Module 1

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

HSCT, haematopoietic stem cell transplantation

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

HLA, human leukocyte antigen; IV, intravenous; SCID, severe combined immunodeficiencySaria MG et al. Clin J Oncol Nurs 2007;11:53–63

Autologous vs allogeneic HSCT

Saria MG et al. Clin J Oncol Nurs 2007;11:53–63; Passweg JR et al. Swiss Med Wkly 2012;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

Autologous transplantation Allogeneic transplantation

Definition Stem cells harvested from patient’s own blood or bone marrow

Stem cells provided by a HLA-matched, related, or unrelated donor

Indications Leukaemias, lymphomas,multiple myeloma

Certain types of leukaemia, lymphomas, and other bone marrow disorders

Advantages No risk of rejection Donor cells may attack remaining cancer cells (graft-versus-cancer effect)

Disadvantages - Cancer cells may be harvested along with stem cells

- Cancer cells may be able to evade immune system

- Risk of rejection- Donor cells may attack the patient’s

body (graft-versus-host disease)- Increased risk of infection

Uses To bridge haematopoietic failure during high dose chemotherapy for treatment of tumours of the haematopoietic system

To replace the haematopoietic system in patients with acquired or congenital failure, and more commonly to exploit the graft-vs-tumour effect

Conditioning is required for HSCT

Prior to HSCT, patients receive conditioning regimens in the form of chemotherapy with or without radiotherapy

Saria MG et al. Clin J Oncol Nurs 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 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

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

Gy, Gray (unit of radiation)Shi M et al. Blood Lymphat Cancer 2013;3:1–9

Patient receiving radiotherapy

Reduced intensity and non-myeloablative regimens

Shi M et al. Blood Lymphat Cancer 2013;3:1–9

• Low-dose (2–3 Gy) total body irradiation with or without fludarabine• Other chemotherapy drugs, such as busulfan or cytarabine and

idarubicin, combined with fludarabine• Treosulfan as a substitute for busulfan

Novel regimens:• Total lymphoid irradiation• Monoclonal antibodies• Radioimmunotherapy

These conditioning regimens have been developed in order to reduce morbidity and mortality

HSCT is associated withmultiple complications

Adapted from Saria MG et al. Clin J Oncol Nurs 2007;11:53–63

Gram-negative bacteria

Conditioningregimentoxicities

Haemorrhagiccystitis

Engraftment syndrome

Diffuse alveolar haemorrhage

Haemorrhagiccardiomyopathy

Pre-engraftment phase Early post-engraftment Late post-engraftment

Gram-positive bacteria

Aspergillus, Candida

Cytomegalovirus infections

Varicella-zoster virus

Chronic GVHD

Idiopathic pneumonia syndrome

Haemorrhagic cystitis

Acute renal failure

(Day 0 = transplant) (Day 30) (Day 100)

Weeks after transplant

Bronchiolitis obliterans

Hepatic veno-occlusive disease

Acute graft-versus-host disease (GVHD)

-1 1 2 3 4 5 8 12 16 20

Chronology of haematopoietic stem cell transplant complications

Neutropenia, GvHD and infection are important complications requiring intervention

• Complications associated with HSCT require prophylaxisor treatment:

GCSF, granulocyte colony-stimulating factor; GvHD, graft-versus-host diseaseSaria MG et al. Clin J Oncol Nurs 2007;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

Growth factors(eg GSCF)

Immunosuppressive drugs(eg corticosteroids,

cyclosporine)

Antimicrobials(eg antibiotics,

antifungals)

Neutropenia

GvHD

Infection

Post-chemotherapy HSCT –requires supportive care

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

Supportive care

Impaired nutritional

statusMucositis

Nausea

Several clinical problems that arise after HSCT frequently require supportive care

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

1. Of the following, which is not a risk of autologous HSCT?a) Harvesting of cancer cells

b) Graft-versus-host disease

c) Evasion of transplanted cells by the cancer

Self-assessment questions

2. For which three reasons are conditioning regimens required prior to HSCT?

Self-assessment questions

3. What is the distinction between myeloablative and non-myeloablative conditioning regimens?

Self-assessment questions

4. Immunosuppressive drugs such as corticosteroids are given in order to manage which HSCT-related condition?a) Neutropenia

b) Graft-versus-host disease

c) Infection

Self-assessment questions

5. Of these three clinical problems arising after HSCT, which is most feared by patients?a) Impaired nutritional status

b) Nausea

c) Mucositis