Autologous Hematopoietic Stem Cell Transplantation in Light Chain Amyloidosis (AL) with Renal Involvement

Background: Immunoglobulin light chain amyloidosis (AL) is characterized by deposition of insoluble fibrils composed of immunoglobulin light chains, causing progressive organ dysfunction. Renal involvement is seen in 50% of cases of AL, which, if left untreated, progresses to end-stage renal disease (ESRD).

Methods: We performed a retrospective analysis in 75 patients (pts) with AL with renal involvement who underwent high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution between 1999 and 2011.  Fifty-five of these AL pts had renal involvement, as defined by the International Consensus Criteria (Ref. Gertz M et al. AJH 2005). Primary objectives were to assess hematologic and organ response, progression-free (PFS) and overall survival (OS) and correlation between hematologic and organ response.

Results: Median age at auto-HCT was 59 years (range, 41-74). Median time from diagnosis to auto-HCT was 6.6 months (2.2-121.9). Additional visceral organs involved were: heart 5 pts (9%), GI tract 3 pts (5%), peripheral nerves 1 pt (2%) and liver 5 pts (9%).  Median baseline 24-hour proteinuria was 5.055 grams (range, 0.17- 27.85 grams).  All pts received melphalan or melphalan-based combinations as their preparative regimen. Median time to neutrophil engraftment was 10 days (range, 7-15). Median follow up from auto-HCT was 24.5 months (range, 0.4-132). Six pts died of non-relapse causes with a non-relapse mortality (NRM) at both 100 days and 1 year of 10.9%.  Fifty pts were evaluable for a hematologic response, while 5 patients were inevaluable due to early death. Eight pts (16%) achieved complete remission (CR), 10 (20%) achieved a very good partial remission (VGPR) and 21 (42%) achieved a partial remission (PR), with an overall response rate of 78%.  Organ response was evaluated at 6, 12, and 24 months, and was defined as a ≥50% decrease in total proteinuria over 24 hours without an increase of ≥25% of serum creatinine.  Organ response was demonstrated in 8 (17%) of 47 evaluable pts at 6 months, in 11 (29%) of 38 evaluable pts at 12 months, and in 12 (44%) of 27 evaluable pts at 24 months, respectively. Organ responses at last follow up were seen in 12 of 28 pts with > hematologic PR and 0 of 11 pts with < hematologic PR (p=0.008). Two pts who were hemodialysis-dependent pre auto-HCT remained on dialysis after the auto-HCT. Median PFS and OS were 43.1 and 69.9 months, respectively. Kaplan-Meier estimates of 3-year PFS and OS were 62% and 73%, respectively (Figure). At the time of last follow-up, 37 pts (67%) were alive and in remission.

Conclusions: High-dose melphalan and auto-HCT is associated with durable hematologic and organ response, and long OS in patients with AL and renal involvement. Achievement of hematologic response is highly predictive of a renal response.