EVOLUTION OF THERAPY FOR ACUTE LYMPHOBLASTIC LEUKEMIA IN CHILDREN: FROM FIRST REMISSIONS TO MOLECULARLY TARGETED IMMUNOTHERAPY (ON THE CENTENARY OF THE BIRTH OF N.S. KISLYAK)

Vollständiger Abstract

Worum geht es in dieser Arbeit?

The centenary of the birth of Academician Natalia Sergeevna Kislyak (1926–2008) — the founder of pediatric hematology in Russia — provides an occasion to reflect on one of the most significant medical achievements of the 20th–21st centuries: the transformation of acute lymphoblastic leukemia (ALL) from a fatal disease into one that is curable in the majority of children. This article traces the logic of that evolution — from the first remission induced by S. Farber in 1948 and D. Pinkel's «total therapy» to the methodology of controlled multicenter trials (A. Bradford Hill), the concept of occult neuroleukemia (A. Bleyer), cooperative study groups (BFM, UKALL, CCG/POG/COG, NOPHO), the monitoring of minimal residual disease (MRD), and modern immunotherapy. Particular attention is given to the contribution of the Russian scientific school originating with N. S. Kislyak: the establishment of the «Moscow–Berlin» clinical research group and the ALL-MB series of protocols (91, 2002, 2008, 2015), which demonstrated that outcomes comparable to those of the leading international groups can be achieved with substantially lower treatment intensity, toxicity, and cost. Bispecific antibodies (blinatumomab), immunoconjugates (inotuzumab ozogamicin), CAR-T cell therapy, and the transcriptomic molecular classification of ALL are also discussed.