When the sexes of a stem cell transplantation (SCT) recipient and donor differ, posttransplant chimerism analysis should include sex chromosomal analysis. Several methodologies can be used to detect sex chromosomes, including karyotype analysis by G-banding and sex chromosome fluorescence in situ hybridization. If the SCT was sex-incompatible, sex chromosomal reconstitution of bone marrow/peripheral blood cells should be monitored, and a transient pattern from the donor to recipient may be observed.
We treated a 65-year-old woman with myeloblastic syndrome with excess blasts-2 (MDS-EB-2). by SCT. She underwent BMT from an HLA fully matched unrelated male donor. The patient received a reduced-intensity regimen of 30 mg/m2 fludarabine for 5 days and 3.2 mg/kg busulfan for 4 days. She achieved neutrophil engraftment on day 22 and both erythrocyte and platelet engraftments on day 30. We then checked her bone marrow and analyzed the chimerism status. The recipient bone marrow cells were 47, XXY (20/20 cells) according to karyotype analysis (Figure 1), with an XYY signal of 91.4%, XY signal of 3.0%, and XX signal of 5.6% in sex chromosome fluorescence in situ hybridization analysis (500 cells).
A chromosomal XYY phenotype is rare in healthy males. XYY syndrome affects only 1 in 1000 males and is often underdiagnosed. The donor in this case was 52-year-old Japanese man, height 175 cm (Japanese average for men in their 50s, 170.2 cm), weight 72.0 kg (body mass index 24.16 kg/m2), with a normal appearance. The donor was judged to be an eligible transplant donor by a transplantation physician. A routine health check arranged by the Japanese Marrow Donor Program included a physical examination and laboratory tests (blood cell counts and biochemical analysis) by the transplant coordination doctor. The donor cells did not undergo karyotype analysis before transplantation upon the pretransplant screening in the setting of Japanese Marrow Donor Program. The XYY sex chromosome karyotype is not associated with any specific hereditary diseases. Furthermore, there have been no reports of XYY chromosome detection after SCT, possibly because of the rarity of this karyotype among healthy men (0.01%).1 A study of chromosomal abnormalities after cord blood transplantation found no cases of donor-derived XYY chromosomal abnormality.1 Thus, although donor-derived XXY abnormalities are relatively common, donor-derived XYY is very rare.1 Another study found no XYY abnormalities among BMTs from healthy donors.2
This is the first case report to detect an XYY chromosomal abnormality after BMT from an HLA fully matched unrelated healthy male donor. The donor’s sex chromosomal abnormality, associated with a normal phenotypic appearance, was only revealed after reconstitution of hematopoiesis in the recipient. This case highlights the need to consider the possibility of rare chromosomal abnormalities in healthy donors.
We thank Mitchell Arico and Susan Furness, PhD, from Edanz Group (www.edanzediting.com/ac) for editing drafts of this article.
1. Kawaguchi K, Nakamura T, Nohara M, et al. Donor-derived 47, XXY in an unrelated cord blood transplant recipient.Springerplus2014372
2. Kuffel DG, Schultz CG, Ash RC, et al. Normal cytogenetic values for bone marrow based on studies of bone marrow transplant donors.Cancer Genet Cytogenet19915539–48