WHAT HAPPENS SUBSEQUENTLY IN AML WHEN CYTOGENETIC ABNORMALITIES PERSIST AT BONE-MARROW HARVEST - RESULTS OF THE 10TH UK MRC AML TRIAL

Cytogenetic analysis performed at diagnosis is widely recognised to pr ovide one of the most valuable prognostic indicators in AML, Yet any r ole for this technique in residual disease assessment, particularly in the context of subsequent transplantation procedures has been incompl etely explored, The present study considers the outcome of 190 patient s drawn from the UK MRC AML 10 trial in whom cytogenetics were assesse d whilst in morphological CR at the time of bone marrow harvest, Cytog enetics at this stage were abnormal in 19 patients (10%), In 11/19 pat ients, the abnormalities detected reflected the acquisition of new clo nal (3/11) or nonclonal changes (8/11) that were not identified at dia gnosis; comparison of this group to patients with normal cytogenetics at harvest provided no evidence that such acquired changes are of prog nostic significance, In 8/19 patients, abnormalities detected were ind icative of persistence of the disease-related clone in harvested marro w, Two of these patients died of sepsis during consolidation therapy, Two received ABMT in first morphological CR: one patient with AML asso ciated with a favourable karyotype (+8,inv(16)) remains in CR, 5.5 yea rs post-transplant, whereas the other with cytogenetic abnormalities c onsidered to confer a poor prognosis (inv(3q),-7), relapsed within 5 m onths of ABMT, All four of the remaining patients with cytogenetic evi dence of persistent disease who were not transplanted in first CR, rel apsed within 6.5 months of harvest, Therefore, among 101 of 190 patien ts with AML characterised by abnormal karyotype at diagnosis, persiste nce of the disease-related clone in eight patients (8%), revealed by c onventional cytogenetic assessment at bone marrow harvest whilst in mo rphological remission, was found to predict a poor prognosis, Neverthe less, transplantation procedures using marrow which is obviously conta minated with the original leukaemic clone may occasionally still be as sociated with long-term survival.