Assessment of residual disease in acute leukemia by means of polymerase chain reaction.
Along a 5-year period in a single institution, specific molecular markers were prospectively looked for in consecutive patients with acute leukemia, by means of polymerase chain reaction (PCR): In patients with acute lymphoblastic leukemia (ALL), the BCR/ABL and TEL-AML1 fusion transcripts as well as clonotypic immunoglobulin gene rearrangements were investigated, whereas in patients with acute myelogenous leukemia (AML) the PML-RAR alpha, AML1-ETO and CBF beta-MYH11 fusion proteins were assessed. Specific molecular markers were identified in 15/75 patients: Four with ALL (three with clonotypic IgG rearrangements and one with BCR/ABL) and 11 with AML (nine with the PML/RAR alpha fusion protein--M3 AML-, and two with the AML1/ETO fusion protein--M2 AML-). During follow-up periods ranging from 1 to 60 months, seven patients cleared the residual disease assessed by PCR (RD-PCR), whereas eight patients had either persistence of RD-PCR or a molecular relapse. For patients without or with RD-PCR, the 30-month survival (SV) was 86% and 14%, respectively, whereas median SV was > 60 and two months, also respectively (p < 0.01). Six of eight patients with detectable RD-PCR died, all of them within three months after the detection of the RD-PCR, whereas two of the patients that relapsed were rescued with treatment and entered a second molecular remission. Two of the three molecular relapses were detected without an overt morphological relapse. It is concluded that PCR is a valuable method for assessing residual disease and that early diagnosis of relapses may lead into effective salvage treatment in some instances.
Ruiz-Argüelles
G J
GJ
Centro de Hematología y Medicina Interna de Puebla, México. gruiz1@pue1.prodigy.net.mx
Garcés-Eisele
J
J
Reyes-Núñez
V
V
Pérez-Romano
B
B
Ruiz-Argüelles
A
A
Ramírez-Cisneros
F J
FJ
López-Martínez
B
B
López-Tapia
J D
JD
Rivadeneyra-Espinoza
L
L
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D006801:Humans; D016130:Immunophenotyping; D007938:Leukemia / Q000235:genetics / Q000401:mortality / Q000473:pathology*; D015993:Life Tables; D008297:Male; D008875:Middle Aged; D018365:Neoplasm, Residual; D014411:Neoplastic Stem Cells / Q000737:chemistry / Q000473:pathology; D015514:Oncogene Proteins, Fusion / Q000032:analysis*; D016133:Polymerase Chain Reaction / Q000379:methods*; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000235:genetics; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D018076:DNA, Complementary; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger