| Title | Efficacious but insidious. A retrospective analysis of fludarabine-induced myelotoxicity using long-term culture -initiating cells in 100 follicular lymphoma patients. | | Author(s) | Janikova A, Koristek Z, Vinklarkova J, Pavlik T, Sticha M, Navratil M, Kral Z, Vasova I, Mayer J | | Institution | Department of Internal Medicine - Haematooncology, University Hospital and Faculty of Medicine of Masaryk University Brno, Czech Republic. | | Source | Exp Hematol 2009 Aug 1. | | Abstract | OBJECTIVE: Fludarabine has been recognized as effective treatment in patients with follicular lymphoma (FL), but can induce myelotoxicity of unknown mechanism.
PATIENTS 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). The pre-treatment amounts of CFU-GM and LTC-IC were correlated to age, sex, stage of disease, bone marrow involvement and previous therapy. The post-treatment comparison of CFU-GM and LTC-IC was performed after different regimens of chemotherapy: fludarabine-based (FND+/-R), procarbazine-based (COPP+/-R) and CHOP+/-R.
RESULTS: A 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- 874 with a median of 77.71 cells/ml and for CFU-GM between 0-531 with a median of 30.58 x 10(2) cells/ml. Bone marrow involvement, sex, 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 in CFU-GM associated with age (p=0.01). The 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. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19654036 |
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