Autologous Transplantation As Consolidation Therapy for Primary and Secondary CNS Lymphoma- A Single Center Experience

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Introduction: Primary CNS lymphoma is a rare form of extranodal  Non Hodgkin’s lymphoma (NHL). Combination chemotherapy followed by whole brain radiation has remained the cornerstone of therapy. Relapse rates are high and delayed neurotoxicity, with severe cognitive dysfunction, is significant. High dose chemotherapy followed by autologous stem cell rescue has been used as consolidation in newly diagnosed patients and as salvage in times of relapse. This approach is considered promising.

Methods: Between 2001 and 2012 we have treated 12 patients with CNS lymphoma (primary and secondary) with high dose chemotherapy as primary consolidation therapy, in lieu of radiation. All patients  received “induction” with a high dose methotrexate containing regimen. Rituximab was used in 8 patients with B Cell NHL. Conditioning chemotherapy for trnaplant consisted of Thiotepa 300mg/m2 (on Days -8 and -7), Busulfan (targeted to achieve an AUC of 5000µMol x Min, as a single dose [from 2008] on days -6 through -3) and Cyclophosphamide 2000mg/m2 on days -3 and -2. Prior to 2008 Busulfan was given at a dose of 0.8mg/kg q6h for 12 doses. One patient received BEAM for conditioning. Stem cells reinfusion occurred on Day 0.Seizure prophylaxis was with Clonazepam or phenytoin. Palifermin was used for prophylaxis against mucositis. Granulocyte Colony Stimulating Factor was administered from Day +6 to facilitate count recovery.

Results: 12 patients with CNS lymphoma underwent an autologous stem cell transplant as primary consolidation. Median age at diagnosis was 56 (range 20-69). 10 patients had Primary CNS lymphoma (9 with Diffuse Large  B Cell Lymphoma  [DLCL]on morphology and 1 with T cell NHL NOS), and 2 had secondary CNS lymphoma (1 with Anaplastic  Large Cell lymphoma and 1 with meningeal relapse of DLCL). Median time to transplant was 8 months (range 4-24 months).  CSF involvement was present only in the 2 patients with secondary CNS NHL. There were no transplant related deaths. All patients developed mucositis, but none required intubation. One patient relapsed during conditioning therapy and was treated successfully with radiation. No VOD or hemorrhagic cystitis was seen. There was no delayed engraftment. Median follow-up post transplant is 68.5 months (range 16-130 months). 11 patients are alive. One patient relapsed soon after transplant but died 44 months later. The remaining 11 patients continue to be in remission.  2 patients have returned to college, 2 are gainfully employed and 3 are functioning retirees.

Conclusion: High dose chemotherapy with Thiotepa - Busulfan - Cyclophosphamide conditioning, is a highly effective consolidation therapy in patients with Primary CNS lymphoma. No delayed neurotoxicity is seen. This approach circumvents the toxicity of radiation, and may improve survival and quality of life, a concept that will need to be tested with a larger cohort.