Monoclonal gammopathy after low-grade MALT lymphoma: evidence for a second neoplasm.

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.

Phase-I study of mafosfamide-cyclohexylamine (ASTA-Z-7557, NSC 345 842) and limited phase-I data on mafosfamide-lysine.

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.

Sequential methotrexate and 5-FU in breast cancer resistant to the conventional application of these drugs.

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, a frequent complication of mitomycin therapy in cancer patients.

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.

Lack of response in nine patients with breast cancer treated with fibroblast interferon.

Nine patients with metastatic breast cancer were treated with a minimum of 6 X 10(6) U/day of beta-interferon (IFN-beta) for at least 6 weeks. In patients whose disease did not progress during this period treatment was continued to a maximum of 13 weeks, while in other patients doses were escalated. With daily treatments over 3 weeks the maximum tolerated dose was found to be around 60 X 10(6) U/day. Fever occurred regularly. The dose-limiting toxicities were granulocytopenia and increasing liver enzymes. No objective remissions were observed. One patient showed stable disease after her cancer en cuirasse had rapidly progressed under chemotherapy. One patient each with nasopharyngeal carcinoma and fibrous sarcoma were also treated without success. IFN-beta at this moderately toxic dose given over a period of 6-13 weeks is of no clinical value in the treatment of metastatic breast cancer in women.

[Microangiopathic haemolytic anaemia as a complication of mitomycin C treatment (author's transl)]. / Mikroangiopathische hämolytische Anämie als Komplikation bei Mitomycin-C-Therapie.

Microangiopathic haemolytic anaemia developed in 5 (out of 14) patients treated with mitomycin C combinations, having received 4 or more treatment cycles. This finding necessitates restricted use of broad and longterm use of mitomycin C, particularly in view of the occasionally fatal outcome of this toxic complication. Adjuvant treatment with mitomycin C does not appear acceptable any longer. Patients treated with mitomycin C should be monitored carefully for occurrence of schistocytosis and platelet deficiency as very early signs of microangiopathic haemolytic anaemia.

[A modified MOPP regimen in the treatment of Hodgkin's disease stage III B and IV (author's transl)]. / Therapieergebnisse bei Lymphogranulomatose im Stadium III B und IV mit einem modifizierten MOPP-Schema.

In a retrospective study 80 patients with Hodgkin's disease of stage III B (n = 32) and IV (n = 48) were investigated, who had been treated with a modified MOPP regimen. 28 patients (35%) were previously untreated. A completed remission was reached in 51 patients, a partial remission in 16, and 13 patients failed to respond. 16 patients had died in the observation period. Complete remissions were twice as frequent with 90% in stage III as compared with 45% in stage IV. The group of patients surviving 4 years was 92% in stage III and 62% in stage IV.

[Polychemotherapy in non-hodgkin lymphoma with a modified MOPP scheme (author's transl)]. / Polychemotherapie bei Nicht-Hodgkin-Lymphomen mit einem modifizierten MOPP-Schema.

64 patients with extensive non-Hodgkin lymphomas were treated with a modified MOPP scheme. 41 patients had stage IV disease. 59 patients responded to treatment. In 22 cases complete remission was obtained and in 37 cases partial remission. The proportion of complete remissions was the same for reticulosarcoma (9 out of 28) and lymphosarcoma (7 out of 22). The remission rate for Brill-Symmers disease was higher (6 out of 14). For patients with lymphosarcoma the average duration of complete remission was 26.9 months and for patients with reticulosarcoma 25 months. 42 of the 59 patients who responded to treatment survived one year, 33 of them two or more years. After a two-year period there were no more deaths.

[On the mechanism of ascorbic acid induced methemoglobin reduction of human erythrocytes (author's transl)]. / Zum Mechanismus der Methämoglobinreduktion in menschlichen Erythrozyten durch Ascorbinsäure.

Ascorbic acid and dehydroascorbic acid penetrate the human erythrocyte membrane. In vitro methemoglobin is reduced nonenzymatically by both substances in concentrations of 10(-2) M to 10(-3) M. Dehydroascorbic acid is reduced nonenzymatically to ascorbic acid by GSH, even with low GSH-content of erythrocytes. Under physiological conditions ascorbic acid induced methemoglobin reduction is far less important than reduction by the NADH dependent methemoglobin reductase system. In methemoglobinemic conditions caused by toxic effects or by congenital methemoglobin reductase deficiency treatment with ascorbic acid is possible. However, critically increased methemoglobin content of the blood higher than 30% makes therapy with methylene blue necessary.

[Culture of leukocytes of patients with hairy cell leukaemia in the diffusion chamber (author's transl)]. / Kulturverhalten weisser Blutzellen bei Patienten mit Haarzell-Leukämie in der Diffusionskammer.

Peripheral blood cells from patients with hairy cell leukaemia were cultured in diffusion chambers implanted intraperitoneally. Proliferation of hairy cells could be observed in all patients. Granulo-, erythro- and monocytopoiesis showed no difference of proliferation and differentiation as compared to normal persons. This demonstrates that the presence of hairy cells in the culture did not influence the growth pattern of the residual haemopoiesis. From this result it can be additionally supposed that patients have a regular content of haemopoietic stem cells in peripheral blood. However the growth of lymphocytes and plasmacells showed a significant difference compared with normal persons. The cause is unknown as yet.