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An Organotypic High Throughput System for Characterization of Drug Sensitivity of Primary Multiple Myeloma Cells
Published on: July 15, 2015
Discrepancia en la estimación de la TFG para la dosificación de melfalán en pacientes con mieloma múltiple en
Benjamin Teruel1, Ashley L Golbus1, Elaine Park1
1Department of Medicine, Medical University of South Carolina, Charleston, SC, USA.
Background:
Accurate renal dosing of high dose melphalan as conditioning chemotherapy is critical for patients with multiple myeloma undergoing autologous stem cell transplant (ASCT). In clinical practice, serum creatinine (sCr) is used to eGFR for dosing calculations. The objective of our study was to compare sCr based eGFR to serum cystatin C based eGFR for melphalan dosing in patients undergoing ASCT for multiple myeloma to determine discrepancies in dosing and the effect on patient centered outcomes including chemotherapy-related toxicity, hospitalization and to assess IMWG response criteria at 3 and 12 months.
Methods:
We conducted a retrospective study including 76 patients with multiple myeloma who received melphalan conditioning before ASCT. Melphalan dosing in all patients was based on pre-transplant eGFR calculated from sCr (200 mg/m2 for eGFR >50 mL/min, 140 mg/m2 for eGFR < 50 mL/min). We calculated eGFR using both sCr and cystatin C levels prior to transplantation and observed the 30-day hospitalization from symptoms of melphalan toxicity. We identified a discordant patient group, whose cystatin C eGFR was calculated less than 50 mL/min compared to sCr eGFR >50 mL/min and would have qualified for a reduced melphalan dose.
Results:
Of 76 patients, 13 (17%) were identified as having received a higher than intended dose of melphalan when eGFR was estimated using sCr rather than cystatin C (200 mg/m2 rather than 140 mg/m2, "discordant dosing"). 100% of discordant patients were hospitalized within 30 days of melphalan dosing compared to 60% of the concordant patients whose eGFR was greater than 50 mL/min with both cystatin C and sCr based eGFR, with melphalan dosing 200 mg/m2 (p = 0.006). Furthermore, patients with discordant dosing had a significantly longer hospitalization duration of 7days compared to 2.5 days in patients with concordant dosing (p=0.0014). More patients qualified for dose reduction using cystatin C based eGFR compared to combined sCr-cystatin C based eGFR (p=0.02).
Conclusions:
Discordance between creatinine- and cystatin C-based eGFR calculations in ASCT patients was linked to inconsistent melphalan dosing and associated with an increase in adverse outcomes.
