Long-Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation

  • Mohammad Mahdi Adib Sereshki Mail Department of Hematology and Oncology, Iran University of Medical Sciences, Tehran, Iran
  • Babak Bahar Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Ardeshir Ghavamzadeh Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Seyed Asadollah Mousavi Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
  • Kamran Alimoghaddam Hematology, Oncology and Stem Cell Transplantation Research Center, Tehran University of Medical Sciences, Tehran, Iran
Keywords:
β-thalassemia; Stem cell, Transplantation, Non-myeloablative, Fludarabine

Abstract

At present, hematopoietic stem cell transplantation is the only curative treatment for β thalassemic patients. Conventional myeloablative stem cell transplantation is associated with significant morbidity and mortality, and non-myeloablative stem cell transplantation is associated with high graft failure rate. Some modification in this treatment approach can result in successful transplantation in thalassemic patients.
Two successful Fludarabine - based non-myeloablative stem cell transplantation in two Class III β thalassemic patients are reported here. The first patient was a 14-year old girl that developed rapid engraftment and full Chimerism after rapid tapering of cyclosporine as graft-versus-host disease (GVHD) prophylaxis drug according to our protocol. Another patient was a 24-year old female patient that developed cyclosporine toxicity, and early tapering of cyclosporine helped for rapid engraftment and successful transplantation.
After these two successful experiments in non-myeloablative peripheral blood stem cell transplantation for our class III β thalassemic patients, we concluded that Fludarabine-based nonmyeloablative stem cell transplantation with adequate number of stem cells at the time of transplantation and rapid tapering of GVHD prophylaxis drugs after transplantation can potentially help for rapid engraftment and successful stem cell transplantation in high risk β-thalassemic patients.

References

1. Caterina B, Galanellao R. Thalassemia and Related Disorders: Quntitative disorders of Hemoglobin Synthesis. John P. Gree et al. Wintrobes Clinical Hematology. Lippincott Williams and Wilkins; 2009.
2. Forman SJ, Blume KG, Thomas ED. Hematopoietic cell transplantation: Blackwell Science; 1999.
3. Lucarelli G, Clift RA, Galimberti M, et al. Marrow transplantation for patients with thalassemia: results in class 3 patients. Blood. 1996;87(5):2082-8.
4. Resnick I, Shapira MY, Slavin S. Nonmyeloablative stem cell transplantation and cell therapy for malignant and non-malignant diseases. Transpl Immunol. 2005;14(3-4):207-19.
5. Hongeng S, Chuansumrit A, Hathirat P, et al. Full chimerism in nonmyeloablative stem cell transplantation in a β-thalassemia major patient (class 3 Lucarelli). Bone Marrow Transplant. 2002;30(6):409-10.
6. Horan J, Liesveld J, Fenton P, et al. Hematopoietic stem cell transplantation for multiply transfused patients with sickle cell disease and thalassemia after low-dose total body irradiation, fludarabine, and rabbit anti-thymocyte globulin. Bone Marrow Transplant. 2005;35(2):171-7.
7. Iannone R, Casella JF, Fuchs EJ, et al. Results of minimally toxic nonmyeloablative transplantation in patients with sickle cell anemia and β-thalassemia. Biol Blood Marrow Transplant. 2003;9(8):519-28.
8. Andreani M, Manna M, Lucarelli G, et al. Persistence of mixed chimerism in patients transplanted for the treatment of thalassemia. Blood. 1996;87(8):3494-9.
9. Khouri IF, Keating M, Körbling M, et al. Transplant-lite: induction of graft-versus-malignancy using fludarabine-based nonablative chemotherapy and allogeneic blood progenitor-cell transplantation as treatment for lymphoid malignancies. J Clin Oncol. 1998;16(8):2817-24.
10. Ringdén O, Shrestha S, da Silva GT, et al. Effect of acute and chronic graft-versus-host disease on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma. Bone Marrow Transplant. 2012;47(6):831-837.
11. Locatelli F, Rocha V, Reed W, et al. Related umbilical cord blood transplantation in patients with thalassemia and sickle cell disease. Blood. 2003;101(6):2137-2143.
12. Aker M, Kapelushnik J, Pugatsch T, et al. Donor lymphocyte infusions to displace residual host hematopoietic cells after allogeneic bone marrow transplantation for beta-thalassemia major. J Pediatr Hematol Oncol. 1998;20(2):145-8.
13. Michallet M, Bilger K, Garban F, et al. Allogeneic hematopoietic stem-cell transplantation after nonmyeloablative preparative regimens: impact of pretransplantation and posttransplantation factors on outcome. J Clin Oncol. 2001;19(14):3340-9.
14. Andreani M, Nesci S, Lucarelli G, et al. Long-term survival of ex-thalassemic patients with persistent mixed chimerism after bone marrow transplantation. Bone Marrow Transplant. 2000;25(4):401-4.
15. Lucarelli G, Galimberti M, Polchi P, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322(7):417-21.
16. Ruiz‐Argüelles GJ, Gómez‐Almaguer D, Ruiz‐Argüelles A, et al. Results of an outpatient‐based stem cell allotransplant program using nonmyeloablative conditioning regimens. Am J Hematol. 2001;66(4):241-4.
17. Woodard P, Tong X, Richardson S, et al. Etiology and outcome of graft failure in pediatric hematopoietic stem cell transplant recipients. J Pediatr Hematol Oncol. 2003;25(12):955-9.
18. Bethge WA, Hegenbart U, Stuart MJ, et al. Adoptive immunotherapy with donor lymphocyte infusions after allogeneic hematopoietic cell transplantation following nonmyeloablative conditioning. Blood. 2004;103(3):790-5.
19. Centis F, Delfini C, Annibali M, et al. Increased serum levels of circulating intercellular adhesion molecule 1 predict the risk of graft rejection after bone marrow transplantation for thalassemia. Bone Marrow Transplant. 1997;20(2):125-8.
20. Giralt S, Estey E, Albitar M, et al. Engraftment of allogeneic hematopoietic progenitor cells with purine analog-containing chemotherapy: harnessing graft-versus-leukemia without myeloablative therapy. Blood. 1997;89(12):4531-6.
21. Lucarelli G, Galimberti M, Giardini C, et al. Bone marrow transplantation in thalassemia: the experience of Pesaro. Ann N Y Acad Sci. 1998;850:270-5.
22. Manna M, Nesci S, Andreani M, et al. Influence of the conditioning regimens on the incidence of mixed chimerism in thalassemic transplanted patients. Bone Marrow Transplant. 1993;12 Suppl 1:70-3.
23. Storb R, Yu C, Zaucha JM, et al. Stable mixed hematopoietic chimerism in dogs given donor antigen, CTLA4Ig, and 100 cGy total body irradiation before and pharmacologic immunosuppression after marrow transplant. Blood. 1999;94(7):2523-9.
24. Herrero C,Pérez-Simón JA. Immunomodulatory effect of mesenchymal stem cells. Braz J Med Biol Res. 2010;43(5):425-30
25. Battiwalla M, Hematti P. Mesenchymal stem cells in hematopoietic stem cell transplantation. Cytotherapy. 2009;11(5):503-15.
Published
2020-04-07
How to Cite
1.
Adib Sereshki MM, Bahar B, Ghavamzadeh A, Mousavi SA, Alimoghaddam K. Long-Term Free Survival of Two Class III β-Thalassemic Patients after Non-Myeloablative Stem Cell Transplantation. Int J Hematol Oncol Stem Cell Res. 14(2):118-122.
Section
Case Report(s)