[Treatment of aggressive non-Hodgkin's lymphoma with the ProMACE- CytaBOM protocol]

The Working Formulation Classification (for clinical use) divides non-Hodgkin's lymphoma (NHL), according to the nature of the disease and response to therapy into the low, medium and high risk lymphomas. Although these subgroups include different pathohistological types of NHL, they are considered sufficiently homogenous for joint therapy planning [1]. The first generation protocol (CHOP) managed to achieve complete remission (CR) in 50-55% of patients with 30-35% of survival rate [2]. A large four-branch comparative study of SWOG group compared CHOP as the first generation protocol with the third generation protocols ProMACE CytaBOM, m-BACOD and MCOD-D. The results have shown a similar CR and survival rates, so that CHOP is considered a gold standard for the treatment of aggressive NHL [6]. In the light of individual reports stating a high CR rate in the treatment of aggressive NHL by ProMACE CytaBOM [3-5] we present our experience and observations related to the use of this protocol.

Over the period from 1991 through May 1996 at the Department of Lymphoproliferative Diseases, Institute of Haematology, Clinical Centre of Serbia in Belgrade, we treated 25 patients with pathohistologic evidence of medium to high risk lymphomas, where cases of lymphoblast lymphoma and Burkit's lymphoma were excluded. The median follow-up was 27 months (maximum 63 months).

Four of 25 patients were > 60 years. Three of these died. Pathohistological analysis revealed that of 20 cases of medium risk aggressive lymphoma five had diffuse, small cleaved cells, 7 had diffuse mixed and 8 diffuse centroblast cells. Although diffuse NHL with small cleaved cells is classified into clinically indolent lymphomas, two of five patients were in the fourth clinical stage, and three of five patients had a large tumorous mass. In the high risk group five patients had immunoblast lymphoma. Karnofsky index was high in 20/25. According to Ann Arbor criteria 19/25 patients were in IVCS and 7/25 had a large tumour mass. Most patients had clinical symptoms (21/25). Extranodal localization was confirmed in 19 patients. Bone marrow and hepatic infiltrations were most common: 9 and 6 patients, respectively. Eleven patients had a single extranodal localization, while 8 had 2 or more. The median follow-up was 27 months (maximum 63 months), and 21/25 (84%) patients responded to therapy (CR + PR). Complete remission was achieved in 14 patients (56%), and PR in 7 (28%) patients. In the CR group two died, and relapse developed in one after 28 months. In 11 cases CR is maintained. The average duration of CR was 16 months (3-38 months), and PR was maintained for 6 months (20 months in one case). The average survival was 24.5 months (range 3-53).

The fact that a half of adult patients with disseminated aggressive NHL can be cured with combined chemotherapy is the major oncological achievement in the last 20 years. The protocol combines 4-8 drugs, and the joint report of the SFOG group for lymphoma in over 1200 patients with lymphoma has shown that the second and third generation protocols are not more effective than the standard CHOP or CHOPBleom protocols [6]. The optimum therapeutic protocol in the treatment of aggressive lymphoma is still unpredictable due to the fact that it is inadequate to compare the results of individual institutions with the results of collaborative groups; there is also a significant difference in the prognostic factors in different research groups; there is no sufficient complete and published results that suggest the lower CR than the original reports (which may be related to the evaluation of tumour and remission). There are not sufficient data on the incidence of secondary carcinoma and leukaemia [1]. The decision on the therapy should be based on two lines of information: those related to each particular patient (age, associated diseases) and those related to the tumour (large mass, immunophenotyping, cytoge