Low-dose or intermediate-dose cyclophosphamide plus granulocyte colony-stimulating factor for progenitor cell mobilisation in patients with multiple myeloma

Abstract

Summary:Cyclophosphamide (CY) combined with granulocyte colony-stimulating factor (G-CSF) is commonly used to mobilise blood progenitor cells to support high-dose therapy in patients with multiple myeloma (MM). The optimal dose of CY in this setting is unknown. We have retrospectively analysed mobilisation efficiency and need for supportive care in 57 patients with newly diagnosed myeloma previously treated with VAD7local radiotherapy. The patients were mobilised either with low-dose CY (LD-CY, 1.2-2 g/m 2 ) (n ¼ 25) or intermediate-dose CY (ID-CY, 4 g/m 2 ) (n ¼ 32) plus G-CSF. Both regimens proved to be effective in the progenitor cell mobilisation. At least 2 Â 10 6 /kg CD34+ cells were collected from 88% and 84% of the patients with a single apheresis, respectively. Only one patient in the LD-CY group (4%) failed to mobilise vs none in the ID-CY group. Patients mobilised with LD-CY plus G-CSF had less toxicity: fewer hospital days during the mobilisation and apheresis procedures (5 vs 9 days, Po0.001), lower frequency of fever (20 vs 73%, Po0.001) and less need for supportive care including platelet transfusions (0 vs 24%, P ¼ 0.004) and days on parenteral antibiotics (0 vs 4 days, Po0.001). While these regimens seem to be equally effective in terms of progenitor cell mobilisation in newly diagnosed patients with MM, LD-CY+G-CSF is preferential because of more optimal resource utilisation and more favourable toxicity profile. Bone Marrow Transplantation (2003) 31, 347-351. doi:10.1038/sj.bmt.1703840 Keywords: cyclophosphamide; progenitor cell mobilisation; efficiency; toxicity; multiple myeloma Patients with multiple myeloma (MM) have a median survival of 3-4 years with conventional chemotherapy. In a randomised trial, high-dose therapy supported by stem cell rescue was superior over conventional chemotherapy in terms of complete remission rate, progression-free survival and overall survival. 1 The superiority of single or tandem autotransplants over conventional therapy has also been suggested in some controlled studies. 2,3 More than 95% of autotransplants for MM are now performed with the support of blood progenitor cells. 4 High-dose (7 g/m 2 ) cyclophosphamide (CY) alone or combined with a growth factor was initially used for mobilisation of progenitor cells in myeloma patients. [5][6][7] Goldschmidt et al 8 found that CY 7 g/m 2 plus G-CSF was superior to CY 4 g/m 2 plus G-CSF in this regard. However, high-dose CY is associated with significant toxicity. 7,9 Recently, Fitoussi et al 9 showed that intermediate-dose CY (ID-CY) (4 g/m 2 ) plus growth factor was equally effective as high-dose CY in mobilising progenitor cells in myeloma patients but was less toxic.Mobilisation with CY 4 g/m 2 plus G-CSF is, however, also associated with significant toxicity and need for supportive care. We hypothesised whether low-dose CY (LD-CY) (up to 2 g/m 2 ) could be as effective and, less toxic mobilisation regimen in patients with newly diagnosed MM. Therefore, a retrospective analysis in myeloma patients previously...

Improving stem cell mobilization strategies: future directions

“…Desikan et al 29 reported increased hospitalization and transfusions in patients who underwent mobilization with G-CSF plus high-dose CY than with G-CSF alone. In addition, Jantunen et al 41 and Fitoussi et al 40 reported more hospital days, more days of i.v. antibiotics and more blood transfusions in patients who underwent mobilization with higher doses of chemotherapy than in those who received lower doses.…”

“…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.…”

Mobilization policy in multiple myeloma: minimum target or law of redundancy? Two different approaches by the two sides of the Atlantic Ocean

“…15 CY has also been included in mobilization regimens with the aim to reduce graft contamination by clonal plasma cells (PCs); however, there are no data suggesting the usefulness of this drug, both in upgrading the quality of response before ASCT and in reducing PCs contamination of the harvest. Moreover, although circulating clonal PCs at diagnosis have been associated with early relapse after ASCT, 16 ex vivo purging had no impact on ASCT outcome in MM patients.…”

The role of plerixafor in optimizing peripheral blood stem cell mobilization for autologous stem cell transplantation

“…20 Chemomobilization is also associated with dose-dependent patient morbidity, greater risk of infection and febrile neutropenia, more hospital admissions and drug-specific toxicities, compared with G-CSF alone. 21 In addition, chemotherapy may damage the bone marrow microenvironment and impair engraftment with possible long-term adverse effects and compromised future mobilization attempts. 3,13 Thus, unless the antitumor activity is proven, chemotherapy to mobilize HSCs may not be cost-effective and may result in some risks for patients.…”