Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia

Initial experience of the National Marrow Donor Program

Philip McGlave, Glenn Bartsch, Claudio Anasetti, Robert Ash, Patrick Beatty, James Gajewski, Nancy A. Kernan

Research output: Contribution to journalArticle

182 Citations (Scopus)

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 mate. 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 ≥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. Proportional hazards analysis revealed that transplantation with HLA-matched donor marrow (P = .01), transplantation at younger age (P = .02), and transplantation in first chronic phase (P = .04) had independent, beneficial effects on disease-free survival. Thirty-eight (50%) of patients surviving at 1 year had normal activity levels (Karnofsky = 100%), whereas 31 recipients (41%) had mild impairment of activity (Karnofsky = 90% to 80%) and 7 recipients (9%) had severe impairment of activity (Karnofsky = 70% to 30%). Development of the NMDP has facilitated the use of HLA-matched unrelated donors for marrow transplantation. This treatment modality can result in prolonged disease-free survival in some patients with CML, especially younger patients transplanted early in their disease course using donors matched at the HLA A, B, and DR loci. A high incidence of graft failure, acute and chronic GVHD, and prolonged convalescence can complicate treatment.

Original languageEnglish (US)
Pages (from-to)543-550
Number of pages8
JournalBlood
Volume81
Issue number2
StatePublished - Jan 15 1993
Externally publishedYes

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Unrelated Donors
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Transplantation
Bone Marrow
Grafts
Tissue Donors
Graft vs Host Disease
Transplants
HLA-A Antigens
Chemotherapy
Therapeutics
Incidence
Disease-Free Survival
Blast Crisis
Dosimetry
HLA-B Antigens
HLA-DR Antigens
T-cells
Drug Therapy
Hazards

ASJC Scopus subject areas

  • Hematology

Cite this

McGlave, P., Bartsch, G., Anasetti, C., Ash, R., Beatty, P., Gajewski, J., & Kernan, N. A. (1993). Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the National Marrow Donor Program. Blood, 81(2), 543-550.

Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia : Initial experience of the National Marrow Donor Program. / McGlave, Philip; Bartsch, Glenn; Anasetti, Claudio; Ash, Robert; Beatty, Patrick; Gajewski, James; Kernan, Nancy A.

In: Blood, Vol. 81, No. 2, 15.01.1993, p. 543-550.

Research output: Contribution to journalArticle

McGlave, P, Bartsch, G, Anasetti, C, Ash, R, Beatty, P, Gajewski, J & Kernan, NA 1993, 'Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the National Marrow Donor Program', Blood, vol. 81, no. 2, pp. 543-550.
McGlave P, Bartsch G, Anasetti C, Ash R, Beatty P, Gajewski J et al. Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia: Initial experience of the National Marrow Donor Program. Blood. 1993 Jan 15;81(2):543-550.
McGlave, Philip ; Bartsch, Glenn ; Anasetti, Claudio ; Ash, Robert ; Beatty, Patrick ; Gajewski, James ; Kernan, Nancy A. / Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia : Initial experience of the National Marrow Donor Program. In: Blood. 1993 ; Vol. 81, No. 2. pp. 543-550.
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T1 - Unrelated donor marrow transplantation therapy for chronic myelogenous leukemia

T2 - Initial experience of the National Marrow Donor Program

AU - McGlave, Philip

AU - Bartsch, Glenn

AU - Anasetti, Claudio

AU - Ash, Robert

AU - Beatty, Patrick

AU - Gajewski, James

AU - Kernan, Nancy A.

PY - 1993/1/15

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N2 - 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 mate. 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 ≥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. Proportional hazards analysis revealed that transplantation with HLA-matched donor marrow (P = .01), transplantation at younger age (P = .02), and transplantation in first chronic phase (P = .04) had independent, beneficial effects on disease-free survival. Thirty-eight (50%) of patients surviving at 1 year had normal activity levels (Karnofsky = 100%), whereas 31 recipients (41%) had mild impairment of activity (Karnofsky = 90% to 80%) and 7 recipients (9%) had severe impairment of activity (Karnofsky = 70% to 30%). Development of the NMDP has facilitated the use of HLA-matched unrelated donors for marrow transplantation. This treatment modality can result in prolonged disease-free survival in some patients with CML, especially younger patients transplanted early in their disease course using donors matched at the HLA A, B, and DR loci. A high incidence of graft failure, acute and chronic GVHD, and prolonged convalescence can complicate treatment.

AB - 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 mate. 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 ≥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. Proportional hazards analysis revealed that transplantation with HLA-matched donor marrow (P = .01), transplantation at younger age (P = .02), and transplantation in first chronic phase (P = .04) had independent, beneficial effects on disease-free survival. Thirty-eight (50%) of patients surviving at 1 year had normal activity levels (Karnofsky = 100%), whereas 31 recipients (41%) had mild impairment of activity (Karnofsky = 90% to 80%) and 7 recipients (9%) had severe impairment of activity (Karnofsky = 70% to 30%). Development of the NMDP has facilitated the use of HLA-matched unrelated donors for marrow transplantation. This treatment modality can result in prolonged disease-free survival in some patients with CML, especially younger patients transplanted early in their disease course using donors matched at the HLA A, B, and DR loci. A high incidence of graft failure, acute and chronic GVHD, and prolonged convalescence can complicate treatment.

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