Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: initial experience of the National Marrow Donor Program

Abstract

In the interval from December 1987 to November 1990, 196 consecutive patients with chronic myelogenous leukemia (CML) received unrelated donor marrow transplantation using marrow procured by the National Marrow Donor Program (NMDP) at 21 NMDP-affiliated marrow transplant centers. Baseline donor and recipient data as well as follow-up data were obtained systematically in all cases by the NMDP. The median interval from the initiation of a search for an unrelated donor to bone marrow transplantation was 8.4 months (range, 1.7 to 34.6 months). Median age of the recipients was 33.3 years (4.5 to 54.5 years). Seventy-five recipients were female and 121 were male. At time of transplant, 115 patients were in chronic phase, 51 in accelerated phase, 14 in blast crisis, and 16 in a second or subsequent chronic phase. In 133 cases, donors and recipients were identical at the HLA A, B, and DR loci using standard serologic typing, and in 63 cases, there was nonidentity at one HLA locus. Patients were prepared for transplantation with a combination of high-dose chemotherapy and total body irradiation (N = 169) or with high-dose chemotherapy only (N = 27). Thirty-five patients received marrow depleted ex vivo of T lymphocytes, whereas 161 patients received non-T-depleted marrow. One hundred seventy-four of 196 patients engrafted (absolute neutrophil count > or = 500/mm3 for 3 consecutive days). The median time to engraftment was 22 days (6 to 69 days). Twenty-two patients failed to engraft, and an additional 10 patients experienced late graft failure. The incidence of grades III or IV acute graft-versus-host disease (GVHD) was 0.54 +/- 0.10, and that of extensive chronic GVHD was 0.52 +/- 0.12. A lower incidence of both grades III and IV acute GVHD (P = .0003) and of extensive chronic GVHD (P = .01) were independently associated with use of T-depleted marrow. The actuarial incidence of hematologic relapse at 2 years is 0.11 +/- 0.06. The 2-year actuarial incidence of disease-free survival for patients transplanted in first chronic phase within 1 year of diagnosis is 0.45 +/- 0.21, in chronic phase more than 1 year from diagnosis is 0.36 +/- 0.11, in accelerated phase is 0.27 +/- 0.12, in second or subsequent chronic phase is 0.22 +/- 0.21, and in blast crisis is 0. Fifteen of 55 patients transplanted at 40 to 50 years of age survive.(ABSTRACT TRUNCATED AT 400 WORDS)

Treatment of advanced acute leukaemia with allogeneic bone marrow transplantation from unrelated donors

“…Complete remission and long-term leukaemia-free survival after bone marrow transplantation probably result from the intensive chemoradiotherapy conditioning and the immunologic effect associated with the engraftment of allogeneic bone marrow (Schiller, 1991;McGlave et al, 1993;McCullough et al, 1989). The purpose of this analysis was to assess major therapeutic endpoints (leukaemia-free and overall survival) and treatment-related complications of unrelated bone marrow transplant as therapy for a specific group of high-risk patients with primary induction failure and relapsed acute leukaemia.…”

“…Transplantation from unrelated donors is now feasible in the United States through the development of the National Marrow Donor Program, and elsewhere through International Registries which have made possible unrelated donor identiiication, procurement, and transplant processing McCullough et al, 1989;Beatty et al, 1991;Gajewski et al, 1990a;Kernan et al, 1993;Hows et al, 1986). In this report we review our experience with 55 patients with advanced acute leukaemia who received highdose chemoradiotherapy followed by transplantation of unrelated allogeneic bone marrow.…”

Comparison between antithymocyte globulin and alemtuzumab and the possible impact of KIR‐ligand mismatch after dose‐reduced conditioning and unrelated stem cell transplantation in patients with multiple myeloma

“…Several reduced-toxicity regimens have been investigated for haematological malignancies and solid tumours, whose antitumour effect relies on a graft versus malignancy effect rather than on chemotherapy effects (Slavin et al, 1998;Childs et al, 2000;Giralt et al, 2001;McSweeney et al, 2001). The use of unrelated donors in standard myeloablative transplantation is associated with a higher rate of graft failure, higher incidence of graft versus host disease (GvHD) and more toxicity in comparison with sibling transplantation, limiting this approach to younger patients with a good performance status (McGlave et al, 1993). Several dose-reduced regimens, including low-dose total body irradiation (Maris et al, 2003), fludarabine and melphalan (Giralt et al, 2001) or busulphan (Nagler et al, 2001) have been used with unrelated donors and minimal regimen-related extramedullary toxicity has been observed.…”

Delayed ABLC prophylaxis after allogeneic stem‐cell transplantation

“…One-third of the patients received grafts from unrelated or partially matched related donors. 4,12 Seventy-five per cent of the patients had intermediate-or poor-risk disease, with one-third of the patients having refractory leukaemia. Forty per cent of the patients received stem-cell grafts that had been T-cell depleted either in vitro or in vivo.…”