Clinical and prognostic significance of histamine monitoring in patients with CML during treatment with imatinib (STI571)

Ann Oncol. 2007 Nov;18(11):1834-41. doi: 10.1093/annonc/mdm343. Epub 2007 Sep 5.

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.

Patients and 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.

Conclusion: Histamine-monitoring during treatment with imatinib is of prognostic significance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Benzamides
  • Biomarkers / blood
  • Cohort Studies
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Histamine / blood*
  • Histamine / metabolism
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / mortality
  • Male
  • Middle Aged
  • Monitoring, Physiologic / methods
  • Neoplasm, Residual / blood*
  • Neoplasm, Residual / diagnosis
  • Piperazines / administration & dosage*
  • Probability
  • Prognosis
  • Pyrimidines / administration & dosage*
  • Radioimmunoassay
  • Risk Assessment
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Survival Analysis
  • Treatment Outcome

Substances

  • Benzamides
  • Biomarkers
  • Piperazines
  • Pyrimidines
  • Histamine
  • Imatinib Mesylate