POSTGRADUATE
SCHOOL OF MEDICINE
HYPERSENSITIVITY
Dr J. A. Green
MDSC156: Acute Clinical Oncology
A MEMBER OF THE RUSSELL GROUP
CONTINUING PROFESSIONAL DEVELOPMENT
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Aims
•
To define types of hypersensitivity reaction (HSR)
•
Identify which anticancer agents are most likely to provoke a
HSR
•
Which interventions can be used to reduce risk of HSR
•
When is it safe to rechallenge?
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Defining Hypersensitivity
• An exaggerated immune response that results in tissue injury or changes
throughout the body in response to an antigen or foreign substance (Gobel,
2005).
• Most reactions to standard chemotherapy agents are consistent with type 1
hypersensitivity;
•
Anaphylaxis reaction (IgE mediated) occurs with prior exposure
•
Anaphylactoid (non IgE mediated) occurs without prior exposure
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Immunologic Mechanism
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Cytokine Release Syndrome
•
Cytokine-release syndrome (CRS) can present almost the same as type I
(IgE) reaction and develop into an anaphylaxis type reaction.
•
CRS is related to changes of serum cytokine levels due to rapid injection of
an antibody (Hrishikesh & Pashtoon, 2012).
•
CRS caused by release of cytokines can cause:
• Fever
• Dyspnea
• Chills
• Hypotension
• Nausea
• Tachycardia
• Rash
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Mechanisms of CRS
Monoclonal
Antibody
Cancer
Cell
Immune
effector cells
Compliment
Cancer
Cell
Breslin, 2007
Cytokines release
into blood stream
Cell Death
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High Risk Antineoplastics
Antineoplastic drugs with a high probability of initiating an HSR include:
•
•
•
•
•
Monoclonal antibodies
Taxanes
Platinum compounds
Asparaginase
Liposomal preparations
(Kuntzsch & Vogue, 2009)
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Premedication
Premedication is required to help prevent/reduce severity of HSRs
and can include;
• Histamine-2 (H2) receptor antagonists
• Ranitidine or Cimetidine
• Corticosteriods
• Dexamethasone
• Histamine-1 (H1) receptor antagonists
• Chlorphenmine
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Treatment in HSR
•
•
Primary treatment is prevention
•
History taking patient previous allergy
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Nursing knowledge of high risk agents, appropriate premedication
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Monitor patient for signs of HSR
Suspected HSR
•
Stop anticancer agent, maintain IV fluids, inform medical staff
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Emergency equipment & medication at hand
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Continue to monitor vital signs
•
Administer emergency drugs & oxygen according to guidelines
•
Document incident and reaction grade
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Rechallenge
•
Most patients who experience mild-moderate reaction (grade 1-2) during 1st exposure i.e.
taxanes and monoclonal antibodies, will tolerate rechallenged using slower infusion rate and
premedication.
•
Rechallening platinum agents is generally less successful than with taxanes, 50% experience
recurrent HSR despite premedication.
•
Desensitization protocols modifying infusion times have been successful at reducing 2nd
reactions.
•
Rechallenge is discouraged in severe initial reactions (grade 3-4).
•
In all cases decision to rechallenge should be based on RISK v BENEFIT highlighting the need
for accurate grading of HSR and CRSs.
(Lenz HJ 2007)
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References
• Breslin S (2007) Cytokine reaction syndrome: overview and nursing implications. Clinical Journal of Oncology 11,
1, 37-41.
• Gobel Holmes B (2005) Chemotherapy-Induced Hypersensitivity Reaction. Oncology Nursing Forum 32, 5, 10271035
• Gonzalez et al (2000) Hypersensitivity reactions to chemotherapy. Alergol Immunol Clin. 15, 161-181.
• Hrishikesh SK & Pashtoon MK (2012) Rituximab and Cytokine Release Syndrome. Case Reports Oncology 5, 1,
134-141.
• Kuntzsch T & Vogue CA (2009) Hypersensitivity Reactions to Chemotherapy. In Chernecky C & Murphy-Ende K
(Eds) Acute Care Oncology Nursing 2nd Ed. Elsevier, Missouri, USA.
• Lenz HJ (2007) Management and Preparedness for Infusion and Hypersensivity reactions. The Oncologist 12,
601-609.
• National Cancer Institute (NCI) (2007) Common Toxicity Criteria version 3.
• Vogel WH (2010) Infusion reactions: diagnosis, assessment and management. Clinical Journal of Oncology 14, 2,
E10-E21.
• Cheng et al (2014) HLA associations and clinical implications in T-cell mediated drug hypersensitivity reactions:
an updated review, J. Immunol Res. ;2014:565320. doi: 10.1155/2014/565320.
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www.liv.ac.uk/learning-and-teaching/cpd
A MEMBER OF THE RUSSELL GROUP