Several types of cancer can cause low neutrophils, a condition called neutropenia. Blood cancers like leukemia, lymphoma, and multiple myeloma are the most common culprits, but solid tumors that spread to the bone marrow can also drive neutrophil counts down. The mechanism is usually the same: cancer cells crowd out or damage the bone marrow where neutrophils are made. An absolute neutrophil count (ANC) below 1,500 cells per microliter is considered low, with counts below 500 classified as severe and below 100 as profound.
Leukemia
Leukemia is the cancer most closely associated with low neutrophils. In all forms of leukemia, abnormal white blood cells multiply in the bone marrow and displace the normal blood-producing cells. This crowding means the marrow can’t produce enough healthy neutrophils, red blood cells, or platelets. The result is a shortage of functional immune cells even though the total white blood cell count may appear normal or high on a blood test.
Acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL) tend to cause the most dramatic drops because they grow quickly and overwhelm the marrow in a short period. Chronic myeloid leukemia (CML) follows a slower course, but as disease progresses, it replaces normal blood-making cells and increases susceptibility to infections through neutropenia. Chronic lymphocytic leukemia (CLL) can produce a similar effect, particularly in advanced stages.
Myelodysplastic Syndromes
Myelodysplastic syndromes (MDS) are a group of bone marrow cancers that primarily affect older adults. Unlike leukemia, where cells multiply out of control, MDS causes the marrow to produce blood cells that are abnormal and don’t function properly. Neutrophils that do get made are often defective, with reduced ability to fight bacteria.
Neutropenia is one of the hallmark features of MDS. Clinically, an ANC below 1,800 cells per microliter is used as a marker when evaluating for the condition. Studies show that neutrophils in MDS patients have abnormal levels of key infection-fighting enzymes, a sign that even the neutrophils that are present may not work as well as they should. This combination of low numbers and poor function makes MDS patients particularly vulnerable to infections. MDS can also progress to acute leukemia over time, worsening the neutropenia further.
Lymphoma and Multiple Myeloma
Lymphoma and multiple myeloma don’t always start in the bone marrow, but they frequently involve it. When they do, they crowd out normal blood cell production the same way leukemia does.
In multiple myeloma, malignant plasma cells accumulate in the bone marrow and create an environment that suppresses the immune system on multiple fronts. Beyond simply taking up space, these cancer cells release chemical signals that recruit abnormal, immunosuppressive neutrophils to the tumor site. Research published in the journal Blood found that myeloma patients with a high concentration of these altered neutrophils also showed elevated markers of immune exhaustion in their T cells, meaning the cancer undermines immune defense in overlapping ways.
Non-Hodgkin lymphoma and, less commonly, Hodgkin lymphoma can infiltrate the bone marrow and reduce neutrophil production. Large cell lymphomas and other aggressive subtypes are more likely to involve the marrow than slower-growing forms.
Solid Tumors That Spread to Bone Marrow
Cancers that originate outside the blood system can also cause low neutrophils if they metastasize to the bone marrow. A study of 64 patients with bone marrow metastases found that the most common primary cancers were breast (28%), lung (23%), stomach (9%), and prostate (8%). Among these patients, 22% developed neutropenia.
The process is called myelophthisis. When non-blood cancer cells invade the marrow, they physically displace normal stem cells and trigger a fibrotic response. The marrow fills with scar tissue made of collagen and reticulin fibers, replacing the healthy tissue that would normally produce neutrophils, red blood cells, and platelets. The invading cancer cells also release chemical signals that suppress whatever healthy marrow remains. Over time, this can lead to complete bone marrow failure.
Neutropenia from solid tumor spread is less common than anemia or low platelets in these patients, but it’s a serious sign that the marrow is significantly compromised.
Cancer Itself vs. Cancer Treatment
It’s worth distinguishing between neutropenia caused by the cancer and neutropenia caused by treatment. Chemotherapy and radiation therapy are the most common reasons cancer patients develop low neutrophils, because these treatments kill rapidly dividing cells, and bone marrow cells divide quickly. Treatment-related neutropenia is usually temporary and recovers between cycles.
Neutropenia caused by the cancer itself tends to be more persistent. It occurs because the disease is physically disrupting the marrow’s ability to work. Cancers that affect bone marrow directly, like leukemia, lymphoma, and myeloma, are the most likely to cause this type. In many patients, both forces are at play: the cancer damages the marrow, and treatment suppresses it further.
Why Low Neutrophils Matter
Neutrophils are the immune system’s first responders against bacterial and fungal infections. When your count drops below 500, your body loses much of its ability to fight off even common bacteria that normally wouldn’t cause problems. Infections can escalate quickly and may not produce the usual warning signs like redness, swelling, or pus, because there aren’t enough neutrophils to create those responses.
Febrile neutropenia, defined as a fever of 100.4°F or higher sustained for at least an hour with an ANC at or below 500, is a medical emergency. Because the body can’t mount its normal inflammatory response, a fever may be the only early sign of a serious infection. Patients with cancer-related neutropenia who develop a fever need immediate evaluation, as delays can be life-threatening.
How Neutropenia Is Graded
Doctors classify neutropenia by severity based on your ANC:
- Mild: 1,000 to 1,500 cells per microliter
- Moderate: 500 to 1,000
- Severe: below 500
- Profound: below 100
Mild neutropenia often causes no symptoms and may be discovered incidentally on a routine blood test. Moderate neutropenia raises infection risk noticeably. Severe and profound neutropenia carry the highest danger, as even organisms that live harmlessly on your skin or in your gut can cause serious bloodstream infections when your defenses are this low.