title: Clonal evolution in Ph-negative, bcr-positive chronic myeloid leukaemia before and after bone marrow transplantation.
abstract: A 26-year-old man, who presented with bilateral fundal haemorrhages, was found to have chronic myeloid leukaemia (CML). The Ph chromosome was not present but a clone with t(1;9) (p32;q34) was detected. On referral for bone marrow transplant (BMT) he was found to be in accelerated phase with clonal evolution in three cell lines inv(3)(q21q26); inv(3)(q),i(17q); inv(3q)+8. Molecular investigation revealed a breakpoint on chromosome 22 within the breakpoint cluster region (bcr) similar to that found in Ph+ cases. After BMT, from an HLA-identical sister, successful engraftment (46,XX) was accompanied by evidence of a residual host cell population with further evolution (del(7)(q22)) and persistence of the bcr+ clone. Acute myeloid leukaemia, detected 5 months later, was associated with predominance of the clone 46XY,t(1;9),inv(3q),del(7)(q22) which failed to respond to treatment and the patient died 6.5 months after BMT. This case indicates that BMT, after the acquisition of additional chromosomal change in accelerated phase, may fail owing to persistence of the leukaemic clone. In addition the BMT conditioning regimen may produce further abnormalities which confer drug resistance on the persisting clone, which can emerge as an intractable myeloid blast crisis.
authors.affiliation: Department of Haematology, Royal Free Hospital, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Secker-Walker
authors.forename: H M
authors.initials: HM
authors.lastname: Cooke
authors.forename: P J
authors.initials: PJ
authors.lastname: Browett
authors.forename: J D
authors.initials: JD
authors.lastname: Norton
authors.forename: C
authors.initials: C
authors.lastname: Kitchen
authors.forename: A G
authors.initials: AG
authors.lastname: Prentice
authors.forename: H G
authors.initials: HG
authors.lastname: Prentice
mesh_terms: D000328:Adult; D016026:Bone Marrow Transplantation; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000235:genetics* / Q000601:surgery; D008297:Male; D014178:Translocation, Genetic / Q000235:genetics*