Demonstration of developing myelodysplasia/acute myeloid leukaemia in haematologically normal patients after high-dose chemotherapy and autologous bone marrow transplantation using X-chromosome inactivation patterns.
Autologous bone marrow or peripheral blood stem cell transplantation may carry an increased risk of secondary myelodysplasia (MDS) and acute myeloid leukaemia (AML), which are already recognized as complications of conventional treatment for lymphoid malignancies. In order to ascertain whether it is possible to detect the evolution of such a clone at an early stage in its development we have studied X-chromosome inactivation patterns (XCIPs) in three informative females who developed abnormal myelopoiesis after high-dose chemotherapy and ABMT. In one patient transplanted for relapsed Hodgkin's disease a leukaemic clone comprising approximately 50% of the patient's myeloid cells was detectable by comparison of peripheral blood granulocyte and T-cell XCIPs when the full blood count and morphology were normal. She presented with AML 7 months later. In two patients transplanted for AML, XCIP analysis was complicated by constitutively skewed Lyonization patterns, nevertheless a progressive alteration could be demonstrated by serial analyses. In one patient a difference was detectable 28 months before presentation with MDS. In the other patient, despite evident mild pancytopenia and alterations in her XCIPs over the past 4 years, she has developed no definitive myelodysplastic features and oligoclonality due to stem cell failure cannot be excluded. These studies show that XCIPs can be used to predict development of MDS/AML in some patients, but the technique is limited by technical variability and frequent constitutional skewing in the haemopoietic system.
Gale
R E
RE
Department of Haematology, University College London Medical School.
Bunch
C
C
Moir
D J
DJ
Patterson
K G
KG
Goldstone
A H
AH
Linch
D C
DC
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D004303:Dosage Compensation, Genetic; D006689:Hodgkin Disease / Q000628:therapy; D006801:Humans; D007951:Leukemia, Myeloid / Q000209:etiology* / Q000235:genetics / Q000628:therapy; D008297:Male; D009190:Myelodysplastic Syndromes / Q000209:etiology* / Q000235:genetics; D011184:Postoperative Period; D011379:Prognosis; D014182:Transplantation, Autologous