Cyclophosphamide and Prednisone Induction Effectively Decreased the Incidence of Engraftment Syndrome In Patients with POEMS Syndrome Who Undergo Stem Cell Transplantation.

Abstract Abstract 1318 POEMS syndrome is a devastating syndrome, characterized by Peripheral neuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cells, Skin changes, papilledema, volume overload, sclerotic bone lesions, and elevated plasma levels of vascular endothelial growth factor (VEGF). High-dose chemotherapy with autologous peripheral blood stem cell transplantation (ASCT) can achieve excellent clinical responses, but there can be signficant peritransplant morbidity. Patients (pts) with POEMS syndrome have an aberrant cytokine milieu that is amplified and exaggerated by the process of marrow reconstitution. Significant increases in the concentration of circulating macrophage colony-stimulating factor, erythropoietin, IL-6 and TNF-α, reach near maximal values at approximately day +12, predating neutrophil engraftment. Engraftment syndrome (ES) occurs in 27–47% of patients who undergo ASCT; mortality rate is reported from 8 to 18%. Authors have consistently demonstrated that ASCT is effective therapy for these pts with improvement of the neuropathy, skin changes, VEGF levels, etc. However, we were impressed by the unexpected, excessive morbidity of the procedure reported in previous series. We have therefore reviewed our experience with ASCT in patients with POEMS syndrome with an emphasis on treatment-related morbidity. Patients and Methods Between March 2004 and March 2010, 15 pts with POEMS syndrome were seen at our institution. Seven pts underwent ASCT at Princess Margaret Hospital and electronic medical charts were reviewed. All pts received oral cyclophosphamide (300 mg/m2) and prednisone (100 mg every other day) before undergoing ASCT; median of 3 cycles were given (range 3 to 7). Peripheral blood stem cells were collected using intravenous cyclophosphamide and granulocyte colony stimulating factor (G-CSF). The median number of CD34 cells collected was 5.16 × 106/kg. Five pts were conditioned using Melphalan 200 mg/m2, and two received Melphalan 140 mg/m2. Standard supportive care with prophylactic antibiotics was provided to all pts. Data were retrospectively collected. Spitzer and Maiolino (Bone Marrow Transplant 2001 and 2003) criteria were used for defining ES. Hematologic responses (HR) were defined according to the International Uniform Response Criteria. Endpoints for the analyses included: ES, need for intubation, need for corticosteroid bolus during transplant course and time from ASCT to hospital discharge. Results Of the seven pts transplanted with POEMS syndrome at our institution, 70% were female. (Table 1) The median age was 56 (42 to 69). IgA lambda was the most prevalent monoclonal protein (85%). Polyneuropathy, edema, organomegaly, endocrine changes and sclerotic lesions were present in all pts. Transplanted pts had a median time to ANC 0.5 × 109/L of 13d. The time to platelets 20 × 109/L was 14.5 days. Median time to discharge was 19 days. Most importantly, no patients exhibited ES. At a median follow up of 74 months (48-187), all patients are alive and progression-free. Treatment related mortality with this approach was 0%. According to International Response Criteria, 57.2% have achieved a complete HR, 14.3% very good PR, and 14.3% PR. All evaluable pts have derived clinical benefit with improvement in peripheral neuropathy, edema and performance status, including those who achieved less than PR. Only one patient received bolus corticosteroids as prophylaxis for ES due to high risk features including abnormal pulmonary function test and splenomegaly. Conclusions We hypothesize that the absence of ES in our cohort, contrary to reports from the literature, may be due to the use of pre-transplant cyclophosphamide and prednisone. The use of this regimen as induction may modulate marrow reconstitution, decreasing the incidence of ES, and subsequently lead to a reduction in peri-transplant morbidity and mortality. Larger studies with correlative biology are necessary Disclosures: Reece: Celgene: Honoraria, Research Funding. Chen:Celgene Corporation: Consultancy, Honoraria, Research Funding. Kukreti:Celgene: Honoraria.

Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.