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      Intrabone Transplant of Cord Blood Stem Cells Establishes a Local Engraftment Store: A Functional PET/FDG Study

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          Abstract

          Background. Despite advancements in comprehension of molecular mechanisms governing bone marrow (BM) homing of hematopoietic stem cells, cord blood transplant (CBT) suffers from a slow rate of hematopoietic recovery. Intrabone (IB) injection has been proposed as a method able to improve speed of BM engraftment with respect to conventional IV protocols. However, the mechanisms underlying this benefit are largely unknown. Aim. To verify whether IB-CBT determines a local engraftment able to predict the reconstitution of recipient hematopoiesis. Design and Methods. Twenty-one patients with hematologic malignancies received IB injection into both iliac crests of 3.2 ± 0.68 ∗ 107/kg cord blood cells. One month following IB-CBT, PET-CT imaging was performed. Maximal standardized uptake values (SUVs) were assessed in BM of both iliac crests and in all lumbar vertebrae. Results. Maximal SUV within iliac crests was higher than in lumbar vertebrae (4.1 ± 1.7 versus 3.2 ± 0.7, resp., P = 0.01). However, metabolic activity in these two different BM districts was significantly correlated ( r = 0.7, P < 0.001). Moreover, FDG uptake values within the injection site closely predicted platelet recovery 100 days after IB-CBT ( r = 0.72, P < 0.01). Conclusions. The metabolic activity of injected BM predicts the subsequent rate of hematopoietic recovery after IB-CBT, suggesting a pivotal role of the local engraftment in the reconstitution of recipient hematopoiesis.

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          Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia.

          Promising results of cord-blood transplants from unrelated donors have been reported in adults. We compared outcomes in 682 adults with acute leukemia who received a hematopoietic stem-cell transplant from an unrelated donor: 98 received cord blood and 584 received bone marrow. The transplantations were performed from 1998 through 2002 and reported to Eurocord and the European Blood and Marrow Transplant Group. 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 0.23x10(8) per kilogram of the recipient's body weight for cord blood and 2.9x10(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. 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. Copyright 2004 Massachusetts Medical Society.
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            Outcome of cord-blood transplantation from related and unrelated donors. Eurocord Transplant Group and the European Blood and Marrow Transplantation Group.

            Cord-blood banks have increased the use of cord-blood transplantation in patients with hematologic disorders. We have established a registry containing information on the outcome of cord-blood transplantation. We sent questionnaires to 45 transplantation centers for information on patients receiving cord-blood transplants from 1988 to 1996. Reports on 143 transplantations, performed at 45 centers, were studied, and the responses were analyzed separately according to whether the donor was related or unrelated to the recipient. Among 78 recipients of cord blood from related donors, the Kaplan-Meier estimate of survival at one year was 63 percent. Younger age, lower weight, transplants from HLA-identical donors, and cytomegalovirus-negative serologic results in the recipient were favorable prognostic factors. Graft-versus-host-disease of at least grade II occurred at estimated rates of 9 percent in 60 recipients of HLA-matched cord blood and 50 percent in 18 recipients of HLA-mismatched cord blood. Neutrophil engraftment was associated with an age of less than six years (P = 0.02) and a weight of less than 20 kg (P = 0.02), and it occurred in 85 percent of patients receiving 37 million or more nucleated cells per kilogram of body weight. Among 65 patients who received cord blood from unrelated donors, the Kaplan-Meier estimate of survival at one year was 29 percent. Cytomegalovirus-negative serologic status in these recipients was associated with improved survival (P = 0.03) and was the most important predictor of graft-versus-host disease (P = 0.04). Neutrophil recovery occurred in 94 percent of the patients who received 37 million or more nucleated cells per kilogram from unrelated donors. Cord blood is a feasible alternative source of hematopoietic stem cells for pediatric and some adult patients with major hematologic disorders, particularly if the donor and the recipient are related.
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              Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and HLA disparity on treatment-related mortality and survival.

              The potential benefits of unrelated donor marrow transplantation are offset by the immunologic complications of graft-versus-host disease (GVHD) and infection. Therefore, we used cryopreserved umbilical cord blood (UCB) as a strategy to reduce the risks of GVHD and treatment-related mortality (TRM) and improve survival. Data on 102 patients (median age 7.4 years) who received transplants between 1994 and 2001 for the treatment of malignant (n = 65; 68% were high-risk patients) and nonmalignant (n = 37) diseases were evaluated. Log-rank tests and Cox regression analyses were used to determine the effects of various demographic, graft-related, and treatment factors on engraftment, GVHD, TRM, relapse, and survival. As of October 15, 2001, the median follow-up was 2.7 years (range, 0.3-7.2). Incidences of neutrophil and platelet engraftment were 0.88 (CI, 0.81-0.95) and 0.65 (CI, 0.53-0.77), respectively. Notably, incidences of severe acute and chronic GVHD were 0.11 (CI, 0.05-0.17) and 0.10 (CI, 0.04-0.16), respectively. At 1 year after transplantation, proportions of TRM and survival were 0.30 (CI, 0.21-0.39) and 0.58 (CI, 0.48-0.68), respectively. In Cox regression analyses, CD34 cell dose was the one factor consistently identified as significantly associated with rate of engraftment, TRM, and survival. Despite the low incidence of GVHD, the proportion of patients with leukemia relapse at 2 years was 0.17 (CI, 0.00-0.38) and 0.45 (CI, 0.28-0.61) for patients with standard and high-risk disease, respectively. There is a high probability of survival in recipients of UCB grafts that are disparate in no more than 2 human leukocyte antigens (HLAs) when the grafts contain at least 1.7 x 10(5) CD34(+) cells per kilogram of recipient's body weight. Therefore, graft selection should be based principally on CD34 cell dose when multiple UCB units exist with an HLA disparity of 2 or less.
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                Author and article information

                Journal
                J Biomed Biotechnol
                J. Biomed. Biotechnol
                JBB
                Journal of Biomedicine and Biotechnology
                Hindawi Publishing Corporation
                1110-7243
                1110-7251
                2012
                2 October 2012
                : 2012
                : 767369
                Affiliations
                1CNR Institute of Bioimages and Molecular Physiology, Section of Genoa, Via De Marini 6, 16149 Genoa, Italy
                2Istituto Giannina Gaslini, Largo Gerolamo Gaslini, 16148 Genoa, Italy
                3Department of Nuclear Medicine, University of Genoa, Largo R. Benzi 10, 16132 Genoa, Italy
                4Department of Hematology and Bone Marrow Transplantation, San Martino Hospital, Largo R. Benzi, 16132 Genoa, Italy
                5Department of Mathematics, University of Genoa, Via Dodecaneso 35, 16146 Genoa, Italy
                6Advanced Biotechnology Center, Largo R. Benzi 10, 16132 Genoa, Italy
                Author notes
                *Gianmario Sambuceti: sambuceti@ 123456unige.it

                Academic Editor: Somayeh Shahrokhi

                Article
                10.1155/2012/767369
                3471032
                23093864
                5f79e959-d0c9-406d-adb4-afda301f6e95
                Copyright © 2012 Cecilia Marini et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 8 May 2012
                : 31 May 2012
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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