Serial monitoring of BCR-ABL in newly diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) treated with imatinib.

Authors

null

Sung-nam Lim

Haeundae Paik Hospital, Busan, Korea South

Sung-nam Lim , Young-Don Joo , Il-Hwan Kim , Won-Sik Lee , Sang Min Lee

Organizations

Haeundae Paik Hospital, Busan, Korea South, Haeundae Paik Hospital, Inje University, Busan, South Korea, Department of internal medicine, Inje University, Haeundae Paik Hospital, Busan, Korea, The Republic of, Busan Paik Hospital, Inje University, Busan, South Korea, Department of internal medicine, Inje University, Busan Paik Hospital, Busan, Korea, The Republic of

Research Funding

Other

Background: The positive impact of imatinib on treatment outcome in Ph+ ALL is well known. The aim of this study was to evaluate the relationship between imatinib dose intensity and molecular response of BCR-ABL. Methods: Molecular response monitoring was performed at the central lab with quantitative RT-PCR assays for BCR-ABL RNA in serial; at the time of diagnosis, at hematologic complete remission (HCR), and every 3 months thereafter. The molecular response was defined as complete (MCR) if the BCR-ABL/G6PDH ratio was less than 1x10-5. Results: Between October 2005 and February 2009, total 87 patients, aged 16-71 years, were enrolled with median follow-up of 5 years among survivors (range: 2.6-8.9 years). Eighty-two patients (94%) achieved HCR at a median 25 days (range, 14-69 days) and 45 patients (57.7%) of 78 evaluable patients achieved MCR at the same time. Within three months after induction treatment, 59 patients (67.8%) achieved MCR. Total MCR rate was 88.5% during the entire study period and the median time from treatment to MCR was 54 days (range, 13-384 days). Among these 77 MCR patients, 32 experienced molecular recurrence. After allogeneic HCT, 49 of 50 evaluated patients (98%) achieved MCR. Median time of MCR duration was 13 months (range, 0.9-60.3 months) and median molecular relapse-free survival (RFS) was 28 months. Thirty two patients who lost of MCR had significantly inferior RFS (P<0.0001) and OS (P=0.001) then 41 who maintained MCR. MCR achievement within 3 months after remission induction was significant predictor of RFS (P=0.004) and OS (P=0.003). Multivariate analyses after adjusting the Cox model was described in Table 1. Conclusions: Prospective assessment of molecular response and imatinib dose intensity is useful in identifying subgroups of Ph+ALL patients at a high risk of relapse. Clinical trial information: NCT00618501

Risk FactorMolecular relapse-free survival
PHR95% CI
Initial imatinib dose intensity within 7 weeks
    ≥90%0.0170.4050.192-0.853
    <90%1
Early complete molecular response within 3 months
    Yes0.0010.2510.111-0.570
    No1
Underwent allogeneic stem cell transplantation
    Yes0.0020.2840.130-0.621
    No1

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Abstract Details

Meeting

2016 ASCO Annual Meeting

Session Type

Publication Only

Session Title

Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Track

Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant

Sub Track

Acute Leukemia

Clinical Trial Registration Number

NCT00618501

Citation

J Clin Oncol 34, 2016 (suppl; abstr e18523)

DOI

10.1200/JCO.2016.34.15_suppl.e18523

Abstract #

e18523

Abstract Disclosures