Starting chemotherapy several days before the first lumbar puncture for diagnosis and treatment of acute lymphoblastic leukemia (ALL) may reduce the risk of central nervous system (CNS) relapse in children, according to a study from St. Jude Children’s Research Hospital and collaborators in China. The findings appear online today in the journal Blood.
The research focused on how clinical care, including availability of total intravenous anesthesia and the diagnostic tool flow cytometry, may influence the risk of CNS relapse.
“This study identified factors to help us predict and better manage the risk of CNS relapse that will be useful for treating ALL patients worldwide, in both resource-rich and resource-limited countries,” said corresponding author Ching-Hon Pui, M.D., chair of the St. Jude Department of Oncology. Pui pioneered pediatric ALL treatment that has achieved 94% long-term survival for St. Jude patients without brain irradiation.
Improved survival, but relapse risk remains
The study is the largest yet of pediatric ALL. The analysis included 7,640 children and adolescents enrolled in a clinical trial conducted at 20 hospitals and medical centers in China.
The treatment protocol was adapted from recent St. Jude clinical trials. Patients were treated in settings that were widely different in available technology and clinical resources. For example, just three of the 20 medical centers offered total intravenous anesthesia for children undergoing spinal taps, and only two had flow cytometry to diagnose leukemia cells in cerebrospinal fluid.
The five-year, overall survival rate was 91% for study patients, and the cancer-free survival rate was 80%, a dramatic improvement from previous clinical trials in China. But 1.9% of patients relapsed in the CNS alone, and in another 2.7% of patients the relapse included the CNS.
CNS relapse risk reduction
Increasing the number of pediatric ALL patients worldwide who become long-term survivors requires identifying those at risk for CNS relapse and preventing it, along with improving their quality of life, Pui said.
The factors associated with CNS relapse are:
- Treatment timing: Patients in this study began dexamethasone treatment several days before their first lumbar puncture for intrathecal therapy. This upfront treatment reduced leukemic cells in the blood and central nervous system, which lowered the risk of introducing cancer cells into the cerebrospinal fluid during later spinal taps.
- Total intravenous anesthesia: Studies have shown total intravenous anesthesia reduced the risk of bleeding during spinal taps (traumatic lumbar punctures) and optimized drug delivery during intrathecal therapy. In this study, central nervous system relapse was lower in patients who received total intravenous anesthesia for spinal taps to deliver intrathecal therapy.
- Flow cytometry: Compared with conventional microscopic examination, flow cytometry analysis allows more accurate diagnosis of the presence of leukemic cells in the cerebrospinal fluid. The test was associated with reduced CNS relapse, but flow cytometry is not widely available in the U.S. or other countries. Flow cytometry was available in only two of the 20 facilities in this study.
Authors and funding
The first authors are Jingyan Tang and Jiaoyang Cai, Shanghai Children’s Medical Center; Jie Yu, Chongqing Medical University; Li Zhang, State Key Laboratory of Experimental Hematology; and Shaoyan Hu, Children’s Hospital of Soochow University. The senior authors are Pui; Chi-Kong Li, Hong Kong Children’s Hospital; Xiaofan Zhu, State Key Laboratory; and Shuhong Shen, Shanghai Children’s Medical Center. The other St. Jude authors are Cheng Cheng and Jun J. Yang.
The research was funded in part by VIVA China Children’s Cancer Foundation; National Cancer Institute (CA21765); St. Baldrick’s Foundation; and ALSAC, the St. Jude fundraising and awareness organization.
St. Jude Children's Research Hospital
St. Jude Children's Research Hospital is leading the way the world understands, treats and cures childhood cancer and other life-threatening diseases. It is the only National Cancer Institute-designated Comprehensive Cancer Center devoted solely to children. Treatments developed at St. Jude have helped push the overall childhood cancer survival rate from 20% to 80% since the hospital opened more than 50 years ago. St. Jude freely shares the breakthroughs it makes, and every child saved at St. Jude means doctors and scientists worldwide can use that knowledge to save thousands more children. Families never receive a bill from St. Jude for treatment, travel, housing and food — because all a family should worry about is helping their child live. To learn more, visit stjude.org or follow St. Jude on social media at @stjuderesearch.