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Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.

Publication ,  Journal Article
Sullivan, KM; Storb, R; Buckner, CD; Fefer, A; Fisher, L; Weiden, PL; Witherspoon, RP; Appelbaum, FR; Banaji, M; Hansen, J
Published in: N Engl J Med
March 30, 1989

The occurrence of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation for leukemia is thought to decrease the probability of recurrence. To study this effect (called adoptive immunotherapy) we modified the prophylaxis of GVHD in patients with advanced hematologic neoplasms (mostly leukemia) who received bone marrow transplants. Patients under 30 years of age were randomly assigned to one of three regimens of post-transplantation immunosuppression: Group I (n = 44) received a standard course of methotrexate for 102 days after transplantation, Group II (n = 40) received an abbreviated (11-day) course of methotrexate, and Group III (n = 25) received the standard course of methotrexate plus viable buffy-coat cells from the marrow donors. All 109 patients received cyclophosphamide (60 mg per kilogram of body weight on each of two days), total-body irradiation (2.25 Gy daily for seven days), and unmodified marrow from HLA-identical sibling donors. The frequency of GVHD of Grades II through IV was 25 percent in Group I, 59 percent in Group II, and 82 percent in Group III (P = 0.0001). The incidence of chronic GVHD, however, did not differ significantly among the groups (33, 51, and 44 percent, respectively), nor did the five-year probability of recurrence of disease (38, 45, and 33 percent, respectively). However, mortality from causes other than cancer was 34 percent in Group I, 45 percent in Group II, and 64 percent in Group III (I vs. III, P = 0.024); the deaths were due primarily to infections complicating the course of GVHD. With a median follow-up of 5.1 years (range, 3.9 to 7.4), disease-free survival was 41 percent in Group I, 30 percent in Group II, and 24 percent in Group III (the differences were not statistically significant). We conclude that abbreviating methotrexate prophylaxis or infusing donor buffy-coat cells increased the incidence of acute GVHD and related mortality without altering the incidence of chronic GVHD or the recurrence of malignant disease.

Duke Scholars

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

March 30, 1989

Volume

320

Issue

13

Start / End Page

828 / 834

Location

United States

Related Subject Headings

  • Recurrence
  • Pulmonary Fibrosis
  • Methotrexate
  • Male
  • Lymphoma
  • Leukocytes
  • Leukemia
  • Infant
  • Immunotherapy
  • Immunosuppression Therapy
 

Citation

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Sullivan, K. M., Storb, R., Buckner, C. D., Fefer, A., Fisher, L., Weiden, P. L., … Hansen, J. (1989). Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med, 320(13), 828–834. https://doi.org/10.1056/NEJM198903303201303
Sullivan, K. M., R. Storb, C. D. Buckner, A. Fefer, L. Fisher, P. L. Weiden, R. P. Witherspoon, F. R. Appelbaum, M. Banaji, and J. Hansen. “Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.N Engl J Med 320, no. 13 (March 30, 1989): 828–34. https://doi.org/10.1056/NEJM198903303201303.
Sullivan KM, Storb R, Buckner CD, Fefer A, Fisher L, Weiden PL, et al. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med. 1989 Mar 30;320(13):828–34.
Sullivan, K. M., et al. “Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms.N Engl J Med, vol. 320, no. 13, Mar. 1989, pp. 828–34. Pubmed, doi:10.1056/NEJM198903303201303.
Sullivan KM, Storb R, Buckner CD, Fefer A, Fisher L, Weiden PL, Witherspoon RP, Appelbaum FR, Banaji M, Hansen J. Graft-versus-host disease as adoptive immunotherapy in patients with advanced hematologic neoplasms. N Engl J Med. 1989 Mar 30;320(13):828–834.
Journal cover image

Published In

N Engl J Med

DOI

ISSN

0028-4793

Publication Date

March 30, 1989

Volume

320

Issue

13

Start / End Page

828 / 834

Location

United States

Related Subject Headings

  • Recurrence
  • Pulmonary Fibrosis
  • Methotrexate
  • Male
  • Lymphoma
  • Leukocytes
  • Leukemia
  • Infant
  • Immunotherapy
  • Immunosuppression Therapy