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Hematopoietic Stem Cell Transplant and Cellular Therapy

  • Priti Tewari
  • Rajinder Bajwa
  • Agne Taraseviciute
  • Jerelyn Moffet
  • David McCall
  • Kris M. MahadeoEmail author
Chapter

Abstract

Hematopoietic cell transplantation (HCT) and cellular therapy (CT) are potentially lifesaving treatments for children with malignant and nonmalignant diseases. Advancements in care have led to expanding patient eligibility, with overall reduced morbidity and improved survival. Survival for HCT patients requiring pediatric intensive care unit (PICU) admission have improved. While almost half of pediatric patients receiving CAR-T therapy may require intensive care support, overall survival remains promising. However, patients undergoing HCT remain at risk for debilitating and life-threatening complications such as sinusoidal obstructive syndrome (S0S), infection, and graft-versus-host disease (GVHD); patients receiving chimeric antigen receptor (CAR) and other T-cell therapies are at risk for unique toxicities such as cytokine release syndrome (CRS) and CAR-T-related encephalopathy syndrome (CRES). Judicious patient and treatment selection, vigilant monitoring, and prompt interventions may reduce the need for PICU admission among HCT and CAR-T recipients. When PICU intervention is required, early intervention, excellent interdisciplinary communication, prognostication, and intensive support may improve outcomes.

Keywords

Chimeric antigen receptor (CAR) Hematopoietic cell transplantation (HCT) Allogeneic Autologous Sinusoidal obstructive syndrome (SOS) Cytokine release syndrome (CRS) CAR-T-related encephalopathy syndrome (CRES) Graft-versus-host disease (GVHD) Critical care 

References

  1. 1.
    Majhail NS, et al. Indications for autologous and allogeneic hematopoietic cell transplantation: guidelines from the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2015;21:1863–9.PubMedPubMedCentralCrossRefGoogle Scholar
  2. 2.
    Peffault de Latour R, et al. Recommendations on hematopoietic stem cell transplantation for inherited bone marrow failure syndromes. Bone Marrow Transplant. 2015;50:1168–72.PubMedCrossRefPubMedCentralGoogle Scholar
  3. 3.
    Sureda A, et al. Indications for Allo- and auto-Sct for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2015. Bone Marrow Transplant. 2015;50:1037–56.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Fish JD, Grupp SA. Stem cell transplantation for neuroblastoma. Bone Marrow Transplant. 2008;41:159–65.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Kasenda B, et al. High-dose chemotherapy with autologous haematopoietic stem cell support for relapsed or refractory primary Cns lymphoma: a prospective multicentre trial by the German cooperative primary central nervous system lymphoma study broup. Leukemia. 2017;31:2623–9.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    DeFilipp Z, et al. High-dose chemotherapy with Thiotepa, Busulfan, and cyclophosphamide and autologous stem cell transplantation for patients with primary central nervous system lymphoma in first complete remission. Cancer. 2017;123:3073–9.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Baird K, et al. Reduced intensity allogeneic stem cell transplantation in children and young adults with ultra-high risk pediatric sarcomas. Biol Blood Marrow Transplant. 2012;18:698–707.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Eapen M, et al. Umbilical cord blood transplantation in children with acute leukemia: impact of conditioning on transplantation outcomes. Biol Blood Marrow Transplant. 2017;23:1714–21.PubMedPubMedCentralCrossRefGoogle Scholar
  9. 9.
    Grupp SA, et al. Chimeric antigen receptor – modified T cells for acute lymphoid leukemia. N Engl J Med. 2013;368:1509–18.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Kumar SRP, Markusic DM, Biswas M, High KA, Herzog RW. Clinical development of gene therapy: results and lessons from recent successes. Mol Ther Methods Clin Dev. 2016;3:16034.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Zinter MS, et al. Pediatric hematopoietic cell transplant patients who survive critical illness frequently have significant but recoverable decline in functional status. Biol Blood Marrow Transplant. 2018;24:330–6.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Zinter MS, Dvorak CC, Spicer A, Cowan MJ, Sapru A. New insights into multicenter Picu mortality among pediatric hematopoietic stem cell transplant patients. Crit Care Med. 2015;43:1986–94.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Duncan CN, et al. Clinical outcomes of children receiving intensive cardiopulmonary support during hematopoietic stem cell transplant. Pediatr Crit Care Med. 2013;14:261–7.CrossRefGoogle Scholar
  14. 14.
    Maude SL, et al. Tisagenlecleucel in children and young adults with B-cell lymphoblastic leukemia. N Engl J Med. 2018;378:439–48.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
  16. 16.
    Samaras P, et al. Mobilization of hematopoietic progenitor cells with standard or reduced dose Filgrastim after Vinorelbine in multiple myeloma patients. A randomized prospective single center phase ii study. Biol Blood Marrow Transplant. 2018;24(4):694–9.  https://doi.org/10.1016/j.bbmt.2017.12.775. Epub 2017 Dec 12.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Clark RE, et al. Plerixafor is superior to conventional chemotherapy for first-line stem cell mobilisation, and is effective even in heavily pretreated patients. Blood Cancer J. 2014;4:e255.PubMedPubMedCentralCrossRefGoogle Scholar
  18. 18.
    Holtan SG, et al. Timing of autologous stem cell transplantation from last chemotherapy affects lymphocyte collection and survival in non-Hodgkin lymphoma. Br J Haematol. 2006;133:628–33.PubMedPubMedCentralCrossRefGoogle Scholar
  19. 19.
    Porrata LF, et al. Infused peripheral blood autograft absolute lymphocyte count correlates with day 15 absolute lymphocyte count and clinical outcome after autologous peripheral hematopoietic stem cell transplantation in non-Hodgkin’s lymphoma. Bone Marrow Transplant. 2004;33:291–8.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Rosinski SL, et al. Prognostic analysis of pre-transplant peripheral T-cell levels in patients receiving an autologous hematopoietic progenitor-cell transplant. Bone Marrow Transplant. 2005;36:425–30.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Bitan M, et al. Determination of eligibility in related pediatric hematopoietic cell donors: ethical and clinical considerations. Recommendations from a Working Group of the Worldwide Network for Blood and Marrow Transplantation Association. Biol Blood Marrow Transplant. 2016;22:96–103.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Michon B, et al. Complications of apheresis in children. Transfusion. 2007;47:1837–42.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Gorlin JB, et al. Pediatric large volume peripheral blood progenitor cell collections from patients under 25kg: a primer. J Clin Apher. 1996;11:195–203.PubMedCrossRefPubMedCentralGoogle Scholar
  24. 24.
    Carausu L, Clapisson G, Philip I, Sebban H, Marec-Beard P. Use of totally implantable catheters for peripheral blood stem cell apheresis. Bone Marrow Transplant. 2007;40:417–22.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Koristek Z, Sterba J, Havranova D, Mayer J. Technique for Pbsc harvesting in children of weight under 10 kg. Bone Marrow Transplant. 2002;29:57–61.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Ohara Y, et al. Comprehensive technical and patient-care optimization in the Management of Pediatric Apheresis for peripheral blood stem cell harvesting. Transfus Apher Sci. 2016;55:338–43.PubMedCrossRefPubMedCentralGoogle Scholar
  27. 27.
    Abate-Daga D, Davila ML. Car models: next-generation Car modifications for enhanced T-cell function. Mol Ther Oncolytics. 2016;3:16014.PubMedPubMedCentralCrossRefGoogle Scholar
  28. 28.
    Brentjens RJ, et al. Cd19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013;5:177.CrossRefGoogle Scholar
  29. 29.
    Cruz CR, et al. Infusion of donor-derived Cd19-redirected virus-specific T cells for B-cell malignancies relapsed after allogeneic stem cell transplant: a phase 1 study. Blood. 2013;122:2965–73.PubMedPubMedCentralCrossRefGoogle Scholar
  30. 30.
    Davila ML, et al. Efficacy and toxicity management of 19–28z Car T cell therapy in B cell acute lymphoblastic leukemia. Sci Transl Med. 2014;6:224ra225.CrossRefGoogle Scholar
  31. 31.
    Kochenderfer JN, et al. Donor-derived Cd19-targeted T cells cause regression of malignancy persisting after allogeneic hematopoietic stem cell transplantation. Blood. 2013;122:4129–39.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Kochenderfer JN, et al. Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-Cd19 chimeric antigen receptor. J Clin Oncol. 2015;33:540–9.PubMedCrossRefGoogle Scholar
  33. 33.
    Kochenderfer JN, et al. Eradication of B-lineage cells and regression of lymphoma in a patient treated with autologous T cells genetically engineered to recognize Cd19. Blood. 2010;116:4099–102.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Maus MV, Levine BL. Chimeric antigen receptor T-cell therapy for the community oncologist. Oncologist. 2016;21:608–17.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Porter DL, Levine BL, Kalos M, Bagg A, June CH. Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia. N Engl J Med. 2011;365:725–33.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Lee DW, et al. T cells expressing Cd19 chimeric antigen receptors for acute lymphoblastic Leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015;385:517–28.PubMedCrossRefGoogle Scholar
  37. 37.
    Garfall AL, et al. Chimeric antigen receptor T cells against Cd19 for multiple myeloma. New Engl J Med. 2015;373:1040–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Brudno JN, et al. Allogeneic T cells that express an anti-Cd19 chimeric antigen receptor induce remissions of B-cell malignancies that Progress after allogeneic hematopoietic stem-cell transplantation without causing graft-versus-host disease. J Clin Oncol. 2016;34:1112.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Turtle CJ, et al. Durable molecular remissions in chronic lymphocytic leukemia treated with Cd19-specific chimeric antigen receptor-modified T cells after failure of Ibrutinib. J Clin Oncol. 2017;35:3010–20.PubMedPubMedCentralCrossRefGoogle Scholar
  40. 40.
    Locke FL, et al. Product characteristics associated with in vivo expansion of anti-Cd19 Car T cells in patients treated with Axicabtagene Ciloleucel (Axi-Cel). J Clin Oncol. 2017;35:3023.CrossRefGoogle Scholar
  41. 41.
    Neelapu SS, et al. Axicabtagene Ciloleucel Car T-cell therapy in refractory large B-cell lymphoma. New Engl J Med. 2017;377:2531–44.PubMedCrossRefGoogle Scholar
  42. 42.
    Rezvani K, Rouce R, Liu E, Shpall E. Engineering natural killer cells for Cancer immunotherapy. Mol Ther. 2017;25:1769–81.PubMedPubMedCentralCrossRefGoogle Scholar
  43. 43.
    Truong TH, et al. Adverse reactions during stem cell infusion in children treated with autologous and allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:680–6.PubMedCrossRefGoogle Scholar
  44. 44.
    Berz D, McCormack EM, Winer ES, Colvin GA, Quesenberry PJ. Cryopreservation of hematopoietic stem cells. Am J Hematol. 2007;82:463–72.PubMedPubMedCentralCrossRefGoogle Scholar
  45. 45.
    Davis JM, Rowley SD, Braine HG, Piantadosi S, Santos GW. Clinical toxicity of cryopreserved bone marrow graft infusion. Blood. 1990;75:781–6.PubMedGoogle Scholar
  46. 46.
    Stroncek DF, et al. Adverse reactions in patients transfused with cryopreserved marrow. Transfusion. 1991;31:521–6.PubMedCrossRefGoogle Scholar
  47. 47.
    Zambelli A, et al. Clinical toxicity of cryopreserved circulating progenitor cells infusion. Anticancer Res. 1998;18:4705–8.PubMedGoogle Scholar
  48. 48.
    Zenhausern R, Tobler A, Leoncini L, Hess OM, Ferrari P. Fatal cardiac arrhythmia after infusion of dimethyl sulfoxide-cryopreserved hematopoietic stem cells in a patient with severe primary cardiac amyloidosis and end-stage renal failure. Ann Hematol. 2000;79:523–6.PubMedCrossRefGoogle Scholar
  49. 49.
    Hoyt R, Szer J, Grigg A. Neurological events associated with the infusion of cryopreserved bone marrow and/or peripheral blood progenitor cells. Bone Marrow Transplant. 2000;25:1285–7.PubMedCrossRefPubMedCentralGoogle Scholar
  50. 50.
    Otrock ZK, et al. Transient global amnesia associated with the infusion of Dmso-cryopreserved autologous peripheral blood stem cells. Haematologica. 2008;93:e36–7.PubMedCrossRefPubMedCentralGoogle Scholar
  51. 51.
    Miniero R, Vai S, Giacchino M, Giubellino C, Madon E. Severe respiratory depression after autologous bone marrow infusion. Haematologica. 1992;77:98–9.PubMedPubMedCentralGoogle Scholar
  52. 52.
    Cruz CR, et al. Adverse events following infusion of T cells for adoptive immunotherapy: a 10-year experience. Cytotherapy. 2010;12:743–9.PubMedPubMedCentralCrossRefGoogle Scholar
  53. 53.
    AABB. Standards for blood banks and transfusion Medicine. 30th ed. Bethesda: AABB; 2016.Google Scholar
  54. 54.
    Rowan CM, et al. Invasive mechanical ventilation and mortality in pediatric hematopoietic stem cell transplantation: a multicenter study. Pediatr Crit Care Med. 2016;17:294–302.CrossRefGoogle Scholar
  55. 55.
    Demaret P, Pettersen G, Hubert P, Teira P, Emeriaud G. The critically-ill pediatric Hemato-oncology patient: epidemiology, management, and strategy of transfer to the pediatric intensive care unit. Ann Intensive Care. 2012;2:14.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Weiss SL, et al. Global epidemiology of pediatric severe Sepsis: the Sepsis prevalence, outcomes, and therapies study. Am J Respir Crit Care Med. 2015;191:1147–57.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Lindell RB, et al. High levels of morbidity and mortality among pediatric hematopoietic cell transplant recipients with severe Sepsis: insights from the Sepsis prevalence, outcomes, and therapies international point prevalence study. Pediatr Crit Care Med. 2017;18:1114–25.PubMedCrossRefGoogle Scholar
  58. 58.
    González-Vicent M, Marín C, Madero L, Sevilla J, Díaz MA. Risk score for pediatric intensive care unit admission in children undergoing hematopoietic stem cell transplantation and analysis of predictive factors for survival. J Pediatr Hematol Oncol. 2005;27:526–31.PubMedCrossRefGoogle Scholar
  59. 59.
    Schneider DT, et al. Introduction of the oncological pediatric risk of mortality score (O-Prism) for Icu support following stem cell transplantation in children. Bone Marrow Transplant. 2000;25:1079.PubMedCrossRefPubMedCentralGoogle Scholar
  60. 60.
    Jaing TH, et al. Evaluation of readmission in children receiving allogeneic hematopoietic stem cell transplantation: an institutional experience. Transplant Proc. 2008;40:3643–5.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Shulman DS, London WB, Guo D, Duncan CN, Lehmann LE. Incidence and causes of hospital readmission in pediatric patients after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2015;21:913–9.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Maher OM, et al. Etiologies and impact of readmission rates in the first 180 days after hematopoietic stem cell transplantation in children, adolescents, and young adults. J Pediatr Hematol Oncol. 2017;39:609–13.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Giralt S, et al. Reduced-intensity conditioning regimen workshop: defining the dose spectrum. Report of a workshop convened by the center for international blood and marrow transplant research. Biol Blood Marrow Transplant. 2009;15:367–9.PubMedPubMedCentralCrossRefGoogle Scholar
  64. 64.
    Tomblyn MB, et al. Myeloablative hematopoietic cell transplantation for acute lymphoblastic leukemia: analysis of graft sources and long-term outcome. J Clin Oncol. 2009;27:3634–41.PubMedPubMedCentralCrossRefGoogle Scholar
  65. 65.
    Neelapu SS, et al. Chimeric antigen receptor T-cell therapy – assessment and management of toxicities. Nat Rev Clin Oncol. 2018;15:47–62.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Nahirniak S, et al. Guidance on platelet transfusion for patients with hypoproliferative thrombocytopenia. Transfus Med Rev. 2015;29:3–13.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Pihusch M, et al. Recombinant activated factor Vii in treatment of bleeding complications following hematopoietic stem cell transplantation. J Thromb Haemost. 2005;3:1935–44.PubMedCrossRefPubMedCentralGoogle Scholar
  68. 68.
    Franchini M, Veneri D, Lippi G. The potential role of recombinant activated Fvii in the management of critical hemato-oncological bleeding: a systematic review. Bone Marrow Transplant. 2007;39:729–35.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Tang Y, et al. Use of recombinant factor Viia in uncontrolled gastrointestinal bleeding after hematopoietic stem cell transplantation among patients with thrombocytopenia. Pak J Med Sci. 2015;31:1389–93.PubMedPubMedCentralCrossRefGoogle Scholar
  70. 70.
    Park JA. Diffuse alveolar hemorrhage and recombinant factor Viia treatment in pediatric patients. Korean J Pediatr. 2016;59:105–13.PubMedPubMedCentralCrossRefGoogle Scholar
  71. 71.
    Abrams D, et al. Extracorporeal membrane oxygenation in the management of diffuse alveolar hemorrhage. ASAIO J. 2015;61:216–8.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Garnock-Jones KP, Keam SJ. Eltrombopag. Drugs. 2009;69:567–76.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Tanaka T, et al. Eltrombopag for treatment of thrombocytopenia after allogeneic hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:919–24.PubMedCrossRefPubMedCentralGoogle Scholar
  74. 74.
    Vose JM, Armitage JO. Clinical applications of hematopoietic growth factors. J Clin Oncol. 1995;13:1023–35.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Tomblyn M, et al. Guidelines for preventing infectious complications among hematopoietic cell transplantation recipients: a global perspective. Biol Blood Marrow Transplant. 2009;15:1143–238.PubMedPubMedCentralCrossRefGoogle Scholar
  76. 76.
    Balian C, Garcia M, Ward J. A retrospective analysis of bloodstream infections in pediatric allogeneic stem cell transplant recipients: the role of central venous catheters and mucosal barrier injury. J Pediatr Oncol Nurs. 2018;35:210–7.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Mehta RS, Rezvani K. Immune reconstitution post allogeneic transplant and the impact of immune recovery on the risk of infection. Virulence. 2016;7:901–16.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Dandoy CE, et al. Healthcare burden, risk factors, and outcomes of mucosal barrier injury laboratory-confirmed bloodstream infections after stem cell transplantation. Biol Blood Marrow Transplant. 2016;22:1671–7.PubMedPubMedCentralCrossRefGoogle Scholar
  79. 79.
    Cesaro S, et al. Incidence, risk factors and long-term outcome of acute leukemia patients with early Candidemia after allogeneic stem cell transplantation. A study by the acute leukemia and infectious diseases working parties of Ebmt. Clin Infect Dis. 2018;67(4):564–72.PubMedCrossRefPubMedCentralGoogle Scholar
  80. 80.
    Simms-Waldrip T, et al. Invasive fungal infections in pediatric hematopoietic stem cell transplant patients. Infect Dis (Lond). 2015;47:218–24.CrossRefGoogle Scholar
  81. 81.
    Abdel-Azim H, et al. A survey of infectious disease clinical practices among pediatric blood and marrow transplant programs in the United States. Pediatr Blood Cancer. 2015;62(4):731–5.  https://doi.org/10.1002/pbc.25355. Epub 2015 Jan 3.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Groll AH, et al. Fourth European conference on infections in Leukaemia (Ecil-4): guidelines for diagnosis, prevention, and treatment of invasive fungal diseases in Paediatric patients with Cancer or allogeneic Haemopoietic stem-cell transplantation. Lancet Oncol. 2014;15:327–40.CrossRefGoogle Scholar
  83. 83.
    Veys P, Owens C. Respiratory infections following Haemopoietic stem cell transplantation in children. Br Med Bull. 2002;61:151–74.PubMedCrossRefPubMedCentralGoogle Scholar
  84. 84.
    Winston DJ. Prophylaxis and treatment of infection in the bone marrow transplant recipient. Curr Clin Top Infect Dis. 1993;13:293–321.PubMedPubMedCentralGoogle Scholar
  85. 85.
    Collin BA, Leather HL, Wingard JR, Ramphal R. Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients. Clin Infect Dis. 2001;33:947–53.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Averbuch D, et al. European guidelines for empirical antibacterial therapy for febrile Neutropenic patients in the era of growing resistance: summary of the 2011 4th European conference on infections in leukemia. Haematologica. 2013;98:1826–35.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Lee JJ, et al. Clinical efficacy and prediction of response to granulocyte transfusion therapy for patients with neutropenia-related infections. Haematologica. 2004;89:632–3.PubMedPubMedCentralGoogle Scholar
  88. 88.
    Lee JJ, et al. Clinical efficacy of granulocyte transfusion therapy in patients with neutropenia-related infections. Leukemia. 2001;15:203–7.PubMedCrossRefPubMedCentralGoogle Scholar
  89. 89.
    Busca A, et al. Oral valganciclovir as preemptive therapy for cytomegalovirus infection post allogeneic stem cell transplantation. Transpl Infect Dis. 2007;9:102–7.PubMedCrossRefGoogle Scholar
  90. 90.
    Tzannou I, et al. Off-the-shelf virus-specific T cells to treat Bk virus, human herpesvirus 6, cytomegalovirus, epstein-barr virus, and adenovirus infections after allogeneic hematopoietic stem-cell transplantation. J Clin Oncol. 2017;35:3547–57.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Marty FM, et al. Cmx001 to prevent cytomegalovirus disease in hematopoietic-cell transplantation. N Engl J Med. 2013;369:1227–36.PubMedCrossRefGoogle Scholar
  92. 92.
    El-Haddad D, et al. Brincidofovir (Cmx-001) for refractory and resistant cmv and Hsv infections in immunocompromised Cancer patients: a single-center experience. Antivir Res. 2016;134:58–62.PubMedCrossRefGoogle Scholar
  93. 93.
    Shah DP, et al. Impact of aerosolized ribavirin on mortality in 280 allogeneic haematopoietic stem cell transplant recipients with respiratory syncytial virus infections. J Antimicrob Chemother. 2013;68:1872–80.PubMedPubMedCentralCrossRefGoogle Scholar
  94. 94.
    Dignan FL, et al. Bcsh/Bsbmt/Uk clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation. Br J Haematol. 2016;173:380–93.PubMedCrossRefGoogle Scholar
  95. 95.
    Boeckh M, et al. Randomized controlled multicenter trial of aerosolized ribavirin for respiratory syncytial virus upper respiratory tract infection in hematopoietic cell transplant recipients. Clin Infect Dis. 2007;44:245–9.PubMedCrossRefGoogle Scholar
  96. 96.
    MEdicine, N.U.S.N.L.o. An open label study to examine the effects of Das181 administered by dry powder inhaler or nebulized formulation in immunocompromised subjects with parainfluenza infection. 2018. [cited 2018 April 16, 2018]. Available from: https://clinicaltrials.gov/ct2/show/NCT01924793?cond=Parainfluenza&rank=1.
  97. 97.
    Hiwarkar P, et al. Brincidofovir is highly efficacious in controlling adenoviremia in pediatric recipients of hematopoietic cell transplant. Blood. 2017;129:2033–7.PubMedPubMedCentralCrossRefGoogle Scholar
  98. 98.
    O’Reilly RJ, Prockop S, Hasan AN, Koehne G, Doubrovina E. Virus-specific T-cell banks for ‘Off the Shelf’ adoptive therapy of refractory infections. Bone Marrow Transplant. 2016;51:1163–72.PubMedPubMedCentralCrossRefGoogle Scholar
  99. 99.
    Ramsay ID, et al. Disseminated adenovirus infection after allogeneic stem cell transplant and the potential role of Brincidofovir – case series and 10 year experience of management in an adult transplant cohort. J Clin Virol. 2017;96:73–9.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Greco R, et al. Human herpesvirus 6 infection following haploidentical transplantation: immune recovery and outcome. Biol Blood Marrow Transplant. 2016;22:2250–5.PubMedCrossRefPubMedCentralGoogle Scholar
  101. 101.
    Mayer K, et al. Intravesical cidofovir application in Bk virus cystitis after allogeneic hematopoetic stem cell transplantation (Hsct) is safe and highly effective. Bone Marrow Transplant. 2018;53(4):495–8.PubMedCrossRefPubMedCentralGoogle Scholar
  102. 102.
    Harkensee C, Vasdev N, Gennery AR, Willetts IE, Taylor C. Prevention and Management of Bk-Virus Associated Haemorrhagic Cystitis in children following Haematopoietic stem cell transplantation—a systematic review and evidence-based guidance for clinical management. Br J Haematol. 2008;142:717–31.PubMedCrossRefPubMedCentralGoogle Scholar
  103. 103.
    Coppoletta S, et al. Rituximab treatment for epstein-barr virus dnaemia after alternative-donor hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2011;17:901–7.PubMedCrossRefPubMedCentralGoogle Scholar
  104. 104.
    Barker JN, et al. Successful treatment of Ebv-associated posttransplantation lymphoma after cord blood transplantation using third-party Ebv-specific cytotoxic T lymphocytes. Blood. 2010;116:5045–9.PubMedPubMedCentralCrossRefGoogle Scholar
  105. 105.
    Du Pasquier RA, Kuroda MJ, Zheng Y, Jean-Jacques J, Letvin NL, Koralnik IJ. A prospective study demonstrates an association between JC virus-specific cyto toxic T lymphocytes and the early control of progressive multifocal leukoencepha lopathy. Brain. 2004;127(Pt 9):1970–8. Epub 2004 Jun 23.PubMedCrossRefGoogle Scholar
  106. 106.
    Tummala S, Rezvani K. Treating progressive multifocal leukoen cephalopathy with expanded third party BK virus specific cytoxic T cells in acute myeloid leukemia patient following cord blood transplantation (S41.004). Neurology. 2018;90(15 Supplement):S41.004.Google Scholar
  107. 107.
    Elad S, et al. Basic Oral Care for Hematology-Oncology Patients and Hematopoietic Stem Cell Transplantation Recipients: a position paper from the joint task force of the multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (Mascc/Isoo) and the European Society for Blood and Marrow Transplantation (Ebmt). Support Care Cancer. 2015;23:223–36.PubMedCrossRefPubMedCentralGoogle Scholar
  108. 108.
    Miller MM, Donald DV, Hagemann TM. Prevention and treatment of oral mucositis in children with cancer. J Pediatr Pharmacol Ther. 2012;17:340–50.PubMedPubMedCentralGoogle Scholar
  109. 109.
    Herbers AH, de Haan AF, van der Velden WJ, Donnelly JP, Blijlevens NM. Mucositis not neutropenia determines bacteremia among hematopoietic stem cell transplant recipients. Transpl Infect Dis. 2014;16:279–85.PubMedCrossRefPubMedCentralGoogle Scholar
  110. 110.
    Van Der Velden WJ, Herbers AH, Netea MG, Blijlevens NM. Mucosal barrier injury, fever and infection in neutropenic patients with cancer: introducing the paradigm febrile mucositis. Br J Haematol. 2014;167:441–52.PubMedCrossRefPubMedCentralGoogle Scholar
  111. 111.
    Sonis ST. Pathobiology of mucositis. Semin Oncol Nurs. 2004;20:11–5.PubMedCrossRefPubMedCentralGoogle Scholar
  112. 112.
    Al-Dasooqi N, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21:2075–83.PubMedCrossRefPubMedCentralGoogle Scholar
  113. 113.
    Chaudhry HM, et al. The incidence and severity of oral mucositis among allogeneic hematopoietic stem cell transplantation patients: a systematic review. Biol Blood Marrow Transplant. 2016;22:605–16.PubMedCrossRefPubMedCentralGoogle Scholar
  114. 114.
    Schmidt V, et al. Efficacy and safety of keratinocyte growth factor (Palifermin) for prevention of oral mucositis in Tbi-based allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018;53(9):1188–92.PubMedCrossRefPubMedCentralGoogle Scholar
  115. 115.
    Sonis ST, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer. 2004;100:1995–2025.PubMedCrossRefPubMedCentralGoogle Scholar
  116. 116.
    Sung L, et al. Guideline for the prevention of oral and oropharyngeal mucositis in children receiving treatment for cancer or undergoing haematopoietic stem cell transplantation. BMJ Support Palliat Care. 2017;7:7–16.PubMedCrossRefPubMedCentralGoogle Scholar
  117. 117.
    Morris J, et al. Safety, pharmacokinetics, and efficacy of palifermin in children and adolescents with acute leukemias undergoing myeloablative therapy and allogeneic hematopoietic stem cell transplantation: a pediatric blood and marrow transplant consortium trial. Biol Blood Marrow Transplant. 2016;22:1247–56.PubMedCrossRefPubMedCentralGoogle Scholar
  118. 118.
    Dunbar PJ, Buckley P, Gavrin JR, Sanders JE, Chapman CR. Use of patient-controlled analgesia for pain control for children receiving bone marrow transplant. J Pain Symptom Manag. 1995;10:604–11.CrossRefGoogle Scholar
  119. 119.
    Pillitteri LC, Clark RE. Comparison of a patient-controlled analgesia system with continuous infusion for administration of diamorphine for mucositis. Bone Marrow Transplant. 1998;22:495–8.PubMedCrossRefPubMedCentralGoogle Scholar
  120. 120.
    U.S. Department of Health and Human Services, N.I.o.H., National Cancer Institute. Common Terminology Criteria for Adverse Events (Ctcae) Version 5.0. 2017 November 27, 2017 [cited 2018 April 16, 2018]; 5.0:[available from: https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_5x7.pdf.
  121. 121.
    Al-Dasooqi N, et al. Emerging evidence on the pathobiology of mucositis. Support Care Cancer. 2013;21:3233–41.PubMedCrossRefPubMedCentralGoogle Scholar
  122. 122.
    Corbacioglu S, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/Veno-occlusive disease in pediatric patients: a new classification from the European society for blood and marrow transplantation. Bone Marrow Transplant. 2018;53(2):138–45.  https://doi.org/10.1038/bmt.2017.161. Epub 2017 Jul 31.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Michael M, Kuehnle I, Goldstein SL. Fluid overload and acute renal failure in pediatric stem cell transplant patients. Pediatr Nephrol. 2004;19:91–5.PubMedPubMedCentralCrossRefGoogle Scholar
  124. 124.
    Lombel RM, et al. Implications of different fluid overload definitions in pediatric stem cell transplant patients requiring continuous renal replacement therapy. Intensive Care Med. 2012;38:663–9.PubMedCrossRefPubMedCentralGoogle Scholar
  125. 125.
    Ingelse SA, et al. Pediatric acute respiratory distress syndrome: fluid management in the PICU. Front Pediatr. 2016;4:21.  https://doi.org/10.3389/fped.2016.00021. eCollection 2016.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Arikan AA, et al. Fluid overload is associated with impaired oxygenation and morbidity in critically ill children. Pediatr Crit Care Med. 2012;13:253–8.CrossRefGoogle Scholar
  127. 127.
    Elbahlawan L, Morrison RR. Continuous renal replacement therapy in children post-hematopoietic stem cell transplantation: the present and the future. Curr Stem Cell Res Ther. 2012;7:381–7.PubMedCrossRefPubMedCentralGoogle Scholar
  128. 128.
    Elbahlawan L, et al. Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation. Pediatr Blood Cancer. 2010;55:540–5.PubMedPubMedCentralCrossRefGoogle Scholar
  129. 129.
    Raina R, Abusin GA, Vijayaraghavan P, Auletta JJ, Cabral L, Hashem H, Vogt BA, Cooke KR, Abu-Arja RF. The role of continuous renal replacement therapy in the management of acute kidney injury associated with sinusoidal obstruction syndrome following hematopoietic cell transplantation. Pediatr Transplant. 2018;22(2)  https://doi.org/10.1111/petr.13139. Epub 2018 Feb 1. PMID:29388370.CrossRefGoogle Scholar
  130. 130.
    Sorensen JB, Andersen MK, Hansen HH. Syndrome of inappropriate secretion of antidiuretic hormone (Siadh) in malignant disease. J Intern Med. 1995;238:97–110.PubMedCrossRefPubMedCentralGoogle Scholar
  131. 131.
    Lim YJ, Park EK, Koh HC, Lee YH. Syndrome of inappropriate secretion of antidiuretic hormone as a leading cause of hyponatremia in children who underwent chemotherapy or stem cell transplantation. Pediatr Blood Cancer. 2010;54:734–7.PubMedCrossRefPubMedCentralGoogle Scholar
  132. 132.
    Abe T, et al. Syndrome of inappropriate antidiuretic hormone secretion (Siadh) in children undergoing high-dose chemotherapy and autologous peripheral blood stem cell transplantation. Pediatr Hematol Oncol. 1995;12:363–9.PubMedCrossRefPubMedCentralGoogle Scholar
  133. 133.
    Shiminski-Maher T. Diabetes insipidus and syndrome of inappropriate secretion of antidiuretic hormone in children with midline suprasellar brain tumors. J Pediatr Oncol Nurs. 1991;8:106–11.PubMedCrossRefPubMedCentralGoogle Scholar
  134. 134.
    Moritz ML, Ayus JC. New aspects in the pathogenesis, prevention, and treatment of hyponatremic encephalopathy in children. Pediatr Nephrol. 2010;25:1225–38.PubMedCrossRefPubMedCentralGoogle Scholar
  135. 135.
    Vion AC, Rautou PE, Durand F, Boulanger CM, Valla DC. Interplay of inflammation and endothelial dysfunction in bone marrow transplantation: focus on hepatic Veno-occlusive disease. Semin Thromb Hemost. 2015;41:629–43.PubMedCrossRefPubMedCentralGoogle Scholar
  136. 136.
    McDonald GB, Hinds MS, Fisher LD, Schoch HG, Wolford JL, Banaji M, et al. Veno-occlusive disease of the liver and multiorgan failure after bone marrow transplantation: a cohort study of 355 patients. Ann Intern Med. 1993;118:255–67.PubMedCrossRefPubMedCentralGoogle Scholar
  137. 137.
    Mahadeo KM, et al. Consensus report by the pediatric acute lung injury and Sepsis investigators and pediatric blood and marrow transplant consortium joint working committees on supportive care guidelines for Management of Veno-Occlusive Disease in children and adolescents: part 2-focus on ascites, fluid and electrolytes, renal, and transfusion issues. Biol Blood Marrow Transplant. 2017;23(12):2023–33.PubMedCrossRefPubMedCentralGoogle Scholar
  138. 138.
    Jones RJ, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987;44:778–83.PubMedCrossRefPubMedCentralGoogle Scholar
  139. 139.
    McDonald GB, Sharma P, Matthews DE, Shulman HM, Thomas ED. Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4:116–22.PubMedCrossRefPubMedCentralGoogle Scholar
  140. 140.
    Shulman HM, Hinterberger W. Hepatic veno-occlusive disease – liver toxicity syndrome after bone marrow transplantation. Bone Marrow Transplant. 1992;10:197–214.PubMedPubMedCentralGoogle Scholar
  141. 141.
    Naples JC, et al. Anicteric veno-occlusive disease after hematopoietic stem cell transplantation in children. Bone Marrow Transplant. 2015;51(1):135.PubMedCrossRefPubMedCentralGoogle Scholar
  142. 142.
    Myers KC, Dandoy C, El-Bietar J, Davies SM, Jodele S. Veno-occlusive disease of the liver in the absence of elevation in bilirubin in pediatric patients after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2015;21:379–81.PubMedCrossRefPubMedCentralGoogle Scholar
  143. 143.
    Carreras E, et al. The incidence of Veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant. 2011;17:1713–20.PubMedCrossRefPubMedCentralGoogle Scholar
  144. 144.
    Coppell JA, et al. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010;16:157–68.PubMedCrossRefPubMedCentralGoogle Scholar
  145. 145.
    Sakai M, et al. Severe hepatocellular injury after hematopoietic cell transplant: incidence, etiology and outcome. Bone Marrow Transplant. 2009;44:441–7.PubMedPubMedCentralCrossRefGoogle Scholar
  146. 146.
    Woods WG, et al. Fatal veno-occlusive disease of the liver following high dose chemotherapy, irradiation and bone marrow transplantation. Am J Med. 1980;68:285–90.PubMedCrossRefPubMedCentralGoogle Scholar
  147. 147.
    Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN. Bchs guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 2013;163:444–57.PubMedCrossRefPubMedCentralGoogle Scholar
  148. 148.
    Bajwa RPS, et al. Consensus report by pediatric acute lung injury and Sepsis investigators and pediatric blood and marrow transplantation consortium joint working committees: supportive care guidelines for management of veno-occlusive disease in children and adolescents, part 1: focus on investigations, prophylaxis, and specific treatment. Biol Blood Marrow Transplant. 2017;23(11):1817–25.PubMedCrossRefPubMedCentralGoogle Scholar
  149. 149.
    Ovchinsky N, Frazier W, Auletta JJ, Dvorak CC, Ardura M, Song E, McArthur J, Jeyapalan A, Tamburro R, Mahadeo KM, Traube C, Duncan CN, Bajwa RPS. Consensus report by the pediatric acute lung injury and sepsis investigators and pediatric blood and marrow transplantation consortium joint working committees on supportive care guidelines for management of veno-occlusive disease in children and adolescents, part 3: focus on cardiorespiratory dysfunction, infections, liver dysfunction, and delirium. Biol Blood Marrow Transplant. 2018;24(2):207–18.  https://doi.org/10.1016/j.bbmt.2017.08.035. Epub 2017 Sep 1. PMID: 28870776.CrossRefPubMedPubMedCentralGoogle Scholar
  150. 150.
    Havelock T, Teoh R, Laws D, Gleeson F, BTS Pleural Disease Guideline Group. Pleural procedures and thoracic ultrasound: British Thoracic Society pleural disease guideline 2010. Thorax. 2010;65(Suppl 2):ii61–76.PubMedCrossRefPubMedCentralGoogle Scholar
  151. 151.
    Willems E, et al. Comparison of thrombotic microangiopathy after allogeneic hematopoietic cell transplantation with high-dose or nonmyeloablative conditioning. Bone Marrow Transplant. 2010;45:689–93.PubMedCrossRefPubMedCentralGoogle Scholar
  152. 152.
    Rosenthal J, et al. Transplant-associated thrombotic microangiopathy in pediatric patients treated with sirolimus and tacrolimus. Pediatr Blood Cancer. 2011;57:142–6.PubMedCrossRefPubMedCentralGoogle Scholar
  153. 153.
    Jodele S, et al. Abnormalities in the alternative pathway of complement in children with hematopoietic stem cell transplant-associated thrombotic microangiopathy. Blood. 2013;122:2003–7.PubMedPubMedCentralCrossRefGoogle Scholar
  154. 154.
    Jodele S, et al. Eculizumab therapy in children with severe hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Biol Blood Marrow Transplant. 2014;20:518–25.PubMedCrossRefPubMedCentralGoogle Scholar
  155. 155.
    Legendre CM, et al. Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome. N Engl J Med. 2013;368:2169–81.PubMedCrossRefPubMedCentralGoogle Scholar
  156. 156.
    Jodele S, et al. A new paradigm: diagnosis and management of Hsct-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015;29:191–204.PubMedCrossRefPubMedCentralGoogle Scholar
  157. 157.
    Hillmen P, et al. Long-term safety and efficacy of sustained eculizumab treatment in patients with paroxysmal nocturnal haemoglobinuria. Br J Haematol. 2013;162:62–73.PubMedPubMedCentralCrossRefGoogle Scholar
  158. 158.
    Peffault de Latour R, et al. Successful use of eculizumab in a patient with post-transplant thrombotic microangiopathy. Br J Haematol. 2013;161:279–80.PubMedCrossRefPubMedCentralGoogle Scholar
  159. 159.
    Przepiorka D, et al. Consensus conference on acute Gvhd grading. Bone Marrow Transplant. 1994;15(1995):825–8.Google Scholar
  160. 160.
    Rowlings PA, et al. Ibmtr severity index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade. Br J Haematol. 1997;97:855–64.PubMedCrossRefPubMedCentralGoogle Scholar
  161. 161.
    Kanakry CG, et al. Multi-institutional study of post-transplantation cyclophosphamide as single-agent graft-versus-host disease prophylaxis after allogeneic bone marrow transplantation using myeloablative busulfan and fludarabine conditioning. J Clin Oncol. 2014;32:3497–505.PubMedPubMedCentralCrossRefGoogle Scholar
  162. 162.
    Luznik L, Fuchs EJ. High-dose, post-transplantation cyclophosphamide to promote graft-host tolerance after allogeneic hematopoietic stem cell transplantation. Immunol Res. 2010;47:65–77.PubMedPubMedCentralCrossRefGoogle Scholar
  163. 163.
    Weisdorf D, et al. Treatment of moderate/severe acute graft-versus-host disease after allogeneic bone marrow transplantation: an analysis of clinical risk features and outcome. Blood. 1990;75:1024–30.PubMedPubMedCentralGoogle Scholar
  164. 164.
    MacMillan ML, et al. Response of 443 patients to steroids as primary therapy for acute graft-versus-host disease: comparison of grading systems. Biol Blood Marrow Transplant. 2002;8:387–94.PubMedCrossRefPubMedCentralGoogle Scholar
  165. 165.
    Messina C, et al. Extracorporeal photochemotherapy for paediatric patients with graft-versus-host disease after haematopoietic stem cell transplantation. Br J Haematol. 2003;122:118–27.PubMedCrossRefPubMedCentralGoogle Scholar
  166. 166.
    Komanduri KV, Couriel D, Champlin RE. Graft-versus-host disease after allogeneic stem cell transplantation: evolving concepts and novel therapies including Photopheresis. Biol Blood Marrow Transplant. 2006;12:1–6.PubMedCrossRefPubMedCentralGoogle Scholar
  167. 167.
    DeSimone RA, Schwartz J, Schneiderman J. Extracorporeal photopheresis in pediatric patients: practical and technical considerations. J Clin Apher. 2017;32:543–52.PubMedCrossRefPubMedCentralGoogle Scholar
  168. 168.
    Chaudhury S, et al. A phase 3 single-arm, prospective study of remestemcel-L, ex-vivo cultured adult human mesenchymal stromal cells, for the treatment of steroid refractory acute Gvhd in pediatric patients. Biol Blood Marrow Transplant. 2018;24:S171–2.CrossRefGoogle Scholar
  169. 169.
    Storb R, et al. Predictive factors in chronic graft-versus-host disease in patients with aplastic-Anemia treated by marrow transplantation from Hla-identical siblings. Ann Intern Med. 1983;98:461–6.PubMedCrossRefPubMedCentralGoogle Scholar
  170. 170.
    Atkinson K, et al. Risk-factors for chronic graft-versus-host disease after Hla-identical sibling bone-marrow transplantation. Blood. 1990;75:2459–64.PubMedPubMedCentralGoogle Scholar
  171. 171.
    Sullivan KM, et al. Chronic graft versus host-disease in 52 patients – adverse natural course and successful treatment with combination immunosuppression. Blood. 1981;57:267–76.PubMedPubMedCentralGoogle Scholar
  172. 172.
    Ochs LA, et al. Predictive factors for chronic graft-versus-host disease after Histocompatible sibling donor bone-marrow transplantation. Bone Marrow Transplant. 1994;13:455–60.PubMedPubMedCentralGoogle Scholar
  173. 173.
    Rouquettegally AM, Boyeldieu D, Prost AC, Gluckman E. Autoimmunity after allogeneic bone-marrow transplantation – a study of 53 long-term-surviving patients. Transplantation. 1988;46:238–40.CrossRefGoogle Scholar
  174. 174.
    Quaranta S, et al. Autoantibodies in human chronic graft-versus-host disease after hematopoietic cell transplantation. Clin Immunol. 1999;91:106–16.PubMedCrossRefGoogle Scholar
  175. 175.
    Allan SE, et al. Activation-induced Foxp3 in human T effector cells does not suppress proliferation or cytokine production. Int Immunol. 2007;19:345–54.PubMedCrossRefGoogle Scholar
  176. 176.
    Schultz KR, Paquet J, Bader S, Hayglass KT. Requirement for B-cells in T-cell priming to minor histocompatibility antigens and development of graft-versus-host disease. Bone Marrow Transplant. 1995;16:289–95.PubMedGoogle Scholar
  177. 177.
    Filipovich AH, et al. National Institutes of Health consensus development project on criteria for clinical trials in chronic graft-versus-host disease: I. diagnosis and staging working group report. Biol Blood Marrow Transplant. 2005;11:945–56.PubMedCrossRefGoogle Scholar
  178. 178.
    Lee SJ, Vogelsang G, Flowers ME. Chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2003;9:215–33.PubMedCrossRefGoogle Scholar
  179. 179.
    Mahadeo KM, et al. Immunologic resolution of human chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2014;20:1508–15.PubMedCrossRefPubMedCentralGoogle Scholar
  180. 180.
    Koreth J, et al. Interleukin-2 and regulatory T cells in graft-versus-host disease. New Engl J Med. 2011;365:2055–66.PubMedCrossRefPubMedCentralGoogle Scholar
  181. 181.
    Barba P, et al. Early and late neurological complications after reduced-intensity conditioning allogeneic stem cell transplantation. Biol Blood Marrow Transplant. 2009;15:1439–46.PubMedCrossRefPubMedCentralGoogle Scholar
  182. 182.
    Kang J-M, et al. Neurologic complications after allogeneic hematopoietic stem cell transplantation in children: analysis of prognostic factors. Biol Blood Marrow Transplant. 2015;21:1091–8.PubMedCrossRefPubMedCentralGoogle Scholar
  183. 183.
    Schmidt K, Schulz AS, Debatin K-M, Friedrich W, Classen CF. Cns complications in children receiving chemotherapy or hematopoietic stem cell transplantation: retrospective analysis and clinical study of survivors. Pediatr Blood Cancer. 2008;50:331–6.PubMedCrossRefPubMedCentralGoogle Scholar
  184. 184.
    Weber C, et al. Diagnostic and therapeutic implications of neurological complications following paediatric haematopoietic stem cell transplantation. Bone Marrow Transplant. 2008;41:253–9.PubMedCrossRefPubMedCentralGoogle Scholar
  185. 185.
    Woodard P, et al. Encephalopathy in pediatric patients after allogeneic hematopoietic stem cell transplantation is associated with a poor prognosis. Bone Marrow Transplant. 2004;33:1151–7.PubMedCrossRefGoogle Scholar
  186. 186.
    Azik F, et al. Neurological complications after allogeneic hematopoietic stem cell transplantation in children, a single center experience. Pediatr Transplant. 2014;18:405–11.PubMedCrossRefGoogle Scholar
  187. 187.
    Openshaw H, Chen BT. Neurologic complications of hematopoietic cell transplantation. Wiley; 2015. https://onlinelibrary.wiley.com/doi/10.1002/9781118416426.ch105.
  188. 188.
    Uckan D, et al. Life-threatening neurological complications after bone marrow transplantation in children. Bone Marrow Transplant. 2005;35:71–6.PubMedCrossRefGoogle Scholar
  189. 189.
    Zaucha-Prazmo A, et al. Neurologic complications in children after hemaopoietic stem cell transplantation: a single-center experience. Transplant Proc. 2007;39:2905–7.PubMedCrossRefGoogle Scholar
  190. 190.
    Najera JE, Alousi A, Lima MD, Ciurea SO. Akinetic mutism – a serious complication to tacrolimus-based Gvhd prophylaxis. Bone Marrow Transplant. 2013;48:157.PubMedCrossRefGoogle Scholar
  191. 191.
    Masetti R, et al. Pres in children undergoing hematopoietic stem cell or solid organ transplantation. Pediatrics. 2015;135:890–901.PubMedCrossRefGoogle Scholar
  192. 192.
    Hedna VS, et al. Posterior reversible encephalopathy syndrome (Pres) and Ct perfusion changes. Int J Emerg Med. 2012;5:12.PubMedPubMedCentralCrossRefGoogle Scholar
  193. 193.
    McArthur J, Duncan C, Rajapreyar P, Talano J-A, Tamburro RT. Critical illness involving children undergoing hematopoietic cell transplantation: cardiac complications. In:Pediatric clinical care. 5th ed. Philadelphia: Elsevier; 2017.Google Scholar
  194. 194.
    Dandoy CE, et al. Abnormal echocardiography 7 days after stem cell transplantation may be an early Indicator of thrombotic microangiopathy. Biol Blood Marrow Transplant. 2015;21:113–8.PubMedPubMedCentralCrossRefGoogle Scholar
  195. 195.
    Dandoy CE, et al. Team-based approach to identify cardiac toxicity in critically ill hematopoietic stem cell transplant recipients. Pediatr Blood Cancer. 2017;64:e26513.CrossRefGoogle Scholar
  196. 196.
    Tichelli A, Bhatia S, Socié G. Cardiac and cardiovascular consequences after haematopoietic stem cell transplantation. Br J Haematol. 2008;142:11–26.PubMedCrossRefPubMedCentralGoogle Scholar
  197. 197.
    Peres E, et al. Cardiac complications in patients undergoing a reduced-intensity conditioning hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45:149–52.PubMedCrossRefPubMedCentralGoogle Scholar
  198. 198.
    Blaes A, Konety S, Hurley P. Cardiovascular complications of hematopoietic stem cell transplantation. Curr Treat Options Cardiovasc Med. 2016;18:25.PubMedPubMedCentralCrossRefGoogle Scholar
  199. 199.
    Majhail NS, Lazarus HM, Burns LJ. Iron overload in hematopoietic cell transplantation. Bone Marrow Transplant. 2008;41:997.PubMedCrossRefGoogle Scholar
  200. 200.
    Yeh ETH, et al. Cardiovascular complications of cancer therapy: diagnosis, pathogenesis, and management. Circulation. 2004;109:3122–31.PubMedCrossRefGoogle Scholar
  201. 201.
    Yoon J-H, et al. Early left ventricular dysfunction in children after hematopoietic stem cell transplantation for acute leukemia: a case control study using speckle tracking echocardiography. Korean Circ J. 2015;45:51–8.PubMedPubMedCentralCrossRefGoogle Scholar
  202. 202.
    Armenian SH, Chow EJ. Cardiovascular disease in survivors of hematopoietic cell transplantation. Cancer. 2014;120:469–79.PubMedCrossRefGoogle Scholar
  203. 203.
    Armenian SH, Ryan TD, Khouri MG. Cardiac dysfunction and heart failure in hematopoietic cell transplantation survivors: emerging paradigms in pathophysiology, screening, and prevention. Heart Fail Clin. 2017;13:337–45.PubMedCrossRefGoogle Scholar
  204. 204.
    Cerveri I, et al. Late pulmonary sequelae after childhood bone marrow transplantation. Thorax. 1999;54:131–5.PubMedPubMedCentralCrossRefGoogle Scholar
  205. 205.
    Griese M, et al. Pulmonary complications after bone marrow transplantation in children: twenty-four years of experience in a single pediatric center. Pediatr Pulmonol. 2000;30:393–401.PubMedCrossRefGoogle Scholar
  206. 206.
    Leneveu H, et al. Respiratory function in children undergoing bone marrow transplantation. Pediatr Pulmonol. 1999;28:31–8.PubMedCrossRefGoogle Scholar
  207. 207.
    Sokol KA, et al. Masks for prevention of respiratory viruses on the Bmt unit: results of a quality initiative. Transpl Infect Dis. 2016;18:965–7.PubMedCrossRefGoogle Scholar
  208. 208.
    Karageorgopoulos DE, et al. Accuracy of beta-D-glucan for the diagnosis of pneumocystis jirovecii pneumonia: a meta-analysis. Clin Microbiol Infect. 2013;19:39–49.PubMedCrossRefGoogle Scholar
  209. 209.
    Jain P, et al. Role of flexible bronchoscopy in immunocompromised patients with lung infiltrates. Chest. 2004;125:712–22.PubMedPubMedCentralCrossRefGoogle Scholar
  210. 210.
    Murray PV, et al. Use of first line bronchoalveolar lavage in the immunosuppressed oncology patient. Bone Marrow Transplant. 2001;27:967–71.PubMedCrossRefPubMedCentralGoogle Scholar
  211. 211.
    Shannon VR, Andersson BS, Lei X, Champlin RE, Kontoyiannis DP. Utility of early versus late Fiberoptic bronchoscopy in the evaluation of new pulmonary infiltrates following hematopoietic stem cell transplantation. Bone Marrow Transplant. 2010;45:647–55.PubMedCrossRefPubMedCentralGoogle Scholar
  212. 212.
    O’Dwyer DN, et al. Transbronchial biopsy in the management of pulmonary complications of hematopoietic stem cell transplantation. Bone Marrow Transplant. 2018;53(2):193–8.  https://doi.org/10.1038/bmt.2017.238. Epub 2017 Oct 23.CrossRefPubMedPubMedCentralGoogle Scholar
  213. 213.
    Tissot F, et al. Ecil-6 guidelines for the treatment of invasive candidiasis, aspergillosis and mucormycosis in leukemia and hematopoietic stem cell transplant patients. Haematologica. 2017;102:433–44.PubMedPubMedCentralCrossRefGoogle Scholar
  214. 214.
    Deresinski S. Principles of antibiotic therapy in severe infections: optimizing the therapeutic approach by use of laboratory and clinical data. Clin Infect Dis. 2007;45:S177–83.PubMedCrossRefPubMedCentralGoogle Scholar
  215. 215.
    Gustinetti G, Mikulska M. Bloodstream infections in neutropenic cancer patients: a practical update. Virulence. 2016;7:280–97.PubMedPubMedCentralCrossRefGoogle Scholar
  216. 216.
    Woods WG, Daigle AE, Hutchinson RJ, Robison LL. Myelosuppression associated with co-trimoxazole as a prophylactic antibiotic in the maintenance phase of childhood acute lymphocytic leukemia. J Pediatr. 1984;105:639–44.PubMedCrossRefPubMedCentralGoogle Scholar
  217. 217.
    Winston D. Infections in bone marrow transplant recipients. In:Principles and practice of infectious disease; 1995. p. 2717–22.Google Scholar
  218. 218.
    Wan L, et al. Effect of granulocyte-macrophage colony-stimulating factor on prevention and treatment of invasive fungal disease in recipients of allogeneic stem-cell transplantation: a prospective multicenter randomized phase Iv trial. J Clin Oncol. 2015;33:3999–4006.PubMedCrossRefPubMedCentralGoogle Scholar
  219. 219.
    Bodey GP, Anaissie E, Gutterman J, Vadhan-Raj S. Role of granulocyte-macrophage colony-stimulating factor as adjuvant treatment in neutropenic patients with bacterial and fungal infection. Eur J Clin Microbiol Infect Dis. 1994;13(Suppl 2):S18–22.PubMedCrossRefGoogle Scholar
  220. 220.
    Tewari P, Allison J, Waters-Pick B, Cash JV, Kurtzberg J, Prasad VK. Collection of G-Csf-mobilized granulocytes from related donors to support hematopoietic stem cell transplant recipients at high risk of infection is safe and feasible. ASBMT. 2011;17, A1–A10:S149–386.Google Scholar
  221. 221.
    Safdar A, Rodriguez GH. Aerosolized amphotericin B lipid complex as adjunctive treatment for fungal lung infection in patients with cancer-related immunosuppression and recipients of hematopoietic stem cell transplantation. Pharmacotherapy. 2013;33:1035–43.PubMedPubMedCentralCrossRefGoogle Scholar
  222. 222.
    Cugno C, Deola S, Filippini P, Stroncek DF, Rutella S. Granulocyte transfusions in children and adults with hematological malignancies: benefits and controversies. J Transl Med. 2015;13:362.PubMedPubMedCentralCrossRefGoogle Scholar
  223. 223.
    Le J, Schiller DS. Aerosolized delivery of antifungal agents. Curr Fungal Infect Rep. 2010;4:96–102.PubMedPubMedCentralCrossRefGoogle Scholar
  224. 224.
    Hertenstein B, et al. Low incidence of invasive fungal infections after bone marrow transplantation in patients receiving amphotericin B inhalations during neutropenia. Ann Hematol. 1994;68:21–6.PubMedCrossRefPubMedCentralGoogle Scholar
  225. 225.
    Busca A, Pagano L. Antifungal therapy in hematopoietic stem cell transplant recipients. Mediterr J Hematol Infect Dis. 2016;8:e2016039.PubMedPubMedCentralCrossRefGoogle Scholar
  226. 226.
    Machado CM, et al. Use of oseltamivir to control influenza complications after bone marrow transplantation. Bone Marrow Transplant. 2004;34:111–4.PubMedCrossRefGoogle Scholar
  227. 227.
    Sparrelid E, et al. Ribavirin therapy in bone marrow transplant recipients with viral respiratory tract infections. Bone Marrow Transplant. 1997;19:905–8.PubMedCrossRefGoogle Scholar
  228. 228.
    Whimbey E, et al. Combination therapy with aerosolized ribavirin and intravenous immunoglobulin for respiratory syncytial virus disease in adult bone marrow transplant recipients. Bone Marrow Transplant. 1995;16:393–9.PubMedPubMedCentralGoogle Scholar
  229. 229.
    Shachor-Meyouhas Y, Ben-Barak A, Kassis I. Treatment with oral ribavirin and Ivig of severe human metapneumovirus pneumonia (Hmpv) in immune compromised child. Pediatr Blood Cancer. 2011;57:350–1.PubMedCrossRefPubMedCentralGoogle Scholar
  230. 230.
    Adams RJ, Christenson JC, Petersen FB, Beatty PG. Pre-emptive use of aerosolized ribavirin in the treatment of asymptomatic pediatric marrow transplant patients testing positive for Rsv. Bone Marrow Transplant. 1999;24:661–4.PubMedCrossRefPubMedCentralGoogle Scholar
  231. 231.
    Jacobsen N, Schafer U, Ostendorf P, Kubaneck B, Wolf H. Intravenous Hyperimmune globulin prophylaxis against cytomegalovirus interstitial pneumonitis after allogenic bone marrow transplantation. Tokai J Exp Clin Med. 1985;10:193–5.PubMedPubMedCentralGoogle Scholar
  232. 232.
    Alexander BT, et al. Use of cytomegalovirus intravenous immune globulin for the adjunctive treatment of cytomegalovirus in hematopoietic stem cell transplant recipients. Pharmacotherapy. 2010;30:554–61.PubMedPubMedCentralCrossRefGoogle Scholar
  233. 233.
    Kempke AP, Leino AS, Daneshvar F, Lee JA, Mueller BA. Antimicrobial doses in continuous renal replacement therapy: a comparison of dosing strategies. Crit Care Res Prac. 2016;2016:3235765.Google Scholar
  234. 234.
    Clark JG, Hansen JA, Hertz MI, et al. Idiopathic pneumonia syndrome after bone marrow transplantation. Am Rev Respir Dis. 1993;147(6 Pt I):1601–6.PubMedPubMedCentralCrossRefGoogle Scholar
  235. 235.
    Cooke KR, et al. Hyporesponsiveness of donor cells to lipopolysaccharide stimulation reduces the severity of experimental idiopathic pneumonia syndrome: potential role for a gut-lung axis of inflammation. J Immunol. 2000;165:6612–9.PubMedCrossRefPubMedCentralGoogle Scholar
  236. 236.
    Williams KM, et al. Fluticasone, azithromycin, and montelukast treatment for new-onset bronchiolitis obliterans syndrome after hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2016;22:710–6.PubMedPubMedCentralCrossRefGoogle Scholar
  237. 237.
    Yanik GA, et al. Tnf-receptor inhibitor therapy for the treatment of children with idiopathic pneumonia syndrome. A joint pediatric blood and marrow transplant consortium and Children’s oncology group study (Asct0521). Biol Blood Marrow Transplant. 2015;21:67–73.PubMedPubMedCentralCrossRefGoogle Scholar
  238. 238.
    Yanik GA, et al. Etanercept for sub-acute lung injury following allogeneic stein cell transplantation. Blood. 2003;102:471a–471a.Google Scholar
  239. 239.
    Williams KM. How I treat bronchiolitis obliterans syndrome after hematopoietic stem cell transplantation. Blood. 2017;129:448–55.PubMedPubMedCentralCrossRefGoogle Scholar
  240. 240.
    Zeiser R, Blazar BR. Acute graft-versus-host disease – biologic process, prevention, and therapy. N Engl J Med. 2017;377:2167–79.PubMedPubMedCentralCrossRefGoogle Scholar
  241. 241.
    Petryk A, Polgreen LE, Chahla S, Miller W, Orchard PJ. No evidence for the reversal of adrenal failure after hematopoietic cell transplantation in X-linked adrenoleukodystrophy. Bone Marrow Transplant. 2012;47:1377–8.PubMedPubMedCentralCrossRefGoogle Scholar
  242. 242.
    Mitchell R, et al. Outcomes of Haematopoietic stem cell transplantation for inherited metabolic disorders: a report from the Australian and New Zealand Children’s Haematology oncology group and the Australasian bone marrow transplant recipient registry. Pediatr Transplant. 2013;17:582–8.PubMedCrossRefPubMedCentralGoogle Scholar
  243. 243.
    Bornstein SR, et al. Diagnosis and treatment of primary adrenal insufficiency: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2016;101:364–89.PubMedPubMedCentralCrossRefGoogle Scholar
  244. 244.
    Ho J, Lewis V, Guilcher GMT, Stephure DK, Pacaud D. Endocrine complications following pediatric bone marrow transplantation. J Pediatr Endocrinol Metab. 2011;24:327–32.PubMedCrossRefPubMedCentralGoogle Scholar
  245. 245.
    Sag E, et al. Hyperthyroidism after allogeneic hematopoietic stem cell transplantation: a report of four cases. J Clin Res Pediatr Endocrinol. 2015;7:349–54.PubMedPubMedCentralCrossRefGoogle Scholar
  246. 246.
    Savani BN, et al. Prolonged chronic graft-versus-host disease is a risk factor for thyroid failure in long-term survivors after matched sibling donor stem cell transplantation for hematologic malignancies. Biol Blood Marrow Transplant. 2009;15:377–81.PubMedPubMedCentralCrossRefGoogle Scholar
  247. 247.
    Minoia F, et al. Development and initial validation of the macrophage activation syndrome/primary hemophagocytic lymphohistiocytosis score, a diagnostic tool that differentiates primary hemophagocytic lymphohistiocytosis from macrophage activation syndrome. J Pediatr. 2017;189:72–8 e73.PubMedCrossRefPubMedCentralGoogle Scholar
  248. 248.
    Lee DW, et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood. 2014;124:188–95.PubMedPubMedCentralCrossRefGoogle Scholar
  249. 249.
    Maude SL, Barrett D, Teachey DT, Grupp SA. Managing cytokine release syndrome associated with novel T cell-engaging therapies. Cancer J. 2014;20:119–22.PubMedPubMedCentralCrossRefGoogle Scholar
  250. 250.
    Klinger M, et al. Immunopharmacologic response of patients with B-lineage acute lymphoblastic leukemia to continuous infusion of T cell-engaging Cd19/Cd3-Bispecific bite antibody blinatumomab. Blood. 2012;119:6226–33.PubMedCrossRefPubMedCentralGoogle Scholar
  251. 251.
    Mahadeo KM, Khazal SJ, Abdel-Azim H, Fitzgerald JC, Taraseviciute A, Bollard CM, Tewari P, Duncan C, Traube C, McCall D, Steiner ME, Cheifetz IM, Lehmann LE, Mejia R, Slopis JM, Bajwa R, Kebriaei P, Martin PL, Moffet J, McArthur J, Petropoulos D, O’Hanlon Curry J, Featherston S, Foglesong J, Shoberu B, Gulbis A, Mireles ME, Hafemeister L, Nguyen C, Kapoor N, Rezvani K, Neelapu SS, Shpall EJ. Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) network. Management guidelines for paediatric patients receiving chimeric antigen receptor T cell therapy. Nat Rev Clin Oncol. 2018.  https://doi.org/10.1038/s41571-018-0075-2. [Epub ahead of print] Review. PMID: 30082906.CrossRefGoogle Scholar
  252. 252.
    Chong SL, et al. A retrospective review of vital signs and clinical outcomes of febrile infants younger than 3 months old presenting to the emergency department. PLoS One. 2018;13:e0190649.PubMedPubMedCentralCrossRefGoogle Scholar
  253. 253.
    Pediatric Acute Lung Injury Consensus Conference, G. Pediatric acute respiratory distress syndrome: consensus recommendations from the pediatric acute lung injury consensus conference. Pediatr Crit Care Med. 2015;16:428–39.CrossRefGoogle Scholar
  254. 254.
    Akcan-Arikan A, et al. Modified rifle criteria in critically ill children with acute kidney injury. Kidney Int. 2007;71:1028–35.PubMedPubMedCentralCrossRefGoogle Scholar
  255. 255.
    Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int. 2012;2:124–38.CrossRefGoogle Scholar
  256. 256.
    Traube C, et al. Cornell assessment of pediatric delirium: a valid, rapid, observational tool for screening delirium in the Picu. Crit Care Med. 2014;42:656–63.PubMedPubMedCentralCrossRefGoogle Scholar
  257. 257.
    Chen F, et al. Measuring Il-6 and Sil-6r in serum from patients treated with tocilizumab and/or siltuximab following Car T cell therapy. J Immunol Methods. 2016;434:1–8.PubMedPubMedCentralCrossRefGoogle Scholar
  258. 258.
    FDA. Actemra® (Tocilizumab) injection, for intravenous or subcutaneous use: highlights of prescribing information. 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/125276s114lbl.pdf, FDA.
  259. 259.
    Gardner, R.S.C.s.H. A pediatric and young adult trial of genetically modified T cells directed against Cd19 for relapsed/refractory Cd19+ Leukemia. 2018, April 10. Available from: https://clinicaltrials.gov/ct2/show/NCT02028455.
  260. 260.
    Liu E, et al. Cord blood Nk cells engineered to express Il-15 and a Cd19-targeted Car show long-term persistence and potent antitumor activity. Leukemia. 2018;32:520–31.PubMedCrossRefPubMedCentralGoogle Scholar
  261. 261.
    Philip B, Kokalaki E, Mekkaoui L, Thomas S, Straathof K, Flutter B, Marin V, Marafioti T, Chakraverty R, Linch D, Quezada SA, Peggs KS, Pule M. A highly compact epitope-based marker/suicide gene for easier and safer T-cell therapy. Blood. 2014;124(8):1277–87.  https://doi.org/10.1182/blood-2014-01-545020. Epub 2014 Jun 26.CrossRefPubMedPubMedCentralGoogle Scholar
  262. 262.
    Trials C. A pediatric and young adult trial of genetically modified T cells directed against Cd19 for relapsed/refractory Cd19+ leukemia. ClinicalTrials.gov. Study Record Detail 2014 [cited]. Available from: https://clinicaltrials.gov/ct2/show/NCT02028455.

Copyright information

© Springer International Publishing 2019

Authors and Affiliations

  • Priti Tewari
    • 1
  • Rajinder Bajwa
    • 2
  • Agne Taraseviciute
    • 3
  • Jerelyn Moffet
    • 4
  • David McCall
    • 1
  • Kris M. Mahadeo
    • 1
    Email author
  1. 1.University of Texas MD Anderson Cancer CenterHoustonUSA
  2. 2.Nationwide Children’s HospitalColumbusUSA
  3. 3.Children’s Hospital Los AngelesUniversity of Southern CaliforniaLos AngelesUSA
  4. 4.Duke Children’s HospitalDurhamUSA

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