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Absence of reverse transcription-polymerase chain reaction detectable
residual disease in patients with acute promyelocytic leukemia in long-
term remission
D Diverio, PP Pandolfi, A Biondi, G Avvisati, MC Petti, F Mandelli, G Pelicci and F Lo Coco
Department of Human Biopathology, University La Sapienza of Rome, Italy.
Hybrid fusion genes are specific tumor markers of several leukemic
subtypes. The use of reverse transcription-polymerase chain reaction
(RT-PCR) to amplify chimeric cDNAs allows sensitive detection of the
neoplastic clone for diagnostic and monitoring studies in these leukemias.
Nonetheless, the clinical relevance of minimal residual disease (MRD)
evaluation by PCR remains controversial. In this study, 9 patients (pts)
with acute promyelocytic leukemia (APL) in long-term remission for 4 to 12
years were analyzed for the presence of MRD by RT- PCR amplification of the
specific PML/RAR-alpha fusion gene. Seven pts had been treated with
conventional chemotherapy (CHT) alone, 1 had undergone allogeneic bone
marrow transplantation (BMT), and 1 autologous BMT as consolidation therapy
after CHT. In 8 cases, the presence of the t(15;17) rearrangement could be
documented in diagnostic BM specimens by cytogenetic and/or molecular
analysis. A two- rounds "nested" RT-PCR assay with sensitivity levels of 1
in 10(5) was used to analyze BM samples collected at 32 to 141 months from
the achievement of complete remission (CR). In no cases were residual
PML/RAR-alpha transcripts detectable in these remission controls. All
patients are in unmaintained CR at 48 to 154 months from CR and at 6 to 17
months from PCR evaluation. These results suggest that long-term survival
of APL is associated with eradication of cells carrying the specific
PML/RAR-alpha rearrangement, indicating that PCR negativity should be
considered the therapeutic goal in these patients. Our findings further
strengthen the clinical relevance of PCR monitoring studies in APL, as
opposite to other leukemic subtypes (chronic myeloid leukemia and acute
myeloid leukemia-M2) in which the prognostic significance of PCR evaluation
is unclear.
Volume 82,
Issue 12,
pp. 3556-3559,
12/15/1993
Copyright © 1993 by The American Society of Hematology
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