Pseudo-Pelger-Huët anomaly induced by transplant medications

A 67-year-old male with myelodysplastic syndrome (MDS) with complex cytogenetic abnormalities developed acute myeloid leukemia (AML) within a short period of darbepoetin-alpha therapy. He received non-ablative chemotherapy followed by an allogeneic hematopoietic stem cell transplant (male donor). His post-transplant course was uneventful and within 1 month he achieved complete engraftment. Post-transplant medications included prednisone (80 mg per day as an initial dose, gradually tapered to 10 mg), mycophenolate mofetil (2,000 mg per day initially, reduced to 1,000 mg per day at 2-month status posttransplant), tacrolimus (1.5 mg per day, starting at 2-month status post-transplant), and other drugs. An automated complete blood count (CBC) 3 months post-transplant demonstrated a Hgb of 120 g/L (reference range 137– 173 g/L), white blood count (WBC) of 2.8 9 10/L (reference range 3.2–9.8 9 10/L) and platelets of 128 9 10/L (reference range 150–450 9 10/L). A concurrent peripheral blood smear showed a few unilobed neutrophils with abnormally clumped chromatin consistent with pseudo-Pelger-Huet anomaly (PPHA). In the subsequent 9 months, the automated CBC demonstrated a mild pancytopenia, but the peripheral blood smear showed continuous increase of the PPHA cells, ultimately affecting 94% of neutrophils at approximately 1-year post-transplant. These PPHAs displayed a spectrum of nuclear contours, including round (a), oval (b), coffee bean-shaped (c), reniform (d), peanut-shaped (e), bilobed (f) and other forms (g). Some PPHAs also contained detached round nuclear fragments in the cytoplasm, so-called Howell-Jolly-like inclusions (g, arrow head; Fig. 1). Eosinophils were unaffected, retaining their lobated morphology (h). A subsequent bone marrow examination demonstrated intermediate PPHA cells (i), but no other identifiable dysplasia or increase in the blasts. Conventional cytogenetics revealed a normal male karyotype (46, XY [20]) and engraftment analyses on the blood and marrow samples confirmed the donor origin of the myeloid elements (CD15 positive fraction). These ancillary studies excluded the possibility of relapsed or chemotherapy-related myeloid neoplasia. The neutrophils resumed their normal segmentation (j) 4 months later. Coincidentally, the clinical note stated that the tacrolimus dose was reduced to 0.5 mg per day from initial dose of 1.5 mg per day and prednisone was further tapered to 5 mg per day 7 weeks before the disappearance of pseudo-Pelger-Huet neutrophils in the routine peripheral blood smear examination. Therefore, the appearance of PPHA seemed to correlate with introduction of tacrolimus, and subsequent normalization of neutrophilic nuclear segmentation could be due to its dose reduction. Administration of multiple other medications confounds definitive delineation of the causative factors in this case. Pelger-Huet anomaly (PHA) was first described by Karl Pelger in 1928 [1], and was documented by G. J. Huet in 1931 as a benign autosomal dominant anomaly affecting granulocytic segmentation [2]. This hereditary anomaly is characterized by granulocytes with abnormally condensed chromatin and hypolobated nuclear contours, which can be round, oval, peanut-shaped, coffee bean-shaped or symmetrically bilobed. Despite the morphologic abnormalities, the granulocytes are functional, thus individuals with hereditary PHA are not more susceptible to bacterial infections. Conversely, PPHA is an acquired neutrophilic E. Wang (&) E. Kulbacki Department of Pathology, Duke University Medical Center, DUMC Box 3712, M-345 Davison Bldg (Green Zone), Duke Hospital South, Durham, NC 27710, USA e-mail: endi.wang@duke.edu