Background: The origin of classical Hodgkin's Disease (HD) remains uncertain, however, neoplastic transformation of B lymphocytes appears to yield diagnostic Reed-Sternberg cells. Bone marrow ...involvement is unusual in HD and malignant cells rarely circulate in the peripheral blood. Autologous hematopoietic stem cell transplantation (HSCT) using peripheral blood stem cells (PBSCs) for relapsed or refractory HD, therefore, is rarely hampered by concerns of reintroducing malignant cells. In this study, we investigated the clinical impact of clonal B cells detected in PBSC collections in patients with HD. Methods: Patients undergoing autologous HSCT for refractory or relapsed classical Hodgkin's Disease between April 2000 and January 2006 were included. Qualitative semi-nested PCR was performed on mononuclear cells from PBSCs to determine the presence of clonal IgH CDR3 gene rearrangements. Factors predictive of relapse and overall survival (OS) were assessed using log-rank analysis. Results: Amongst 39 patients with HD undergoing HSCT, 12 (31%) were PCR-positive for clonal IgH rearrangements in at least one PBSC collection. Progressive disease occurred in 5 of 12 patients in the PCR-positive group at a median of 138 + or - 101days. In the PCR-negative group (n = 27), 7 patients developed progressive disease at a median of 250 + or - 128 days following transplant. Median follow-up was 3.2 yrs (0.1 -7.9 yrs). OS was significantly better in the PCR-negative group (p = 0.040) with estimated 5-yr survival of 81% compared with 39% in the PCR-positive group. The hazard ratio for mortality was 3.1 (95% CI 1.02-14.6). A trend towards better progression-free survival was observed in PCR-negative patients (p = 0.12) with estimated 5 yr PFS of 71% compared with 41% for PCR-positive patients. In univariate analysis, the presence of clonal IgH rearrangements was the only factor associated with reduced OS in our population. Conclusions: Detecting clonal B-lymphocytes in the PBSC collections of patients with classical HD identifies patients at increased risk of disease recurrence and death following autologous HSCT. Whether monoclonal B-cells represent malignant clones that were reinfused and caused subsequent tumour growth, clonal responses to etiologic pathogenic antigens, or immune dysregulation at risk for the emergence of recurrent disease remains uncertain. Innovative strategies to improve patient outcomes will rely on greater insight regarding the etiology of the monoclonal B cells.
This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation ...(ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) microg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to > or = 20 x 10(9)/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred.
Two different complex translocations from newly diagnosed cases of Philadelphia chromosome-positive chronic myelogenous leukemia (CML) were characterized by G-banding and fluorescence in situ ...hybridization (FISH) analysis. In one case, a unique balanced t(9;22;9;11)(q34;q11;p22;q23) was identified by G-banding, and confirmed by FISH using MBCR/ABL and painting probes. In the second case, an apparently balanced t(19;22) was identified by G-banding analysis. FISH using MBCR/ABL probe detected the fusion gene on the derivative chromosome 22, indicating the involvement of chromosome 9. Further FISH analysis with selected painting probes showed that the t(19;22) was a result of a complex translocation involving chromosomes 9, 19, 21, and 22.
Although many hematologic malignancies are more common in older patients, autologous blood and marrow transplantation (ABMT) has traditionally been restricted to patients younger than 60 years ...because of concerns that older patients would be either unable to provide a graft or unable to tolerate the therapy. From June 1995 to May 1998, 30 patients > or = 60 years underwent ABMT at our institution for low-grade lymphoma (4 patients), relapsed intermediate-grade lymphoma (17 patients), or multiple myeloma (9 patients). The median patient age was 62.5 years (range 60-73). Pretransplantation conditioning regimens were CBV (cyclophosphamide, BCNU carmustine, etoposide) or BEAM (carmustine, etoposide, cytarabine, melphalan) for intermediate-grade lymphoma patients and melphalan 140 mg/m2 + etoposide 60 mg/kg + total body irradiation 500 cGy for the others. The rescue product was bone marrow (BM; 4 patients), peripheral blood stem cells (PBSC; 23 patients), or BM+PBSC (3 patients). The median number of CD34+ cells/kg infused was 3.60 x 10(6) (range 0.53-31.0), by the International Society for Hematotherapy and Graft Engineering method. The treatment-related mortality at day 100 and at 6 months was 10% and 16.7%, respectively. The median days to neutrophil > 0.5 x 10(9)/L was 11 (range 9-25) and platelets > 20 x 10(9)/L was 16 (range 6-70). Three patients died of infection (days 26, 27, and 38), and 1 died of an intracranial hemorrhage related to persistent thrombocytopenia (day 130). Bearman regimen-related toxicity was moderate, with most toxicities < or = grade 2. Seven patients developed significant gut toxicity: 4 patients with Clostridium difficile colitis and 3 patients with neutropenic enterocolitis. Depressive symptoms and signs were noted in 4 patients. Three male patients developed decreased gonadal function after transplantation. These transplantations accounted for 997 patient days, of which 266 days (27%) were in the outpatient BMT program--a smaller percentage than in patients < 60 years (56%, P = .002). Twenty patients are alive 153 to > or = 1224 days after transplantation. ABMT in patients > or = 60 years of age is feasible. Further studies addressing supportive care particular to older patients and comparisons of ABMT with traditional approaches to multiple myeloma and relapsed non-Hodgkin's lymphoma in older patients are needed. Further work to identify elderly patients most likely to benefit from this approach is also required.
Biol Blood Marrow Transplant 2000;6(2A):204-10.
PDF
