Prognostic Significance of Molecular Follow-up by Qualitative and Real-Time Quantitative Reverse-Transcriptase Polymerase Chain Reaction in TEL/AML1–Positive Childhood Acute Lymphoblastic Leukemia

Background

Minimal residual disease (MRD) detection and quantification in children with TEL/AML1–positive acute lymphoblastic leukemia was performed by qualitative and quantitative polymerase chain reaction (PCR) in 28 patients, uniformly treated.

Patients and Methods

More than 600 bone marrow (BM) or peripheral blood samples were analyzed during 2 years of therapy and subsequent follow-up.

Results

All the patients reached complete hematologic remission at day 42 of treatment, when a BM evaluation was scheduled. At this time, 22 of 28 patients were already negative in the BM at qualitative and quantitative PCR analysis, 6 of 28 showed a quantifiable MRD that lasted between 1 and 10 months, and only 1 patient remained persistently PCR positive and finally relapsed and died of progressive disease. After a median follow-up of 104 months, 18 of 28 patients (64%) are in continuous complete remission and persistently PCR negative. Ten of 28 patients relapsed: 4 died of progressive disease, and 6 are in second complete hematologic and molecular remission after salvage therapy. The event-free survival at 8 years is 64%, and the overall survival is 86%. Notably, all relapses were preceded by a return to PCR positivity between 1.5 and 8 months before hematologic relapse. Moreover, PCR positivity in the BM taken at day 42 after induction therapy was observed in 5 of the 10 patients who subsequently relapsed and only in 1 of the 18 patients who are still in continuous complete remission.

Conclusion

This supports the notion that persistence of detectable MRD at day 42 after induction is associated with an increased risk of subsequent relapse.