Kimiyoshi Sakaguchi1,2, Toshihiko Imamura2,3, Sae Ishimaru4,5, Chihaya Imai6, Hidemi Shimonodan7, Naoto Fujita8, Keiko Okada9, Takeshi Taketani10, Rie Kanai10, Hisamichi Tauchi11, Motohiro Kato12, Yasuko Kojima13, Arata Watanabe14, Takao Deguchi15, Yoshiko Hashii16, Nobutaka Kiyokawa17, Tomohiko Taki18, Akiko M Saito2, Keizo Horibe2, Atsushi Manabe19, Atsushi Sato20, Katsuyoshi Koh21. 1. Department of Pediatrics, Hamamatsu University School of Medicine, Hamamatsu, Japan. 2. Clinical Research Center, National Hospital Organization Nagoya Medical Center, Nagoya, Japan. 3. Department of Pediatrics, Kyoto Prefectural University of Medicine, Kyoto, Japan. 4. Department of Hematology and Oncology, Tokyo Metropolitan Children's Medical Center, Tokyo, Japan. 5. Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan. 6. Department of Pediatrics, Niigata University, Niigata, Japan. 7. Department of Pediatrics, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan. 8. Department of Pediatrics, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan. 9. Department of Pediatric Hematology/Oncology, Osaka City General Hospital, Osaka, Japan. 10. Department of Pediatrics, Shimane University Faculty of Medicine, Izumo, Japan. 11. Department of Pediatrics, Ehime University, Toon, Japan. 12. Division of Stem Cell Transplant and Cellular Therapy, Children's Cancer Center, National Center for Child Health and Development, Tokyo, Japan. 13. Department of Pediatrics, Toho University Omori Medical Center, Tokyo, Japan. 14. Department of Pediatrics, Nakadori General Hospital, Akita, Japan. 15. Department of Pediatrics, Mie University, Tsu, Japan. 16. Department of Pediatrics, Osaka University, Suita, Japan. 17. Department of Pediatric Hematology and Oncology Research, Research Institute, National Center for Child Health and Development, Tokyo, Japan. 18. Department of Medical Technology, Kyorin University Faculty of Health Sciences, Mitaka, Japan. 19. Department of Pediatrics, Hokkaido University Graduate School of Medicine, Sapporo, Japan. 20. Department of Hematology/Oncology, Miyagi Children's Hospital, Sendai, Japan. 21. Department of Hematology/Oncology, Saitama Children's Medical Center, Saitama, Japan.
Abstract
BACKGROUND: Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood. PROCEDURE: A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL. RESULTS: Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease. CONCLUSIONS: The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.
BACKGROUND: Rearrangements of chromosome 8q24/MYC (8q24/MYC-r), resulting from t(8;14)(q24;q32), t(2;8)(p11;q24), or t(8;22)(q24;q11), are mainly associated with Burkitt lymphoma/leukemia (BL) and rarely observed in patients with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). The characteristics of BCP-ALL with 8q24/MYC-r are poorly understood. PROCEDURE: A retrospective nationwide study of data from patients with pediatric BCP-ALL with 8q24/MYC-r in Japan was conducted to clarify the clinical and biological characteristics associated with 8q24/MYC-r BCP-ALL. RESULTS: Ten patients with BCP-ALL with 8q24/MYC-r, including three with double-hit leukemia (DHL) (two with t(8;14)(q24;q32) and t(14;18)(q32;q21) and one with t(8;14) and t(3;22)(q27;q11)), were identified. Patients with BCP-ALL with 8q24/MYC-r had higher median age and uric acid and lactate dehydrogenase levels, than those without 8q24/MYC-r. All patients were initially treated with ALL-type chemotherapy; however, four, including one with DHL, were switched to BL-type chemotherapy, based on cytogenetic findings. One patient relapsed after standard-risk ALL-type chemotherapy, and two patients with DHL did not attain complete remission with chemotherapy; all three died within 11 months. The other seven patients treated with BL-type or high-risk ALL-type chemotherapy are alive without disease. CONCLUSIONS: The clinical and laboratory features of BL with IG-MYC rearrangement, displaying a BCP immunophenotype (Wagener et al. and Herbrueggen et al. termed it as pre-BLL), are similar to those of BCP-ALL with 8q24/MYC-r. Low-risk ALL-type chemotherapy may not be appropriate for them, and further studies are required to establish an adequate therapeutic strategy. Further studies of DHL to identify new treatment strategies are also needed.