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Biol Blood Marrow Transplant. 2018 Aug;24(8):1621-1628. doi: 10.1016/j.bbmt.2018.04.020. Epub 2018 Apr 23.

Impact of an Additional Chromosome on the Clinical Outcomes of Hematopoietic Stem Cell Transplantation in Philadelphia Chromosome-Positive Acute Myeloid Leukemia in Adults.

Author information

1
Department of Hematology, Leukemia Research Institute, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
2
Department of Hematology, Leukemia Research Institute, Seoul St. Mary's Hematology Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: cumckim@catholic.ac.kr.

Abstract

The incidence of Philadelphia chromosome positivity (Ph+) in adults with acute myeloid leukemia (AML) is very low. Ph+ AML is considered to be high risk for failure to attain remission or for early relapse after standard chemotherapy. Because of the low incidence of the disease, it has been difficult to determine the best treatment, including the effects of tyrosine kinase inhibitors. We retrospectively analyzed 29 patients with Ph+ AML (median age, 45 years; range, 18 to 80) managed at our center between 2002 and 2016. Two patients were not treated at all, 3 received repeated low-dose cytarabine, and 24 were treated with 3 + 7 standard induction chemotherapy. All 27 treated patients also received interim imatinib 400 mg orally until the day of the next chemotherapy cycle began or as conditioning for allogeneic hematopoietic cell transplantation (HCT), which was performed in 17 patients. Of the 29 patients with Ph+ AML, 7 (24.1%) had additional inv(16), 3 of whom had therapy-related AML. In the 7 with inv(16), the median age was younger (31 versus 44 years, P = .083) and the complete remission (CR) rate was relatively higher (85.7% versus 54.5%, P = .214) than in those without inv(16). Among the 27 treated patients, 20 (74.1%) achieved CR after standard chemotherapy with interim imatinib and 2 (7.4%) achieved CR after low-dose cytarabine with interim imatinib. After a median follow-up of 65.5 months (range, 13.4 to 156.6), the 5-year overall survival (OS) among all 27 treated patients was 43.1%. For the 17 patients who underwent HCT the 5-year OS of 17 patients (10 in subgroup without inv(16) and 7 in subgroup with inv(16)) treated with allogeneic HCT was 69.3%. All 7 with inv(16) were still alive at the end of the study. In contrast, all patients not treated with HCT died within a median of 6.25 months (range, .2 to 18.2). Interim imatinib combined with chemotherapy yielded an acceptable remission rate in adult patients with Ph+ AML. Allogeneic HCT as a postremission therapy provided long-term disease control in two-thirds of those who underwent the transplant. We also demonstrated that inv(16) was related to a favorable outcome in Ph+ AML, including therapy-related AML.

KEYWORDS:

Acute myeloid leukemia; Imatinib; Philadelphia chromosome; inv(16); t(9;22)

PMID:
29698793
DOI:
10.1016/j.bbmt.2018.04.020

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