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Gastrointestinal toxicity of high-dose melphalan in autologous hematopoietic stem cell transplantation: identification of risk factors and a benchmark for experimental therapies
Open accessAbstract
Gastrointestinal side effects are the dose-limiting toxicity of high-dose melphalan (HDM) in autologous hematopoietic stem-cell transplantation, but there are limited contemporary data on the incidence and severity of gastrointestinal toxicity associated with this regimen. We retrospectively studied 100 consecutive patients who received HDM alone or in combination with other conditioning agents. Patients had a median age of 56 (range 20-73); underlying diseases were myeloma (42%), lymphoma (42%), or amyloidosis (16%) and melphalan dosages were 200 (40%), 140 (59%), or 100 mg/m 2 (1%). Ninety-seven percent of patients experienced diarrhea with a range of 1-18 bowel movements per day, 88% developed nausea, and 60% experienced vomiting. Abdominal CT scans rarely altered patient management, but stool studies were useful in identifying a treatable infectious source. Grade ≥ 2 diarrhea was associated with longer duration of diarrhea, longer length of stay, worse hypoalbuminemia, higher use of antibiotics, abdominal imaging, electrolyte repletions, and anti-diarrheal agents. Risk factors for severe diarrhea were female sex, melphalan dose, age > 50, creatinine clearance < 60 ml/min, and having a plasma cell neoplasm as opposed to lymphoma. Female sex was also associated with more severe nausea and vomiting. In summary, diarrhea remains an important toxicity of HDM and novel therapies for chemotherapy-induced diarrhea for patients undergoing stem-cell transplantation are needed. Grade 2 or higher diarrhea is associated with significant clinical consequences and should be used as the primary endpoint in prospective clinical trials.
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Non-targeted drugs can harm normal healthy cells, leading to adverse effects such as gastrointestinal problems, myelosuppression, alopecia, anemia, liver and kidney impairment, and increased risk of infections.
“Non-targeted drugs, while effective, can also harm normal healthy cells, leading to adverse effects such as gastrointestinal problems (nausea, vomiting, diarrhea, and constipation) [57], myelosuppression (reduction in white blood cells and platelets), alopecia, anemia, liver and kidney impairment, and an increased risk of infections [58, 59].”
From Multiple myeloma: signaling pathways and targeted therapy (2024) · cites this paper as [57]
The Introduction and Results > GI toxicities report nausea, vomiting, and diarrhea as toxicities of high-dose melphalan. The paper does not identify constipation as a toxicity. This citation is attached to the gastrointestinal-effects clause, not the later list of adverse effects cited to other sources. (LLM, conf=0.88)
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Research works printed but not linked: 19
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Cited by
Sorted by citations
Multiple myeloma: signaling pathways and targeted therapy
Lu, Q., Yang, D., Li, H., Niu, T., & Tong, A. (2024) · Molecular biomedicine · doi:10.1186/s43556-024-00188-w · Cited by 90
Metadata
- Authors
- Gordillo, C. A., Parmar, S., Blanco, M., Delille, E. M., Assal, A., Mapara, M., & Reshef, R.
- Affiliations
- Columbia University Irving Medical Center (US)
- NewYork–Presbyterian Hospital (US)
- Corresponding author
- Reshef, Ran
- Venue
- Annals of Hematology
- Published
- 2021-01-03
- Volume
- 100
- Issue
- 7
- Pages
- 1863-1870
- ISSN
- 0939-5555 (ISSN-L)
- 1432-0584
- PMC
- PMC11531332
- OpenAlex
- W3119899800
- Cited by
- 29
- References
- 0
- Citations by year
- 2026: 7 · 2025: 4 · 2024: 6 · 2023: 8 · 2022: 2 · 2021: 1
- FWCI
- 2.78
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Annals of Hematology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (R01HL14342)
- U.S. Department of Defense (CA180898)
- Topics
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Surgery › Nausea and vomiting management
- Keywords
- melphalan, high-dose chemotherapy, autologous stem cell transplantation, gastrointestinal toxicity, chemotherapy-induced diarrhea, nausea and vomiting, risk factors, plasma cell neoplasms, multiple myeloma, lymphoma, amyloidosis, conditioning regimen, hypoalbuminemia, antidiarrheal agents
- MeSH terms
- Adult, Aged, Dose-Response Relationship, Drug, Female, Gastrointestinal Diseases, Humans, Male, Melphalan, Middle Aged, Prognosis, Retrospective Studies, Risk Factors, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Transplantation Conditioning, Hematologic Neoplasms, Benchmarking, Therapies, Investigational, Young Adult, Drug-Related Side Effects and Adverse Reactions
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