A general practitioner's guide to hematopoietic stem-cell transplantation

A Bazinet, G Popradi, A Bazinet, G Popradi

Abstract

Hematopoietic stem-cell transplantation (hsct) is a medical procedure that consists of infusing stem cells after a short course of chemotherapy or radiotherapy, or both. It can be used in the treatment of various cancers, as well as some benign conditions. In the present review, we discuss the various types of hsct and their main indications. The principles of the transplant procedure itself and the basics of recipient selection are reviewed. Special attention is given to both the immediate and the long-term complications of hsct and their management strategies. Hematopoietic stem-cell transplantation is a potentially life-saving procedure and often the only curative option for a variety of diseases; however, it is not without significant toxicities.

Keywords: Allogeneic transplantation; autologous transplantation; complications of transplantation; graft-versus-host disease; hematologic malignancies.

Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES We have read and understood Current Oncology’s policy on disclosing conflicts of interest, and we declare that we have none.

References

    1. Thomas ED, Lochte HL, Jr, Lu WC, Ferrebee JW. Intravenous infusion of bone marrow in patients receiving radiation and chemotherapy. N Engl J Med. 1957;257:491–6. doi: 10.1056/NEJM195709122571102.
    1. Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. 2007;357:1472–5. doi: 10.1056/NEJMp078166.
    1. World Health Organization (who) Haematopoietic Stem Cell Transplantation HSCtx [Web page] Geneva, Switzerland: who; 2018. [Available at: ; cited 6 January 2019]
    1. Thomas ED, Buckner CD, Banaji M, et al. One hundred patients with acute leukemia treated by chemotherapy, total body irradiation, and allogeneic marrow transplantation. Blood. 1977;49:511–33.
    1. Gertz MA. Current status of stem cell mobilization. Br J Haematol. 2010;150:647–62. doi: 10.1111/j.1365-2141.2010.08313.x.
    1. Anasetti C, Logan BR, Lee SJ, et al. on behalf of the Blood and Marrow Transplant Clinical Trials Network. Peripheral-blood stem cells versus bone marrow from unrelated donors. N Engl J Med. 2012;367:1487–96. doi: 10.1056/NEJMoa1203517.
    1. Stem Cell Trialists’ Collaborative Group. Allogeneic peripheral blood stem-cell compared with bone marrow transplantation in the management of hematologic malignancies: an individual patient data meta-analysis of nine randomized trials. J Clin Oncol. 2005;23:5074–87. doi: 10.1200/JCO.2005.09.020.
    1. Wagner JE, Barker JN, DeFor TE, et al. Transplantation of unrelated donor umbilical cord blood in 102 patients with malignant and nonmalignant diseases: influence of CD34 cell dose and hla disparity on treatment-related mortality and survival. Blood. 2002;100:1611–18.
    1. Kanakry CG, Fuchs EJ, Luznik L. Modern approaches to hla -haploidentical blood or marrow transplantation. Nat Rev Clin Oncol. 2016;13:132. doi: 10.1038/nrclinonc.2015.234. [Erratum in: Nat Rev Clin Oncol 2016;13:132]
    1. Ringden O, Karlsson H, Olsson R, Omazic B, Uhlin M. The allogeneic graft-versus-cancer effect. Br J Haematol. 2009;147:614–33. doi: 10.1111/j.1365-2141.2009.07886.x.
    1. Center for International Blood and Marrow Transplant Research. Summary slides—HCT trends and survival data [Web resource] Milwaukee, WI: The Medical College of Wisconsin; 2017. [Available at: ; cited 12 January 2019]
    1. Adra N, Abonour R, Althouse SK, Albany C, Hanna NH, Einhorn LH. High-dose chemotherapy and autologous peripheral-blood stem-cell transplantation for relapsed metastatic germ cell tumors: the Indiana University experience. J Clin Oncol. 2017;35:1096–102. doi: 10.1200/JCO.2016.69.5395.
    1. Pasqualini C, Dufour C, Goma G, Raquin MA, Lapierre V, Valteau-Couanet D. Tandem high-dose chemotherapy with thiotepa and busulfan–melphalan and autologous stem cell transplantation in very high-risk neuroblastoma patients. Bone Marrow Transplant. 2016;51:227–31. doi: 10.1038/bmt.2015.264.
    1. Laurence V, Pierga JY, Barthier S, et al. Long-term follow up of high-dose chemotherapy with autologous stem cell rescue in adults with Ewing tumor. Am J Clin Oncol. 2005;28:301–9. doi: 10.1097/01.coc.0000156921.28880.e1.
    1. Gajjar A, Chintagumpala M, Ashley D, et al. Risk-adapted craniospinal radiotherapy followed by high-dose chemotherapy and stem-cell rescue in children with newly diagnosed medulloblastoma (St Jude Medulloblastoma-96): long-term results from a prospective, multicentre trial. Lancet Oncol. 2006;7:813–20. doi: 10.1016/S1470-2045(06)70867-1.
    1. Peinemann F, Grouven U, Kroger N, Bartel C, Pittler MH, Lange S. First-line matched related donor hematopoietic stem cell transplantation compared to immunosuppressive therapy in acquired severe aplastic anemia. PLoS One. 2011;6:e18572. doi: 10.1371/journal.pone.0018572.
    1. Dalle JH, Peffault de Latour R. Allogeneic hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Int J Hematol. 2016;103:373–9. doi: 10.1007/s12185-016-1951-0.
    1. Gluckman E, Cappelli B, Bernaudin F, et al. on behalf of the Eurocord, the Pediatric Working Party of the European Society for Blood and Marrow Transplantation, and the Center for International Blood and Marrow Transplant Research. Sickle cell disease: an international survey of results of hla -identical sibling hematopoietic stem cell transplantation. Blood. 2017;129:1548–56. doi: 10.1182/blood-2016-10-745711.
    1. Baronciani D, Angelucci E, Potschger U, 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 Transplant. 2016;51:536–41. doi: 10.1038/bmt.2015.293.
    1. Wahlstrom JT, Dvorak CC, Cowan MJ. Hematopoietic stem cell transplantation for severe combined immunodeficiency. Curr Pediatr Rep. 2015;3:1–10. doi: 10.1007/s40124-014-0071-7.
    1. Krivit W, Sung JH, Shapiro EG, Lockman LA. Microglia: the effector cell for reconstitution of the central nervous system following bone marrow transplantation for lysosomal and peroxisomal storage diseases. Cell Transplant. 1995;4:385–92. doi: 10.1177/096368979500400409.
    1. Hugle T, Daikeler T. Stem cell transplantation for autoimmune diseases. Haematologica. 2010;95:185–8. doi: 10.3324/haematol.2009.017038.
    1. Mancardi G, Sormani MP, Muraro PA, Boffa G, Saccardi R. Intense immunosuppression followed by autologous haematopoietic stem cell transplantation as a therapeutic strategy in aggressive forms of multiple sclerosis. Mult Scler. 2018;24:245–55. doi: 10.1177/1352458517742532.
    1. National Marrow Donor Program/Be The Match and the American Society for Blood and Marrow Transplantation. Transplant referral timing guidelines [Web page] Minneapolis, MN: National Marrow Donor Program; 2019. [Available at: ; cited 19 January 2019]
    1. Sorror ML, Maris MB, Storb R, et al. Hematopoietic Cell Transplantation (hct)–Specific Comorbidity Index: a new tool for risk assessment before allogeneic hct. Blood. 2005;106:2912–19. doi: 10.1182/blood-2005-05-2004.
    1. Muffly LS, Kocherginsky M, Stock W, et al. Geriatric assessment to predict survival in older allogeneic hematopoietic cell transplantation recipients. Haematologica. 2014;99:1373–9. doi: 10.3324/haematol.2014.103655.
    1. Gertz MA, Ansell SM, Dingli D, et al. Autologous stem cell transplant in 716 patients with multiple myeloma: low treatmentrelated mortality, feasibility of outpatient transplant, and effect of a multidisciplinary quality initiative. Mayo Clin Proc. 2008;83:1131–8. doi: 10.4065/83.10.1131.
    1. Guru Murthy GSG, Hari PN, Szabo A, et al. Outcomes of reduced- intensity conditioning allogeneic hematopoietic cell transplantation performed in the inpatient versus outpatient setting. Biol Blood Marrow Transplant. 2019;25:827–33. doi: 10.1016/j.bbmt.2018.12.069.
    1. Nash RA, Pineiro LA, Storb R, et al. FK506 in combination with methotrexate for the prevention of graft-versus-host disease after marrow transplantation from matched unrelated donors. Blood. 1996;88:3634–41.
    1. Ruutu T, Eriksson B, Remes K, et al. on behalf of the Nordic Bone Marrow Transplantation Group. Ursodeoxycholic acid for the prevention of hepatic complications in allogeneic stem cell transplantation. Blood. 2002;100:1977–83. doi: 10.1182/blood-2001-12-0159.
    1. Tomblyn M, Chiller T, Einsele H, et al. on behalf of the Center for International Blood and Marrow Research, the National Marrow Donor program, the European Blood and Marrow Transplant Group, the American Society of Blood and Marrow Transplantation, the Canadian Blood and Marrow Transplant Group, the Infectious Diseases Society of America, the Society for Healthcare Epidemiology of America, the Association of Medical Microbiology and Infectious Disease Canada, and the Centers for Disease Control and Prevention. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15:1143–238. doi: 10.1016/j.bbmt.2009.06.019.
    1. Dalle JH, Giralt SA. Hepatic veno-occlusive disease after hematopoietic stem cell transplantation: risk factors and stratification, prophylaxis, and treatment. Biol Blood Marrow Transplant. 2016;22:400–9. doi: 10.1016/j.bbmt.2015.09.024.
    1. Carreras E, Dufour C, Mohty M, Kröger N, editors. The EBMT Handbook: Hematopoietic Stem Cell Transplantation and Cellular Therapies. 7th ed. Cham, Switzerland: Springer Nature Switzerland; 2019.
    1. Cutler C. Acute graft-vs-host disease. In: Wingard J, editor. Hematopoietic Stem Cell Transplantation: A Handbook for Clinicians. Bethesda, MD: American Association of Blood Banks; 2009. pp. 331–43.
    1. Jagasia MH, Greinix HT, Arora M, et al. National Institutes of Health Consensus Development project on criteria for clinical trials in chronic graft-versus-host disease: i. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant. 2015;21:389–401. doi: 10.1016/j.bbmt.2014.12.001.
    1. Flowers ME, Apperley JF, van Besien K, et al. A multicenter prospective phase 2 randomized study of extracorporeal photopheresis for treatment of chronic graft-versus-host disease. Blood. 2008;112:2667–74. doi: 10.1182/blood-2008-03-141481.
    1. Miklos D, Cutler CS, Arora M, et al. Ibrutinib for chronic graft-versus-host disease after failure of prior therapy. Blood. 2017;130:2243–50. doi: 10.1182/blood-2017-07-793786.
    1. Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015;29:2062–8. doi: 10.1038/leu.2015.212.
    1. National Marrow Donor Program (nmdp)/Be The Match. Long-Term Survival Guidelines—Post-Transplant Care Recommendations [Web page] Minneapolis, MN: nmdp; 2018. 2018. [Available at: ; cited 10 March 2019]
    1. Tichelli A, Bucher C, Rovo A, et al. Premature cardiovascular disease after allogeneic hematopoietic stem-cell transplantation. Blood. 2007;110:3463–71. doi: 10.1182/blood-2006-10-054080.
    1. Majhail NS, Flowers ME, Ness KK, et al. High prevalence of metabolic syndrome after allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2009;43:49–54. doi: 10.1038/bmt.2008.263.
    1. Tauchmanova L, Colao A, Lombardi G, Rotoli B, Selleri C. Bone loss and its management in long-term survivors from allogeneic stem cell transplantation. J Clin Endocrinol Metab. 2007;92:4536–45. doi: 10.1210/jc.2006-2870.
    1. Medinger M, Zeiter D, Heim D, et al. Hypothyroidism following allogeneic hematopoietic stem cell transplantation for acute myeloid leukemia. Leuk Res. 2017;58:43–7. doi: 10.1016/j.leukres.2017.04.003.
    1. Baker KS, DeFor TE, Burns LJ, Ramsay NK, Neglia JP, Robison LL. New malignancies after blood or marrow stem-cell transplantation in children and adults: incidence and risk factors. J Clin Oncol. 2003;21:1352–8. doi: 10.1200/JCO.2003.05.108.
    1. Hammond C, Abrams JR, Syrjala KL. Fertility and risk factors for elevated infertility concern in 10-year hematopoietic cell transplant survivors and case-matched controls. J Clin Oncol. 2007;25:3511–17. doi: 10.1200/JCO.2007.10.8993.
    1. Poppelreuter M, Weis J, Mumm A, Orth HB, Bartsch HH. Rehabilitation of therapy-related cognitive deficits in patients after hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41:79–90. doi: 10.1038/sj.bmt.1705884.
    1. Inamoto Y, Lee SJ. Late effects of blood and marrow transplantation. Haematologica. 2017;102:614–25. doi: 10.3324/haematol.2016.150250.
    1. Pidala J, Kurland B, Chai X, et al. Patient-reported quality of life is associated with severity of chronic graft-versus-host disease as measured by nih criteria: report on baseline data from the Chronic GVHD Consortium. Blood. 2011;117:4651–7. doi: 10.1182/blood-2010-11-319509.

Source: PubMed

3
Se inscrever