Article

Double Unrelated Reduced-Intensity Umbilical Cord Blood Transplantation in Adults

Division of Hematology/Oncology, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Biology of Blood and Marrow Transplantation (Impact Factor: 3.35). 02/2007; 13(1):82-9. DOI: 10.1016/j.bbmt.2006.08.041
Source: PubMed

ABSTRACT Umbilical cord blood (UBC) stem cells are a useful stem cell source for patients without matched related or unrelated donors. Adult transplantation with single UBC units is associated with high transplantation-related mortality (TRM). In most cases, mortality is due to infection related to slow engraftment and immunoincompetence. In this study, we used a reduced-intensity conditioning regimen of fludarabine, melphalan, and antithymocyte globulin followed by 2 partially matched UBC units. The UBC units were a 4/6 HLA match or better with each other and with the patient and achieved a minimum precryopreservation cell dose of 3.7 x 10(7) nucleated cells/kg. A total of 21 patients (median age, 49 years) were treated. The median time to an absolute neutrophil count > 0.5 x 10(9)/L was 20 days, and the median time to an unsupported platelet count > 20 x 10(9)/L was 41 days. Two patients experienced primary graft failure and underwent a second UBC transplantation. One patient had a late graft failure. Acute graft-versus-host disease (GVHD) grade II-IV occurred in 40% of patients. The 100-day TRM was 14%, and the 1-year disease-free survival was 67%. Mixed chimerism was associated with a higher risk of chronic GVHD. Our findings indicate that adult patients can tolerate double UBC transplantation well and achieve sustained antitumor responses using this reduced-intensity conditioning regimen.

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Available from: Grace S Kao, Jul 24, 2015
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    • "Low cell doses may preclude transplantation or contribute to delayed engraftment [6], transplant-related mortality, and survival [7] [8]. Combining more than one UCB unit for transplantation into adults has been one approach to overcome limiting cell doses [9] [10], but this approach "
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    ABSTRACT: Umbilical cord blood (UCB) is used increasingly in allogeneic transplantation. The size of units remains limiting, especially for adult recipients. Whether modest improvements in the yield of cells surviving storage and thawing allow more patients to proceed to transplant was examined. The impact of improved cell yield on the number of available UCB units was simulated using 21 consecutive anonymous searches. The number of suitable UCB units was calculated based on hypothetical recipient weight of 50 kg, 70 kg, and 90 kg and was repeated for a 10%, 20%, and 30% increase in the fraction of cells surviving storage. Increasing the percentage of cells that survive storage by 30% lowered the threshold of cells needed to achieve similar engraftment rates and increased numbers of UCB units available for patients weighing 50 (P = 0.011), 70 (P = 0.014), and 90 kg (P = 0.003), controlling for differences in HLA compatibility. Moreover, if recipients were 90 kg, 12 out of 21 patients had access to at least one UCB unit that met standard criteria, which increased to 19 out of 21 patients (P = 0.035) when the fraction of cells surviving storage and thawing increased by 30%. Modest increases in the yield of cells in banked UCB units can significantly increase donor options for adult patients undergoing HSCT.
    Stem cell International 02/2013; 2013:124834. DOI:10.1155/2013/124834 · 2.81 Impact Factor
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    • "The significantly higher incidence of primary graft failure following umbilical cord blood transplantation (UCBT) is well recognized, with rates of 10–16% in reported series (Rodrigues et al, 2009). Stem cell dose and immunogenetic disparity are recognized risk factors (Lauglin et al, 2001; Ballen et al, 2007). Primary graft failure is associated with a high mortality and management options include autologous reinfusion (if feasible), or re-transplantation with an alternative haematopoietic stem cell source (Chan et al, 2008; Dvorak et al, 2009) with its attendant risks. "
    British Journal of Haematology 05/2012; 158(3):419-20. DOI:10.1111/j.1365-2141.2012.09147.x · 4.96 Impact Factor
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    • "As an alternative, most centers now use double cord blood unit transplant strategies. Although this technique has helped to overcome cell dose limitations, there continues to be delayed engraftment and immune reconstitution, and it is typical to see a single unit emerge as the dominant source of long-term hematopoiesis (Ballen et al., 2007). However, the benefits of ex vivo expansion of stem cells reach beyond cord blood transplantation; other applications include increasing the number of gene-modified cells in gene therapy protocols and boosting cell numbers for transplant following nonmyeloablative conditioning. "
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