P. Stiff

Purging of Autologous Peripheral-Blood Stem Cells Using CD34 Selection Does Not Improve Overall or Progression-Free Survival After High-Dose Chemotherapy for Multiple Myeloma: Results of a Multicenter Randomized Controlled Trial

PURPOSEnAlthough high-dose chemotherapy supported by autologous peripheral-blood progenitor-cell (PBPC) transplantation improves response rates and survival for patients with multiple myeloma, all patients eventually develop progressive disease after transplantation. It has been hypothesized that depletion of malignant plasma cells from autografts may improve outcome by reducing infused cells contributing to relapse.nnnPATIENTS AND METHODSnA randomized phase III study using the CEPRATE SC System (Cellpro, Bothell, WA) to enrich CD34(+) autograft cells and passively purge malignant plasma cells was completed in 190 myeloma patients randomized to receive an autograft of CD34-selected or unselected PBPCs.nnnRESULTSnAfter CD34 selection, tumor burden was reduced by 1.6 to 6.0 logs (median, 3.1), with 54% of CD34-enriched products having no detectable tumor. Median time to count recovery, number of transfusions, transplantation-related mortality, and days in hospital were equivalent between the two transplantation arms. With a median follow-up of 37 months, 33 patients (36%) in the selected and 34 patients (35%) in the unselected arm had died (P =.784). Median overall survival in the selected arm was reached at 50 months and is not reached at this time in the unselected arm (P =.78). Median disease-free survival was 100 versus 104 weeks (P =.82), with 67% of patients in the selected arm and 66% of patients in the unselected arm relapsing.nnnCONCLUSIONnThis phase III trial demonstrates that although CD34 selection significantly reduces myeloma cell contamination in PBPC collections, no improvement in disease-free or overall survival was achieved.

A randomized placebo-controlled trial of lisofylline in HLA-identical, sibling-donor, allogeneic bone marrow transplant recipients

the purpose of the study was to evaluate the effect of lisofylline (lsf) on engraftment, regimen-related toxicities (rrt), and mortality in patients undergoing allogeneic bone marrow transplantation (bmt). we performed a multicenter, randomized placebo-controlled trial in 60 patients with hematologic malignancies receiving bmt from hla-identical sibling donors. patients were randomized to receive either placebo, 2u2009mg/kg lsf or 3u2009mg/kg lsf every 6u2009h, beginning before conditioning and continuing to day 21 or hospital discharge. treatment groups were balanced with respect to conditioning regimen and disease stage. however, significantly more patients in the 2u2009mg/kg lsf group were at high risk for rrt due to performance status ⩾1, age ⩾40 years, and prior exposure to cmv. nausea and vomiting were the only adverse events observed in a higher proportion of lsf-treated patients that led to study withdrawal in six of 42 patients (14%). the times to neutrophil recovery to ⩾500/μl and platelet recovery (>20u2009000/μl) were not improved by LSF treatment. Nevertheless, no patient who received treatment with 3u2009mg/kg LSF developed a documented infection between day 0 and 35 or had a serious or fatal infection between day 0 and 100 (Pu2009=u20090.003 vs placebo for both). The day-100 survival rate was also significantly improved in the 3u2009mg/kg LSF group (89%), compared with either the 2u2009mg/kg LSF (48%) or placebo (61%) groups (log-rank test, 3u2009mg/kg LSF vs placebo, Pu2009=u20090.026). We conclude that treatment with LSF 3u2009mg/kg reduced the incidence of infections and improved 100-day survival in patients receiving related-donor allogeneic bone marrow transplantation. Bone Marrow Transplantation (2000) 25, 283–291.

Collection of peripheral blood progenitor cells (PBPC) based on a rising WBC and platelet count significantly increases the number of CD34 + cells

The kinetics of mobilization and optimal timing of peripheral blood progenitor cell (PBPC) collection were evaluated in 190 patients with multiple myeloma undergoing stem cell harvest after mobilization with cyclophosphamide, prednisone and G-CSF. There was a strong correlation between the WBC count and the number of CD34+ cells circulating in peripheral blood (ru2009=u20090.875). Initiating leukapheresis based on rising WBC and platelet counts rather than on a fixed day increased the mean number of CD34+cells 115% (9.7 to 20.9 × 106 CD34+ cells/kg; Pu2009=u20090.010) for the total of all leukaphereses and 59% for the total of all CD34-selected products (5.1 to 8.1 × 106 CD34+ cells/kg; Pu2009=u20090.011). Although the yield and purity of the CD34-selected product were not significantly affected (Pu2009⩾u20090.071), the percentage of patients with concentrations of CD34+ cells in the initial leukapheresis of >1% increased from 47% to 70% (Pu2009=u20090.004). The mean purity of the selected product was related to the starting percentage: 48.9% if <1% and 81.5% if ⩾1% (Pu2009<u20090.001). collection of stem cells based on rising wbc and platelet counts significantly increased the number of cd34+ cells in leukaphereses and CD34-selected products in comparison with collection on a fixed day.

Successful autologous peripheral blood stem cell transplantation in transformed follicular lymphoma previously treated with radioimmunotherapy (iodine 131I tositumomab)

While the use of radioimmunotherapy for lymphoma increases, the feasibility and efficacy of autologous stem cell transplant for subsequent relapse remains unknown. We report a 48-year-old male with transformed follicular mixed non-Hodgkins lymphoma. After treatment with three different combination chemotherapy regimens, at relapse he received radioimmunotherapy with iodineu2002131I tositumomab (anti-CD20), with very good response. At later relapse, a second course ofu2002131I tositumomab was given unsuccessfully. He underwent peripheral blood stem cell harvest, chemoradiotherapy conditioning and autologous transplantation with prompt engraftment and without significant complications. He remains in complete remission with normal blood counts 25 months post autograft.Bone Marrow Transplantation (2002) 29, 523–525. doi:10.1038/sj.bmt.1703398

Human herpesvirus 8 (KSHV) contamination of peripheral blood and autograft products from multiple myeloma patients

Human herpesvirus 8 (HHV-8), also known as Kaposis sarcoma-associated herpesvirus (KSHV), has recently been identified within the bone marrow dendritic cells of multiple myeloma (MM) patients. This virus contains homologues to human cytokines such as IL-6 that could potentially stimulate myeloma cell growth and contribute to disease pathogenesis. Since mobilization chemotherapy may increase circulating dendritic cell numbers, we searched for HHV-8 in peripheral blood mononuclear cells (PBMCs) before and after mobilization chemotherapy given to MM patients. Furthermore, we determined if autograft purging using the CEPRATE SC device would reduce the percentage of HHV-8 infected stem cell products. Only two of the 39 PBMC samples collected prior to mobilization chemotherapy contained PCR detectable virus, yet nine of 37 PBMCs collected on the first day of leukapheresis had detectable HHV-8 (Pu2009=u20090.016). HHV-8 was more frequently identified in autograft products before vs after Ceprate SC selection (40% vs 15%, Pu2009=u20090.016). Although the role HHV-8 plays in myeloma pathogenesis remains unclear, these results imply that mobilization chemotherapy increases the numbers of circulating HHV-8-infected dendritic cells within the peripheral blood. In addition, CD34 selection of autograft products in MM patients may reduce the reintroduction of virally infected cells following high-dose chemotherapy. Bone Marrow Transplantation (2000) 25, 153–160.