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We report the case of a patient with lymphoma of the salivary gland, at first diagnosed as lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but later found to infiltrate the bone marrow. At diagnosis, the patient had a polyclonal increase of gamma-globulins. Five years after initial diagnosis, the patient presented with monoclonal gammopathy and infiltration of the bone marrow with neoplastic cells. Initially, the patient had received chemotherapy with different protocols (including etoposide, cyclophosphamide, fludarabin, methotrexate, and vincristine), none of which induced a lasting response. Therapy with rituximab (chimeric anti-CD20 monoclonal antibody) finally led to partial remission. Eighteen months after rituximab, progressive lymphoma in the abdomen and a monoclonal gammopathy developed. The bone marrow showed infiltration by lymphoplasmacytoid cells (monoclonal expression of the light-chain type lambda, positive for CD20, heterogeneous expression of CD45). The patient achieved another short clinical response with 4 cycles of the CHOP-protocol, but soon the lymphoma progressed again. Five years and 8 months after the initial diagnosis, the patient died from septicemia and progressive lymphoma. By polymerase chain reaction (PCR) for the IgH gene it was shown that lymphoma cells were initially oligoclonal in the salivary gland and, later, biclonal in the bone marrow. Sequencing of two bands of apparently same length showed that these manifestations of lymphoma were not identical. Taken together, our data show that the initial low-grade oligoclonal MALT lymphoma was no longer present and a more aggressive biclonal lymphoma with plasmacytoid differentiation had developed. The new lymphoma was clonally distinct and produced high amounts of monoclonal IgG lambda by immunoelectrophoresis. The relationship of the second lymphoma to the initial MALT lymphoma is discussed., (Copyright 2002 Wiley-Liss, Inc.)

Methotrexate and 5-FU were given sequentially with a 7-hour interval to 43 evaluable patients with heavily pretreated metastatic breast cancer. Partial remissions were seen in 12 patients (28%), indicating efficacy of this regimen in patients resistant to the conventional simultaneous application of these drugs.

Microangiopathic hemolytic anemia (MAHA) has long been recognized as a rare complication in far-advanced malignant tumors. Recently several patients have been described in whom MAHA and renal insufficiency developed as a result of mitomycin therapy. We here describe another five such cases among 50 patients treated with mitomycin. All five cases were observed among the 14 patients who had received four or more doses of the drug. We conclude that MAHA is a frequent and potentially fatal complication of long-term mitomycin treatment. Careful monitoring for the early appearance of schistocytes is mandatory as the syndrome tends to be self-limited if this therapy is discontinued early.

Mafosfamide-cyclohexylamine is a new oxazaphosphorine derivative. It was chosen for phase-I clinical testing because of an expected higher therapeutic index and lack of complete cross resistance in animal tumors compared to cyclophosphamide. The schedule consisted of a single iv dose repeated every three weeks. The compound was found to cause as it's dose limiting toxicity severe pain along the injected vein and acute irritation of mucous membranes. The maximal tolerated dose was around 1000 mg/m2 given as a slow infusion over 2-3 hours. Hematological toxicity was mild. A limited phase-I study with the lysine salt of mafosfamide showed an identical type of toxicity. Mafosfamide given iv in a high-dose intermittent schedule is of little interest for further clinical trials. It is probable, that the severe venous pain and the mucosal irritation are caused by the high local concentration of 4-hydroxy-cyclophosphamide or by a metabolite. An oxazaphosphorine derivative undergoing slower hydrolysis therefore leading to lower active drug concentrations within the injected vein may be more promising.