Neutropenia Severity Grading Interpreter
Neutropenia Severity Grading Interpreter
Grade neutropenia by absolute neutrophil count. First, the thing that matters more than the grade: a temperature of 38.3 °C once, or 38.0 °C for over an hour, with a neutrophil count below 0.5 ×10⁹/L is a medical emergency needing antibiotics within one hour.
Neutropenia Severity Grading
ANC + fever → grade and actionANC 0.8 ×10⁹/L, no fever, laboratory lower limit 2.0 ×10⁹/L
CTCAE version 5 grades, and the definition that matters more
Grade 2 — below 1.5 to 1.0
Grade 3 — below 1.0 to 0.5
Grade 4 — below 0.5
Febrile neutropenia — 38.3 °C once, or 38.0 °C for over an hour, with an ANC below 0.5 ×10⁹/L (or below 1.0 and expected to fall). Antibiotics within one hour.
- grade 1 depends on your laboratory
- it is defined against the lower limit of normal, so where that limit is 1.5 ×10⁹/L there is no grade 1 at all
- a grade is not a decision
- CTCAE grades exist to describe toxicity consistently in trials. Fever, not the grade, is what triggers emergency treatment
- CTCAE version 6
- released in 2025 and regrades these bands — 1.0 to 1.5 ×10⁹/L becomes grade 1, the old grade 1 is no longer graded, and grade 4 moves to below 0.1 ×10⁹/L. State which version a grade came from
- Duffy-null
- a normal variant, not acquired neutropenia, and not an infection risk. It must not be treated as toxicity
Worked example
ANC 0.8 ×10⁹/L, no fever, laboratory lower limit 2.0 ×10⁹/L
0.8 ×10⁹/L is 0.5 or above but under 1.0 → grade 3 neutropenia on CTCAE version 5
No fever recorded, so this is a grading rather than an emergency
But a temperature of 38.0 °C at this count would be febrile neutropenia, needing antibiotics within one hour and no waiting for a repeat count
With a laboratory lower limit of 2.0, grade 1 covers 1.5 to under 2.0. Had the limit been 1.5, there would be no grade 1 at all
Fever on chemotherapy — what counts, and what to do
| Question | Answer | Why |
|---|---|---|
| What temperature counts? | 38.3 °C once, or 38.0 °C for more than an hour | Either meets the guideline definition. Many UK units also act on 37.5 °C recorded twice, an hour apart |
| What neutrophil count counts? | Below 0.5 ×10⁹/L, or below 1.0 and expected to fall | NICE uses 0.5 ×10⁹/L or lower; CTCAE defines febrile neutropenia below 1.0 |
| Do I wait for the blood result? | No | Antibiotics are started before the count is back and stopped later if they turn out not to be needed |
| How quickly? | Within one hour of arriving | Neutropenic sepsis can kill within hours, and delay is the single modifiable factor |
| Should I take paracetamol first? | No | It hides the fever and delays treatment without changing the risk |
| Where do I go? | Your 24-hour chemotherapy helpline, or the emergency department | Say you are on chemotherapy and may be neutropenic — that is a triage category, not a queue |
CTCAE grades — and why the version has to be stated
| Grade | CTCAE version 5 (2017) | CTCAE version 6 (2025) |
|---|---|---|
| 1 | Below the lower limit of normal to 1.5 ×10⁹/L | 1.0 to 1.5 ×10⁹/L — the old grade 1 range is no longer graded |
| 2 | Below 1.5 to 1.0 ×10⁹/L | Shifted downward accordingly |
| 3 | Below 1.0 to 0.5 ×10⁹/L | Shifted downward accordingly |
| 4 | Below 0.5 ×10⁹/L | Below 0.1 ×10⁹/L |
The emergency first, the grading second
Grading matters far less than one fact, so it comes first. A temperature of 38.3 °C measured once, or 38.0 °C sustained for more than an hour, in someone whose neutrophil count is below 0.5 ×10⁹/L — or below 1.0 and expected to fall — is febrile neutropenia, and it is a medical emergency. Empirical broad-spectrum intravenous antibiotics are given within one hour of arrival, before any culture or repeat blood count is available. If you are having chemotherapy and your temperature reaches 38 °C, ring the 24-hour helpline you were given, or go to the emergency department now and say you are on chemotherapy and may be neutropenic. Do not wait to see whether it settles, and do not take paracetamol first: it hides the fever without reducing the danger.
The grading exists to describe toxicity consistently in trials and dose modification tables, and is written around the absolute neutrophil count rather than the percentage. On CTCAE version 5, grade 1 runs from below the laboratory's lower limit of normal down to 1.5 ×10⁹/L, grade 2 from below 1.5 to 1.0, grade 3 from below 1.0 to 0.5, and grade 4 below 0.5. Grade 1 is therefore defined against a number that differs between laboratories: where the lower limit of normal is 1.5 ×10⁹/L, grade 1 has no range at all and a count between 1.5 and 2.0 is simply normal.
The version has to be stated alongside the grade. CTCAE version 6, released in 2025, deliberately regrades the cytopenias downward: 1.0 to 1.5 ×10⁹/L, grade 2 on version 5, becomes grade 1; the old grade 1 range is no longer graded; and grade 4 moves from below 0.5 to below 0.1 ×10⁹/L. The same result therefore carries different grades under the two versions, so a grade recorded without a version is ambiguous. This page grades on version 5, which remains the version in general use.
One low count is not neutropenia at all. Duffy-null associated neutrophil count — long called benign ethnic neutropenia — is a normal variant associated with the ACKR1 genotype that abolishes Duffy antigen expression on red cells. It is commonest in people of African ancestry, is present from birth, typically produces a stable, isolated count around 1.0 to 1.5 ×10⁹/L with no other cytopenia, and carries no increased risk of infection. Treating it as acquired neutropenia leads to unnecessary marrow biopsies and, more seriously, to chemotherapy dose reductions and delays in people who need full-dose treatment. A lifelong, stable, isolated mild neutropenia should raise this possibility rather than an investigation.
Frequently asked questions
What is febrile neutropenia and what should I do about it?
A temperature of 38.3 °C once, or 38.0 °C for more than an hour, with a neutrophil count below 0.5 ×10⁹/L or below 1.0 and expected to fall. It is a medical emergency. Ring your 24-hour chemotherapy helpline or go to the emergency department immediately — antibiotics are needed within one hour, before any blood result is back. Do not take paracetamol first.
What are the CTCAE neutropenia grades?
On version 5: grade 1 is below the lower limit of normal to 1.5 ×10⁹/L, grade 2 is below 1.5 to 1.0, grade 3 is below 1.0 to 0.5, and grade 4 is below 0.5 ×10⁹/L. Grade 1 depends on your laboratory's lower limit, so where that limit is 1.5 there is no grade 1.
Have the CTCAE neutropenia grades changed?
Yes. CTCAE version 6, released in 2025, regrades the cytopenias downward: 1.0 to 1.5 ×10⁹/L becomes grade 1, the old grade 1 range is no longer graded, and grade 4 moves to below 0.1 ×10⁹/L. Any recorded grade should therefore name its version. Check the current NCI document before applying version 6 boundaries.
What is benign ethnic neutropenia?
Now usually called Duffy-null associated neutrophil count. It is a normal variant linked to the ACKR1 genotype, commonest in people of African ancestry, giving a lifelong stable count of roughly 1.0 to 1.5 ×10⁹/L with no other cytopenia and no increased infection risk. It must not be treated as acquired neutropenia or as chemotherapy toxicity.
When is the neutrophil count lowest after chemotherapy?
For most cytotoxic regimens the nadir is 7 to 14 days after the dose, with recovery over the following week. A normal count a few days after treatment therefore says nothing about the count at the nadir, which is why a fever is treated on suspicion rather than on the last available result.
Related calculators
References
- National Institute for Health and Care Excellence. Neutropenic sepsis: prevention and management in people with cancer. NICE clinical guideline CG151; 2012.
- Freifeld AG, Bow EJ, Sepkowitz KA, et al. Clinical practice guideline for the use of antimicrobial agents in neutropenic patients with cancer: 2010 update by the Infectious Diseases Society of America. Clin Infect Dis. 2011;52(4):e56–e93.
- Merz LE, Story CM, Achebe MO, et al. Absolute neutrophil count by Duffy status among healthy Black and African American adults. Blood Adv. 2023;7(3):317–320.
- National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE). Version 5.0, 2017; version 6.0, 2025.