Serial measurement of BCR-ABL transcripts in the peripheral blood after allogeneic stem cell transplantation for chronic myeloid leukemia: an attempt to define patients who may not require further therapy.
We identified 243 patients with Philadelphia (Ph) chromosome-positive chronic myeloid leukemia (CML) who had BCR-ABL transcripts monitored by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) after allogeneic stem cell transplantation for a median of 84.3 months. Individual patients were regarded as having achieved molecular relapse (MR) if the BCR-ABL/ABL ratio exceeded 0.02% on 3 occasions or reached 0.05% on 2 occasions. Patients were allocated to 1 of 4 categories: (1) 36 patients were "persistently negative" or had a single low-level positive result; (2) 51 patients, "fluctuating positive, low level," had more than 1 positive result but never more than 2 consecutive positive results; (3) 27 patients, "persistently positive, low level," had persisting low levels of BCR-ABL transcripts but never more than 3 consecutive positive results; and (4) 129 patients relapsed. In 107 of these, relapse was based initially only on molecular criteria; in 72 (67.3%) patients the leukemia progressed to cytogenetic or hematologic relapse either prior to or during treatment with donor lymphocyte infusions. We conclude that the pattern of BCR-ABL transcript levels after allograft is variable; only a minority of patients with fluctuating or persistent low levels of BCR-ABL transcripts satisfied our definitions of MR, whereas the majority of patients who did so were likely to progress further.
Kaeda
Jaspal
J
Department of Haematology, Imperial College at Hammersmith Hospital, London, UK.
O'Shea
Derville
D
Szydlo
Richard M
RM
Olavarria
Eduardo
E
Dazzi
Francesco
F
Marin
David
D
Saunders
Susan
S
Khorashad
Jamshid S
JS
Cross
Nicholas C P
NC
Goldman
John M
JM
Apperley
Jane F
JF
D000328:Adult; D015415:Biomarkers / Q000097:blood; D018450:Disease Progression; D005260:Female; D016044:Fusion Proteins, bcr-abl / Q000097:blood / Q000235:genetics*; D006801:Humans; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000235:genetics* / Q000628:therapy; D008297:Male; D033581:Stem Cell Transplantation; D017741:Survivors; D014158:Transcription, Genetic; D014184:Transplantation, Homologous / Q000502:physiology*; D016896:Treatment Outcome
D015415:Biomarkers; D016044:Fusion Proteins, bcr-abl