High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy ( BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.