Autologous Peripheral Blood Stem Cell Transplantation for POEMS Syndrome

Background: POEMS syndrome is a rare plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes associated with multiorgan involvement and monoclonal plasma cell dyscrasia. The pathogenesis of POEMS syndrome is not well understood, but overproduction of vascular endothelial growth factor (VEGF) probably secreted by plasma cells is considered to be responsible. High-dose melphalan (Mel) with autologous stem cell transplantation (ASCT) has been recently considered to be an effective strategy, but its treatment related mortality is considered to be high. Here, we report the results of ASCT for POEMS syndrome.

Methods: Between January 2004 and June 2008, twelve patients with POEMS syndrome underwent ASCT at Chiba University Hospital and were retrospectively analyzed in the study. Conditioning treatment for ASCT was Mel 200 mg/m², while Mel dose was reduced to 140 mg/m² if a patient had poor performance status (PS).

Results: Ten out of twelve patients were male and their median age was 48 years (range 34–61). Median time from first symptom and diagnosis to ASCT was 21 and 10 months, respectively. Seven patients received induction therapy before preparation of ASCT, thalidomide-dexamethasone in four, intravenous Mel in two, and bevacizumab followed by thalidomide in one patient. Peripheral blood stem cells were mobilized by cyclophosphamide/G-CSF in nine cases and G-CSF alone in three. Median serum VEGF level before ASCT was 2835 pg/ml (range; 334–5300). Median number of infused CD34+ cells was 2.3 × 10⁶/kg (range; 2.1–4.3 × 10⁶/kg). Eleven patients were conditioned with Mel 200 mg/m², while one patient with poor PS (Karnofsky score 30%) received Mel 140 mg/m². Median time to neutrophil recovery (>500/mm³) was 13 days post transplant (range 9–17 days). Only two patients developed respiratory distress during neutrophil engraftment period. Both cases were successfully treated with corticosteroid therapy, none of them required intubation. During a median follow up period of 16.5 months (range 2–54), there was no transplant related death. Neurologic improvement was significantly observed in all patients and median post transplantation serum VEGF level was decreased to 330 pg/ml (range 87–3250). Only one patient experienced relapse of polyneuropathy at 43 months post transplant following reincrease of serum VEGF level.

Conclusions: ASCT is an effective therapy for POEMS syndrome. Despite previous published reports arousing potential risk of life-threatening engraftment syndrome, treatment related mortality and periengraftment pulmonary complications were significantly low in our patient series. We speculate that stabilization of serum VEGF level by induction therapy before ASCT could play a potential role for reducing the risk of peritransplant complications.