![[Visit Client Website]](images/banner.gif)
Treatment of AL amyloidosis (AL) with high dose melphalan and autologous stem cell transplant (HDM/SCT) results in a high rate of durable complete hematologic responses (CHR) associated with systemic clinical responses and improvement in survival. However, patients with cardiac involvement are at increased risk of treatment-related mortality (TRM).
HDM/SCT was performed for thirty patients between 2000 and 2011. Risk stratification based on organ dysfunction was performed. Analyses of pre and post SCT treatments, TRM in patients with and without cardiac involvement, hematologic (HR) and organ responses, progression free (PFS) and overall survival (OS) was performed.
The median age was 60 years (range, 41-72) and there were 20 males (67%). Twenty (67%) had multi-organ involvement, 7 (24%) had single organ involvement, 18 (60%) had renal involvement and 12 (40%) had cardiac involvement.
Peripheral blood stem cells were mobilized with G-CSF alone for 3–4 days. HDM was administered over two days and adjusted depending on age, severity of cardiac disease and performance status. Twenty (67%) patients received 200 mg/m2, 9 (30%) received 140 mg/m2 and 1 received 100mg/m2 HDM.
TRM, defined as deaths within 100 days of SCT, occurred in 3 patients (10%), 2 had cardiac disease and 1 did not. No deaths occurred during stem cell mobilization. Of the 12 patients with cardiac involvement, 2 died within 100 days (from CHF and sepsis with NYHA III and I prior to SCT). Of the 18 patients without cardiac involvement, 1 patient died of exsanguination from AL-involved splenic rupture (Fisher's exact test, p= 0.54). Of the 12 patients with cardiac involvement, 8 had a septal wall thickness >1.1cm and 6 were > 1.3cm. Of the 9 patients that had BNP measurements, all were >100 pg/mL and 4 were >500 pg/mL.
Fourteen patients (47%) patients achieved CHR and 7 (23%) achieved at least a partial hematologic response at 1 year following HDM/SCT. Organ specific responses at 1 year were confirmed in 8 subjects. Fifteen patients received chemotherapy prior to HDM/SCT leading to a deeper HR prior to transplant in 7 patients. Two patients received a 2nd autologous transplant, 4 and 7 years after the first and remain alive and in remission.
HDM/SCT for patients with AL amyloidosis with and without cardiac involvement is feasible and is associated with excellent 2 and 5 -year PFS and OS rates (figure). Due to the inherent flaws in using traditional biomarkers and cardiac MRI for staging cardiac disease in the setting of renal dysfunction, improved strategies are needed. We are currently assessing the utility of speckle tracking derived myocardial strain indices as a means for early diagnosis of cardiac involvement and response to therapy- an area in which standard echocardiographic measurements have been disappointing. Informative data have been identified in the serial strain analyses on 5 patients who are currently undergoing therapy for AL.