The Evaluation of Clinical and Molecular Response to High-Dose Chemotherapy Protocol NHL BFM-90 in Adults with Anaplastic Large Cell ALK-Positive Lymphoma

Anaplastic large cell ALK-positive lymphoma (ALCL) is a rare disease in adult population and represents 3% of all lymphomas. It‘s characterized by the expression of surface antigen CD30, translocations involving gene 2p23, and leading to the formation of chimeric transcripts with ALK protein. The optimal treatment and predictive factors are not well defined in adult patients. The most commonly used regimens are CHOP-like programs, which have shown 30–65% 5-year overall survival (without stage stratification). The application of the protocol NHL BFM-90 in pediatric practice in Germany has improved the results of the treatment and allowed to achieve 80–100% overall survival rate (Reiter A. 2001). So we decided to initiate a pilot study aiming to intensity treatment approach in adults with ALCL.

to evaluate the efficacy of chemotherapy intensification with NHL BFM-90 protocol and to investigate the prognostic significance of molecular markers in adults with ALCL.

Materials and methods: From 2000 to 2011 year 20 patients with a median age of 26 years (17–65 years old) were enrolled in the study (14 men and 6 women). We have found generalized lymphadenopathy in all patients, high frequency of extranodal sites involvement (40%), bone marrow involvement proved by morphology in 2 patients (10%). II stage was diagnosed in 5 patients (25%), III-IV stage - in 15 patients (75%). We used program NHL BFM-90, branches K2 or K3 (the dose of methotrexate was different in two branches: 1g/m2 in branch K2, 5g/m2 in branch K3). The choice of the branch depended on the stage and clinical prognostic factors (III and IV stage, mediastinum, skin, lung, testis, central nervous system and bone marrow involvement). ALK gene rearrangement was determined by fluorescent in situ hybridization in all patients.

Blood and bone marrow samples have been examined for the quantity of chimeric transcript by real time PCR before the treatment and after the end of protocol NHL BFM-90 (median treatment duration 4 months). The informed consent was obtained from all patients.

19 from 20 patients (95%) have achieved complete remission (usually after 4 courses of chemotherapy). One patient died of infectious complications during the first course of chemotherapy. Early relapse was occurred in two patients (11%). 5-year overall survival is 90%. Blood and bone marrow samples before and after treatment were available in 12 from 20 patients. We were able to determine the chimeric transcript in 4 patients (3 cases NPM-ALK, 1 case ATIC-ALK) before treatment including those without morphological bone marrow involvement.

After chemotherapy only one patient had chimeric transcript in blood (1,12% copies of gene NPM-ALK/ABL expressed in percents). He has relapsed one year after the end of the treatment. Other patients with the absence of the chimeric transcript are still in remission.

protocol NHL BFM-90 has shown the high efficacy in adult patients with ALCL compared with currently used chemotherapy regimens. The presence of minimal residual disease after the treatment is probably a new adverse prognostic factor.

No relevant conflicts of interest to declare.