Induction of graft-versus-leukemia using flu-darabine-based allogeneic mini-transplants as treatment for lymphoid malignancies

Chronic lymphocytic leukemia (CLL) and lymphoma typically affect older, and often debilitated patients and only a small fraction have been considered eligible for transplantation therapies. As an alternative strategy, we evaluated induction of graft-versus-leukemia (GVL) as the primary treatment modality. We employed a non-myeloablative preparative regimen with the goal of producing sufficient immunosuppression to allow sustained engraftment of allogeneic blood progenitor cells and generation of a GVL effect. Nine patients were entered (5 with CLL, 4 with transformed lymphoma). Median age was 58 (range, 47-63). Fludarabine (FAMP)-based chemotherapy was used at conventional doses. Patients with CLL received cyclophosphamide at 300 rng/mVday on days(d) -5, -4, -3 and FAMP 30 mg/nr/d on d -5, -4, -3. Patients with lymphoma received cisplatin 25 mg/m2/d on d -6, -5, -4, -3, FAMP 30 mg/m2/d on d -4 and -3, and cytarabine 500 mg/m2/d on d -4 and -3. Allogeneic stem cell transplantation (ASCT) from HLA-identical donor was administered on d 0. No patients developed a non-hematologic toxicity of greater than 2. Six of the nine patients had evidence of engraftment by RFLP. The % of donor cells in the marrow ranged between 50 to 100%, at one month posttransplant. Four patients received donor lymphocyte infusions (DLI) at 55 to 100 d post transplant, to augment the GVL effect .One patient achieved an initial partial remission and converted to complete response (CR) months after DLL Of the engrafted patients, four achieved CR and two had decreased tumor burden. This indicates the feasibility of ASCT using a nonablative preparative regimen in CLL and lymphoma. If successful, this approach may be extended to other transplantation applications with a goal of reducing morbidity and treatment related mortality.