Clofarabine can reduce the risk of cardiotoxicity and secondary tumor in children with leukemia

Original pie In recent years, the 5-year disease-free survival rate of children with acute lymphocytic leukemia (all) is more than 80% However, the prognosis of all children with relapse or first-line chemotherapy resistance is still poor The late cardiac toxicity caused by anthracycline exposure is also an important problem Clofarabine is the second generation of purine nucleoside analogues It was developed by bioenvision company in the United States and produced by Genzyme company In December 2004, it was approved by FDA rapid review channel to be marketed for the treatment of childhood acute lymphocytic leukemia Recently, the Journal of Clinical Oncology (JCO) published an aml08 phase III clinical trial online The results show that the use of clofarabine instead of daunorubicin and etoposide can improve the clinical prognosis of children, and reduce the risk of cardiotoxicity and secondary tumors From 2008 to 2017, 285 patients were enrolled from 8 clinical centers, 262 of whom were randomly assigned to receive clofarabine and cytarabine (CLO + AraC, n = 129) or high-dose cytarabine, daunorubicin and etoposide (hd-ade, n = 133) as the first induction course The second induction course included low-dose ade alone or in combination with sorafenib or vorinolta In addition, consolidation therapy includes additional 2-3 courses of chemotherapy or hematopoietic cell transplantation The final risk classification was based on genetic abnormalities and MRD levels on the 22nd day of initial remission induction The primary end point was MRD on day 22 The results showed that 263 (92.3%) of the 285 patients had complete remission after two courses of treatment The failure cases included 4 early death and 15 drug resistance Among 121 patients who received clo + AraC and could be evaluated, 57 (47%) had positive MRD on the 22nd day, while the proportion of patients who had positive MRD on the 22nd day in hd-ade group was significantly lower (42 / 121, 35%, or1.86, P = 0.04) However, there was no significant difference in 3-year event free survival (52.9% vs 52.4%, P = 0.94) and total survival (74.8% vs 64.6%, P = 0.1) between the clo + AraC and hd-ade groups The results showed that the combination of clofarabine and cytarabine during remission induction could reduce the demand of anthracycline and etoposide in children with AML, and reduce the incidence of cardiotoxicity and treatment-related tumors Clofarabine is a cytotoxin antitumor drug After phosphorylation in cells, it can inhibit DNA synthesis by inhibiting ribonucleotide reductase and DNA polymerase, and induce apoptosis by releasing cytochrome c and other apoptosis factors in mitochondria Clofarabine was approved by FDA in December 2004 It was listed in the United States in January 2005 It can be phosphorylated by deoxycytidine kinase, and it can be eliminated slowly in human leukemia cells It has good cytotoxic effect and low neurotoxicity To sum up, clofarabine is an effective and well tolerated new treatment option for relapsed / refractory all In the future, the clinical study of clofarabine will focus on the combination of other chemotherapy drugs to further improve the remission rate, reduce the side effects of chemotherapy, and improve the prognosis of children with relapsed / refractory acute leukemia.