Blood Res 2019; 54(1): 45-51  https://doi.org/10.5045/br.2019.54.1.45
Outcome and prognostic factors of children with Philadelphia chromosome-positive acute lymphoblastic leukemia treated with imatinib followed by allogeneic hematopoietic cell transplantation in first remission
Juae Shin, Na Yeong Lee, Seongkoo Kim, Jae Wook Lee, Pil-Sang Jang, Nack-Gyun Chung, Bin Cho
Department of Pediatrics, The Catholic University of Korea, Seoul, Korea
Correspondence to: Bin Cho, M.D., Ph.D. Nack-Gyun Chung, M.D., Ph.D. Department of Pediatrics, Seoul Saint Mary’s Hospital, The Catholic University of Korea, Seocho-gu, Banpo-daero 222, Seoul 06591, Korea, E-mail: B.C., chobinkr@catholic.ac.kr N.G.C., cngped@catholic.ac.kr
Received: September 15, 2018; Revised: October 6, 2018; Accepted: October 10, 2018; Published online: March 31, 2019.
© The Korean Journal of Hematology. All rights reserved.

cc This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background
Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is a subset of ALL with poor prognosis. Here, we analyzed the outcomes and prognostic factors of children with Ph+ ALL who received imatinib and chemotherapy followed by allogeneic hematopoietic cell transplantation (HCT) in first complete remission (CR).

Methods
Thirty-one Ph+ ALL patients (female 10) diagnosed from January 2005 to December 2016 were included in the study. All patients were treated with imatinib and chemotherapy before HCT. Bone marrow (BM) evaluations included real-time quantitative polymerase chain reaction (RQ-PCR) study of the BCR-ABL1 fusion transcript. All patients received HCT with total body irradiation (TBI)-based conditioning at a median of 6.4 (range, 4.2‒ 47.1) months from diagnosis.

Results
Compared to values at diagnosis, the median decrement of RQ-PCR value post-consolidation, and prior to HCT was -3.7 Log and -4.8 Log, respectively. The 5-year event-free survival (EFS) and overall survival of the patients were 64.5±9.4% (20/31) and 75.0±8.3% (23/31) respectively. Events included relapse (N=5) and death in CR post-HCT (N=6). The 5-year incidence of molecular relapse was 30.9±9.1% (9/31). An RQ-PCR decrement of at least -4 Log post-consolidation significantly predicted lower incidence of molecular relapse: 7.7±7.7% for ≥-4 Log decrement, 50.0±13.8% for <-4 Log decrement (P=0.027).

Conclusion
Decrement in RQ-PCR for the BCR-ABL1 transcript that was determined after consolidation was the only significant prognostic factor for incidence of molecular relapse. In the post-induction TKI initiation setting, steadfast imatinib treatment during consolidation may allow for optimum post-HCT outcomes.
Keywords: Acute lymphoblastic leukemia, Philadelphia chromosome, Children, RQ-PCR


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