Evaluation of minimal residual disease using reverse-transcription polymerase chain reaction in t(8;21) acute myeloid leukemia: a multicenter study of 51 patients.
OBJECTIVE
Most studies using various reverse-transcription polymerase chain reaction (RT-PCR) techniques reported that the detection of the AML1-ETO fusion transcript was a common finding in long-term complete remission (CR) in acute myeloid leukemia (AML) with t(8;21) translocation. However, larger prospective studies with interlaboratory quality control may be important to investigate more precisely the clinical usefulness of studying minimal residual disease with RT-PCR in t(8;21) AML.


METHODS
We collected 223 marrow samples from 51 patients with t(8;21) AML diagnosed in five centers and tested all samples by two different RT-PCR techniques (a nested technique and a one-step technique, with a sensitivity of 10(-6) and 10(-5), respectively) in two different laboratories.


RESULTS
Samples from 14 patients in long persistent CR (median follow-up duration, 112 months) were taken at least twice, and all were PCR-negative by both techniques. Samples were prospectively taken from 37 patients after achievement of first CR and/or second CR, before intensive consolidation treatment, and every 3 to 6 months after completion of therapy. Patients who converted to PCR negativity with the one-step technique (60%) or both techniques (48%) after CR achievement had a longer CR duration than those with persistently positive PCR results (two-sided log-rank test, P =.0001). Patients who became PCR-negative with the one-step technique before intensive consolidation (23%) had a lower relapse rate (11% v 72%) and a longer CR duration than those who remained persistently PCR-positive at that point (two-sided log-rank test, P =.0015).


CONCLUSIONS
Patients with AML with t(8;21) in long-term remission were all PCR-negative. In prospectively studied patients, a good correlation was found between negative PCR results and absence of relapse. Early negative results with the one-step RT-PCR technique, before consolidation treatment, seemed to carry an especially good prognosis, suggesting that RT-PCR analysis could help in choosing the type of consolidation therapy in patients with t(8;21) AML.
Morschhauser
F
F
Service des Maladies du Sang and Laboratoire d'H¿ematologie A, Centre Hospitalier Universitaire, and Unité L'Institut National de la Sant¿e et de la Recherche M¿edicale (INSERM) U524, Lille, France.
Cayuela
J M
JM
Martini
S
S
Baruchel
A
A
Rousselot
P
P
Socié
G
G
Berthou
P
P
Jouet
J P
JP
Straetmans
N
N
Sigaux
F
F
Fenaux
P
P
Preudhomme
C
C
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D019677:Artificial Gene Fusion; D001854:Bone Marrow Cells / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D050676:Core Binding Factor Alpha 2 Subunit; D005069:Evaluation Studies as Topic; D005260:Female; D005500:Follow-Up Studies; D015321:Gene Rearrangement; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics* / Q000628:therapy; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011446:Prospective Studies; D000075142:RUNX1 Translocation Partner 1 Protein; D012074:Remission Induction; D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic; D014178:Translocation, Genetic / Q000235:genetics
C107844:AML1-ETO fusion protein, human; D050676:Core Binding Factor Alpha 2 Subunit; D015514:Oncogene Proteins, Fusion; D000075142:RUNX1 Translocation Partner 1 Protein; D014157:Transcription Factors