scholarly journals Clofarabine: a next-generation deoxyadenosine analogue

2018 ◽  
Vol 7 (5) ◽  
pp. 1048
Author(s):  
Amit Bhalla
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Ribonucleotide Reductase ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Dna Polymerases ◽  
Lymphoproliferative Disorders ◽  
Deoxycytidine Kinase ◽  
Prolonged Retention ◽  
Leukaemia Relapse

Acute lymphoblastic leukaemia (ALL) is the most common of the paediatric leukaemias. It is estimated that the use of modern combination chemotherapy results in long-term remission in nearly 80% of children diagnosed with ALL. Despite therapy advances, approximately 20% of children with ALL, experience leukaemia relapse. Clofarabine (2-chloro-2’-fluoro-2’-deoxy-9-β-D-arabinofuranosyladenine) is a second-generation nucleoside analogue and is structurally related to fludarabine and cladribine which are widely used in the treatment of lymphoproliferative disorders. Clofarabine exhibits greater affinity to deoxycytidine kinase (dCyd kinase) and prolonged retention in leukaemic blasts compared to fludarabine and cladribine. Clofarabine inhibits both DNA polymerases and ribonucleotide reductase (RNR). This results in impaired DNA synthesis through inhibition of DNA elongation as well as depletion of deoxyribonucleotides. Accumulation of clofarabine triphosphate, in the blasts of patients with refractory leukemia has been demonstrated. Prolonged intracellular half-life of 24 hours for clofarabine triphosphate. Clofarabine is indicated for the treatment of pediatric patients 1 to 21 years old with relapsed or refractory acute lymphoblastic leukemia after at least two prior regimens.

scholarly journals Association of Bacteremic Sepsis With Long-term Neurocognitive Dysfunction in Pediatric Patients With Acute Lymphoblastic Leukemia

2018 ◽  
Vol 172 (11) ◽  
pp. 1092 ◽  
Author(s):  
Yin Ting Cheung ◽  
Aaron Eskind ◽  
Hiroto Inaba ◽  
Melissa M. Hudson ◽  
Ching-Hon Pui ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Neurocognitive Dysfunction

scholarly journals Balancing cure and long-term risks in acute lymphoblastic leukemia

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 190-197 ◽  
Author(s):  
Lewis B. Silverman
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Late Effects ◽  
Pediatric Patients ◽  
Lymphoblastic Leukemia ◽  
Malignant Neoplasms ◽  
Second Malignant Neoplasms ◽  
Current Therapies ◽  
Cure Rates ◽  
Long Term Survivors

Abstract Cure rates for children and adolescents with acute lymphoblastic leukemia (ALL) have improved dramatically over the last few decades. With this success has come increasing recognition of the adverse late effects of treatment. The significant long-term sequelae in the earliest cohort of long-term survivors treated in the 1970s and 1980s are well documented. To reduce the incidence of these late effects, the majority of pediatric patients treated on more contemporary regimens receive less intensive treatment than did those treated 30-40 years ago. However, current therapies are not risk free; children treated with contemporary regimens remain at risk for developing long-term toxicities, including cardiac dysfunction, osteonecrosis, neurocognitive impairment, and second malignant neoplasms. One of the great challenges facing clinical investigators today is to identify interventions that will reduce the frequency and severity of long-term toxicities without adversely affecting cure rates. The use of dexrazoxane as a cardioprotectant (to prevent anthracycline-associated cardiotoxicity) and alternate-week dosing of dexamethasone (to reduce the risk of osteonecrosis) are examples of 2 such successful strategies. This article provides an overview of the long-term toxicities associated with current therapies and reviews results of clinical trials designed to minimize the burden of cure in long-term survivors.

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