LETTER TO THE EDITOR Can intra-osseous transplantation improve results of umbilical cord blood transplantation in adult patients? Bone Marrow Transplantation (2006) 37, 335. doi:10.1038/sj.bmt.1705237; published online 28 November 2005 Some recently published studies 1–3 have raised intriguing questions which may be clinically relevant for future clinical trials of umbilical cord blood (UCB) transplant- ation in adults. Using a nonobese diabetic/severe combined immunodeficiency (NOD/SCID) xenotransplant model for studying the engraftment of human rapid short-term SCID repopulating cells (R-SRC), McKenzie et al. 1 demonstrated higher engraftment 2 and 6 weeks after transplanting Lin  CD34 þ CD38 þ /lo cells from human UCB by direct intrafemoral injection compared with the usual intravenous (IV) route. 1 Earlier Castello et al. 2 demonstrated that intraosseous (IO) transplantation of UCB mononuclear cells was associated with a seeding efficiency 15 times greater than IV transplantation. 2 Based on their findings in mice and monkey models, Ikehara et al. 3 considered intra-bone marrow (BM) transplantation a potentially important strategy. The concept of using the IO route of infusion in emergencies is re-emerging 4 and its safety is well estab- lished. 5 In addition to IO needles and BM biopsy needles, semiautomated devices are being evaluated for this purpose. The IO route of BM transplantation, using posterior iliac crests, has already been tested successfully in a prospective randomized fashion both in children 6 and adults. 7 Although engraftment was not faster, a significant reduction in the number of days on total parenteral nutrition and a tendency toward a reduction in the number of days on antibiotics was noted in the IO compared with the IV group. 7 Interestingly bacteremia did not occur in the IO group. 7 Major obstacles in the success of UCB transplantation in adult patients include relatively smaller dose of stem cells in the graft and delayed engraftment leading to high infectious morbidity and mortality. 8 In spite of being a rich source for CD34 þ CD38  stem cells and R-SRC, 9 some of the repopulating cells in UCB may have significantly reduced homing levels when injected IV. 1,10 McKenzie et al. 1 showed that anti-CD122 antibody was useful in overcoming CD122 þ cell-related resistance in this xenotransplantation model, and also pointed out that faster and better engraftment in IO transplantation as compared with usual IV transplantation might be related to host resistance factors other than CD122 þ cells, prevent- ing the homing of UCB R-SRC to appropriate hemato- poetic niches within the BM. 1 Now, with the availability of a variety of growth factors, and the strategies of multiunit UCB transplantation and ex vivo expansion of UCB units being explored in studies, 8 the time may be right for testing the approach of IO transplantation of UCB as a way of overcoming the problem of delayed engraftment. We propose that this strategy be tested prospectively to compare IO route, IV route and combined IV and IO route using single or multiple UCB units. SZA Zaidi, EA Sahovic, AS Al-Shanqeeti and M Aljurf Section of Adult Hematology & Hematopoietic Stem Cell Transplantation, King Faisal Cancer Center (MBC 59), King Faisal Specialist Hospital & Research Center, PO Box 3354, Riyadh 11211, Saudi Arabia E-mail: zaidi@kfshrc.edu.sa References 1 McKenzie J, Gan O, Doedens M, Dick J. Human short-term repopulating stem cells are efficiently detected following intrafemoral transplantation into NOD/SCID recipients depleted of CD122+ cells. Blood 2005; 106: 1259–1261. 2 Castello S, Podesta M, Menditto VG, Ibatici A, Pitto A, Figari O et al. Intra-bone marrow injection of bone marrow and cord blood cells: an alternative way of transplantation associated with a higher seeding efficiency. Exp Hematol 2004; 32: 782–787. 3 Ikehara S. Intra-bone marrow–bone marrow transplantation: a new strategy for treatment of stem cell disorders. Ann NY Acad Sci 2005; 1051: 626–634. 4 Bohn D. Intraosseous vascular access: from the archives to the ABC. Crit Care Med 1999; 27: 1053–1054. 5 Glaeser PW, Hellmich TR, Szewczuga D, Losek JD, Smith DS. Five-year experience in prehospital intraosseous infusions in children and adults. Ann Emerg Med 1993; 22: 1119–1124. 6 Trig ME. Inoculation of a portion of marrow for transplant as a way to accelerate marrow recovery. Bone Marrow Transplant 1998; 22: 616–617. 7 Hagglund H, Ringden O, Agren B, Wennberg L, Remberger M, Rundquist L et al. Intraosseous compared to intravenous infusion of allogeneic bone marrow. Bone Marrow Transplant 1998; 21: 331–335. 8 Ballen KK. New trends in umbilical cord blood transplant- ation. Blood 2005; 105: 3786–3792. 9 Hao QL, Shah AJ, Thiemann FT, Smogorzewska EM, Crooks GM. A functional comparison of CD34+CD38  cells in cord blood and bone marrow. Blood 1995; 86: 3745–3753. 10 Lapidot T, Dar A, Kollet O. How do stem cells find their way home? Blood 2005; 106: 1901–1910. Bone Marrow Transplantation (2006) 37, 335 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt