High GVHD Prevalence in Travel-Based SCT despite Young Patients and HLA Matching
-
Naveed Syed
,
Imrana Afrooz
,
Farooq Ahmed Mir
,
Azmat Ali Khan
,
Nada J.M.H Abdulla
,
Shakir Hussain
,
Ashok Uttam Chandani
,
Amera Hassan
,
Hanin Abdel Samad
,
Gehad El Ghazali
,
Shahrukh Hashmi
Abstract
Background: Patients from regions without stem cell transplantation (SCT) facilities often seek treatment abroad and return home for post-transplant care. Although extensive data exist on graft-versus-host disease (GVHD) and its risk factors, information on international SCT patients returning to countries that lack transplant facilities and expertise is scarce and not well documented.
Materials and Methods: We screened 149 transplant recipients and analyzed the data of 91 patients who received transplants abroad and were followed up at our center from January 2019 to December 2022. This observational study used data from electronic medical records and employed descriptive statistics, inferential tests, and relative risk calculations with forest plots to analyze the prevalence of GVDH and its key risk factors.
Results: Of the recipients, 31.8% were residents of nine countries residing in the UAE, and 67.2% were UAE citizens. Adults comprised 48.3% of the recipients, whereas 51.7% were pediatric patients. Hematological malignancy was the most common indication (49%), primarily in adults. Siblings comprised the majority of donors (52.6%), followed by related (23.09%) and unrelated donors (8.9%). Most patients (69.2%) received HLA-identical transplants, followed by 21.9% who received haplo-identical transplants. Among adults, 62.2% developed GVHD compared to 26% of pediatric patients. Recipients from related HLA-identical donors had a 50% prevalence of GVDH, whereas those from unrelated identical donors had a 71% prevalence. The overall prevalence of GVDH was 50% in 87.9% of patients who received allogeneic SCTs.
Conclusion: Despite favorable factors, such as young age and matched related donors, we found a high prevalence of GVDH. Ocular GVHD was less prevalent than expected, and lung GVHD was weakly correlated with established risk factors. Larger multicenter studies are needed to assess and confirm the effect of contributing factors.
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2. Niederwieser D, Baldomero H, Bazuaye N, et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors. Haematologica. 2022, 107(5):1045–53.
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Available from: https://www.thenationalnews.com/uae/ health/uae-s-first-bone-marrow-transplant-patient-tells-of-life-saving-treatment-1.1055930
6. Socié G, Stone JV, Wingard JR, et al. Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation. N Engl J Med. 1999;341(1):14-21.
7. Kiss TL, Abdolell M, Jamal N, et al. Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation. J Clin Oncol. 2002; 20(9):2334–43.
8. Jacobsohn DA. Acute graft-versus-host disease in children. Bone Marrow Transplant. 2007, 41(2):215–21.
9. Greinix HT, Eikema DJ, Koster L, et al. Incidence of Acute Graft-Versus-Host Disease and Survival after Allogeneic Hematopoietic Cell Transplantation over Time: A Study from the Transplant Complications and Chronic Malignancies Working Party of the EBMT. Blood. 2018; 132 (Supplement 1): 2120.
10. Arai S, Arora M, Wang T, et al. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015; 21(2):266–74.
11. Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000, 96(6):2062–8.
12. Mohyeddin Bonab M, Alimoghaddam K, Vatandoust S, et al. Are HLA antigens a risk factor for acute GVHD in thalassemic patients receiving HLA-identical stem cell transplantation? Transplant Proc. 2004, 36(10):3190–3.
13. Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11):3214–9.
14. Urbano-Ispizua A, Rozman C, Pimentel P, et al. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood. 2002; 100(2):724–7.
15. Gale RP, Bortin MM, Bekkum DW, et al. Risk factors for acute graft-versus-host disease. Br J Haematol. 1987; 67(4):397–406.
16. Weisdorf D, Hakke R, Blazar B, et al. Risk Factors For Acute Graft-Versus-Host Disease In Histocompatible Donor Bone Marrow Transplantation. Transplantation. 1991; 51(6):1197–203.
17. DiRienzo CG, Murphy GF, Jones SC, et al. T-Cell Receptor Vα Spectratype Analysis of a CD4-Mediated T-Cell Response against Minor Histocompatibility Antigens Involved in Severe Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2006; 12(8):818–27.
18. Jagasia M, Arora M, Flowers MED, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012; 119(1):296–307.
19. Zecca M. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood. 2002; 100(4):1192–200.
20. Atkinson K, Horowitz MM, Gale RP, et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood. 1990; 75(12):2459–64.
21. Ozawa S, Nakaseko C, Nishimura M, et al. Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse. A report from the Japan Marrow Donor Program. Br J Haematol. 2007; 137(2):142–51.
22. Beschorner WE, Di KA, Hess AD, et al. Cyclosporine and the thymus: Influence of irradiation and age on thymic immunopathology and recovery. Cell Immunol. 1987; 110(2):350–64.
23. Davies SM, Wang D, Wang T, et al. Recent Decrease in Acute Graft-versus-Host Disease in Children with Leukemia Receiving Unrelated Donor Bone Marrow Transplants. Biol Blood Marrow Transplant. 2009; 15(3):360–6.
24. D’Souza A, Fretham C, Lee SJ, et al. Current Use of and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2020; 26(8):e177–e82.
25. Eisner MD, August CS. Impact of donor and recipient characteristics on the development of acute and chronic graft-versus-host disease following pediatric bone marrow transplantation. Bone Marrow Transplant. 1995;15(5):663-8.
26. Loren AW, Bunin GR, Boudreau C, et al. Impact of Donor and Recipient Sex and Parity on Outcomes of HLA-Identical Sibling Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2006; 12(7):758–69.
27. Ochs LA, Miller WJ, Filipovich AH, et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant. 1994;13(4):455-60.
28. Nagler A, Brautbar C, Slavin S, et al. Bone marrow transplantation using unrelated and family related donors: the impact of HLA-C disparity. Bone Marrow Transplant. 1996;18(5):891-7.
29. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors. N Engl J Med. 2012; 367(16):1487-96.
30. Cutler C, Giri S, Jeyapalan S, et al. Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis. J Clin Oncol; 2001; 19(16):3685–91.
31. Shinozawa T, Beschorner WE, Hess AD. The Thymus And Prolonged Administration Of Cyclosporine. Transplantation. 1990; 50(1):106–11.
32. Bhushan V. Chronic Graft-vs-Host Disease. JAMA. 2003; 290(19):2599-603.
33. Inamoto Y, Flowers MED, Sandmaier BM, et al. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood. 2014; 124(8):1363–71.
34. Pidala J, Chai X, Kurland BF, et al. Analysis of Gastrointestinal and Hepatic Chronic Grant-versus-Host Disease Manifestations on Major Outcomes: A Chronic Grant-versus-Host Disease Consortium Study. Biol Blood Marrow Transplant. 2013; 19(5):784–91.
35. Espana EM, Shah S, Santhiago MR, et al. Graft versus host disease: clinical evaluation, diagnosis and management. Graefes Arch Clin Exp Ophthalmol. 2013;251(5):1257-66.
36. Hildebrandt GC, Fazekas T, Lawitschka A, et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant. 2011; 46(10):1283–95.
37. Rabanus R, Hahn J, Andreesen R, et al. Risk factor analysis for the development of restrictive and obstructive pulmonary function changes after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008; 14(6):780–90.
2. Niederwieser D, Baldomero H, Bazuaye N, et al. One and a half million hematopoietic stem cell transplants: continuous and differential improvement in worldwide access with the use of non-identical family donors. Haematologica. 2022, 107(5):1045–53.
3. Al-Shamsi HO. Establishing and launching a comprehensive bone marrow transplant unit in the UAE amidst the COVID-19 pandemic: overcoming barriers through international collaboration and resilience. Am Soc Clin Oncol. 2021. Available from: https://connection .asco.org/blogs/establishing-and-launching-comprehen-sive-bone-marrow-transplant-unit-uae-amidst-covid-19.
4. Al-Shamsi HO, Abu-Gheida I, Rana SK, et al. Challenges for cancer patients returning home during SARS-COV-19 pandemic after medical tourism - a consensus report by the emirates oncology task force. BMC Cancer. 2020, 20(1):641.
5. Al Nowais S. UAE’s first bone marrow transplant patient tells of life-saving treatment. The National News. 2020.
Available from: https://www.thenationalnews.com/uae/ health/uae-s-first-bone-marrow-transplant-patient-tells-of-life-saving-treatment-1.1055930
6. Socié G, Stone JV, Wingard JR, et al. Long-Term Survival and Late Deaths after Allogeneic Bone Marrow Transplantation. N Engl J Med. 1999;341(1):14-21.
7. Kiss TL, Abdolell M, Jamal N, et al. Long-term medical outcomes and quality-of-life assessment of patients with chronic myeloid leukemia followed at least 10 years after allogeneic bone marrow transplantation. J Clin Oncol. 2002; 20(9):2334–43.
8. Jacobsohn DA. Acute graft-versus-host disease in children. Bone Marrow Transplant. 2007, 41(2):215–21.
9. Greinix HT, Eikema DJ, Koster L, et al. Incidence of Acute Graft-Versus-Host Disease and Survival after Allogeneic Hematopoietic Cell Transplantation over Time: A Study from the Transplant Complications and Chronic Malignancies Working Party of the EBMT. Blood. 2018; 132 (Supplement 1): 2120.
10. Arai S, Arora M, Wang T, et al. Increasing Incidence of Chronic Graft-versus-Host Disease in Allogeneic Transplantation: A Report from the Center for International Blood and Marrow Transplant Research. Biol Blood Marrow Transplant. 2015; 21(2):266–74.
11. Nash RA, Antin JH, Karanes C, et al. Phase 3 study comparing methotrexate and tacrolimus with methotrexate and cyclosporine for prophylaxis of acute graft-versus-host disease after marrow transplantation from unrelated donors. Blood. 2000, 96(6):2062–8.
12. Mohyeddin Bonab M, Alimoghaddam K, Vatandoust S, et al. Are HLA antigens a risk factor for acute GVHD in thalassemic patients receiving HLA-identical stem cell transplantation? Transplant Proc. 2004, 36(10):3190–3.
13. Flowers MED, Inamoto Y, Carpenter PA, et al. Comparative analysis of risk factors for acute graft-versus-host disease and for chronic graft-versus-host disease according to National Institutes of Health consensus criteria. Blood. 2011; 117(11):3214–9.
14. Urbano-Ispizua A, Rozman C, Pimentel P, et al. Risk factors for acute graft-versus-host disease in patients undergoing transplantation with CD34+ selected blood cells from HLA-identical siblings. Blood. 2002; 100(2):724–7.
15. Gale RP, Bortin MM, Bekkum DW, et al. Risk factors for acute graft-versus-host disease. Br J Haematol. 1987; 67(4):397–406.
16. Weisdorf D, Hakke R, Blazar B, et al. Risk Factors For Acute Graft-Versus-Host Disease In Histocompatible Donor Bone Marrow Transplantation. Transplantation. 1991; 51(6):1197–203.
17. DiRienzo CG, Murphy GF, Jones SC, et al. T-Cell Receptor Vα Spectratype Analysis of a CD4-Mediated T-Cell Response against Minor Histocompatibility Antigens Involved in Severe Graft-versus-Host Disease. Biol Blood Marrow Transplant. 2006; 12(8):818–27.
18. Jagasia M, Arora M, Flowers MED, et al. Risk factors for acute GVHD and survival after hematopoietic cell transplantation. Blood. 2012; 119(1):296–307.
19. Zecca M. Chronic graft-versus-host disease in children: incidence, risk factors, and impact on outcome. Blood. 2002; 100(4):1192–200.
20. Atkinson K, Horowitz MM, Gale RP, et al. Risk factors for chronic graft-versus-host disease after HLA-identical sibling bone marrow transplantation. Blood. 1990; 75(12):2459–64.
21. Ozawa S, Nakaseko C, Nishimura M, et al. Chronic graft-versus-host disease after allogeneic bone marrow transplantation from an unrelated donor: incidence, risk factors and association with relapse. A report from the Japan Marrow Donor Program. Br J Haematol. 2007; 137(2):142–51.
22. Beschorner WE, Di KA, Hess AD, et al. Cyclosporine and the thymus: Influence of irradiation and age on thymic immunopathology and recovery. Cell Immunol. 1987; 110(2):350–64.
23. Davies SM, Wang D, Wang T, et al. Recent Decrease in Acute Graft-versus-Host Disease in Children with Leukemia Receiving Unrelated Donor Bone Marrow Transplants. Biol Blood Marrow Transplant. 2009; 15(3):360–6.
24. D’Souza A, Fretham C, Lee SJ, et al. Current Use of and Trends in Hematopoietic Cell Transplantation in the United States. Biol Blood Marrow Transplant. 2020; 26(8):e177–e82.
25. Eisner MD, August CS. Impact of donor and recipient characteristics on the development of acute and chronic graft-versus-host disease following pediatric bone marrow transplantation. Bone Marrow Transplant. 1995;15(5):663-8.
26. Loren AW, Bunin GR, Boudreau C, et al. Impact of Donor and Recipient Sex and Parity on Outcomes of HLA-Identical Sibling Allogeneic Hematopoietic Stem Cell Transplantation. Biol Blood Marrow Transplant. 2006; 12(7):758–69.
27. Ochs LA, Miller WJ, Filipovich AH, et al. Predictive factors for chronic graft-versus-host disease after histocompatible sibling donor bone marrow transplantation. Bone Marrow Transplant. 1994;13(4):455-60.
28. Nagler A, Brautbar C, Slavin S, et al. Bone marrow transplantation using unrelated and family related donors: the impact of HLA-C disparity. Bone Marrow Transplant. 1996;18(5):891-7.
29. Anasetti C, Logan BR, Lee SJ, et al. Peripheral-Blood Stem Cells versus Bone Marrow from Unrelated Donors. N Engl J Med. 2012; 367(16):1487-96.
30. Cutler C, Giri S, Jeyapalan S, et al. Acute and Chronic Graft-Versus-Host Disease After Allogeneic Peripheral-Blood Stem-Cell and Bone Marrow Transplantation: A Meta-Analysis. J Clin Oncol; 2001; 19(16):3685–91.
31. Shinozawa T, Beschorner WE, Hess AD. The Thymus And Prolonged Administration Of Cyclosporine. Transplantation. 1990; 50(1):106–11.
32. Bhushan V. Chronic Graft-vs-Host Disease. JAMA. 2003; 290(19):2599-603.
33. Inamoto Y, Flowers MED, Sandmaier BM, et al. Failure-free survival after initial systemic treatment of chronic graft-versus-host disease. Blood. 2014; 124(8):1363–71.
34. Pidala J, Chai X, Kurland BF, et al. Analysis of Gastrointestinal and Hepatic Chronic Grant-versus-Host Disease Manifestations on Major Outcomes: A Chronic Grant-versus-Host Disease Consortium Study. Biol Blood Marrow Transplant. 2013; 19(5):784–91.
35. Espana EM, Shah S, Santhiago MR, et al. Graft versus host disease: clinical evaluation, diagnosis and management. Graefes Arch Clin Exp Ophthalmol. 2013;251(5):1257-66.
36. Hildebrandt GC, Fazekas T, Lawitschka A, et al. Diagnosis and treatment of pulmonary chronic GVHD: report from the consensus conference on clinical practice in chronic GVHD. Bone Marrow Transplant. 2011; 46(10):1283–95.
37. Rabanus R, Hahn J, Andreesen R, et al. Risk factor analysis for the development of restrictive and obstructive pulmonary function changes after allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2008; 14(6):780–90.
| Files | ||
| Issue | Vol 19 No 2 (2025) | |
| Section | Original Article(s) | |
| Keywords | ||
| Graft-versus-host disease; Stem cell transplantation; United Arab Emirates; Risk factors for GVHD; Organ-specific correlations; Travel tourism | ||
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How to Cite
1.
Syed N, Afrooz I, Mir F, Khan A, Abdulla N, Hussain S, Chandani A, Hassan A, Samad H, Ghazali G, Hashmi S. High GVHD Prevalence in Travel-Based SCT despite Young Patients and HLA Matching. Int J Hematol Oncol Stem Cell Res. 2025;19(2):138-150.
