The Efficacy and Long-Term Outcomes of ASCT in POEMS Syndrome: A Multicenter Retrospective Study in Japan
Authors: Kawajiri Chika , Sakaida Emiko , Ohwada Chikako , Miyamoto Toshihiro , Azuma Taichi , Taguchi Jun , Mori Takehiko , Hasegawa Yuichi , Kondo Tadakazu , Yujiri Toshiaki , Yoshimitsu Makoto , Tsudo Mitsuru , Iwasaki Toshihiko , Shigematsu Akio , Suzuki Ritsuro , Atsuta Yoshiko , Hirokawa Makoto , Sakamaki Hisashi , Nakaseko Chiaki 
Published: October 2019

Abstract
Backgrounds: POEMS syndrome is a rare plasma cell dyscrasia presenting with polyneuropathy, l-type M protein, VEGF elevation and systemic manifestations. The standard treatment of the disease has not been established through clinical trials, but autologous stem cell transplantation (ASCT) has been shown to be effective in patients with the syndrome. However, the efficacy and long-term outcomes of POEMS patients underwent ASCT have not been systematically studied.
Purpose and Methods: To clarify the efficacy and long-term outcomes of the patients underwent ASCT, we performed a multicenter retrospective study assessing the clinical course of patients registered to the Japan Society for Hematopoietic Cell Transplantation (JSHCT) TRUMP database. The definition and evaluation of response and progression/relapse was according to the criteria of Mayo Clinic (Blood.2012; 120:56-62).
Results: Between January 2000 and December 2011, 94 patients were registered to the TRUMP database, male 57 and female 37, with the median age of 52 years (range 28-72). All patients underwent PBSCT except for one who received both PBSCT and BMT. Two patients underwent 2nd ASCT. The median time to ASCT from the time of diagnosis of POEMS was 205 days (range: 16-3870 days). Peripheral blood stem cells were collected using either cyclophosphamide with G-CSF, G-CSF alone, or etoposide with G-CSF as mobilizing agents with a median of 1 apheresis procedure. Thirteen of the 68 patients (19.1%) needed additional harvest procedures, and two patients received G-CSF with plerixafor. Median total collected CD34+ cell dose was 4.0x106/kg (0.6-37.2x106/kg).The conditioning regimen was melphalan in 93/94 (99%): 68 patients (70.8%) received melphalan ≥ 200 mg/m2. Median infused CD34+ cell dose was 3x106/kg (0.02-20x106/kg). Periengraftment syndrome was recognized in 11 of the evaluable 68 patients (16.2%). After ASCT, patients' performance status (PS) was dramatically improved (ECOG PS 3-4; 33.7% to 8.2%). The best initial responses were as follows: hematologic response; CRH/VGPR H/PRH 38/51 (74.5%), NR H 13/51 (25.4%), clinical response; CR/PR 56/61 (91.2%), SD 4/61 (6.6%), PD 1/61 (1.6%), VEGF response; CRv/PRv 34/35 (97.1%), NRv 1/35 (2.9%). 17 patients relapsed/progressed after ASCT. Four patients had radiographic relapse, 7 patients had symptomatic progression, and 10/12 (83.3%) patients had elevated VEGF. There was no hematologic relapse/progression. With the median follow up of 26 months (range 1-102 months), 10 patients died and the overall survival at 4 years was 89.9%. Sixteen patients received post-transplant treatment (planned tandem ASCT:1, steroids: 7, Bor: 1, Thal: 11, Ren: 9, VAD: 1, RT: 1). The causes of death were; disease progression (4), infection (3; PCP 1, bacterial 2), and others (3).
Conclusion: We show the long-term outcomes of patients with POEMS syndrome treated with ASCT. These data suggest the promising role of ASCT in patients with POEMS syndrome both in producing prolonged survival and improving quality of life.
Figure 1. Figure 1. Kaplan-Meier analysis for OS post SCT

Disclosures
No relevant conflicts of interest to declare.