Oscar F Ballester

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.

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.

Randomized clinical trials for hematopoietic stem cell transplantation: lessons to be learned from the European experience

We evaluated the number and characteristics of randomized controlled trials (RCTs) addressing hematopoietic stem cell transplantation (HSCT) for patients with hematological malignancies, comparing the productivity of US and Europe. A MEDLINE search was conducted to identify all published RCTs for the management of adult patients with hematological malignancies from January 1992 to December 2003. Eighty-three of the 306 trials identified included HSCT as one of the treatment arms. The US produced 25, Europe 54, and all other countries four. Four European countries, France, Italy, Germany, and UK (FIGU), produced 32 out of the 54 European studies. Significant differences emerged when focus of the study and accrual numbers were analyzed. Trials comparing HSCT to standard dose therapy represented 34.9% of the 83 trials and 59.4% of FIGU trials, but only 4% of US studies (P=0.001). US trials accrued a mean of 110.2 patients per study, as compared to 222.6 in FIGU studies (P=0.006) and 205.3 when all non-US countries are considered (P=0.01). Our conclusions are that US transplant RCT have focused on issues other than the comparison of HSCT to standard therapies. There is serious paucity of US trials defining the role of HSCT in the management of hematological malignancies.