Late Events in Adult Patients with ALK-Positive Anaplastic Large Cell Lymphoma

ALK-positive anaplastic large cell lymphoma is a lymphoproliferative disorder of "young age"; its incidence among all non-Hodgkin lymphomas in adult patient cohort is 2-15%. Cytogenetic aberrations associated with ALK rearrangements mainly include t(2;5)(p23;q32) and the chimeric fusion gene NPM-ALK, while less than 10-15% of cases are associated with variant translocations involving 2p23 and resulting in formation of rare oncogenes.

Favorable prognosis in patients with this type of the disorder who receive high-dose chemotherapy regimens (NHL BFM-90) is associated with 75%-92% overall and event-free survival rates, including in adult patients. Therapy failures are generally diagnosed during the first 1.5-2 years of follow-up. The risk of development of secondary tumor lesions following high-dose chemotherapy does not exceed 10% (in children).

The goal of the study was to evaluate the development of late events (relapse, secondary tumors) in 52 adult patients (median age 33 years) with ALK-positive anaplastic large cell lymphoma who had received unified program of high-dose chemotherapy according to NHL BFM-90 protocol.

The results: this therapy program was associated with 83% and 79% overall and event-free survival rates, respectively (median follow-up - 83 months), early relapses (median time to development 12 months) were verified in 3 patients (6%), disease progression - in 3 (6%) cases. Three patients developed late events (>5.5 years following the end of treatment). In two cases, a tumor relapse was diagnosed: in one patient who initially had stage IV disease and extranodal lesions in the skin and soft tissues - after 5.5 years of follow-up; and in another patient - after 7 years of follow-up. Peculiar features of the first clinical case - minimal disseminated disease was revealed at the moment of diagnosis verification, with the ATIC-ALK chimeric transcript detected in peripheral blood and bone marrow (which was consistent with a variant translocation, inv (2)(p23;q35)); no chimeric oncogene has been detected after the courses of induction therapy and during subsequent years of follow-up. In the second case, at the moment of the relapse verification, the ATIC-ALK transcript was detected again in the specimens of bone marrow and peripheral blood, indicating the development of a distant relapse from the identical primary tumor clone.

The third late event (diagnosed in >11 years after the end of chemotherapy) was the development of epithelioid sarcoma with primary spleen involvement.

Thus, high-dose first-line chemotherapy in adult patients with ALK+ ALGL has proven to be highly effective. Early relapses and progressions were verified not more than in 6% of cases. The characteristics of these late events are of special interest: a relapse in the form of development of new skin lesions (as was observed at the time of the disease manifestation); in the second case - relapse from the identical tumor cell clone in 7 years, and, finally, the development of a rare secondary tumor (epithelioid sarcoma) together with non-conventional clinical course (tumor nodes in the spleen and retroperitoneal lymphadenopathy).