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CD6+ donor marrow T-cell depletion as the sole form of graft-versus-host disease prophylaxis in patients undergoing allogeneic bone marrow transplant from unrelated donors.
Soiffer, R J; Weller, E; Alyea, E P; Mauch, P; Webb, I L; Fisher, D C; Freedman, A S; Schlossman, R L; Gribben, J; Lee, S; Anderson, K C; Marcus, K; Stone, R M; Antin, J H; Ritz, J.
Affiliation
  • Soiffer RJ; Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. robert_soiffer@dfci.harvard.edu
J Clin Oncol ; 19(4): 1152-9, 2001 Feb 15.
Article in En | MEDLINE | ID: mdl-11181681
PURPOSE: The role of donor marrow T-cell depletion (TCD) in preventing graft-versus-host disease (GVHD) after transplantation of unrelated allogeneic marrow remains undefined. Because different TCD methodologies differ in the degree and specificity with which T cells are removed, it is likely that transplant outcomes would depend on which technique is used. Herein, we report results in the first 48 recipients of unrelated marrow using CD6+ TCD as the sole form of GVHD prophylaxis. PATIENTS AND METHODS: Median age of patients was 46 years (20 to 58 years). Donors were matched at A/B HLA loci. Ablation consisted of cyclophosphamide and fractionated total-body irradiation (TBI; 14 Gy). To facilitate engraftment, patients also received 7.5 Gy (22 patients) [corrected] or 4.5 Gy (26 patients) [corrected] of total lymphoid irradiation (TLI) before admission. No additional immune suppressive prophylaxis was administered. Granulocyte colony-stimulating factor was administered daily from day +1 to engraftment. RESULTS: All 48 patients demonstrated neutrophil engraftment. An absolute neutrophil count of 500 x 10(6)/L was achieved at a median of 12 days (range, 9 to 23 days). There were no cases of late graft failure. The number of CD34+ cells infused/kg was associated with speed of platelet and neutrophil recovery. The dose of TLI did not influence engraftment. Grades 2-4 acute GVHD occurred in 42% of patients (95% confidence interval [CI], 0.28 to 0.57). Mortality at day 100 was 19%. There have been only five relapses. Estimated 2-year survival was 44% (95% CI, 0.28 to 0.59) for the entire group, 58% for patients less than 50 years of age. In multivariable analysis, age less than 50 years (P =.002), cytomegalovirus seronegative status (P =.04), and early disease status at bone marrow transplant (P =.05) were associated with superior survival. CONCLUSION: CD6+ TCD does not impede engraftment of unrelated bone marrow after low-dose TLI, cyclophosphamide, and TBI. CD6+ TCD as the sole form of GVHD prophylaxis results in an incidence of GVHD that compares favorably with many adult studies of unrelated transplantation using unmanipulated marrow and immune-suppressive medications, especially in light of the median age of our patients (46 years). Although event-free survival in patients less than 50 years of age is very encouraging, older patients experience frequent transplantation-related complications despite TCD.
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Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Antineoplastic Combined Chemotherapy Protocols / Antigens, Differentiation, T-Lymphocyte / Antigens, CD / Bone Marrow Transplantation / Lymphocyte Depletion / Graft vs Host Disease Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: J Clin Oncol Year: 2001 Document type: Article Affiliation country: United States Country of publication: United States
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Collection: 01-internacional Database: MEDLINE Main subject: T-Lymphocytes / Antineoplastic Combined Chemotherapy Protocols / Antigens, Differentiation, T-Lymphocyte / Antigens, CD / Bone Marrow Transplantation / Lymphocyte Depletion / Graft vs Host Disease Limits: Adult / Female / Humans / Male / Middle aged Language: En Journal: J Clin Oncol Year: 2001 Document type: Article Affiliation country: United States Country of publication: United States