Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease

K. M. Sullivan, R. P. Witherspoon, R. Storb, H. J. Deeg, S. Dahlberg, J. E. Sanders, F. R. Appelbaum, K. C. Doney, P. Weiden, C. Anasetti, T. P. Loughran, R. Hill, A. Shields, Gary C Yee, H. Shulman, J. Nims, S. Strom, E. D. Thomas

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Abstract

Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts <100,000/μL. Surival at 5 years after marrow transplant is only 26% in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 103/μL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone ± azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51% (group I) and 67% (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90% to 100%, scores for six survivors are 70% to 89%, and scores for five survivors are <70%. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.

Original languageEnglish (US)
Pages (from-to)555-561
Number of pages7
JournalBlood
Volume72
Issue number2
StatePublished - Jan 1 1988

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Prednisone
Grafts
Cyclosporine
Transplants
Sulfamethoxazole Drug Combination Trimethoprim
Platelets
Survivors
Toxicity
Therapeutics
Platelet Count
Salvaging
Dialysis
Azathioprine
Medical problems
Nervous System Malformations
Salvage Therapy
Tablets
Survival
Interstitial Lung Diseases
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Sullivan, K. M., Witherspoon, R. P., Storb, R., Deeg, H. J., Dahlberg, S., Sanders, J. E., ... Thomas, E. D. (1988). Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood, 72(2), 555-561.

Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. / Sullivan, K. M.; Witherspoon, R. P.; Storb, R.; Deeg, H. J.; Dahlberg, S.; Sanders, J. E.; Appelbaum, F. R.; Doney, K. C.; Weiden, P.; Anasetti, C.; Loughran, T. P.; Hill, R.; Shields, A.; Yee, Gary C; Shulman, H.; Nims, J.; Strom, S.; Thomas, E. D.

In: Blood, Vol. 72, No. 2, 01.01.1988, p. 555-561.

Research output: Contribution to journalArticle

Sullivan, KM, Witherspoon, RP, Storb, R, Deeg, HJ, Dahlberg, S, Sanders, JE, Appelbaum, FR, Doney, KC, Weiden, P, Anasetti, C, Loughran, TP, Hill, R, Shields, A, Yee, GC, Shulman, H, Nims, J, Strom, S & Thomas, ED 1988, 'Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease', Blood, vol. 72, no. 2, pp. 555-561.
Sullivan KM, Witherspoon RP, Storb R, Deeg HJ, Dahlberg S, Sanders JE et al. Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. Blood. 1988 Jan 1;72(2):555-561.
Sullivan, K. M. ; Witherspoon, R. P. ; Storb, R. ; Deeg, H. J. ; Dahlberg, S. ; Sanders, J. E. ; Appelbaum, F. R. ; Doney, K. C. ; Weiden, P. ; Anasetti, C. ; Loughran, T. P. ; Hill, R. ; Shields, A. ; Yee, Gary C ; Shulman, H. ; Nims, J. ; Strom, S. ; Thomas, E. D. / Alternating-day cyclosporine and prednisone for treatment of high-risk chronic graft-v-host disease. In: Blood. 1988 ; Vol. 72, No. 2. pp. 555-561.
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abstract = "Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts <100,000/μL. Surival at 5 years after marrow transplant is only 26{\%} in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 103/μL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone ± azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51{\%} (group I) and 67{\%} (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90{\%} to 100{\%}, scores for six survivors are 70{\%} to 89{\%}, and scores for five survivors are <70{\%}. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.",
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AU - Deeg, H. J.

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AU - Sanders, J. E.

AU - Appelbaum, F. R.

AU - Doney, K. C.

AU - Weiden, P.

AU - Anasetti, C.

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AU - Hill, R.

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AU - Yee, Gary C

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N2 - Therapy of chronic graft-v-host disease (GVHD) has been unsatisfactory in patients with platelet counts <100,000/μL. Surival at 5 years after marrow transplant is only 26% in such patients treated with trimethoprim-sulfamethoxazole (TMP-SMX) and every other day with prednisone. Since October 1982, 61 patients with high-risk extensive chronic GVHD were treated with a new alternating-day regimen of prednisone (1 mg/kg every other day) and oral cyclosporine (6 mg/kg every 12 hours every other day) with one double-strength TMP-SMX tablet twice daily. Forty patients (group I) received primary treatment of thrombocytopenic chronic GVHD (median platelet count 35 [range 7 to 87] x 103/μL). Twenty-one patients (group II) received salvage treatment after failing initial prednisone ± azathioprine. Twenty-one patients in group I and 15 in group II survive with a minimum of 2 years and a median of 3.7 years follow-up. At 4 years after transplant, actuarial survival is 51% (group I) and 67% (group II). Causes of death included interstitial pneumonia (six), relapse (five), GVHD without infection (five), infection (four), organ failure (three), and hemorrhage (two). Mortality increased with the progressive type onset of chronic GVHD and treatment failure. Toxicity included hypertension (13), nephrotoxicity (nine), nausea (seven), aseptic necrosis (five), neurologic abnormalities (four), and diabetes (three). Median cyclosporine levels at four and 36 hours were 296 and 64 ng/mL, respectively. Four patients required permanent discontinuation of cyclosporine, but none required renal dialysis. Karnofsky performance scores for 25 survivors are 90% to 100%, scores for six survivors are 70% to 89%, and scores for five survivors are <70%. Alternating-day cyclosporine and prednisone has acceptable toxicity and appears to improve survival in patients with high-risk chronic GVHD.

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