Vol 54, No 6 (2023)
Review article
Published online: 2023-09-22
Emergencies in patients undergoing hematopoietic stem cell transplantation
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DOI: 10.5603/ahp.96092
Acta Haematol Pol 2023;54(6):372-381.
Abstract
Despite its high effectiveness, hematopoietic stem cell transplantation (HSCT) can sometimes be associated with multiple peri-transplant complications requiring urgent intervention. Life-threatening complications in the transplantation unit affect non-relapse mortality. This article sets out a practical approach to the essential peri-transplant clinical conditions, divided into infectious complications and complications related to immune response and endothelial damage. An early diagnosis of life-threatening conditions, and prompt implementation of the best therapy, can save patients’ lives. This is especially the case regarding infectious complications in neutropenic patients and in the advanced stages of immunological complications such as graft-versus-host disease, veno-occlusive disease, graft failure, diffuse alveolar hemorrhage, and thrombotic microangiopathy associated with HSCT. These emergencies are discussed below, along with their risk factors and a summary of the management of patients in the early post-transplant period.
Keywords: hematopoietic stem cell transplantationHSCTinfectious complications after HSCTimmunological complications after HSCT
References
- Appelbaum FR. Hematopoietic-cell transplantation at 50. N Engl J Med. 2007; 357(15): 1472–1475.
- Sorror ML, Maris MB, Storb R, et al. Hematopoietic cell transplantation (HCT)-specific comorbidity index: a new tool for risk assessment before allogeneic HCT. Blood. 2005; 106(8): 2912–2919.
- Snowden JA, Sánchez-Ortega I, Corbacioglu S, et al. European Society for Blood and Marrow Transplantation (EBMT). Indications for haematopoietic cell transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe, 2022. Bone Marrow Transplant. 2022; 57(8): 1217–1239.
- Ustawa z dnia 8 września 2006 r. o Państwowym Ratownictwie Medycznym. Dz.U. 2006 nr 191 poz. 1410. https://isap.sejm.gov.pl/isap.nsf/DocDetails.xsp?id=wdu20061911410 (January 28, 2023).
- Gratwohl A, Sureda A, Baldomero H, et al. Joint Accreditation Committee (JACIE) of the International Society for Cellular Therapy (ISCT) and the European Society for Blood and Marrow Transplantation (EBMT) and the European Leukemia Net (ELN). Economics and outcome after hematopoietic stem cell transplantation: a retrospective cohort study. EBioMedicine. 2015; 2(12): 2101–2109.
- Styczyński J, Tridello G, Koster L, et al. Infectious Diseases Working Party EBMT. Death after hematopoietic stem cell transplantation: changes over calendar year time, infections and associated factors. Bone Marrow Transplant. 2020; 55(1): 126–136.
- Rupa-Matysek J, Gil L, Mozer-Lisewska I, et al. Neutropenia — there are always two sides to a story. Acta Haematol Pol. 2020; 51(3): 133–141.
- Auletta JJ, Kou J, Chen M, Shaw BE. Current use and outcome of hematopoietic stem cell transplantation: CIBMTR US summary slides, 2021.
- Styczynski J, Piekarska A, Zaucha-Prażmo A, et al. Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations. Acta Haematol Pol. 2021; 52(6): 528–542.
- Carreras E, Dufour C, Mohty M, Kröger N. eds. The EBMT handbook: hematopoietic stem cell transplantation and cellular therapies. 7th ed. Springer, Cham 2019.
- Mikulska M, Del Bono V, Viscoli C. Bacterial infections in hematopoietic stem cell transplantation recipients. Curr Opin Hematol. 2014; 21(6): 451–458.
- Averbuch D, Orasch C, Cordonnier C, et al. ECIL4, a joint venture of EBMT, EORTC, ICHS, ESGICH/ESCMID and ELN. 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(12): 1826–1835.
- Averbuch D, Tridello G, Hoek J, et al. Antimicrobial resistance in gram-negative rods causing bacteremia in hematopoietic stem cell transplant recipients: Intercontinental Prospective Study of the Infectious Diseases Working Party of the European Bone Marrow Transplantation Group. Clin Infect Dis. 2017; 65(11): 1819–1828.
- Freifeld AG, Bow EJ, Sepkowitz KA, et al. Infectious Diseases Society of America. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the infectious diseases society of america. Clin Infect Dis. 2011; 52(4): e56–e93.
- Donnelly JP, Chen SC, Kauffman CA, et al. Revision and update of the consensus definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer and the Mycoses Study Group Education and Research Consortium. Clin Infect Dis. 2020; 71(6): 1367–1376.
- Annaloro C, Serpenti F, Saporiti G, et al. Viral Infections in HSCT: detection, monitoring, clinical management, and immunologic implications. Front Immunol. 2020; 11: 569381.
- Ljungman P, de la Camara R, Robin C, et al. 2017 European Conference on Infections in Leukaemia group. Guidelines for the management of cytomegalovirus infection in patients with haematological malignancies and after stem cell transplantation from the 2017 European Conference on Infections in Leukaemia (ECIL 7). Lancet Infect Dis. 2019; 19(8): e260–e272.
- Styczynski J, Einsele H, Gil L, et al. Outcome of treatment of Epstein-Barr virus-related post-transplant lymphoproliferative disorder in hematopoietic stem cell recipients: a comprehensive review of reported cases. Transpl Infect Dis. 2009; 11(5): 383–392.
- Styczynski J, Reusser P, Einsele H, et al. Second European Conference on Infections in Leukemia. Management of HSV, VZV and EBV infections in patients with hematological malignancies and after SCT: guidelines from the Second European Conference on Infections in Leukemia. Bone Marrow Transplant. 2009; 43(10): 757–770.
- Marjanska A, Styczynski J. Who is the patient at risk for EBV reactivation and disease: expert opinion focused on post-transplant lymphoproliferative disorders following hematopoietic stem cell transplantation. Expert Opin Biol Ther. 2023; 23(6): 539–552.
- Penack O, Marchetti M, Ruutu T, et al. Prophylaxis and management of graft versus host disease after stem-cell transplantation for haematological malignancies: updated consensus recommendations of the European Society for Blood and Marrow Transplantation. Lancet Haematol. 2020; 7(2): e157–e167.
- Zeiser R, Burchert A, Lengerke C, et al. Ruxolitinib in corticosteroid-refractory graft-versus-host disease after allogeneic stem cell transplantation: a multicenter survey. Leukemia. 2015; 29(10): 2062–2068.
- Martini DJ, Chen YB, DeFilipp Z. Recent FDA approvals in the treatment of graft-versus-host disease. Oncologist. 2022; 27(8): 685–693.
- Zhang H, Chen R, Cheng J, et al. Systematic review and meta-analysis of prospective studies for ECP treatment in patients with steroid-refractory acute GVHD. Patient Prefer Adherence. 2015; 9: 105–111.
- Malard F, Huang XJ, Sim JPY. Treatment and unmet needs in steroid-refractory acute graft-versus-host disease. Leukemia. 2020; 34(5): 1229–1240.
- Bonifazi F, Barbato F, Ravaioli F, et al. Diagnosis and treatment of VOD/SOS after allogeneic hematopoietic stem cell transplantation. Front Immunol. 2020; 11: 489.
- Mohty M, Malard F, Abecasis M, et al. Prophylactic, preemptive, and curative treatment for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a position statement from an international expert group. Bone Marrow Transplant. 2020; 55(3): 485–495.
- Stutz L, Halter JP, Heim D, et al. Low Incidence of hepatic sinusoidal obstruction syndrome/veno-occlusive disease in adults undergoing allogenic stem cell transplantation with prophylactic ursodiol and low-dose heparin. Bone Marrow Transplant. 2022; 57(3): 391–398.
- Nauffal M, Kim HT, Richardson PG, et al. Defibrotide: real-world management of veno-occlusive disease/sinusoidal obstructive syndrome after stem cell transplant. Blood Adv. 2022; 6(1): 181–188.
- Mohty M, Blaise D, Peffault de Latour R, et al. Real-world use of defibrotide for veno-occlusive disease/sinusoidal obstruction syndrome: the DEFIFrance Registry Study. Bone Marrow Transplant. 2023; 58(4): 367–376.
- McCann S. Graft failure. Bone Marrow Transplant. 2020; 55(10): 1888–1889.
- Olsson RF, Logan BR, Chaudhury S, et al. Primary graft failure after myeloablative allogeneic hematopoietic cell transplantation for hematologic malignancies. Leukemia. 2015; 29(8): 1754–1762.
- Ozdemir ZN, Civriz Bozdağ S. Graft failure after allogeneic hematopoietic stem cell transplantation. Transfus Apher Sci. 2018; 57(2): 163–167.
- Locatelli F, Lucarelli B, Merli P. Current and future approaches to treat graft failure after allogeneic hematopoietic stem cell transplantation. Expert Opin Pharmacother. 2014; 15(1): 23–36.
- Diab M, ZazaDitYafawi J, Soubani AO. Major pulmonary complications after hematopoietic stem cell transplant. Exp Clin Transplant. 2016; 14(3): 259–270.
- Keklik F, Alrawi EB, Cao Q, et al. Diffuse alveolar hemorrhage is most often fatal and is affected by graft source, conditioning regimen toxicity, and engraftment kinetics. Haematologica. 2018; 103(12): 2109–2115.
- Rathi NK, Tanner AR, Dinh A, et al. Low-, medium- and high-dose steroids with or without aminocaproic acid in adult hematopoietic SCT patients with diffuse alveolar hemorrhage. Bone Marrow Transplant. 2015; 50(3): 420–426.
- Afessa B, Tefferi A, Litzow MR, et al. Outcome of diffuse alveolar hemorrhage in hematopoietic stem cell transplant recipients. Am J Respir Crit Care Med. 2002; 166(10): 1364–1368.
- Majhail NS, Parks K, Defor TE, et al. Diffuse alveolar hemorrhage and infection-associated alveolar hemorrhage following hematopoietic stem cell transplantation: related and high-risk clinical syndromes. Biol Blood Marrow Transplant. 2006; 12(10): 1038–1046.
- Epperla N, Li A, Logan B, et al. Incidence, risk factors for and outcomes of transplant-associated thrombotic microangiopathy. Br J Haematol. 2020; 189(6): 1171–1181.
- Scully M, Cataland S, Coppo P, et al. International Working Group for Thrombotic Thrombocytopenic Purpura. Consensus on the standardization of terminology in thrombotic thrombocytopenic purpura and related thrombotic microangiopathies. J Thromb Haemost. 2017; 15(2): 312–322.
- Lazana I. Transplant-associated thrombotic microangiopathy in the context of allogenic hematopoietic stem cell transplantation: where we stand. Int J Mol Sci. 2023; 24(2).
- George JN, Li X, McMinn JR, et al. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. 2004; 44(2): 294–304.