Abstract
12524 Background: CNS involvement is a grave complication of malignant lymphoma. Therapy traditionally includes intrathecal chemotherapy, radiotherapy and systemic chemotherapy for concomitant systemic lymphoma. However, optimal therapy has not been established thus far for CNS lymphoma. In this pilot study a combination of systemic high-dose (HD) methotrexate (MTX) and ifosfamide (IFO) was evaluated for toxicity and response rate. Methods: 10 patients (pts.) with CNS relapses of aggressive lymphoma (5 nodal DLBCL, 4 PCNSL/PIOL and 1 T-NHL) were treated. Nine pts. had intracerebral lesions, the meningeal compartment was involved in three. Three pts. had systemic manifestations. Median age was 63 years (32 - 83). Therapy consisted of 4g/m2 MTX (4h infusion on day 1) with dose adjustment for creatinine clearance (CC) < 100ml/min (CC/100 * 4g/m2) and 1.5 to 2g/m2/day IFO (3h infusion day 3 to 5). Supportive therapy included mesna and a leucovorin rescue beginning at 24h after start of MTX. Two pts. were treated with intrathecal chemotherapy before MTX/IFO. Results: A median of 4 cycles chemotherapy was administered. Treatment response was documented in 9 pts. (3 CR, 6 PR), and one patient had stable disease. The toxicity was mainly hematologic with grade 3/4 neutropenia in 6 pts., grade 3/4 thrombocytopenia in 4 pts. and grade 3 anemia in 2 pts. One pat. died from sepsis in neutropenia and one pat. with long-term corticosteroid therapy developed an aspergillus pneumonia grade 3. Nephrotoxicity grade 1/2 was observed in 6 pts.. Four pts. were further treated with HD chemotherapy followed by autologous stem cell transplantation or salvage radio-/chemotherapy. A median progression free survival of 6.5+ months (range 1–41+) for all pts. has been reached with persisting remission after 4 to 41 months in 5 pts.. Conclusions: Systemic combination therapy with MTX and IFO is feasible and exhibits a promising activity in CNS relapses of aggressive lymphoma. No significant financial relationships to disclose.
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