Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies

J Clin Oncol. 1998 Aug;16(8):2817-24. doi: 10.1200/JCO.1998.16.8.2817.


Purpose: To investigate the use of a nonmyeloablative fludarabine-based preparative regimen to produce sufficient immunosuppression to allow engraftment of allogeneic stem cells and induction of graft-versus-leukemia/lymphoma (GVL) as the primary treatment modality for patients with chronic lymphocytic leukemia (CLL) and lymphoma.

Patients and methods: Fifteen patients were studied. Six patients were in advanced refractory relapse, and induction therapy had failed in two patients. Patients with CLL or low-grade lymphoma received fludarabine 90 to 150 mg/m2 and cyclophosphamide 900 to 2,000 mg/m2. Patients with intermediate-grade lymphoma or in Richter's transformation received cisplatin 25 mg/m2 daily for 4 days; fludarabine 30 mg/m2; and cytarabine 500 mg/m2 daily for 2 days. Chemotherapy was followed by allogeneic stem-cell infusion from HLA-identical siblings. Patients with residual malignant cells or mixed chimerism could receive a donor lymphocyte infusion of 0.5 to 2 x 10(8) mononuclear cells/kg 2 to 3 months posttransplantation if graft-versus-host disease (GVHD) was not present.

Results: Eleven patients had engraftment of donor cells, and the remaining four patients promptly recovered autologous hematopoiesis. Eight of 11 patients achieved a complete response (CR). Five of six patients (83.3%) with chemosensitive disease continue to be alive compared with two of nine patients (22.2%) who had refractory or untested disease at the time of study entry (P = .04).

Conclusion: These findings indicate the feasibility of allogeneic hematopoietic transplantation with a nonablative preparative regimen to produce engraftment and GVL against lymphoid malignancies. The ability to induce remissions with donor lymphocyte infusion in patients with CLL, Richter's, and low-grade and intermediate-grade lymphoma is direct evidence of GVL activity against these diseases. This approach appears to be most promising in patients with chemotherapy-responsive disease and low tumor burden.

MeSH terms

  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Combined Modality Therapy
  • Female
  • Graft Enhancement, Immunologic*
  • Graft vs Host Disease / prevention & control
  • Graft vs Host Reaction
  • Hematopoiesis
  • Hematopoietic Stem Cell Transplantation*
  • Humans
  • Immunosuppressive Agents / therapeutic use*
  • Leukemia, Lymphocytic, Chronic, B-Cell / therapy*
  • Lymphoma, Non-Hodgkin / therapy*
  • Male
  • Middle Aged
  • Recurrence
  • Remission Induction
  • Vidarabine / analogs & derivatives
  • Vidarabine / therapeutic use


  • Immunosuppressive Agents
  • Vidarabine
  • fludarabine