Cord-Blood Transplants from Unrelated Donors in Hurler's Syndrome
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《新英格兰医药杂志》
To the Editor: Staba et al. (May 6 issue)1 show the feasibility of cord-blood transplantation for Hurler's syndrome. The high rate of engraftment in their study is greater than one might expect. Allogeneic transplantation for Hurler's syndrome is associated with a high rate of engraftment failure, ranging from 15 to 37 percent.2,3 Transplantation of umbilical cord blood also carries a high risk of graft rejection. Furthermore, studies of the use of reduced-intensity allogeneic stem-cell transplants from unrelated donors suggest that antithymocyte globulin, which has observable effects on T cells for four days,4 might deplete donor-derived T cells and thus contribute to the graft failure.5 Thus, cord-blood transplantation for Hurler's syndrome after conditioning with the use of antithymocyte globulin might carry a high risk of graft failure. We would appreciate it if the authors could provide further explanations for the high rate of engraftment in this study.
George Fujisaki, M.D.
Masahiro Kami, M.D.
Yukiko Kishi, M.D.
National Cancer Center Hospital
Tokyo 1040045, Japan
jfujisak@ncc.go.jp
References
Staba SL, Escolar ML, Poe M, et al. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 2004;350:1960-1969.
Peters C, Balthazor M, Shapiro EG, et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996;87:4894-4902.
Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 1998;91:2601-2608.
Eiermann TH, Lambrecht P, Zander AR. Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant 1999;23:779-781.
Kusumi E, Kami M, Yuji K, et al. Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor. Bone Marrow Transplant 2004;33:697-702.
The authors reply: Dr. Fujisaki and colleagues express surprise at the high rate of donor-cell engraftment among the patients in our study, given previous reports of graft rejection in recipients of allogeneic bone-marrow transplants for Hurler's syndrome. It was our objective to define a chemotherapy regimen that would facilitate cord-blood engraftment. We believe that there are several reasons why we did not see more graft failure in our cohort of patients. First, we performed transplantation in small patients who received relatively high doses of cells per kilogram of body weight. Second, despite the overall decrease in the total dose of nucleated cells in a cord-blood transplant as compared with a bone marrow transplant, the dose of T cells was relatively high (median, 7x106 CD3 T cells per kilogram). Furthermore, although cord-blood transplantation in adults is associated with a 20 to 25 percent rate of graft failure, rates in children are lower.1,2 Antithymocyte globulin was added to the preparative regimen to facilitate engraftment by inducing immunosuppression in the host without damaging the graft T cells. In the previous studies mentioned by Fujisaki et al., patients received T-cell–depleted bone marrow,3 which is associated with increased rates of graft failure, regardless of the diagnosis.
Susan L. Staba, M.D.
Joanne Kurtzberg, M.D.
Duke University Medical Center
Durham, NC 27710
staba001@mc.duke.edu
References
Rubinstein P, Rosenfield RE, Adamson JW, Stevens CE. Stored placental blood for unrelated bone marrow reconstitution. Blood 1993;81:1679-1690.
Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001;97:2962-2971.
Peters C, Balthazor M, Shapiro EG, et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996;87:4894-4902.
George Fujisaki, M.D.
Masahiro Kami, M.D.
Yukiko Kishi, M.D.
National Cancer Center Hospital
Tokyo 1040045, Japan
jfujisak@ncc.go.jp
References
Staba SL, Escolar ML, Poe M, et al. Cord-blood transplants from unrelated donors in patients with Hurler's syndrome. N Engl J Med 2004;350:1960-1969.
Peters C, Balthazor M, Shapiro EG, et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996;87:4894-4902.
Peters C, Shapiro EG, Anderson J, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. Blood 1998;91:2601-2608.
Eiermann TH, Lambrecht P, Zander AR. Monitoring anti-thymocyte globulin (ATG) in bone marrow recipients. Bone Marrow Transplant 1999;23:779-781.
Kusumi E, Kami M, Yuji K, et al. Feasibility of reduced intensity hematopoietic stem cell transplantation from an HLA-matched unrelated donor. Bone Marrow Transplant 2004;33:697-702.
The authors reply: Dr. Fujisaki and colleagues express surprise at the high rate of donor-cell engraftment among the patients in our study, given previous reports of graft rejection in recipients of allogeneic bone-marrow transplants for Hurler's syndrome. It was our objective to define a chemotherapy regimen that would facilitate cord-blood engraftment. We believe that there are several reasons why we did not see more graft failure in our cohort of patients. First, we performed transplantation in small patients who received relatively high doses of cells per kilogram of body weight. Second, despite the overall decrease in the total dose of nucleated cells in a cord-blood transplant as compared with a bone marrow transplant, the dose of T cells was relatively high (median, 7x106 CD3 T cells per kilogram). Furthermore, although cord-blood transplantation in adults is associated with a 20 to 25 percent rate of graft failure, rates in children are lower.1,2 Antithymocyte globulin was added to the preparative regimen to facilitate engraftment by inducing immunosuppression in the host without damaging the graft T cells. In the previous studies mentioned by Fujisaki et al., patients received T-cell–depleted bone marrow,3 which is associated with increased rates of graft failure, regardless of the diagnosis.
Susan L. Staba, M.D.
Joanne Kurtzberg, M.D.
Duke University Medical Center
Durham, NC 27710
staba001@mc.duke.edu
References
Rubinstein P, Rosenfield RE, Adamson JW, Stevens CE. Stored placental blood for unrelated bone marrow reconstitution. Blood 1993;81:1679-1690.
Rocha V, Cornish J, Sievers EL, et al. Comparison of outcomes of unrelated bone marrow and umbilical cord blood transplants in children with acute leukemia. Blood 2001;97:2962-2971.
Peters C, Balthazor M, Shapiro EG, et al. Outcome of unrelated donor bone marrow transplantation in 40 children with Hurler syndrome. Blood 1996;87:4894-4902.