Dynamics of cytomegalovirus populations harbouring mutations in genes UL54 and UL97 in a haematopoietic stem cell transplant recipient

We characterised by pyrosequencing, the dynamics of cytomegalovirus populations harbouring mutations A594V in gene UL97 and A834P and Q578H in gene UL54 in a haematopoietic stem cell transplant recipient. Unexpected re-emergence of A594V and decrease of A834P under CMX001 were shown to depend on both the selection pressure exerted by the antiviral treatments and the immune response

Allogeneic hematopoietic stem cell transplant in children and adults with sickle cell disease: Indications and modalities

La drépanocytose est une pathologie associée à des complications sévères et une mortalité précoce chez l'adulte. Chez l'enfant, l'allogreffe familiale HLA-identique de cellules souches hématopoïétiques permet de stopper la progression de la maladie et ainsi de « guérir » plus de 95 % patients, mais cette thérapeutique reste peu proposée chez les adultes du fait de sa toxicité potentielle. Cet atelier a eu pour objectif de définir les indications et les modalités d'allogreffe chez l'enfant et l'adulte atteints de drépanocytose. Les indications d'allogreffe familiale HLA-identique retenues chez l'enfant et chez l'adulte sont : la vasculopathie cérébrale, la survenue d'événements vaso-occlusifs sous hydroxycarbamide, l'atteinte rénale ou l'hépatopathie chronique secondaire à la drépanocytose, l'anémie chronique < 7 g/dL malgré l'hydroxycarbamide, la nécessité de maintenir plus de six mois un programme d'échange érythrocytaire, les difficultés transfusionnelles majeures par allo-immunisation antiglobules rouges. Chez l'enfant ayant un donneur familial HLA-identique, le conditionnement myéloablatif à base debusulfan, cyclophosphamide et sérum anti-lymphocytaire reste la référence compte tenu des excellents résultats obtenus avec cette approche. Chez les patients de plus de 15 ans, nous recommandons l'utilisation d'un conditionnement d'intensité réduite tel que celui rapporté par l'équipe du NIH (association d'alemtuzumab, d'irradiation corporelle totale à 3 Gy) suivie d'un greffon de cellules souches périphériques puis de sirolimus. En l'absence de donneur familial HLA- identique, il n'y a pas d'argument formel pour privilégier une allogreffe à partir d'un donneur non apparenté versus une allogreffe haplo-identique, mais nous recommandons que ces allogreffes alternatives soient évaluées dans le cadre de protocoles prospectifs

Semen Cryopreservation in Adolescents and Young Adults with Hematologic Diseases: from Bed to Benchside

International audiencePurpose: Infertility in adolescents and young adult (AYA) survivors of malignant disease remains a major long-term adverse effect, but semen collection for fertility preservation in fertility centers is not always feasible and makes AYAs uncomfortable. We evaluated the feasibility of collecting sperm samples on the ward versus in fertility centers. Methods: Consecutive hospitalized AYA-aged male patients in the Hematology AYA unit (Saint-Louis Hospital, France) between August 2010 and June 2016 with hematological disease and indication of semen collection (n = 95) were included in this retrospective study. Semen quality was analyzed according to World Health Organization guidelines and was compared according to semen collection place: on the ward (n = 46) or in fertility center (n = 49). Results: The median age was median age 19.1 years (range: 13.7-33.3; interquartile range: 17.1-22.8) and 85 patients successfully collected semen. Sperm collection failure was ∼11% and was comparable between the two modalities as were main sperm quality characteristics (semen volume, sperm concentration, total sperm count, progressive motility and vitality, sperm morphology, and multiple anomalies index). Oligospermia was significantly higher in the samples obtained in fertility center (47.7%) than on the ward (26.8%), p = 0.047. Average frozen straws were comparable, 12.2 ± 6.4 on the ward versus 11.9 ± 6.3 in fertility center. Conclusion: Semen collection on the ward is feasible and would be particularly interesting for AYA male patients without altering semen quality characteristics

Home spirometry in bronchiolitis obliterans after allogeneic haematopoietic cell transplant

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Flow cytometry minimal residual disease after allogeneic transplant for chronic lymphocytic leukemia

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A randomized study of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in elderly patients with acute lymphoblastic leukemia: the GRAALL-SA1 study

International audienceBACKGROUND: The prognosis of acute lymphoblastic leukemia in the elderly is poor. The GRAALL-SA1 phase II, randomized trial compared the efficacy and toxicity of pegylated liposomal doxorubicin versus continuous-infusion doxorubicin in patients 55 years or older with Philadelphia chromosome-negative acute lymphoblastic leukemia. DESIGN AND METHODS: Sixty patients received either continuous-infusion doxorubicin (12 mg/m(2)/day) and continuous-infusion vincristine (0.4 mg/day) on days 1-4 or pegylated liposomal doxorubicin (40 mg/m(2)) and standard vincristine (2 mg) on day 1, accompanied by dexamethasone, followed at day 28 by a second cycle, reinforced by cyclophosphamide. End-points were safety, outcome and prognostic factors. RESULTS: Myelosuppression was reduced in the pegylated liposomal doxorubicin arm with shorter severe neutropenia (P=0.05), shorter severe thrombocytopenia (P=0.03), and fewer red blood cell transfusions (P=0.04). Grade 3/4 infections and Gram-negative bacteremia were reduced in the pegylated liposomal doxorubicin arm (P=0.04 and P=0.02, respectively). There was a trend towards fewer cardiac events among the patients who received pegylated liposomal doxorubicin (1/29 versus 6/31). The complete remission rate was 82% and, with a median follow-up of 4 years, median event-free survival and overall survival were 9 and 10 months, respectively. Despite the better tolerance of pegylated liposomal doxorubicin, no differences in survival were observed between the two arms, due to trends towards more induction refractoriness (17 versus 3%, P=0.10) and a higher cumulative incidence of relapse (52% versus 32% at 2 years, P=0.20) in the pegylated liposomal doxorubicin arm. CONCLUSIONS: With the drug schedules used in this study, pegylated liposomal doxorubicin did not improve the outcome of elderly patients with acute lymphoblastic leukemia despite reduced toxicities

Recent results of hematopoietic stem cell transplantation for thalassemia with busulfan-based conditioning regimen in France: improved thalassemia free survival despite frequent mixed chimerism. A retrospective study from the Francophone Society of Stem Cell Transplantation and Cellular Therapy (SFGM-TC)

International audience[No abstract available

Role of allogeneic stem cell transplantation in adult patients with Ph-negative acute lymphoblastic leukemia

Because a pediatric-inspired Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) protocol yielded a markedly improved outcome in adults with Philadelphia chromosome-negative ALL, we aimed to reassess the role of allogeneic stem cell transplantation (SCT) in patients treated in the GRAALL-2003 and GRAALL-2005 trials. In all, 522 patients age 15 to 55 years old and presenting with at least 1 conventional high-risk factor were candidates for SCT in first complete remission. Among these, 282 (54%) received a transplant in first complete remission. At 3 years, posttransplant cumulative incidences of relapse, nonrelapse mortality, and relapse-free survival (RFS) were estimated at 19.5%, 15.5%, and 64.7%, respectively. Time-dependent analysis did not reveal a significant difference in RFS between SCT and no-SCT cohorts. However, SCT was associated with longer RFS in patients with postinduction minimal residual disease (MRD) ≥10(-3) (hazard ratio, 0.40) but not in good MRD responders. In B-cell precursor ALL, SCT also benefitted patients with focal IKZF1 gene deletion (hazard ratio, 0.42). This article shows that poor early MRD response, in contrast to conventional ALL risk factors, is an excellent tool to identify patients who may benefit from allogeneic SCT in the context of intensified adult ALL therapy. Trial GRAALL-2003 was registered at www.clinicaltrials.gov as #NCT00222027; GRAALL-2005 was registered as #NCT00327678

Post-transplant outcome of ovarian tissue cryopreserved after chemotherapy in hematological malignancies

International audienc

Long-term event-free survival, chimerism and fertility outcomes in 234 patients with sickle-cell anemia younger than 30 years after myeloablative conditioning and matched-sibling transplantation in France

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