Advertisement

Late Complications of Allogenic Stem Cells Transplantation in Leukaemia

  • Sharmilla Kanagasundram
  • Farhanaz Amini
Review Article

Abstract

Background:

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) can cure leukaemia. However, long term complications of post transplantation interfere with the patients’ full recovery. The objective of this review was to identify the various long term complications and to assess their individual prevalences.

Methods:

Electronic databases including PubMed, Google Scholar and Cochrane were searched for years 2004–2017. The keywords used were leukaemia, allogenic stem cell transplantation, prevalence, side effects, long term, delayed, adverse effects, complications and outcome.

Results:

A total of ten articles were included for analysis. There were 5 prospective studies, 3 retrospective studies and 2 cross sectional studies. A total of 40,069 patients, (20,189 males and 17,191 females) participated in these 10 studies. The gender of 2689 patients were not disclosed. Most common late complications and prevalence were chronic graft versus host disease (43% at 5 years post HSCT), secondary tumor (21% at 20 years post HSCT), hypothyroidism (11% at 15 years), bronchiolitis obliterans (9.7% at 122 days), cardiovascular disease (7.5% at 15 years) and avascular necrosis (5.4% at 10 years). The prevalence of azoospermia was 71.1% and depression, 18%. For the latter two conditions no time limit was available. Follow up duration ranged from 2 years till 30 years post HSCT.

Conclusion:

While allogenic stem cell transplantation is an effective cure for leukaemia, the procedure is associated with complications that can have their onset many years after the procedure.

Keywords

Allogenic stem cells Chronic graft Late complications Leukaemia 

Notes

Author’s contribution

Associate Professor Dr. Sharmilla Kanagasundram acquisition, interpretation and analysis, drafting article and revising it for intellectual content. Associate Professor Farhanaz Amini concept and design of study and revising it for intellectual content.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Ethical statement

There are no animal experiments carried out for this article.

References

  1. 1.
    Antin JH. Clinical practice. Long-term care after hematopoietic-cell transplantation in adults. Engl J Med. 2002;347:36–42.CrossRefGoogle Scholar
  2. 2.
    Rizzo JD, Curtis RE, Socié G, Sobocinski KA, Gilbert E, Landgren O, et al. Solid cancers after allogenic heamatopoietic stem cell transplantation. Blood. 2009;113:1175–83.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Mohty M, Apperley JF. Long-term physiological side effects after allogeneic bone marrow transplantation. Hematol Am Soc Hematol Educ Program. 2010;2010:229–36.Google Scholar
  4. 4.
    Nivison-Smith I, Simpson JM, Dodds AJ, Ma DD, Szer J, Bradstock KF. Relative survival of long-term hematopoietic cell transplant recipients approaches general population rates. Biol Blood Marrow Transplant. 2009;15:1323–30.CrossRefGoogle Scholar
  5. 5.
    Martin PJ, Counts GW Jr, Appelbaum FR, Lee SJ, Sanders JE, Deeg HJ, et al. Life expectancy in patients surviving more than 5 years after haemopoietic cell transplantation. J Clin Oncol. 2010;28:1011–6.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Gyurkocza B, Storb R, Storer BE, Chauncey TR, Lange T, Shizuru JA, et al. Nonmyeloablative allogenic haematopoietic cell transplantation in patients with acute myeloid leukaemia. J Clin Oncol. 2010;28:2859–67.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Friedman DL, Rovo A, Leisenring W, Locasciulli A, Flowers ME, Tichelli A, et al. Increased risk of breast cancer among survivors of allogeneic hematopoietic cell transplantation: a report from the FHCRC and the EBMT-Late Effect Working Party. Blood. 2008;111:939–44.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Yoshihara S, Tateisha U, Ando T, Kunitah H, Suyama H, Onishi Y, et al. Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning. Bone Marrow Transplant. 2005;35:1195–2000.CrossRefPubMedGoogle Scholar
  9. 9.
    Tichelli A, Passweg J, Wójcik D, Rovó A, Harousseau JL, Masszi T, et al. Late cardiovascular events after allogeneic hematopoietic stem cell transplantation: a retrospective multicenter study of the Late Effects Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2008;93:1203–10.CrossRefPubMedGoogle Scholar
  10. 10.
    Campbell S, Sun CL, Kurian S, Francisco L, Carter A, Kulkarni S, et al. Predictors of avascular necrosis of bone in long term survivors of haematopietic stem cells. Cancer. 2009;115:4127–35.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Rovó A, Tichelli A, Passweg JR, Heim D, Meyer-Monard S, Holzgreve W, et al. Spermatogenesis in long-term survivors after allogenic haematopoietic stem cell transplantation is associated with age, time interval since transplantations, and apparently absence of chronic GvHD. Blood. 2006;108:1100–5.CrossRefPubMedGoogle Scholar
  12. 12.
    Robin M, Guardiola P, Devergie M, Yeshurun M, Shapiro S, Esperou H, et al. A 10-year median follow-up study after allogenic stem cell transplantation for chronic myeloid leukaemia in chronic phase from HLA-identical sibling donors. Leukemia. 2005;19:1613–20.CrossRefPubMedGoogle Scholar
  13. 13.
    Michelis FV, Kotchetkov R, Grunwald RM, Azeem A, Atenafu EG, Lipton JH, et al. Long-term incidence of secondary malignancies after allogenic stem cell transplantation: a single-center experience. Biol Blood Marrow Transplant. 2017;23:945–51.CrossRefPubMedGoogle Scholar
  14. 14.
    Vajdic CM, Mayson E, Dodds AJ, O'Brien T, Wilcox L, Nivison-Smith I, et al. Second cancer risk and late mortality in adult Australians receiving allogeneic hematopoietic stem cell transplantation: a population-based cohort study. Biol Blood Marrow Transplant. 2016;22:949–56.CrossRefPubMedGoogle Scholar
  15. 15.
    Chen D, Zhou D, Guo D, Xu P, Chen B. Comparison of outcomes in hematological malignancies treated with haploidentical or HLA-identical sibling hematopoietic stem cell transplantation following myeloablative conditioning: a meta-analysis. PLoS One. 2018;13:e0191955.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Kumar AJ, Kim S, Hemmer MT, Arora M, Spellman SR, Pidala JA, et al. Graft-versus-host disease in recipients of male unrelated donor compared with parous female sibling donor transplants. Blood Adv. 2018;2:1022–31.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Cohen SB, Madrigal JA. Immunological and functional differences between cord and peripheral blood. Bone Marrow Transplant. 1998;21 Suppl 3:S9–12.Google Scholar
  18. 18.
    Atsuta Y, Suzuki R, Nagamura-Inoue T, Taniguchi S, Takahashi S, Kai S, et al. Disease-specific analyses of unrelated cord blood transplantation compared with unrelated bone marrow transplantation in adult patients with acute leukemia. Blood. 2009;113:1631–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Tanimoto TE, Yamaguchi T, Tanaka Y, Saito A, Tajima K, Karasuno T, et al. Comparative analysis of clinical outcomes after allogeneic bone marrow transplantation versus peripheral blood stem cell transplantation from a related donor in Japanese patients. Br J Haematol. 2004;125:480–93.CrossRefPubMedGoogle Scholar
  20. 20.
    Bleakley M, Heimfeld S, Loeb KR, Jones LA, Chaney C, Seropian S, et al. Outcomes of acute leukemia patients transplanted with naive T cell–depleted stem cell grafts. J Clin Invest. 2015;125:2677–89.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Lönnqvist B, Ringdén O, Wahren B, Gahrton G, Lundgren G. Cytomegalovirus infection associated with and preceding chronic graft-versus-host disease. Transplantation. 1984;38:465–8.CrossRefPubMedGoogle Scholar
  22. 22.
    Bhatia S. Long-term health impacts of hematopoietic stem cell transplantation inform recommendations for follow-up. Expert Rev Hematol. 2011;4:437–54.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Santo Tomas LH, Loberiza FR Jr, Klein JP, Layde PM, Lipchik RJ, Rizzo JD, et al. Risk factors for bronchiolitis obliterans in allogeneic hematopoietic stem-cell transplantation for leukemia. Chest. 2005;128:153–61.CrossRefPubMedGoogle Scholar
  24. 24.
    Hingman MA, Vogelsang GB. Chronic graft versus host disease. Br J Haematol. 2004;125:435–54.CrossRefGoogle Scholar
  25. 25.
    Mielcarek M, Martin PJ, Leisering W, Flowers ME, Maloney DG, Sandmaier BM, et al. Graft-versus-host disease after nonmyeloablative versus conventional hematopoietic stem cell transplantation. Blood. 2003;102:756–62.CrossRefPubMedGoogle Scholar
  26. 26.
    Skert C, Patricia F, Sperotto A, Cerno M, Fili C, Zaja F, et al. Sclerodermatous chronic graft-versus-host disease after allogeneic hematopoietic stem cell transplantation: incidence, predictors and outcome. Haematologica. 2006;91:258–61.PubMedGoogle Scholar
  27. 27.
    Cutler C, Antin JH. Peripheral blood stem cells for allogeneic transplantation: a review. Stem Cells. 2001;19:108–17.CrossRefPubMedGoogle Scholar
  28. 28.
    Kolb HJ, Socié G, Duell T, Van Lint MT, Tichelli A, Apperley JF, et al. Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group. Ann Intern Med. 1999;131:738–44.CrossRefPubMedGoogle Scholar
  29. 29.
    Heilmeier B, Stowasser N, Socie G, Van Lint MT, Tichelli A, Salooja N, et al. Malignant neoplasms in long-term survivors of bone marrow transplantation—follow up. Blood. 2008;112:453.CrossRefGoogle Scholar
  30. 30.
    Chien JW, Duncan S, Williams KM, Pavletic SZ. Bronchiolitis obliterans syndrome after allogeneic hematopoietic stem cell transplantation-an increasingly recognized manifestation of chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2010;16:S106–14.CrossRefPubMedGoogle Scholar
  31. 31.
    Au BK, Au MA, Chien JW. Bronchiolitis obliterans syndrome epidemiology after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2011;17:1072–8.CrossRefPubMedGoogle Scholar
  32. 32.
    Wiesmann A, Pereira P, Böhm P, Faul C, Kanz L, Einsele H. Avascular necrosis of bone following allogeneic stem cell transplantation: MR screening and therapeutic options. Bone Marrow Transplant. 1998;22:565–9.CrossRefPubMedGoogle Scholar

Copyright information

© The Korean Tissue Engineering and Regenerative Medicine Society and Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Psychological Medicine, Faculty of MedicineUniversity MalayaKuala LumpurMalaysia
  2. 2.School of Healthy Aging, Medical Aesthetics and Regenerative MedicineUniversity College Sedaya International (UCSI)Kuala LumpurMalaysia

Personalised recommendations