Tracking APL progress with RT-PCR Testing
Testing disease status helps to predict relapse and potentially improve outcomes for acute
promyelocytic leukemia (APL) patients.
1-4
One method of assessing APL status is reverse transcriptase-polymerase chain reaction testing, or RT-PCR
testing. RT-PCR testing presents the opportunity to detect impending relapse rather than wait
for signs of clinical relapse. Based on a review of the literature, Tallman and colleagues
concluded that a reasonable schedule of testing is to obtain at least two successive marrow
samples at the end of treatment performed every three months for the first two years of CR and
then every six months for the next two to three years.
1
Genetic testing can help track disease status, predict relapse, and improve outcomes.
RT-PCR testing analyzes the chromosome abnormalities that define APL specifically. APL is usually
marked by a translocation of genes between chromosomes 15 and 17, represented as t(15;17).
5-8
Part of the PML (promyelocytic leukemia) gene transfers to chromosome 17 and part of the RAR-alpha
(retinoic acid receptor-alpha) gene transfers to chromosome 15. The result is a fusion protein
product with characteristics of both the PML gene and the RAR-alpha receptor protein.
5-8
Expression of the fusion produced by the translocation of genes between chromosomes 15 and 17 is
detected with the RT-PCR test, which offers the following two benefits:
1. The test is predictive of relapse and survival.
A positive PML/RAR-alpha test after consolidation therapy reliably predicts subsequent hematologic
relapse, whereas repeatedly negative results are associated with long-term survival in the
majority of patients.
1 In one study, 163 patients were induced into remission by ATRA
combined with chemotherapy, and were tested at regular intervals after the end of treatment.
Twenty of the 21 patients who converted to a positive PCR relapsed within a median of 3 months,
whereas the 3-year estimate of relapse risk of patients who tested negative at least twice after
consolidation was less than 10%.
2
2. Test results can guide therapy, leading to improved patient outcomes.
Patients who convert to a positive PCR can be salvaged early with chemotherapy prior to overt
disease.
1,3 This results in a significantly improved outcome compared to delaying
treatment until morphologic evidence of relapse. It is anticipated that therapy at the time of
molecular relapse will be associated with a lower mortality rate than that observed with
reinduction of overt disease.
1,3 In one study, 14 APL patients were prospectively
monitored after consolidation therapy with the AIDA protocol (all-trans retinoic acid [ATRA]
plus idarubicin). Patients were treated at the time of molecular relapse (defined as two
successive RT-PCR positive samples), rather than at clinical relapse. Early treatment for
relapse with 30 days of oral ATRA followed by four daily courses of chemotherapy with
cytarabine and mitoxantrone resulted in achievement of a second molecular remission in 12
patients (86%).
3
>> Click here to review how TRISENOX may work to achieve
remission for your relapsed or refractory APL patients.
1. Lowenberg B, Griffin JD, Tallman MS. Acute myeloid leukemia and acute promyelocytic leukemia. Hematology Am Soc Hematol Educ Program. 2003;82-101.
2. Diverio D, Rossi V, Avvisati G. Early detection of relapse by prospective reverse transcriptase-polymerase chain reaction analysis of the PML/RAR alpha fusion gene in patients with acute promyelocytic leukemia enrolled in the GIMEMA-AIEOP multicenter "AIDA" trial. GIMEMA-AIEOP Multicenter "AIDA" Trial. Blood. 1998;92:784-789.
3. Lo Coco F, Diverio D, Avvisati G, et al. Therapy of molecular relapse in acute promyelocytic leukemia. Blood. 1999;94:2225-2229.
4. Lo Coco F, Diverio D, Falini B. Genetic diagnosis and molecular monitoring in the management of acute promyelocytic leukemia. Blood. 1999;94:12-22.
5. Grignani F, Fagioli M, Alcalay M, et al. Acute promyelocytic leukemia: from genetics to treatment. Blood. 1994;83:10-25.
6. Douer D, Tallman MS. Arsenic trioxide: new clinical experience with an old medication in hematologic malignancies. J Clin Oncol. 2005;23:2396-2410.
7. Miller WH Jr, Schipper HM, Lee JS, et al. Mechanisms of action of arsenic trioxide. Cancer Res. 2002;62:3893-3903.
8. Davison K, Mann KK, Miller WH Jr. Arsenic trioxide: mechanisms of action. Semin Hematol. 2002;39(2 Suppl 1):3-7.