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: 3.4). 02/2007; 13(1):82-9. DOI: 10.1016/j.bbmt.2006.08.041
Source: PubMed


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
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    • "Cell dose titration of co-injected donor cells revealed that relative initial CD34 + cell content was strongly predictive of BM graft dominance (Fig. 2, B and C), reflecting clinical observations made in the context of human transplantation with mixed CB cells from two combined donors (Ballen et al., 2007). Furthermore , earlier transplantation provided a competitive repopulation advantage if donor cells were instead transplanted in a successive fashion (unpublished data), again recapitulating clinical reports (Ballen et al., 2007; Avery et al., 2011). In no instance did we observe evidence of immune recognition between donor cells (Yahata et al., 2004), as assured by the use of lineage-depleted (Lin  ) CB samples lacking CD2 + T cells (Fig. 2 B), and the application of the NOD SCID recipient background, which precludes terminal maturation of immune competent lymphocytes (Shultz et al., 2005). "
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    • "However, treatment-related mortality (TRM) or chronic GVHD were not higher but a higher graft-versus-leukemia effect was anticipated17,18,19,20,21,22). When 2 units of CB were transplanted, very interesting engraftment kinetics were revealed: early after double CBT (day +21) both CB units contributed to hematopoiesis in 40%-50% of patients, but by day +100 one unit predominated in the vast majority of the patients17,23). The unit predominance may be influenced by postthaw viability24), length of time interval between the infusion of the two CB units25) and ex vivo expansion26,27). The importance of T cells to establish chimerism and to ensure stem cell engraftment has been widely documented28,29,30,31,32,33). "
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    • "However, use of UCB as a stem cell source has been limited until recently by the delayed engraftment and relatively high rate of primary graft failures due to the low volume and low CD34+ cell content. Use of double, instead of single, UCB has partially overcome these issues [36,37]. "
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