From July 1983 to January 1991 a total of 622 patients were randomized (585 eligible) to compare the effects of hydroxyurea, interferon alpha (IFN), and busulfan on the duration of chronic phase, and survival. Further goals included the determination of prognostic parameters. 598 CML patients were documented and 575 evaluable. The Ph-status was known for 547 patients. 89.4% of the patients were Ph-positive (+). 11% had additional chromosome aberrations. The median survival of Ph+ patients by now is 4.2 years, that of Ph-patients 1.4 years. Ph-negative patients are older, tend to have lower cell counts and, as a group are more ill at diagnosis. A survival difference of about one year is expected between busulfan and hydroxyurea treated patients. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, number of erythroblasts and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined which was superior to Sokal's score in the study population. 164 patients were randomized to receive IFN. In 54 patients (33%) IFN had to be terminated because of adverse effects, therapy resistance or other reasons. Clinically relevant neutralizing antibodies were detected in 9 cases. Most frequent adverse events were flu-like symptoms in 74%, gastrointestinal symptoms in 52%, and neurologic-psychiatric symptoms in 30% of patients. Reduction of the Ph-chromosome was observed in 13% of evaluable patients (10 of 75). In 4 patients complete cytogenetic remissions were observed, in three of these ongoing. Cytogenetic responders have a survival advantage. Interferon treated Philadelphia-negative CML patients have no survival disadvantage. The study is expected to allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

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.

We report the case of a patient with lymphoma of the salivary gland, at ®rst diagnosed as lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) but later found to in®ltrate the bone marrow. At diagnosis, the patient had a polyclonal increase of gammaglobulins. Five years after initial diagnosis, the patient presented with monoclonal gammopathy and in®ltration of the bone marrow with neoplastic cells. Initially, the patient had received chemotherapy with different protocols (including etoposide, cyclophosphamide,¯udarabin, methotrexate, and vincristine), none of which induced a lasting response. Therapy with rituximab (chimeric anti-CD20 monoclonal antibody) ®nally led to partial remission. Eighteen months after rituximab, progressive lymphoma in the abdomen and a monoclonal gammopathy developed. The bone marrow showed in®ltration 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. Am.

In einer multizentrischen Studie wird geprüft, ob der Einsatz von Hydroxyurea oder von Interferon alpha anstatt von Bulsulfan die Dauer der chronischen Phase bei Patienten mit Philadelphia-Chromo-som-positiver CML verlängert. Zusätzliche Ziele sind die Prüfung, ob sich der Typ der Krankheitsevolution und die terminalen Phasen bei den verschiedenen Therapiegruppen unterscheiden, sowie die pro-, spektive Erkennung von Prognosekriterien für die Dauer der chronischen Phase. Bis zum 5.9.1990 waren 593 CML-Patienten randomisiert, 221 für Busulfan, 228 für Hydroxyurea und 144 für Interferon alpha. Das Durchschnittsalter aller Patienten liegt bei etwa 51 Jahren. Bis zum Stichtag am 30.4.1990 hatten 106 Patienten das Ende der chronischen Phase erreicht, 126 waren verstorben. Die mediane Überlebenszeit der Philadelphia-positiven Patienten betrug 3,95 Jahre, die aller Patienten 3,75 Jahre. Die mittlere Beobachtungszeit betrug 1,34 (1,60) Jahre. Erwartungsgemäß besteht bisher noch kein signifikanter Unterschied zwischen den drei Studienarmen, wenn auch im Hydroxyurea-Arm weniger Nebenwirkungen beobachtet wurden.