Clinical and laboratory data are presented of a 29 year female patient with BAALC- and BCL-2-positive T-cell acute lymphoblastic leukemia developed from early leukemic progenitors which was treated unsuccessfully with high-dose chemotherapy and allogeneic stem cell transplant (allo-HSCT), but revealed an impressive effect of venetoclax. For reasons beyond our control, allo-HSCT with myeloablative fludarabine-busulfan (14 mg/ kg) conditioning regimen was performed at the peak of relapse when blast count in bone marrow aspirate was 77.5%, whereas level of BAALC-expressing earlier progenitors (EP) reached 186%. HSCT was ineffective, since the number of blasts on day+30 reached 86%, whereas the burden of BAALC-expressing EP decreased to the cutoff values. Later, at post-transplant stage, an impressive response to venetoclax coupled with hypomethylating agent was observed. Following allo-HSCT and combined venetoclax therapy a severe pancytopenia developed, which required the second transplantation of peripheral blood stem cells from her haplo-matched father. After transplantation hematopoietic recovery started on day 10+. Although bone marrow aspirate at this point was hypo cellular, it contained all types of granulocytic and erythroid elements and 2.2% of blasts only.

A new concept of acute myeloid leukemia (AML) relapses is proposed which is linked with direct participation of BAALC-expressing earlier leukemic progenitors (ELP). The latter may be studied effectively by means of real-time quantitative polymerase chain reaction (RT-qPCR). Recent findings in support of this conception and ongoing prospective studies in the field are shortly discussed.