Abstract
Cardiac involvement in light chain amyloidosis (AL) predicts poor prognosis and is associated with higher treatment related mortality and morbidity during autologous stem cell transplantation (ASCT). We studied the outcomes of AL patients with cardiac involvement undergoing ASCT at our center between January 2002 and December 2012.
Out of a total of 264 AL patients, 53 patients had cardiac involvement according to the International Consensus Criteria (Gertz M et al. AJH 2005) and 27 underwent ASCT. Cardiac staging was assessed using the Revised Prognostic Staging System for Light Chain Amyloidosis (Kumar S et al, JCO 2012). Hematologic and cardiac responses were evaluated before and at 1 year after ASCT using the guidelines established by the 10th International Symposium on Amyloid and Amyloidosis (Gertz M et al. AJH 2005).
The median age of the patients was 53 years (range 36-74) with a median duration from diagnosis to ASCT of 6 months (range 3-95). The estimated median follow up for the entire cohort was 41 months (range 6-173). Twenty-four patients (89%) had an additional organ involvement, besides heart. Cardiac stage ≥3 was seen in 14 patients. The median troponin-T, Troponin-I, BNP and NT-proBNP levels and free light chain difference (FCL-diff) were 0.054 ng/ml, 0.05 ng/ml, 376 pg/ml, 1888 pg/ml, and 116.4 mg/l respectively (table1). Twenty-four patients (89%) received induction chemotherapy and 22 of those (81%) received novel chemotherapy agents. Eighteen patients (66.6%) achieved at least PR prior to ASCT. Four patients (14.8%) received reduced doses melphalan conditioning (140-180 mg/m2). One-year transplant related mortality (TRM) was 3.7% (1 patient died at day 11 post-transplant due to cardiac event). At 1-year post ASCT, overall HR was seen in 24 patients (89%) (CR=26% and PR=63%) while 3 patients (11%) had cardiac responses. At the time of last follow up, 17 patients (63%) were alive. The median overall survival (OS) from diagnosis and from ASCT was 58 months (95% CI; 46-69) and 46 months (95% CI; 36-55) respectively (figure1). The median progression free survival (PFS) was 25 months (95% CI; 6-44). Cumulative incidence of hematologic relapse at 3 year was 38.5% (95%CI 23.7-62.5). Cardiac progression at last follow up was seen in 1 patient (3.7%). Negative factors affecting OS included lack of induction therapy prior to ASCT and NT-proBNP more than 5000 pg/ml. We conclude that ASCT is well tolerated in patients with high-risk cardiac amyloidosis and the incorporation of induction therapy can improve overall outcomes of these patients.
Figure1.
Overall Survival
Table1
Patient Characteristics
| Baseline characteristics | Total (N=27) | Interquartile range |
|---|---|---|
| Median age (year) | 53 | 36-71 |
| Gender: male (%) | 20 (74.1) | |
| Median time from diagnosis to transplant, (month) | 6 | 3-95 |
| Receive induction chemotherapy (%) | 24 (88.9) | |
| Receive novel induction chemotherapy (%) | 22 (81.5) | |
| Light chain type (%)-Kappa-Lambda | .6 (22.2) 21 (77.8) | |
| Other organ involvement (%) | 24 (88.9) | |
| History of cardiac complications prior ASCT (%) | 17 (63) | |
| History of cardiac complications after ASCT (%) | 20 (74.1) | |
| ICU admission prior ASCT (%) | 3 (11.1) | |
| Cardiac event prior ASCT (%) | 17 (62.9%) | |
| Median FLC-diff (mg/l) (N=15) | 116.4 | 15-1168 |
| Median EF (%) (N=19) | 60 | 30-82 |
| Median IVS (mm.) (N=14) | 1.35 | 0.7-2.1 |
| Median Troponin-T (ng/ml) (N=20) | 0.019 | 0.01-0.22 |
| Median Troponin-I (ng/ml) (N=19) | 0.06 | 0.03-9.09 |
| Median BNP (pg/ml) (N=23) | 376 | 15.2-1782 |
| Median NT-proBNP (pg/ml) (N=12) | 1888.5 | 19-9911 |
| Median serum calcium (mg/dl) | 9.2 | 7-11 |
| Median serum albumin (g/dl) | 3.9 | 2.4 |
| Median Creatinine (mg/dl) | 1.0 | 1-9 |
| Median B2 microglobulin (mg/l) | 3.15 | 1-15 |
| Median 24-hr urine protein (mg) | 574 | 120-36006 |
| Median serum M protein (g/dl) | 0.5 | 0-4 |
| Median LDH (IU/l) | 377 | 146-770 |
| Median BM plasma cell (%) | 11 | 0-58 |
| Cardiac stage at diagnosis | . | |
| Stage 1 | 1 | |
| Stage 2 | 5 | |
| Stage 3 | 6 | |
| Stage 4 | 8 | |
| Cardiac stage at transplant | . | |
| Stage 1 | 3 | |
| Stage 2 | 5 | |
| Stage 3 | 4 | |
| Stage 4 | 6 |
| Baseline characteristics | Total (N=27) | Interquartile range |
|---|---|---|
| Median age (year) | 53 | 36-71 |
| Gender: male (%) | 20 (74.1) | |
| Median time from diagnosis to transplant, (month) | 6 | 3-95 |
| Receive induction chemotherapy (%) | 24 (88.9) | |
| Receive novel induction chemotherapy (%) | 22 (81.5) | |
| Light chain type (%)-Kappa-Lambda | .6 (22.2) 21 (77.8) | |
| Other organ involvement (%) | 24 (88.9) | |
| History of cardiac complications prior ASCT (%) | 17 (63) | |
| History of cardiac complications after ASCT (%) | 20 (74.1) | |
| ICU admission prior ASCT (%) | 3 (11.1) | |
| Cardiac event prior ASCT (%) | 17 (62.9%) | |
| Median FLC-diff (mg/l) (N=15) | 116.4 | 15-1168 |
| Median EF (%) (N=19) | 60 | 30-82 |
| Median IVS (mm.) (N=14) | 1.35 | 0.7-2.1 |
| Median Troponin-T (ng/ml) (N=20) | 0.019 | 0.01-0.22 |
| Median Troponin-I (ng/ml) (N=19) | 0.06 | 0.03-9.09 |
| Median BNP (pg/ml) (N=23) | 376 | 15.2-1782 |
| Median NT-proBNP (pg/ml) (N=12) | 1888.5 | 19-9911 |
| Median serum calcium (mg/dl) | 9.2 | 7-11 |
| Median serum albumin (g/dl) | 3.9 | 2.4 |
| Median Creatinine (mg/dl) | 1.0 | 1-9 |
| Median B2 microglobulin (mg/l) | 3.15 | 1-15 |
| Median 24-hr urine protein (mg) | 574 | 120-36006 |
| Median serum M protein (g/dl) | 0.5 | 0-4 |
| Median LDH (IU/l) | 377 | 146-770 |
| Median BM plasma cell (%) | 11 | 0-58 |
| Cardiac stage at diagnosis | . | |
| Stage 1 | 1 | |
| Stage 2 | 5 | |
| Stage 3 | 6 | |
| Stage 4 | 8 | |
| Cardiac stage at transplant | . | |
| Stage 1 | 3 | |
| Stage 2 | 5 | |
| Stage 3 | 4 | |
| Stage 4 | 6 |
Disclosures:
No relevant conflicts of interest to declare.
