Anaplastic Large-Cell Lymphomas in Adults: The Cytogenetic and Molecular Genetic Characteristics, Treatment Results (a single institutional experience)

Anaplastic large cell lymphomas in adults is a group of rare diseases that are characterized by aggressive clinical course, generalization of the process, high frequency of extranodal lesions, typical morpho-immunophenotyping peculiarities (diffuse infiltration with specific anaplastic giant cells and high expression of the activating CD30 antigen). The prognosis varies greatly depending on the genetic profile of the disease (the presence of ALK, DUSP22, TP-63 genetic rearrangements). In case of presence of ALK and DUSP22 rearrangements, the prognosis is favorable (overall survival [OS] is 70-90%); triple-negative profile is characterized by intermediate prognosis (OS 40-50%), while TP63 gene rearrangements are associated with extremely poor prognosis (OS 8-17%).

The goal of the study was to evaluate cytogenetic characteristics and the results of high-dose chemotherapy in patients with anaplastic large cell lymphoma.

The results: 91 patients who were followed up at one center were enrolled in the study over the period 2000 to 2017. The majority of patients had advanced stages of the disease: 72 patients (79%; including ALK+ ALGL in 71% of cases and ALK- ALGL in 90% of cases) had stage III-IV disease and were in the intermediate-high and high-risk groups according to the International Prognostic Index (IPI) (60% of patients).

The testing results were as follows: ALK gene rearrangements and, correspondingly, ALK overexpression were revealed in 52 patients (57%; median age 33 years). 39 patients (43%; median age 51 years) did not demonstrate any ALK-related cytogenetic aberrations. The results of FISH assay of ALK-negative ALGL were as follows: DUSP22, TP63 rearrangements and triple-negative profile were observed in 20%, 13% and 67% of cases, respectively.

The majority of patients in the general group received high-dose chemotherapy - 42 patients with ALK+ ALGL, 27 patients with ALK- ALGL; the rest of the patients received CHOP/CHOEP therapy courses.

ALK, DUSP22, TP63 rearrangements and triple-negative profile were associated with 83% and 79%, 100% and 100%, 8% and 10%, 60% and 39% overall survival (OS) and event-free survival (EFS) rates, respectively. The analysis of treatment failures (relapse/progression) in ALK+ ALGL group showed that detection of minimal residual disease in the bone marrow and peripheral blood specimens after 2 courses of chemotherapy was an important factor (real-time PCR demonstrated different ALK-based chimeric translocation products, including NPM-ALK, ATIC-ALK, TPM3-ALK).

Thus, the results of high-dose chemotherapy in patients with anaplastic large-cell lymphoma in adults (namely overall survival and event-free survival rates) demonstrate statistically significant differences depending on the cytogenetic profile of the disease. The least favorable profiles are TP63 rearrangements in patients with ALK- ALGL, as well as minimal residual disease in ALK+ ALGL, which allows to optimize induction chemotherapy regimens