Umbilical Cord Blood Transplantation for Fanconi Anemia With a Special Focus on Late Complications: a Study on Behalf of Eurocord and SAAWP-EBMT.

Hematopoietic cell transplantation (HCT) remains the sole available curative treatment for Fanconi anemia (FA), with particularly favorable outcomes reported after matched sibling donor (MSD) HCT. This study aimed to describe outcomes, with a special focus on late complications, of FA patients who underwent umbilical cord blood transplantation (UCBT). In this retrospective analysis of allogeneic UCBT for FA performed between 1988 and 2021 in European Society for Blood and Marrow Transplantation (EBMT)-affiliated centers, a total of 205 FA patients underwent UCBT (55 related and 150 unrelated) across 77 transplant centers. Indications for UCBT were bone marrow failure in 190 patients and acute leukemia/myelodysplasia in 15 patients. The median age at transplantation was 9 years (range, 1.2 to 43 years), with only 20 patients aged >18 years. Among the donor-recipient pairs, 56% (n = 116) had a 0 to 1/6 HLA mismatch. Limited-field radiotherapy was administered to 28% (n = 58) and 78% (n = 160) received a fludarabine (Flu)-based conditioning regimen. Serotherapy consisted of antithymocyte globulin (n = 159; 78%) or alemtuzumab (n = 12; 6%). The median follow-up was 10 years for related UCBT and 7 years for unrelated UCBT. Excellent outcomes were observed in the setting of related UCBT, including a 60-day cumulative incidence (CuI) of neutrophil recovery of 98.1% (95% confidence interval [CI], 93.9% to 100%), a 100-day CuI of grade II-IV acute graft-versus-host disease (GVHD) of 17.3% (95% CI, 9.5% to 31.6%), and a 5-year CuI of chronic GVHD (cGVHD) of 22.7% (95% CI, 13.3% to 38.7%; 13% extensive). Five-year overall survival (OS) was 88%. In multivariate analysis, none of the factors included in the model predicted a better OS. In unrelated UCBT, the 60-day CuI of neutrophil recovery was 78.7% (95% CI, 71.9% to 86.3%), the 100-day CuI of grade II-IV aGVHD was 31.4% (95% CI, 24.6% to 40.2%), and the 5-year CuI of cGVHD was 24.3% (95% CI, 17.8% to 32.2%; 12% extensive). Five-year OS was 44%. In multivariate analysis, negative recipient cytomegalovirus serology, Flu-based conditioning, age <9 years at UCBT, and 0 to 1/6 HLA mismatch were associated with improved OS. A total of 106 patients, including 5 with acute leukemia/myelodysplasia, survived for >2 years after UCBT. Nine of these patients developed subsequent neoplasms (SNs), including 1 donor-derived acute myelogenous leukemia and 8 solid tumors, at a median of 9.7 years (range, 2.3 to 21.8 years) post-UCBT (1 related and 8 unrelated UCBT). In a subset of 49 patients with available data, late nonmalignant complications affecting various organ systems were observed at a median of 8.7 years (range, 2.7 to 28.8 years) post-UCBT. UCB is a valid source of stem cells for transplantation in patients with FA, with the best results observed after related UCBT. After unrelated UCBT, improved survival was observed in patients who underwent transplantation at a younger age, with Flu-based conditioning, and with better HLA parity. The incidence of organ-specific complications and SNs was relatively low. The incidence of SNs, mostly squamous cell carcinoma, increases with time. Rigorous follow-up and lifelong screening are crucial in survivors of UCBT for FA.

Retrospective, real-life study of venetoclax plus azacitidine or low-dose cytarabine in French patients with acute myeloid leukemia ineligible for intensive chemotherapy.

BACKGROUND: Recently, the combination of venetoclax plus a hypomethylating agent (HMA; azacitidine ordecitabine) or low-dose cytarabine (LDAC) showed promise in Phase III trials in previously untreated AML. In France at the time of this study, venetoclax was not yet approved for AML and there were therefore no formal usage recommendations. Here we report the first study in a French cohort that assessed venetoclax in combination with existing treatments for AML under real-life conditions. METHOD: This retrospective, real-life study collected data on venetoclax use and management in a French cohort with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. RESULT: Of 118 patients, 81 were in second line/beyond (71.6% also hypomethylating agent [HMA]; 23.5% lowdose cytarabine [LDAC]) and 37 in first line. For venetoclax initiation, 57.3% underwent ramp up and 74.6% were hospitalized. Median venetoclax duration was 2.5 months (range 0.03-16.2). With all treatment lines and regimens, most common grade 3/4 adverse events were hematologic (overall 96.4% of patients) and infections (57.1%). Dosage adjustments for drug interactions and safety varied between centers. In second-line/beyond, median progression-free survival was 4.0 months (95% confidence interval [CI] 2.7-12.8) with venetoclax-HMA and 3.4 months (1.3-8.9) with venetoclax-LDAC; overall response rate was 51.9% and 41.2%, respectively. Thus, we showed that venetoclax-based treatment yields promising findings in patients with AML, but to address treatment complexity, practice harmonization is needed.

[DESCAR-T, a nationwide registry for patient treated by CAR-T Cells in France]. / DESCAR-T, le registre national des patients traités par CAR-T Cells.

CAR-T Cells have opened new doors for cellular immunotherapies and provides new therapeutic options for patients with refractory B-cell malignancies, B-cell acute lymphoblastic leukemia and diffuse large B-cel lymphoma. CAR-T Cells have benefited from an accelerated approval procedure in many countries. Indeed, The French health authorities have approved the specialties Tisacel ® and Axicel ®, but additional data including the use of CAR-T Cells in real life were also mandatory. In regard to the scientific interest of the project, LYSA-LYSARC committed itself to prospectively and retrospectively collect information on patients eligible for CAR-T Cells as required by French health authorities. Other academic cooperating groups (GRAALL, IFM, SFCE, FILO and the scientific society SFGM-TC) were associated to this initiative which aims to build a nationwide CAR-T Cells devoted registry, so-called DESCART (Dispositif d'Enregistrement et Suivi des patients traités par CAR-T cells). DESCAR-T is a real-life multicentric registry set up in French sites qualified for CAR-T Cells treatment. DESCAR-T objective is to describe the use of CAR-T Cells in real life. All paediatric and adult patients with hematological malignancy fulfilling CAR-T Cells approval criteria and for whom a CAR-T Cells therapy has been discussed are included from 1 July 2018. Clinical data are directly collected from medical records and patients are treated according to the centers' routine practices. One of the distinctive features of DESCAR-T is its link with HTA for CAR-T Cells s reimbursement by the French public health system. DESCAR-T is the first national registry promoted by an academic group allowing centralized data collection for both academic and HTA/health authorities' purposes.