Skip to main content
SpringerLink
Log in

Overview of Hematopoietic Stem Cell Transplantation for Nonmalignant Diseases

  • Chapter
  • First Online:
Sickle Cell Disease and Hematopoietic Stem Cell Transplantation

Abstract

As overall outcomes from hematopoietic stem cell transplantation (HSCT) continue to improve, the repertoire of nonmalignant indications for transplant also continues to expand. Nonmalignant conditions accounted for approximately 30% of all transplants performed in the USA from 2009–2013 with this number expected to continue rising. In addition, HSCT is now being performed for many disorders for which it was previously reserved for severe clinical phenotypes only. This chapter provides an overview of the transplant process for nonmalignant disorders (NMD). It highlights the unique experiences of NMD HSCT based on disease category: primary immunodeficiency syndromes, hemoglobinopathies and disorders of red cells, inherited disorders of metabolism, and aplastic anemia and bone marrow failure syndromes. Furthermore, it touches on recent developments in reduced intensity conditioning regimens, GVHD prophylaxis, and the management of post-transplant infection risks.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 99.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 139.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ATG:

Antithymocyte globulin

BMF:

Bone marrow failure

Bu/Flu:

Busulfan/fludarabine

CMV:

Cytomegalovirus

CNS:

Central nervous system

Css:

Concentration at steady state

DLI:

Donor lymphocyte infusion

EBV:

Epstein-Barr virus

EFS:

Event-free survival

GVHD:

Graft-versus-host disease

GVLE:

Graft-versus-leukemia effect

HLA:

Human leukocyte antigen

HLH:

Hemophagocytic lymphohistiocytosis

HSCT:

Hematopoietic stem cell transplant

IMD:

Inherited disorders of metabolism

IST:

Immunosuppressive therapy

MSD:

Matched sibling donor

MUD:

Matched unrelated donor

NMD(s):

Nonmalignant disorder(s)

OS:

Overall survival

PTLD:

Post-transplant lymphoproliferative disease

RIC:

Reduced intensity conditioning

SAA:

Severe aplastic anemia

SCD:

Sickle cell disease

SCID:

Severe combined immunodeficiency syndrome

SOS:

Sinusoidal obstruction syndrome

TRM:

Transplant-related mortality

UCB:

Umbilical cord blood

URD:

Unrelated donor

VST:

Virus-specific T-cell therapy

References

  1. Gatti RA, et al. Immunological reconstitution of sex-linked lymphopenic immunological deficiency. Lancet (London, England). 1968;2(7583):1366–9.

    Article  CAS  Google Scholar 

  2. Svenberg P, et al. Improved overall survival for pediatric patients undergoing allogeneic hematopoietic stem cell transplantation – a comparison of the last two decades. Pediatr Transplant. 2016;20(5):667–74.

    Article  PubMed  Google Scholar 

  3. Center for International Blood and Marrow Transplant, a.c.f.t.C.W.B.Y.C.T.P. Number of HCTs performed in the United States and reported to CIBMTR by disease category and age, by year. Last updated 18 May 2015; Available from: http://bloodcell.transplant.hrsa.gov/research/transplant_data/transplant_activity_report/year-disease_category_and_age.pdf.

  4. Brown L, et al. Neonatal diagnosis of severe combined immunodeficiency leads to significantly improved survival outcome: the case for newborn screening. Blood. 2011;117(11):3243–6.

    Article  CAS  PubMed  Google Scholar 

  5. Myers LA. Hematopoietic stem cell transplantation for severe combined immunodeficiency in the neonatal period leads to superior thymic output and improved survival. Blood. 2002;99(3):872–8.

    Article  CAS  PubMed  Google Scholar 

  6. Gennery AR, et al. Transplantation of hematopoietic stem cells and long-term survival for primary immunodeficiencies in Europe: entering a new century, do we do better? J Allergy Clin Immunol. 2010;126(3):602.

    Article  PubMed  Google Scholar 

  7. Buckley RH, et al. Hematopoietic stem-cell transplantation for the treatment of severe combined immunodeficiency. N Engl J Med. 1999;340(7):508–16.

    Article  CAS  PubMed  Google Scholar 

  8. Routes JM, et al. Statewide newborn screening for severe T-cell lymphopenia. JAMA. 2009;302(22):2465–70.

    Article  CAS  PubMed  Google Scholar 

  9. Buckley RH. Transplantation of hematopoietic stem cells in human severe combined immunodeficiency: longterm outcomes. Immunol Res. 2011;49(1–3):25–43.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Dvorak CC, et al. Comparison of outcomes of hematopoietic stem cell transplantation without chemotherapy conditioning by using matched sibling and unrelated donors for treatment of severe combined immunodeficiency. J Allergy Clin Immunol. 2014;134(4):935.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Pai S-Y, et al. Transplantation outcomes for severe combined immunodeficiency, 2000–2009. N Engl J Med. 2014;371(5):434–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sarzotti-Kelsoe M, et al. Thymic output, T-cell diversity, and T-cell function in long-term human SCID chimeras. Blood. 2009;114(7):1445–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Buckley RH. Molecular defects in human severe combined immunodeficiency and approaches to immune reconstitution. Annu Rev Immunol. 2004;22(1):625–55.

    Article  CAS  PubMed  Google Scholar 

  14. Hassan A, et al. Host natural killer immunity is a key indicator of permissiveness for donor cell engraftment in patients with severe combined immunodeficiency. J Allergy Clin Immunol. 2014;133(6):1660–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Parkman R, et al. Complete correction of the Wiskott-Aldrich syndrome by allogeneic bone-marrow transplantation. N Engl J Med. 1978;298(17):921–7.

    Article  CAS  PubMed  Google Scholar 

  16. Rimm IJ, Rappeport JM. Bone marrow transplantation for the Wiskott-Aldrich syndrome. Long-term follow-up. Transplantation. 1990;50(4):617–20.

    Article  CAS  PubMed  Google Scholar 

  17. Brochstein JA, et al. Marrow transplantation from human leukocyte antigen-identical or haploidentical donors for correction of Wiskott-Aldrich syndrome. J Pediatr. 1991;119(6):907–12.

    Article  CAS  PubMed  Google Scholar 

  18. Ozsahin H, et al. Bone marrow transplantation in 26 patients with Wiskott-Aldrich syndrome from a single center. J Pediatr. 1996;129(2):238–44.

    Article  CAS  PubMed  Google Scholar 

  19. Burroughs LM, et al. Treosulfan-based conditioning and hematopoietic cell transplantation for nonmalignant diseases: a prospective multicenter trial. Biol Blood Marrow Transplant. 2014;20(12):1996–2003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Güngör T, et al. Reduced-intensity conditioning and HLA-matched haemopoietic stem-cell transplantation in patients with chronic granulomatous disease: a prospective multicentre study. Lancet. 2014;383(9915):436–48.

    Article  PubMed  CAS  Google Scholar 

  21. Marsh RA, et al. Experience with alemtuzumab, fludarabine, and melphalan reduced-intensity conditioning hematopoietic cell transplantation in patients with nonmalignant diseases reveals good outcomes and that the risk of mixed chimerism depends on underlying disease, stem cell source, and alemtuzumab regimen. Biol Blood Marrow Transplant. 2015;21(8):1460–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Morillo-Gutierrez B, et al. Treosulfan-based conditioning for allogeneic HSCT in children with chronic granulomatous disease: a multicenter experience. Blood. 2016;128(3):440–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Angelucci E, 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(5):811–20.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Thomas DE, et al. Marrow transplantation for thalassaemia. Lancet. 1982;320(8292):227–9.

    Article  Google Scholar 

  25. Lucarelli G, et al. Marrow transplantation in patients with thalassemia responsive to iron chelation therapy. N Engl J Med. 1993;329(12):840–4.

    Article  CAS  PubMed  Google Scholar 

  26. Lucarelli G, et al. Bone marrow transplantation in patients with thalassemia. N Engl J Med. 1990;322(7):417–21.

    Article  CAS  PubMed  Google Scholar 

  27. King AA, et al. Successful matched sibling donor marrow transplantation following reduced intensity conditioning in children with hemoglobinopathies. Am J Hematol. 2015;90(12):1093–8.

    Article  CAS  PubMed  Google Scholar 

  28. Walters MC, et al. Indications and results of HLA-identical sibling hematopoietic cell transplantation for sickle cell disease. Biol Blood Marrow Transplant. 2016;22(2):207–11.

    Article  PubMed  Google Scholar 

  29. Gaziev J, et al. Bone marrow transplantation for thalassemia from alternative related donors: improved outcomes with a new approach. Blood. 2013;122(15):2751–6.

    Article  CAS  PubMed  Google Scholar 

  30. Li C, et al. A novel conditioning regimen improves outcomes in β-thalassemia major patients using unrelated donor peripheral blood stem cell transplantation. Blood. 2012;120(19):3875–81.

    Article  CAS  PubMed  Google Scholar 

  31. Sodani P, et al. New approach for bone marrow transplantation in patients with class 3 thalassemia aged younger than 17 years. Blood. 2004;104(4):1201–3.

    Article  CAS  PubMed  Google Scholar 

  32. Bernaudin F, et al. Long-term results of related myeloablative stem-cell transplantation to cure sickle cell disease. Blood. 2007;110(7):2749–56.

    Article  CAS  PubMed  Google Scholar 

  33. Bernardo M, et al. Allogeneic hematopoietic stem cell transplantation in thalassemia major: results of a reduced-toxicity conditioning regimen based on the use of treosulfan. Blood. 2012;120(2):473–6.

    Article  CAS  PubMed  Google Scholar 

  34. Bernardo M, et al. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major. Br J Haematol. 2008;143(4):548–51.

    PubMed  Google Scholar 

  35. Hsieh MM, et al. Allogeneic hematopoietic stem-cell transplantation for sickle cell disease. N Engl J Med. 2009;361(24):2309–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Gragert L, et al. HLA match likelihoods for hematopoietic stem-cell grafts in the U.S. registry. N Engl J Med. 2014;371(4):339–48.

    Article  CAS  PubMed  Google Scholar 

  37. Walters MC, Patience M, Leisenring W, Eckman JR, Buchanan GR, Rogers ZR, Olivieri NE, Vichinsky E, Davies SC, Mentzer WC, Powars D, Scott JP, Bernaudin F, Ohene-Frempong K, Darbyshire PJ, Wayne A, Roberts IA, Dinndorf P, Brandalise S, Sanders JE, Matthews DC, Appelbaum FR, Storb R, Sullivan KM. Barriers to bone marrow transplantation for sickle cell anemia. Biol Blood Marrow Transplant. 1996;2:100–4.

    CAS  PubMed  Google Scholar 

  38. Shenoy S, et al. Results of the blood and marrow transplant clinical trials network study BMT CTN 0601: SCURT – a multicenter phase II trial of unrelated donor reduced intensity bone marrow transplantation (BMT) for children with severe sickle cell disease. Biol Blood Marrow Transplant. 2016;22(3):S104.

    Article  Google Scholar 

  39. Bolanos-Meade J, et al. HLA-haploidentical bone marrow transplantation with posttransplant cyclophosphamide expands the donor pool for patients with sickle cell disease. Blood. 2012;120(22):4285–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Walters MC. Update of hematopoietic cell transplantation for sickle cell disease. Curr Opin Hematol. 2015;22(3):227.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Prasad VK, Kurtzberg J. Cord blood and bone marrow transplantation in inherited metabolic diseases: scientific basis, current status and future directions. Br J Haematol. 2010;148(3):356–72.

    Article  PubMed  Google Scholar 

  42. Hobbs JR, et al. Reversal of clinical features of Hurler's disease and biochemical improvement after treatment by bone-marrow transplantation. Lancet (London, England). 1981;2(8249):709–12.

    Article  CAS  Google Scholar 

  43. Kögler G, et al. A new human somatic stem cell from placental cord blood with intrinsic pluripotent differentiation potential. J Exp Med. 2004;200(2):123–35.

    Article  PubMed  PubMed Central  Google Scholar 

  44. Kurtzberg J, et al. 222Umbilical cord blood cells engraft and differentiate in neural tissues after human transplantation. Biol Blood Marrow Transplant. 2003;9(2):128–9.

    Article  Google Scholar 

  45. Peters C, et al. Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group. Blood. 1998;91(7):2601–8.

    CAS  PubMed  Google Scholar 

  46. Aldenhoven M, Kurtzberg J. Cord blood is the optimal graft source for the treatment of pediatric patients with lysosomal storage diseases: clinical outcomes and future directions. Cytotherapy. 2015;17(6):765–74.

    Article  CAS  PubMed  Google Scholar 

  47. Martin PL, et al. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006;12(2):184–94.

    Article  PubMed  Google Scholar 

  48. Prasad VK, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood. 2008;112(7):2979–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Aldenhoven M, et al. Hematopoietic cell transplantation for mucopolysaccharidosis patients is safe and effective: results after implementation of international guidelines. Biol Blood Marrow Transplant. 2015;21(6):1106–9.

    Article  CAS  PubMed  Google Scholar 

  50. Peters C, et al. Hematopoietic cell transplantation for inherited metabolic diseases: an overview of outcomes and practice guidelines. Bone Marrow Transplant. 2003;31(4):229–39.

    Article  CAS  PubMed  Google Scholar 

  51. Aldenhoven M, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015;125(13):2164–72.

    Article  CAS  PubMed  Google Scholar 

  52. Dufour C, et al. Outcome of aplastic anemia in adolescence. A survey of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation. Haematologica. 2014;99(10):1574–81.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Dufour C, et al. Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant. Br J Haematol. 2015;169(4):565–73.

    Article  PubMed  Google Scholar 

  54. Yoshida N, et al. First-line treatment for severe aplastic anemia in children: bone marrow transplantation from a matched family donor versus immunosuppressive therapy. Haematologica. 2014;99(12):1784–91.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Samarasinghe S, Webb DKH. How I manage aplastic anaemia in children. Br J Haematol. 2012;157(1):26–40.

    Article  CAS  PubMed  Google Scholar 

  56. Bacigalupo A, et al. Current outcome of HLA identical sibling versus unrelated donor transplants in severe aplastic anemia: an EBMT analysis. Haematologica. 2015;100(5):696–702.

    Article  PubMed  PubMed Central  Google Scholar 

  57. Dufour C, et al. Similar outcome of upfront-unrelated and matched sibling stem cell transplantation in idiopathic paediatric aplastic anaemia. A study on behalf of the UK Paediatric BMT Working Party, Paediatric Diseases Working Party and Severe Aplastic Anaemia Working Party of EBMT. Br J Haematol. 2015;171(4):585–94.

    Article  CAS  PubMed  Google Scholar 

  58. Peffault de Latour R. Transplantation for bone marrow failure: current issues. Hematology Am Soc Hematol Educ Program. 2016;2016(1):90–8.

    PubMed  Google Scholar 

  59. Alter BP, et al. Cancer in dyskeratosis congenita. Blood. 2009;113(26):6549–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Gluckman E. 9 bone marrow transplantation for Fanconi’s anaemia. Baillieres Clin Haematol. 1989;2(1):153–62.

    Article  CAS  PubMed  Google Scholar 

  61. Kapelushnik J, et al. A fludarabine-based protocol for bone marrow transplantation in Fanconi's anemia. Bone Marrow Transplant. 1997;20(12):1109–10.

    Article  CAS  PubMed  Google Scholar 

  62. Ayas M, et al. The Saudi experience in fludarabine-based conditioning regimens in patients with Fanconi anemia undergoing stem cell transplantation: excellent outcome in recipients of matched related stem cells but not in recipients of unrelated cord blood stem cells. Biol Blood Marrow Transplant. 2012;18(4):627–32.

    Article  CAS  PubMed  Google Scholar 

  63. de Latour PR, et al. Allogeneic hematopoietic stem cell transplantation in Fanconi anemia: the European Group for Blood and Marrow Transplantation experience. Blood. 2013;122(26):4279–86.

    Article  CAS  Google Scholar 

  64. Locatelli F, et al. The outcome of children with Fanconi anemia given hematopoietic stem cell transplantation and the influence of fludarabine in the conditioning regimen: a report from the Italian pediatric group. Haematologica. 2007;92(10):1381–8.

    Article  PubMed  Google Scholar 

  65. Stepensky P, et al. Bone marrow transplantation for Fanconi anemia using fludarabine-based conditioning. Biol Blood Marrow Transplant. 2011;17(9):1282–8.

    Article  CAS  PubMed  Google Scholar 

  66. Tan P-L, et al. Successful engraftment without radiation after fludarabine-based regimen in Fanconi anemia patients undergoing genotypically identical donor hematopoietic cell transplantation. Pediatr Blood Cancer. 2006;46(5):630–6.

    Article  PubMed  Google Scholar 

  67. Tolar J, Mehta PA, Walters MC. Hematopoietic cell transplantation for nonmalignant disorders. Biol Blood Marrow Transplant. 2012;18(1):S166–71.

    Article  PubMed  Google Scholar 

  68. Schifferli A, Kühne T. Fanconi anemia: overview of the disease and the role of hematopoietic transplantation. J Pediatr Hematol Oncol. 2015;37(5):335.

    Article  CAS  PubMed  Google Scholar 

  69. Mehta PA. Chemotherapy-only prepartive regimen for alternative donor hematopoietic cell transplantation for patients with Fanconi anemia (FA): results of a multi-institutional study. In BMT tandem meetings, San Diego, CA. 2015.

    Google Scholar 

  70. Agarwal S. Minimal intensity BMT for DC. San Diego, CA: American Society of Hematology; 2016.

    Google Scholar 

  71. Bartelink IH, et al. Fludarabine and exposure-targeted busulfan compares favorably with busulfan/cyclophosphamide-based regimens in pediatric hematopoietic cell transplantation: maintaining efficacy with less toxicity. Biol Blood Marrow Transplant. 2014;20(3):345–53.

    Article  CAS  PubMed  Google Scholar 

  72. Bolinger AM, et al. An evaluation of engraftment, toxicity and busulfan concentration in children receiving bone marrow transplantation for leukemia or genetic disease. Bone Marrow Transplant. 2000;25(9):925–30.

    Article  CAS  PubMed  Google Scholar 

  73. Maheshwari S, et al. Targeted Busulfan therapy with a steady-state concentration of 600–700 ng/mL in patients with sickle cell disease receiving HLA-identical sibling bone marrow transplant. Bone Marrow Transplant. 2013;49(3):366–9.

    Article  PubMed  CAS  Google Scholar 

  74. Horn B, et al. Reduced intensity conditioning using intravenous busulfan, fludarabine and rabbit ATG for children with nonmalignant disorders and CML. Bone Marrow Transplant. 2005;37(3):263–9.

    Article  CAS  Google Scholar 

  75. Greystoke B, et al. Treosulfan-containing regimens achieve high rates of engraftment associated with low transplant morbidity and mortality in children with non-malignant disease and significant co-morbidities. Br J Haematol. 2008;142(2):257–62.

    Article  CAS  PubMed  Google Scholar 

  76. Slatter MA, et al. Treosulfan-based conditioning regimens for hematopoietic stem cell transplantation in children with primary immunodeficiency: United Kingdom experience. Blood. 2011;117(16):4367–75.

    Article  CAS  PubMed  Google Scholar 

  77. Choudhary D, et al. Treosulfan-thiotepa-fludarabine-based conditioning regimen for allogeneic transplantation in patients with thalassemia major: a single-center experience from North India. Biol Blood Marrow Transplant. 2013;19(3):492–5.

    Article  CAS  PubMed  Google Scholar 

  78. Lehmberg K, et al. Treosulfan-based conditioning regimen for children and adolescents with hemophagocytic lymphohistiocytosis. Haematologica. 2014;99(1):180–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Strocchio L, et al. Treosulfan-based conditioning regimen for allogeneic haematopoietic stem cell transplantation in children with sickle cell disease. Br J Haematol. 2015;169(5):726–36.

    Article  CAS  PubMed  Google Scholar 

  80. Madden LM, Hayashi RJ, Chan KW, Pulsipher MA, Douglas D, Hale GA, Chaudhury SHP, Kasow KA, Gilman AL, Murray LM, Shenoy S. Long-term follow-up after reduced-intensity conditioning and stem cell transplantation for childhoood nonmalignant disorders. Biol Blood Marrow Transplant. 2016;22:1467–72.

    Article  PubMed  Google Scholar 

  81. Straathof KC, et al. Haemopoietic stem-cell transplantation with antibody-based minimal-intensity conditioning: a phase 1/2 study. Lancet. 2009;374(9693):912–20.

    Article  CAS  PubMed  Google Scholar 

  82. Mawad R, et al. Radiolabeled anti-CD45 antibody with reduced-intensity conditioning and allogeneic transplantation for younger patients with advanced acute myeloid leukemia or myelodysplastic syndrome. Biol Blood Marrow Transplant. 2014;20(9):1363–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Chandrakasan S, et al. KIT blockade is sufficient for donor hematopoietic stem cell engraftment in Fanconi anemia mice. Blood. 2017;129(8):1048–52.

    Article  PubMed  Google Scholar 

  84. Czechowicz A, et al. Efficient transplantation via antibody-based clearance of hematopoietic stem cell niches. Science. 2007;318(5854):1296–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Chhabra A, et al. Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy. Sci Transl Med. 2016;8(351):351ra105.

    Article  PubMed  Google Scholar 

  86. Palchaudhuri R, et al. Non-genotoxic conditioning for hematopoietic stem cell transplantation using a hematopoietic-cell-specific internalizing immunotoxin. Nat Biotechnol. 2016;34(7):738–45.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Locatelli F, et al. Cyclosporin A and short-term methotrexate versus cyclosporin A as graft versus host disease prophylaxis in patients with severe aplastic anemia given allogeneic bone marrow transplantation from an HLA-identical sibling: results of a GITMO/EBMT randomized trial. Blood. 2000;96(5):1690–7.

    CAS  PubMed  Google Scholar 

  88. Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res. 2010;47(1–3):65–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Luznik L, et al. HLA-haploidentical bone marrow transplantation for hematologic malignancies using nonmyeloablative conditioning and high-dose, posttransplantation cyclophosphamide. Biol Blood Marrow Transplant. 2008;14(6):641–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Robinson TM, et al. Haploidentical bone marrow and stem cell transplantation: experience with post-transplantation cyclophosphamide. Semin Hematol. 2016;53(2):90–7.

    Article  PubMed  PubMed Central  Google Scholar 

  91. Brodsky RA, et al. Reduced intensity HLA-haploidentical BMT with post transplantation cyclophosphamide in nonmalignant hematologic diseases. Bone Marrow Transplant. 2008;42(8):523–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Parta M, et al. Haploidentical hematopoietic cell transplantation with post-transplant cyclophosphamide in a patient with chronic granulomatous disease and active infection: a first report. J Clin Immunol. 2015;35(7):675–80.

    Article  CAS  PubMed  Google Scholar 

  93. Thakar MS, et al. Cyclophosphamide-based in vivo T-cell depletion for HLA-haploidentical transplantation in Fanconi anemia. Pediatr Hematol Oncol. 2012;29(6):568–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Klein OR, et al. Alternative-donor hematopoietic stem cell transplantation with post-transplantation cyclophosphamide for nonmalignant disorders. Biol Blood Marrow Transplant. 2016;22(5):895–901.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Gupta V, et al. Favorable effect on acute and chronic graft-versus-host disease with cyclophosphamide and in vivo anti-CD52 monoclonal antibodies for marrow transplantation from HLA-identical sibling donors for acquired aplastic anemia. Biol Blood Marrow Transplant. 2004;10(12):867–76.

    Article  CAS  PubMed  Google Scholar 

  96. Koura DT, et al. In vivo T cell costimulation blockade with abatacept for acute graft-versus-host disease prevention: a first-in-disease trial. Biol Blood Marrow Transplant. 2013;19(11):1638–49.

    Article  CAS  PubMed  Google Scholar 

  97. Teschner D, et al. Depletion of naive T cells using clinical grade magnetic CD45RA beads: a new approach for GVHD prophylaxis. Bone Marrow Transplant. 2014;49(1):138–44.

    Article  CAS  PubMed  Google Scholar 

  98. Touzot F, et al. CD45RA depletion in HLA-mismatched allogeneic hematopoietic stem cell transplantation for primary combined immunodeficiency: a preliminary study. J Allergy Clin Immunol. 2015;135(5):1303–1309000.

    Article  CAS  PubMed  Google Scholar 

  99. Airoldi I, et al. T-cell reconstitution after HLA-haploidentical hematopoietic transplantation depleted of TCR-+/CD19+ lymphocytes. Blood. 2015;125(15):2349–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  100. Bertaina A, et al. HLA-haploidentical stem cell transplantation after removal of αβ+ T and B cells in children with nonmalignant disorders. Blood. 2014;124(5):822–6.

    Article  CAS  PubMed  Google Scholar 

  101. Bleakley M, et al. Outcomes of acute leukemia patients transplanted with naive T cell-depleted stem cell grafts. J Clin Investig. 2015;125(7):2677–89.

    Article  PubMed  PubMed Central  Google Scholar 

  102. Daniele N, et al. Transplantation in the onco-hematology field: focus on the manipulation of αβ and γδ T cells. Pathol Res Pract. 2012;208(2):67–73.

    Article  CAS  PubMed  Google Scholar 

  103. Locatelli F, et al. Negative depletion of α/β+ T cells and of CD19+ B lymphocytes: a novel frontier to optimize the effect of innate immunity in HLA-mismatched hematopoietic stem cell transplantation. Immunol Lett. 2013;155(1–2):21–3.

    Article  CAS  PubMed  Google Scholar 

  104. Lehrnbecher T, et al. Therapy-induced alterations in host defense in children receiving therapy for cancer. J Pediatr Hematol Oncol. 1997;19(5):399–417.

    Article  CAS  PubMed  Google Scholar 

  105. van Burik J-AH, et al. Higher risk of cytomegalovirus and Aspergillus infections in recipients of T cell-depleted unrelated bone marrow: analysis of infectious complications in patients treated with T cell depletion versus immunosuppressive therapy to prevent graft-versus-host disease. Biol Blood Marrow Transplant. 2007;13(12):1487–98.

    Article  PubMed  Google Scholar 

  106. Chakrabarti S, et al. Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppression, and immune recovery. Blood. 2002;100(5):1619–27.

    Article  CAS  PubMed  Google Scholar 

  107. Myers GD, et al. Adenovirus infection rates in pediatric recipients of alternate donor allogeneic bone marrow transplants receiving either antithymocyte globulin (ATG) or alemtuzumab (Campath). Bone Marrow Transplant. 2005;36(11):1001–8.

    Article  CAS  PubMed  Google Scholar 

  108. Shields AF, et al. Adenovirus infections in patients undergoing bone-marrow transplantation. N Engl J Med. 1985;312(9):529–33.

    Article  CAS  PubMed  Google Scholar 

  109. La Rosa AM, et al. Adenovirus infections in adult recipients of blood and marrow transplants. Clin Infect Dis. 2001;32(6):871–6.

    Article  PubMed  Google Scholar 

  110. Symeonidis N, et al. Invasive adenoviral infections in T-cell-depleted allogeneic hematopoietic stem cell transplantation: high mortality in the era of cidofovir. Transpl Infect Dis. 2007;9(2):108–13.

    Article  CAS  PubMed  Google Scholar 

  111. Gerritsen EJ, et al. Risk factors for developing EBV-related B cell lymphoproliferative disorders (BLPD) after non-HLA-identical BMT in children. Bone Marrow Transplant. 1996;18(2):377–82.

    CAS  PubMed  Google Scholar 

  112. Shapiro RS, et al. Epstein-Barr virus associated B cell lymphoproliferative disorders following bone marrow transplantation. Blood. 1988;71(5):1234–43.

    CAS  PubMed  Google Scholar 

  113. Zutter MM, et al. Epstein-Barr virus lymphoproliferation after bone marrow transplantation. Blood. 1988;72(2):520–9.

    CAS  PubMed  Google Scholar 

  114. Gavin PJ, Katz BZ. Intravenous ribavirin treatment for severe adenovirus disease in immunocompromised children. Pediatrics. 2002;110(1 Pt 1):e9.

    Article  PubMed  Google Scholar 

  115. Tomblyn M, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15(10):1143–238.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  116. Yusuf U, et al. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation. 2006;81(10):1398–404.

    Article  CAS  PubMed  Google Scholar 

  117. Boeckh M, Ljungman P. How we treat cytomegalovirus in hematopoietic cell transplant recipients. Blood. 2009;113(23):5711–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Faye A, et al. Chimaeric anti-CD20 monoclonal antibody (rituximab) in post-transplant B-lymphoproliferative disorder following stem cell transplantation in children. Br J Haematol. 2001;115(1):112–8.

    Article  CAS  PubMed  Google Scholar 

  119. Heslop HE. How I treat EBV lymphoproliferation. Blood. 2009;114(19):4002–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  120. van Esser JWJ, et al. Prevention of Epstein-Barr virus–lymphoproliferative disease by molecular monitoring and preemptive rituximab in high-risk patients after allogeneic stem cell transplantation. Blood. 2002;99(12):4364–9.

    Article  PubMed  Google Scholar 

  121. Kolb HJ, et al. Donor leukocyte transfusions for treatment of recurrent chronic myelogenous leukemia in marrow transplant patients. Blood. 1990;76(12):2462–5.

    CAS  PubMed  Google Scholar 

  122. Papadopoulos EB, et al. Infusions of donor leukocytes to treat Epstein-Barr virus-associated lymphoproliferative disorders after allogeneic bone marrow transplantation. N Engl J Med. 1994;330(17):1185–91.

    Article  CAS  PubMed  Google Scholar 

  123. Pasquale M, et al. Unmanipulated donor lymphocytes for EBV-related PTLD after T-cell depleted HLA-haploidentical transplantation. Pediatrics. 2012;129(1):e189–94.

    Article  PubMed  Google Scholar 

  124. Hromas R, et al. Donor leukocyte infusion as therapy of life-threatening adenoviral infections after T-cell-depleted bone marrow transplantation. Blood. 1994;84(5):1689–90.

    CAS  PubMed  Google Scholar 

  125. Chakrabarti S, et al. Adenovirus infections following haematopoietic cell transplantation: is there a role for adoptive immunotherapy? Bone Marrow Transplant. 2000;26(3):305–7.

    Article  CAS  PubMed  Google Scholar 

  126. Stasi A, et al. Inducible apoptosis as a safety switch for adoptive cell therapy. N Engl J Med. 2011;365(18):1673–83.

    Article  PubMed  PubMed Central  Google Scholar 

  127. Zhou X, et al. Inducible caspase-9 suicide gene controls adverse effects from alloreplete T cells after haploidentical stem cell transplantation. Blood. 2015;125(26):4103–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Bollard CM, Heslop HE. T cells for viral infections after allogeneic hematopoietic stem cell transplant. Blood. 2016;127(26):3331–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. Riddell SR, et al. Restoration of viral immunity in immunodeficient humans by the adoptive transfer of T cell clones. Science (New York, NY). 1992;257(5067):238–41.

    Article  CAS  Google Scholar 

  130. Einsele H, et al. Infusion of cytomegalovirus (CMV)-specific T cells for the treatment of CMV infection not responding to antiviral chemotherapy. Blood. 2002;99(11):3916–22.

    Article  CAS  PubMed  Google Scholar 

  131. Heslop HE, Leen AM. T-cell therapy for viral infections. Hematology Am Soc Hematol Educ Program. 2013;2013(1):342–7.

    PubMed  Google Scholar 

  132. Moss P, Rickinson A. Cellular immunotherapy for viral infection after HSC transplantation. Nat Rev Immunol. 2005;5(1):9–20.

    Article  CAS  PubMed  Google Scholar 

  133. Peggs K, Verfuerth S, Mackinnon S. Induction of cytomegalovirus (CMV)-specific T-cell responses using dendritic cells pulsed with CMV antigen: a novel culture system free of live CMV virions. Blood. 2001;97(4):994–1000.

    Article  CAS  PubMed  Google Scholar 

  134. Peggs KS, et al. Adoptive cellular therapy for early cytomegalovirus infection after allogeneic stem-cell transplantation with virus-specific T-cell lines. Lancet (London, England). 2003;362(9393):1375–7.

    Article  Google Scholar 

  135. Rooney CM, et al. Use of gene-modified virus-specific T lymphocytes to control Epstein-Barr-virus-related lymphoproliferation. Lancet. 1995;345(8941):9–13.

    Article  CAS  PubMed  Google Scholar 

  136. Heslop HE, et al. Long-term outcome of EBV-specific T-cell infusions to prevent or treat EBV-related lymphoproliferative disease in transplant recipients. Blood. 2010;115(5):925–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Leen AM, et al. Monoculture-derived T lymphocytes specific for multiple viruses expand and produce clinically relevant effects in immunocompromised individuals. Nat Med. 2006;12(10):1160–6.

    Article  CAS  PubMed  Google Scholar 

  138. Gaundar SS, et al. In vitro generation of influenza-specific polyfunctional CD4+ T cells suitable for adoptive immunotherapy. Cytotherapy. 2012;14(2):182–93.

    Article  CAS  PubMed  Google Scholar 

  139. Blyth E, et al. Donor-derived CMV-specific T cells reduce the requirement for CMV-directed pharmacotherapy after allogeneic stem cell transplantation. Blood. 2013;121(18):3745–58.

    Article  CAS  PubMed  Google Scholar 

  140. Papadopoulou A, et al. Activity of broad-spectrum T cells as treatment for AdV, EBV, CMV, BKV, and HHV6 infections after HSCT. Sci Transl Med. 2014;6(242):242ra83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  141. Ma C, et al. Addition of varicella zoster virus-specific T cells to cytomegalovirus, Epstein-Barr virus and adenovirus tri-specific T cells as adoptive immunotherapy in patients undergoing allogeneic hematopoietic stem cell transplantation. Cytotherapy. 2015;17(10):1406–20.

    Article  CAS  PubMed  Google Scholar 

  142. Dvorak CC, et al. Complications of transplant for nonmalignant disorders: autoimmune cytopenias, opportunistic infections, and PTLD. Biol Blood Marrow Transplant. 2012;18(1 Suppl):10.

    Google Scholar 

  143. Leen AM, et al. Multicenter study of banked third-party virus-specific T cells to treat severe viral infections after hematopoietic stem cell transplantation. Blood. 2013;121(26):5113–23.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Pulsipher MA, et al. National Cancer Institute, National Heart, Lung and Blood Institute/Pediatric Blood and Marrow Transplantation Consortium First International Consensus Conference on late effects after pediatric hematopoietic cell transplantation: the need for pediatric-specific long-term follow-up guidelines. Biol Blood Marrow Transplant. 2012;18(3):334–47.

    Article  PubMed  PubMed Central  Google Scholar 

  145. Anur P, et al. Late effects in patients with Fanconi anemia following allogeneic hematopoietic stem cell transplantation from alternative donors. Bone Marrow Transplant. 2016;51(7):938–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  146. Allewelt H, et al. Late effects after umbilical cord blood transplantation in very young children after busulfan-based, myeloablative conditioning. Biol Blood Marrow Transplant. 2016;22(9):1627–35.

    Article  PubMed  Google Scholar 

  147. Bunin N, et al. NCI, NHLBI/PBMTC first international conference on late effects after pediatric hematopoietic cell transplantation: persistent immune deficiency in pediatric transplant survivors. Biol Blood Marrow Transplant. 2012;18(1):6–15.

    Article  PubMed  Google Scholar 

  148. Majhail NS, et al. Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2012;18(3):348–71.

    Article  PubMed  Google Scholar 

  149. Chow EJ, et al. Late effects surveillance recommendations among survivors of childhood hematopoietic cell transplantation: a children’s oncology group report. Biol Blood Marrow Transplant. 2016;22(5):782–95.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Conflicts of Interest

The authors declare no competing financial interests. No honorarium, grant, or other form of payment was given to anyone to produce this manuscript.

Author information

Authors and Affiliations

  1. Division of Bone Marrow Transplantation, Department of Pediatrics, Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, Emory University School of Medicine, 2015 Uppergate Drive, ECC Room 418, Atlanta, GA, 30322, USA

    Karen L. Zimowski & Shanmuganathan Chandrakasan

Authors
  1. Karen L. Zimowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shanmuganathan Chandrakasan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Shanmuganathan Chandrakasan .

Editor information

Editors and Affiliations

  1. Indiana Hemophilia and Thrombosis Center, Indianapolis, Indiana, USA

    Emily Riehm Meier

  2. Division of Blood and Marrow Transplantation, Children’s National Medical Center, Washington, DC, USA

    Allistair Abraham

  3. Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia, USA

    Ross M. Fasano

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Zimowski, K.L., Chandrakasan, S. (2018). Overview of Hematopoietic Stem Cell Transplantation for Nonmalignant Diseases. In: Meier, E., Abraham, A., Fasano, R. (eds) Sickle Cell Disease and Hematopoietic Stem Cell Transplantation . Springer, Cham. https://doi.org/10.1007/978-3-319-62328-3_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-62328-3_7

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-62327-6

  • Online ISBN: 978-3-319-62328-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation