The Early- and Intermediate-Term Toxicity to Primitive Hematopoietic Progenitor Cells of Three Chemotherapy Regimens for Advanced Hodgkin Lymphoma

The early stem cell reservoir can be impaired by a few cycles of chemotherapy, and this impairment might persist after normalization of peripheral cytopenias. We directly evaluated the damage caused to marrow progenitor cells by 3 currently used chemotherapy regimens for advanced Hodgkin lymphoma. Bone marrow samples from 37 patients randomly treated according to either the ABVD (doxorubicin/bleomycin/vinblastine/dacarbazine), COPPEBVCAD (cyclophosphamide/vincristine/procarbazine/prednisone/epirubicin/bleomycin/vinblastine/lomustine/melphalan/vindesine), or BEACOPP (bleomycin/etoposide/doxorubicin/cyclophosphamide/vincristine/procarbazine/prednisone)schedule were taken a few days before the start of chemotherapy and 30 days and 6 months after its completion. Samples were cryopreserved, thawed in a single session, and cultured for 5 weeks to detect long-term culture-initiating cells (LTC-IC). On the basis of the numbers of LTC-IC detected and of their relative variations, the ABVD regimen was associated with the least early reduction and the best late recovery of LTC-IC. COPPEBVCAD produced the greatest early damage, but recovery was nearly complete by 6 months. BEACOPP caused intermediate early toxicity that persisted at 6 months. The different late toxicity exerted on marrow progenitors by these chemotherapy regimens should be carefully weighed in relation to both the expected early response rate and subsequent possibility of rescue in the case of first treatment failure.