title: Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme.
abstract: The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors for response, we analysed a cohort of 90 MDS, CMML and AML patients who have been treated in a Dutch compassionate named patient programme. Patients received azacitidine for a median of five cycles (range 1-19). The overall response rate (complete/partial/haematological improvement) was 57% in low risk MDS, 53% in high risk MDS, 50% in CMML, and 39% in AML patients. Median overall survival (OS) was 13·0 (9·8-16·2) months. Multivariate analysis confirmed circulating blasts [Hazard Ratio (HR) 0·48, 95% confidence interval (CI) 0·24-0·99; P = 0·05] and poor risk cytogenetics (HR 0·45, 95% CI 0·22-0·91; P = 0·03) as independent predictors for OS. Interestingly, this analysis also identified platelet doubling after the first cycle of azacitidine as a simple and independent positive predictor for OS (HR 5·4, 95% CI 0·73-39·9; P = 0·10). In conclusion, routine administration of azacitidine to patients with variable risk groups of MDS, CMML and AML is feasible, and subgroups with distinct efficacy of azacitidine treatment can be identified.
authors: Department of Haematology, University Medical Centre Groningen, Hanzeplein 1, Groningen, The Netherlands.
authors: Lieke H
authors: LH
authors: van der Helm
authors: Canan
authors: C
authors: Alhan
authors: Pierre W
authors: PW
authors: Wijermans
authors: Marinus
authors: M
authors: van Marwijk Kooy
authors: Ron
authors: R
authors: Schaafsma
authors: Bart J
authors: BJ
authors: Biemond
authors: Aart
authors: A
authors: Beeker
authors: Mels
authors: M
authors: Hoogendoorn
authors: Bastiaan P
authors: BP
authors: van Rees
authors: Okke
authors: O
authors: de Weerdt
authors: Jurgen
authors: J
authors: Wegman
authors: Ward J
authors: WJ
authors: Libourel
authors: Sylvia A
authors: SA
authors: Luykx-de Bakker
authors: Monique C
authors: MC
authors: Minnema
authors: Rolf E
authors: RE
authors: Brouwer
authors: Fransien
authors: F
authors: Croon-de Boer
authors: Matthijs
authors: M
authors: Eefting
authors: Kon-Siong G
authors: KS
authors: Jie
authors: Arjan A
authors: AA
authors: van de Loosdrecht
authors: Jan
authors: J
authors: Koedam
authors: Nic J G M
authors: NJ
authors: Veeger
authors: Edo
authors: E
authors: Vellenga
authors: Gerwin
authors: G
authors: Huls
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D001792:Blood Platelets / Q000187:drug effects*; D015331:Cohort Studies; D057176:Compassionate Use Trials; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood* / Q000188:drug therapy; D015477:Leukemia, Myelomonocytic, Chronic / Q000097:blood* / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000097:blood* / Q000188:drug therapy; D009426:Netherlands; D012189:Retrospective Studies; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine