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

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, Sep 27, 2015
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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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    ABSTRACT: Cord blood (CB) has been used as an important and ethical source for hematopoietic stem cell transplantation (SCT) as well as cell therapy by manufacturing mesenchymal stem cell, induced pleuripotential stem cell or just isolating mononuclear cell from CB. Recently, the application of cell-based therapy using CB has expanded its clinical utility, particularly, by using autologous CB in children with refractory diseases. For these purposes, CB has been stored worldwide since mid-1990. In this review, I would like to briefly present the historical development of clinical uses of CB in the fields of SCT and cell therapy, particularly to review the experiences in Korea. Furthermore, I would touch the recent banking status of CB.
    Korean Journal of Pediatrics 03/2014; 57(3):110-116. DOI:10.3345/kjp.2014.57.3.110
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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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    ABSTRACT: Haploidentical related donors are alternative stem cell sources for patients without human leukocyte antigen (HLA)-matched related or unrelated donors. Immediate access to the donor, availability for patients with rare haplotypes, ease of stem cell procurement, and lack of a requirement for a physical cord blood bank or an extensive HLA database render this type of hematopoietic stem cell transplantation particularly attractive despite the high histoincompatibility barrier between the recipient and the haploidentical graft. In this review, we answer the following questions: 1) What are the current transplant strategies used to overcome the histoincompatibility barrier in haploidentical stem cell transplantation and their clinical results? 2) How should we choose the donor when there is more than one available haploidentical donor? 3) How does transplantation from haploidentical donors compare to that from umbilical cord blood? Conflict of interest:None declared.
    Turkish Journal of Haematology 12/2013; 30(4):342-350. DOI:10.4274/Tjh.2013.0054 · 0.36 Impact Factor
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    • "This leads to significantly delayed engraftment and increased peri-transplant complications [3-6]. One approach to overcome this problem is to use two unrelated hUCB units for the transplantation [7,8]. While this strategy improved adult engraftment rates, it brought about worse GVHD (graft-versus-host disease) [9]. "
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    ABSTRACT: Hematopoietic stem cells (HSCs) are widely used in transplantation therapy to treat a variety of blood diseases. The success of hematopoietic recovery is of high importance and closely related to the patient's morbidity and mortality after Hematopoietic stem cell transplantation (HSCT). We have previously shown that SALL4 is a potent stimulator for the expansion of human hematopoietic stem/progenitor cells in vitro. In these studies, we demonstrated that systemic administration with TAT-SALL4B resulted in expediting auto-reconstitution and inducing a 30-fold expansion of endogenous HSCs/HPCs in mice exposed to a high dose of irradiation. Most importantly, TAT-SALL4B treatment markedly prevented death in mice receiving lethal irradiation. Our studies also showed that TAT-SALL4B treatment was able to enhance both the short-term and long-term engraftment of human cord blood (CB) cells in NOD/SCID mice and the mechanism was likely related to the in vivo expansion of donor cells in a recipient. This robust expansion was required for the association of SALL4B with DNA methyltransferase complex, an epigenetic regulator critical in maintaining HSC pools and in normal lineage progression. Our results may provide a useful strategy to enhance hematopoietic recovery and reconstitution in cord blood transplantation with a recombinant TAT-SALL4B fusion protein.
    Journal of Hematology & Oncology 11/2013; 6(1):84. DOI:10.1186/1756-8722-6-84 · 4.81 Impact Factor
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