Acquired Pelger-Huët anomaly in a patient treated with valganciclovir.

A follow-up blood count was performed on a 74-year-old woman diagnosed with colitis due to cytomegalovirus and under treatment with valganciclovir. The automated complete blood count revealed an abnormal white blood cells (WBC) scattergram together with WBC alert flags. The peripheral blood smear showed neutrophils with markedly hyposegmented nuclei or bilobed nuclei and very condensed chromatin or clumping chromatin all consistent with Pelger-Huët anomaly (PHA). We checked previous blood counts, ruling out an inherited PHA. We assessed the haematological, infectious and iatrogenic aetiologies for an acquired PHA. Once the valganciclovir treatment was completed and the drug was withdrawn, without changing the rest of the treatment, the morphological abnormalities of neutrophils were completely resolved. We conclude therefore that the acquired PHA presented by our patient is probably related to valganciclovir treatment.

[Acquired Pelger-Huët anomaly/abnormal chromatin clumping of granulocytes after allogeneic hematopoietic stem cell transplantation for acute myeloid leukaemia: medication or relapse? ]. / Anomalie de Pelger-Huët acquise/condensation anormale de la chromatine des granulocytes après allogreffe médullaire pour leucémie aiguë myéloïde : iatrogène ou signe de rechute ?

An acute myeloid leukemia was diagnosed in a 53-year-old female patient. She received an allogeneic stem cell transplant. After this transplant, some neutrophils with hyposegmented nucleus and abnormal chromatin clumping appeared in the peripheral blood, and their number gradually increased. The hypothesis of early relapse after transplant was ruled out and drug-related anomaly was suspected. The authors discuss about morphological features of constitutional and acquired Pelger-Huët anomaly. In the patient reported here, ciclosporine seemed to be involved in the phenomenon, as the morphological anomaly of the neutrophils gradually decreased after the drug was discontinued.

A case report on reversible Pelger-Huët anomaly depending on serum free fraction of valproic acid.

Pelger-Huët anomalies, which are characterized by an abnormal nuclear shape and chromatin organization in blood granulocytes, and are frequently confused with myelodysplastic syndrome. We herein report a case of Lenox syndrome in a patient treated with VPA for more than 25 years who developed significant Pelger-Huët anomalies. Despite the lack of any changes in the total VPA level throughout the patient's clinical course, the free fraction of VPA potently increased, likely due to a reduction in serum albumin. Following the administration of a smaller dose of VPA that reduced the serum free fraction of VPA to the normal range, the Pelger-Huët anomalies completely disappeared. It is necessary to monitor the free fraction of VPA in order to detect an overdose, which may induce adverse effects under conditions of hypoalbuminemia. The present case showed, for the first time, that VPA-induced Pelger-Huët anomalies occur in a dose-dependent and reversible manner.

Pseudo-Pelger-Huët anomaly induced by medications: a clinicopathologic study in comparison with myelodysplastic syndrome-related pseudo-Pelger-Huët anomaly.

Pseudo-Pelger-Huët anomaly (PPHA) has been documented in association with transplant medications and other drugs. This iatrogenic neutrophilic dysplasia is reversible with cessation or adjustment of medications but is frequently confused with myelodysplastic syndrome (MDS) based on the conventional concept that PPHA is a marker for dysplasia. We investigated the clinicopathologic features in iatrogenic PPHA and compared them with MDS-related PPHA. The 13 cases studied included 5 bone marrow/stem cell transplantations, 3 solid organ transplantations, 1 autoimmune disease, 3 chronic lymphocytic leukemias, and 1 breast carcinoma. For 12 cases, there was follow-up evaluation, and all demonstrated at least transient normalization of neutrophilic segmentation. All 9 cases of MDS demonstrated at least 2 of the following pathologic abnormalities on bone marrow biopsy: hypercellularity (8/9), morphologic dysplasia (8/9), clonal cytogenetic abnormality (7/9), and increased blasts (3/9), whereas these abnormalities were typically absent in iatrogenic PPHA. Iatrogenic PPHA displayed a higher proportion of circulating PPHA cells than in MDS (mean, 47.4%; SD, 31.6% vs mean, 12.3%; SD, 9.8; P < .01). A diagnostic algorithm is proposed in which isolated PPHA is indicative of transient or benign PPHA unless proven otherwise.

Neutrophil dysplasia (acquired pseudo-pelger anomaly) caused by ganciclovir.

Two thoracic organ-transplant recipients with persistent cytomegalovirus infection developed morphologic abnormalities in their circulating neutrophils while receiving either ganciclovir or its prodrug valganciclovir. Neither patient was receiving concomitant treatment with mycophenolate mofetil or azathioprine. In both patients, the morphologic abnormalities preceded the development of neutropenia and bone-marrow hypoplasia. The morphologic changes most likely reflected interference of DNA polymerization within bone marrow progenitor cells. The changes resolved completely after the drug was withdrawn.

Acquired and reversible Pelger-Huët anomaly of polymorphonuclear neutrophils in three transplant patients receiving mycophenolate mofetil therapy.

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.

Acquired Pelger-Huët anomaly in association with concomitant tacrolimus and fluconazole therapy following allogeneic bone marrow transplantation.

A 38-year-old Japanese woman with severe aplastic anemia received an allogeneic bone marrow transplant from her serologically HLA-identical father. Cyclosporine and methotrexate were administered to prevent graft-versus-host disease (GVHD). However, grade III acute GVHD developed on day 44, which was successfully treated with methylprednisolone and tacrolimus. Fluconazole therapy was started for oral candidiasis on day 112, but she complained of headache soon after. In addition to glycosuria and increased serum creatinine levels, Pelger-Huët anomaly of granulocytes was found in her blood, which disappeared after discontinuation of tacrolimus. Transient occurrence of Pelger-Huët cells may be associated with tacrolimus toxicity due to drug interaction with fluconazole.

Association of acquired Pelger-Huet anomaly with taxoid therapy.

We describe the occurrence of acquired Pelger-Huet anomaly (APHA) in 23 patients treated with paclitaxel (13) or docetaxel (10). A consistent peak of Pelger-Huet cells (PHC) within a range of 3-9 d after treatment with taxoids was noted. The APHA generally disappeared by day 21 after treatment. Peak PHC values for the first course were significantly different in paclitaxel versus docetaxel versus control groups (P < 0.0001) with the maximum PHC counts being significantly higher for docetaxel compared with paclitaxel (P < 0.001) and for paclitaxel compared with controls (P = 0.007). We conclude that taxoid therapy produces transient APHA which peaks between days 3 and 9 and is more pronounced with docetaxel than with paclitaxel.

Hematologic manifestations of long-term valproate therapy.

Sixty patients receiving long-term valproate (VPA) monotherapy were studied for hematologic side effects. All were patients in a long-term care facility and ranged in age from 2 to 29 years (mean 14.6 years). Twenty developed at least one prominent hematologic abnormality. Thrombocytopenia and macrocytosis were the most common findings. In patients with macrocytosis, platelet counts were inversely related to VPA levels. Serum B12 levels were increased in 51 of the patients. In 12 patients with macrocytosis who were extensively studied, no etiology for the increased MCV could be identified. An increased number of Pelger-Huet-like cells was noted in these 12 patients. None of the patients demonstrated hepatic dysfunction. Hematologic toxicity was never severe enough to discontinue therapy and always responded to small decrements in VPA therapy. VPA was discontinued in only 1 patient, owing to poor seizure control.

Reversible Pelger-Huët anomaly associated with ibuprofen therapy.

A patient had a case of acquired-reversible pseudo-Pelger-Huët anomaly associated with a hypersensitivity reaction. Seven weeks after the illness, the hematologic anomaly was no longer present.