Thirty-seven patients with previously treated multiple myeloma (MM) underwent peripheral blood progenitor cell (PBPC) collection following high-dose cyclophosphamide and GM-CSF or sequential IL-3 and GM-CSF. Patients with an inadequate collection were considered for a second or third collection. 25 patients underwent subsequent autotransplant. The only variable predictive of CFU-GM yield was the extent of prior melphalan therapy. All repeat collections were unsuccessful and patients infused with an autograft obtained from multiple sets of collections had a high incidence of delayed engraftment. We conclude that melphalan should be avoided or PBPC collection performed early in the disease course in patients who are potential transplant candidates.
"Among nearly 1000 MM patients, <12 months of prior therapy, a platelet count >200 × 109/L, and lower age were predictive of successful mobilization.38 In other studies, prior use of melphalan,39 interferon,40 and radiation therapy,41 elevated serum lactate dehydrogenase,42 renal impairment, and lower albumin level43 were associated with reduced mobilization. Prolonged use of lenalidomide is consistently associated with failure to mobilize, particularly with G-CSF alone.44–47 "
[Show abstract][Hide abstract] ABSTRACT: Multiple myeloma and non-Hodgkin's lymphoma remain the most common indications for high-dose chemotherapy and autologous peripheral blood stem cell rescue. While a CD34+ cell dose of 1 × 10(6)/kg is considered the minimum required for engraftment, higher CD34+ doses correlate with improved outcome. Numerous studies, however, support targeting a minimum CD34+ cell dose of 2.0 × 10(6)/kg, and an "optimal" dose of 4 to 6 × 10(6)/kg for a single transplant. Unfortunately, up to 40% of patients fail to mobilize an optimal CD34+ cell dose using myeloid growth factors alone. Plerixafor is a novel reversible inhibitor of CXCR4 that significantly increases the mobilization and collection of higher numbers of hematopoietic progenitor cells. Two randomized multi-center clinical trials in patients with non-Hodgkin's lymphoma and multiple myeloma have demonstrated that the addition of plerixafor to granulocyte-colony stimulating factor increases the mobilization and yield of CD34+ cells in fewer apheresis days, which results in durable engraftment. This review summarizes the pharmacology and evidence for the clinical efficacy of plerixafor in mobilizing hematopoietic stem and progenitor cells, and discusses potential ways to utilize plerixafor in a cost-effective manner in patients with these diseases.
Stem Cells and Cloning: Advances and Applications 02/2011; 4(1):11-22. DOI:10.2147/SCCAA.S6713
"Commonly employed induction regimens in younger patients prior to SCT include thalidomide-Dex, lenalidomide-Dex, bortezomib-Dex, and bortezomib-thalidomide-Dex (VTD), none of which utilize the benefits of alkylating agents. The alkylating drugs melphalan and cyclophosphamide are active in MM but early use of melphalan has been shown to damage stem cells and often prevent successful stem cell harvest24, 25. Similar data concerning a diminished ability to collect stem cells are now emerging for lenalidomide (at least when G-CSF mobilization alone is attempted) which along with cost and a need for DVT prophylaxis may make combination therapies with this agent and with thalidomide less attractive26,27. "
[Show abstract][Hide abstract] ABSTRACT: We have studied a three-drug combination with cyclophosphamide, bortezomib and dexamethasone (CyBorD) on a 28-day cycle in the treatment of newly diagnosed multiple myeloma (MM) patients to assess response and toxicity. The primary endpoint of response was evaluated after four cycles. Thirty-three newly diagnosed, symptomatic patients with MM received bortezomib 1.3 mg/m(2) intravenously on days 1, 4, 8 and 11, cyclophosphamide 300 mg/m(2) orally on days 1, 8, 15 and 22 and dexamethasone 40 mg orally on days 1-4, 9-12 and 17-20 on a 28-day cycle for four cycles. Responses were rapid with a mean 80% decline in the sentinel monoclonal protein at the end of two cycles. The overall intent to treat response rate (>or= partial response) was 88%, with 61% of very good partial response or better (>or=VGPR) and 39% of complete/near complete response (CR/nCR). For the 28 patients who completed all four cycles of therapy, the CR/nCR rate was 46% and VGPR rate was 71%. All patients undergoing stem cell harvest had a successful collection. Twenty-three patients underwent stem cell transplantation (SCT) and are evaluable through day 100 with CR/nCR documented in 70% and >or=VGPR in 74%. In conclusion, CyBorD produces a rapid and profound response in patients with newly diagnosed MM with manageable toxicity.
Leukemia: official journal of the Leukemia Society of America, Leukemia Research Fund, U.K 02/2009; 23(7):1337-41. DOI:10.1038/leu.2009.26 · 10.43 Impact Factor
"HEAVILY PRETREATED PATIENTS HAVE A LOWER PBSC YIELD Many studies proved that prior radiotherapy and chemotherapy with alkylating agents (melphalan, carmustine) adversely affect mobilization (Watts et al, 1997; Clark & Brammer, 1998; Ketterer et al, 1998; Marit et al, 1998; Russell et al, 1998; Perea et al, 2001). Melphalan is particularly stem-cell toxic and even a low dose given orally before mobilization results in reduced CD34 + cell mobilization (Tricot et al, 1995; Prince et al, 1996; Demirer et al, 1997; Goldschmidt et al, 1997; Boccadoro et al, 2002). Fludarabine pretreatment was proven in several studies to be associated with poor PBSC mobilization (e.g. "
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