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Allo-SCT in a patient with CRMCC with aplastic anemia using a reduced intensity conditioning regimen

Bone Marrow Transplantation volume 47, pages 1126–1127 (2012)Cite this article

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Cerebroretinal microangiopathy with calcifications and cysts (CRMCC; Revesz syndrome)1, 2, 3 is a rare congenital systemic disorder that was first described by Revesz et al. in 1992.1 It is characterized by intrauterine growth retardation, bilateral exudative retinopathy, intracranial calcification and cysts, leukoencephalopathy, sparse hair, nail dystrophy, and skeletal defects. Approximately one-third of cases are complicated by the development of hematological disorders; in particular, aplastic anemia similar to that observed in dyskeratosis congenita (DKC).4, 5, 6 CRMCC with aplastic anemia and DKC both belong to the congenital BM-failure disease spectrum and additional similarities between these two diseases have been reported, including shortened telomere length and mutations of the TINF2, which encodes TIN2 (a regulator of telomere length in human cells).4, 7, 8 Similar to DKC, aplastic anemia associated with CRMCC can be cured only by hematopoietic SCT (HSCT); however, to date HSCT has not been widely used in this patient population.4, 7, 8 Herein, we report a case of CRMCC associated with a TINF2 mutation, which was successfully treated with HSCT using a fludarabine-based reduced-intensity conditioning (RIC) regimen.

On the basis of these findings, a diagnosis of CRMCC was made. At the age of 17 months, the exudative retinopathy was successfully treated with laser coagulation, pars plana vitrectomy and the intra-vitreal administration of vascular endothelial growth factor inhibitors. However, at the age of 22 months, the bicytopenia became more severe and treatment with prednisolone (1 mg/kg/day) and danazol (5 mg/kg/day) was initiated. In response, the anemia improved slightly, but there was no effect on the thrombocytopenia, although bleeding tendency was not evident. Thus, we decided to perform allogeneic HSCT with an HLA-matched, related, healthy female donor. The conditioning regimen was as follows: 25 mg/m2 fludarabine daily on days −5 to −2; 25 mg/kg CY daily on days −5 to −2 and 1.25 mg/kg anti-thymocyte globulin (Thymoglobulin) daily on days −5 to −2. Total nucleated cell and CD34+ doses were 2.48 × 108 and 2.08 × 106 per kg recipient body weight, respectively. GVHD prophylaxis consisted of CsA and short term MTX. Desired neutrophil counts (>500perμL) were obtained by day 12, reticulocyte counts (>1.0%) by day 20, and platelet counts (>5.0 × 104 per μL) by day 48. Genotyping using XY-FISH analysis of a BM sample taken at day 48 revealed that 98.4% of total nucleated cells were of donor origin. The post-transplant course was uneventful with grade 1 oral mucositis being the only complication. Neither acute nor chronic GVHD was evident. The patient is currently 20 months post transplant without any immunosuppressants and transplantation-related complication.

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References

  1. Revesz T, Fletcher S, al-Gazali LI, DeBuse P . Bilateral retinopathy, aplastic anaemia, and central nervous system abnormalities: A new syndrome? J Med Genet 1992; 29: 673–675.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Goutieres F, Dollfus H, Becquet F, Duffer JL . Extensive brain calcification in two children with bilateral Coats disease. Neuropediatrics 1999; 30: 19–21.

    Article  CAS  PubMed  Google Scholar 

  3. Briggs TA, Abdel-Salam GMH, Balicki M . Cerebroretinal microangiopathy with calcifications and cysts (CRMCC). Am J Med Genet A 2008; 146A: 182–190.

    Article  CAS  PubMed  Google Scholar 

  4. Kajtar P, Mehes K . Bilateral coats retinopathy associated with aplastic anaemia and mild dyskeratotic signs. Am J Med Genet 1994; 49: 374–377.

    Article  CAS  PubMed  Google Scholar 

  5. Duprey PA, Steger JW . An unusual case of dyskeratosis congenita with intracranial calcifications. J Am Acad Dermatol 1988; 19: 760–762.

    Article  CAS  PubMed  Google Scholar 

  6. Gayatri NA, Hughes MI, Lloyd IC, Wynn RF . Association of the congenital bone marrow failure syndromes with retinopathy, intracerebral calcification and progressive neurological impairment. Eur J Paediatr Neurol 2002; 6: 125–128.

    Article  CAS  PubMed  Google Scholar 

  7. Savage SA, Giri N, Baerlocher GM, Orr N, Lansdorp PM, Alter BP . TINF2, a component of sheltrin telomere protection complex, is mutated in dyskeratosis congenita. Am J Hum Genet 2008; 82: 501–509.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Walne AJ, Vulliamy T, Beswick R, Kirwan M, Dokal I . TINF2 mutations result in very short telomeres: analysis of a large cohort of patients with dyskeratosis congenita and related bone marrow failure syndromes. Blood 2008; 112: 3594–3600.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Crow YJ, McMenamin J, Haenggeli CA, Hadley DM, Tirupathi S, Treacy EP et al. Coat’s Plus:A progressive familial syndrome of bilateral Coat’s disease, characteristic cerebral calcification, leukoencephalopathy, slow pre- and post-natal linear growth and defects of bone marrow and integument. Neuropediatrics 2004; 35: 10–19.

    Article  CAS  PubMed  Google Scholar 

  10. M’kacher R, Laithier V, Valent A, Delhommeau F, Violot D, Deutsch E et al. Sensitivity to radiation and alkylation agent of peripheral lymphocytes and fibroblasts in a Hoyeraal-Hreidarsson syndrome patient. Pediatr Hematol Oncol 2003; 20: 651–656.

    Article  PubMed  Google Scholar 

  11. Dietz AC, Orchard PJ, Baker KS, Giller RH, Savage SA, Alter BP et al. Disease-specific hematopoietic cell transplantation: nonmyeloablative conditioning regimen for dyskeratosis congenita. Bone Marrow Transplant 2011; 46: 98–104.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr Shinsaku Imashuku for his critical reading of the manuscript and Ms Yasuko Hashimoto for her secretarial assistance.

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Authors and Affiliations

  1. Department of Pediatrics, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kyoto, Japan

    D Asai, T Imamura & H Hosoi

  2. Division of Pediatrics, Kyoto City Hospital, Kyoto, Japan

    S Osone & H Kuroda

  3. Department of Pediatrics, Nagoya University Graduate School of Medicine, Nagoya, Japan

    H Sakaguchi, N Nishio & S Kojima

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  1. D Asai
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Correspondence to T Imamura.

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Asai, D., Osone, S., Imamura, T. et al. Allo-SCT in a patient with CRMCC with aplastic anemia using a reduced intensity conditioning regimen. Bone Marrow Transplant 47, 1126–1127 (2012). https://doi.org/10.1038/bmt.2011.221

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