Clinical Relevance of Acute Mixed-lineage Leukemia

A recent report by Pui et all focused on the biologic and clinical relevance of acute mixed-lineage leukemia; namely, acute lymphoblastic leukemia expressing myeloid-associated antigens (My+ ALL) and acute myeloid antigens expressing lymphoid antigens (Ly+ AML) were analyzed in a pediatric series. In our opinion, a major point in the field of hybrid acute leukemia remaining undetermined is which “ectopic” antigens and what level of ectopic expression significantly affect the clinical outcome. The findings regarding My+ ALL are quite controversial? On the contrary, T-cell antigens expression in AML seems to characterize a distinct clinical entity in both children and ad~l ts .3 .~ From an analysis of 107 AML samples, we demonstrated that CD7 and CD2 simultaneous expression on myeloid blasts is a nonrandom event, recurring in a substantial proportion of patients5 In our series, CD7+/ CD2+ AML patients presented with a higher incidence of adenopathy and meningeal leukemia than did patients with “pure” AML, and were characterized by a poor response to chemotherapy in terms of complete remission (CR) achievement and d ~ r a t i o n . ~ On a clinical ground, our findings were closely in keeping with those reported by Cross et a1.3 Also, in the report by Pui et all CD7+/CD2+ AML was the most frequent hybrid pattern in 16 Ly+ AML cases. As in our series, most patients were classifiable as M1 according to the French-American-British classification, and in a consistent number of them a coexistence of large myeloid blasts and small blasts with hand-mirror morphology was found. Notwithstanding, Pui et all stated that “event free survival did not differ between Ly+ AML patients and other AML patients.” What would have been the results if only CD7+/CD2+ patients had been analyzed? Furthermore, it is noteworthy that in Pui et al’s series four Ly+ AML cases who failed AML induction therapy subsequently entered CR with prednisone, vincristine, and L-Asparaginase (a quite unusual chemotherapy program for classical AML). The outcome for the CD7+/CD2+ AML cases probably would have been different if this approach had not been used. In our opinion, the analytical subtyping of AML on the basis of T-cell antigen ectopic expression needs further investigating. For example, different combinations of T-cell antigens (eg, CD7, CD2, CD5, CD6) on AML blasts may represent quite distinct biological phenomena, possibly corresponding to different hemopoietic steps. In this respect, we consider CD7+/CD2+ AML to be a distinct clinico-hematologic entity sharing, in an extremely balanced fashion, both myeloid and lymphoid features. We feel that these patients should be allocated to unique clinical trials using combined AML/ALL regimens during the induction as well as the consolidation chemotherapy, with particular emphasis on the prevention of meningeal leukemia, and, whenever possible, included in a bone marrow transplantation program. Finally, further efforts should be addressed toward the classification of promiscuous phenotypes on the basis of their clinical relevance.