title: Allogeneic transplantation for recurrent or refractory non-Hodgkin's lymphoma with poor prognostic features after conditioning with thiotepa, busulfan, and cyclophosphamide: experience in 44 consecutive patients.
abstract: We report the outcomes of 44 consecutive patients with non-Hodgkin's lymphoma (NHL) who participated in prospective studies of allogeneic transplantation after conditioning with thiotepa, busulfan and cyclophosphamide. Within a range of 27-57 years, the median age was 37. Of the 44 patients, 12 (27.2%) had high-grade lymphomas, 27 (61.4%) had intermediate-grade lymphomas, and five (11.3%) had low-grade lymphomas. Twenty-eight (63.6%) patients had chemotherapy refractory disease. Thirty (68.2%) patients had stage IV disease at the time of transplantation, involving the bone marrow in 19 (43.2%). Eight (18.1%) patients had undergone previous transplantation, and 13 (29.5%) patients had received high-dose CVP as induction within 2 months prior to transplantation. Thirty-eight (86.3%) patients had an HLA-identical donor, and 6 (13.6%) had a one-antigen mismatched related donor. Twenty (45.4%) patients received bone marrow and 24 (54.6%) received granulocyte colony-stimulating factor (G-CSF) mobilized stem cells. The graft-versus-host disease (GVHD) prophylaxis contained cyclosporine or tacrolimus in combination with either methylprednisolone in 32 (72.7%) patients or with methotrexate in 12 (27.2%) patients. The actuarial probability of disease-free survival at 2 years is 23% (95% CI 13%-40%). Donor stem cell use was associated with a significantly decreased risk of treatment-related toxicity (p < 0.001), but with an increased risk for GVHD and delayed fungal and viral infections. These infections are linked not only to the use of donor-stem cells, but also to the methylprednisolone in the GVHD prophylaxis regimen. Improvements in the outcome of patients with advanced NHL and undergoing allogeneic transplantation will depend on the development of effective and non-toxic regimens for conditioning, GVHD prophylaxis, and opportunistic infections prophylaxis.
authors.affiliation: Department of Hematology, University of Texas, M.D. Anderson Cancer Center, Houston, USA. kvbesien@uic.edu
authors.forename: K
authors.initials: K
authors.lastname: van Besien
authors.forename: P
authors.initials: P
authors.lastname: Thall
authors.forename: M
authors.initials: M
authors.lastname: Korbling
authors.forename: W C
authors.initials: WC
authors.lastname: Pugh
authors.forename: I
authors.initials: I
authors.lastname: Khouri
authors.forename: R
authors.initials: R
authors.lastname: Mehra
authors.forename: S
authors.initials: S
authors.lastname: Giralt
authors.forename: P
authors.initials: P
authors.lastname: Anderlini
authors.forename: K
authors.initials: K
authors.lastname: Amin
authors.forename: N
authors.initials: N
authors.lastname: Mirza
authors.forename: D
authors.initials: D
authors.lastname: Seong
authors.forename: J
authors.initials: J
authors.lastname: Gajewski
authors.forename: J
authors.initials: J
authors.lastname: Hester
authors.forename: B
authors.initials: B
authors.lastname: Andersson
authors.forename: F
authors.initials: F
authors.lastname: Cabanillas
authors.forename: R
authors.initials: R
authors.lastname: Champlin
authors.forename: D
authors.initials: D
authors.lastname: Przepiorka
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D002066:Busulfan / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000009:adverse effects / Q000627:therapeutic use*; D018572:Disease-Free Survival; D004359:Drug Therapy, Combination; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000139:chemically induced / Q000188:drug therapy / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use; D008228:Lymphoma, Non-Hodgkin / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012008:Recurrence; D013852:Thiotepa / Q000009:adverse effects / Q000627:therapeutic use*; D019172:Transplantation Conditioning; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D013852:Thiotepa; D002066:Busulfan