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The deep recession of the Ukrainian economy connected with a political and military conflict in the region “Donbass” intensifies the problem of its further stable and balanced development. The depression phase is characterized by irreversible changes in the institutional sphere, synchrony breaking of the economic interests of economic subjects, destabilization of the Caspian and Black Sea borders. The authors carried out an integrated assessment of geo-economics of the south of Russia and the south-east of Ukraine on the basis of three methods related to the basic and fundamental applied research: economic and geographical method, method of multiplexed serial-parallel cross with adaptive deploy systems, dynamic approximation. Analyzing the mechanisms of the processes of the geo transit character under the condition of the creation of a new megaregion “global city-region of Donbass” the following statement is put forward: leading institutions and the main link in the creation of new “reference areas” or “lines of force” of reproduction economic cycles under the process of a continuous cargo traffic become the Seversky Donets River and the access in the region to the hydrogen energy. The analysis of cartograms, adaptation of the data of “reference areas” allows grouping the existing administrative units into four reproductive cycles of a new mega region “Donbass” with epicenters: reproduction center with its epicenter in Rostov-on-Don, Shakhty, Donetsk, Lugansk; reproduction center number 1 with the epicenter in Sevastopol; reproduction center number 2 with the epicenter in Kharkov, Belgorod, Voronezh; reproduction center number 3 with the epicenter in Volgograd. The analysis determines the indispensable inclusion of the geo-economic development of these spaces in the public territorial policy with the launch of the federal target program of the international level.