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Graft-versus-host disease and graft-versus-tumor effects after allogeneic hematopoietic cell transplantation. J Clin Oncol 2013 Apr 20;31(12):1530-8 PMID: 23478054 PMCID: PMC3625710

Pubmed ID

23478054

DOI

10.1200/JCO.2012.45.0247

Abstract

PURPOSE: We designed a minimal-intensity conditioning regimen for allogeneic hematopoietic cell transplantation (HCT) in patients with advanced hematologic malignancies unable to tolerate high-intensity regimens because of age, serious comorbidities, or previous high-dose HCT. The regimen allows the purest assessment of graft-versus-tumor (GVT) effects apart from conditioning and graft-versus-host disease (GVHD) not augmented by regimen-related toxicities.

PATIENTS AND METHODS: Patients received low-dose total-body irradiation ± fludarabine before HCT from HLA-matched related (n = 611) or unrelated (n = 481) donors, followed by mycophenolate mofetil and a calcineurin inhibitor to aid engraftment and control GVHD. Median patient age was 56 years (range, 7 to 75 years). Forty-five percent of patients had comorbidity scores of ≥ 3. Median follow-up time was 5 years (range, 0.6 to 12.7 years).

RESULTS: Depending on disease risk, comorbidities, and GVHD, lasting remissions were seen in 45% to 75% of patients, and 5-year survival ranged from 25% to 60%. At 5 years, the nonrelapse mortality (NRM) rate was 24%, and the relapse mortality rate was 34.5%. Most NRM was a result of GVHD. The most significant factors associated with GVHD-associated NRM were serious comorbidities and grafts from unrelated donors. Most relapses occurred early while the immune system was compromised. GVT effects were comparable after unrelated and related grafts. Chronic GVHD, but not acute GVHD, further increased GVT effects. The potential benefit associated with chronic GVHD was outweighed by increased NRM.

CONCLUSION: Allogeneic HCT relying on GVT effects is feasible and results in cures of an appreciable number of malignancies. Improved results could come from methods that control progression of malignancy early after HCT and effectively prevent GVHD.

Author List

Storb R, Gyurkocza B, Storer BE, Sorror ML, Blume K, Niederwieser D, Chauncey TR, Pulsipher MA, Petersen FB, Sahebi F, Agura ED, Hari P, Bruno B, McSweeney PA, Maris MB, Maziarz RT, Langston AA, Bethge W, Vindeløv L, Franke GN, Laport GG, Yeager AM, Hübel K, Deeg HJ, Georges GE, Flowers ME, Martin PJ, Mielcarek M, Woolfrey AE, Maloney DG, Sandmaier BM

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84876329801   112 Citations

MESH terms used to index this publication - Major topics in bold

Adolescent
Adult
Aged
Child
Child, Preschool
Combined Modality Therapy
Female
Follow-Up Studies
Graft Rejection
Graft vs Host Disease
Graft vs Tumor Effect
HLA Antigens
Hematologic Neoplasms
Hematopoietic Stem Cell Transplantation
Humans
Infant
Infant, Newborn
Male
Middle Aged
Neoplasm Recurrence, Local
Neoplasm Staging
Prognosis
Survival Rate
Transplantation Conditioning
Transplantation, Homologous
Young Adult
jenkins-FCD Prod-331 a335b1a6d1e9c32173c9534e6f6ff51494143916