Safety of autologous hematopoietic stem cell transplantation in patients with multiple myeloma and chronic renal failure

Abstract

Patients with multiple myeloma (MM) and chronic renal failure have generally been excluded from myeloablative therapy programs followed by hematopoietic stem cell support because of the potential increase in transplant-related morbidity and mortality. We here report our experience treating six MM patients with moderate to severe renal insufficiency, with autologous stem cell transplantation. One of these patients required chronic hemodialysis since the diagnosis of MM was made.

Melphalan 200 mg/m2 in patients with renal impairment is associated with increased short-term toxicity but improved response and longer treatment-free survival

“…[10][11][12] Despite the limited pharmacokinetic data, previous published clinical experience clearly suggests increased toxicity in patients with RI. [13][14][15][16] The Arkansas group has reported a prospective study evaluating the relationship between melphalan pharmacokinetics and renal function in 20 patients with MM. 17 Six patients had renal insufficiency (CrCl o 40 mL/min), including five on hemodialysis.…”

“…Median time to neutrophil engraftment was 10 (range 7-12) and 9 (range 8-13) days in patients with CrCl o 60 mL/min and ⩾ 60 mL/min, respectively (P = 0.008). Median time to platelet engraftment was 12 (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)) and 10 (8-18) days in each group, respectively (P o 0.001). The median duration of hospitalization was significantly longer in patients with RI (14 (range 12-36) versus 16 (range 11-47) days, P = 0.02).…”

Efficacy, toxicity and mortality of autologous SCT in multiple myeloma patients with dialysis-dependent renal failure

“…[1][2][3] Approximately 20-40% percent of patients with MM have renal impairment at the time of diagnosis and up to 2-3% of patients will require dialysis during their disease course. [4][5][6][7] Although ASCT appears feasible and safe in patients with mild to moderate renal impairment, [8][9][10][11] there are limited data in those with dialysis-dependent renal failure. Studies on patients with renal dysfunction undergoing ASCT include only a small subset of patients on dialysis.…”

“…Studies on patients with renal dysfunction undergoing ASCT include only a small subset of patients on dialysis. 8,10,[12][13][14] It is encouraging, however, that even in patients with severe renal failure, improvements in renal function following transplantation can be observed. 9,[15][16][17] Unfortunately, patients with renal failure appear to have higher rates of treatment-related toxicities and transplantrelated mortality (TRM) compared with patients without renal failure.…”

Pharmacokinetics of high-dose chemotherapy

“…49,50 However, other groups have reported the safety of high-dose melphalan in renal failure, including some on chronic hemodialysis, either administered at 200 mg/m 2 , 51 or at 80 mg/m 2 in combination with high-dose busulfan. 52 There is up to 10-fold interpatient variability in the PK exposure to high-dose melphalan, which makes PKTD an attractive prospect. The feasibility of PKTD of melphalan administered at standard doses after a smaller test dose has been proven feasible, with less than 15% deviation from the target AUC.…”