title: Nonmyeloablative stem cell transplantation is an effective therapy for refractory or relapsed hodgkin lymphoma: results of a spanish prospective cooperative protocol.
abstract: We report the results of reduced-intensity conditioning allogeneic stem cell transplantation (allo-RIC) in patients with advanced Hodgkin lymphoma (HL). Forty patients with relapsed or refractory HL were homogeneously treated with an RIC protocol (fludarabine 150 mg/m(2) intravenously plus melphalan 140 mg/m(2) intravenously) and cyclosporin A and methotrexate as graft-versus-host disease (GVHD) prophylaxis. Twenty-one patients (53%) had received >2 lines of chemotherapy, 23 patients (58%) had received radiotherapy, and 29 patients (73%) had experienced treatment failure with a previous autologous stem cell transplantation. Twenty patients (50%) were allografted in resistant relapse, and 38 patients received hematopoietic cells from an HLA-identical sibling. Five patients (12%) died from early transplant-related mortality (before day +100 after allo-RIC). One-year transplant-related mortality was 25%. Acute GVHD developed in 18 patients (45%). Chronic GVHD developed in 17 (45%) of the 31 evaluable patients. The response rate 3 months after the allo-RIC was 67% (21 [52%] complete remissions and 6 [15%] partial remissions). Eleven patients received donor lymphocyte infusions (DLIs) for disease relapse. The response rate after DLI was 54% (3 complete remissions and 3 partial remissions). Overall survival (OS) and progression-free survival (PFS) were 48% +/- 10% and 32% +/- 10% at 2 years, respectively. Refractoriness to chemotherapy was the only adverse prognostic factor for both OS (63% +/- 12% versus 35% +/- 13%; P = .05) and PFS (55% +/- 16% versus 10% +/- 9%; P = .006). For patients with failure of a prior autologous hematopoietic stem cell transplantation, results were especially good for those who experienced late relapses (>/=12 months: 2-year OS and PFS were 75% +/- 16% and 70% +/- 18%, respectively). These data suggest that allo-RIC is feasible in heavily pretreated HL patients and has an acceptable early transplant-related mortality. Results are better in patients allografted in sensitive disease. Both responses observed after the development of GVHD and DLI may suggest a graft-versus-HL effect. Allo-RIC has to be considered an effective therapeutic approach for patients who have had treatment failure with a previous autologous hematopoietic stem cell transplantation.
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: Iván
authors.initials: I
authors.lastname: Alvarez
authors.forename: Anna
authors.initials: A
authors.lastname: Sureda
authors.forename: Maria D
authors.initials: MD
authors.lastname: Caballero
authors.forename: Alvaro
authors.initials: A
authors.lastname: Urbano-Ispizua
authors.forename: Josep M
authors.initials: JM
authors.lastname: Ribera
authors.forename: Miguel
authors.initials: M
authors.lastname: Canales
authors.forename: Javier
authors.initials: J
authors.lastname: García-Conde
authors.forename: Guillermo
authors.initials: G
authors.lastname: Sanz
authors.forename: Reyes
authors.initials: R
authors.lastname: Arranz
authors.forename: Maria T
authors.initials: MT
authors.lastname: Bernal
authors.forename: Javier
authors.initials: J
authors.lastname: de la Serna
authors.forename: José L
authors.initials: JL
authors.lastname: Díez
authors.forename: José M
authors.initials: JM
authors.lastname: Moraleda
authors.forename: Daniel
authors.initials: D
authors.lastname: Rubió-Félix
authors.forename: Blanca
authors.initials: B
authors.lastname: Xicoy
authors.forename: Carmen
authors.initials: C
authors.lastname: Martínez
authors.forename: Marivi V
authors.initials: MV
authors.lastname: Mateos
authors.forename: Jorge
authors.initials: J
authors.lastname: Sierra
mesh_terms: D000293:Adolescent; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage; D018572:Disease-Free Survival; D005260:Female; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000401:mortality* / Q000517:prevention & control; D006689:Hodgkin Disease / Q000401:mortality* / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012008:Recurrence; D013030:Spain; D033581:Stem Cell Transplantation / Q000401:mortality; D015996:Survival Rate; D019172:Transplantation Conditioning / Q000379:methods / Q000401:mortality; D014184:Transplantation, Homologous