Service dHematologie greffe

Port-Saint-Louis-du-Rhône, France

Service dHematologie greffe

Port-Saint-Louis-du-Rhône, France
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Kharfan-Dabaja M.A.,H. Lee Moffitt Cancer Center and Research Institute | Labopin M.,Acute Leukemia Working Party of EBMT | Bazarbachi A.,American University of Beirut | Hamladji R.M.,Center Pierre et Marie Curie | And 9 more authors.
Bone marrow transplantation | Year: 2014

This retrospective analysis compared two regimens of fludarabine combined with i.v. BU 6.4 mg/kg (FB2) or BU 12.8 mg/kg (FB4) for allografting of AML in first CR. A total of 437 patients (median age: 50 years) were administered FB2 (n = 225, 51%) or FB4 (n = 212, 49%). Median follow-up time was 28 months. Use of FB2 resulted in a longer time to neutrophil engraftment (17 vs 15 days, P < 0.0001) but no difference in incidence of grade II-IV acute (P = 0.54) or chronic GVHD (P = 0.51). In patients < 50 years of age, FB2 was associated with a higher 2-year cumulative incidence of relapse (33 ± 6% vs 20 ± 4%, P = 0.04), but there was no difference in 2-year leukemia-free survival (LFS) (P = 0.45), OS (P = 0.53) or non-relapse mortality (P = 0.17). In recipients ⩾ 50 years of age, FB2 resulted in better 2-year LFS (63 ± 4% vs 42 ± 7%, P = 0.02) and OS (68 ± 4% vs 45 ± 7%, P = 0.006); a lower 2-year non-relapse mortality, albeit not statistically significant (15 ± 3% vs 29 ± 6%, P = 0.06), was observed with FB2. FB2 is an effective and well-tolerated regimen in patients ⩾ 50 years of age and does not compromise survival when used in patients <50 years undergoing allogeneic transplantation for AML in first CR.


De Latour R.P.,Service dHematologie Greffe | Porcher R.,Assistance Publique des Hopitaux de Paris | Dalle J.-H.,Service dHematologie Pediatrique | Aljurf M.,King Faisal Specialist Hospital And Research Center | And 12 more authors.
Blood | Year: 2013

Although allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment for patients with Fanconi anemia (FA), published series mostly refer to single-center experience with limited numbers of patients. We analyzed results in 795 patients with FA who underwent first HSCT between May 1972 and January 2010. With a 6-year median follow-up, overall survival was 49% at 20 years (95% confidence interval, 38-65 years). Better outcome was observed for patients transplanted before the age of 10 years, before clonal evolution (ie, myelodysplastic syndrome or acute myeloid leukemia), from a matched family donor, after a conditioning regimen without irradiation, the latter including fludarabine. Chronic graft-versus-host disease and secondary malignancy were deleterious when considered as time-dependent covariates. Age more than 10 years at time of HSCT, clonal evolution as an indication for transplantation, peripheral blood as source of stem cells, and chronic graft-versus-host disease were found to be independently associated with the risk for secondary malignancy. Changes in transplant protocols have significantly improved the outcome of patients with FA, who should be transplanted at a young age, with bone marrow as the source of stem cells. © 2013 by The American Society of Hematology.


Rondelli T.,Instituto Toscano Tumori | Risitano A.M.,University of Naples Federico II | de Latour R.P.,Service dHematologie Greffe | Sica M.,Instituto Toscano Tumori | And 13 more authors.
Haematologica | Year: 2014

Complement blockade by eculizumab is clinically effective in hemolytic paroxysmal nocturnal hemoglobinuria. However, the response is variable and some patients remain dependent on red blood cell transfusions. In 72 patients with hemolytic paroxysmal nocturnal hemoglobinuria on eculizumab we tested the hypothesis that response may depend on genetic polymorphisms of complement-related genes. We found no correlation between the complement component C3 genotypes and the need for blood transfusions. On the other hand, we found a significant correlation with the HindIII polymorphism of a complement regulatory gene, the complement receptor 1 (CR1) gene. At this locus two co-dominant alleles are known, of which H (common) is associated with high expression, whereas L (rare) is associated with low expression of CR1 on red blood cells. Patients who still needed blood transfusion on eculizumab accounted for 18% of the H/H homozygotes, 33% of the H/L heterozygotes and 68% of the L/L homozygotes (P=0.016). Thus, patients with paroxysmal nocturnal hemoglobinuria who have the L/L genotype are seven times more likely to be sub-optimal responders to eculizumab. Both in vitro and in vivo we found that the CR1 HindIII genotype correlates with the abundance of paroxysmal nocturnal hemoglobinuria red cells that have bound C3, and with the kinetics of C3 binding. These results are consistent with the notion that by affecting C3 binding the CR1 genotype influences the response to eculizumab treatment, and this emerges as a novel example of pharmacogenetics. © 2013 Ferrata Storti Foundation.


De Latour R.P.,Service dHematologie Greffe | De Latour R.P.,University Paris Diderot | De Latour R.P.,European Group for Blood and Marrow Transplantation | Soulier J.,University Paris Diderot | Soulier J.,French Institute of Health and Medical Research
Blood | Year: 2016

Fanconi anemia (FA) is the most frequent inherited cause of bone marrow failure (BMF). Most FA patients experience hematopoietic stem cell attrition and cytopenia during childhood, which along with intrinsic chromosomal instability, favor clonal evolution and the frequent emergence in their teens or young adulthood of myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). To early identify and further predict bone marrow (BM) clonal progression and enable timely treatment, the follow-up of FA patients includes regular BM morphological and cytogenetic examinations. Allogeneic hematopoietic stem cell transplantation (HSCT) remains the only curative treatment of FA patients with MDS or AML. Although questions remain concerning HSCT itself (including the need for pretransplant chemotherapy, the best conditioning regimen, and the optimal long-termfollow-upofsuchpatients especially regarding secondary malignancies), clonal evolution in the absence of significant BMdysplasia and blast cells can be difficult to address in FA patients, for whom the concept of preemptive HSCT is discussed. Illustrated by 3 representative clinical vignettes showing specific features of MDS and AML in FA patients, this paper summarizes our practical approach from diagnosisthroughtreatment inthisparticular situation. © 2016 by The American Society of Hematology.


De Latour R.P.,Service dHematologie Greffe | Fremeaux-Bacchi V.,Laboratoire dImmunologie | Fremeaux-Bacchi V.,Institute National Of La Sante Et Of La Recherche Medicale Unite Mixte Of Recherche Scientifiques 1138 | Porcher R.,Center dEpidemiologie Hotel Dieu | And 16 more authors.
Blood | Year: 2015

Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by intravascular hemolysis, which is effectively controlled with eculizumab, a humanized monoclonal antibody that binds complement protein 5 (C5). The residual functional activity of C5 can be screened using a 50% hemolytic complement (CH50) assay, which is sensitive to the reduction, absence, and/or inactivity of any components of the classical and terminal complement pathway. Little data exist on complement blockade during treatment. From 2010 to 2012, clinical data, hemolysis biomarkers, complement assessment, and free eculizumab circulating levels were systematically measured immediately before every injection given to 22 patients with hemolytic PNH while receiving eculizumab therapy. During the study, 6 patients received ≥1 red blood cell transfusion. Lack of detectable CH50 activity (defined by CH50 ≤ 10% of normal values) was found in 184 samples (51%) and was significantly associated with lower lactate dehydrogenase levels (P = .002). Low levels of circulating free eculizumab (<50 μg/mL) correlated with detectable CH50 activity (CH50 > 10%; P = .004), elevated bilirubin levels (P < .0001), and the need for transfusions (P = .034). This study suggests that both CH50 activity and circulating free eculizumab levelsmay help physicians tomanage PNH patients receiving eculizumab. © 2015 by The American Society of Hematology.


Tichelli A.,University of Basel | Rovo A.,University of Basel | Socie G.,Service DHematologie Greffe
Current Problems in Dermatology | Year: 2012

Today, long-term prognosis after hematopoietic stem cell transplantation (HSCT) has greatly improved. Nevertheless, there are still a number of malignant and nonmalignant late effects that can cause substantial morbidity, with considerable impact on the health status and quality of life in the long-term survivors. Transplant-preparative regimen and graft-versus-host disease are considered the main risk factors after allogeneic HSCT. The continuous changes in the transplantation practice and in the type of patients selected are responsible that the pattern of the late effects after HSCT is changing over time. Relevant recent changes concern the avoidance of total body irradiation conditioning whenever possible, the higher age of the patients transplanted, the increasing use of unrelated donors as well as the introduction of reduced intensity conditioning. The detection of an increasing number of late effects should not be considered as a drawback of HSCT. The experience gathered during the past decades has become the main source of information on which the current management of the long-term survivors is based. A broad expertise is mandatory to manage long-term survivors. Aftercare of long-term survivors includes a standardized screening, counseling of the patients as well as prevention and treatment of late effects. Counseling should include self-examination for early cancer detection, and advice for healthy lifestyle behavior. Beyond immediate survival, allogeneic HSCT is a lifelong commitment between long-term survivors and the transplant team, involving the recipient's family and the general health care providers. Proper information on 'life after HSCT' should also be provided to the whole community, which plays a key role in the social reinsertion of the long-term survivors. © 2012 S. Karger AG, Basel.


Peffault de Latour R.,Service dHematologie Greffe | Peffault de Latour R.,University Paris Diderot | Brunstein C.G.,University of Minnesota | Porcher R.,University Paris Diderot | And 11 more authors.
Biology of Blood and Marrow Transplantation | Year: 2013

For older patients with acute myeloid leukemia (AML), allogeneic hematopoietic cell transplantation (HCT) provides the best chance of long-term survival. A formal comparison between matched sibling (SIB), unrelated donor (URD), or umbilical cord blood (UCB) transplantation has not yet been reported in this setting. We compared reduced-intensity conditioning HCT in 197 consecutive patients 50years and older with AML in complete remission from SIB (n=82), URD (n=35), or UCB (n=80) transplantation. The 3-year cumulative incidences of transplantation-related mortality were 18%, 14%, and 24% with SIB, URD, and UCB transplantation, respectively (. P=.22). The 3-year leukemia-free survival rates were 48%, 57%, and 33% with SIB, URD, and UCB transplantation, respectively (. P=.009). In multivariate analysis, poor-risk cytogenetics was associated with relapse (hazard ratio, 1.7 [95% confidence interval, 1.0 to 3.0]; P=.04) and worse leukemia-free survival (hazard ratio, 1.6 [95% confidence interval, 1.0 to 2.5]; P=.03), whereas donor choice had no significant impact on overall survival (. P=.73). Adjusted 3-year overall survival rates were 55% with SIB, 45% with URD, and 43% with UCB transplantation (. P=.26). Until prospective studies are completed, this study supports the recommendation to consider SIB donor, URD, or UCB for HCT for older patients with AML in complete remission. © 2013 American Society for Blood and Marrow Transplantation.


Warlick E.D.,University of Minnesota | Peffault de Latour R.,Service dHematologie Greffe | Shanley R.,University of Minnesota | Robin M.,Service dHematologie Greffe | And 9 more authors.
Biology of Blood and Marrow Transplantation | Year: 2015

The use of alternative donor transplants is increasing as the transplantation-eligible population ages and sibling donors are less available. We evaluated the impact of donor source on transplantation outcomes for adults with acute myeloid leukemia undergoing myeloablative (MA) or reduced-intensity conditioning (RIC) transplantation. Between January 2000 and December 2010, 414 consecutive adult patients with acute myeloid leukemia in remission received MA or RIC allogeneic transplantation from either a matched related donor (n=187), unrelated donor (n=76), or umbilical cord blood donor (n=151) at the University of Minnesota or HÔpital St. Louis in Paris. We noted similar 6-year overall survival across donor types: matched related donor, 47% (95% confidence interval [CI], 39% to 54%); umbilical cord blood, 36% (95% CI, 28% to 44%); matched unrelated donor, 54% (95% CI, 40% to 66%); and mismatched unrelated donor, 51% (95% CI, 28% to 70%) (. P <.11). Survival differed based on conditioning intensity and age, with 6-year survival of 57% (95% CI, 47% to 65%), 39% (95% CI, 28% to 49%), 23% (95% CI, 6% to 47%), 47% (95% CI, 36% to 57%), and 28% (95% CI, 17% to 41%) for MA age 18 to 39, MA age 40+, or RIC ages 18 to 39, 40 to 56, and 57 to 74, respectively (. P<.01). Relapse was increased with RIC and lowest in younger patients receiving MA conditioning (hazard ratio, 1.0 versus 2.5 or above for all RIC age cohorts), P <.01. Transplantation-related mortality was similar across donor types. In summary, our data support the use of alternative donors as a graft source with MA or RIC for patients with acute myeloid leukemia when a sibling donor is unavailable. © 2015 American Society for Blood and Marrow Transplantation.


Malcovati L.,University of Pavia | de Latour R.P.,Service dHematologie Greffe | Risitano A.,University of Naples Federico II
Leukemia Research | Year: 2011

Aplastic anemia (AA) and myelodysplastic syndromes (MDS) are a heterogeneous group of rare hematological disorders belonging to the Bone Marrow Failure (BMF) syndromes. The Aplastic Anemia and Myelodysplastic Syndromes International Foundation (AA&MDSIF) is a non-profit organization dedicated to supporting patients and families living with a BMF disease. They work to bring investigators together in a collaborative manner. This article summarizes key presentations from the last AA&MDSIF scientific symposium held in Bethesda, Maryland on March 2010. © 2010 Elsevier Ltd.


Genital chronic graft-versus-host disease (GVHD) is a frequent but underdiagnosed complication of allogeneic stem-cell transplantation impairing quality of life. We identified 32 female patients with genital chronic GVHD (cGVHD) who underwent allogeneic hematopoietic stem-cell transplantation in our center between 2000 and 2010 and who were followed after transplantation in a specialized gynecological consultation. Pre- and posttransplantation clinical data and detailed acute and cGVHD data were collected. All patients received the same local treatment for genital lesions. At presentation, most patients complained about vaginal dryness and dyspareunia with impairment in sexual activity. Fifty percent of patients had grade I genital lesions and 50% had grade II or III lesions. Patients seen later in gynecological consultation had more severe lesions than patients seen early after transplantation. At the time of diagnosis, most patients had other cutaneous or mucous localizations of cGVHD. In most cases, lesions were stabilized or decreased with local steroids and estrogen treatment, and most patients could resume sexual activity. Treatment was more efficient in patients with mild lesions than in others. Genital cGVHD should be systematically searched for in women who have received allogeneic hematopoietic stem-cell transplantation in an early specialized consultation, especially in case of other cutaneous or mucous localizations of cGVHD. Local treatment associating steroids and estrogen seemed to prevent further evolution of grade I genital lesions and to avoid surgical treatment.

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