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Thrombosis in unusual sites account for approximately 4% of venous thromboembolic events. The safety of direct oral anticoagulants (DOACs) has led to the widespread use of these treatments. However, they have mainly been studied in deep vein thrombosis of the lower limbs and in pulmonary embolism. This review of the literature assesses the current knowledge of the use of DOACs for venous thrombosis in unusual sites (splanchnic, cerebral, ovarian, upper-extremity deep vein thrombosis). Numerous case reports or observational studies have been published, but very few randomized trials. Nevertheless, experts-based guidelines suggest that these anticoagulants may be considered in specific cases.La maladie thromboembolique veineuse de localisation atypique (MTEV-LA) représente environ 4 % des événements thromboemboliques veineux. Les anticoagulants oraux directs (ACOD), faciles d’utilisation et sécuritaires, ont essentiellement été étudiés dans la MTEV classique (thrombose veineuse profonde des membres inférieurs et embolie pulmonaire). Dans cette revue de la littérature, nous dressons un état des lieux sur les connaissances actuelles concernant l’utilisation des ACOD dans la MTEV-LA, notamment les thromboses splanchnique, cérébrale, ovarienne et des membres supérieurs. De nombreuses descriptions de cas et études observationnelles ont été publiées mais très peu d’essais randomisés l’ont été. Malgré cela, plusieurs sociétés savantes proposent la prescription d’ACOD dans certains cas spécifiques de MTEV-LA.

Outcomes of hematopoietic stem cell transplantation (HSCT) are influenced by comorbidities, disease type, and status at transplantation. Several prognostic scores can be used, such as the disease risk index (DRI) or the hematopoietic cell transplantation-specific comorbidity index (HCT-CI). Recently, a new prognostic tool, the disease risk comorbidity index (DRCI), combining the DRI and the HCT-CI, was published. The DRCI determines 6 patient groups (very low risk [VLR], low risk [LR], intermediate risk 1 [IR-1], intermediate risk 2 [IR-2], high risk [HR], and very high risk [VHR]) with a significant predictive value for overall survival (OS), disease-free survival (DFS), relapse incidence (RI), and graft-versus-host disease-free/relapse-free survival (GRFS). However, the DRCI has not been evaluated for patients allografted with partially in vitro T cell depleted (pTDEP) grafts. In our center, we offer pTDEP to reduce graft-versus-host disease for patients in complete remission at transplant time. In this retrospective study, we investigated the DRCI in 404 adult patients (including 37.6% pTDEP) undergoing a first HSCT for hematological malignancies from 2008 to 2018. Because of the small number of patients in LR, VLR and LR were combined for analysis. In the entire cohort, 2-year OS was 84.4% (95% CI, 71.6% to 97.2%) for LR, 61.6% (54.8% to 68.4%) for IR-1, 45.7% (33.3% to 58.1%) for IR-2, 31% (19.4% to 42.6%) for HR, and 30.9% (14.5% to 47.3%) for VHR (P < .001). In addition, the DRCI was predictive of DFS, RI, and GRFS but not of nonrelapsed mortality and graft-versus-host disease. Our study confirms similar results with the original publication but gives less accurate prognosis information than the DRI and HCT-CI when used separately. In conclusion, the DRCI does not seem to offer more relevant information than the DRI and HCT-CI to help physicians and patients for the HSCT decision.

Introduction Allogeneic hematopoietic stem cell transplantation (HSCT) is a well-established therapeutic modality for a variety of hematological malignancies and congenital disorders. One of the major complications of the procedure is graft-versus-host-disease (GVHD) initiated by T cells co-administered with the graft. Removal of donor T cells from the graft is a widely employed and effective strategy to prevent GVHD, although its impact on post-transplant immune reconstitution might significantly affect anti-tumor and anti-infectious responses. Several approaches of T cell depletion (TCD) exist, including in vivo depletion using anti-thymocyte globulin (ATG) and/or post-transplant cyclophosphamide (PTCy) as well as in vitro manipulation of the graft. In this work, we analyzed the impact of different T cell depletion strategies on immune reconstitution after allogeneic HSCT. Methods We retrospectively analysed data from 168 patients transplanted between 2015 and 2019 at Geneva University Hospitals. In our center, several methods for TCD are being used, alone or in combination: 1) In vivo T cell depletion using ATG (ATG-Thymoglobulin 7.5 mg/kg or ATG-Fresenius 25 mg/kg); 2) in vitro partial T cell depletion (pTCD) of the graft obtained through in vitro incubation with alemtuzumab (Campath [Genzyme Corporation, Cambridge, MA]), washed before infusion and administered at day 0, followed on day +1 by an add-back of unmanipulated grafts containing about 100 × 106/kg donor T cells. The procedure is followed by donor lymphocyte infusions at incremental doses starting with 1 × 106 CD3/kg at 3 months to all patients who had received pTCD grafts with RIC in the absence of GVHD; 3) post-transplant cyclophosphamide (PTCy; 50 mg/kg) on days 3 and 4 post-HSCT. Absolute counts of CD3, CD4, CD8, CD19 and NK cells measured by flow cytometry during the first year after allogeneic HSCT were analyzed. Measures obtained from patients with mixed donor chimerism or after therapeutic DLI were excluded from the analysis. Cell numbers during time were compared using mixed-effects linear models depending on the TCD. Multivariable analysis was performed taking into account the impact of clinical factors differing between patients groups (patient's age, donor type and conditioning). Results ATG was administered to 77 (46%) patients, 15 (9%) patients received a pTCD graft and 26 (15%) patients received a combination of both ATG and pTCD graft. 24 (14%) patients were treated with PTCy and 26 (15%) patients received a T replete graft. 60% of patients had a reduced intensity conditioning (RIC). 48 (29%) patients received grafts from a sibling identical donor, 94 (56%) from a matched unrelated donor, 13 (8%) from mismatched unrelated donor and 13 (8%) received haploidentical grafts. TCD protocols had no significant impact on CD3 or CD8 T cell reconstitution during the first year post-HSCT (Figure 1). Conversely, CD4 T cells recovery was affected by the ATG/pTCD combination (coefficient ± SE: -67±28, p=0.019) when compared to the T cell replete group (Figure 1). Analysis of data censored for acute or chronic GVHD requiring treatment or relapse revealed a delay of CD4 T cell reconstitution in the ATG and/or pTCD treated groups on (ATG:-79±27, p=0.004; pTCD:-100±43, p=0.022; ATG/pTCD:-110±33, p Conclusion Our results indicate that all TCD protocols with the only exception of PTCy are associated with a delayed recovery of CD4 T cells whereas pTCD of the graft, alone or in combination with ATG, significantly improves NK and B cell reconstitution. Figure 1 Disclosures No relevant conflicts of interest to declare.

Background: The AML EBMT Cytogenetic Risk score is a new prognostic model recently published (Canaani et al. Leukemia. 2019 Aug;33(8):1944-1952; Nagler el al. Am J Hematol. 2020 Jun 12) combining cytogenetics and FLT3ITD status for AML patients in complete remission (CR) at transplant time. The AML EBMT Cytogenetic Risk score is prognostic for leukemia-free survival (LFS), overall survival (OS), GVHD-free/relapse-free survival (GRFS) and cumulative incidence of relapse (CIR). In our centre, we frequently offer in-vitro partial T-cell depleted graft (pTDEP) for patient in CR to decrease morbidity and mortality associated with graft-versus-host disease (GvHD). Currently, The AML EBMT Cytogenetic Risk score has not been evaluated in this population. Aims: We investigate the impact of the AML EBMT Cytogenetic Risk score for 3 years OS, LFS, GRFS, CIR and NRM in a cohort with patients allografted with pTDEP graft. Methods: All consecutive ≥18 years patients who received a first allograft for AML between 2008 and 2018 with data available to determine The AML EBMT Cytogenetic Risk score in CR at transplant time were included. OS and LFS were investigated with the Kaplan-Meier method and we used the cumulative incidence estimator as defined by Fine and Gray to calculate CIR (with NRM as competing event), NRM (with relapse as competing event) and GvHD (with relapse as competing event). Results: 135 patients were included, median age at transplant time was 56 years (range: 19-74), 44% were female, median Karnofsky index was 90 (80-100). 21% of graft were from HLA identical, 57% from matched unrelated donor, 10% from mismatched unrelated donor and 12% from haploidentical donor. Stem cell source was peripheral blood in 89% and bone marrow in 11%. Partial in-vitro T-cell depletion (pTDEP) was performed in 40% of HSCT. Reduced-intensity (RIC) was performed in 62%. Median follow-up was 3.1 year (range 1.3-10 years) for living patients. Among the 135 patients, 4 (3%) were assigned in the favourable (Fav), 58 (43%) in the intermediate/FLT3wt (Int/FLT3wt), 36 (27%) in the intermediate/FLT3ITD (Int/FLT3ITD), and 37 (27%) in the adverse (adv) risk group. 3-years OS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (32-100%), 65% (52-77%), 60% (43-77%) and 28% (10-45%), respectively (p=0.033) (Fig 1A). 3-years LFS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (95%CI: 32-100%), 60% (47-73%), 49% (32-66%) and 25% (8-42%), respectively (p=0.028) (Fig 1B). 3-years GRFS for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 75% (32-100%), 45% (31-58%), 39% (22-55%) and 14% (0-27%), respectively (p=0.008) (Fig 1C). 3-years CIR for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 0%, 22% (11-33%), 31% (15-47%) and 56% (37-75%), respectively (p=0.02). 3-years NRM for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 25% (95%CI: 0-75%), 17% (7-28%), 21% (6-35%) and 17% (2-32%), respectively (p=0.92). 3-years grade 2-4 aGVHD for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 0%, 35% (22-47%), 19% (2-36%) and 42% (25-58%), respectively (p=0.46). 3-years cGVHD for Fav, Int/FLT3wt, Int/FLT3ITD and Adv was 25% (95%CI: 0-75%), 17% (6-27%), 22% (7-38%) and 21% (6-35%), respectively (p=0.9). In addition to The AML EBMT Cytogenetic Risk score, variables with a significance in univariate for OS with a p-value ≤0.1 (Karnofsky index [ Conclusion: In the analysis of our retrospective cohort including 40% of pTDEP patients, we confirm that the AML EBMT cytogenetic risk is prognostic for relevant outcomes (OS, LFS, GRFS, CIR) of HSCT. Similarly with recently published data, we confirm this prognostic model can help physicians and patients in transplant choice and remains valid for patients undergoing HSCT with in-vitro graft manipulation. Disclosures No relevant conflicts of interest to declare.

ANTI-PD-1 ANTIBODIES THERAPEUTIC USE IN LYMPHOID NEOPLASMS: Immune checkpoints blockade is under investigation in oncology, and has demonstrated its clinical efficacy. In hematology, immune checkpoints blockade is in earlier stages of development, but there are strong evidences of PD-1 blockade anti-tumor efficacy in some lymphoid malignancies. In this review, we will discuss the main clinical results of PD-1 inhibitors in lymphoid neoplasms and the main perspectives of development.

Introduction. Chronic lymphocytic leukemia (CLL) has typically an indolent course but can undergo transformation into a more aggressive lymphoma (mainly of diffuse large B-cell lymphoma histology) that is called Richter's syndrome. While the advent of novel therapies targeting the BCR signaling or the BCL-2 protein is transforming the management of patients with CLL, these drugs failed to prevent the risk of RS that is estimated to be 0.5-1% per year. RS is associated with a very poor outcome and is thus becoming the main obstacle to long term CLL cure. Allogeneic stem-cells transplantation (allo-SCT) has been recommended as the treatment of choice in eligible patients with clonally related RS (Rossi Blood 2018) but previous experience is still limited to less than 50 cases. We here aimed to investigate the safety and efficacy of allo-SCT for patients with RS. Methods. We report on a retrospective study of consecutive patients with RS who underwent allo-HSCT between 2005 and 2016 in 15 French and Belgian centers from the Société Francophone de Greffe de Moelle et de Transplantation Cellulaire (SFGM-TC). Inclusion criteria were: age >18, confirmed RS diagnosis, allo-HCST from either sibling or unrelated donor. Data quality was ensured using computerized discrepancy errors and on-site data verification. Results. A total of 24 patients (median age=59 years [19-69], M/F= 18/6) were included in the present study. Median time from CLL to RS diagnosis was 59 months [0-198]. The histology was DLBCL (86%) or HL (14%). The patients received a median of 1 [0-4] therapeutic line for CLL and 1 [0-3] for RS. Nine (38%) patients underwent auto-SCT prior to allo-HCT. At allo-HCT, 17 (71%) of patients were in complete and 7 (29%) in partial response. Most patients received reduced intensity conditioning (RIC) regimen (n= 18, 75%) and peripheral blood (76%) as source of stem-cells. Two (8%) patients received bone marrow stem cells and 4 (16%) cord blood stem cells. Donors were related (n=8) or unrelated (mismatched, n=8; matched, n=5; missing, n=3). A total of 15 patients (63%) received total body irradiation (TBI) within the conditioning. With a median follow-up of 27 months, 2-year OS was 44% (figure 1). The 100-day non-relapse mortality was 25%. Cause of death was relapse (n=3), treatment toxicity (n=10; GVHd, n=3; infectious complications, n=6; pulmonary toxicity, n=1), infection complications (n=1) and cerebral stroke (n=1). 2-year OS was significantly shorter for older patients (20% if >59 years old vs 64% if ≤59,P = 0.031). The 2-year OS was influenced by presence of cGVHD (73% vs 25%,P = 0.006). Neither donor type, prior auto-SCT, disease status prior to allo-HCT, use of antilymphocyte serum infusions nor the regimen conditioning significantly impact OS. Conclusion. Our study suggests that allo-HCT is a strategy achieving prolonged survival but should be performed in young patients to limit the risk of NRM. The favorable impact of GVHd suggests an anti-RS allogenic effect. Disclosures Guieze: abbvie: Honoraria; janssen: Honoraria; gilead: Honoraria.