Randomized Trial of G-CSF Alone Versus Intermediate-dose Ara-C Plus G-CSF Mobilization in Multiple Myeloma Patients.

Autologous hematopoietic stem cell transplantation (autoHSCT) is a standard treatment of eligible patients suffering from multiple myeloma (MM). Tandem autoHSCT allows to further improve results of the therapy. Nowadays, 99% of the procedures are performed using peripheral blood as a source of stem cells. Hence, the crucial point is to harvest adequate number of stem cells allowing hematopoietic recovery. The number of 5 × 10^6 CD34+ cells/kg is considered the optimal level, as far as double autoHSCT is concerned. There are two main mobilization strategies being used: based on G-CSF alone or in combination with chemotherapy (cyclophosphamide (CY) at dose range 1.5-7 g/m2 is mainly used in MM setting). However, a proportion of patients (5-40%) fail to collect the minimum number of cells required. Novel agents, like plerixafor, CXCR4 inhibitor, may enable effective CD34+ cell harvest in "poor mobilizers". Nevertheless, the optimal first-line and cost-effective protocol for mobilization of hematopoietic stem cells has not been determined so far.

Randomized trials comparing chemomobilization with use of CY + G-CSF to G-CSF alone, which had been conducted so far, did not demonstrate clear advantage of addition of CY to growth factor. Intermediate-dose cytosine arabinoside (AraC), 1.6 g/m2 plus filgrastim, has been shown to produce very high efficacy as a first or second-line mobilization regimen in patients with lymphoid malignancies, including MM. In a retrospective comparison, this strategy was significantly more effective than CY + filgrastim. This suggest that the type of chemotherapy agent added to G-CSF may play role in mobilization efficacy and that the combination of AraC and G-CSF may be more effective than G-CSF used alone. The goal of current study is to verify this hypothesis in randomized controlled trial.

Inclusion criteria

• Multiple myeloma patients considered eligible for tandem autologous stm cell transplantation procedure.
• Must have received at least one line of therapy including six or more cycles containing components like thalidomide, bortezomib, lenalidomide or melphalan.
• Must have achieved a partial remission (PR) or better response as assessed by International Myeloma Working Group guidelines.
• Must be 18-65 years of age.
• Must have World Health Organization performance status 0-1.
• Time form discontinuation of administration of any chemotherapy agent must be at least four weeks and immunomodulatory drug at least seven days.
• Hemoglobin level > 8 g/dl, Absolute neutrophil count (ANC) > 1.5 x 109/L, Platelet count >100 x 109/L.
• Serum creatinine < 1.5 x upper limit of normal (ULN), serum bilirubin < 1.5 ULN, serum aspartate transaminase (AST/SGOT) < 2.5 x ULN, serum alanine transaminase (ALT/SGPT) < 2.5 x ULN.
• Negative human immunodeficiency virus (HIV) infection test.
• Negative pregnancy test.
• Must understand and voluntarily sign informed consent form.

Exclusion criteria

• Failure of prior, first-line mobilization regimen.
• Bone marrow plasma cell infiltration of above 20%.
• Administration of growth-factor other than G-CSF within 4 weeks before starting study treatment.
• Administration of G-CSF within 14 days before starting study treatment.
• Ongoing or active infection.
• Coexisting neoplasm, other than multiple myeloma.
• Pregnant or lactating females.
• Patients treated with use of autologous or allogenic stem cell transplantation in the past.
• Positive human immunodeficiency virus (HIV) infection test.