title: Acquired and reversible Pelger-Huët anomaly of polymorphonuclear neutrophils in three transplant patients receiving mycophenolate mofetil therapy.
abstract: Deficient nuclear segmentation and abnormal chromatin condensation define Pelger-Huët anomaly of polymorphonuclear neutrophils. Next to the hereditary irreversible form, acquired forms both reversible and irreversible have been described. We describe three transplant patients who were all investigated for a left shift in the absence of symptoms or signs of infection and in whom acquired reversible Pelger-Huët anomaly was discovered. The abnormal PMN phenotype was induced by mycophenolate mofetil (MMF). MMF is a necessary but not sufficient condition for the development of the anomaly. In our three patients a dose-response effect was observed regarding plasma MMF concentration and severity of neutrophil dysplasia. Except for one slightly elevated value, the patients' plasma MMF levels were within the therapeutic range. None of the patients, one who was neutropenic at presentation and two who were non-neutropenic, developed infectious complications. From our three cases as well as those of other authors, we identify previous graft rejection episodes as a potential predisposing factor for the development of PHA. In the first patient, drug withdrawal led to normalization of PMN morphology. In the other two patients, the left shift disappeared after dose reduction. In these latter two patients, a form of desensitization to the effect of MMF on neutro- phils was observed following re-augmentation of MMF dose.
authors.affiliation: Division of Hematology, Geneva University Hospital, Switzerland. lars.asmis2jhmi.edu
authors.forename: Lars M
authors.initials: LM
authors.lastname: Asmis
authors.forename: Karine
authors.initials: K
authors.lastname: Hadaya
authors.forename: Pietro
authors.initials: P
authors.lastname: Majno
authors.forename: Christian
authors.initials: C
authors.lastname: Toso
authors.forename: Frédéric
authors.initials: F
authors.lastname: Triponez
authors.forename: Michel
authors.initials: M
authors.lastname: Starobinski
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006084:Graft Rejection; D006801:Humans; D008297:Male; D008875:Middle Aged; D009173:Mycophenolic Acid / Q000009:adverse effects* / Q000031:analogs & derivatives / Q000627:therapeutic use; D009504:Neutrophils / Q000473:pathology*; D016377:Organ Transplantation / Q000009:adverse effects*; D010381:Pelger-Huet Anomaly / Q000139:chemically induced*; D010641:Phenotype; D012307:Risk Factors
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D009173:Mycophenolic Acid