LETTER TO THE EDITOR Allogeneic stem cell transplantation from donors with mosaic Turner syndrome Bone Marrow Transplantation (2006) 38, 385–386. doi:10.1038/sj.bmt.1705456 Turner syndrome (TS) is a genetic disorder affecting 1/2500–3000 live-born females. It is characterized by the complete or partial absence of one of the X-chromosomes, and is frequently accompanied by mosaicism (45,X/46,XX). Its most consistent clinical features are short stature and ovarian failure. Loss of specific genes located on the X- chromosome are thought to be responsible for a range of disorders, including osteoporosis, hypothyroidism, diabetes mellitus (DM), cardiovascular and gastrointestinal dis- eases, ophthalmic disorders, as well as various immuno- logical defects. 1,2 We report two cases of allogeneic stem cell transplantation (SCT) in which 45,X/46,XX stem cells derived from donors with mosaic TS were used. Patient 1, a 27-year-old woman, had common acute lymphoblastic leukemia with an abnormal karyotype: 46,X,t(X;22)(p11.3;q12),t(2;16)(p11;q11)[15]/46,XX[5]. She underwent a consolidative allogeneic SCT after a busulfan– cyclophosphamide (Bu–Cy) conditioning regimen from her phenotypically human leukocyte antigen (HLA)-matched 2.5-year-old daughter. The post transplant course was unremarkable and mild acute and chronic graft-versus-host disease (GVHD) were seen. A routine cytogenetic study of the marrow at 6 months revealed 45,X[9]/46,XX[11]. To investigate the origin of 45,X cells, the donor’s constitu- tional karyotype was evaluated, confirming a mosaic TS 45,X[15]/46,XX[5]. The disease relapsed at 9 months and cytogenetic analysis revealed 45,X[8]/46,X,t(X;22)(p11.3; q12),t(2;16)(p11;q11)[2]/46,XX[16]. A second allograft was performed from the same donor in second remission after total body irradiation-based conditioning and attenuated GVHD prophylaxis. The patient developed grade II acute GVHD again. The disease relapsed 5 months after the second allograft and the patient died of relapse. Patient 2, a 47-year-old man, had acute myeloid leukemia with a normal karyotype who was allografted in first relapse after Bu–Cy conditioning from his 54-year-old one HLA-A antigen-mismatched sister. Post transplant course was characterized by grade II acute GVHD and thrombotic microangiopathy. Cytogenetic analysis of the bone marrow revealed 45,X[12]/46,XX[12]/46,XY[1]. Donor’s peripheral blood cultures stimulated with phyto- hemagglutinin showed a mosaic TS 45,X[7]/46,XX[18], confirming donor origin of 45,X cells. Two months later, chromosome studies showed complete donor karyotype 45,X[7]/46,XX[13] and chimerism analysis, by short tandem repeats of polymorphic DNA segments, was 99.5% of donor origin. On day þ 105, the patient developed extensive chronic cutaneous GVHD with conjuctival and oral involvement. The post transplant course was further complicated by the development of DM, severe osteoporo- sis with a pathologic fracture of L2 and cytomegalovirus (CMV) infection. Reports of leukemia in patients with TS are rare. Therefore, toxicity and outcome after intensive chemother- apy for patients with 45,X/46,XX mosaicism are still unclear. 3 Various immunological disturbances have been detected in patients with TS, including decreased numbers of circulating T-lymphocytes. 2,4 Consequently, the study of immune recovery of the donor’s 45,X T cells following SCT is particularly interesting, because it might influence infectious complications, antitumor activity, the develop- ment and the extent of acute and chronic GVHD, as well as the process of engraftment of hematopoietic stem cells. It is also not clear if 45,X hematopoietic stem cells would respond normally to immunosuppression. A prompt hematopoietic recovery and immune recon- stitution were noticed in both of our cases. Both recipients manifested acute GVHD and CMV infections, which were successfully treated. The second patient developed severe osteoporosis and DM, which are common after steroid therapy. In the early post-transplantation period, the effects of high-dose glucocorticosteroids combined with other immunosuppressive drugs, such as cyclosporin A, might have been implicated in the manifestation of osteoporosis. 5 DM has been reported to be multifactorial, involving pancreatic irradiation, endocrine replacement and corticosteroid therapy. 6,7 Osteoporosis and DM are very common in adults with TS, possibly owing to the dosage of specific genes located on X-chromosome in 45,X cells. 1 Women with TS show a reduction in their bone mass and an increased risk of osteoporotic fractures. A genome-wide linkage scan for bone mineral density, which characterizes osteoporosis, has shown linkage on chromo- somes 11q23 and Xq27. 8 Type II DM is 2–4 times more frequent in women with TS compared with the general population. As a prompt hematopoietic recovery and immune reconstitution were noticed in both our patients, with no unusual transplant-related complications, we believe that a donor with TS is probably acceptable if no other donor is available. However, these patients should be followed closely after transplantation. KN Manola 1 , C Sambani 1 , D Karakasis 2 , I Baltathakis 2 , N Zoumbos 3 and A Symeonidis 3 1 Laboratory of Health Physics & Environmental Hygiene, Inst. NT-RP, National Center for Scientific Research (NCSR) ‘Demokritos’, Athens, Greece; Bone Marrow Transplantation (2006) 38, 385–386 & 2006 Nature Publishing Group All rights reserved 0268-3369/06 $30.00 www.nature.com/bmt