Elimination of minimal residual disease in chronic lymphocytic leukemia using allogeneic stem cell transplantation

The kinetics of minimal residual disease (MRD) in peripheral blood were prospectively measured using real-time immunoglobulin heavy chain polymerase chain reaction (PCR) in nine patients with unmutated chronic lymphocytic leukemia (CLL) after non-myeloablative allogeneic stem cell transplantation (allo-NST). NST conditioning provided only a moderate reduction in median MRD levels (5.4x10-2 pretransplant vs. 5.0x10-3 at +3 months). However, after withdrawal of immunosuppression, MRD levels progressively declined to 5.0x10-5 at +5 months and to MRD negativity at +12 months in seven of nine patients. With a median follow-up of 40 months (range 31–53 months), six of these seven patients remained in continuing clinical and molecular remission. In one patient, however, CLL relapsed as high-grade gastric lymphoma 3 years post-allo-NST despite long-term and ongoing MRD negativity in the peripheral blood. These results, taken together, show for the first time that a progressive decline in MRD levels to negativity can be obtained following NST for unmutated CLL, suggesting a crucial role for graft-versus-leukemia activity-mediated immunotherapy in complete disease eradication in this subset of high-risk patients. [>Read full article in PDF]