Simultaneous cord blood transplantation of ex vivo expanded together with non-expanded cells for high risk leukemia

Abstract

Summary:In the absence of a donor alternative a stem cell transplantation consisting of two cord blood components originating from the haploidentical brother was performed in a 2-year-old girl with c-ALL, early CNS relapse and 7% of blast cells in the BM 14 days before transplantation. Because of various ongoing infectious complications at that time, 1/8 of the immunogenetically acceptable sibling cord blood was ex vivo expanded 10 days before the transplantation date. The total CB consisting of 1.17 ؋ 10 9 NC was cryopreserved in four separate bags. The one containing 1/8 of the total CB with 1.4 ؋ 10 8 NC CliniMACS selected CD34 ؉ cells was expanded in the presence of 100 ng/ml G-CSF, 100 ng/ml TPO and 100 ng/ml flt3-L in 10% autologous CB plasma and X-VIVO 10 medium at day ؊10 before transplantation. This expanded cell population was sterile and consisted of about 60% granulocytic cells (CD13 ؉ Cord blood (CB) has clearly become an alternative and even a promising source of marrow repopulating cells for the treatment of pediatric patients over the past 10 years. Hitherto, over 1000 unrelated and related cord blood transplants have been performed, mostly in pediatric patients. [1][2][3][4][5] In spite of one or two HLA-antigen mismatches these patients have engrafted with no or only moderate acute or chronic GVHD. [1][2][3][4][5] Due to the relatively low numbers of cells in the primary residual cord blood including colony-forming units and CD34 ϩ cells, presently there are certain limitations for the widespread use of CB as a source of hematopoietic cells for transplantation, particularly in adults or overweight patients. Delays in engraftment for neutrophils and platelets have been observed when lower cell numbers were transplanted, resulting in more frequent infectious complications after transplantation. With about 40% frequency the latter were the major cause of death in the most recent analysis published.,5 Therefore, ex vivo expanded CB infused into the patient at the time of transplantation as the nonexpanded cord blood from the same donor could increase the number of immediately available progenitor cells responsible for short-term engraftment. While expansion with recombinant hematopoietic growth factors has been shown to increase the number of multipotent colony-

Unrelated donor umbilical cord blood transplantation in adults

“…26,30,44,45 Another potential approach to reduce TRM in UD-UCBT is to reduce the time of engraftment by using ex vivo expanded cord blood units. 24,46,47,48 However, some concerns have Leukemia been expressed because of the possible negative impact of these methods on long-term engraftment. 49,50 The combination of expanded and unmanipulated fractions of UCB graft could provide rapid short-and long-term engraftment.…”

Umbilical cord blood for allogeneic transplantation in children and adults

“…Attempts to increase UCB cell dose has laid the basis for laboratory 56 and phase I clinical trials [57][58][59] focused on ex vivo expansion of UCB grafts. Although early clinical trials reported thus far do not point to more rapid hematopoietic recovery in UCB recipients, there is improved day 100 survival compared with historical controls.…”

Prompt and durable engraftment in two older adult patients with high risk chronic myelogenous leukemia (CML) using ex vivo expanded and unmanipulated unrelated umbilical cord blood

“…Completion of ongoing studies is needed to determine if similar improvements in outcome will be observed in future patients with CML, and at even lower UCB doses. Moreover, through identification of the hematopoietic and/or accessory cells that facilitate engraftment and by optimization of the infusion sequence of expanded and unexpanded cells as reported elsewhere, 10 it may be possible to develop better expansion strategies that translate into a more consistent improvement in outcomes for unrelated UCB recipients.…”