Dr. Jiao ZONG × Dr. Yuehui LIN: A 5% Blast Count Does Not Automatically Mean Relapse — How to Read a Bone Marrow Report

Summary: Jiao ZONG and Dr. Yuehui LIN of Beijing GoBroad Boren Hospital explain how to read a cell morphology report from both laboratory and clinical perspectives. The article reviews the clinical meaning of differential cell counts and morphologic descriptions, and emphasizes that blasts above 5% are a warning sign rather than proof of relapse. Physiologic factors, medication history, infection, flow cytometry, molecular testing, and other findings must be considered together. The goal is to help patients and families understand common report terminology more accurately and avoid unnecessary panic or misinterpretation.

When patients and families receive a cell morphology report from a bone marrow or peripheral blood smear, the page can feel overwhelming: numbers, symbols, and unfamiliar terms everywhere. Blasts, immature lymphocytes, atypical lymphocytes — what do these terms actually mean, and which findings deserve the most attention?

In this article, Jiao ZONG and Dr. Yuehui LIN of Beijing GoBroad Boren Hospital explain the report from both laboratory and clinical perspectives, helping readers make sense of this important “map” of what may be happening in the blood and bone marrow.

1. What Is Cell Morphology, and Why Is It Tested?

A complete blood count (CBC) tells us how many blood cells are present. Think of looking at a supermarket from far away: you can count how many apples and bananas there are, but you cannot tell whether the fruit is fresh, unripe, or spoiled.

Cell morphology takes a much closer look. Special stains are used to make different cell types and stages of development easier to distinguish. Under a microscope, laboratory specialists assess each cell’s size, shape, internal structure, degree of maturity, and overall appearance, then classify normal, immature, and abnormal cells one by one.

A CBC alone has important limitations. Sometimes cell counts appear to be within the normal range even though the cells themselves are abnormal. Subtle problems such as immaturity or abnormal cell shape may not be visible from blood counts alone.

Cell morphology is often one of the first steps in diagnosis. It can quickly detect abnormalities and help point the clinical team toward a likely benign or malignant process. You can think of it as a signpost: it helps show which direction further testing should take and where the most suspicious findings may be.

During treatment, repeat morphology testing can also provide a direct view of treatment response, bone marrow recovery, and sometimes early warning signs of change.

For example, a patient may initially have blasts and immature lymphoid cells in the bone marrow. After treatment, those cells may gradually disappear. Later, a new group of large, uniform-looking cells may appear. With special cytochemical staining, the laboratory may find that these cells look different from the original disease, raising the possibility of a lineage change. Recognizing this difference early can alert the clinical team and help avoid misinterpretation.

That is the value of morphology: it is not only about whether certain cells are present or how many there are, but also whether they look normal and, most importantly, what kind of cells they are.

2. How Do You Read a Cell Morphology Report, and What Should You Focus On?

A CBC is relatively straightforward, with arrows often showing whether a value is high or low. A morphology report is different. It does not only ask whether a cell count is outside the reference range; the appearance of the cells also matters.

A morphology report generally contains four parts:

◆ Patient information

◆ Differential cell count

◆ Morphologic description

◆ Interpretive conclusion

For a peripheral blood smear, the laboratory specialist classifies 100–200 cells or more and records the proportions of neutrophils, lymphocytes, monocytes, and other cell types.

In normal adult peripheral blood, neutrophils account for about 50%–70%, lymphocytes 20%–40%, and monocytes 3%–8%; eosinophils and basophils are uncommon. In young children, especially those under 6, lymphocytes may physiologically reach 40%–60% without indicating disease.

If a report says “atypical lymphocytes are seen” or “increased lymphocyte proportion,” do not panic. These findings are warning signals, not a diagnosis by themselves. Whether they are clinically significant depends on the overall picture and may require correlation with symptoms, flow cytometry, and molecular testing.

Q1: If Blasts Are Seen, Does That Mean the Disease Has Relapsed?

Cell development is a little like human growth from infancy to adulthood. Blasts are like newborns: only a small number should normally be present in the bone marrow. Immature cells are more like children, while mature cells are like adults.

A small number of blasts can be present in normal bone marrow. If they have a normal appearance and are not increased, they may simply represent normal developing cells.

Q2: What Kind of Blasts Should Raise Concern?

Normal blasts are generally medium-sized, with a regular nucleus and fine chromatin, giving them a relatively uniform, orderly appearance.

Malignant blasts may look different: they can be larger, have irregular nuclei, prominent nucleoli, finely dispersed chromatin, or other abnormal features. Their morphology can therefore provide important clues that the cells may not be normal.

Two things matter most: how many cells there are and what they look like.

From a numerical standpoint, 5% is an important threshold. If blasts in the bone marrow exceed 5%, morphology raises a “yellow flag.” But a blast count at or above 5% on morphology alone does not automatically prove relapse — it means the finding needs further investigation.

Why? Several situations can cause a temporary increase in blast-like or immature cells:

◆ Normal physiologic states: In growing children, the bone marrow can be highly active, and blasts may occasionally reach 5% or even higher without representing disease.

◆ After growth factor treatment or during recovery from chemotherapy: When the marrow responds strongly to granulocyte colony-stimulating factor or recovers after chemotherapy, the blast proportion may temporarily increase as a reactive change.

◆ Infection and certain other conditions: Reactive bone marrow proliferation can sometimes resemble a leukemoid response. Some viral infections may also cause lymphocytes to take on a more immature appearance, even though they are not malignant leukemia cells.

◆ After immunotherapies such as CAR-T: Some reactive lymphocytes may look blast-like under the microscope but are actually part of a normal treatment-related immune response.

This is why morphology is only the first step. The word “abnormal” on a morphology report does not automatically mean the disease has relapsed.

Do Atypical Lymphocytes Always Mean Something Is Wrong?

Not necessarily. “Atypical lymphocytes” are commonly reported, and the term can understandably worry patients and parents.

Normal lymphocytes usually have a fairly regular appearance. Atypical lymphocytes may be larger, have more abundant cytoplasm, and appear irregular. One of the most common reasons is viral infection. After infections such as Epstein-Barr virus (EBV) or cytomegalovirus (CMV), lymphocytes can become activated and change in appearance as part of a normal immune response.

After CAR-T therapy, reports may also describe “a small number of lymphocytes with irregular morphology, abundant cytoplasm, and purplish-red granules.” These cells are often reactive rather than malignant and may return to normal over time.

True leukemic immature lymphoid cells look different. They may be large, have prominent nucleoli, vacuoles, and irregular morphology. These are the cells that require closer attention. Flow cytometry and molecular testing can then be used together to help determine their significance.

Three Tools Together Give the Clearest Answer

A morphology report is best interpreted together with three complementary tools:

◆ Morphology — shows what the cells look like, including both number and appearance.

◆ Flow cytometry — identifies the cell-surface “ID card” by using antibodies to detect specific antigens and helps determine whether a cell population is normal or malignant.

◆ Molecular testing — looks for abnormalities inside the cells, such as mutations or chromosomal rearrangements, providing additional evidence.

The article emphasizes that flow cytometry and molecular testing provide important confirmation of cell identity. Morphology may identify a suspicious population, but the final interpretation of relapse should integrate these findings rather than rely on morphology alone.

So How Should You Interpret the 5% Warning Threshold?

The 5% threshold needs context. The article gives a real example of a healthy child being evaluated as a stem cell donor. On bone marrow examination, immature lymphoid cells accounted for 20%–30% — a surprisingly high proportion — but they were confirmed to be normal B-cell precursors related to the child’s stage of development.

This illustrates that bone marrow activity varies from person to person. In children especially, active growth can be accompanied by a naturally higher proportion of immature cells.

In other words, the identity of the cells matters just as much as the number. If the cells are from the expected lineage and look normal, a somewhat higher proportion may still be benign. If their origin is unclear or their morphology is abnormal, even a small population may deserve further evaluation.

The key message for patients and parents is not to panic simply because a morphology report mentions abnormal cells or blasts. Morphology acts like an early scout: it helps detect and flag possible problems, but the final interpretation should be made together with flow cytometry, molecular testing, and the patient’s clinical context.