Peripheral blood progenitor cell collections in multiple myeloma: Predictors and management of inadequate collections

University of Toronto, Toronto, Ontario, Canada
British Journal of Haematology (Impact Factor: 4.96). 10/2003; 93(1):142 - 145. DOI: 10.1046/j.1365-2141.1996.448987.x

ABSTRACT 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.

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    • "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. "
    British Journal of Haematology 08/2003; 122(3):360-375. DOI:10.1046/j.1365-2141.2003.04483.x · 4.96 Impact Factor
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    • "In patients, biological responses to G-CSF vary widely. These differences are partly explained by prior chemotherapy (Haas et al, 1994; Breems et al, 1996; Prince et al, 1996), but in patients who have undergone apparently equally cytotoxic treatments and even in healthy volunteers or normal mice, wide variations in mobilization responses have also been noted (Roberts et al, 1995b,1997; Hasegawa et al 2000). Conceivably, such variation may be caused by different clearance rates for pharmacological substances in general that vary from individual to individual and, in fact, are the focus of many current pharmacogenomic approaches (Housman & Ledley, 1998). "
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    ABSTRACT: We have compared the efficacy of a single injection of SD/01, a newly engineered, pegylated form of recombinant human granulocyte colony stimulating factor (rhG-CSF), with a single injection of glycosylated rhG-CSF (Filgrastim). SD/01 was administered to regular and recombinant inbred strains of mice (AKR, C57L/J, DBA/2, C57BL/6, AKXL) known to have widely distinct marrow-cell pool sizes and proliferation kinetics. A single injection of G-CSF was unable to mobilize granulocyte–macrophage colony-forming units (CFU-GM). In sharp contrast, a single dose of SD/01 resulted in massive mobilization of progenitors and stem cells. Although all mice strains showed qualitatively similar mobilization responses, large interstrain differences remained. C57L and C57BL/6 mice mobilized relatively poorly, whereas AKR and DBA/2 mice showed threefold to tenfold superior responses. In order to explain these different phenotypes, we studied the effects of SD/01 in nine AKXL recombinant inbred strains, derived from well-responding AKR and poorly responding C57L parental strains. The best predictor for SD/01 responsiveness in these strains was marrow cellularity prior to mobilization. Comparison of the AKXL strain distribution pattern for marrow cellularity with loci previously mapped in these strains showed complete concordance with Aat, a serine protease inhibitor mapping to chromosome 12.
    British Journal of Haematology 08/2000; 110(3):638 - 646. DOI:10.1046/j.1365-2141.2000.02252.x · 4.96 Impact Factor
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    ABSTRACT: Multiple myeloma (MM) has an incidence of approximately four per 100,000 per year. Ninety-nine percent of patients with MM have a monoclonal (M-) protein in the serum or urine during the course of their disease. MM must be differentiated from smoldering multiple myeloma (SMM), which has an M-protein value of more than 30 g/l and more than 10% plasma cells in the bone marrow, but no other features of MM. The plasma cell labeling index (PCLI) and the presence of circulating plasma cells in the peripheral blood help to differentiate monoclonal gammopathy of undetermined significance and SMM from MM. The current median duration of survival with chemotherapy is about three years. Patients with low PCLI and low &bgr; subset2-microglobulin values have a median duration of survival of approximately six years. Melphalan and prednisone produce an objective response in 50% to 60% of patients. Combinations of chemotherapy produce a higher response rate, but the survival rate is not different. Allogeneic bone marrow transplantation is associated with a mortality rate of 25% within six months and an actuarial survival rate of 28% at seven years. Autologous peripheral stem cell transplantation is applicable to more patients and is reported to produce a higher response rate and longer survival than chemotherapy, but most patients will eventually have relapse.
    The Oncologist 02/1996; 1(5):315-323. · 4.54 Impact Factor
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