Autologous bone marrow support for submyeloablative chemotherapy dose intensification in canine lymphoma

We are studying the clinical utility of chemotherapy dose intensification in the submyeloablative range, using autologous bone marrow as support to prevent toxicity. Canine lymphoma (CL) is chemosensitive but relapses frequently, and serves as a comparative model for chemotherapy. We have treated CL using an experimental protocol based on a standard dose CL protocol followed by escalating cyclophosphamide (CXN) with autologous marrow support. The escalation uses cohorts of 3 dogs, beginning at 300 mg/m2 IV CXN (standard canine dose is 200 mg/m2). Pet dogs with CL receive standard chemotherapy for remission induction, followed by recombinant canine G-CSF (Amgen, Inc.), then marrow is harvested and cryopreserved. Dogs then receive a single high dose of CXN with mesna, and marrow re-infusion on an outpatient basis; oral antibiotics are given until recovery. Three cohorts of escalation are complete with a fourth underway. The current dose of CXN is 500 mg/m2. No dog has been hospitalized for treatment-related toxicity. Neutropenia and thrombocytopenia but no fever, sepsis, or bleeding have occurred. A schedule effect has been observed, indicating that re-infusion of marrow at 48 and 96 hours post-CXN is more protective than one infusion at 48 hours. Using mesna and autologous marrow, the standard canine CXN dose can be more than doubled. The median remission is approximately 10% longer than that of historical controls.