Predicting infections in high-risk patients with myelodysplastic syndrome/acute myeloid leukemia treated with azacitidine: a retrospective multicenter study.
Hypomethylating agents have become the standard therapy for patients with high-risk myelodysplastic syndrome (MDS). In Israel, azacitidine (AZA) is routinely used. Yet, infectious complications are common during AZA therapy. The current study was aimed to evaluate the incidence and predisposing risk factors for infections in AZA-treated patients. This retrospective study included patients treated with AZA in 18 Israeli medical institutions between 2008 and 2011. Data on 184 patients [157 high-risk MDS and 27 acute myeloid leukemia (AML)], with a median age of 71.6 (range 29-92) were recorded. Overall, 153 infectious events were reported during 928 treatment cycles (16.5%) administered to 100 patients. One hundred fourteen, 114/153 (75%) events required hospitalization and 30 (19.6%) were fatal. In a univariate analysis, unfavorable cytogenetics, low neutrophil, hemoglobin (Hb) and platelet (PLT) counts were found to be associated with infections (24.4% vs. 12.9%, P < 0.0001; 27% vs. 13.5%, P < 0.0001; 20.4% vs. 11%, P < 0.0001 and 29.2% vs. 14.2%, P < 0.0001, respectively). In multivariate analysis, only low Hb level, low PLT count, and unfavorable cytogenetics remained significant. Prior to therapy, poor cytogenetics, PLT count below 20 × 10⁹/L and neutrophil count below 0.5 × 10⁹/L were predictive of the risk of infection during the first two cycles of therapy. In conclusion, patients with unfavorable cytogenetics, presenting with low neutrophil and PLT counts, are susceptible to infections. Evaluation of infection risk should be repeated prior to each cycle. Patients with poor cytogenetics in whom AZA is prescribed despite low PLT count are particularly at high risk for infections and infection prophylaxis may be considered.
Division of Hematology, Sheba Medical Center, Tel-Hashomer, Tel Aviv University, Israel.
Drorit
D
Merkel
Kalman
K
Filanovsky
Anat
A
Gafter-Gvili
Liat
L
Vidal
Ariel
A
Aviv
Moshe E
ME
Gatt
Itay
I
Silbershatz
Yair
Y
Herishanu
Ariela
A
Arad
Tamar
T
Tadmor
Najib
N
Dally
Anatoly
A
Nemets
Ory
O
Rouvio
Aharon
A
Ronson
Katrin
K
Herzog-Tzarfati
Luiza
L
Akria
Andrei
A
Braester
Ilana
I
Hellmann
Shay
S
Yeganeh
Arnon
A
Nagler
Ronit
R
Leiba
Moshe
M
Mittelman
Yishai
Y
Ofran
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001374:Azacitidine / Q000627:therapeutic use*; D002869:Chromosome Aberrations; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D015994:Incidence; D007239:Infections / Q000150:complications* / Q000453:epidemiology / Q000276:immunology / Q000503:physiopathology; D007557:Israel / Q000453:epidemiology; D015470:Leukemia, Myeloid, Acute / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D008297:Male; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000150:complications* / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D009503:Neutropenia / Q000209:etiology; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000209:etiology
D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine