Showing papers by "Eliane Gluckman published in 2004"

Transplants of Umbilical-Cord Blood or Bone Marrow from Unrelated Donors in Adults with Acute Leukemia

Abstract: results Recipients of cord blood were younger than recipients of bone marrow (median, 24.5 vs. 32 years of age; P<0.001), weighed less (median, 58 vs. 68 kg; P<0.001), and had more advanced disease at the time of transplantation (52 percent vs. 33 percent, P<0.001). All marrow transplants were HLA matched, whereas 94 percent of cord-blood grafts were HLA mismatched (P<0.001). The median number of nucleated cells that were infused was 0.23¬10 8 per kilogram of the recipient’s body weight for cord blood and 2.9¬10 8 per kilogram for bone marrow (P<0.001). Multivariate analysis showed lower risks of grade II, III, or IV acute graft-versus-host disease (GVHD) after cord-blood transplantation (relative risk, 0.57; 95 percent confidence interval, 0.37 to 0.87; P=0.01), but neutrophil recovery was significantly delayed (relative risk, 0.49; 95 percent confidence interval, 0.41 to 0.58; P<0.001). The incidence of chronic GVHD, transplantation-related mortality, relapse rate, and leukemia-free survival were not significantly different in the two groups. conclusions Cord blood from an unrelated donor is an alternative source of hematopoietic stem cells for adults with acute leukemia who lack an HLA-matched bone marrow donor.

Autologous stem cell transplantation in the treatment of systemic sclerosis: Report from the EBMT/EULAR Registry

Abstract: OBJECTIVE: To analyse the durability of the responses after haematopoietic stem cell transplantation (HSCT) for severe systemic sclerosis (SSc) and determine whether the high transplant related mortality (TRM) improved with experience. This EBMT/EULAR report describes the longer outcome of patients originally described in addition to newly recruited cases. METHODS: Only patients with SSc, treated by HSCT in European phase I-II studies from 1996 up to 2002, with more than 6 months of follow up were included. Transplant regimens were according to the international consensus statements. Repeated evaluations analysed complete, partial, or non-response and the probability of disease progression and survival after HSCT (Kaplan-Meier). RESULTS: Given as median (range). Among 57 patients aged 40 (9.1-68.7) years the skin scores improved at 6 (n = 37 patients), 12 (n = 30), 24 (n = 19), and 36 (n = 10) months after HSCT (p<0.005). After 22.9 (4.5-81.1) months, partial (n = 32) or complete response (n = 14) was seen in 92% and non-response in 8% (n = 4) of 50 observed cases. 35% of the patients with initial partial (n = 13/32) or complete response (n = 3/14) relapsed within 10 (2.2-48.7) months after HSCT. The TRM was 8.7% (n = 5/57). Deaths related to progression accounted for 14% (n = 8/57) of the 23% (n = 13/57) total mortality rate. At 5 years, progression probability was 48% (95% CI 28 to 68) and the projected survival was 72% (95% CI 59 to 75). CONCLUSION: This EBMT/EULAR report showed that response in two thirds of the patients after HSCT was durable with an acceptable TRM. Based on these results prospective, randomised trials are proceeding.

Treatment With Granulocyte Colony-Stimulating Factor After Allogeneic Bone Marrow Transplantation for Acute Leukemia Increases the Risk of Graft-Versus-Host Disease and Death: A Study From the Acute Leukemia Working Party of the European Group for Blood and Marrow Transplantation

Abstract: Purpose Granulocyte colony-stimulating factor (G-CSF) is given after bone marrow transplantation (BMT) to shorten the neutropenic phase. Its effects have not been evaluated in a large patient population. Patients and Methods We studied 1,789 patients with acute leukemia receiving BMT and 434 patients receiving peripheral-blood stem cells (PBSCs) from HLA-identical siblings from 1992 to 2002 and reported the findings to the European Group for Blood and Marrow Transplantation. Among the BMT and PBSC patients, 501 (28%) and 175 (40%), respectively, were treated with G-CSF during the first 14 days after the transplantation. The outcome variables were entered into a Cox proportional hazards model. Results BMT and PBSC patients treated with G-CSF had a faster engraftment of absolute neutrophils greater than 0.5 × 109/L (P 50 × 109/L) was slower (P < .001). In the BMT patients, acute graft-versus-host disease (GVHD) grades II to IV was 50% ± 5% (± 95% CI) in the G-CSF group v...

Genetic polymorphisms predicting the outcome of bone marrow transplants

Abstract: Analysis of non-histocompatibility leucocyte antigen (HLA) functional genomics, together with conventional risk factors in haematopoietic stem cell transplantation (HSCT) can lead to predicting outcome in HLA-matched sibling transplant recipients. Polymorphisms of cytokine genes including tumour necrosis factor alpha, interleukin-10, interferon gamma and interleukin (IL)-6, associate with more severe acute graft-versus-host disease (aGvHD). Donor genotype for IL-1 receptor antagonist (IL-1Ra) has been associated with reduced aGvHD severity. Other genotypes (patient IL-1Ra, IL-6 and donor IL-1 alpha) have been associated with chronic GvHD, or overall survival (Vitamin D receptor and oestrogen receptor). Polymorphisms within genes associated with host defence/inflammatory responses (mannose binding lectin genes, myeloperoxidase genes and the FC gamma receptors) have been associated with infections. Polymorphisms of pharmacogenes, such as methylenetetrahydrofolate-reductase, have been associated with aGvHD and other post-transplant complications. The NOD2 gene polymorphism, associated with Crohn's disease, has been shown to be associated with risk of gut GvHD. The majority of the studies have been carried out in single centre HLA-matched sibling cohorts and in relatively few matched unrelated donor transplants. This review gives an overall perspective of the current field of non-HLA genetics with regard to HSCT outcome, clinical relevance and potential application of the results to clinical management of HSCT.

Epstein-Barr virus (EBV) reactivation in allogeneic stem-cell transplantation: relationship between viral load, EBV-specific T-cell reconstitution and rituximab therapy.

Abstract: Background. Monitoring of Epstein-Barr virus (EBV) reactivation after allogeneic hematopoietic stem-cell transplantation markedly improved with quantitative real-time polymerase chain reaction amplification of EBV DNA and visualization of EBV-specific CD8 + T cells with peptide-human leukocyte antigen (HLA) class I tetramers. We decided to combine these methods to evaluate posttransplant EBV reactivation and rituximab therapy. Methods. We followed 56 patients treated with an HLA-genoidentical sibling (n=32), an HLA-matched unrelated donor (MUD, n=19), or an unrelated cord-blood transplant (n=5). EBV DNA was quantified in plasma and in peripheral blood mononuclear cells (PBMC). Patient CD8 + T cells were stained with a panel of eight tetramers. Results. EBV DNA was detected in half of the patients, mainly in the MUD group (17/19). In 19 patients, viral DNA was detected only in the cellular compartment. All patients who controlled reactivation without rituximab and despite a viral load of greater than 500 genome equivalents (gEq)/150,000 PBMC mounted an EBV-specific CD8 + T-cell response in greater than 1.4% of CD3 + CD8 + T cells. Plasmatic EBV genome was found in nine patients preceded by a high cellular viral load. Three of these patients controlled the reactivation before or without the introduction of rituximab, and they all developed a significant and increasing EBV-specific T-cell response. Patients with EBV-specific T cells at the onset of reactivation controlled viral reactivation without rituximab. Conclusion. This study emphasizes the benefit of an early and close monitoring of EBV reactivation and CD8 + -specific immune responses to initiate rituximab only when necessary and before the immune response becomes overwhelmed by the viral burden.

Umbilical cord blood transplantation.

Abstract: Purpose of review Familiar and unrelated umbilical cord blood is an appealing alternative source of hematopoietic stem cells patients undergoing transplantation for a wide variety of diseases. In the unrelated donor transplant setting, shorter time to transplant, which is particularly relevant to patients requiring urgent transplantation, and tolerance of 1-2 human leukocyte antigen mismatch, which increases the chance of finding a suitable donor, are evident advantages over bone marrow transplantation. The speed of engraftment is slower after cord blood transplantation but it is counterbalanced by a lower incidence of severe graft-versus-host disease. Cell dose and human leukocyte antigen are major factors influencing outcome after umbilical cord blood transplantation. Recent findings Unrelated donor cord blood transplantation is considered an acceptable option to bone marrow for pediatric transplantation, and recent data in adults point the same way. Summary This review describes the recent clinical results of cord blood transplantation and discusses developing research strategies aimed at optimizing this kind of transplantation.

The London Cord Blood Bank: analysis of banking and transplantation outcome.

Abstract: Cord blood units (n = 5500) stored at the London Cord Blood Bank, including 59 units transplanted into a high risk and heterogeneous group of patients, were analysed. Transplant outcome data was available for 44 patients with a median clinical follow-up of 14 months (range 3-44 months). Over 40% of the collected units were of ethnic minority origin with a median volume of 79 ml (range 40-240 ml) and a median total nucleated cell (TNC) count of 11.9 x 10(9)/l (range 10.0-24.8 x 10(9)/l). The average patient's weight was 28 kg (range 5-80 kg) and the median age was 8 years (range 0.7-40 years). The median number of nucleated cells infused was 4 x 10(7)/kg (range 1.10-16 x 10(7)/kg). Neutrophil engraftment of 0.5 x 10(9)/l was observed in 33 (74+/-%) patients with an average time of 28 days (range 11-60). The Kaplan-Meier estimate of acute graft-versus-host disease (grade II >) at day 100 was 37 +/- 7% and in 27 (62%) patients, it was grade I or absent. The overall survival and disease-free survival at 2 years was 49 +/- 8% and 41 +/- 8%, respectively. Two years after transplantation the survival rate was 69% and 54% for patients receiving a 6/6 or 5/6 HLA matched units, respectively. Infection was the main cause of transplanted related mortality in these patients.

Predicting the costs of allogeneic sibling stem-cell transplantation: results from a prospective, multicenter, French study.

Abstract: BACKGROUND Allogeneic hematopoietic stem-cell transplantation is a widely used, cost-intensive procedure. Our purpose was to estimate costs and determine cost predictors. METHODS We used data from a prospective French study comparing four doses of immunoglobulins. Resource use of hematopoietic stem-cell transplant recipients during the first 6 months posttransplant, both inpatient and ambulatory costs, in 85 patients from five centers were collected prospectively and costed. Baseline data and clinical events were retrieved. Protocol-driven costs were excluded. Multivariable analysis evaluated the association between costs and patient's pretransplant status and transplant-related complications. Because of the absence of differences in outcome among the four randomization groups, cost data for all patients were pooled. RESULTS Total costs per patient were the following: mean 76,237 Euros; standard deviation 32,565 Euros; median 69,516 Euros; range 183,758 to 14,761Euros. The major cost driver was hospital days. No association was found between costs and baseline status. The "predictors" of higher costs (adding an average 20,000 Euros/patient) were the occurrence of transplant-related complications: graft-versus-host disease and repeated infections that were unpredictable before transplant in this homogeneous group of patients. CONCLUSION Our data highlight the discrepancy between the Diagnosis Related Group prospective payment system and actual costs. The actual cost of geno-identical stem-cell transplantation results from posttransplant complications that cannot be predicted prospectively and require ex post cost adjustment.

Cord blood transplantation for children with acute leukaemia: a Eurocord registry analysis.

Abstract: Objectives Report results of unrelated cord blood transplants collected by Eurocord Registry in children with acute leukemia. Results Children with AML: 95 children were analyzed. The two year leukemia free survival was 42% in patients transplanted in first remission, 50% in second remission and 21% in children not in remission. Children with poor prognostic cytogenetic features had the same survival compared to other patients. Children with ALL: 195 patients with ALL were analyzed. The two year leukemia free survival was 36% in patients transplanted in remission and 15% in patients transplanted in relapse. Results of unrelated cord blood transplants compared to unrelated bone marrow transplants in children with acute leukemia: 416 children with acute leukemia received a HLA matched unrelated bone marrow transplant and were compared to 99 children transplanted with an unrelated HLA mismatched cord blood. The long term outcome between these groups were comparable with delayed engraftment in cord blood transplant, more relapse in T cell depleted bone marrow transplant and more GVH in the unmanipulated bone marrow transplant resulting in similar 5 years leukemia free survival. Conclusion These results show that use of unrelated cord blood transplant is an option in patients lacking an HLA identical sibling donor.

Cord blood transplant: strategy of alternative donor search.

Abstract: Unrelated cord blood transplantation has been used to treat patients with malignant and non-malignant hematopoietic disorders for whom an HLA-compatible hematopoietic stem cell donor is not available. The establishment of cord blood banks worldwide, the increased number of cord blood units frozen, and the shorter time to find a donor, have made it possible to use this source of hematopoietic stem cells to treat more than 2,500 patients. The Eurocord registry was established to study the clinical results of cord blood transplantation and to compare the outcomes of unrelated transplants using either cord blood or bone marrow. Briefly, we have found, in two distinct retrospective analyses of children or adults with acute leukemia given either an unrelated cord blood or bone marrow transplant, that leukemia-free survival and relapse were similar in both types of graft (with adjustment for confounding clinical factors). Cord blood recipients experienced a decreased incidence of acute graft-versus-host disease and delayed hematopoietic recovery compared to bone marrow recipients. To improve the delayed hematopoietic recovery after cord blood transplantation, certain approaches have been investigated such as ex vivo expansion of cord blood cells, double cord blood transplantation and reduced intensity conditioning regimen. We have also attempted to establish some guidelines for cord blood-donor choice based on cord blood cell dose and number of HLA disparities that have been found to be associated with hematopoietic recovery. In conclusion, an unrelated hematopoietic stem cell donor should be simultaneously searched for in cord blood banks and in bone marrow donor registries for patients lacking an HLA-identical sibling hematopoietic stem cell donor. The option of performing cord blood transplants should be based on urgency of the transplant, cord blood cell dose and number of HLA disparities.

Lack of mutations in the human telomerase RNA component (hTERC) gene in Fanconi's anemia.

Abstract: As some patients with Fanconi s anemia (FA) present excessive telomere shortening correlating with poor outcome, we investigated whether human telomerase RNA component (hTERC) mutations also play a role in telomere shortening in 115 FA patients. Only one patient was heterozygous for the G58A polymorphism. No other mutation or deletion was found. We conclude that hTERC gene mutations do not contribute to telomere shortening in FA.