Hematopoietic stem cell mobilization with intravenous melphalan and G-CSF in patients with chemoresponsive multiple myeloma: report of a phase II trial

Abstract

Summary:Multiple myeloma (MM) is an incurable hematologic malignancy for which autologous hematopoietic stem cell transplantation (HCT) is a standard therapy. The optimal method of stem cell mobilization is not defined. We evaluated intravenous melphalan (60 mg/m 2 ), the most effective agent for MM, and G-CSF (10 lg/kg/day) for mobilization. End points were safety, adequacy of CD34 þ collections, MM response, and contamination of stem cell components (SCC). In total, 32 patients were mobilized. There were no deaths or significant bleeding episodes; 14 patients (44%) required hospitalization for neutropenic fever. Median days of grade 3 or 4 neutropenia or thrombocytopenia were 7 (2-20) and 8 (3-17). Median mobilization days, CD34 þ cells/kg and total leukaphereses were 16 (12-30), 12.1 million (2.6-52.8), and 2 (1-5) respectively. Four patients (12.5 %) failed to achieve the target of 4 million CD34 þ cells/kg in five leukaphereses. Reduction in myeloma was seen in 11 patients (34%) with 3 (9%) achieving complete response; 15 (47%) maintained prior responses. Estimated MM contamination per SCC (N ¼ 48) was 0.0009% (range 0-0.1) and 0.21 Â 10 4 cells per kg (range 0-41.2). Increased contamination was associated with increased patient age. This strategy for mobilization is feasible, frequently requires hospitalization and transfusion, and controls disease in most patients.

Improving stem cell mobilization strategies: future directions

“…Compared with mobilization regimens using G-CSF alone, chemomobilization is associated with increased morbidity, greater risk of infection, more hospital admissions, transfusions, antibiotic therapy and considerably greater cost overall. 29,[39][40][41][42] Although treatment-related mortality is rare, significant morbidity related to neutropenia that can often require hospitalization has been described, and many reports point to greater resource utilization with chemomobilization than with cytokine-alone mobilization. 29,37,39 Koc et al 39 found that although treatment with CY plus G-CSF resulted in greater stem cell yield than did treatment with GM-CSF plus G-CSF, it also caused greater morbidity.…”

“…29,39 As a result, this mobilization strategy requires increased resource use, hospitalizations, transfusions and the use of antibiotic therapy. 29,[39][40][41][42] Furthermore, variation among individual responses to chemomobilization can result in irregular collection schedules that can increase resource utilization and potentially delay transplantation. 43,44 The utility of all current mobilization regimens is limited by their high failure rates, which are estimated to be from 5 to 30%, regardless of the approach.…”

Results of a phase I/II trial adding carmustine (300 mg/m2) to melphalan (200 mg/m2) in multiple myeloma patients undergoing autologous stem cell transplantation

“…PBSC were infused on day 0 and patients received standard supportive-care measures as previously described. [20][21][22] Toxicities were scored using National Cancer Institute clinical toxicity criteria. 23 No maintenance therapy was employed.…”

“…22 Two patients were mobilized with G-CSF alone. Responses after initial therapy and mobilization are shown in Table 2 by DurieSalmon stage; responses by ISS stage were similar except that none of the ISS stage three patients achieved CR or nCR.…”

Stem Cell Mobılızatıon in Multıple Myeloma

“…60mg/m 2 plus G-CSF 10 μg/kg/day was successful in mobilizing PBPC from myeloma patients. However, toxicity was notable and duration of mobilization was longer compared with CY 3 g/m 2 (16.5 days vs 10 days) (Gupta et al, 2005). Melphalan is a highly effective anti-myeloma drug but due to its stem cell toxicity, it is neither used for PBSC mobilization, nor recommended as an initial therapy for patients elligible for AHCT.…”