Hepatitis-associated aplastic anemia.

Abstract Hepatitis-associated aplastic anemia (HAAA) is a rare illness, characterized by onset of pancytopenia with a hypoplastic bone marrow that traditionally occurs within 6 months of an increase in serum aminotransferases. HAAA is observed in 1% to 5% of all newly diagnosed cases of acquired aplastic anemia. Several hepatitis viruses have been linked to the disease, but in many cases no specific virus is detected. The exact pathophysiology is unknown; however, immune destruction of hematopoietic stem cells is believed to be the underlying mechanism. HAAA is a potentially lethal disease if left untreated. Management includes immunosuppression with antithymocyte globulin and cyclosporine and allogeneic hematopoietic stem cell transplantation

Allogeneic hematopoietic cell transplant in HCV-infected patients

Hepatitis C virus (HCV) is a major cause of liver disease worldwide. After allogeneic Hematopoietic Cell Transplant (HCT), HCV is known to be associated with transient hepatitis in the immediate post-transplant period, and a potential risk factor of veno-occlusive disease (SOS). Very recently, HCV-infected HCT recipients have been shown to be at higher risk of earlier cirrhosis, leading to greater morbidity and mortality. Long-term survivors after HCT are thus at a high risk for HCV-related complications and, as a consequence, the treatment of HCV infection becomes critical. We describe here the potential clinical complications in HCV-infected recipients, in the short, but also the long-term follow-up after HCT. The pathophysiology of liver fibrosis is discussed as well as the present recommended therapy in this particular population

Reconstitution of adaptive immunity after umbilical cord blood transplantation and clinical implication regarding risk of infections

In comparison with allogeneic stem cell transplantation (alloHSCT) with other stem cell sources, umbilical cord blood transplantation (UCBT) was traditionally associated with increased risk of infections, particularly during the first 3 months after transplantation. Longitudinal studies of immune monitoring reported peculiar patterns of T- and B-cell recovery in the peripheral blood of UCB recipients during the first months post-transplantation. Overall, current data suggest delayed reconstitution of naive and memory CD4+ and CD8+ T-cell pools after UCBT. This is particularly true for adult recipients and for patients who received in vivo T-cell depleting approaches before the transplantation. Such delayed T-cell recovery may increase susceptibility of UCB recipients for developing opportunistic infections and viral reactivations. Regarding B-cell recovery, UCBT was associated with accelerated B-lymphopoiesis. Recent studies also reported evidence for faster functional memory B-cell recovery in UCB recipients. In this article, we briefly review T- and B-cell reconstitution after alloHSCT, with emphasis on peculiarities observed after UCBT. We further put these data in lines with risks of infections after UCBT

Polyomaviruses KI and WU in Immunocompromised Patients with Respiratory Disease

Polyomaviruses KI (KIPyV) and WU (WUPyV) were recently identified, mainly in respiratory specimens from children. Among 200 patients with respiratory disorders admitted to Saint Louis Hospital, Paris, France, KIPyV was detected in 8% and WUPyV in 1%. KIPyV was significantly more frequent among human stem cell transplant patients (17.8% vs. 5.1%; p = 0.01)

Allogenic hematopoietic stem cell transplantation after reduced intensity conditioning regimen for elderly patients (60 years and older) with hematologic malignancies using unrelated donors: a retrospective study for the French society for stem cell transplantation (SFGM-TC)

Peer reviewe

Outcome after failure of allogeneic hematopoietic stem cell transplantation in children with acute leukemia: a study by the Société Francophone de Greffe de Moelle et de Thérapie Cellulaire (SFGM-TC)

Allogeneic hematopoietic stem cell transplantation (SCT) contributes to improved outcome in childhood acute leukemia (AL). However, therapeutic options are poorly defined in case of post-transplantation relapse. We aimed to compare treatment strategies in 334 consecutive children with acute leukemia relapse or progression after SCT in a recent ten-year period. Data could be analyzed in 288 patients (157 ALL, 123 AML and 8 biphenotypic AL) with a median age of 8.16 years at transplantation. The median delay from first SCT to relapse or progression was 182 days. The treatment consisted in chemotherapy alone (n=108), chemotherapy followed by second SCT (n=70), supportive/palliative care (n=67), combination of chemotherapy and DLI (n=30), or isolated reinfusion of donor lymphocytes (DLI) (n=13). The median OS duration after relapse was 164 days and differed according to therapy: DLI after chemotherapy = 385 d, second allograft = 391d, chemotherapy = 174d, DLI alone = 140d, palliative care = 43d. A second SCT or a combination of chemotherapy and donor lymphocytes infusion yielded similar outcome (HR=0.85, p=0.53) unlike chemotherapy alone (HR 1.43 p=0.04), palliative care (HR=4.24, p<0.0001) or isolated DLI (HR=1,94, p<0.04). Despite limitations in this retrospective setting, strategies including immunointervention appear superior to other approaches, mostly in AML

Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

peer reviewedLate relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity

Hépatite C et allogreffe de moelle osseuse (suivi à long terme)

PARIS6-Bibl. St Antoine CHU (751122104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Comparaison de l utilisation d un conditionnement à intensité réduite avec celle d un conditionnement standard chez des patients de plus de 35 ans allogreffés pour une leucémie aiguë myéloide

L allogreffe de cellules souches hématopoiétique confère les meilleures chances de survie à long terme aux patients atteints de leucémie aigue myéloides (LAM) de groupe favorable ou intermédiaire. Cependant, sa toxicité limite souvent son indication, ce qui a favorisé le développement des conditionnements d intensité réduite (RIC) ces quinze dernières années. Le RIC est utilisé depuis des années chez des patients âgés ou ayant des comorbidités, mais son utilisation chez les plus jeunes est encore controversé en comparaison au conditionnement standard de référence (MAC). Nous avons comparé l utilisation de ces deux conditionnements chez 132 patients de plus de 35 ans atteints de LAM, allogreffés consécutivement dans notre centre avec des donneurs géno-identiques (N=87) ou non apparentés 10/10 (N=45) entre Janvier 2000 et Décembre 2010. Les conditionnements MAC (N=72) et RIC (N=60) ont été définis comme décrit précédemment par Bacigalupo et al (2009).Le suivi médian a été de 47 mois [10-134]. La prise de greffe a été observée chez tous les patients. L incidence cumulée de maladie du greffon contre l hôte (GVH) aiguë grade II-IV après ajustement était plus importante dans le groupe MAC (HR: 2,5, p = 0,0006) et aucune différence n a été observée concernant la GVH chronique entre les deux groupes. 71 patients sont décédés au cours de l étude. L incidence cumulée de mortalité liée à la greffe (TRM) à 4 ans était de 21% (13% après RIC vs. 28% après MAC, p = 0,009), sans différence significative après ajustement. Aucune différence d incidence cumulée de rechute à 4 ans n a été retrouvée après ajustement selon le risque cytogénétique, le sexe, la compatibilité du sexe donneur/receveur et le nombre de cellules injectées (HR 0,8, 95%CI 0,4 1,5, p = 0,50). La survie globale à 4 ans était de 46% (50% après RIC vs. 43% après MAC, p = 0,38). Les résultats en survie globale sont restés similaires après utilisation d un modèle de Cox et d inverse probability-of-treatment weighting .Cette étude permet de montrer que l utilisation d un conditionnement MAC a entraîné un taux plus élevé de TRM sans apporter de bénéfice en termes de rechute en comparaison avec un RIC. En attendant des études prospectives, cette étude est en faveur de l utilisation d un conditionnement RIC chez les patients de plus de 35 ans allogreffés pour des LAM.PARIS6-Bibl.Pitié-Salpêtrie (751132101) / SudocSudocFranceF