LINEAGE SWITCH IN ACUTE-LEUKEMIA

Abstract

Conversions of leukemic cell lineage (lymphoid or myeloid) were reported only rarely. Review of the cytochemical and immunophenotypic features of 89 cases of childhood leukemia in marrow relapse indicated lineage switch (lymphoid to myeloid or the reverse) in 6 patients (6.7%). Five patients with acute lymphoblastic leukemia (ALL) at diagnosis had converted to acute nonlymphoblastic leukemia (ANLL), and 1 had converted from ANLL to ALL. Each child received lineage-specific multiagent chemotherapy when initially diagnosed, and all achieved a complete remission. After conversion, 4 patients readily achieved 2nd remissions with treatment for the phenotype evident at lineage switch. Two patients with ANLL at conversion failed ALL-directed reinduction, while 1 of the 2 responded to high-dose cytarabine but died during bone marrow hypoplasia, emphasizing the importance of prompt recognition of lineage switch and selection of an appropriate plan of retreatment. Cytogenetic studies disclosed evidence of clonal selection in 1 patient and clonal stability in 2. An unexpectedly high frequency of lineage switch was indicated in patients who relapse in the bone marrow after intensive chemotherapy. Although specific causative factors could not be identified, at least 2 general mechanisms for lineage switch in acute leukemia were suggested. In 1, chemotherapy appears to eradicate the dominant clone present at diagnosis, permitting expansion of a secondary clone with a different phenotype. In the 2nd, drug-induced changes in the original clone may either amplify or suppress differentiation programs so that phenotypic shift is possible.