Peritransplant Complications and Long-Term Outcomes of Patients with Newly Diagnosed POEMS Syndrome after Upfront Autologous Stem Cell Transplantation

Background: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and skin changes) syndrome is a rare plasma cell dyscrasia, without standardized therapeutic algorithm. Autologous stem cell transplantation (ASCT) has been reported to be effective, but can be complicated by excessive peritransplant events. Risk factors predictive for these complications are largely unknown. Moreover, long-term outcomes of ASCT have also not been studied comprehensively, especially in China.

Methods: One-hundred and thirty eight patients, who met the diagnostic criteria proposed by Dispenzieri and underwent upfront ASCT at Peking Union Medical College Hospital between January 2005 and January 2016, were included in the current study. In these patients, 32 with severe end organ dysfunctions at diagnosis, received induction therapy (27 lenalidomide, 3 bortezomib and 2 melphalan based regimen; median 2, range 1-6 cycles) before ASCT. Clinical and laboratory information were reviewed, and outcomes were updated on July 1, 2016.

Results: Median age at transplantation was 45 years (range 24-66 years), and 92 (67%) were male. Serum levels of vascular endothelial growth factor (VEGF) were dramatically elevated (median 4794, range 142-13867 pg/mL). Patients received pretransplant induction showed more pleural effusion, ascites, DLCO < 40% predicted and renal impairment (eGFR < 60 mL/min/1.73 m²). After induction, median value of serum VEGF was reduced from 4933 pg/mL to 804 pg/mL. Peripheral blood stem cells were mobilized by either cyclophosphamide with G-CSF (92%) or G-CSF alone (8%). Median dose of CD34+ cell collected was 2.58¡Á10⁶/kg (0.77-10.90x10⁶/kg). The conditioning regimen was melphalan 200 mg/m² in 126 (91%), and the remaining patients received reduced dose (140 mg/m²). All collected CD34+ cells were infused.

Severe peritransplant complications were recognized in 32 patients (16 engraftment syndrome, 5 cardiac events, 2 cerebrovascular events, 6 acute kidney injury and 3 treatment-related death). Baseline risk factors, identified through multivariate logistic regression, included age > 50 years (odds ratio [OR] 2.94, p = 0.025), time from symptom onset to transplant > 5 years (OR 4.89, p = 0.033) and pleural effusion (OR 3.17, p = 0.024). In contrast, induction therapy was associated with reduced complications (OR 0.19, p = 0.021), and more significant protective value was observed, if induction therapy was replaced by post-induction VEGF complete remission (CR) (OR 0.06, p = 0.012).

After ASCT, most patients achieved systemic improvement, and the best responses were as follow: 50% hematological CR, 72% VEGF CR, 90% neurological response, and 65-86% responses of other involved organs. With median follow-up of 37 months (range 6-132 months), 6 patients died, and another 18 had disease progression. The 5-year overall survival and progression-free survival were 94% and 76%, respectively. Hematological (p = 0.008) and VEGF CRs (p = 0.021) were associated with superior PFS.

Conclusion: Upfront ASCT is an effective therapy that can generate universal and durable responses in most POEMS patients. Pretransplant induction may make those cases with severe end organ dysfunction at diagnosis eligible for ASCT, and further reduce peritransplant complications.