Treatment of Leukemic Meningeosis by CD 14 Depleted Adoptive Intrathecal Cell Therapy.

Background: Leukemic relapse within the central nervous system (CNS) is generally difficult to treat and results in poor outcome. Limiting factors for effective treatment are mainly extended neurotoxicity and availability of only few agents that will effectively act across the blood brain barrier (BBB). Although graft versus leukemia effects after allogeneic stem cell transplantation are well documented, its application is not recommended in patients with CNS disease. Since the CNS represents an immunologically privileged organ, conventional donor lymphocyte infusion (DLI) has not proven to be effective in CNS relapse situation after stem cell transplantation. Here we present results from three patients suffering from isolated CNS relapse of CML or AML after allogeneic stem cell transplantation receiving for the first time intrathecal cell therapy using CD14 depleted peripheral blood mononuclear cells from their allogeneic donor. Besides leukemic blast cell counts of the CSF molecular genetic analyses for chimerism as well as for translocations were applied for monitoring in addition to MRI and to neuroclinical symptoms.

Results: Up to eight consecutive CD14 depleted intrathecal infusions were applied in escalating doses starting at 1x10⁶ CD3+ cells. In all cases we did not observe any immediate or delayed side effects post application. In the case of the CML patient we observed disappearance of the leukemic blasts and of bcr-abl translocations and reversal to full donor chimerism of the CSF. In one AML patient we observed a transient disappearance of leukemic blasts, followed by a delayed increase. No clear and sustained response was recorded in the other AML patient. All patients are still under observation (9–14 months) and remained full chimeras in peripheral blood and bone marrow; however, the AML patients meanwhile developed chloroma lesions.

Conclusion: Intrathecal DLI for CNS relapse of leukemia after allogeneic stem cell transplantation is a new still experimental approach. The first applications indicate no side effects e.g. cerebral or meningeal GVHD and a possible efficacy in CNS relapse of CML. This new approach merits further investigation in the setting of a clinical trial.