title: Clinical and prognostic significance of histamine monitoring in patients with CML during treatment with imatinib (STI571).
abstract: BACKGROUND
  Although imatinib is highly effective in chronic myeloid leukemia (CML), drug-resistance may occur. Therefore, monitoring of minimal residual disease (MRD) during treatment with imatinib is important. However, most MRD-parameters are expensive and require special technology. We determined the value of histamine as MRD-marker in CML.
  
  
  METHODS
  Histamine levels were measured serially in whole blood samples before and during imatinib therapy in 80 CML patients by radioimmunoassay.
  
  
  RESULTS
  Histamine levels were highly upregulated in CML at diagnosis compared to healthy controls, and correlated with the presence of basophils. During treatment with imatinib, histamine levels decreased and returned to normal levels in those achieving a complete cytogenetic response (CCR). Loss of CCR during therapy was invariably accompanied by an increase in histamine. Moreover, a histamine level of >100 ng/ml three or six months after start of imatinib was associated with a significantly reduced probability of survival (p<0.05). Whereas basophils were found to correlate well with histamine during imatinib, no correlations were found between histamine and Ph+ metaphases or histamine and BCR/ABL.
  
  
  CONCLUSIONS
  Histamine-monitoring during treatment with imatinib is of prognostic significance.
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology, Center of Excellence for Clinical and Experimental Oncology (CLEXO), Medical University of Vienna, Austria.
authors.forename: H
authors.initials: H
authors.lastname: Agis
authors.forename: W R
authors.initials: WR
authors.lastname: Sperr
authors.forename: S
authors.initials: S
authors.lastname: Herndlhofer
authors.forename: H
authors.initials: H
authors.lastname: Semper
authors.forename: H
authors.initials: H
authors.lastname: Pirc-Danoewinata
authors.forename: O A
authors.initials: OA
authors.lastname: Haas
authors.forename: C
authors.initials: C
authors.lastname: Mannhalter
authors.forename: H
authors.initials: H
authors.lastname: Esterbauer
authors.forename: K
authors.initials: K
authors.lastname: Geissler
authors.forename: C
authors.initials: C
authors.lastname: Sillaber
authors.forename: U
authors.initials: U
authors.lastname: Jäger
authors.forename: P
authors.initials: P
authors.lastname: Valent
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001549:Benzamides; D015415:Biomarkers / Q000097:blood; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006632:Histamine / Q000097:blood* / Q000378:metabolism; D006801:Humans; D000068877:Imatinib Mesylate; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D008991:Monitoring, Physiologic / Q000379:methods; D018365:Neoplasm, Residual / Q000097:blood* / Q000175:diagnosis; D010879:Piperazines / Q000008:administration & dosage*; D011336:Probability; D011379:Prognosis; D011743:Pyrimidines / Q000008:administration & dosage*; D011863:Radioimmunoassay; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D016896:Treatment Outcome