Neutrophil dysplasia characterised by a pseudo-Pelger-Huet anomaly occurring with the use of mycophenolate mofetil and ganciclovir following renal transplantation: a report of five cases

The 2008 revision of the World Health Organization (WHO) classification of myeloid neoplasms and acute leukemia: rationale and important changes

“…Diagnostic problems can arise when the clinical and laboratory findings suggest MDS but the morphologic findings are inconclusive; when there is secondary dysplasia caused by nutritional deficiencies, medications, toxins, growth factor therapy, inflammation or infection; or when marrow hypocellularity or myelofibrosis obscures the underlying disease process. 6,[55][56][57][58] In addition, for occasional patients in whom the diagnosis of MDS is clear, there may be difficulties in subclassification according to the previous WHO scheme, for example, in patients with isolated refractory thrombocytopenia accompanied by unilineage dysplasia of megakaryocytes. Although some diagnostic issues can be addressed in individual patients only by clinical evaluation and follow-up, the members of the CAC recommended that the minimal diagnostic criteria be more clearly stated, particularly for cases in which there is no increase in the blast percentage in the PB and/or BM, that the diagnostic role of cytogenetics and flow cytometry be clarified, and that the classification be modified to allow for more clinically relevant classification of patients who currently may fall into the "MDS, unclassifiable" category.…”

Hematologic abnormalities following renal transplantation

“…Other commonly utilized drugs applied in the transplantation setting, such as TMP-SMX for P. jirovecii prophylaxis and gancyclovir/valgancyclovir for CMV infection/disease, not infrequently cause pancytopenia and leucopenia, respectively. Dysmorphic changes involving neutrophil precursors and circulating neutrophils manifesting as pseudo-pelger cells have been associated with concomitant administration of MMF and gancyclovir [51] and tacrolimus and fluconazole [52]. Pathogenic mechanisms of drug-induced hematologic toxicity are complex, but a few salient features will be discussed.…”

Pseudo-Pelger-Huët anomaly induced by transplant medications

“…One of the dominant etiologies for this morphologic deviation is the increased use of transplant medications due to increased allogeneic organ or bone marrow transplants in the recent years. This neutrophilic abnormality in allogeneic transplant recipients has been reported to be associated with the use of tacrolimus and/or mycophenolate mofetil [4,5], and the effects may be synergistic with the concomitant use of other drugs [4,6]. The change is apparently reversible since neutrophils resume their segmentation following dose reduction or discontinuation of transplant medications in the reported cases [4][5][6].…”

“…This neutrophilic abnormality in allogeneic transplant recipients has been reported to be associated with the use of tacrolimus and/or mycophenolate mofetil [4,5], and the effects may be synergistic with the concomitant use of other drugs [4,6]. The change is apparently reversible since neutrophils resume their segmentation following dose reduction or discontinuation of transplant medications in the reported cases [4][5][6]. Because of the conventional opinion of PPHA as a marker for myelodysplasia [3], the presence of these iatrogenic PPHA in peripheral blood may cause diagnostic confusion, particularly in patients with bone marrow or hematopoietic stem cell transplant for MDS/AML.…”