Hidemasa Matsuo1,2, Naomi Nakamura1, Daisuke Tomizawa3, Akiko Moriya Saito4, Nobutaka Kiyokawa5, Keizo Horibe4, Yoko Nishinaka-Arai1,6, Mayu Tokumasu7, Hiroshi Itoh1, Yasuhiko Kamikubo1, Hideki Nakayama8, Akitoshi Kinoshita9, Takashi Taga10, Akio Tawa11, Tomohiko Taki12, Shiro Tanaka13, Souichi Adachi1. 1. Department of Human Health Sciences, Kyoto University, Kyoto, Japan. 2. Department of Clinical Laboratory, Kyoto University Hospital, Kyoto, Japan. 3. Division of Leukemia and Lymphoma, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan. 4. Clinical Research Center, National Nagoya Hospital, Aichi, Japan. 5. Department of Pediatric Hematology and Oncology Research, National Research Institute for Child Health and Development, Tokyo, Japan. 6. Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan. 7. Department of Pediatrics, Kyoto University, Kyoto, Japan. 8. Department of Pediatrics, National Hospital Organization, Fukuoka-Higashi Medical Center, Fukuoka, Japan. 9. Department of Pediatrics, St. Marianna University School of Medicine, Kanagawa, Japan. 10. Department of Pediatrics, Shiga University of Medical Science, Shiga, Japan. 11. Department of Pediatrics, Osaka National Hospital, Osaka, Japan. 12. Department of Molecular Diagnostics and Therapeutics, Kyoto Prefectural University of Medicine, Kyoto, Japan. 13. Department of Pharmacoepidemiology, Kyoto University, Kyoto, Japan.
Abstract
BACKGROUND: Overexpression of CXC chemokine receptor 4 (CXCR4+) is a poor prognostic factor in adult acute myeloid leukemia (AML); however, its prognostic significance in pediatric AML is unclear. PROCEDURE: This retrospective study examined the prognostic significance of CXCR4+ in pediatric AML patients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. RESULTS: In the total cohort (n = 248), no significant differences were observed between CXCR4+ patients (n = 81) and CXCR4- patients (n = 167) in terms of 3-year overall survival (OS) (69.4% vs. 75.2%, P = 0.44). However, there was a significant difference in 3-year OS between CXCR4+ and CXCR4- patients in the low-risk (LR) group (n = 93; 79.2% vs. 98.3%, P = 0.007). CXCR4+ patients in the t(8;21) AML without KIT mutation group had a significantly worse 3-year OS than CXCR4- patients (n = 44; 76.1% vs. 100.0%, P = 0.01). Multivariate Cox regression analysis identified CXCR4+ as a poor prognostic factor for OS in LR AML patients (hazard ratio, 11.47; P = 0.01). Consistent with the data for survival analysis, CXCR4+ patients in the t(8;21) AML group had a higher incidence of splenomegaly than CXCR4- patients (25.9% vs. 5.9%, P = 0.03). CONCLUSIONS: These results suggest that CXCR4+ is a poor prognostic factor for LR patients, particularly t(8;21) patients without KIT mutation. The poor outcome was only applicable to OS, not relapse-free survival (RFS); thus, CXCR4+ may be associated with a poor prognosis after recurrence. Intensive therapy, including administration of CXCR4 antagonists, may be promising for pediatric AML patients with LR.
BACKGROUND: Overexpression of CXC chemokine receptor 4 (CXCR4+) is a poor prognostic factor in adult acute myeloid leukemia (AML); however, its prognostic significance in pediatric AML is unclear. PROCEDURE: This retrospective study examined the prognostic significance of CXCR4+ in pediatric AMLpatients enrolled in the Japanese Pediatric Leukemia/Lymphoma Study Group AML-05 study. RESULTS: In the total cohort (n = 248), no significant differences were observed between CXCR4+ patients (n = 81) and CXCR4- patients (n = 167) in terms of 3-year overall survival (OS) (69.4% vs. 75.2%, P = 0.44). However, there was a significant difference in 3-year OS between CXCR4+ and CXCR4- patients in the low-risk (LR) group (n = 93; 79.2% vs. 98.3%, P = 0.007). CXCR4+ patients in the t(8;21) AML without KIT mutation group had a significantly worse 3-year OS than CXCR4- patients (n = 44; 76.1% vs. 100.0%, P = 0.01). Multivariate Cox regression analysis identified CXCR4+ as a poor prognostic factor for OS in LR AMLpatients (hazard ratio, 11.47; P = 0.01). Consistent with the data for survival analysis, CXCR4+ patients in the t(8;21) AML group had a higher incidence of splenomegaly than CXCR4- patients (25.9% vs. 5.9%, P = 0.03). CONCLUSIONS: These results suggest that CXCR4+ is a poor prognostic factor for LR patients, particularly t(8;21) patients without KIT mutation. The poor outcome was only applicable to OS, not relapse-free survival (RFS); thus, CXCR4+ may be associated with a poor prognosis after recurrence. Intensive therapy, including administration of CXCR4 antagonists, may be promising for pediatric AMLpatients with LR.