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Takach S.,University of Ottawa | Yang L.,Stem Cell Processing Laboratory | Ho J.,University of Ottawa | Sabri E.,Ottawa Health Research Institute | And 13 more authors.
Bone Marrow Transplantation | Year: 2010

Autologous peripheral blood stem cell transplantation (PBSCT) for Hodgkin lymphoma (HL) is curative for many patients with r lapsed 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, P0.041). 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, P0.12), 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. © 2010 Macmillan Publishers Limited.


Wu L.,Ottawa Hospital Research Program | Wu L.,University of Ottawa | Al-Hejazi A.,University of Ottawa | Al-Hejazi A.,Ottawa Hospital Research Institute | And 8 more authors.
Cytotherapy | Year: 2012

Background aims. Delayed neutrophil recovery following autologous hematopoietic stem cell transplantation (aHSCT) increases transplant-related morbidity. Apoptosis induced by cryopreservation and thawing of hematopoietic progenitor cells collected by apheresis (HPC-A) was investigated in this nested case-control study as a factor associated with delayed neutrophil recovery following aHSCT. Methods. Among patients with lymphoma who underwent aHSCT between 2000 and 2007 (n = 326), 13 cases of primary delayed neutrophil recovery and 22 age- and sex-matched controls were identified. Apoptosis and viability were measured using multiparameter flow cytometry, and colony-forming capacity was determined using semi-solid methylcellulose assays. Results. HPC-A grafts from cases and controls had similar percentages of viable mononuclear cells (MNC) and CD34+progenitor cells, as determined by standard 7AAD dye exclusion methods measured before and after cryopreservation. Patients with delayed neutrophil recovery received increased numbers of apoptotic MNC (P = 0.02) but similar numbers of apoptotic CD34+ cells per kilogram measured after thawing. Apoptosis was more pronounced in MNC compared with CD34+ cells after thawing, and apoptosis was negligible in freshly collected HPC-A products. Patients with delayed neutrophil recovery had fewer total colony-forming unites (CFU) and CFU-granulocytemacrophages (GM) per 105 viable post-thaw MNC compared with controls (P < 0.05). Conclusions. Increased numbers of apoptotic MNC in thawed HPC-A products are associated with delayed neutrophil recovery after aHSCT. Studies that address factors contributing to increased apoptosis are needed, and measuring apoptosis in thawed HPC-A may have a role in the assessment of graft adequacy. © 2012 Informa Healthcare.

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