title: Pharmacodynamics of cytarabine induced leucopenia: a retrospective cohort study.
abstract: OBJECTIVE
  Cytarabine is a pyrimidine analogue used to treat a variety of haematological malignancies. There are few data regarding the pharmacodynamics of cytarabine. The only publications regarding this issue cite a biphasic pattern of decline in white blood cell (WBC) counts following low and intermediate doses, in patients with various malignancies, most of them non-haematological. Our purpose was to establish the pharmacodynamics of cytarabine induced leucopenia in acute myeloid leukaemia (AML) patients treated with contemporary cytarabine containing protocols.
  
  
  METHODS
  We conducted a retrospective cohort study, including 56 patients with AML in complete remission who had received 89 cycles of intermediate or high dose cytarabine. Daily counts for WBCs and neutrophils (ANC) were collected during the first 15 days after the initiation of cytarabine administration and pharmacodynamics were analyzed. Further analysis was carried out to correlate between WBC and ANC pharmacodynamics and different cytarabine protocols [high dose cytarabine (HiDAC) vs. intermediate dose cytarabine (IDAC)].
  
  
  RESULTS
  Analysis of blood counts demonstrated a monophasic decline of WBCs and ANCs, unlike a previous depiction of a biphasic pattern. HiDAC was associated with a significantly sharper decline of WBCs than IDAC.
  
  
  CONCLUSIONS
  Our data support a monophasic decline pattern of WBCs and ANCs following contemporary cytarabine protocols. The decline rate is steeper for patients receiving HiDAC than for those receiving IDAC. These results might help form evidence based guidelines regarding patient monitoring intensity, timing of prophylactic antibacterial and antifungal treatment as well as growth factors' support following cytarabine based consolidation for AML.
authors.affiliation: Medicine A, Rabin Medical Centre, Beilinson Hospital, Tel Aviv, Israel; Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Daniel
authors.initials: D
authors.lastname: Shepshelovich
authors.forename: Yonatan
authors.initials: Y
authors.lastname: Edel
authors.forename: Hadar
authors.initials: H
authors.lastname: Goldvaser
authors.forename: Tal
authors.initials: T
authors.lastname: Dujovny
authors.forename: Ofir
authors.initials: O
authors.lastname: Wolach
authors.forename: Pia
authors.initials: P
authors.lastname: Raanani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D015331:Cohort Studies; D003561:Cytarabine / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000097:blood / Q000188:drug therapy*; D007958:Leukocyte Count; D007970:Leukopenia / Q000097:blood / Q000139:chemically induced*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine
keywords: AML; cytarabine; leucopenia; pharmacodynamics