Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation

D. Przepiorka, I. Khouri, C. Ippoliti, N. T. Ueno, R. Mehra, M. Körbling, S. Giralt, J. Gajewski, H. Fischer, M. Donato, K. Cleary, D. Claxton, K. W. Chan, I. Braunschweig, K. Van Besien, B. S. Andersson, P. Anderlini, R. Champlin

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Abstract

Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69% of patients had a doubling of creatinine, 56% had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45%), hyperkalemia (17%), hyperglycemia (14%), seizures (13%), headache (3%) and hemolytic uremic syndrome (3%). Grades 2-4 GVHD occurred in 59% (95% CI, 38-70%), and grades 3-4 GVHD in 17% (95% CI, 1-32%). Overall survival at 1 year was 29% (95% CI, 12-45%). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.

Original languageEnglish (US)
Pages (from-to)763-768
Number of pages6
JournalBone Marrow Transplantation
Volume24
Issue number7
StatePublished - 1999
Externally publishedYes

Fingerprint

Stem Cell Transplantation
Tacrolimus
Graft vs Host Disease
Methotrexate
Blood Cells
Bone Marrow
Creatinine
Tissue Donors
Transplants
Antigens
Hemolytic-Uremic Syndrome
Hyperkalemia
Hyperglycemia
Immunosuppression
Headache
Lymphoma
Leukemia
Seizures
Stem Cells
Hypertension

Keywords

  • Graft-versus-host disease
  • Mismatched marrow transplantation
  • Tacrolimus

ASJC Scopus subject areas

  • Hematology
  • Transplantation

Cite this

Przepiorka, D., Khouri, I., Ippoliti, C., Ueno, N. T., Mehra, R., Körbling, M., ... Champlin, R. (1999). Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. Bone Marrow Transplantation, 24(7), 763-768.

Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. / Przepiorka, D.; Khouri, I.; Ippoliti, C.; Ueno, N. T.; Mehra, R.; Körbling, M.; Giralt, S.; Gajewski, J.; Fischer, H.; Donato, M.; Cleary, K.; Claxton, D.; Chan, K. W.; Braunschweig, I.; Van Besien, K.; Andersson, B. S.; Anderlini, P.; Champlin, R.

In: Bone Marrow Transplantation, Vol. 24, No. 7, 1999, p. 763-768.

Research output: Contribution to journalArticle

Przepiorka, D, Khouri, I, Ippoliti, C, Ueno, NT, Mehra, R, Körbling, M, Giralt, S, Gajewski, J, Fischer, H, Donato, M, Cleary, K, Claxton, D, Chan, KW, Braunschweig, I, Van Besien, K, Andersson, BS, Anderlini, P & Champlin, R 1999, 'Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation', Bone Marrow Transplantation, vol. 24, no. 7, pp. 763-768.
Przepiorka, D. ; Khouri, I. ; Ippoliti, C. ; Ueno, N. T. ; Mehra, R. ; Körbling, M. ; Giralt, S. ; Gajewski, J. ; Fischer, H. ; Donato, M. ; Cleary, K. ; Claxton, D. ; Chan, K. W. ; Braunschweig, I. ; Van Besien, K. ; Andersson, B. S. ; Anderlini, P. ; Champlin, R. / Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after HLA-mismatched marrow or blood stem cell transplantation. In: Bone Marrow Transplantation. 1999 ; Vol. 24, No. 7. pp. 763-768.
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abstract = "Thirty adults with leukemia or lymphoma transplanted with marrow or blood stem cells from 1-antigen mismatched related donors received tacrolimus and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 42 years (range 18-56 years). Twenty-seven patients had advanced disease, and 13 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/day i.v. by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued to day 180 post-transplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6 and 11. Mild nephrotoxicity was common before day 100; 69{\%} of patients had a doubling of creatinine, 56{\%} had a peak creatinine greater than 2 mg/dl, and two patients were dialyzed. Other toxicities prior to day 100 thought to be related to tacrolimus included hypertension (45{\%}), hyperkalemia (17{\%}), hyperglycemia (14{\%}), seizures (13{\%}), headache (3{\%}) and hemolytic uremic syndrome (3{\%}). Grades 2-4 GVHD occurred in 59{\%} (95{\%} CI, 38-70{\%}), and grades 3-4 GVHD in 17{\%} (95{\%} CI, 1-32{\%}). Overall survival at 1 year was 29{\%} (95{\%} CI, 12-45{\%}). We conclude that tacrolimus and minidose methotrexate is active post-transplant immunosuppression for patients with 1-antigen mismatched donors.",
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AU - Ueno, N. T.

AU - Mehra, R.

AU - Körbling, M.

AU - Giralt, S.

AU - Gajewski, J.

AU - Fischer, H.

AU - Donato, M.

AU - Cleary, K.

AU - Claxton, D.

AU - Chan, K. W.

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AU - Van Besien, K.

AU - Andersson, B. S.

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AU - Champlin, R.

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