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KMID : 0366220010360010060
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Korean Journal of Hematology
2001 Volume.36 No. 1 p.60 ~ p.70
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The Implications of E2A-PBX1 Positivity and Effect of Delayed Intensification Chemotherapy in t(1;19)-positive Childhood Acute Lymphoblastic Leukemia
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Seo Jong-Jin
Kim Eun-Jung
Park Jun-Eun
Seo Eul-Ju
Chi Hyun-Sook
Moon Hyung-Nam
Ghim Thae-T.
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Abstract
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Purpose: We studied the E2A-PBX1 positivity in t(1;19)-positive childhood acute lymphoblastic leukemia (ALL) patients during chemotherapy and follow-up period to evaluate the clinical implications of minimal residual disease (MRD) and the effect of delayed intensification chemotherapy on long-term survival.
Methods: Fifty-six bone marrow or peripheral blood samples collected retrospectively or prospectively before or during chemotherapy from 14 childhood ALL patients who had t(1;19) or E2A-PBX1 transcript at initial diagnosis were studied for the presence of E2A-PBX1 by RT-PCR. All patients received delayed intensification chemotherapy regardless of standard prognostic grouping for childhood ALL to evaluate its effect on the improvement of long-term survival.
Results: There were 11 t(1;19)-positive cases documented by karyotyping and 3 E2A-PBX1 transcript-positive cases amplified by PCR from the initial bone marrow samples. There were 11 cases of FAB L1 and 3 cases of L2. Immunophenotypic classification revealed 10 cases of group Ⅴ, 2 cases of group Ⅳ, and 1 case of group Ⅲ. Among 11 cases with documented karyotype, 9 cases (81.8%) had der(19)t(1;19) and the other 2 had balanced t(1;19). Fifty-six samples collected at 2 to 7 different time points of 14 patients revealed 4 cases of MRD immediately after completion of induction chemotherapy despite hematologic complete remission. Three of these cases relapsed eventually, and 1 was lost to follow-up. Among 12 cases who received adequate delayed intensificiation chemotherapy, 10 are alive in complete remission.
Conclusion: MRD detection by RT-PCR amplification of E2A-PBX1 transcript of induction chemotherapy was most informative for the prediction of long-term survival and relapse. The presence of MRD after completion of induction chemotherapy conferred poor prognosis. The addition of delayed intensification chemotherapy to standard chemotherapy regimen could abolish the adverse effect of t(1;19) in childhood ALL patients.
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KEYWORD
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E2A-PBX1, t(1, 19), Minimal residual disease, Childhood ALL, Chemotherapy
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