Abstract
Background
High dose melphalan with autologous stem cell transplantation (ASCT) is a standard treatment for eligible patients with systemic light chain (AL) amyloidosis. Treatment-related mortality (TRM) of ASCT for AL amyloidosis was previously reported being as high as 40%; however, risk-adapted melphalan dosing reduced TRM to about 10% or less in experienced institutes. Several ways to determine the dose of melphalan have been proposed. They were focusing on organ failures especially cardiac dysfunction shown by ejection fraction (EF). EF represents contractile function of the heart; however, in AL amyloidosis, EF is known to be maintained until late stage whereas diastolic function is damaged earlier. We here present the outcomes of AL patients who received ASCT following risk-adapted melphalan with our criteria including B type natriuretic peptide (BNP) which is a practical marker for diastolic function of the heart and less affected by the renal function than NT-proBNP.
Patients and Methods
A total of 12 patients with primary systemic AL amyloidosis treated with HD-Mel with ASCT at Sapporo Medical University Hospital between 2004 and 2012 were evaluated. Patients with age older than 65 years, poor performance status or severe organ dysfunction were determined not to eligible for ASCT. The dose of melphalan for conditioning regimen was modified due to patients' condition. A dose of 200 mg/m2 was administered to patients in performance status (ECOG) 0 or 1, number of organ involvement 2 or less, serum creatinine <1.5 mg/dl, EF >50%, and BNP <200 pg/ml; otherwise 140 mg/m2. Hematological response (HR) and organ response (OR) were evaluated according to the Consensus Opinion from the 10th International Symposium on Amyloid and Amyloidosis. The Kaplan-Meier method was used to estimate event-free survival (EFS) and overall survival (OS); both of them were measured from the day of ASCT.
Results
Twelve patients were included in this study, 4 were women. The median age at transplantation was 54 years (range, 32 - 65 years). Involvement of 1 organ was present in 1 patient (8.3%), 2 organs were involved in 8, and 3 or more organs in the remaining 3. Ten patients had a lambda monoclonal protein, and the median percentage of plasma cells in the bone marrow was 2.5% (range, 0.2% - 9.6%). No patients received treatment before HDM/ASCT, except 2 patients treated high-dose dexamethasone or 1 course of VAD regimen before referring to our hospital. Six patients received 200 mg/m2 of melphalan and remaining six received reduced dose based on the criteria in Patient and Methods. Notably, it was possible to screen patients with only the value of BNP; i.e., all the patients who received 140 mg/m2 of melphalan by the criteria had a high level (more than 200 pg/ml) of BNP. The median time from diagnosis of AL to ASCT was 95 days (range, 47 to 195 days). The median number of CD34-positive cells infused was 3.55 x106/kg, and all patients were engrafted. The hematologic CR was achieved in 5 patients and PR in 2. The organ response was observed in 2 patients who achieved hematologic CR. The median EFS of all patients was 21.1 months (range, 3.4 to 70.8 months), and median OS was 21.1 months (range, 3.4 to 112.5 months). EFS and OS were significantly longer for patients who received 200 mg/m2 of melphalan that are same with patients who had BNP less than 200 pg/ml, compared with a lower dose of melphalan and higher level of BNP (EFS: 15.0 months vs not reached, p=0.0166; OS: 15.0 months vs not reached, p=0.0166). No TRM was observed.
Conclusions
AL patients with less than 200 pg/ml of BNP can be safely performed HD-Mel with ASCT and expected longer survival.
Disclosures:
No relevant conflicts of interest to declare.
An elective single autograft with high-dose melphalan: single-center study of 451 patients
