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 immunodeficiency
Saria MG et al. Clin J Oncol Nurs 2007;11:53–63
Autologous vs allogeneic HSCT
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
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-celltransplant-types-of-transplant, accessed February 2014
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
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 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
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 cytarabine and
idarubicin, combined with fludarabine
• Treosulfan as a substitute for busulfan
Novel regimens:
• Total lymphoid irradiation
• Monoclonal antibodies
• Radioimmunotherapy
Shi M et al. Blood Lymphat Cancer 2013;3:1–9
HSCT is associated with
multiple complications
Pre-engraftment phase
Early post-engraftment
Late post-engraftment
Gram-positive bacteria
Gram-negative bacteria
Cytomegalovirus infections
Aspergillus, Candida
Conditioning
regimen
toxicities
Varicella-zoster virus
Engraftment syndrome
Chronic GVHD
Acute graft-versus-host disease (GVHD)
Hepatic veno-occlusive disease
Bronchiolitis obliterans
Diffuse alveolar haemorrhage
Idiopathic pneumonia syndrome
Haemorrhagic
cystitis
Haemorrhagic cystitis
Haemorrhagic
cardiomyopathy
-1
1
Acute renal failure
2
(Day 0 = transplant)
3
4
5
8
(Day 30)
Weeks after transplant
Chronology of haematopoietic stem cell transplant complications
Adapted from Saria MG et al. Clin J Oncol Nurs 2007;11:53–63
12
16
(Day 100)
20
Neutropenia, GvHD and infection are important
complications requiring intervention
• Complications associated with HSCT require prophylaxis
or treatment:
Neutropenia
Growth factors
(eg GSCF)
GvHD
Immunosuppressive drugs
(eg corticosteroids,
cyclosporine)
Infection
Antimicrobials
(eg antibiotics,
antifungals)
GCSF, granulocyte colony-stimulating factor; GvHD, graft-versus-host disease
Saria 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. ESHEBMT Handbook on Haematopoietic Stem Cell Transplantation. Genova: Forum Service Editore, 2012 pp 156–74
Post-chemotherapy HSCT –
requires supportive care
Several clinical problems that arise after HSCT frequently
require supportive care
Impaired
nutritional
status
Mucositis
Supportive
care
Nausea
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 at
http://www.ebmt.org/Contents/Resources/Library/Slidebank/EBMT2013SlideBank/Documents/Nurses/N1239.pdf, accessed February 2014
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 morbidity
and 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 nonmyeloablative 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