Front line clinical trials and minimal residual disease monitoring in acute promyelocytic leukemia

F. Lo-Coco*, E. Ammatuna

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

21 Citaten (Scopus)

Samenvatting

In spite of the very high cure rate (70%-80%) achieved in APL with combinatorial all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy regimens, a number of issues are still open for investigation in front-line therapy of this disease. These include, among others, improvements in early death rate, the role of arsenic trioxide (ATO) and maintenance treatment, and, finally, optimization of molecular monitoring to better identify patients at increased risk of relapse. The current consensus on the most appropriate induction therapy consists of the concomitant administration of ATRA and anthracycline-based chemotherapy. Although the antileukemic benefit provided by the addition of ATRA to consolidation therapy has not been demonstrated in randomized studies, historical comparisons of consecutive studies carried out by Spanish and Italian cooperative groups suggest that the combination of ATRA and chemotherapy for consolidation may also contribute to improving therapeutic results. While a variety of distinct treatments are being investigated for front-line therapy, most experts agree that a risk-adapted therapy represents the optimal approach, through the use of more intensive therapy in patients with initial hyperleukocytosis. Longitudinal RT-PCR of PML/RARα allows sensitive assessment of response to treatment and minimal residual disease (MRD) monitoring in APL. Achievement of negative PCR status or molecular remission at the end of consolidation is now universally accepted and recommended as a therapeutic objective in this disease. On the other hand, persistence of, or conversion to, PCR positive in the marrow during follow-up is associated with impending relapse. Preliminary studies on therapy of molecular relapse indicate a survival advantage as compared to administering salvage treatment at time of hematologic relapse. The more accurate and reproducible real-time PCR method to detect at quantitative levels the PML/RARα hybrid will likely provide better inter-laboratory standardization and trial results comparison in the near future.

Originele taal-2English
TitelAcute Promyelocytic Leukemia
SubtitelMolecular Genetics, Mouse Models and Targeted Therapy
RedacteurenPier Paolo Pandolfi, Peter K. Vogt
UitgeverijSpringer Verlag
Pagina's145-156
Aantal pagina's12
ISBN van geprinte versie3540345922, 9783540345923
DOI's
StatusPublished - 2007
Extern gepubliceerdJa

Publicatie series

NaamCurrent Topics in Microbiology and Immunology
Volume313
ISSN van geprinte versie0070-217X

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