title: Long-term outcomes of patients with persistent indolent B cell malignancies undergoing nonmyeloablative allogeneic transplantation.
abstract: Relapse is least common in patients with indolent B cell (iB) malignancies (ie, iB non-Hodgkin lymphoma [NHL]) who undergo nonmyeloablative allogeneic transplantation (NMAT) in complete remission (CR). However, for the many patients unable to achieve this state, outcomes are poorly described and methods to improve results are unknown. We sought to describe the long-term follow-up and predictive factors for these poor-risk patients unable to achieve CR before NMAT. We identified and evaluated patients with iB-NHL including chronic lymphocytic leukemia treated with fludarabine/total body irradiation-based NMAT that had evidence of persistent disease before NMAT. From December 1998 to April 2009, 89 patients were identified, most commonly with small/chronic lymphocytic lymphoma (n = 62) and follicular lymphoma (n = 24). Pretransplant anti-CD20 radioimmunotherapy (RIT) using standard yttrium-90-ibritumomab tiuxetan was administered to 18 patients (20%) who more frequently had chemoresistant disease (81% versus 39%, P = .003), disease bulk > 5 cm (61% versus 15%, P < .001), thrombocytopenia < 25k/μL (33% versus 7%, P = .002), and Hematopoietic Cell Transplant Comorbidity Index scores ≥ 3 (72% versus 37%, P = .006). After adjusting for these imbalances, RIT-treated patients had improved rates of progression-free survival (PFS) (hazard ratio [HR] = .4; 95% confidence interval [CI], .2 to .9, P = .02) and overall survival (OS) (HR = .3; 95% CI, .1 to .8, P = .008) compared with the non-RIT group. The 3-year adjusted estimates of PFS and OS for the RIT and non-RIT groups were 71% and 87% versus 44% and 59%, respectively. The use of RIT was the only factor independently associated with improved PFS and OS. Rates of nonrelapse mortality and graft-versus-host disease (GVHD) were similar between the 2 groups, although over 70% of patients developed clinically significant acute or chronic GVHD. In conclusion, despite relatively high rates of GVHD, patients with persistent iB-NHL can derive durable benefit from NMAT.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Ryan D
authors.initials: RD
authors.lastname: Cassaday
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Barry E
authors.initials: BE
authors.lastname: Storer
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Mohamed L
authors.initials: ML
authors.lastname: Sorror
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Brenda M
authors.initials: BM
authors.lastname: Sandmaier
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: Katherine A
authors.initials: KA
authors.lastname: Guthrie
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Department of Radiology, University of Washington, Seattle, Washington.
authors.forename: Joseph G
authors.initials: JG
authors.lastname: Rajendran
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: John M
authors.initials: JM
authors.lastname: Pagel
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Mary E
authors.initials: ME
authors.lastname: Flowers
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Damian J
authors.initials: DJ
authors.lastname: Green
authors.affiliation: Division of Blood & Marrow Transplantation, Stanford University, Stanford, California.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Rezvani
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Rainer F
authors.initials: RF
authors.lastname: Storb
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Press
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington. Electronic address: agopal@uw.edu.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018951:Antigens, CD20 / Q000276:immunology; D002908:Chronic Disease; D015331:Cohort Studies; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000401:mortality / Q000473:pathology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008224:Lymphoma, Follicular / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D008297:Male; D008875:Middle Aged; D019653:Myeloablative Agonists / Q000627:therapeutic use; D016499:Radioimmunotherapy / Q000379:methods; D016019:Survival Analysis; D019172:Transplantation Conditioning / Q000379:methods*; D014740:Vidarabine / Q000031:analogs & derivatives / Q000627:therapeutic use; D014916:Whole-Body Irradiation; D015021:Yttrium Radioisotopes / Q000627:therapeutic use
chemical_list: D000911:Antibodies, Monoclonal; D018951:Antigens, CD20; D019653:Myeloablative Agonists; D015021:Yttrium Radioisotopes; C422802:ibritumomab tiuxetan; D014740:Vidarabine; C024352:fludarabine
keywords: Indolent lymphoma; Nonmyeloablative transplantation; Radioimmunotherapy