title: Oral Ezatiostat HCl (TLK199) and Myelodysplastic syndrome: a case report of sustained hematologic response following an abbreviated exposure.
abstract: Treatment options for patients with lower risk non-del(5q) myelodysplastic syndromes (MDS) who fail erythroid stimulating agents are restricted to one of the hypomethylating drugs with an expected response rate of approximately 50%. Ezatiostat HCl, an agent with the potential for producing multi-lineage responses in this population is currently in clinical investigation phase. This case report describes a 77 year old male who received less than two cycles of therapy with ezatiostat HCl which had to be aborted due to intolerable side effects, but which produced a sustained normalization of all three blood counts. This trilineage response has now lasted for more than a year. Interestingly, the patient began with a del(5q) abnormality and responded briefly to lenalidomide. Upon relapse of the anemia, a bone marrow showed the disappearance of the del(5q) but the appearance of a new clonal abnormality t(2;3). Given that the patient had a complete cytogenetic response to a truncated exposure to lenalidomide followed by a trilineage response to an even briefer course of ezatiostat HCl suggests a potential role for ezatiostat HCl in del(5q) patients who relapse following lenalidomide.
authors.affiliation: Dept of Hematology and Oncology, University of Nebraska Medical Center, Omaha, NE 68198, USA.
authors.forename: Fahd
authors.initials: F
authors.lastname: Quddus
authors.forename: Jessica
authors.initials: J
authors.lastname: Clima
authors.forename: Helen
authors.initials: H
authors.lastname: Seedham
authors.forename: Ghulam
authors.initials: G
authors.lastname: Sajjad
authors.forename: Naomi
authors.initials: N
authors.lastname: Galili
authors.forename: Azra
authors.initials: A
authors.lastname: Raza
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002872:Chromosome Deletion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D041905:Erythroid Cells / Q000187:drug effects*; D005978:Glutathione / Q000008:administration & dosage / Q000031:analogs & derivatives*; D006454:Hemoglobins / Q000378:metabolism; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D009190:Myelodysplastic Syndromes / Q000188:drug therapy* / Q000235:genetics; D012074:Remission Induction; D013792:Thalidomide / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D006454:Hemoglobins; C096329:gamma-Glu-S-BzCys-PhGly diethyl ester; D013792:Thalidomide; D000077269:Lenalidomide; D005978:Glutathione