CLONAL REMISSIONS IN ACUTE MYELOID-LEUKEMIA ARE COMMONLY ASSOCIATED WITH FEATURES OF TRILINEAGE MYELODYSPLASIA DURING REMISSION

Clonal haemopoiesis has previously been demonstrated in some 30% of pa tients in remission of acute myeloid leukaemia (AML). Whilst a 'clonal remission' in many such patients may represent a skewed X-chromosome inactivation pattern in haemopoietic cells, its relationship to an und erlying preleukaemic state remains uncertain. We therefore analysed th e clonal status of 48 female patients in remission of AML using X-chro mosome linked restriction fragment length polymorphisms (RFLPs) within the X-linked PGK and HPRT genes and the DXS255 (M27beta) locus, and c arried out in conjunction a detailed study of the morphological and ka ryotypic features of the patients' bone marrows. During remission, 35 patients (73%) with AML demonstrated non-clonal haemopoiesis, and thei r bone marrows were morphologically normal. Remission haemopoietic tis sue in nine cases (19%) showed a skewed X-chromosome inactivation patt ern and remission bone marrows in these patients had features of trili neage myelodysplasia (TMDS), with seven having similar features at pre sentation. Analysis of constitutional DNA showed a non-clonal pattern in seven of these patients, but was unsuccessful in two cases. These n ine patients with post-chemotherapy TMDS were considered to have true clonal haemopoiesis. Four patients (8%) with a skewed X-chromosome ina ctivation pattern had normal remission bone marrows. Analysis of const itutional DNA showed a skewed pattern in two of these patients, but wa s unsuccessful in two cases. Cytogenetic investigation during remissio n in the nine patients with TMDS showed a normal karyotype in four cas es and the acquisition of new karyotypic abnormalities in three cases. In contrast, 10 female patients in remission of de novo acute lymphob lastic leukaemia (ALL) were shown to have non-clonal haemopoiesis. We conclude that the majority of patients with AML who achieve remission after cytoreductive chemotherapy have non-clonal haemopoiesis, and whe n clonal remissions are observed these are commonly associated with th e development of trilineage myelodysplasia in the bone marrow, with or without karyotypic abnormalities. True clonal remission in associatio n with morphologically normal haemopoiesis is a rare entity, the signi ficance and frequency of which remain uncertain.