Experience of allogeneic hematopoietic stem cell transplantation in a pediatric patient with hemolytic anemia due to unstable hemoglobin Calgary (HBB: c.194G>T)
https://doi.org/10.21682/2311-1267-2025-12-4-68-75
Abstract
This article describes the only case of unstable hemoglobin Calgary in Russia in a two-year-old Russian boy with severe transfusiondependent anemia caused by a de novo point mutation in the β-globin gene (HBB: c.194G>T). The combination of the clinical picture of severe anemia, occurring as a major form of β-thalassemia, with the absence of specific laboratory signs complicated the diagnostic search, which was completed only thanks to modern molecular genetic methods. Currently, the only radical method of treating transfusion-dependent hemoglobinopathies is allogeneic hematopoietic stem cell transplantation. A literature review is presented demonstrating general information about the disease, international literature data on allogeneic hematopoietic stem cell transplantation for unstable hemoglobinopathies, as well as our own experience of successful use of this method. The patient's parents have given consent for the use of information, including photographs of the child, in scientific research and publications.
About the Authors
L. V. Olkhova
Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Russian Federation
Russian Federation
Cand. of Sci. (Med.), Pediatric Oncologist, Hematologist of Department of Bone Marrow Transplantation
117 Leninskiy Prosp., Moscow, 117997
E. V. Skorobogatova
Russian Children’s Clinical Hospital – Branch of the N.I. Pirogov Russian National Research Medical University of Ministry of Healthcare of the Russian Federation
Russian Federation
Russian Federation
Dr. of Sci. (Med.), Head of the Department of Bone Marrow Transplantation
117 Leninskiy Prosp., Moscow, 117997
References
1. Kattamis A., Kwiatkowski J.L., Aydinok Y. Thalassaemia. Lancet. 2022;399(10343):2310–24. doi: 10.1016/S0140-6736(22)00536-0. Epub 2022 Jun 9. PMID: 35691301.
2. Hemoglobinopathies and thalassemic syndromes. Ed. by A.G. Rumyantsev, Yu.N. Tokarev, N.S. Smetanina. M.: Practical Medicine, 2015. 448 p. (In Russ.)].
3. Tesio N., Bauer D.E. Molecular basis and genetic modifi ers of thalassemia. Hematol Oncol Clin North Am. 2023;37(2):273–99. doi: 10.1016/j.hoc.2022.12.001. PMID: 36907603; PMCID: PMC10122828.
4. Thein S.L. The molecular basis of β-thalassemia. Cold Spring Harb Perspect Med. 2013;3(5):a011700. doi: 10.1101/cshperspect.a011700. PMID: 23637309; PMCID: PMC3633182.
5. Lv A., Li J., Chen M., Wang W., Xu L., Huang H. Global trends on β-thalassemia research over 10 years: a bibliometric analysis. Int J Gen Med. 2024;17:3989–4001. doi: 10.2147/IJGM.S479493. PMID: 39281038; PMCID: PMC11402362.
6. Bienz M.N., Hsia C., Waye J.S., Bode M., Solh Z. A novel human β-globin gene variant [Hb London–Ontario, HBB: c.332T>G] is associated with transfusion-dependent anemia in a patient with a hemoglobin electrophoresis pattern consistent with β-thalassemia trait. Hemoglobin. 2019;43(2):129–31. doi: 10.1080/03630269.2019.1619575. Epub 2019 Jun 27. PMID: 31246535.
7. Kanathezhath B., Hazard F.K., Guo H., Kidd J., Azimi M., Kuypers F.A., Vichinsky E.P., Lal A. Hemoglobin Hakkari: an autosomal dominant form of beta thalassemia with inclusion bodies arising from de novo mutation in exon 2 of beta globin gene. Pediatr Blood Cancer. 2010;54(2):332–5. doi: 10.1002/pbc.22167. PMID: 19852066.
8. Coleman M.B., Steinberg M.H., Adams J.G. 3rd. Hemoglobin Terre Haute arginine beta 106. A posthumous correction to the original structure of hemoglobin Indianapolis. J Biol Chem. 1991;266(9):5798–800. PMID: 2005117.
9. Adams J.G. 3rd, Boxer L.A., Baehner R.L., Forget B.G., Tsistrakis G.A., Steinberg M.H. Hemoglobin Indianapolis (beta 112[G14] arginine). An unstable beta-chain variant producing the phenotype of severe beta-thalassemia. J Clin Invest. 1979;63(5):931–8. doi: 10.1172/JCI109393. PMID: 447835; PMCID: PMC372034.
10. Thein S.L., Best S., Sharpe J., Paul B., Clark D.J., Brown M.J. Hemoglobin Chesterfi eld (beta 28 Leu–Arg) produces the phenotype of inclusion body beta thalassemia. Blood. 1991;77(12):2791–3. PMID: 1675132.
11. Podda A., Galanello R., Maccioni L., Melis M.A., Rosatelli C., Perseu L., Cao A. Hemoglobin Cagliari (beta 60 [E4] Val–Glu): a novel unstable thalassemic hemoglobinopathy. Blood. 1991;77(2):371–5. PMID: 1985702.
12. Henderson S.J., Timbs A.T., McCarthy J., Gallienne A.E., Proven M., Rugless M.J., Lopez H., Eglinton J., Dziedzic D., Beardsall M., Khalil M.S., Old J.M. Ten years of routine α- and β-globin gene sequencing in UK hemoglobinopathy referrals reveals 60 novel mutations. Hemoglobin. 2016;40(2):75–84. doi: 10.3109/03630269.2015.1113990. Epub 2015 Dec 4. PMID: 26635043.
13. Martin G., Grimholt R.M., Le D., Bechensteen A.G., Klingenberg O., Fjeld B., Fourie T., Perrier R., Proven M., Henderson S.J., Roy N.B.A. Hb Calgary (HBB: c.194G>T): a highly unstable hemoglobin variant with a β-thalassemia major phenotype. Hemoglobin. 2021;45(4):215–9. doi: 10.1080/03630269.2021.1956947. Epub 2021 Jul 26. PMID: 34311670.
14. Jiang H., Li D.Z. Early onset of severe anemia caused by Hb Calgary (HBB: C.194G > T): another case report. Hemoglobin. 2024;48(2):118–20. doi: 10.1080/03630269.2024.2315188. Epub 2024 Feb 12. PMID: 38344813.
15. Gratwohl A., Apperley J., Baldomero H., Chabannon C., Corbacioglu S., Gluckman E. et al. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 8th ed. Cham: Springer; 2024. Available from: https://www.ebmt.org/sites/default/files/2024-04/978-3-031-44080-9.pdf.
16. Yusuf U., Hale G.A., Carr J., Gu Z., Benaim E., Woodard P., Kasow K.A., Horwitz E.M., Leung W., Srivastava D.K., Handgretinger R., Hayden R.T. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. 2006;81(10):1398–404. doi: 10.1097/01.tp.0000209195.95115.8e. PMID: 16732176.
17. Chen Y.B., Mohty M., Zeiser R., Teshima T., Jamy O., Maertens J., Purtill D., Chen J., Cao H., Rossiter G., Jansson J., Fløisand Y. Vedolizumab for the prevention of intestinal acute GVHD after allogeneic hematopoietic stem cell transplantation: a randomized phase 3 trial. Nat Med. 2024;30(8):2277–7. doi: 10.1038/s41591-024-03016-4. Epub 2024 Jun 6. PMID: 38844797; PMCID: PMC11333288.
18. Giardine B.M., Joly P., Pissard S., Wajcman H., Chui D.H.K., Hardison R.C., Patrinos G.P. Clinically relevant updates of the HbVar database of human hemoglobin variants and thalassemia mutations. Nucleic Acids Res. 2021;49(D1):D1192–6. doi: 10.1093/nar/gkaa959. PMID: 33125055; PMCID: PMC7778921.
19. Patrinos G.P., Giardine B., Riemer C., Miller W., Chui D.H., Anagnou N.P., Wajcman H., Hardison R.C. Improvements in the HbVar database of human hemoglobin variants and thalassemia mutations for population and sequence variation studies. Nucleic Acids Res. 2004;32(Database issue):D537–41. doi: 10.1093/nar/gkh006. PMID: 14681476; PMCID: PMC308741.
20. Richards S., Aziz N., Bale S., Bick D., Das S., Gastier-Foster J., Grody W.W., Hegde M., Lyon E., Spector E., Voelkerding K., Rehm H.L.; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405–24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5. PMID: 25741868; PMCID: PMC4544753.
21. Coleman M.B., Lu Z.H., Smith C.M. 2nd, Adams J.G. 3rd, Harrell A., Plonczynski M., Steinberg M.H. Two missense mutations in the betaglobin gene can cause severe beta thalassemia. Hemoglobin Medicine Lake (beta 32[B14]leucine – >glutamine; 98 [FG5] valine – >methionine). J Clin Invest. 1995;95(2):503–9. doi: 10.1172/JCI117691. PMID: 7860732; PMCID: PMC295500.
22. Kazazian H.H. Jr, Dowling C.E., Hurwitz R.L., Coleman M., Stopeck A., Adams J.G. 3rd. Dominant thalassemia-like phenotypes associated with mutations in exon 3 of the beta-globin gene. Blood. 1992;79(11):3014–8. PMID: 1586746.
23. Thom C.S., Dickson C.F., Olson J.S., Gell D.A., Weiss M.J. Normal and abnormal hemoglobins. In: Orkin S.H., Fischer D.E., Look A.S., Look A.T., Fisher D.E., Lux S. (eds.). Nathan and Oski’s Hematology and Oncology of Infancy and Childhood, 8th ed. Philadelphia (PA, USA): Elsevier, 2015. Pp. 652–665.
24. Taher A.T., Musallam K.M., Cappellini M.D. β-Thalassemias. N Engl J Med. 2021;384(8):727–43. doi: 10.1056/NEJMra2021838. PMID: 33626255.
25. Yesilipek M.A., Uygun V., Kupesiz A., Karasu G., Ozturk G., Ertem M., Şaşmaz İ., Daloğlu H., Güler E., Hazar V., Fisgin T., Sezgin G., Kansoy S., Kuşkonmaz B., Akıncı B., Özbek N., İnce E.Ü., Öztürkmen S., Küpesiz F.T., Yalçın K., Anak S., Bozkurt C., Karakükçü M., Küpeli S., Albayrak D., Öniz H., Aksoylar S., Okur F.V., Albayrak C., Yenigürbüz F.D., Bozkaya İ.O., İleri T., Gürsel O., Karagün B.Ş., Kintrup G.T., Çelen S., Elli M., Aksoy B.A., Yılmaz E., Tanyeli A., Akyol Ş.T., Siviş Z.Ö., Özek G., Uçkan D., Kartal İ., Atay D., Akyay A., Bilir Ö.A., Çakmaklı H.F., Kürekçi E., Malbora B., Akbayram S., Demir H.A., Kılıç S.Ç., Güneş A.M., Zengin E., Özmen S., Antmen A.B. Thalassemia-free and graftversus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience. Bone Marrow Transplant. 2022;57(5):760–7. doi: 10.1038/s41409-022-01613-w. Epub 2022 Feb 24. PMID: 35210564.
26. Santarone S., Angelini S., Natale A., Vaddinelli D., Spadano R., Casciani P., Papola F., Di Lembo E., Iannetti G., Di Bartolomeo P. Survival and late eff ects of hematopoietic cell transplantation in patients with thalassemia major. Bone Marrow Transplant. 2022;57(11):1689–97. doi: 10.1038/s41409-022-01786-4. Epub 2022 Aug 24. PMID: 36002533; PMCID: PMC9400570.
27. Oikonomopoulou C., Goussetis E. HSCT remains the only cure for patients with transfusion-dependent thalassemia until gene therapy strategies are proven to be safe. Bone Marrow Transplant. 2021;56(12):2882–8. doi: 10.1038/s41409-021-01461-0. Epub 2021 Sep 16. PMID: 34531544.
28. Urban C., Preisegger K.H., Krugluger W., Hopmeier P., Schwinger W., Lackner H., Kerbl R., Dornbusch H.J., Benesch M. Allogeneic bone marrow transplantation in a child with hemoglobinopathy olmsted. J Pediatr Hematol Oncol. 2002;24(5):417–9. doi: 10.1097/00043426-200206000-00020. PMID: 12142796.
29. Croteau S.E., Luo H.Y., Lehmann L.E., Chui D.H., Neufeld E.J. Novel dominant β-thalassemia: Hb Boston-Kuwait [codon 139/140(+T)]. Pediatr Blood Cancer. 2013;60(10):E131–4. doi: 10.1002/pbc.24611. Epub 2013 Jun 15. PMID: 23776097.
30. Kumar K., Badiger S., Damodar S., Bhat S. Haploidentical stem cell transplantation with TCR alpha/beta and CD19 depletion in a case of unstable hemoglobin disease. Transplantation. 2018;102(2):e45–6. doi: 10.1097/TP.0000000000001986. PMID: 29084024.
31. Li S., Chen K., Huang C., Zhang N., Jiang H., Jiang S. First report of successful treatment for hemoglobin Bristol-Alesha by hemopoietic stem cell transplantation. Ann Hematol. 2022;101(3):617–9. doi: 10.1007/s00277-021-04721-7. Epub 2021 Dec 1. PMID: 34851438.
32. Chan W.Y.K., Chan N.C.N., So J.C.C., Lee P.P.W., Cheuk D.K.L., Ha S.Y., Chan G.C.F., Leung W. Successful haploidentical hematopoietic stem cell transplantation (HSCT) and durable engraftment by repeated donor lymphocyte infusions for a Chinese patient with transfusion-dependent hemoglobin (Hb) Hammersmith and massive splenomegaly. Pediatr Transplant. 2022;26(5):e14278. doi: 10.1111/petr.14278. Epub 2022 Apr 9. PMID: 35396908.
33. Zhang Q., Huo Y., Sun Q., Liu N., Shi H., Wang M., Xiao J., Yuan H., Tang X. Case report: curing a rare, unstable hemoglobin variant Hb Bristol-Alesha using haploidentical hematopoietic stem cell transplantation. Front Immunol. 2023;14:1188058. doi: 10.3389/fimmu.2023.1188058. PMID: 37457725; PMCID: PMC10348747.
34. Li C., Yang G.H., Liu L.J., Chen Y.H., Zhou X.M., Lai Y.R., Liu R.R. Allogeneic hematopoietic stem cell transplantation in Hb Mizuho of unstable hemoglobinopathy: a case report. Zhonghua Xue Ye Xue Za Zhi. 2023;44(6):524. [In Chinese]. doi: 10.3760/cma.j.issn.0253-2727.2023.06.018. PMID: 37550215; PMCID: PMC10450552.
Review
For citations:
Olkhova L.V., Skorobogatova E.V. Experience of allogeneic hematopoietic stem cell transplantation in a pediatric patient with hemolytic anemia due to unstable hemoglobin Calgary (HBB: c.194G>T). Russian Journal of Pediatric Hematology and Oncology. 2025;12(4):68-75. (In Russ.) https://doi.org/10.21682/2311-1267-2025-12-4-68-75
Views:
23
JATS XML
Email this article 