Long Term Results of High-Dose Melphalan and Autologous Stem Cell Transplantation in Non-Amyloid Monoclonal Immunoglobulin Deposition Disorders.

Abstract 4356

Monoclonal Immunoglobulin Deposition Disorder (MIDD) is a plasma cell dyscrasia in which whole immunoglobulins or heavy or light chain subunits form non-fibrillar deposits in various tissues, causing organ dysfunction. Several studies have previously reported that high dose melphalan and autologous stem cell transplantation (HDM/SCT) is safe and effective at achieving a complete hematologic response in this disease, but long term data is sparse. Hematological complete response is defined as normalization of serum free light chain ratio and concentration, bone marrow exam with less than 5% plasma cells, and absence of monoclonal gammopathy in serum and urine by immunofixation electrophoresis. Between 2003 and 2008, ten patients with MIDD were treated with HDM/SCT at a dose of 200mg/m² (n=6) or 100-140 mg/m² (n=4) depending upon age and clinical status and were assessed for hematologic responses and improvements in organ function at 3-6 and 12 months, and annually thereafter. The median age was 45 years (range, 34 to 70); all but one patient were male. Six patients had kappa clonal predominance and four patients had lambda clonal predominance. All ten patients had renal involvement, two were on dialysis and one had undergone a renal transplant. Two patients also had extrarenal manifestations with cardiac involvement. The median creatinine clearance was 26 mL/min (range 20 to 100) and the median 24 hour urine total protein excretion was 4,037 mg (range, 458 to 15,632). Peripheral blood stem cells were collected after GCSF mobilization and a median of 6.9 ×10⁶ CD34cells/kg were collected. There was no treatment related mortality within 100 days of SCT. One patient developed end stage renal disease during the peri-transplant period. Of the seven patients who have had follow-up of at least a year, five (71%) achieved a complete hematological response (CR) and two (29%) had a partial hematological response. One patient died six months after HDM/SCT due to progressive disease. Clinical and organ responses were also evident after HDM/SCT in 5 out of 7 patients. The median creatinine clearance was 42 mL/min (range, 38-55) and the median 24 hour urine total protein excretion was 179 mg (range, 150 to 349) at 2 years after treatment. Of the five patients with hematologic CR, 3 (60%) have relapsed at a median of 3 years (range, 2-3). Two of the 5 patients continue to have hematologic CRs at four and six years after HDM/SCT. In summary, HDM/SCT in MIDD often results in hematological CRs, as well as an improvement in renal function. However, the 5-year relapse rate is high. This group of patients may benefit from maintenance anti-plasma cell therapy.