Port-Saint-Louis-du-Rhône, France
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Sideri A.,Hygeia Hospital | Neokleous N.,Hygeia Hospital | Grange P.B.G.,French Institute of Health and Medical Research | Guerton B.,French Institute of Health and Medical Research | And 4 more authors.
Haematologica | Year: 2011

Umbilical cord blood transplantation has been increasingly used over the past years for both malignant and non-malignant hematologic and other diseases as an alternative to mismatched-related or matched-unrelated bone marrow or peripheral blood hematopoietic stem cell transplantation. A disadvantage of cord blood is its low cell content which limits cord blood transplantation to generally low weight recipients, such as children. Various alternatives have been used to overcome this limitation, including co-infusion of two partially HLA-matched cord blood units. According to Eurocord Registry data, this strategy has been applied in approximately 993 adult patients with hematologic diseases since the first double umbilical cord blood transplantation in 1999. In fact, since 2005, the number of adult patients receiving double umbilical cord blood transplantation has surpassed the number of adults transplanted with single cord blood units. The engraftment rate is comparable for both single and double umbilical cord blood transplantation, although the latter is accompanied by a higher incidence of grade II acute graft-versus-host disease and lower leukemia relapse for patients in first complete remission. In the majority of patients undergoing double umbilical cord blood transplantation, transient chimerism, due to the presence of cells from both donor units early post transplant, is replaced by sustained dominance of one unit from which long-term hematopoiesis is derived. Although the biology and the factors that determine unit dominance have not been clarified, the implication of immune-mediated mechanisms has been reported. Preliminary data have demonstrated the safety of double umbilical cord blood transplantation. Ongoing clinical trials and prolonged follow up of the patients will clarify the immunology and determine the efficacy of this approach. We present here a brief overview of the clinical experience on double umbilical cord blood transplantation and its underlying biology. © 2011 Ferrata Storti Foundation.

Locatelli F.,Instituto Of Ricovero E Cura A Carattere Scientifico Irccs | Locatelli F.,University of Pavia | Kabbara N.,Eurocord | Ruggeri A.,Eurocord | And 14 more authors.
Blood | Year: 2013

We analyzed the outcomes of 485 patients with thalassemia major (TM) or sickle cell disease (SCD) receiving HLA-identical sibling cord blood transplantation (CBT, n = 96) or bone marrow transplantation (BMT, n = 389). Compared with patients given BMT, CBT recipients were significantly younger (median age 6 vs 8 years, P = .02), and were treated more recently (median year 2001 vs 1999, P < .01). A higher proportion of patients with TM belonging to classes II-III of the Pesaro classification received BMT (44%) compared with CBT (39%, P < .01). In comparison with patients receiving BMT(n = 259, TM; n = 130, SCD), those given CBT (n = 66, TM; n = 30, SCD) had slower neutrophil recovery, less acute graft-versus-host disease (GVHD) and none had extensive chronic GVHD. With a median follow-up of 70 months, the 6-year overall survival was 95% and 97% after BMT and CBT, respectively (P = .92). The 6-year disease-free survival (DFS) was 86% and 80% in TM patients after BMT and CBT, respectively, whereas DFS in SCD patients was 92% and 90%, respectively. The cell dose infused did not influence outcome of patients given CBT. In multivariate analysis, DFS did not differ between CBT and BMT recipients. Patients with TMor SCD have excellent outcomes after both HLA-identical sibling CBT and BMT. © 2013 by The American Society of Hematology.

Eapen M.,Medical College of Wisconsin | Klein J.P.,Medical College of Wisconsin | Sanz G.F.,Hospital Universitario La Paz | Spellman S.,Center for International Blood and Marrow Transplant Research | And 15 more authors.
The Lancet Oncology | Year: 2011

Background: The importance of matching at the HLA C locus has not been well defined for unrelated umbilical-cord blood transplantation. The selection algorithm for umbilical-cord blood units generally considers intermediate resolution HLA typing at A and B and allele-level typing at DRB1. We aimed to establish the relative importance of additional matching at HLA C. Methods: We used Cox regression to assess retrospectively the effect of donor-recipient HLA matching on outcomes of single umbilical-cord blood transplantations for leukaemia and myelodysplastic syndrome. Our primary endpoint was transplant-related mortality. HLA typing was done with molecular techniques with a minimum of intermediate resolution for HLA A, B, and C, and at the allele-level for DRB1. Findings: The median age of our study population was 10 years (range <1-62) and 552 (69%) of 803 patients were aged 16 years or younger at transplantation. Compared with transplantations matched at HLA A, B, C, and DRB1 (n=69), transplant-related mortality risk was higher after transplantations matched at HLA A, B, and DRB1 and mismatched at HLA C (n=23; HR 3·97, 95% CI 1·27-12·40; p=0·018). Transplant-related mortality risk was also higher after transplantations with a single mismatch at HLA A, B, or DRB1 and mismatched at HLA C (n=234; 1·70, 1·06-2·74; p=0·029) compared with transplantations matched at HLA C with a single mismatch at HLA A, B, or DRB1 (n=127). Assessing the overall effect of HLA disparity on transplant-related mortality, risks were higher with units mismatched at two (n=259; 3·27, 1·42-7·54; p=0·006), three (n=253; 3·34, 1·45-7·71; p=0·005), or four (n=75; 3·51, 1·44-8·58; p=0·006) loci compared with matched units (n=69). Interpretation: Our data suggest that the present strategy for umbilical-cord blood unit selection should be reassessed; matching at HLA C for units that are matched at HLA A, B, or DRB1 or in the presence of a single locus mismatch at HLA A, B, or DRB1 should be included to minimise mortality risks. Funding: National Cancer Institute, National Heart Lung and Blood Institute, National Institute for Allergy and Infectious Diseases, Leukemia and Lymphoma Society, US Department of the Navy, Children's Leukemia Research Association, and INSERM. © 2011 Elsevier Ltd.

Rocha V.,Eurocord | Crotta A.,Eurocord | Ruggeri A.,Eurocord | Purtill D.,Eurocord | And 4 more authors.
Best Practice and Research: Clinical Haematology | Year: 2010

Unrelated umbilical cord blood (UCB) has been widely used to treat patients lacking a well-matched HLA donor. Cell dose is a critical determinant of outcomes in cord blood transplantation, limiting the use of this strategy for low body weight patients. To overcome this limitation, infusion of two partially HLA-matched cord units was adopted as a new strategy. Since 2005, number of adult patients treated with UCB transplant is increased due to the higher number of cells available using two units and to the feasibility of reduced intensity conditioning regimen, extending successfully this strategy to heavier patients or for those with co-morbidities. Approximately 993 adults with hematological diseases have been transplanted with double UCB graft, and reported to Eurocord registry from 1999 to 2010. This article reviews the state of art and future directions with double umbilical cord blood units as a source of hematopoietic stem cells for transplantation. © 2010 Elsevier Ltd. All rights reserved.

Angelucci E.,Hematology | Matthes-Martin S.,Medical University of Vienna | Baronciani D.,Ospedale Oncologico di Riferimento Regionale Armando Businco | Bonanomi S.,Hospital San Gerardo | And 19 more authors.
Haematologica | Year: 2014

Thalassemia major and sickle cell disease are the two most widely disseminated hereditary hemoglobinopathies in the world. The outlook for affected individuals has improved in recent years due to advances in medical management in the prevention and treatment of complications. However, hematopoietic stem cell transplantation is still the only available curative option. The use of hematopoietic stem cell transplantation has been increasing, and outcomes today have substantially improved compared with the past three decades. Current experience world-wide is that more than 90% of patients now survive hematopoietic stem cell transplantation and disease-free survival is around 80%. However, only a few controlled trials have been reported, and decisions on patient selection for hematopoietic stem cell transplantation and transplant management remain principally dependent on data from retrospective analyses and on the clinical experience of the transplant centers. This consensus document from the European Blood and Marrow Transplantation Inborn Error Working Party and the Paediatric Diseases Working Party aims to report new data and provide consensus-based recommendations on indications for hematopoietic stem cell transplantation and transplant management. © 2014 by the Ferrata Storti Foundation.

Baron F.,University of Liège | Labopin M.,Hopital Saint Antoine | Niederwieser D.,University of Leipzig | Vigouroux S.,University of Bordeaux Segalen | And 12 more authors.
Leukemia | Year: 2012

This report investigated the impact of graft-versus-host disease (GVHD) on transplantation outcomes in 1859 acute myeloid leukemia patients given allogeneic peripheral blood stem cells after reduced-intensity conditioning (RIC allo-SCT). Grade I acute GVHD was associated with a lower risk of relapse (hazards ratio (HR)=0.7, P=0.02) translating into a trend for better overall survival (OS; HR=1.3; P=0.07). Grade II acute GVHD had no net impact on OS, while grade III-IV acute GVHD was associated with a worse OS (HR=0.4, P<0.0.001) owing to high risk of nonrelapse mortality (NRM; HR=5.2, P<0.0001). In time-dependent multivariate Cox analyses, limited chronic GVHD tended to be associated with a lower risk of relapse (HR=0.72; P=0.07) translating into a better OS (HR=1.8; P<0.001), while extensive chronic GVHD was associated with a lower risk of relapse (HR=0.65; P=0.02) but also with higher NRM (HR=3.5; P<0.001) and thus had no net impact on OS. In-vivo T-cell depletion with antithymocyte globulin (ATG) or alemtuzumab was successful at preventing extensive chronic GVHD (P<0.001), but without improving OS for ATG and even with worsening OS for alemtuzumab (HR=0.65; P=0.001). These results highlight the role of the immune-mediated graft-versus-leukemia effect in the RIC allo-SCT setting, but also the need for improving the prevention and treatment of severe GVHD. © 2012 Macmillan Publishers Limited. All rights reserved.

Weisdorf D.,University of Minnesota | Weisdorf D.,Medical College of Wisconsin | Eapen M.,Medical College of Wisconsin | Ruggeri A.,Eurocord | And 8 more authors.
Biology of Blood and Marrow Transplantation | Year: 2014

We studied patients with acute myeloid leukemia (AML) over age 50 and in first complete remission (CR1) after adult unrelated donor (URD) (n = 441, 8/8 HLA matched; n = 94, 7/8 HLA matched) or umbilical cord blood (UCB; n = 205) transplantations. UCB recipients achieved CR1 within 8 weeks less often, and received reduced-intensity conditioning and cyclosporine-based graft-versus-host disease (GVHD) prophylaxis more often. Neutrophil recovery was slower in UCB (69% by day 28) compared with 8/8 HLA-matched URD (97%) and 7/8 HLA-matched (91%) (P < .001) recipients. Three-year transplantation-related mortality (TRM) was higher and leukemia-free survival (LFS) lower with UCB (35% and 28%, respectively) versus 8/8 HLA-matched URD (27% and 39%, respectively). TRM was higher in 7/8 HLA-matched URD (41%, P = .01), but LFS was similar at 34% (P = .39). Three-year chronic GVHD was the lowest in UCB (28%) versus 53% and 59% in 8/8 and 7/8 HLA-matched URD recipients, respectively. Three-year survival was 43% in 8/8 HLA-matched URD (95% confidence interval [CI], 38% to 48%), 30% in UCB (95% CI, 23% to 37%) (P = .002) and 37% in 7/8 URD (95% CI, 27 to 46). Allotransplantation for AML in CR1 with any of these grafts extends LFS for over one third of older patients. In the absence of an 8/8 HLA-matched URD or when transplantation is needed urgently, UCB can provide extended survival. Less frequent chronic GVHD with UCB transplantation may be of particular value for older patients. © 2014 American Society for Blood and Marrow Transplantation.

Wagner J.E.,University of Minnesota | Gluckman E.,Eurocord
Seminars in Hematology | Year: 2010

In October 1988, the world's first umbilical cord blood transplant (UCBT) was performed. Despite considerable skepticism initially by both scientists and clinical specialists in the field, umbilical cord blood (UCB) has now become one of the most commonly used sources of hematopoietic stem cells (HSCs) for allogeneic transplantation. Today, an estimated 600,000 UCB units have been banked and 20,000 UCB units have been distributed worldwide for both adults and children with life-threatening malignant and nonmalignant diseases. During this first generation of UCBT, substantial advances have been made resulting in better outcomes for our patients. UCB serves as an extraordinary example of translational medicine at its best, where clinical problems compel scientists to move basic discoveries into novel therapeutic approaches. This chapter briefly summarizes the highpoints of the history of UCBT with speculations as to what the next generation of research promises to discover. © 2010 Elsevier Inc. All rights reserved.

Eapen M.,Center for International Blood and Marrow Transplant Research | Klein J.P.,Center for International Blood and Marrow Transplant Research | Klein J.P.,Medical College of Wisconsin | Ruggeri A.,Eurocord | And 19 more authors.
Blood | Year: 2014

We studied the effect of allele-level matching at human leukocyte antigen (HLA)-A, -B, -C, and -DRB1 in 1568 single umbilical cord blood (UCB) transplantations for hematologic malignancy. The primary end point was nonrelapse mortality (NRM). Only 7% of units were allele matched at HLA-A, -B, -C, and -DRB1; 15% were mismatched at 1, 26% at 2, 30% at 3, 16% at 4, and 5% at 5 alleles. In a subset, allele-level HLA match was assigned using imputation; concordance between HLA-match assignment and outcome correlation was confirmed between the actual and imputed HLA-match groups. Compared with HLA-matched units, neutrophil recovery was lower with mismatches at 3, 4, or 5, but not 1 or 2 alleles.NRM was higher with units mismatched at 1, 2, 3, 4, or 5 alleles compared with HLAmatched units. The observed effects are independent of cell dose and patient age. These data support allele-levelHLAmatching in the selection of single UCB units. (Blood. 2014;123(1):133-140). © 2011 by The American Society of Hematology; all rights reserved.

PubMed | Baylor University, University of Rome La Sapienza, Royal Perth Hospital, University Hospital of Marseille and 8 more.
Type: Journal Article | Journal: Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation | Year: 2016

The effect of killer cell immunoglobulin-like receptor (KIR)-ligand matching on outcomes after unrelated cord blood (CB) transplantation was studied in 461 patients with acute myeloid leukemia, categorizing KIR ligand for HLA-C groups C1 and C2 and Bw4. Donor-recipient HLA matching considered allele-level matching at HLA-A, -B, -C, and -DRB1. Separate analyses were conducted for 6-7/8 HLA-matched and 3-5/8 HLA-matched transplants because HLA matching confounded KIR-ligand matching (ie, KIR-ligand mismatching was less likely with better HLA matching). All patients received single CB unit and myeloablative conditioning. There were no significant differences in nonrelapse mortality (NRM), relapse, and overall mortality by KIR-ligand match status. However, among recipients of 3-5/8 HLA-matched transplants, NRM (HR, 2.26; P=.008) and overall mortality (HR, 1.78; P=.008) but not relapse were higher with KIR-ligand mismatched (host-versus-graft direction) compared with KIR-ligand matched transplants. These data do not support selecting CB units based on KIR-ligand match status for transplants mismatched at 1 or 2 HLA loci. Although transplants mismatched at 3 or more HLA loci are not recommended, avoiding KIR-ligand mismatching in this setting lowers mortality risks.

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