Autologous Hematopoietic Stem Cell Transplantation May Reverse Renal Failure in Patients with Multiple Myeloma

Abstract

Approximately 20% of patients with multiple myeloma (MM) have renal failure at diagnosis, and about 5% are dialysis-dependent. Many of these patients are considered ineligible for autologous hematopoietic stem cell transplantation (auto-HSCT) because of a high risk of treatment-related toxicity. We evaluated the outcome of 46 patient with MM and renal failure, defined as serum creatinine >2 mg/dL sustained for >1 month before the start of preparative regimen. Patients received auto-HSCT at our institution between September 1997 and September 2006. Median serum creatinine and creatinine clearance (CrCl) at auto-HSCT were 2.9 mg/dL (range: 2.0–12.5) and 33 mL/min (range: 8.7–63), respectively. Ten patients (21%) were dialysis-dependent. Median follow-up in surviving patients was 34 months (range: 5–81). Complete (CR) and partial responses (PR) after auto-HSCT were seen in 9 (22%) and 22 (53%) of the 41 evaluable patients, with an overall response rate of 75%. Two patients (4%) died within 100 days of auto-HSCT. Grade 2–4 nonhematologic adverse events were seen in 18 patients (39%) and included cardiac arrythmias, pulmonary edema, and hyperbilirubinemia. Significant improvement in renal function, defined as an increase in flomerular filtration rate (GFR) by 25% above baseline, was seen in 15 patients (32%). Kaplan-Meier estimates of 3-year progression-free survival (PFS) and overall survival (OS) were 36% and 64%, respectively. In conclusion, auto HSCT can be offered to patients with MM and renal failure with acceptable toxicity and with a significant improvement in renal function in approximately one-third of the transplanted patients. In this analysis, a melphalan (Mel) dose of 200 mg/m2 was not associated with an increase in toxicity or nonrelapse (Mel) mortality (NRM).

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

“…[19][20][21] Conversely, Parikh et al 22 evaluated outcomes of 46 patients with MM and renal failure and showed that MEL200 was not associated with increased toxicity and renal function improved in 32% of patients. Despite these conflicting data, major working groups such as IMWG and ABSMT recommend reducing the dose from 200 to 100-140 mg/m 2 in patients with CrCl o 60 mL/min based on decreased tolerability in this population.…”

“…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

“…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.…”

“…[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.…”

Renal allografts in plasma cell myeloma hematopoietic cell graft recipients: on the verge of an explosion?

“…16,17 In fact, several manuscripts reported the finding of some patients achieving hemodialysis independence after autologous HCT. 15,18,19 Variables predicting recovery from hemodialysis included requiring dialysis for o6 months prior to undertaking autologous HCT, attainment of complete CR or near-CR and creatinine clearance at time of autologous HCT 410 mL/min.…”