| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2134994 | Experimental Hematology | 2009 | 8 Pages |
ObjectiveFludarabine has been recognized as effective treatment in patients with follicular lymphoma (FL), but can induce myelotoxicity of unknown mechanism.Materials and MethodsMyelotoxicity 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).ResultsOne-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 × 102 cells/mL with a median of 30.58 × 102 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).ConclusionsFludarabine 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.
