160 likes | 331 Views
Module 1. Haematopoietic stem cell transplantation. HSCT, haematopoietic stem cell transplantation. Learning objectives. To understand the difference between allogeneic and autologous HSCT To understand the types of and reasons for the different HSCT conditioning regimens
E N D
Module 1 Haematopoietic stem cell transplantation
HSCT, haematopoietic stem cell transplantation Learning objectives • To understand the difference between allogeneic and autologous HSCT • To understand the types of and reasons for the different HSCT conditioning regimens • To recognise potential complications associated with HSCT • To understand the most common aspects of supportive care and to be able to implement this in clinical practice
HLA, human leukocyte antigen; IV, intravenous; SCID, severe combined immunodeficiencySaria MG et al. Clin J OncolNurs2007;11:53–63 Haematopoietic stem cell transplantation • Haematopoietic stem cell transplantation (HSCT) • Formerly called bone marrow transplantation (BMT) • Transplantation of multipotent haematopoietic stem cells usually derived from bone marrow, peripheral blood, or umbilical cord blood • Transplanted in order to re-establish haematopoietic function in patients with a damaged or defective haematopoietic system • Patients with malignant cancers require HSCT in order rescue their bone marrow from the toxic effects of chemotherapy • The goal of HSCT in patients with non-malignant diseases is to replace non-functional or failed marrow • HSCT is categorised by the donor source • Autologous: from the patient’s own bone marrow • Allogeneic: from another person, related or unrelated, who has been selected as suitably HLA-matched
Autologous vs allogeneic HSCT Saria MG et al. Clin J OncolNurs2007;11:53–63; Passweg JR et al. Swiss Med Wkly2012;142:w13696; American Cancer Society - Stem Cell Transplants. Available at http://www.cancer.org/treatment/treatmentsandsideeffects/treatmenttypes/bonemarrowandperipheralbloodstemcelltransplant/stem-cell-transplant-types-of-transplant, accessed February 2014
Saria MG et al. Clin J OncolNurs 2007;11:53–63; Passweg JR et al. Swiss Med Wkly 2012;142:13696; Gratwohl A & Carreras E. Principles of conditioning. In: Apperley J, Carreras E, Gluckman E Masszi T eds. ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation. Genova: Forum Service Editore, 2012 pp 122–37 Conditioning is required for HSCT Prior to HSCT, patients receive conditioning regimens in the form of chemotherapy with or without radiotherapy • Conditioning regimens for autologous HSCT aim to eradicate the disease • Allogeneic HSCT requires conditioning in order to: • Eradicate the disease • Provide immunosuppression to the recipient to prevent rejection due to graft-versus-host reaction • Create a stem cell niche in the bone marrow to allow engraftment of donor cells Histological section of the bone marrow
Gy, Gray (unit of radiation)Shi M et al. Blood Lymphat Cancer 2013;3:1–9 Conditioning regimen types • Conditioning regimens play a key role in HSCT, and are required for long-term disease control • Traditionally, myeloablative conditioning regimens were used for HSCT • Myeloablative regimens destroy the bone marrow, and include: • High-dose (8–10 Gy) total body irradiation • Busulfan and cyclophosphamide chemotherapy • These regimens however are associated with significant morbidity and mortality • This led to the development of non-myeloablative and reduced-intensity regimens Patient receiving radiotherapy
Shi M et al. Blood Lymphat Cancer 2013;3:1–9 Reduced intensity and non-myeloablative regimens These conditioning regimens have been developed in order to reduce morbidity and mortality • Low-dose (2–3 Gy) total body irradiation with or without fludarabine • Other chemotherapy drugs, such as busulfan or cytarabineand idarubicin, combined with fludarabine • Treosulfan as a substitute for busulfan Novel regimens: • Total lymphoid irradiation • Monoclonal antibodies • Radioimmunotherapy
HSCT is associated withmultiple complications Adapted from Saria MG et al. Clin J OncolNurs 2007;11:53–63 Pre-engraftment phase Early post-engraftment Late post-engraftment Gram-positive bacteria Gram-negative bacteria Cytomegalovirus infections Aspergillus, Candida Varicella-zoster virus Conditioningregimentoxicities Engraftment syndrome Chronic GVHD Acute graft-versus-host disease (GVHD) Hepatic veno-occlusive disease Bronchiolitis obliterans Diffuse alveolar haemorrhage Idiopathic pneumonia syndrome Haemorrhagiccystitis Haemorrhagic cystitis Haemorrhagiccardiomyopathy Acute renal failure -1 1 2 3 4 5 8 12 16 20 (Day 100) (Day 0 = transplant) (Day 30) Weeks after transplant Chronology of haematopoietic stem cell transplant complications
GCSF, granulocyte colony-stimulating factor; GvHD, graft-versus-host diseaseSaria MG et al. Clin J OncolNurs2007;11:53–63; Masszi T & Mank A. Supportive Care. In: Apperley J, Carreras E, Gluckman E Masszi T eds. ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation. Genova: Forum Service Editore, 2012 pp 156–74 Neutropenia, GvHD and infection are important complications requiring intervention • Complications associated with HSCT require prophylaxisor treatment: Growth factors (eg GSCF) Neutropenia Immunosuppressive drugs (eg corticosteroids, cyclosporine) GvHD Antimicrobials (eg antibiotics, antifungals) Infection
Masszi T & Mank A. Supportive Care. In: Apperley J, Carreras E, Gluckman E Masszi T eds. ESH-EBMT Handbook on Haematopoietic Stem Cell Transplantation. Genova: Forum Service Editore, 2012 pp 156–74; Chemotherapy Induced Nausea & Vomiting; A Nurse’s Perspective. Available athttp://www.ebmt.org/Contents/Resources/Library/Slidebank/EBMT2013SlideBank/Documents/Nurses/N1239.pdf, accessed February 2014 Post-chemotherapy HSCT –requires supportive care Several clinical problems that arise after HSCT frequently require supportive care Impaired nutritional status Mucositis Supportive care Nausea
Summary of HSCT • Autologous HSCT uses stem cells derived from the patient’s own bone marrow; allogeneic HSCT uses stem cells from a related or unrelated donor • Autologous HSCT has no risk of rejection, however cancer cells may be transplanted along with stem cells • Allogeneic HSCT may result in a beneficial graft-versus-cancer effect, although it also carries a risk of rejection and GvHD • Conditioning prior to HSCT is required in order to eradicate the disease, prevent rejection, or aid engraftment • Reduced-intensity conditioning regimens aim to reduce morbidityand mortality • HSCT and conditioning are associated with multiple complications such as neutropenia, mucositis and nausea that require treatment and supportive care
Self-assessment questions • Of the following, which is not a risk of autologous HSCT? • Harvesting of cancer cells • Graft-versus-host disease • Evasion of transplanted cells by the cancer
Self-assessment questions • For which three reasons are conditioning regimens required prior to HSCT?
Self-assessment questions • What is the distinction between myeloablative and non-myeloablative conditioning regimens?
Self-assessment questions • Immunosuppressive drugs such as corticosteroids are given in order to manage which HSCT-related condition? • Neutropenia • Graft-versus-host disease • Infection
Self-assessment questions • Of these three clinical problems arising after HSCT, which is most feared by patients? • Impaired nutritional status • Nausea • Mucositis