Module 1

1. Module 1 Haematopoietic stem cell transplantation

2. 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

3. 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

4. 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

5. 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

6. 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

7. 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

8. 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

9. 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

10. 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

11. 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

12. 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

13. Self-assessment questions • For which three reasons are conditioning regimens required prior to HSCT?

14. Self-assessment questions • What is the distinction between myeloablative and non-myeloablative conditioning regimens?

15. Self-assessment questions • Immunosuppressive drugs such as corticosteroids are given in order to manage which HSCT-related condition? • Neutropenia • Graft-versus-host disease • Infection

16. Self-assessment questions • Of these three clinical problems arising after HSCT, which is most feared by patients? • Impaired nutritional status • Nausea • Mucositis