Clofarabine in the treatment of myelodysplastic syndromes

Abstract

DNA-methyltransferase inhibitors are the mainstay of therapy for many patients with MDS who require treatment. Although these agents are very well tolerated and represent a significant advancement in the treatment of MDS by improving transfusion requirements and prolonging survival in various subgroups of patients, response rates are modest and the duration of response is short. In addition to providing a valuable treatment option for pediatric ALL patients, clofarabine has substantial activity against MDS and is well tolerated by elderly patients, thus rendering it a potential therapeutic option.

Outlook and Management of Patients with Myelodysplastic Syndromes Failed by Hypomethylating Agents

“…Clofarabine, a second-generation nucleoside analog active in AML and MDS, is sometimes used as post-HMA salvage therapy [35,72]. Clofarabine's use in the specific population of HMA failures was described in abstract form in 2014 [37].…”

Life after hypomethylating agents in myelodysplastic syndrome

“…Because hypomethylating drugs have shown the greatest efficacy in the treatment of MDS, old [46] and newly synthesized nucleoside analogs have been evaluated in clinics. An interesting feature of HMTs is that in addition to (or because of) the decrease in DNA methylation, they may induce immunomodulation [47 && ].…”

Aproximación a la genotoxicodinámica de antimetabolitos antineoplásicos análogos de purina usando como referente la acción de la radiación ionizante (⁶⁰CO)

“…Los antimetabolitos análogos de desoxiadenina comparten una estructura química similar, pero presentan una ligera afinidad hacía algún tipo celular, p.e. la cladribina inhibe principalmente la ADN polimerasa α (Hentosch et al, 1990), presenta mejor eficacia en pacientes con leucemias del tipo B (Piro et al, 1988) y esclerosis múltiple (EM) (Lizak et al, 2020); la fludarabina inhibe la ADN polimerasa α, β y ε, y es un potente inhibidor de la ribonucleótido reductasa (Huang y Plunkett, 1995;Lukenbill y Kalaycio, 2013), es más eficiente para linfomas de bajo grado de leucemia linfoblástica crónica (McLaughlin et al, 1997); la clofarabina inhibe la ADN polimerasa α e inhibe a la ribonucleótido reductasa (Parker et al, 1991), es más eficiente para células de leucemia mieloide aguda (LMA) (Larson y Venugopal, 2009) y Síndrome mielodisplásico (SMD) (Bryan et al, 2014).…”