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G Socié

Publications and source records attributed to G Socié.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors.

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

Adolescent↗
PubMed2006

Activating KIR genes are associated with CMV reactivation and survival after non-T-cell depleted HLA-identical sibling bone marrow transplantation for malignant disorders.

Combinations of HLA and killer immunoglobulin-like receptors (KIR) may affect outcome in T-cell depleted haematopoietic stem cell transplantation (HSCT). The KIR gene family includes inhibitory (KIR2DL and 3DL) and activating receptors (KIR2DS). Ligands are HLA-C (KIR2D) and HLA-Bw4 (KIR3DL1) for inhibitory KIR and are still unknown for activating KIR. The impact of activating KIR genotypes from donor and recipient is poorly documented in HSCT outcome. Here, HLA and KIR genotypes were determined in 131 pairs from non-T-cell depleted HLA-identical sibling HSCT. No effect of 'missing KIR ligand' was detected on acute graft-versus-host disease (GVHD), relapse, survival or infections even in myeloid malignancies. However, additional activating KIR genes in the donor compared to the recipient's genotype or an identity between donor and recipient activating KIR genotypes was associated with a lower transplant-related mortality (TRM) (P=0.005) and in a multivariate analysis with a better survival (P=0.02, HR=0.28; P=0.013, HR=0.29) and a lower incidence of cytomegalovirus (CMV) reactivation (P=0.009, HR=0.36). These data highlight the impact of donor-activating KIR genes on TRM, overall survival and CMV reactivation in HLA-identical sibling HSCT.

Adolescent↗
PubMed2006

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT).

More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.

Delivery of Health Care↗
PubMed2006

Bone marrow transplants from mismatched related and unrelated donors for severe aplastic anemia.

For patients with acquired severe aplastic anemia without a matched sibling donor and not responding to immunosuppressive treatment, bone marrow transplantation from a suitable alternative donor is often attempted. We examined risks of graft failure, graft-versus-host disease and overall survival after 318 alternative donor transplants between 1988 and 1998. Sixty-six patients received allografts from 1-antigen and 20 from >1-antigen mismatched related donors; 181 from matched and 51 from mismatched unrelated donors. Most patients were young, had had multiple red blood cell transfusions and poor performance score at transplantation. We did not observe differences in risks of graft failure and overall mortality by donor type. The probabilities of graft failure at 100 days after 1-antigen mismatched related donor, >1-antigen mismatched related donor, matched unrelated donor and mismatched unrelated donor transplants were 21, 25, 15 and 18%, respectively. Corresponding probabilities of overall survival at 5 years were 49, 30, 39 and 36%, respectively. Although alternative donor transplantation results in long-term survival, mortality rates are high. Poor performance score and older age adversely affect outcomes after transplantation. Therefore, early referral for transplantation should be encouraged for patients who fail immunosuppressive therapy and have a suitable alternative donor.

Adolescent↗
PubMed2006

Assessing the potential role of photopheresis in hematopoietic stem cell transplant.

The First International Symposium on Photopheresis in Hematopoietic Stem Cell Transplantation was held in Vienna, Austria with an educational grant from Therakos Inc. from 25 May to 27 May 2005. Three general issues were addressed: (1) pathophysiology of graft-versus-host disease (GvHD), (2) induction of immune tolerance and the immunology of phototherapy and (3) current standard treatment and prevention strategies of acute and chronic GvHD and the use of extracorporeal photopheresis (ECP). The objectives of the meeting were to open a dialogue among leading researchers in photobiology, immunology, and hematopoietic stem cell transplantation; foster discussions and suggestions for future studies of the mechanism of action of ECP in acute and chronic GvHD; and promote collaboration between basic scientists and clinicians. As can be seen from the summaries of the individual presentations, important advances have been made in our understanding of GvHD, including the use of photoimmunology interventions and the development of robust model systems. It is our expectation that data from photoimmunology studies can be used to generate hypotheses in animal models that can further define the mechanism of action of ECP and help translate the findings to clinical trials of ECP for the prophylaxis and treatment of both chronic and acute GvHD.

Graft vs Host Disease↗
PubMed2005

Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

SUMMARY: A survey was carried out among EBMT centres to describe the current practice concerning intrathecal (i.t.) prophylaxis in allogeneic stem cell transplantation for malignant diseases in patients with no central nervous system (CNS) manifestations of the disease at any time. A total of 90 centres reported their practice: 42 centres (47%) never used pre-transplant i.t. prophylaxis as part of the conditioning, whereas 48 centres (53%) gave i.t. prophylaxis to selected groups. The main indications were acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and lymphoma (53, 33, and 23% of all centres, respectively). Prophylaxis was usually given to all patients with ALL, but often restricted to high-risk patients in AML and lymphoma. Of the 90 centres, 29 (32%) gave prophylactic i.t. treatment after the transplantation, mainly for the same indications as pre-transplant. This survey illustrates the heterogeneity in the current practice of i.t. prophylaxis in allogeneic transplantation for malignant blood disorders in Europe. The documentation in the literature to support the use of i.t. prophylaxis as part of transplantation for malignant diseases in patients without preceding CNS involvement is sparse. Based on the rarity of isolated CNS relapse after allogeneic stem cell transplantation, EBMT does not recommend routine i.t. prophylaxis to patients without prior CNS involvement.

Antineoplastic Agents↗
PubMed2005

Allogeneic stem cell transplantation in second rather than first complete remission in selected patients with good-risk acute myeloid leukemia.

Through two consecutive trials, a policy that considered allogeneic stem cell transplantation (SCT) from a sibling donor in second rather than first complete remission (CR) in selected younger patients with acute myeloid leukemia (AML) with t(8;21)/inv(16) (core binding factor (CBF) group) or a normal karyotype (NN group) was followed by Acute Leukemia French Association (ALFA) centers. The outcome of 92 of these patients in first relapse (32 CBF, 60 NN) was reviewed with the aim of validating this strategy. The presence of an FLT3 internal tandem duplication (ITD) was retrospectively assessed in 50 patients. A total of 61 patients (66%) reached a second CR. Donor availability was an independent prognostic factor for survival in the whole patient population as well as in the CBF subset, but not in NN patients, further supporting this strategy for CBF-AMLs. In NN patients, FLT3-ITD was the main bad-prognosis factor for second CR achievement and survival, leading to consider SCT earlier, at least in FLT3-ITD patients with a donor.

Adult↗
PubMed2005

Treatment of chronic hepatitis C virus in allogeneic bone marrow transplant recipients.

We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.

Adolescent↗
PubMed2005

Occurrence of Pneumocystis jiroveci pneumonia after allogeneic stem cell transplantation: a 6-year retrospective study.

Pneumocystis jiroveci pneumonia (PCP) has become a rare opportunistic infection due to the efficacy of prophylactic regimens. We conducted a 6-year retrospective study at our institution. A total of 13 cases of PCP were diagnosed among 519 patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) (2.5%). In three patients, PCP occurred within the first 5 months following HSCT. These severely immunocompromised patients were receiving prophylaxis and had concomitant aspergillosis that caused rapid death in two of them. In 10 other patients, PCP occurred a median of 14.5 months after HSCT. In all these patients, PCP prophylaxis had been discontinued, mainly because of the suspected bone-marrow toxicity of the prophylactic regimen. Median CD4+ T cell count was 131/microl at diagnosis. Seven of these 10 patients were receiving immunosuppressive therapy for chronic graft versus host disease and three had a relapse of their hematological malignancy. One patient died from PCP despite high doses of cotrimoxazole. We conclude that PCP is still occurring after allogeneic HSCT, mainly as a late complication in patients in whom PCP prophylaxis had been prematurely discontinued. Long-term PCP prophylaxis should be maintained in patients receiving immunosuppressive drugs, and in those with low CD4+ T cell counts or a relapse of their hematological malignancy.

CD4 Lymphocyte Count↗
PubMed2005

Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party.

We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (<or=14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n=3), graft failure (n=2), Epstein-Barr virus lymphoma (n=2) and hemorrhage (n=2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults.

Adolescent↗
PubMed2005

A 10-year median follow-up study after allogeneic stem cell transplantation for chronic myeloid leukemia in chronic phase from HLA-identical sibling donors.

We report long-term outcome in 102 patients with cCML transplanted from an HLA-identical sibling donor from 1982 to 1998. The conditioning regimen was based on cyclophosphamide associated with either total body irradiation (TBI) (37 patients) or with busulfan (63 patients). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporin and methotrexate in the majority of the patients. Fifteen year overall survival was estimated at 53% (95% confidence interval (CI), 44-65) with a plateau after 2.5 years. Long-term survival was adversely affected by: longer time from chronic myeloid leukemia (CML) diagnosis to transplantation, older age at time of transplantation and GvHD (acute grade III-IV or chronic extensive). The main cause of death was infection, related to GvHD in 69% of patients. Splenectomy also significantly increased the risk of bacterial infection. 15-year relapse was estimated at 8% (95% CI, 0.1-14). Late malignancies occurred in seven patients, four of whom had an invasive cancer. Other frequent late complications included cataracts, psychological depression, osteonecrosis and hypothyroidism. These complications were more frequent following splenectomy, TBI and in patients with chronic extensive GvHD. We conclude that allogeneic transplantation with a related donor can cure more than half of CML patients in chronic phase, although physicians should be alert to long-term complications.

Follow-Up Studies↗
PubMed2003

Allogeneic bone marrow transplantation for acute myeloblastic leukaemia in remission: risk factors for long-term morbidity and mortality.

In this single-centre retrospective study, we analysed risk factors for nonrelapse long-term morbidity and mortality in patients with acute myeloblastic leukaemia (AML) who had undergone allogeneic transplantation. A total of 112 patients with de novo AML in first complete remission (CR1), n=90 or second complete remission (CR2, n=22) who received un-manipulated bone marrow grafts from human leukocyte antigen identical siblings between January 1985 and August 2000 were included. Of these, 97 patients alive and disease-free for at least 100 days after transplant were selected for the purpose of this long-term analysis. The use of an intensified conditioning regimen, Gram-negative bacteriaemia before transplantation, year of transplantation and number of pretransplant chemotherapy courses for patients in CR1 significantly affected the 7-year event-free survival which was 57%. 7-year transplant-related mortality TRM was 22%. Significant predictors for TRM were: bacterial infections before transplantation, major ABO blood group incompatibility, late severe bacterial infections, and chronic (graft-versus-host disease) GvHD. Predictive factors for late severe bacterial infections were infections before transplant, total body irradiation and GvHD. Incidence and risk factors for other late events including, chronic GvHD, late infections, osteonecrosis, cataract, endocrine- cardiac- and lung-complications, cancer and performance status at last follow-up were also studied. The analysis strongly suggests that the combination of pretransplant factors such as chemotherapy and conditioning, and posttransplant factors such as chronic GvHD had a major impact on late nonrelapse morbidity and mortality.

Adolescent↗
PubMed2002

DPB1 disparities contribute to severe GVHD and reduced patient survival after unrelated donor bone marrow transplantation.

In order to evaluate the impact of HLA-DBP1 incompatibilities on the occurrence of acute graft-versus-host disease (GVHD) in unrelated hematopoietic cell transplantation, we studied 57 donor/recipient pairs characterized by their allelic identity for HLA-A, B, C, DRB1 and DQB1 and also for DRB3, 4, 5 loci and aimed to correlate DPB1 mismatches to already described risk factors for GVHD using multivariate Cox regression analysis. DPB1 identity between donor and recipient was observed in 24% and DPB1 compatibility (GVHD vector) in 42%. Two factors were independently associated with severe acute GVHD: two DP incompatibilities (RR = 8.25, 95% confidence interval (CI): 1.67-40.10, P = 0.010) and disease risk (RR = 10.23, 95% CI: 1.12-93.13, P = 0.012). Two DPB1 incompatibilities appeared also to be a factor in poorer survival independent of its effect on acute GVHD (RR = 4.97, 95% Cl: 1.80-13.71, P = 0.002). A correlation between acute GVHD and matching for each individual DPB1 polymorphic region and for residue 69 of the DP beta molecule, which seems to be a key residue in the alloimmune response, was not observed. Our data indicate that the outcome of unrelated hematopoietic cell transplantation in terms of GVHD but also survival, could be improved through HLA-DPB1 matching or at least by avoiding two DPB1 mismatches.

Adolescent↗
PubMed2001

Busulfan plus cyclophosphamide compared with total-body irradiation plus cyclophosphamide before marrow transplantation for myeloid leukemia: long-term follow-up of 4 randomized studies.

In the early 1990s, 4 randomized studies compared conditioning regimens before transplantation for leukemia with either cyclophosphamide (CY) and total-body irradiation (TBI), or busulfan (Bu) and CY. This study analyzed the long-term outcomes for 316 patients with chronic myeloid leukemia (CML) and 172 patients with acute myeloid leukemia (AML) who participated in these 4 trials, now with a mean follow-up of more than 7 years. Among patients with CML, no statistically significant difference in survival or disease-free survival emerged from testing the 2 regimens. The projected 10-year survival estimates were 65% and 63% with Bu-CY versus CY-TBI, respectively. Among patients with AML, the projected 10-year survival estimates were 51% and 63% (95% CI, 52%-74%) with Bu-CY versus CY-TBI, respectively. At last follow-up, most surviving patients had unimpaired health and had returned to work, regardless of the conditioning regimen. Late complications were analyzed after adjustment for patient age and for acute and chronic graft-versus-host disease (GVHD). CML patients who received CY-TBI had an increased risk of cataract formation, and patients treated with Bu-CY had an increased risk of irreversible alopecia. Chronic GVHD was the primary risk factor for late pulmonary disease and avascular osteonecrosis. Thus, Bu-CY and CY-TBI provided similar probabilities of cure for patients with CML. In patients with AML, a nonsignificant 10% lower survival rate was observed after Bu-CY. Late complications occurred equally after both conditioning regimens (except for increased risk of cataract after CY-TBI and of alopecia with Bu-CY).

Adolescent↗
PubMed2001

Both genetic and clinical factors predict the development of graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Graft-versus-host disease is the main complication of hematopoietic stem cell transplantation. Recently, pro- and anti-inflammatory cytokines and mismatches of minor histocompatibility antigens between HLA-identical sibling donor/recipient pairs have been implicated in the development of acute graft-versus-host disease. It is not known, however, whether these factors are independent of other clinically recognized risk factors such as age and disease stage. METHODS: In this study, we searched for risk factors of acute graft-versus-host disease using multivariate Cox regression analysis in 100 consecutive patients who underwent allogeneic stem cell transplantation from an HLA-identical sibling donor. Eight polymorphisms from five different cytokine genes were studied (tumor necrosis factor alpha, tumor necrosis factor beta, interleukin (IL) 6, IL-10, and interferon gamma). Mismatches for the minor histocompatibility antigen HA-1 were searched in HLA-A*0201 individuals. In addition to these new risk factors, patient, donor, disease, and transplant risk factors were analyzed by multivariate analysis using the Cox proportional hazards model. RESULTS: Acute graft-versus-host disease was independently associated with IL-10 gene polymorphisms both from the recipient (relative risk=7.9, P<0.0001) and the donor (relative risk=3.5, P=0.02), a donor's positive serology for cytomegalovirus, and HA-1 mismatches in HLA-A*0201 individuals (relative risk=2.8, P=0.05). Chronic graft-versus-host disease was independently associated with IL-6 gene polymorphism from the recipient (relative risk=4.2, P=0.02), older age (relative risk=2.5, P=0.0009), and previous acute graft-versus-host disease (relative risk=9.7, P=0.003). CONCLUSION: In addition to previously described clinical risk factors, genetic risk factors are independently associated with the risk of developing graft-versus-host disease and may, thus, be considered for the selection of the donor.

Adolescent↗
PubMed2001

Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome.

PURPOSE: To analyze the impact of pre- and posttransplantation factors on the outcome of allogeneic transplantation after nonmyeloablative conditioning regimens. PATIENTS AND METHODS: Ninety-two allogeneic transplantations after nonmyeloablative preparative regimens were reported to the Société Française de Greffe de Moelle Registry registry. Initial diagnoses were lymphoid diseases (n = 22), myeloma (n = 14), acute leukemia and myelodysplasia (n = 41), chronic myelogenous leukemia (n = 12), and solid tumors (n = 3). Forty-six patients had previously received a transplant, and 49 had progressive disease before transplantation. Three types of conditioning regimens were used with fludarabine or antithymocyte globulins. Eighty-nine patients underwent transplantation, 60 from peripheral-blood progenitor cells. Eighty-six patients received graft-versus-host disease (GHVD) prophylaxis for a median duration of 53 days. RESULTS: Seventy-nine patients engrafted, with 40 complete and 21 mixed chimerisms. The acute GHVD rate at 3 months was 50% +/- 11%. Fifty-two patients achieved complete remission and 12, partial remission. At 18 months after transplantation, the overall survival (OS) and the transplant-related mortality (TRM) were 32% +/- 12% and 38% +/- 14%, respectively. Initial diagnosis and disease status before transplantation significantly influenced survival. Age and GHVD prophylaxis type significantly influenced TRM. We also showed an impact of GHVD prophylaxis duration on OS and TRM. In multivariate analysis, three factors remained of prognostic value on OS: initial diagnosis, disease status at transplantation, and GHVD prophylaxis duration. CONCLUSION: This series shows encouraging results from nonmyeloablative conditioning regimens before allotransplantation and demonstrates the impact of some pre- and posttransplantation factors on outcome after transplantation.

Adolescent↗