BK virus cystitis remains a matter of concern and strategies must be developed to prevent this complication. Overall, the high incidence IRM, haplo-SCT appears to be an effective strategy in patients with a 2-years overall survival of 60%. Finally, further improvements are required to decrease the incidence of infectious complication and improve patients' outcome after haplo-SCT. Disclosures Mohty: Sanofi: Honoraria, Speakers Bureau.
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