Primary amyloidosis, an uncommon plasma cell disorder that leads to organ dysfunction and short survival, poses a major therapeutic challenge. Oral melphalan and prednisone has a response rate of only 18%. High dose melphalan (200 mg/m2) supported by G-CSF mobilized peripheral blood progenitor cells (G-PBPC) has been used for the treatment of primary amyloidosis with encouraging results. However, treatment-related mortality and morbidity were substantial. In order to minimize toxicity and improve efficacy, we explored tandem intermediate dose melphalan (140 mg/m2) administered 2 month apart and supported by G-PBPC (10 H/kg/d). Four patients were enrolled on this study between December 1996 and March 1997. All had nephrotic syndrome, 1 had definite and 1 had probable cardiac involvement. Leukaphersis was completed in single (2 subjects) and 2 (2 subjects) sessions. CD34 AGC PRBC PLT CD34 1 AGC PRBC PLT 13.7 8 4 2 14.7 8 0 1 2.9 10 0 2 3.4 10 0 0 2.8 10 ND ND NA NA NA NA 4 9 2 1 4 10 2 0 (CD34+ cell dose for first transplant (x 106/kg). AGC= days to AGC>1000. 1 data for the second transplant. Number of red blood cells and platelet units infused =RBC and PLT infused. NA=not available, ND=not determined. Data in each row correspond to subject 1 through 4) All 4 patients developed neutropenic fever. Grade l-II mucositis was seen during 5 cycles and grade III in one cycle. Subject 2 (with definite cardiac involvement) developed sudden cardiac death on day 10 after the second cycle of high-dose chemotherapy. Subject 3 developed sepsis and gastrointestinal bleeding following the first cycle, leading to renal failure requiring hemodialysis. He died 22 months later from complications related to peritoneal dialysis. Subject 1 continues to show resolution of his nephrotic range proteinuria 44 months following transplantation and enjoys good performance status. Subject 4 has stable proteinuria with 41 months of follow up with good health. Tandem intermediate dose melphalan supported by autologous PBPC warrants further investigation in primary amyloidosis.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology