Abstract
Background: Light chain deposition disease (LCDD) is a systemic disorder characterized by monoclonal light chain deposition in organs, most often the kidney but also in the liver, heart and nervous system. Treatment aims to suppress the monoclonal plasma cell population producing the light chains to allow for improvement in or delay deterioration of organ function. Treatments are generally modeled on those for myeloma and light chain amyloidosis. The options are cyclical chemotherapy lately using a novel agent based conditioning regime and, in selected patients, high dose melphalan followed by autologous stem cell transplantation. Due to LCDD being an immunoglobulin disease, based on experience with systemic AL amyloidosis, there is a reluctance to consider ASCT due perceived risks of morbidity and transplant related mortality. There is limited data on the safety and outcomes after ASCT in LCDD. We report here the role of autologous stem cell transplantation to treat LCDD in the largest cohort of patients to date.
Methods: This study included all patients between 2003 and 2013 with LCDD who had undergone ASCT from the database of the UK National Amyloidosis Centre (NAC). Data on disease status (clonal markers and organ involvement) at diagnosis, pre and post ASCT was collected from the respective transplant centres for patient progress during and immediately after ASCT. Organ function and clonal response data were serially collected for all patients including clinical course, renal, cardiac and neurological function.
Results: A total of ten patients with LCDD were identified who underwent ASCT. This accounted for 23% of all LCDD patients seen at the NAC over this time period. The baseline characteristics were: median age 48 (range 36-60), eGFR 17 ml/min (<10-51), Alkaline phosphatise 92 (51-334), LV wall thickness 10 mm, NT-proBNP 1121 (range 318-4346). Serum monoclonal M protein was quantifiable in 2/10 patients. 9/10 patients had elevated kappa serum free light chains (SFLC) with median level of 1069 mg/dl (range 281-2962) with median κ/λ ratio of 21 (range 0.1-151, NR 0.26-1.65). Only 1/10 had elevated lambda LC. All patients had clonal plasma cells on marrow aspirate with 5/10 patients having >10% (median 15; range 12-50%) and 5/10 , </= 10% (range 2-10%). All patients received chemotherapy prior to ASCT. The median time from diagnosis to ASCT was 13.5 months (Range 4-27). Median follow up post ASCT was 4.8 years (range 6 months-11 years). Haematological responses were seen in all patients with 7/10 acheiving a complete clonal response, 1 patient achieving a VGPR and 2 patients achieving PR. All patients had renal impairment prior to ASCT and 5/10 were on renal dialysis. There was no transplant related mortality and all patients are still alive. After ASCT, 4 patients’ renal function improved, 4/5 remained unchanged on dialysis and 2 patients showed a deterioration in renal function. Of the patients whose renal function improved, one came off dialysis post ASCT, the other three were not on dialysis at any time point. Of the two patients whose renal function deteriorated post ASCT, one required dialysis 3 years after ASCT.
Conclusion: This largest study of autologous stem cell transplantation in LCDD to date shows a very high clonal response rate post ASCT. 50% patients had improvement in renal function after transplant. ASCT in LCDD is safe with no transplant related mortality. None of the patients progressed to active myeloma after ASCT. This data supports the use of ASCT in patients with LCDD. Given the rarity of the condition, international registry data would be important to confirm these encouraging findings.
Disclosures
No relevant conflicts of interest to declare.
Blood stem cell transplantation to treat cystic lung light chain deposition disease
