Outpatient Autotransplants for Persons with Multiple Sclerosis

Background. High-dose cyclophosphamide and a haematopoietic cell autotransplant is an effective therapy of multiple sclerosis (MS). This is often done in an inpatient setting using frozen blood cells either blood or bone marrow cells.

Objective. Determine if this procedure can be safely and effectively simplified.

Methods. We developed an autotransplant protocol actionable in an outpatient setting using refrigerated blood cells collected after giving cyclophosphamide, 50 mg/kg/d x 2 d and filgrastim, 10 μg/kg/d. A 2nd identical dose of cyclophosphamide was given 9 d later followed by infusion of blood cells stored at 4º C for 1-4 d. Subjects received rituximab after bone marrow recovery, 100 mg, every 2 mo for 1 y or rituximab, 1 g in 1 dose based on the subject's residence country (Figure 1). The co-primary outcomes were rate of bone marrow recovery and therapy-related mortality (TRM). Secondary outcomes included MS relapse-free survival (MS-RFS) and survival. Cumulative dose of cyclophosphamide was 200 mg/Kg

Results. We treated 426 consecutive subjects. Median age was 47 y (range, 21-68 y). 145 (34%) were male. 84 (20%) had primary progressive MS, 173 (41%), relapsing remitting MS and 169 (39%), secondary progressive MS. Median blood cell storage time was 1 d (range, 1-4 d). Median intervals to granulocytes >0.5 x10E+9/L was 8 d (range, 2-12) and to platelets >20 x10E+/L, 8 days (range, 1-12). 412 subjects (96%) were treated as outpatients. Median follow-up is 6 mo (range, 3-30 mo). There was 1 death from TRM. In 304 subjects (71%) with data from neurologic evaluations ≥3 posttransplant median MS RFS is 27 mo (95% confidence interval [CI], 24, 30 mo). Estimated 1 y MS RFS is 85% (80, 90%) with no significant difference between the 3 MS variants. Median survival will exceed 30 mo. An unusual aspect of our study was giving two 2-d blocks of cyclophosphamide 8 days apart rather than 4 d continuously done for 3 reasons: (1) use of cyclophosphamide to mobilize blood cells for the autograft; (2) facilitate using a refrigerated rather than frozen autograft; and (3) decrease toxicity. Our finding of rapid bone marrow recovery using refrigerated grafts is like our experience in persons with plasma cell myeloma and lymphomas receiving high-dose therapy and an autotransplant.

Conclusion. The strategy we developed was actionable in an outpatient setting with rapid recovery of granulocytes and platelets and only 1 early death. Estimated MS-RFS and survival were good. MS variant type did not correlate with MS-RFS or survival.

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