It affects approximately 10 patients per million per year, including 10%-15% of patients with multiple myeloma (MM).2,3The treatment approaches used for AL amyloidosis are directed toward the eradication of the abnormal plasma cell clone with the aim of eliminating the supply of the amyloidogenic light chains.4Compared with myeloma, AL is typically associated with a lower burden of Granisetron clonal plasma cells.5High-dose melphalan (HDM) and peripheral blood stem cell transplantation (SCT) have been used since the mid-1990s and remain an effective treatment for AL amyloidosis.68However, the transplantation-related mortality (TRM) in AL amyloidosis (approximately 10%-15%) is significantly higher than that seen in patients with MM and lymphoma (1%-2%) and is often attributed to the presence of underlying cardiac and/or multiorgan involvement.9The outcome with HDM among patients with cardiac amyloidosis has not been examined systematically. (P< .01). In multivariate analysis of baseline factors, only reduced-dose melphalan predicted shorter OS. HDM is feasible in patients with cardiac amyloidosis, and achievement of HR and organ response is associated with improved survival. == Introduction == Amyloidosis is a group of rare diseases characterized by multiorgan deposition of amyloid fibrils. In light-chain (AL) amyloidosis or primary systemic amyloidosis, the fibrils are derived from the immunoglobulin light chains secreted by clonal plasma cells.1AL amyloidosis represents the most common type of systemic amyloidosis and cardiac involvement is seen in more than half of patients at diagnosis. It affects approximately 10 patients per million per year, including 10%-15% of patients with multiple myeloma (MM).2,3The treatment approaches used for AL amyloidosis are directed toward the eradication of the abnormal plasma Granisetron cell clone with the aim of eliminating the Granisetron supply of the amyloidogenic light chains.4Compared with myeloma, AL is typically associated with a lower burden of clonal plasma cells.5High-dose melphalan (HDM) and peripheral blood stem cell transplantation (SCT) have been used since the mid-1990s and remain an effective treatment for AL amyloidosis.68However, the transplantation-related mortality (TRM) in AL amyloidosis (approximately 10%-15%) is significantly higher than that seen in patients with MM and lymphoma (1%-2%) and is often attributed to the presence of underlying cardiac and/or multiorgan involvement.9The outcome with HDM among patients with cardiac amyloidosis has not been examined systematically. Therefore, we undertook the present study to examine the outcome of patients with AL amyloidosis receiving HDM, with particular focus on transplantation-related complications, hematologic response (HR) and organ response rates, impact on cardiac function, and factors predicting post-HDM survival. == Methods == We selected the patients for the present study from 382 patients with AL amyloidosis who underwent HDM at our institution between May 1996 and September 2008. We used a cutoff of September 2008 to allow for adequate long-term follow-up given the potentially slow rate of organ improvement in this disease. The follow-up status was updated as of December 31, 2010. Among this group, 193 patients had documented cardiac involvement, which was defined by the presence of echocardiographic findings consistent with an infiltrative cardiomyopathy or cardiac biopsy that confirmed the presence of heart involvement.10Six patients who underwent orthotopic heart transplantation were excluded from the analysis, and the remaining 187 (49%) patients were included. The histological diagnosis of AL amyloidosis was confirmed using Congo red staining of biopsy specimens in all patients. All patients had either a demonstrable monoclonal protein in the serum and/or urine or a clonal plasma cell population in the BM. Patients with secondary, familial, or localized amyloidosis and those with overt MM were excluded. The organ involvement and responses (hematologic and organ) were assessed using the consensus criteria reported in the 10th International Symposium on Amyloid and Amyloidosis.10A hematologic partial response (PR) requires a 50% reduction in serum M protein, along with a 90% reduction or a reduction to < 200 mg/24 hours in urine M protein. Complete response (CR) requires the disappearance of the M protein by serum and urine immunofixation along with a BM showing < 5% plasma cells. A cardiac response required either a 2-mm reduction in the interventricular septal thickness by echocardiogram or improvement of ejection fraction (EF) by 20% (baseline EF must be 45%). All patients provided written informed consent for the use of their medical records. Approval from the Mayo Clinic Institutional Review Board was obtained in accordance with federal regulations and the Rabbit Polyclonal to 14-3-3 beta Declaration of Helsinki. The baseline evaluation included BM examination with confirmation of plasma cell clonality and Congo red staining for amyloid, echocardiogram, electrocardiogram, 24-hour urine protein measurement, serum and urine protein electrophoresis with immunofixation, and an abdominal fat pad aspirate. Although the inclusion criteria for HDM in patients with AL amyloidosis have changed over the years, patients with an Eastern Cooperative Oncology Group performance status 2 and a New York Heart Association classification of < III were considered eligible to undergo the procedure.6A total of 164 patients (88%) had G-CSF alone for stem cell mobilization, and the remaining required cyclophosphamide in addition to G-CSF. Melphalan 200/m2(n =.
