Lymphomatous meningitis (LM) occurs in approximately 7–15% of patients with lymphoma and carries an extremely poor prognosis (Chamberlain et al. CNS Drugs 1998; 10:25; Chowdary & Chamberlain J Natl Compr Canc Netw 2005; 3:693). Intrathecal (IT) chemotherapy with standard agents (cytarabine, methotrexate and thiotepa) is limited by the need for multiple injections per week via lumbar puncture or an Ommaya reservoir. Liposomal cytarabine (DepoCyte®) has an extended half-life in cerebrospinal fluid that permits fortnightly administration, improving convenience and reducing the potential for injection-related trauma and infections. Thirty-two Spanish patients (median age 43.5 years [range 19–78]; 22 male) with NHL received IT liposomal cytarabine for the treatment of LM between 2004 and 2006 at 21 treatment centers. Half of the patients had diffuse large B-cell lymphoma (DLBCL; n = 16); the remainder had Burkitt's lymphoma (n = 4), T-cell NHL (n = 3), mucosa-associated lymphoid tissue lymphoma (n = 3), lymphoblastic lymphoma (n = 2), follicular lymphoma (n = 2) or primary CNS lymphoma (n = 1). A full histological diagnosis was not available for 1 patient. The dosage of liposomal cytarabine was 50 mg per cycle, with a median of 4 cycles (range 1–10). All patients received oral dexamethasone (4 mg 2–4 × daily for 4–7 days per cycle) as prophylaxis for chemical arachnoiditis. Neurological and cytological responses were obtained in 20 (62%; 16 complete responses, 4 partial responses; Figure 1) and 25 (78%) patients, respectively. Neurological progression was subsequently reported in 23 (72%) patients, with a median time to progression of 45 days (range 7–570). Twelve patients were still alive at the time of reporting, including 5 of 16 patients with DLBCL and 2 of 3 patients with T-cell NHL. Eighteen patients reported no adverse effects from treatment. The most commonly reported adverse effects were headache (n = 11), nausea (n = 4) and vomiting (n = 4). Data from this case series show that IT liposomal cytarabine is effective and well tolerated in the treatment of LM; the less intensive administration schedule of the agent may offer additional benefits to patients and their carers during the final months of life.
INTRODUCTION. Treatment with IFN and chemotherapy induces a significant improvement of PFS in patients with low-grade NHL, specially in patients with responsive disease. However, the best IFN schedule is still pending as benefits are observed when IFN is administered associated to the induction therapy or, as maintenance treatment or, in both treatment phases.
PURPOSE:To evaluate the effectiveness of adding interferon (IFN) alfa-2b to chemotherapy in the induction treatment of low-grade non-Hodgkin's lymphoma (NHL), and to assess the role of maintenance IFN.PATIENTS AND METHODS:A multicenter, two-phase controlled trial with double randomization was conducted in 155 patients with low-grade NHL. In the first randomization, 78 patients received cyclophosphamide, vincristine, and prednisone (CVP) and IFN, 3 MU/m2 three times a week for 3 months, and 77 patients received CVP alone. Responding patients were randomized to receive IFN for 1 year versus observation.RESULTS:Of 144 assessable patients, 73 received CVP + IFN and 71 received CVP. Responses were similar: CVP + IFN 79% versus CVP 76% (P = .62). The number of patients who did not complete the treatment was higher in the CVP + IFN group than in the CVP group (18% v 4%; P = .009), although the received dose-intensity of chemotherapy was comparable. Duration of response and progression-free survival (PFS) were significantly higher in the CVP + IFN group than in the CVP group (P = .0004). However, we observed no differences in overall survival (OS) (P = .30), with a median follow-up for the surviving patients of 3 years. Grade 3/4 granulocytopenia was the most frequent toxicity and was similar in both groups (33% v32%). Eighty-three (74%) of the 112 responding patients were randomized to maintenance IFN or observation. The duration of response was similar between 42 patients that received IFN compared with 41 control patients (P = .83), independently of treatment previously administered.CONCLUSION:Adding IFN alfa-2b to induction CVP in low-grade NHL did not induce a higher response rate, but it significantly increased the duration of the responses. We found significant differences in PFS that favored the patients who received CVP + IFN, but not in OS. To date, no additional benefit has been seen from the administration of IFN for maintenance.
We report the results of treatment with MACOP-B in 11 young patients with low grade lymphoma (LGL). Complete remission was obtained in 4 (57%) and partial remission in 3 (42.8%) of 7 evaluable patients. However, this aggressive chemotherapy has not offered any advantage because of an unacceptably high treatment-related morbidity and mortality (17%). Serious infection during neutropenia was the most common complication.
We describe here a patient with Philadelphia-positive chronic myeloid leukemia who had a hematologic and cytogenetic relapse after bone marrow transplantation. A diagnosis of accelerated phase was made when an additional malignant clone was detected. This clone was probably derived from the primitive Philadelphia clone, with duplication and rearrangement of the Philadelphia chromosome. The patient was treated with interferon alpha 2a and experienced a complete cytogenetic and molecular remission, with full reconstitution of the donor marrow.