Efficacious but insidious: a retrospective analysis of fludarabine-induced myelotoxicity using long-term culture-initiating cells in 100 follicular lymphoma patients
Language English Country Netherlands Media print-electronic
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
19654036
DOI
10.1016/j.exphem.2009.07.011
PII: S0301-472X(09)00312-9
Knihovny.cz E-resources
- MeSH
- Colony-Forming Units Assay MeSH
- Cyclophosphamide administration & dosage MeSH
- Dexamethasone administration & dosage MeSH
- Adult MeSH
- Doxorubicin administration & dosage MeSH
- Lymphoma, Follicular drug therapy pathology radiotherapy surgery MeSH
- Hematopoietic Stem Cells classification drug effects MeSH
- Interferon-alpha therapeutic use MeSH
- Combined Modality Therapy MeSH
- Bone Marrow drug effects pathology MeSH
- Middle Aged MeSH
- Humans MeSH
- Mitoxantrone administration & dosage MeSH
- Antibodies, Monoclonal administration & dosage MeSH
- Antibodies, Monoclonal, Murine-Derived MeSH
- Follow-Up Studies MeSH
- Bone Marrow Diseases chemically induced pathology MeSH
- Prednisone administration & dosage MeSH
- Procarbazine administration & dosage adverse effects toxicity MeSH
- Antimetabolites, Antineoplastic administration & dosage adverse effects toxicity MeSH
- Antineoplastic Combined Chemotherapy Protocols administration & dosage MeSH
- Retrospective Studies MeSH
- Rituximab MeSH
- Aged MeSH
- Peripheral Blood Stem Cell Transplantation MeSH
- Vidarabine administration & dosage adverse effects analogs & derivatives toxicity MeSH
- Vincristine administration & dosage MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Comparative Study MeSH
- Names of Substances
- Cyclophosphamide MeSH
- Dexamethasone MeSH
- Doxorubicin MeSH
- fludarabine MeSH Browser
- Interferon-alpha MeSH
- Mitoxantrone MeSH
- Antibodies, Monoclonal MeSH
- Antibodies, Monoclonal, Murine-Derived MeSH
- Prednisone MeSH
- Procarbazine MeSH
- Antimetabolites, Antineoplastic MeSH
- Rituximab MeSH
- Vidarabine MeSH
- Vincristine MeSH
OBJECTIVE: Fludarabine has been recognized as effective treatment in patients with follicular lymphoma (FL), but can induce myelotoxicity of unknown mechanism. MATERIALS AND METHODS: Myelotoxicity was assessed by cultivation of two types of hematopoietic progenitor cells: colony-forming units granulocyte-macrophage (CFU-GM) and long-term culture-initiating cells (LTC-IC). Pretreatment amounts of CFU-GM and LTC-IC were correlated to age, gender, stage of disease, bone marrow involvement, and previous therapy. Posttreatment comparison of CFU-GM and LTC-IC was performed after different regimens of chemotherapy: fludarabine-based (FND +/- R), procarbazine-based (COPP +/- R), and CHOP(cyclophosphamide, doxorubicin, vincristine, prednisone) +/- R(Rituximab). RESULTS: One-hundred patients (median age 55 years; 21 patients relapsed) treated for FL were analyzed. The total number of progenitor hematopoietic cells in both types of cultures varied in wide ranges; for LTC-IC between 0 and 874 cells/mL with a median of 77.71 cells/mL and for CFU-GM between 0 and 531 x 10(2) cells/mL with a median of 30.58 x 10(2) cells/mL. Bone marrow involvement, gender, stage of disease, or previous therapy had no influence on LTC-IC and CFU-GM counts. We identified an increase in LTC-IC, but not CFU-GM, associated with age (p = 0.01). Median figures for CFU-GM and LTC-IC were found to be significantly lower after FND +/- R and COPP +/- R than after CHOP +/- R therapy, compared to baseline values (p < 0.01). CONCLUSIONS: Fludarabine and procarbazine have a dramatic influence, especially on the most immature hematopoietic cells, mirrored in reduced numbers of LTC-IC. This finding is consistent with clinical observations (poor mobilization after fludarabine) and offers an insight into the mechanism of fludarabine-induced myelotoxicity.
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