THE JOURNAL OF PEDIATRICS
www.jpeds.com
converting enzyme 2 in fetal programmed hypertension. Hypertension 2009;53:404-8. 30. Goodfellow J, Bellamy MF, Gorman ST, Brownlee M, Ramsey MW, Lewis MJ, et al. Endothelial function is impaired in fit young adults of low birth weight. Cardiovasc Res 1998;40:600-6. 31. McEniery CM, Bolton CE, Fawke J, Hennessy E, Stocks J, Wilkinson IB, et al. Cardiovascular consequences of extreme prematurity: the EPICure study. J Hypertens 2011;29:1367-73. 32. Hovi P, Andersson S, Eriksson JG, Jarvenpaa AL, Strang-Karlsson S, Makitie O, et al. Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356:2053-63.
Vol. 167, No. 1 33. Zhang J, Zhang Y, Deng W, Chen B. Elevated serum uric acid is associated with angiotensinogen in obese patients with untreated hypertension. J Clin Hypertens 2014;16:569-74. 34. Bae JS, Shin DH, Park PS, Choi BY, Kim MK, Shin MH, et al. The impact of serum uric acid level on arterial stiffness and carotid atherosclerosis: The Korean Multi-Rural Communities Cohort Study. Atherosclerosis 2013;231:145-51. 35. Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003;42: 474-80.
50 Years Ago in THE JOURNAL OF PEDIATRICS A Long-Term Study of Cerebrospinal Leukemia Haghbin M, Zuelzer WW. J Pediatr 1965;67:23-8
ifty years ago in The Journal, Haghbin and Zuelzer reported leukemic involvement of the central nervous system (CNS) in 205 children with acute “stem cell” leukemia. The results represent an impressive collection of data from Children’s Hospital of Michigan between 1955 and 1964. The incidence of CNS involvement was 29.8%, of which 63.9% occurred prior to bone marrow relapse and 91.8% occurred within 30 months of remission. The 61 patients with CNS leukemia were treated for 135 episodes of CNS disease either with 0.1 mg/kg of intrathecal aminopterin, which is an anti-folate predating methotrexate, radiation therapy, or a combination. Interestingly, remissions with intrathecal aminopterin experienced longer time to CNS recurrence (mean 5.9 months, range 0-26 months) than with radiation (mean 3.6 months, range 1-10 months) or a combination (mean 5.1 months, range 1-17 months). This study is a milestone for its cohort size, follow-up, length, and evaluation of the natural course of CNS recurrences in the age of systemic treatment without CNS prophylaxis. This laid groundwork for St. Jude Children’s Research Hospital’s “Total Therapy” for childhood acute leukemia using prophylactic craniospinal irradiation and intrathecal methotrexate, which decreased CNS relapse to 10% and increased survival to over 50%.1 Further advances in the treatment of childhood leukemia over the past 50 years have led to overall survival rates approaching 90%, though CNS relapse persists in 5% to 10% of patients. In these patients with CNS relapse, bone marrow transplantation has not yielded better outcomes than further chemotherapy with irradiation.2 As childhood leukemia undergoes greater molecular stratification with newer targeted agents that increase cure rates while mitigating toxicity, such approaches might also prevent CNS relapse and build upon the work of pioneers like Haghbin and Zuelzer.
F
Nicholas A. Vitanza, MD Department of Neurology Stanford University Palo Alto, California
References
http://dx.doi.org/10.1016/j.jpeds.2015.01.018
1. Simone J, Aur RJ, Hustu HO, Pinkel D. “Total therapy” studies of acute lymphocytic leukemia in children: current results and prospects for cure. Cancer 1972;30:1488-94. 2. Eapen M, Zhang MJ, Devidas M, Raetz E, Ritchey AK, Godder K, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia 2008;22:281-6.
80
Washburn et al
www.jpeds.com
converting enzyme 2 in fetal programmed hypertension. Hypertension 2009;53:404-8. 30. Goodfellow J, Bellamy MF, Gorman ST, Brownlee M, Ramsey MW, Lewis MJ, et al. Endothelial function is impaired in fit young adults of low birth weight. Cardiovasc Res 1998;40:600-6. 31. McEniery CM, Bolton CE, Fawke J, Hennessy E, Stocks J, Wilkinson IB, et al. Cardiovascular consequences of extreme prematurity: the EPICure study. J Hypertens 2011;29:1367-73. 32. Hovi P, Andersson S, Eriksson JG, Jarvenpaa AL, Strang-Karlsson S, Makitie O, et al. Glucose regulation in young adults with very low birth weight. N Engl J Med 2007;356:2053-63.
Vol. 167, No. 1 33. Zhang J, Zhang Y, Deng W, Chen B. Elevated serum uric acid is associated with angiotensinogen in obese patients with untreated hypertension. J Clin Hypertens 2014;16:569-74. 34. Bae JS, Shin DH, Park PS, Choi BY, Kim MK, Shin MH, et al. The impact of serum uric acid level on arterial stiffness and carotid atherosclerosis: The Korean Multi-Rural Communities Cohort Study. Atherosclerosis 2013;231:145-51. 35. Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003;42: 474-80.
50 Years Ago in THE JOURNAL OF PEDIATRICS A Long-Term Study of Cerebrospinal Leukemia Haghbin M, Zuelzer WW. J Pediatr 1965;67:23-8
ifty years ago in The Journal, Haghbin and Zuelzer reported leukemic involvement of the central nervous system (CNS) in 205 children with acute “stem cell” leukemia. The results represent an impressive collection of data from Children’s Hospital of Michigan between 1955 and 1964. The incidence of CNS involvement was 29.8%, of which 63.9% occurred prior to bone marrow relapse and 91.8% occurred within 30 months of remission. The 61 patients with CNS leukemia were treated for 135 episodes of CNS disease either with 0.1 mg/kg of intrathecal aminopterin, which is an anti-folate predating methotrexate, radiation therapy, or a combination. Interestingly, remissions with intrathecal aminopterin experienced longer time to CNS recurrence (mean 5.9 months, range 0-26 months) than with radiation (mean 3.6 months, range 1-10 months) or a combination (mean 5.1 months, range 1-17 months). This study is a milestone for its cohort size, follow-up, length, and evaluation of the natural course of CNS recurrences in the age of systemic treatment without CNS prophylaxis. This laid groundwork for St. Jude Children’s Research Hospital’s “Total Therapy” for childhood acute leukemia using prophylactic craniospinal irradiation and intrathecal methotrexate, which decreased CNS relapse to 10% and increased survival to over 50%.1 Further advances in the treatment of childhood leukemia over the past 50 years have led to overall survival rates approaching 90%, though CNS relapse persists in 5% to 10% of patients. In these patients with CNS relapse, bone marrow transplantation has not yielded better outcomes than further chemotherapy with irradiation.2 As childhood leukemia undergoes greater molecular stratification with newer targeted agents that increase cure rates while mitigating toxicity, such approaches might also prevent CNS relapse and build upon the work of pioneers like Haghbin and Zuelzer.
F
Nicholas A. Vitanza, MD Department of Neurology Stanford University Palo Alto, California
References
http://dx.doi.org/10.1016/j.jpeds.2015.01.018
1. Simone J, Aur RJ, Hustu HO, Pinkel D. “Total therapy” studies of acute lymphocytic leukemia in children: current results and prospects for cure. Cancer 1972;30:1488-94. 2. Eapen M, Zhang MJ, Devidas M, Raetz E, Ritchey AK, Godder K, et al. Outcomes after HLA-matched sibling transplantation or chemotherapy in children with acute lymphoblastic leukemia in a second remission after an isolated central nervous system relapse: a collaborative study of the Children’s Oncology Group and the Center for International Blood and Marrow Transplant Research. Leukemia 2008;22:281-6.
80
Washburn et al
