What are the considerations for mobilization with cyclophosphamide (CY), filgrastim (G-CSF), and prednisone for multiple sclerosis (MS) patients?

From the Guidelines

Mobilization with cyclophosphamide, filgrastim, and prednisone for multiple sclerosis patients should be approached with caution, considering the potential benefits and risks, and the recommended regimen typically includes cyclophosphamide at 2-4 g/m² administered intravenously, followed by filgrastim (G-CSF) at 5-10 μg/kg/day subcutaneously for 4-7 days, with oral prednisone at 1 mg/kg/day for 3-5 days to mitigate inflammatory reactions, as supported by the guidelines for the use of white blood cell growth factors 1.

Key Considerations

• Patient selection: typically those with aggressive, treatment-refractory MS
• Comprehensive pre-mobilization assessment: including cardiac function, infection screening, and baseline blood counts
• Close monitoring for potential complications: such as hemorrhagic cystitis, infections, and cardiac toxicity
• Mesna administration with cyclophosphamide to prevent bladder toxicity
• Adequate hydration (2-3 liters daily) is essential

Filgrastim Administration

• The recommended dose of filgrastim is 5-10 μg/kg/day subcutaneously for 4-7 days 1
• Filgrastim should be started 1-3 days after administration of myelotoxic chemotherapy, and continued until reaching ANC 2-3 x 10^9/L 1
• In the setting of PBPC mobilization, filgrastim should be started 4 days before the first leukapheresis procedure and continued until the last leukapheresis 1

Risks and Benefits

• The immunoablative effect of this regimen potentially interrupts the autoimmune process in MS by eliminating autoreactive immune cells and allowing reconstitution of a new immune repertoire
• Significant risks include infertility, secondary malignancies, and treatment-related mortality
• This approach is generally reserved for patients who have failed conventional therapies due to its significant risks

Guidelines and Recommendations

• The American Society of Clinical Oncology (ASCO) guidelines recommend the use of filgrastim at 5-10 μg/kg/day subcutaneously for 4-7 days in the setting of PBPC mobilization 1
• The guidelines also recommend the use of mesna to prevent bladder toxicity and adequate hydration to prevent complications 1

From the Research

Considerations for Mobilization with Cyclophosphamide, Filgrastim, and Prednisone for MS Patients

• The use of cyclophosphamide and prednisone for the treatment of multiple sclerosis (MS) has been studied in several trials, with some showing improvement in patients with chronic progressive MS 2, 3, 4.
• Filgrastim, a granulocyte-colony stimulating factor (G-CSF), is used to mobilize autologous hematopoietic stem cells into the circulation for autologous hematopoietic stem cell transplantation (aHSCT) in MS patients 5.
• The Ottawa Protocol for aHSCT in MS patients involves the use of cyclophosphamide and filgrastim for stem cell mobilization, followed by busulphan, cyclophosphamide, and rabbit anti-thymocyte globulin to destroy the patient's autoreactive immune system, and finally, infusion of the previously collected stem cells to reconstitute a naïve and self-tolerant immune system 5.
• Reduced cyclophosphamide dosing for mobilization has been shown to be feasible in patients with systemic sclerosis, with no significant difference in stem cell yield between high and reduced dose cyclophosphamide 6.
• Risk factors for poor mobilization may include low body weight, prior rituximab therapy, and cardiac involvement 6.
• Patient selection and a highly trained multidisciplinary team are crucial to minimize morbidity and mortality associated with aHSCT in MS patients 5.