Graft-Versus-Tumor Effects After Allogeneic Hematopoietic Cell Transplantation With Nonmyeloablative Conditioning

• Published in: Journal of clinical oncology Vol. 23; no. 9; pp. 1993 - 2003
• Main Authors: BARON, Frédéric, MARIS, Michael B, MALONEY, David G, STORB, Rainer, SANDMAIER, Brenda M, STORER, Barry E, SORROR, Mohamed, DIACONESCU, Razvan, WOOLFREY, Ann E, CHAUNCEY, Thomas R, FLOWERS, Mary E. D, MIELCAREK, Marco
• Format: Journal Article Web Resource
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20-03-2005; Lippincott Williams & Wilkins; Amer Soc Clinical Oncology
• Subjects: Adolescent; Adult; Aged; Biological and medical sciences; Child; Child, Preschool; Comorbidity; Female; Graft Rejection; Graft vs Tumor Effect - drug effects; Graft vs Tumor Effect - radiation effects; Hematology; Hematopoietic Stem Cell Transplantation - methods; Human health sciences; Humans; Hématologie; Immunosuppressive Agents - therapeutic use; Leukemia - mortality; Leukemia - therapy; Male; Medical sciences; Middle Aged; Oncologie; Oncology; Probability; Sciences de la santé humaine; Transplantation Conditioning - methods; Treatment Outcome; Tumors; Vidarabine - analogs & derivatives; Vidarabine - therapeutic use; Cancerology; Graft versus tumor reaction; Stem cell; Hematopoietic cell; Homograft; Graft; Non myeloablative treatment
• ISSN: 0732-183X; 1527-7755; 1527-7755
• DOI: 10.1200/JCO.2005.08.136

We have used a nonmyeloablative conditioning regimen consisting of total-body irradiation (2 Gy) with or without fludarabine (30 mg/m(2)/d for 3 days) for related and unrelated hematopoietic cell transplantation (HCT) in patients with hematologic malignancies who were not candidates for conventional HCT because of age, medical comorbidities, or preceding high-dose HCT. This approach relied on graft-versus-tumor (GVT) effects for control of malignancy.
We analyzed GVT effects in 322 patients given grafts from HLA-matched related (n = 192) or unrelated donors (n = 130).
Of the 221 patients with measurable disease at HCT, 126 (57%) achieved complete (n = 98) or partial (n = 28) remissions. In multivariate analysis, there was a higher probability trend of achieving complete remissions in patients with chronic extensive graft-versus-host disease (GVHD; P = .07). One hundred eight patients (34%) relapsed or progressed. In multivariate analysis, achievement of full donor chimerism was associated with a decreased risk of relapse or progression (P = .002). Grade 2 to 4 acute GVHD had no significant impact on the risk of relapse or progression but was associated with increased risk of nonrelapse mortality and decreased probability of progression-free survival (PFS). Conversely, extensive chronic GVHD was associated with decreased risk of relapse or progression (P = .006) and increased probability of PFS (P = .003).
New approaches aimed at reducing the incidence of grade 2 to 4 acute GVHD might improve survival after allogeneic HCT after nonmyeloablative conditioning.