[Show abstract][Hide abstract] ABSTRACT: Although TNFRSF17 (also designated as B-cell maturation antigen (BCMA)) is expressed on tumour cells in B-cell malignancies, it has not been found in serum. The present study found that BCMA concentrations were higher in the supernatants of cultured bone marrow mononuclear cells from multiple myeloma (MM) patients than in healthy subjects. Serum BCMA levels were measured in samples from MM patients (n = 209), monoclonal gammopathy of undetermined significance (MGUS) individuals (n = 23) and age-matched controls (n = 40). BCMA was detected in the serum of untreated MM patients (n = 50) and levels were higher than in MGUS patients (P = 0·0157) and healthy subjects (P < 0·0001). Serum BCMA levels were higher among patients with progressive disease (n = 80) compared to those with responsive disease (n = 79; P = 0·0038). Among all MM patients, overall survival was shorter among patients whose serum BCMA levels were above the median (P = 0·001). We also demonstrated that sera from mice with human MM xenografts contained human BCMA, and levels correlated with the change in tumour volume in response to melphalan or cyclophosphamide with bortezomib. These results suggest that serum BCMA levels may be a new biomarker for monitoring disease status and overall survival of MM patients.
British Journal of Haematology 07/2012; 158(6):727-38. DOI:10.1111/j.1365-2141.2012.09241.x · 4.71 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Preclinical and clinical studies have demonstrated synergy between bortezomib and pegylated liposomal doxorubicin (PLD) for relapsed/refractory (R/R) multiple myeloma (MM) patients compared to bortezomib as a single agent. This retrospective study evaluated the efficacy and safety of a more frequent low-dose schedule of PLD, bortezomib, and intravenous dexamethasone (DVD) for patients with R/R MM, many of whom were previously treated with bortezomib. Twenty-eight patients with R/R MM were treated, and 23 (83%) had been previously treated with ≥ 1 bortezomib-containing regimen. Treatment consisted of dexamethasone 40 mg intravenously, bortezomib 1.0 mg/m(2), and PLD 5.0 mg/m(2) on days 1, 4, 8, and 11 of a 28-day cycle for a maximum of eight cycles. Patients ranged from 33 to 81 years of age (median, 67) and had received 1-14 prior therapies (median, 5). At baseline, ten, nine, and nine patients were in stages I, II, and III, respectively, as defined by the International Staging System, and eight (29%) patients had elevated serum creatinine levels. The overall response rate was 61%, which included one (4%) complete response, three (11%) very good partial responses, eight (29%) partial responses, and five (18%) minimal responses. Of the 23 patients who had previously received bortezomib, 12 (52%) responded. The regimen was well tolerated with only six patients (21%) who showed worsening of their baseline peripheral neuropathy (PN). One patient discontinued this regimen due to an adverse event (grade II PN). DVD appears to represent a well-tolerated regimen with a high response rate for the treatment of R/R MM patients.
Annals of Hematology 02/2011; 90(2):193-200. DOI:10.1007/s00277-010-1052-8 · 2.63 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Pleiotrophin (PTN), a tightly regulated angiogenic and mitogenic heparin-binding protein, is markedly elevated in a variety of aggressive solid tumours. The role of PTN in haematological malignancies, however, has not been previously evaluated. This study demonstrated that PTN serum levels were elevated in multiple myeloma (MM) patients when compared with healthy subjects (P < 0.0001). Serum levels of this protein significantly increased during progression of disease, and decreased during response to anti-MM therapy (P < 0.001). These results suggest that serum PTN may be a new biomarker for monitoring the disease status and therapeutic response of MM patients.
British Journal of Haematology 07/2006; 133(5):526-9. DOI:10.1111/j.1365-2141.2006.06052.x · 4.71 Impact Factor