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Updated: Apr 3, 2026
Percutaneous Hepatic Perfusion PHP with Melphalan as a Treatment for Unresectable Metastases Confined to the Liver
Published on: July 31, 2016
A case of melphalan sustained accumulation in an 80-year old patient
Pierre-Alain Jolivot1,2, Vianney Poinsignon3, Angelo Paci3
1Service de Pharmacie, Hôpital Saint-Antoine, Assistance Publique - Hôpitaux de Paris, 75012, Paris, France. pierrealain.jolivot@aphp.fr.
Abstract:
Case We report the case of melphalan accumulation in an 80-year old female with multiple myeloma. Her initial health status was good except for a moderate chronic renal failure (estimated glomerular filtration rate: 31 ml/min) and anemia. Among other drugs, her usual treatment included trimethoprim/sulfamethoxazole and the patient received melphalan from day 1 to day 4 for multiple myeloma. On day 13, she was admitted in intensive care unit for acute renal failure and severe sepsis with pancytopenia. Usual treatments were stopped. Melphalan blood concentrations were 123.6 ng/ml on day 16 and 87.5 ng/ml on day 17 while cerebrospinal fluid concentration was 173.8 ng/ml on day 25. Patient recovered on day 30. Melphalan accumulation may be explained by substrate competition between sulfamethoxazole and melphalan in metabolism pathway and chronic renal failure. Conclusion close clinical and renal monitoring should be performed in patient receiving melphalan and sulfamethoxazole.
Insights
Melphalan accumulation occurred in a multiple myeloma patient with renal failure, exacerbated by trimethoprim/sulfamethoxazole. Close monitoring of renal function is crucial when these drugs are co-administered.
Area of Science:
- Pharmacology
- Nephrology
- Oncology
Background:
- Multiple myeloma is a hematologic malignancy.
- Melphalan is a chemotherapeutic agent used in multiple myeloma treatment.
- Chronic renal failure can impact drug metabolism and excretion.
Observation:
- An 80-year-old female with multiple myeloma and chronic renal failure experienced melphalan accumulation.
- The patient was treated with melphalan and trimethoprim/sulfamethoxazole.
- She developed acute renal failure, sepsis, and pancytopenia, with high melphalan levels detected in blood and cerebrospinal fluid.
Findings:
- Melphalan accumulation was observed, indicated by elevated blood and cerebrospinal fluid concentrations.
- The accumulation is hypothesized to result from competitive inhibition of metabolic pathways by trimethoprim/sulfamethoxazole and impaired renal excretion due to pre-existing chronic renal failure.
- These factors likely contributed to the patient's severe adverse events, including acute renal failure and pancytopenia.
Implications:
- This case highlights the potential for severe drug interactions and toxicity when melphalan is co-administered with trimethoprim/sulfamethoxazole, particularly in patients with impaired renal function.
- It underscores the necessity for vigilant clinical and renal monitoring in such patients to prevent adverse events.
- Optimizing melphalan dosing and monitoring drug levels may be critical for improving patient outcomes in multiple myeloma treatment.
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