title: Monoclonal B cells detected in autologous PBSC grafts from patients with classical Hodgkin lymphoma: impact on relapse and survival following transplantation.
abstract: Autologous peripheral blood stem cell transplantation (PBSCT) for Hodgkin lymphoma (HL) is curative for many patients with relapsed or refractory disease. Relapsing disease, however, remains a major problem. Neoplastic transformation of B-lymphocytes probably underlies the development of classical HL. Whether clonal B cells are critical for disease evolution and response to therapy in HL remains uncertain. We investigated the impact of clonal B cells detected in peripheral blood stem cell (PBSC) collections on the outcome of patients with HL undergoing transplant. Qualitative semi-nested PCR was carried out on genomic DNA from mononuclear cells from PBSCs to determine the presence of clonal immunoglobulin heavy chain (IgH) complementary-determining region 3 (CDR3) gene rearrangements. Clinical factors were assessed for their association with relapse, overall survival (OS) and progression-free survival (PFS). Among 39 patients undergoing PBSCT, 12 grafts (31%) were PCR positive for clonal IgH rearrangements. OS was better in the PCR-negative group (logrank test, P=0.041). The OS at 5 years was 81% in PCR-negative versus 39% in PCR-positive patients; hazard ratio was 3.23 (95% confidence interval: 0.98-10.63). There was a trend towards better PFS (logrank test, P=0.12), estimated as 71% at 5 years in PCR-negative versus 41% in PCR-positive patients. Clonal B-lymphocytes in PBSC collections of patients with HL identify patients at risk of poor outcome. Larger series are needed to confirm our observations. Insight regarding the role of monoclonal B cells may lead to improved therapies.
authors.affiliation: Division of Hematology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: S
authors.initials: S
authors.lastname: Takach
authors.forename: L
authors.initials: L
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Ho
authors.forename: E
authors.initials: E
authors.lastname: Sabri
authors.forename: L
authors.initials: L
authors.lastname: Martin
authors.forename: M
authors.initials: M
authors.lastname: Halpenny
authors.forename: H
authors.initials: H
authors.lastname: Atkins
authors.forename: M
authors.initials: M
authors.lastname: Sabloff
authors.forename: S A
authors.initials: SA
authors.lastname: McDiarmid
authors.forename: L B
authors.initials: LB
authors.lastname: Huebsch
authors.forename: I
authors.initials: I
authors.lastname: Bence-Bruckler
authors.forename: A
authors.initials: A
authors.lastname: Giulivi
authors.forename: D S
authors.initials: DS
authors.lastname: Allan
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002999:Clone Cells / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D005260:Female; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics; D006689:Hodgkin Disease / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D036102:Peripheral Blood Stem Cell Transplantation; D012008:Recurrence; D016019:Survival Analysis; D014182:Transplantation, Autologous
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region