Allogeneic Stem Cell Transplantation from Donors with Mosaic Turner Syndrome

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LETTER TO THE EDITOR Allogeneic stem cell transplantation from donors with mosaic Turner syndrome

Bone Marrow Transplantation (2006) 38, 385–386. extensive chronic cutaneous GVHD with conjuctival and doi:10.1038/sj.bmt.1705456 oral involvement. The post transplant course was further complicated by the development of DM, severe osteoporosis with a pathologic fracture of L2 and cytomegalovirus (CMV) infection. Turner syndrome (TS) is a genetic disorder affecting Reports of leukemia in patients with TS are rare. 1/2500–3000 live-born females. It is characterized by the Therefore, toxicity and outcome after intensive chemother- complete or partial absence of one of the X-chromosomes, apy for patients with 45,X/46,XX mosaicism are still and is frequently accompanied by mosaicism (45,X/46,XX). unclear.3 Various immunological disturbances have been Its most consistent clinical features are short stature and detected in patients with TS, includingdecreased numbers ovarian failure. Loss of specific genes located on the X- of circulatingT-lymphocytes. 2,4 Consequently, the study of chromosome are thought to be responsible for a range of immune recovery of the donor’s 45,X T cells followingSCT disorders, includingosteoporosis, hypothyroidism, diabetes is particularly interesting, because it might influence mellitus (DM), cardiovascular and gastrointestinal dis- infectious complications, antitumor activity, the develop- eases, ophthalmic disorders, as well as various immuno- ment and the extent of acute and chronic GVHD, as well as logical defects.1,2 We report two cases of allogeneic stem the process of engraftment of hematopoietic stem cells. It is cell transplantation (SCT) in which 45,X/46,XX stem cells also not clear if 45,X hematopoietic stem cells would derived from donors with mosaic TS were used. respond normally to immunosuppression. Patient 1, a 27-year-old woman, had common acute A prompt hematopoietic recovery and immune recon- lymphoblastic leukemia with an abnormal karyotype: stitution were noticed in both of our cases. Both recipients 46,X,t(X;22)(p11.3;q12),t(2;16)(p11;q11)[15]/46,XX[5]. She manifested acute GVHD and CMV infections, which were underwent a consolidative allogeneic SCT after a busulfan– successfully treated. The second patient developed severe cyclophosphamide (Bu–Cy) conditioningregimenfrom her osteoporosis and DM, which are common after steroid phenotypically human leukocyte antigen (HLA)-matched therapy. In the early post-transplantation period, the 2.5-year-old daughter. The post transplant course was effects of high-dose glucocorticosteroids combined with unremarkable and mild acute and chronic graft-versus-host other immunosuppressive drugs, such as cyclosporin A, disease (GVHD) were seen. A routine cytogenetic study of might have been implicated in the manifestation of the marrow at 6 months revealed 45,X[9]/46,XX[11]. To osteoporosis.5 DM has been reported to be multifactorial, investigate the origin of 45,X cells, the donor’s constitu- involvingpancreatic irradiation, endocrine replacement tional karyotype was evaluated, confirminga mosaic TS and corticosteroid therapy.6,7 Osteoporosis and DM are 45,X[15]/46,XX[5]. The disease relapsed at 9 months and very common in adults with TS, possibly owingto the cytogenetic analysis revealed 45,X[8]/46,X,t(X;22)(p11.3; dosage of specific genes located on X-chromosome in 45,X q12),t(2;16)(p11;q11)[2]/46,XX[16]. A second allograft was cells.1 Women with TS show a reduction in their bone performed from the same donor in second remission after mass and an increased risk of osteoporotic fractures. A total body irradiation-based conditioningand attenuated genome-wide linkage scan for bone mineral density, which GVHD prophylaxis. The patient developed grade II acute characterizes osteoporosis, has shown linkage on chromo- GVHD again. The disease relapsed 5 months after the somes 11q23 and Xq27.8 Type II DM is 2–4 times more second allograft and the patient died of relapse. frequent in women with TS compared with the general Patient 2, a 47-year-old man, had acute myeloid population. leukemia with a normal karyotype who was allografted in As a prompt hematopoietic recovery and immune first relapse after Bu–Cy conditioningfrom his 54-year-old reconstitution were noticed in both our patients, with no one HLA-A antigen-mismatched sister. Post transplant unusual transplant-related complications, we believe that a course was characterized by grade II acute GVHD and donor with TS is probably acceptable if no other donor is thrombotic microangiopathy. Cytogenetic analysis of the available. However, these patients should be followed bone marrow revealed 45,X[12]/46,XX[12]/46,XY[1]. closely after transplantation. Donor’s peripheral blood cultures stimulated with phyto- hemagglutinin showed a mosaic TS 45,X[7]/46,XX[18], confirmingdonor originof 45,X cells. Two months later, KN Manola1, C Sambani1, D Karakasis2, I Baltathakis2, chromosome studies showed complete donor karyotype N Zoumbos3 and A Symeonidis3 45,X[7]/46,XX[13] and chimerism analysis, by short tandem 1Laboratory of Health Physics & Environmental Hygiene, repeats of polymorphic DNA segments, was 99.5% of Inst. NT-RP, National Center for Scientific Research donor origin. On day þ 105, the patient developed (NCSR) ‘Demokritos’, Athens, Greece; Letter to the Editor 386 2Bone Marrow Transplantation Unit, Hematology and lymphoblastic leukemia complicated with Turner’s syndrome. Lymphoma Department, ‘Evangelismos’ General Hospital, Intern Med 2005; 44: 145–148. Athens, Greece and 4 Cacciari E, Masi M, Fantini MP, Licastro F, Cicognani A, 3Stem Cell Transplantation Unit, Department of Internal Pirazzoli P et al. Serum immunoglobulins and lymphocyte Medicine, Hematology Division, University of Patras subpopulations derangement in Turner’s syndrome. J Immuno- Medical School, Patras, Greece genet 1981; 8: 337–344. 5 Cohen A, Shane E. Osteoporosis after solid organ and bone E-mail: [email protected] marrow transplantation. Osteoporosis Int 2003; 14: 617–630. 6 Baker KS, Gurney JG, Ness KK, Bhatia R, Forman SJ, Francisco L et al. Late effects in survivors of chronic myeloid References leukemia treated with hematopoietic cell transplantation: results from the Bone Marrow Transplant Survivor Study. Blood 2004; 1 Elsheikh M, Dunger DB, Conway GS, Wass JAH. Turner’s 104: 1898–1906. syndrome in adulthood. Endocr Rev 2002; 23: 120–140. 7 Traggiai C, Stanhope R, Nussey S, Leiper AD. Diabetes 2 Gupta S, Chiplunkar S, Gupta A, Gollapudi S. Increased mellitus after bone marrow transplantation duringchildhood. spontaneous, tumor necrosis factor receptor- and CD95 (Fas)- Med Pediatr Oncol 2003; 40: 128–129. mediated apoptosis in cord blood T-cell subsets from Turner’s 8 Shen H, ZhangYY, LongJR, Xu FH, Liu YZ, Xiao P et al. A syndrome. Genes Immun 2003; 4: 239–243. genome-wide linkage scan for bone mineral density in an 3 Saito T, Usui N, Asai O, Yano S, Sugiyama K, Hisatomi M extended sample: evidence for linkage on 11q23 and Xq27. et al. Toxicity and outcome of intensive chemotherapy for acute J Med Genet 2004; 41: 743–751.

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