Autologous Haematopoietic Stem Cell Transplantation in Patients with Multiple Myeloma Complicated By Dialysis-Dependent Renal Failure
Authors: Firsova Maiia V. , Mendeleeva Larisa P. , Rekhtina Irina G. , Solovev Maxim V. , Pokrovskaya Olga S. , Gemdzhian Eduard , Biryukova Ludmila S. , Savchenko Valery G. 
Published: October 2019

Abstract
Introduction. Multiple myeloma (MM) in its early onset is complicated by myeloma nephropathy in 20-30% of patients, 10% of whom require haemodialysis. Early studies have shown that renal dysfunction has no adverse effect on melphalan pharmacokinetics. Auto-HSCT in some patients allows to restore renal function and to stop hemodialysis.
Aim of the study. To assess the safety and efficacy of auto- HSCT in MM patients with dialysis-dependent renal failure.
Materials and methods. During a period from May 2010 to December 2016 thirteen (3 males, 10 females) MM patients with dialysis-dependent renal failure aged 48 to 65 years (median 58) underwent auto-HSCT. The diagnosis was made according to IMWG criteria. In the onset of the disease, the median creatinine level was 1091 μmol /L, and GFR (CKD-EPI) ranged 3 to 10 ml / min / 1.73 m2 (median 3). Induction therapy included bortezomib-containing regimens in all patients, bendamustine was used in 5 (38.5%) patients, immunomodulatory drugs were used in 2 (15%) patients. HSC mobilization was performed according to the scheme: G-CSF 10 μg/kg. The median number of harvested CD34+ cells was 3.46x106/kg. Subsequently, against the background of programmed hemodialysis and in the setting of high-dosed melphalan (100-200 mg/m2), 12 patients underwent a single and one patient underwent a tandem auto-HSCT. On Day 100 after auto-HSCT, an antitumor response and renal response were assessed. Survival curves were constructed using the Kaplan-Meier method. Statistical analysis was done using Statistica 10.
Results. Before auto-HSCT CR was documented in 8 (61%) patients, VGPR was documented in 4 (31%) patients, PR was documented in 1 (8%) patient, with no renal response registered, GFR: 4-10 ml/min/1.73 m2 (median 5). The period of agranulocytosis after auto-HSCT was accompanied by infectious complications, cardiac and neurological dysfunctions (Table 1). The resulting complications were stopped; the mortality associated with transplantation (TRM) was 0%. At +100 days after auto-HSCT, the PR was confirmed in 9 (70%) patients and VGPR was confirmed in 4 (30%) patients. GFR: 5 - 17 ml/min/1.73 m2 (median 7). The minimal renal response was registered in 2 patients (15%), hemodialysis was stopped. After a median follow-up of 52 months 5-year progression-free survival (PFS) was 71%, and OS was 92%.
Conclusion. Auto-HSCT in MM patients with dialysis-dependent renal failure is a feasible and effective treatment method, nevertheless, characterized by a high rate of early post-transplantation complications. Dialysis-dependent renal failure is not a contraindication for the use of high dosed melphalan followed by auto-HSCT. The probability of hemodialysis discontinuation after auto-HSCT was 15%. Survival rates are comparable to those in patients without renal impairment.

Disclosures
No relevant conflicts of interest to declare.