Review
Oncology
Khalil Saleh, Alexis Fernandez, Florence Pasquier
Summary: The outcome of patients with Philadelphia-chromosome positive acute lymphoblastic leukemia (Ph+ ALL) has dramatically improved in the past 20 years with the introduction of tyrosine kinase inhibitors and monoclonal antibodies. These treatments have shown great efficacy in young and fit patients, leading to questioning the reliance on chemotherapy and stem cell transplantation. They can also be safely used in elderly patients, who make up the majority of Ph+ ALL patients. This review focuses on the recent changes in the management of Ph+ ALL patients and the development of new therapeutic strategies.
Review
Medicine, General & Internal
Robin Foa, Sabina Chiaretti
Summary: Current frontline therapy for Ph-positive acute lymphoblastic leukemia, which includes tyrosine kinase inhibitors, glucocorticoids, and blinatumomab, has significantly improved survival and achieved high-level clearance of measurable tumor cells.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Wendy Stock, Giovanni Martinelli, Matthias Stelljes, Daniel J. DeAngelo, Nicola Goekbuget, Anjali S. Advani, Susan O'Brien, Michaela Liedtke, Akil A. Merchant, Ryan D. Cassaday, Tao Wang, Hui Zhang, Erik Vandendries, Elias Jabbour, David Marks, Hagop M. Kantarjian
Summary: The study demonstrated that InO was more effective than standard intensive chemotherapy for patients with R/R Ph+ ALL, showing higher rates of complete remission and minimal residual disease negativity, as well as improved hematopoietic stem cell transplantation rates. However, there was no significant benefit in overall survival, and the probability of being event-free at 12 months was higher with InO treatment.
Letter
Oncology
Satoshi Nishiwaki, Isamu Sugiura, Daisuke Koyama, Yukiyasu Ozawa, Masahide Osaki, Yuichi Ishikawa, Hitoshi Kiyoi
Summary: The study utilized the eXtreme Gradient Boosting algorithm to predict events in Philadelphia chromosome-positive acute lymphoblastic leukemia. Important features such as BCR-ABL lineage, polymerase chain reaction value, age, and white blood cell count were identified and used to stratify risk groups, leading to clear differences in event-free survival and overall survival. The machine learning-aided analysis successfully identified clinically useful prognostic factors using data from a relatively small number of patients.
BIOMARKER RESEARCH
(2021)
Review
Cell Biology
Jiale Ma, Shan Chen, Yanqing Huang, Jie Zi, Jinlong Ma, Zheng Ge
Summary: The case report describes a rare instance of a patient with MPL-mutated essential thrombocythemia developing into Philadelphia positive B lymphoblastic leukemia after 13 years. Treatment with a new tyrosine kinase inhibitor led to remission, but the patient eventually relapsed. This case provides evidence on the clonal relationship of myeloproliferative neoplasms and post-MPN acute lymphoblastic leukemia.
Article
Hematology
Shengxuan Fan, Lina Wang, Yaoyao Lu, Zijian Li
Summary: TKIs play a crucial role in the treatment of a specific type of acute lymphoblastic leukemia, but certain mutations can cause resistance to most inhibitors. Olverembatinib, a newly developed inhibitor, has shown promise in treating a different type of leukemia and further research is needed for its application in another type. The combination therapy of blinatumomab and olverembatinib has shown efficacy in treating relapsed diseases.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Huan Chen, Lan -ping Xu, Xiao-hui Zhang, Yu Wang, Yu-hong Chen, Chen-hua Yan, Yi-fei Cheng, Wei Han, Yao Chen, Ya-zhen Qin, Yanrong Liu, Ying-jun Chang, Kai-yan Liu, Xiao-jun Huang
Summary: This study evaluated the safety and outcomes of ponatinib maintenance therapy after hematopoietic cell transplantation (HCT) in patients with Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ALL) who harbor the T315I mutation. The results showed that maintenance therapy with ponatinib is safe after HCT, and patients with T315I mutation who received prophylactic regimen showed promising results with an acceptable relapse rate and encouraging survival.
Article
Medicine, General & Internal
Miaomiao Zhao, Xiya Gui, Qiuling Wu, Linghui Xia, Yadan Wang
Summary: The survival rate of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) was around 30% until recently. Tyrosine kinase inhibitors (TKIs) have shown efficacy in treating Ph+ ALL in adults, but resistance mechanisms can lead to disease recurrence. A 71-year-old Chinese female patient diagnosed with Ph+ ALL (B-cell) based on abnormal blood counts and bone marrow analysis achieved complete remissions with different TKIs but eventually relapsed and died from infection. Emerging multidrug-resistant mutations within the BCR-ABL1 kinase domain present challenges for sequential TKIs therapy. Identifying new pan-inhibitor compounds and exploring potential drug combinations are crucial for overcoming resistance.
Article
Hematology
Hisashi Ishida, Yuki Arakawa, Daiichiro Hasegawa, Ikuya Usami, Yoshiko Hashii, Yasuyuki Arai, Satoshi Nishiwaki, Dai Keino, Keisuke Kato, Maho Sato, Nao Yoshida, Yukiyasu Ozawa, Keiko Okada, Moe Hidaka, Yuki Yuza, Masatsugu Tanaka, Kenichiro Watanabe, Junko Takita, Yoshiyuki Kosaka, Naoto Fujita, Junji Tanaka, Atsushi Sato, Yoshiko Atsuta, Toshihiko Imamura
Summary: In this study, data of Ph+ALL patients receiving HSCT in Japan were retrospectively collected, showing that RIC regimen in HSCT for younger patients had comparable long-term leukemia-free survival rates to the traditional MAC regimen, with RIC being an independent favorable prognostic factor.
ANNALS OF HEMATOLOGY
(2023)
Article
Oncology
Tatsuya Masuda, Shintaro Maeda, Sae Shimada, Naoya Sakuramoto, Ken Morita, Asami Koyama, Kensho Suzuki, Yoshihide Mitsuda, Hidemasa Matsuo, Hirohito Kubota, Itaru Kato, Kuniaki Tanaka, Junko Takita, Masahiro Hirata, Tatsuki R. Kataoka, Tatsutoshi Nakahata, Souichi Adachi, Hideyo Hirai, Shuichi Mizuta, Kazuhito Naka, Yoichi Imai, Shinya Kimura, Hiroshi Sugiyama, Yasuhiko Kamikubo
Summary: This report demonstrates that targeting the transcriptional regulation of BCR-ABL1 by the RUNX1 transcription factor may help overcome TKI resistance in Ph+ ALL cells, with Chb-M' being a potential novel drug for patients with TKI-resistant refractory Ph+ ALL.
Article
Oncology
Yang Dai, Jingcao Huang, Pu Kuang, Yiguo Hu, Qiang Zeng, Wanhua Zhang, He Li, Fangfang Wang, Tingting Guo, Dan Zhang, Dongni Yi, Yuhuan Zheng, Ting Liu
Summary: The combination of dasatinib and interferon-alpha has potential synergistic activity against Ph+ALL and shows promise as maintenance therapy for Ph+ALL patients who are unfit for allo-HSCT.
AMERICAN JOURNAL OF CANCER RESEARCH
(2022)
Article
Health Care Sciences & Services
Jiaoyang Cai, Hu Liu, Yumei Chen, Jie Yu, Ju Gao, Hua Jiang, Xiaowen Zhai, Xiuli Ju, Xuedong Wu, Ningling Wang, Xin Tian, Changda Liang, Yongjun Fang, Fen Zhou, Hong Li, Lirong Sun, Liangchun Yang, Jing Guo, Aiguo Liu, Chi-kong Li, Yiping Zhu, Jingyan Tang, Jun J. Yang, Shuhong Shen, Cheng Cheng, Ching-Hon Pui
Summary: This study aimed to compare the effects of first-generation and second-generation ABL-targeted tyrosine kinase inhibitors (TKIs) on the growth of children with Ph+ ALL. The results showed that dasatinib and imatinib had similar adverse impacts on children's growth.
LANCET REGIONAL HEALTH-WESTERN PACIFIC
(2023)
Article
Oncology
Kiyomi Morita, Hagop M. Kantarjian, Koji Sasaki, Ghayas C. Issa, Nitin Jain, Marina Konopleva, Nicholas J. Short, Koichi Takahashi, Courtney D. DiNardo, Tapan M. Kadia, Guillermo Garcia-Manero, Naval Daver, Guillermo Montalban Bravo, Jorge E. Cortes, Farhad Ravandi, Elias Jabbour
Summary: Dasatinib monotherapy has shown modest clinical activity in CML-LBP, while combination therapy of hyper-CVAD and dasatinib has significantly improved the outcome of Ph-positive ALL. Patients with CML-LBP are less likely to achieve deep molecular remission compared to those with Ph-positive ALL, but their survival outcomes are similar. In Ph-positive ALL, achieving deeper molecular remission is associated with better survival outcomes.
Article
Oncology
Marie-Anne Couturier, Xavier Thomas, Emmanuel Raffoux, Francoise Huguet, Celine Berthon, Celestine Simand, Maria-Pilar Gallego-Hernanz, Yosr Hicheri, Mathilde Hunault Berger, Colombe Saillard, Thibaut Leguay, Clemence Loiseau, Marie-Christine Bene, Patrice Chevallier
Summary: The study retrospectively examined the efficacy of a new chemo-free approach combining blinatumomab with ponatinib in treating Ph+ ALL patients, showing promising results with most patients achieving complete remission. Differences were observed in relapse/progression rates between allo and non allo cases, highlighting the need for further research to confirm the findings. Prospective studies are warranted to evaluate the safety, tolerability, and efficacy of the combination therapy.
LEUKEMIA & LYMPHOMA
(2021)
Article
Oncology
Yong Guo, Fang-Fang Wang, Bing Xiang, Hong-Bing Ma, Yu-Ping Gong
Summary: The study revealed that tanshinone IIA significantly enhanced the cytotoxic and apoptotic induction effects of imatinib in Ph+ ALL cells by regulating signaling pathways and inhibiting specific proteins. The experimental results in animal models also showed that the combination therapy of imatinib and tanshinone IIA synergistically reduced leukemia burden without increasing side effects.