Monoclonal B cells detected in autologous PBSC grafts from patients with classical Hodgkin lymphoma: impact on relapse and survival following transplantation.
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.
Takach
S
S
Division of Hematology, Faculty of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Yang
L
L
Ho
J
J
Sabri
E
E
Martin
L
L
Halpenny
M
M
Atkins
H
H
Sabloff
M
M
McDiarmid
S A
SA
Huebsch
L B
LB
Bence-Bruckler
I
I
Giulivi
A
A
Allan
D S
DS
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
D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region