Association of three factors (ABCB1 gene expression, steroid response, early response at day + 8) on the response to ind
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ORIGINAL ARTICLE
Association of three factors (ABCB1 gene expression, steroid response, early response at day + 8) on the response to induction in patients with acute lymphoblastic leukemia Christian Ramos-Peñafiel 1 & Irma Olarte-Carrillo 2 & Rafael Cerón Maldonado 2 & Adrián de la Cruz Rosas 2 & Juan Collazo-Jaloma 1 & Adolfo Martínez-Tovar 1 Received: 20 March 2020 / Accepted: 17 September 2020 / Published online: 27 September 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Treatment of acute lymphoblastic leukemia (ALL) requires the combination of multiple drugs to integrate a complete remission. The different prognostic factors (age, leukocytes, risk, cytogenetic alterations) allow identifying those patients with a high risk of relapse, but there are few described factors that impact the induction response. The objective was to identify the utility of different risk factors (overexpression of the ABCB1 drug resistance gene, favorable response to steroids (FRS) and early response at day + 8 of treatment) on the percentage of complete remissions and overall survival. This is a prospective, observational study in adult patients with B-ALL without specific cytogenetic alterations, who started induction treatment based on a pretreatment with prednisone and subsequently vincristine (1.6 mg/m2 subcutaneous) plus daunorubicin (45 mg/m2 subcutaneously) on days + 1, + 8, + 15. The ABCB1 resistance gene was evaluated at diagnosis, the FRS at the end of the pretreatment and the early response during day + 8. A total of 53 adult patients diagnosed with ALL Philadelphia negative chromosome (Ph−), with immunophenotype B, with a normal karyotype, were studied. Cases with genetic abnormalities with a poor prognosis were excluded in order to reduce bias. The mean age was 48 years (range 17–68 years). 62.3% of patients were at high risk of relapse. When analyzing the risk factors, 30.2% showed high levels of the ABCB1 resistance gene, without showing an impact on the induction response (OR: 1.218, p = 0.743), but its overexpression was associated with a poor response to steroids as in the absence of early response. Individually, both the FRS (OR: 5.7, p = 0.004) and the absence of early response to day + 8 (OR: 6.42, p = 0.002) showed significance. By combining the different factors, having more than 2 was directly related to a failure (OR: 9.514, p = 0.000). The identification of factors such as FRS such as the persistence of blasts at the end of the first week of treatment is useful to identify patients at risk of failure in induction. Keywords ABCB1 = ATP binding cassette subfamily B member 1 . qRT-PCR = quantitative real-time polymerase chain reaction . RFE = Favorable response to steroids . BM + 8 = Early morphological response . ALL = Acute lymphoblastic leukemia
Introduction Currently, the treatment of acute lymphoblastic leukemia is based on the identification of different potential targets identified by flow cytometry (antiCD19, CD20, CD22, CD52), * Adolfo Martínez-Tovar [email protected]
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