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

doi:10.5045/br.2019.54.1.45

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Original Article

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Blood Res 2019; 54(1):

Published online March 31, 2019

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^*, and Bin Cho^*

Author Info. +

Department of Pediatrics, The Catholic University of Korea, Seoul, Korea.

Correspondence to : Correspondence to Bin Cho, 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. chobinkr@catholic.ac.kr

Received: September 15, 2018; Revised: October 6, 2018; Accepted: October 10, 2018

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

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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

Article

Original Article

Blood Res 2019; 54(1): 45-51

Published online March 31, 2019 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^*, and Bin Cho^*

Department of Pediatrics, The Catholic University of Korea, Seoul, Korea.

Correspondence to:Correspondence to Bin Cho, 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. chobinkr@catholic.ac.kr

Received: September 15, 2018; Revised: October 6, 2018; Accepted: October 10, 2018

Abstract

Background

Methods

Results

Conclusion

Keywords: Acute lymphoblastic leukemia, Philadelphia chromosome, Children, RQ-PCR

Abstract

Fig 1.

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Figure 1.

Estimated 5-year EFS (A) and OS (B) of study patients.

Blood Research 2019; 54: 45-51https://doi.org/10.5045/br.2019.54.1.45

Table 1 Patient characteristics.

^a)A good steroid response indicates <1,000/µL blasts after one week of prephase steroid treatment..

Abbreviations: abn, abnormalities; NCI, National Cancer Institute..

Table 2 Transplant characteristics.

^a)HLA matching based on high resolution typing of HLA-A, -B, -C, -DR alleles..

Abbreviations: Ara, cytarabine; ATG, anti-thymocyte globulin; BM, bone marrow; CB, cord blood; Cy, cyclophosphamide; Flu, fludarabine; GVHD, graft-versus-host disease; HLA, human leukocyte antigen; MMF, mycophenolate mofetil; MTX, methotrexate; PBSC, peripheral blood stem cells; TBI, total body irradiation..

Table 3 Changes in RQ-PCR value for BCR-ABL1 fusion transcript.

^a)Calculated by log (RQ-PCR value at time point/RQ-PCR value at baseline). ^b)RQ-PCR value of ‘0.’.

Abbreviations: HCT, hematopoietic cell transplantation; RQ-PCR, real time quantitative polymerase chain reaction..

Table 4 Impact of risk factors for 5-year EFS and incidence of molecular relapse.<sup>a)</sup>

^a)Data for a subset of all risk factors analyzed. ^b)Additional cytogenetic abnormalities besides Ph. ^c)Based on RQ-PCR of the fusion transcript. ^d)RQ-PCR value of ‘0.’.

Abbreviations: Consol., Consolidation; Dexa, dexamethasone; HCT, hematopoietic cell transplantation; HLA, human leukocyte antigen; Pred, prednisolone..