Management of anticoagulation and factor XIII replacement in a patient with severe factor XIII deficiency and recurrent venous thromboembolic disease: case report and review of literature.

Background: Thrombotic events in congenital factor (F)XIII deficiency are extremely rare. To our knowledge, we describe the first case of severe congenital FXIII deficiency associated with recurrent venous thrombotic events. Key Clinician Question: How to deal with anticoagulation treatment in patients with severe FXIII deficiency? Clinical Approach: The patient was treated with rivaroxaban and plasma-derived FXIII substitution therapy as prophylaxis without bleeding complications. We aimed at FXIII trough levels of 50% during the loading doses of rivaroxaban, then 30% during the maintenance dose of rivaroxaban, and finally 20% during the long-term use of prophylactic dose of rivaroxaban. Conclusion: Treatment of thrombotic events with rivaroxaban in patients with severe bleeding disorders seems to be safe, requiring an adaptation of the intensity of the replacement therapy.

[Direct oral anticoagulant for venous thrombosis in unusual sites]. / Place des anticoagulants oraux directs dans le traitement des thromboses veineuses de localisation inhabituelle.

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.

Clinical presentation, outcome, and prognostic markers in patients with intravascular large B-cell lymphoma, a lymphoma study association (LYSA) retrospective study.

BACKGROUND: Intravascular large B-cell lymphoma (lVLBCL) is a very rare type of large B-cell lymphoma. METHODS: We conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers. RESULTS: Sixty-five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23-92). Thirty-four patients (64%) had an IPI score >3 and 40 patients (67%) had a performance status ≥2. The most frequent extra-nodal locations were bone marrow (n = 34; 52%), central nervous system (n = 25; 39%), and skin (n = 21; 33%). Nodal involvement and endocrine system were observed in 34% (n = 22) and 18% (n = 12) of all cases, respectively. Twenty-six patients (41%) had macrophage activation syndrome. Tumor cells were frequently CD5 positive (52%) with a non-germinal center origin (86%). BCL2 was expressed in 87% of all samples analyzed (n = 20) and 43% of patients had a MYC/BCL2 double expression. Fifty-six patients were treated with a regimen of chemotherapy containing rituximab, among whom 73% reached complete remission. The median progression-free survival (PFS) and median overall survival (OS) were 29.4 months and 63.8 months, respectively. History of autoimmune disorder (Hazard ratio [HR] 3.3 [1.4-7.8]; p < 0.01), nodal involvement (HR 2.6 [1.4-5.1]; p < 0.01), lack of anthracycline (HR 0.1 [0-0.4] for use; p < 0.001), or no intensification at first-line regimen (p = 0.02) were associated with worse PFS. High-dose methotrexate use was not associated with better PFS or OS. CONCLUSIONS: Our study highlights the aggressive clinical picture of IVLBCL, in particular the frequency of macrophage activation syndrome, and the need for new therapies despite a response to R-CHOP-like regimen similar to non-intravascular diffuse large B-cell lymphomas.

Evaluation of Disease Risk Comorbidity Index after Allogeneic Stem Cell Transplantation in a Cohort with Patients Undergoing Transplantation with In Vitro Partially T Cell Depleted Grafts.

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 [HiR], 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 HiR, 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.

Utilisation des inhibiteurs de PD-1 dans les hémopathies lymphoïdes.

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.