Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type: Long-term follow-up in acute promyelocytic leukemia

Joseph G. Jurcic, Stephen D Nimer, David A. Scheinberg, Tony Deblasio, Raymond P. Warrell, Wilson H. Miller

Research output: Contribution to journalArticle

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Abstract

The t(15;17) translocation in acute promyelocytic leukemia (APL) yields a PML/RAR-α fusion messenger RNA species that can be detected by reverse transcription-polymerase chain reaction (RT-PCR) amplification. Breakpoints within intron 3 of PML produce a short PML/RAR-α Isoform, whereas breakpoints within intron 6 result in a longer form. Using RT-PCR, serial evaluations were performed on the bone marrow of 82 patients with APL (median follow-up, > 63 months) who received retinoic acid (RA) induction followed by postremission treatment with chemotherapy, RA, and biologic agents. Sixty-four patients attained a clinical complete remission and had at least 2 RT-PCR assays performed after completing therapy. Forty of 47 patients (85%) with newly diagnosed APL who were induced using RA had residual disease detectable by RT-PCR before additional therapy. After 3 cycles of consolidation therapy, residual disease was found in only 4 of 40 evaluable patients (10%). Among newly diagnosed patients who had 2 or more negative RT-PCR assays, only 3 of 41 (7%) had a relapse, whereas all 4 patients (100%) who had 2 or more positive results had a relapse. Among 63 newly diagnosed patients, those who expressed the short isoform appeared to have shorter disease-free and overall survival durations than patients who expressed the long isoform. These data indicate that 2 or more negative RT-PCR assays on bone marrow, performed at least 1 month apart after completing therapy, are strongly associated with long-term remissions. Conversely, a confirmed positive test is highly predictive of relapse.

Original languageEnglish
Pages (from-to)2651-2656
Number of pages6
JournalBlood
Volume98
Issue number9
DOIs
StatePublished - Nov 1 2001
Externally publishedYes

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Acute Promyelocytic Leukemia
Polymerase chain reaction
Residual Neoplasm
Transcription
Protein Isoforms
Reverse Transcription
Tretinoin
Polymerase Chain Reaction
Assays
Introns
Bone
Recurrence
Chemotherapy
Bone Marrow
Biological Factors
Therapeutics
Consolidation
Amplification
Fusion reactions
Disease-Free Survival

ASJC Scopus subject areas

  • Hematology

Cite this

Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type : Long-term follow-up in acute promyelocytic leukemia. / Jurcic, Joseph G.; Nimer, Stephen D; Scheinberg, David A.; Deblasio, Tony; Warrell, Raymond P.; Miller, Wilson H.

In: Blood, Vol. 98, No. 9, 01.11.2001, p. 2651-2656.

Research output: Contribution to journalArticle

Jurcic, Joseph G. ; Nimer, Stephen D ; Scheinberg, David A. ; Deblasio, Tony ; Warrell, Raymond P. ; Miller, Wilson H. / Prognostic significance of minimal residual disease detection and PML/RAR-α isoform type : Long-term follow-up in acute promyelocytic leukemia. In: Blood. 2001 ; Vol. 98, No. 9. pp. 2651-2656.
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