Abstract
We conducted a pilot study to evaluate the feasibility of reduced-intensity cord blood transplantation (RI-CBT) using a non-total body irradiation (TBI) regimen in adult patients with advanced hematologic malignancies. Seventeen patients with a median age of 58 years (range, 38–74) underwent RI-CBT at Tsukuba Memorial Hospital between April 2004 and November 2005. Preparative regimens were fludarabine 30 mg/m2 for 6 days, and busulfan 4 mg/kg for 2 days. Tacrolimus was used for prophylaxis of graft-vs-host disease (GVHD). Median numbers of infused total nucleated were 2.6×107/kg (range, 2.0–3.3). HLA disparity was found in 2/6 antigens (n=16) and 1/6 antigens (n=1). Underlying diseases progressed despite preparative regimens in four patients. Of the remaining 13 patients, nine patients achieved engraftment at a median of day 18 (range, 17–28). Six of the nine patients with engraftment achieved complete donor-type chimerism by day 100. Six patients were alive in remission at median follow-up of 13.1 months (range, 1.0–19.0). This study demonstrated the feasibility of RI-CBT using a non-TBI regimen in adults. When disease progression is controlled by the preparative regimen, RI-CBT carries a clinically significant graft-vs-tumor effect. Further studies are required to identify patients who benefit from this regimen.
Similar content being viewed by others
References
Sanz GF, Saavedra S, Planelles D, Senent L, Cervera J, Barragan E, Jimenez C, Larrea L, Martin G, Martinez J, Jarque I, Moscardo F, Plume G, Andreu R, Regadera AI, Garcia I, Molla S, Solves P, de La Rubia J, Bolufer P, Benlloch L, Soler MA, Marty ML, Sanz MA (2001) Standardized, unrelated donor cord blood transplantation in adults with hematologic malignancies. Blood 98:2332–2338
Rocha V, Labopin M, Sanz G, Arcese W, Schwerdtfeger R, Bosi A, Jacobsen N, Ruutu T, de Lima M, Finke J, Frassoni F, Gluckman E (2004) Transplants of umbilical-cord blood or bone marrow from unrelated donors in adults with acute leukemia. N Engl J Med 351:2276–2285
Laughlin MJ, Eapen M, Rubinstein P, Wagner JE, Zhang MJ, Champlin RE, Stevens C, Barker JN, Gale RP, Lazarus HM, Marks DI, van Rood JJ, Scaradavou A, Horowitz MM (2004) Outcomes after transplantation of cord blood or bone marrow from unrelated donors in adults with leukemia. N Engl J Med 351:2265–2275
Miyakoshi S, Yuji K, Kami M, Kusumi E, Kishi Y, Kobayashi K, Murashige N, Hamaki T, Kim SW, Ueyama J, Mori S, Morinaga S, Muto Y, Masuo S, Kanemaru M, Hayashi T, Takaue Y, Taniguchi S (2004) Successful engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with advanced hematological diseases. Clin Cancer Res 10:3586–3592
Barker JN, Weisdorf DJ, DeFor TE, Blazar BR, Miller JS, Wagner JE (2003) Rapid and complete donor chimerism in adult recipients of unrelated donor umbilical cord blood transplantation after reduced-intensity conditioning. Blood 102:1915–1919
Narimatsu H, Matsumura T, Kami M, Miyakoshi S, Kusumi E, Takagi S, Miura Y, Kato D, Inokuchi C, Myojo T, Kishi Y, Murashige N, Yuji K, Masuoka K, Yoneyama A, Wake A, Morinaga S, Kanda Y, Taniguchi S (2005) Bloodstream infection after umbilical cord blood transplantation using reduced-intensity stem cell transplantation for adult patients. Biol Blood Marrow Transplant 11:429–436
Kishi Y, Miyakoshi S, Kami M, Ikeda M, Katayama Y, Murashige N, Kusumi E, Yuji K, Kobayashi K, Kato D, Hamaki T, Matsumura T, Kim SW, Morinaga S, Mori S, Kanemaru M, Hayashi T, Takaue Y, Taniguchi S (2004) Early central nervous system complications after reduced-intensity stem cell transplantation. Biol Blood Marrow Transplant 10:561–568
Kodera Y, Morishima Y, Kato S, Akiyama Y, Sao H, Matsuyama T, Kawa K, Sakamaki H, Nakagawa S, Hirabayashi N, Dohi H, Okamoto S, Hiraoka A, Gondo H, Tsuchida M, O H, Harada M, Asano S, Juji T, Sasazuki T, Takaku F (1999) Analysis of 500 bone marrow transplants from unrelated donors (UR-BMT) facilitated by the Japan marrow donor program: confirmation of UR-BMT as a standard therapy for patients with leukemia and aplastic anemia. Bone Marrow Transplant 24:995–1003
Nishihira H, Kato K, Isoyama K, Takahashi TA, Kai S, Kato S, Takanashi M, Sato N, Sato H, Kitajima K, Naoe T, Saito H (2003) The Japanese cord blood bank network experience with cord blood transplantation from unrelated donors for haematological malignancies: an evaluation of graft-versus-host disease prophylaxis. Br J Haematol 120:516–522
Trotti A, Colevas AD, Setser A, Rusch V, Jaques D, Budach V, Langer C, Murphy B, Cumberlin R, Coleman CN, Rubin P (2003) CTCAE v3.0: development of a comprehensive grading system for the adverse effects of cancer treatment. Semin Radiat Oncol 13:176–181
Thiede C, Florek M, Bornhauser M, Ritter M, Mohr B, Brendel C, Ehninger G, Neubauer A (1999) Rapid quantification of mixed chimerism using multiplex amplification of short tandem repeat markers and fluorescence detection. Bone Marrow Transplant 23:1055–1060
Gooley TA, Leisenring W, Crowley J, Storer BE (1999) Estimation of failure probabilities in the presence of competing risks: new representations of old estimators. Stat Med 18:695–706
Hori A, Kami M, Kim SW, Murashige N, Sakiyama M, Kojima R, Hamaki T, Makimoto A, Miyakoshi S, Masuo S, Taniguchi S, Kunitoh H, Takaue Y (2004) Urgent need for a validated tumor response evaluation system for use in immunotherapy. Bone Marrow Transplant 33:255–256
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Komatsu, T., Narimatsu, H., Yoshimi, A. et al. Successful engraftment of mismatched unrelated cord blood transplantation following reduced intensity preparative regimen using fludarabine and busulfan. Ann Hematol 86, 49–54 (2007). https://doi.org/10.1007/s00277-006-0190-5
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00277-006-0190-5