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Abstract: SA-PO145

One Serum Creatinine, Several Dosings of Cytotoxic Drugs: Different Estimations of Filtration Rate Influence Conditioning Intensity (N=959)

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Heinze, Luca-Marie, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Brueder, Nicole, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Talbot, Steven, Hannover Medical School, Institute for Laboratory Animal Science and Central Animal Laboratory, Hannover, Germany
  • Dammann, Elke, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Koehler, Sophia, Hannover Medical School, Enterprise Clinical Research Data Warehouse, Hannover, Germany
  • Ganser, Arnold, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Eder, Matthias, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Heuser, Michael, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany
  • Kielstein, Jan T., Academic Teaching Hospital Brunswick, Clinic for Nephrology, Rheumatology and Blood Purification, Brunswick, Germany
  • Beutel, Gernot, Hannover Medical School, Department of Hematology, Hemostaseology, Oncology and Stem Cell Transplantation, Hannover, Germany

Group or Team Name

  • HON Circle of the iCHOP initiative (www.ichop.eu)
Background

Allogeneic stem cell transplantation (alloSCT) is a potentially curative therapy for high-risk patients with hematologic diseases. However, since conditioning is based on classical chemotherapy, dose reduction of cytostatic drugs is required in case of impaired renal function. Our study aimed to evaluate different methods for estimating renal function using creatinine clearance (CrCl) and estimated glomerular filtration rate (eGFR) and to compare the calculated dosage of drugs.

Methods

Between 2003 and 2020, 1394 alloSCT were performed at our center. In 959 patients, clinical data were linked to serum creatinine (N=92,229) exported from our data warehouse. CrCl/eGFR was calculated with Cockcroft-Gault, MDRD, and CKD-EPI, classified according to KDIGO criteria, and compared against each other based on the creatinine before the start of conditioning. Within the current recommendations, the required dose reduction for each cytostatic drug was calculated based on the aforementioned methods.

Results

CrCl/eGFR show different results depending on the method used. Before conditioning, the proportion of patients with a GFR <60 ml/min was 4.4% (Cockcroft-Gault), 7.1% (MDRD) and 5.0% (CKD-EPI). The need for dose reduction ranged from 0.1% (cyclophosphamide) to 5.8% (fludarabine). In the case of fludarabine, the SmPC recommendation is based on CrCl and requires dose reduction in 8.4% of cases. Using MDRD, reduction would be necessary in 14.2% of cases, 5.8% more than with the SmPC recommendation. Applied to all conditioning regimens, the use of Cockroft-Gault causes the need for action in only a few cases, while MDRD displays a considerably higher rate of dose adjustments (Fig 1).

Conclusion

Dosing of cytotoxic drugs depends on renal function. Although Cockcroft-Gault is rarely used in the clinic nowadays, many dose adjustments still utilize this method. However, our data show that compared with MDRD or CKD-EPI, Cockcroft-Gault usually overestimates renal function. Since a rapid determination of renal function is currently unavailable, therapeutic success and toxicity predictions are hampered by the use of various methods.