Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia

Department of Hematopoietic Stem Cell Transplantation Data Management, Nagoya University School of Medicine, Higashi-ku Nagoya, Japan.
Blood (Impact Factor: 10.45). 02/2009; 113(8):1631-8. DOI: 10.1182/blood-2008-03-147041
Source: PubMed


We made a disease-specific comparison of unrelated cord blood (CB) recipients and human leukocyte antigen allele-matched unrelated bone marrow (BM) recipients among 484 patients with acute myeloid leukemia (AML; 173 CB and 311 BM) and 336 patients with acute lymphoblastic leukemia (ALL; 114 CB and 222 BM) who received myeloablative transplantations. In multivariate analyses, among AML cases, lower overall survival (hazard ratio [HR]=1.5; 95% confidence interval [CI], 1.0-2.0, P= .028) and leukemia-free survival (HR=1.5; 95% CI, 1.1-2.0, P= .012) were observed in CB recipients. The relapse rate did not differ between the 2 groups of AML (HR=1.2; 95% CI, 0.8-1.9, P= .38); however, the treatment-related mortality rate showed higher trend in CB recipients (HR=1.5; 95% CI, 1.0-2.3, P= .085). In ALL, there was no significant difference between the groups for relapse (HR=1.4, 95% CI, 0.8-2.4, P= .19) and treatment-related mortality (HR=1.0; 95% CI, 0.6-1.7, P= .98), which contributed to similar overall survival (HR=1.1; 95% CI, 0.7-1.6, P= .78) and leukemia-free survival (HR=1.2; 95% CI, 0.9-1.8, P= .28). Matched or mismatched single-unit CB is a favorable alternative stem cell source for patients without a human leukocyte antigen-matched related or unrelated donor. For patients with AML, decreasing mortality, especially in the early phase of transplantation, is required to improve the outcome for CB recipients.

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Available from: Keisei Kawa, Nov 11, 2015
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    • "In children with acute leukemia who received better HLA-matched grafts and higher cell dose achieved better survival [85]. In adults with acute leukemia, recent studies [33, 34, 86–90] showed that outcomes after UCBT were manifested by lower risk of TRM and similar EFS compared to unrelated (matched or mismatched) donor BM after myeloablative conditioning (cyclophosphamide/total body irradiation). Interestingly, double UBCT can overcome the cell dose limitation imposed by UCB grafts in adults while favoring a lower relapse risk [91]. "
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    ABSTRACT: Over 20.000 umblical cord blood transplantations (UCBT) have been carried out around the world. Indeed, UCBT represents an attractive source of donor hematopoietic stem cells (HSCs) and, offer interesting features (e.g., lower graft-versus-host disease) compared to bone marrow transplantation (BMT). Thereby, UCBT often represents the unique curative option against several blood diseases. Recent advances in the field of UCBT, consisted to develop strategies to expand umbilical stem cells and shorter the timing of their engraftment, subsequently enhancing their availability for enhanced efficacy of transplantation into indicated patients with malignant diseases (e.g., leukemia) or non-malignant diseases (e.g., thalassemia major). Several studies showed that the expansion and homing of UCBSCs depends on specific biological factors and cell types (e.g., cytokines, neuropeptides, co-culture with stromal cells). In this review, we extensively present the advantages and disadvantages of current hematopoietic stem cell transplantations (HSCTs), compared to UBCT. We further describe the importance of cord blood content and obstetric factors on cord blood selection, and report the recent approaches that can be undertook to improve cord blood stem cell expansion as well as engraftment. Eventually, we provide two majors examples underlining the importance of UCBT as a potential cure for blood diseases.
    BioMed Research International 10/2012; 2012(6022):572821. DOI:10.1155/2012/572821 · 2.71 Impact Factor
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    • "According to the study conducted by the Japan Cord Blood Bank Network, the results showed similar relapse rates, TRM, and overall survival rates between the recipients of CB and BM9). In a recent international retrospective analysis in adults with acute leukemia, 94% of the patients were transplanted with 1 or 2 antigen-mismatched CB and TRM was higher than in the recipients of 8/8 allele-matched PBPC or BM (Fig. 1C). "
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    ABSTRACT: Since the first umbilical cord blood transplantation (CBT) in 1998, cord blood (CB) has now become one of the most commonly used sources of hematopoietic stem cells for transplantation. CBT has advantages of easy procurement, no risk to donor, low risk of transmitting infections, immediate availability and immune tolerance allowing successful transplantation despite human leukocyte antigen disparity. Several studies have shown that the number of cells transplanted is the most important factor for engraftment in CBT, and it limits the wide use of CB in adult patients. New strategies for facilitating engraftment and reducing transplantation-related mortality are ongoing in the field of CBT and include the use of a reduced-intensity conditioning regimen, double-unit CBT, ex vivo expansion of CB, and co-transplantation of CB and mesenchymal stem cells. Recently, the results of two international studies with large sample sizes showed that CB is an acceptable alternative source of hematopoietic stem cells for adult recipients who lack human leukocyte antigen-matched adult donors. Along with the intensive researches, development in banking process of CB will amplify the use of CB and offer the chance for cure in more patients.
    Korean Journal of Pediatrics 07/2012; 55(7):219-23. DOI:10.3345/kjp.2012.55.7.219
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    • "Primary graft failure after allogeneic hematopoietic cell transplantation is a life-threatening complication because patients are at a high risk of severe infection owing to prolonged neutropenia after the initial transplantation. Several risk factors for graft failure have been suggested: transplantation of inadequate stem cell doses,1 use of human leukocyte antigen (HLA)-mismatched donors2–4 or cord blood units,5–7 viral infections such as cytomegalovirus (CMV) and human herpesvirus 6 (HHV-6),8–10 use of a non-myeloablative or reduced-intensity conditioning regimen,11,12 and presence of donor-specific HLA antibody.13–15 Graft rejection due to the immune response of the recipient is a major mechanism underlying graft failure. "
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    ABSTRACT: Primary graft failure after allogeneic hematopoietic cell transplantation is a life-threatening complication. A shortened conditioning regimen may reduce the risk of infection and increase the chance of survival. Here, we report the outcome of 11 patients with hematologic diseases (median age, 44; range, 25-67 years, seven males) who received a 1-day reduced-intensity preparative regimen given as a re-transplantation for primary graft failure. The salvage regimen consisted of fludarabine, cyclophosphamide, alemtuzumab and TBI, all administered 1 day before re-transplantation. All patients received T-cell replete PBSCs from the same or a different haploidentical donor (n=10) or from the same matched sibling donor (n=1). Neutrophil counts promptly increased to >500/μL for 10 of the 11 patients at a median of 13 days. Of these, none developed grade III/IV acute GVHD. At present, 8 of the 11 patients are alive with a median follow-up of 11.2 months from re-transplantation and 5 of the 8 are in remission. In conclusion, this series suggests that our 1-day preparative regimen is feasible, leads to successful engraftment in a high proportion of patients, and is appropriate for patients requiring immediate re-transplantation after primary graft failure following reduced-intensity transplantation.
    Bone marrow transplantation 08/2011; 47(5):700-5. DOI:10.1038/bmt.2011.158 · 3.57 Impact Factor
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