Autologous Hematopoietic Stem Cell Transplantation in Multiple Myeloma Patients with Renal Insufficiency: a Single Centre Experience.

Multiple myeloma (MM) might be a cause a of the malignancy-related renal insufficiency, often present at diagnosis. Severity of it implicates further therapy. Patients with severe renal failure are generally excluded from high dose therapy even though they display a poor prognosis with conventional chemotherapy regimens. The goal of this study was to evaluate the eligibility and efficacy of autologous hematopoietic stem cell transplantation (AHCT) in MM patients with concomitant renal insufficiency. 239 MM patients were treated in our department with high-dose chemotherapy followed by AHCT between 1993 and 2009. Twenty of them (8%) were also diagnosed with renal impairment.

20 patients (8 women, 12 men), age 40-65 years (median 51) were enrolled. MM subtype at diagnosis was: IgG, n=14 (kappa-9, lambda-5); IgA kappa, n=1; light chain disease (LCD), n=4 (kappa-3, lambda-1); non-secretory, n=1. Chronic kidney disease (CKD) stage at MM diagnosis was 2-5 (median 3). One pt. was on chronic hemodialysis, two required plasmapheresis. Before AHCT pts. were treated with 1-4 (1) regimens, mainly VAD and CTD. 8/20 pts. received radiotherapy.

Mobilization regimen was high-dose cyclophosphamide in 8 and IVE (iphosphamide, etoposide, epirubicin) in 12 cases. Stem cell collection yield was effective in all pts. (median 17.6 (1.9 - 44.7) x 10e6 CD34+ cells/kg). Disease stage at AHSCT: CR n=6, VGPR n=2, PR n=12.

Renal function measured before transplantation significantly improved due to MM treatment compared to that at diagnosis, p=0.008. CKD stage before transplantation equaled 1-4 (median 2). The only one patient who initially required hemodialysis became dialysis independent before AHCT.

Conditioning regimen with melphalan (range 75-200mg/m²) was generally well tolerated. The median numbers of transplanted cells were following: NC 2.5 (1-7.6) x10e8/kg; CD34+ 7.9 (0.8-21.7) x 10e6/kg. All patients engrafted. Median regeneration time of granulocytes up to >0.5 G/l and of platelets to >50 G/l equaled 14 (12-19) and 14 (12-101) days, respectively. Transplant related mortality at day 100 was 0%. Mucositis, diarrhoea, bacterial and HSV infections were main complications after AHCT. Regeneration time, hospital stay, days of intravenous antibiotics or antifungal drugs administration and number of transfusion were comparable to pts. transplanted without renal impairment. No renal complications were observed. On the contrary creatinine clearance after transplantation showed trend towards further improvement compared to that before AHCT, p=0.07. The probability of overall (OS) and progression free (PFS) survival for studied group of pts. were 84% and 63%, respectively. Median observation time 2.3 years (0.1-12.5).

Our observation demonstrates that AHCT is an effective and well tolerated option for MM patients with mild or moderate renal insufficiency. Treatment before transplantation and also high-dose chemotherapy followed by AHCT may even improve renal function. No relationship between CKD and stem cell collection yield, engraftment or severity of post-transplant complications was observed in this group of patients.

No relevant conflicts of interest to declare.