Abstract
We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
Baronciani D, Angelucci E, Potschger U, Gaziev J, Yesilipek A, Zecca M, et al. Hemopoietic stem cell transplantation in thalassemia: a report from the European Society for Blood and Bone Marrow Transplantation Hemoglobinopathy Registry, 2000-2010. Bone Marrow Transpl. 2016;51:536–41.
Angelucci E, Matthes-Martin S, Baronciani D, Bernaudin F, Bonanomi S, Cappellini MD, et al. Hematopoietic stem cell transplantation in thalassemia major and sickle cell disease: indications and management recommendations from an international expert panel. Haematologica. 2014;99:811–20.
Yesilipek MA, Ertem M, Cetin M, Oniz H, Kansoy S, Tanyeli A, et al. HLA-matched family hematopoetic stem cell transplantation in children with beta thalassemia major: the experience of the Turkish Pediatric Bone Marrow Transplantation Group. Pediatr Transplant 2012;16:846–51.
Angelucci E. Complication free survival long-term after hemopoietic cell transplantation in thalassemia. Haematologica. 2018;103:1094–6.
Glucksberg H, Storb R, Fefer A, Buckner CD, Neiman PE, Clift RA, et al. Clinical manifestations of graft-versus-host disease in human recipients of marrow from HL-A-matched sibling donors. Transplantation. 1974;18:295–304.
Filipovich AH, Weisdorf D, Pavletic S, Socie G, Wingard JR, Lee SJ, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. Diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.
Lucarelli G, Galimberti M, Polchi P, Angelucci E, Baronciani D, Giardini C, et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med. 1993;329:840–4.
Sabloff M, Chandy M, Wang Z, Logan BR, Ghavamzadeh A, Li CK, et al. HLA-matched sibling bone marrow transplantation for beta-thalassemia major. Blood. 2011;117:1745–50.
La Nasa G, Caocci G, Efficace F, Dessi C, Vacca A, Piras E, et al. Long-term health-related quality of life evaluated more than 20 years after hematopoietic stem cell transplantation for thalassemia. Blood. 2013;122:2262–70.
Rahal I, Galambrun C, Bertrand Y, Garnier N, Paillard C, Frange P, et al. Late effects after hematopoietic stem cell transplantation for beta-thalassemia major: the French national experience. Haematologica. 2018;103:1143–9.
Uygun V, Tayfun F, Akcan M, Karasu GT, Kupesiz A, Hazar V, et al. Quality of life assessment in hematopoietic stem cell transplantation performed on thalassemia major patients. Pediatr Hematol Oncol. 2012;29:461–71.
Ramprakash S, Agarwal R, Dhanya R, Marwah P, Soni R, Yaqub N, et al. Low-cost matched sibling bone marrow transplant for standard-risk thalassemia in a limited-resource setting. Pediatr Hematol Oncol J 2017;2:107–13. 2017/12/01/
Li Q, Luo J, Zhang Z, Liu L, Luo L, Yang G, et al. G-CSF-Mobilized blood and bone marrow grafts as the source of stem cells for HLA-identical sibling transplantation in patients with thalassemia major. Biol Blood Marrow Transplant. 2019;25:2040–4.
Lai X, Liu L, Zhang Z, Shi L, Yang G, Wu M, et al. Hepatic veno-occlusive disease/sinusoidal obstruction syndrome after hematopoietic stem cell transplantation for thalassemia major: incidence, management, and outcome. Bone Marrow Transplant. 2021;56:1635–41. 2021/07/01
van Besien K, Dew A, Lin S, Joseph L, Godley LA, Larson RA, et al. Patterns and kinetics of T-cell chimerism after allo transplant with alemtuzumab-based conditioning: mixed chimerism protects from GVHD, but does not portend disease recurrence. Leuk Lymphoma. 2009;50:1809–17.
Galambrun C, Pondarre C, Bertrand Y, Loundou A, Bordigoni P, Frange P, et al. French multicenter 22-year experience in stem cell transplantation for beta-thalassemia major: lessons and future directions. Biol Blood Marrow Transplant. 2013;19:62–8.
Korula A, Devasia AJ, Fouzia NA, Nisham PN, Kulkarni U, Lakshmi KM, et al. Outcomes following allogeneic stem cell transplantation using non-sibling family donors. Indian J Hematol Blood Transfus. 2019;35:43–9.
Gaziev J, Marziali M, Isgro A, Sodani P, Paciaroni K, Gallucci C, et al. Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach. Blood. 2013;122:2751–6.
Aydogdu S, Toret E, Aksoy BA, Aydin MF, Cipe FE, Bozkurt C, et al. Comparison of hematopoietic stem cell transplantation results in patients with beta-thalassemia major from three different graft types. Hemoglobin. 2021;45:25–9.
La Nasa G, Argiolu F, Giardini C, Pession A, Fagioli F, Caocci G, et al. Unrelated bone marrow transplantation for beta-thalassemia patients: the experience of the Italian Bone Marrow Transplant Group. Ann NY Acad Sci. 2005;1054:186–95.
Li C, Mathews V, Kim S, George B, Hebert K, Jiang H, et al. Related and unrelated donor transplantation for beta-thalassemia major: results of an international survey. Blood Adv. 2019;3:2562–70.
Anurathapan U, Hongeng S, Pakakasama S, Songdej D, Sirachainan N, Pongphitcha P, et al. Hematopoietic stem cell transplantation for severe thalassemia patients from haploidentical donors using a novel conditioning regimen. Biol Blood Marrow Transplant. 2020;26:1106–12.
Oevermann L, Schulte JH, Hundsdorfer P, Hakimeh D, Kogel F, Lang P, et al. HLA-haploidentical hematopoietic stem cell transplantation in pediatric patients with hemoglobinopathies: current practice and new approaches. Bone Marrow Transplant. 2019;54:743–8.
Yesilipek MA, Hazar V, Kupesiz A, Kizilors A, Uguz A, Yegin O. Peripheral blood stem cell transplantation in children with beta-thalassemia. Bone Marrow Transplant. 2001;28:1037–40.
Ghavamzadeh A, Kasaeian A, Rostami T, Kiumarsi A. Comparable outcomes of allogeneic peripheral blood versus bone marrow hematopoietic stem cell transplantation in major thalassemia: a multivariate long-term cohort analysis. Biol Blood Marrow Transplant. 2019;25:307–12.
Sun L, Wang N, Chen Y, Tang L, Xing C, Lu N, et al. Unrelated donor peripheral blood stem cell transplantation for patients with beta-thalassemia major based on a novel conditioning regimen. Biol Blood Marrow Transplant. 2019;25:1592–6.
Locatelli F, Rocha V, Reed W, Bernaudin F, Ertem M, Grafakos S, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood. 2003;101:2137–43.
Strocchio L, Locatelli F. Hematopoietic stem cell transplantation in thalassemia. Hematol Oncol Clin North Am. 2018;32:317–28.
Kanathezhath B, Walters MC. Umbilical cord blood transplantation for thalassemia major. Hematol Oncol Clin North Am. 2010;24:1165–77.
Ruggeri A, Eapen M, Scaravadou A, Cairo MS, Bhatia M, Kurtzberg J, et al. Umbilical cord blood transplantation for children with thalassemia and sickle cell disease. Biol Blood Marrow Transplant. 2011;17:1375–82.
Tucunduva L, Volt F, Cunha R, Locatelli F, Zecca M, Yesilipek A, et al. Combined cord blood and bone marrow transplantation from the same human leucocyte antigen-identical sibling donor for children with malignant and non-malignant diseases. Br J Haematol. 2015;169:103–10.
Choudhary D, Doval D, Sharma SK, Khandelwal V, Setia R, Handoo A. Allogenic hematopoietic cell transplantation in thalassemia major: a single-center retrospective analysis from India. J Pediatr Hematol Oncol. 2019;41:e296–e301.
Alonso L, Gonzalez-Vicent M, Belendez C, Badell I, Sastre A, Rodriguez-Villa A, et al. Hematopoietic stem cell transplantation in pediatric patients with thalassemia and sickle cell disease: an experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON). Med Clin. 2019;152:135–40.
Caocci G, Orofino MG, Vacca A, Piroddi A, Piras E, Addari MC, et al. Long-term survival of beta thalassemia major patients treated with hematopoietic stem cell transplantation compared with survival with conventional treatment. Am J Hematol. 2017;92:1303–10.
Acknowledgements
We would like to thank Vedat Uygun for contributing to the statistics of the study. This study was supported by the Turkish Society of Pediatric Hematology.
Author information
Authors and Affiliations
Contributions
AY was responsible for designing the study, analyzing data and writing the report. AY and VU extracted the data, interpreted the results, and do the statistical analysis. AK, GK, GO, ME, IS, HD, EG, VH, TF, GS, SK, BK, BA, NO, EUI, SO, FTK, KY, SA, CB, MK, SK, DA, HO, SA, FVO, CA, FDY, IOB, TI, OG, BSK, GTK, SC, ME, BAA, EY, AT, STA, ZOS, GO, DU, IK, DA, AA, OAB, HFC, EK, BM, SA, HAD, SCK, AMG, EZ, SO, and ABA collected the data and contributed to improve the text.
Corresponding author
Ethics declarations
Competing interests
The authors declare no competing interests.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Yesilipek, M.A., Uygun, V., Kupesiz, A. et al. Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience. Bone Marrow Transplant 57, 760–767 (2022). https://doi.org/10.1038/s41409-022-01613-w
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41409-022-01613-w
