Leukemia: Types, Symptoms, Diagnosis, and Modern Treatments

What is Leukemia?

Leukemia is a cancer that originates in the blood-forming cells of the body. The term does not refer to a single disease, but rather to a large family of malignancies that can first be distinguished by their speed of progression:

• In acute forms, the number of cancer cells increases rapidly, and symptoms develop quickly and severely.
• In chronic forms, malignant cells tend to proliferate more slowly, and the disease may remain silent for extended periods without obvious symptoms.

Taken together, leukemia affects children far more often than most people realize. In fact, acute leukemias are the most common childhood cancer. Chronic forms, however, are more prevalent in adults.

Early symptoms vary depending on the specific type of leukemia. Unfortunately, many cases are initially asymptomatic or present with vague, non-specific complaints. For example, patients may experience persistent fatigue that does not resolve, which makes early diagnosis challenging.

Modern treatment offers numerous options tailored to each individual case:

• Watchful waiting (active surveillance)
• Chemotherapy
• Targeted molecular therapy
• Biological therapy (immunotherapy)
• Radiation therapy
• Stem cell transplantation

The choice among these depends on the specific type of leukemia, the patient’s age and overall health, and the aggressiveness of the disease. Prognosis likewise varies considerably by type and age. Unfortunately, it is rarely possible to prevent leukemia, as the triggering causes are almost always unknown.

Fulminating Leukemia

The term fulminating leukemia, though not a formal medical classification, refers to acute cases that follow an especially rapid and life-threatening course. A prime example is acute promyelocytic leukemia (APL), considered the most aggressive subtype of blood cancer. If not diagnosed and treated immediately, it can be fatal within days.

Initial symptoms typically include:

• Cutaneous hemorrhages (nosebleeds, bleeding gums, gastrointestinal bleeding)
• Severe fatigue
• General malaise

For more detail on APL specifically, refer to our dedicated article on fulminating leukemia.

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Causes

When receiving a leukemia diagnosis, it’s natural to ask why. However, in most cases, no single identifiable cause can be found. Doctors can rarely determine with certainty why a specific individual develops leukemia.

However, research has identified several risk factors that increase the likelihood of developing the disease. These likely differ between leukemia subtypes:

Radiation Exposure

People exposed to high doses of ionizing radiation have a significantly increased risk of developing acute myeloid leukemia (AML), chronic myeloid leukemia (CML), or acute lymphocytic leukemia (ALL). Historical examples include survivors of the atomic bomb explosions in Japan during World War II. Children, in particular, showed dramatically elevated rates of leukemia in the years that followed.

• Radiation therapy (radiotherapy): Used to treat cancer and other diseases, radiotherapy itself increases leukemia risk and is therefore prescribed only when the benefit clearly outweighs this risk.
• Diagnostic imaging (X-rays, CT scans): These expose patients to very low doses of radiation. Whether repeated imaging during childhood is linked to leukemia risk remains under investigation. However, current evidence suggests that any risk, if it exists at all, is very small.

Chemical Exposure

• Tobacco smoke: Smoking increases the risk of acute myeloid leukemia.
• Benzene: Occupational exposure to benzene, a chemical widely used in industrial manufacturing and also found in cigarette smoke and diesel fuel, is associated with myeloid leukemia, CML, and ALL.

Prior Chemotherapy

Patients treated with certain chemotherapeutic agents for other cancers may later develop AML or ALL. Drugs such as alkylating agents and topoisomerase inhibitors carry a small but recognized risk of secondary leukemia years after treatment.

Underlying Medical Conditions and Genetic Factors

• Down syndrome and other hereditary disorders: These significantly increase leukemia risk.
• Myelodysplasia and other blood disorders: Pre-existing blood conditions increase the risk of AML.
• HTLV-I virus (Human T-lymphotropic virus type 1): Infection with this virus raises the risk of a rare form called T-cell leukemia. Importantly, like all leukemias, this is not contagious.

Family History

Leukemia within a family is uncommon, but when it does occur, it most often involves chronic lymphocytic leukemia (CLL). Even so, only a small proportion of CLL patients have a first-degree relative with the same condition.

Important: Having one or more risk factors does not mean that a person will necessarily develop leukemia.

An Intriguing Scientific Hypothesis: The “Hygiene Theory”

A compelling and widely debated hypothesis, supported by a study published in Nature, suggests that paradoxically, certain leukemias may be triggered not by a specific infection but by the absence of childhood infections. The research was motivated by the observation that leukemia rates are higher in industrialized countries, and points to a complex interplay between genetic predisposition and the early-life immune environment.

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Blood Cells: How They Work

To understand leukemia, it helps to understand how blood cells are normally produced.

Most blood cells originate from stem cells located in the bone marrow, which is the spongy tissue found at the center of most bones. As these stem cells mature, they differentiate into three main types of blood cells, each with a specific function:

• White blood cells (leukocytes): Fight infections. Several subtypes exist with different roles.
• Red blood cells (erythrocytes): Transport oxygen to the body’s tissues.
• Platelets (thrombocytes): Enable blood clotting to stop bleeding.

Blood stem cells follow two main developmental pathways:

• Myeloid lineage: gives rise to myeloblasts, which mature into red blood cells, platelets, and several types of white blood cells (neutrophils, eosinophils, basophils, monocytes)
• Lymphoid lineage: gives rise to lymphoblasts, which mature into lymphocytes (B cells, T cells, NK cells)

When blood cells age or become damaged, they die and are replaced by new ones. This process is finely regulated, but in leukemia, it becomes disrupted.

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How Leukemia Cells Behave

In patients with leukemia, the bone marrow produces abnormal white blood cells (cancer cells). Unlike normal white blood cells, these malignant cells do not die when they should. Instead, they accumulate, crowding out healthy white blood cells, red blood cells, and platelets. This progressive displacement of normal blood cells is what leads to the symptoms of leukemia.

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Types of Leukemia

Leukemias are classified using two key criteria:

1. Speed of progression:

• Chronic leukemia: In early stages, cancer cells can still partially perform the functions of normal white blood cells. Patients may have no symptoms initially, and diagnosis may happen incidentally during routine blood tests. Symptoms appear gradually as the disease progresses.
• Acute leukemia: Cancer cells cannot function as normal white blood cells. They multiply rapidly, and the disease worsens very quickly without treatment.

2. Type of white blood cell affected:

• Lymphoid (lymphocytic/lymphoblastic) leukemia: Originates from lymphoid precursor cells.
• Myeloid (myelogenous/myeloblastic) leukemia: Originates from myeloid precursor cells.

Combining these two criteria gives the four main subtypes:

• CLL is the most common leukemia in adults in Western countries, accounting for over 15,000 new cases per year in the United States alone. It rarely affects children.
• CML causes approximately 5,000 cases per year in the US and primarily affects adults.
• ALL is the most frequent leukemia in children, though it can affect adults too, causing over 5,000 cases per year in the US.
• AML affects both adults and children, with over 13,000 new cases per year in the US.

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Symptoms

Because leukemia cells circulate through the body like normal blood cells, they can accumulate in virtually any tissue or organ. The symptoms depend on the number of cancer cells present and where they accumulate.

Patients with chronic leukemia may have no symptoms at all for years, with diagnosis occurring incidentally during routine check-ups. Patients with acute leukemia usually seek medical attention because they feel acutely unwell.

Central Nervous System Involvement

If leukemia cells reach the brain, symptoms may include:

• Headache
• Vomiting
• Mental confusion
• Loss of muscle control
• Seizures (convulsions)

Other Organ Involvement

Leukemia can also affect the:

• Digestive system
• Kidneys
• Lungs
• Heart
• Testicles

Common Symptoms Across Leukemia Types

• Painless swelling of lymph nodes (especially in the neck or armpits)
• Fever
• Night sweats
• Frequent infections
• Muscle weakness
• Persistent fatigue
• Abnormal bleeding and/or bruising, such as bleeding gums, skin bruises, or tiny red spots under the skin (also called petechiae), can be concerning. Learn more about petechiae here
• Abdominal swelling or discomfort (enlarged spleen or liver)
• Unexplained weight loss
• Bone or joint pain

🩺 Note: These symptoms are largely non-specific and in the vast majority of cases are not caused by leukemia. However, anyone experiencing a persistent combination of these symptoms should see their doctor promptly so that the cause can be identified and treated as early as possible.

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Survival Rates and Epidemiology

Leukemia is a relatively common group of blood cancers, with incidence varying by age, sex, and geographic region. Survival rates have improved dramatically over the past two decades, driven largely by advances in targeted molecular therapies and immunotherapy:

• For chronic forms such as CML, life expectancy for most patients is now comparable to that of the general population, thanks to highly effective oral targeted drugs.
• For acute leukemias, survival varies significantly:
  • In children with ALL, the 5-year survival rate approaches 90%.
  • In adults with acute leukemias, outcomes depend heavily on the specific genetic mutations present, the patient’s age, and how quickly treatment is initiated.

Early diagnosis remains the single most important factor in improving outcomes.

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Diagnosis

The modern diagnostic pathway for leukemia is multidisciplinary and aims not only to confirm the presence of cancer. It also seeks to precisely characterize the disease’s genetic and molecular identity, as this information is essential for selecting the most effective personalized treatment.

Clinical Assessment and Blood Tests

The first suspicion often arises from a routine complete blood count (CBC). In leukemia, blood tests may show:

• An abnormal white blood cell count, either dramatically elevated or, paradoxically, very low, can indicate underlying health issues
• Reduced platelet count (thrombocytopenia)
• Reduced hemoglobin and red blood cell count (anemia)

A peripheral blood smear is also performed. During this test, a drop of blood is examined under a microscope to look for blasts, which are immature, abnormal cells. These cells should not normally appear in the circulating blood.

Bone Marrow Analysis

If blood tests raise suspicion of leukemia, examination of the bone marrow is essential. Two types of samples are usually collected from the iliac crest (the pelvic bone):

• Aspirate (needle aspiration): A small amount of liquid bone marrow is extracted.
• Trephine biopsy: A small solid core of bone and marrow tissue is removed for histological analysis.

These samples are subjected to advanced tests that represent today’s diagnostic gold standard:

• Immunophenotyping (Flow Cytometry): Identifies proteins on the surface of cells to definitively distinguish between lymphoid and myeloid subtypes.
• Cytogenetics (Karyotyping): This test analyzes chromosome structure to detect specific abnormalities, such as the Philadelphia chromosome, which is characteristic of CML.
• Molecular diagnostics (Next-Generation Sequencing, NGS): Sequences the DNA of leukemic cells to identify specific mutations (e.g., FLT3, NPM1, IDH1/2 in AML; BCR-ABL in CML) that guide prognosis and the selection of targeted drugs.

Further Investigations and Staging

To assess whether the disease has spread beyond the blood and bone marrow:

• Lumbar puncture (spinal tap): Examines cerebrospinal fluid for the presence of leukemic cells that may have reached the central nervous system.
• Imaging studies: Abdominal ultrasound to evaluate the liver and spleen; CT scan to assess deep lymph nodes in the chest and abdomen.

A critically important component of modern leukemia diagnosis and monitoring is the assessment of Minimal Residual Disease (MRD). This involves detecting infinitesimally small numbers of remaining leukemic cells, which are invisible under a microscope but can be identified using ultra-sensitive molecular techniques. MRD status is now used to evaluate treatment response and predict relapse risk.

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Treatment

The therapeutic landscape for leukemia has been revolutionized over the past decade, evolving from protocols based almost exclusively on chemotherapy toward a precision medicine approach that integrates targeted biological agents and immunotherapies.

Goals of Therapy and Overview of Options

The primary goal is to achieve complete remission, which means the disappearance of all clinical and instrumental signs of disease. Available treatment options include:

• Chemotherapy: Remains the backbone of treatment for many acute leukemias.
• Targeted molecular therapy: “Smart” drugs that selectively attack cells carrying specific genetic mutations, sparing healthy tissue.
• Immunotherapy and CAR-T cell therapy: Treatments that harness and engineer the patient’s own immune system to recognize and destroy leukemia cells.
• Stem cell transplantation: Used to consolidate cure or in high-risk relapse situations.
• Watchful waiting (Watch and Wait): Active monitoring without treatment, reserved for selected asymptomatic chronic leukemias.

Treatment of Acute Leukemias

In acute forms (ALL and AML), treatment must be initiated urgently and is structured in phases:

1. Induction: An intensive initial phase aimed at eliminating the vast majority of leukemic cells and achieving remission.
2. Consolidation: Additional treatment cycles to eradicate residual invisible disease (as detected by MRD).
3. Maintenance: Low-dose, prolonged therapy is used to prevent relapse, and this is particularly important in ALL.

For older or frail patients who cannot tolerate intensive chemotherapy, newer drug combinations now offer excellent outcomes with significantly reduced toxicity. These include BCL-2 inhibitors, such as venetoclax, combined with hypomethylating agents.

Treatment of Chronic Leukemias

For chronic forms (CLL and CML), treatment often aims to manage the disease as a long-term chronic condition:

• Chronic Myeloid Leukemia (CML): The introduction of tyrosine kinase inhibitors (TKIs), oral targeted drugs like imatinib, dasatinib, or nilotinib, has transformed CML. The majority of patients can now live essentially normal lives, with disease reduced to undetectable levels. A proportion of patients who achieve deep molecular remission may even be able to safely discontinue treatment under close monitoring.

• Chronic Lymphocytic Leukemia (CLL): Asymptomatic patients are frequently managed with watchful waiting, a strategy of active surveillance without treatment. Therapy begins only when signs of disease progression appear. When treatment is required, modern protocols rely predominantly on monoclonal antibodies (e.g., rituximab, obinutuzumab) and targeted inhibitors (BTK inhibitors such as ibrutinib or acalabrutinib; BCL-2 inhibitors such as venetoclax), dramatically reducing the role of conventional chemotherapy.

Innovative Frontiers: CAR-T Cells and Bispecific Antibodies

For patients who do not respond to conventional therapies or experience relapse, modern hematology offers two transformative approaches:

CAR-T cell therapy involves:

1. Collecting the patient’s own T lymphocytes (a type of white blood cell)
2. Genetically engineering them in the laboratory to express a Chimeric Antigen Receptor (CAR) that specifically recognizes leukemia cells
3. Re-infusing the engineered cells back into the patient, where they seek out and destroy tumor cells

CAR-T therapy has achieved remarkable responses, including long-term remissions, in patients with relapsed or refractory ALL and CLL.

Bispecific antibodies are engineered proteins that simultaneously bind to a protein on the cancer cell and to a T lymphocyte, physically bridging the two and facilitating immune-mediated destruction of the tumor. Agents such as blinatumomab are already established in ALL treatment.

The Role of Stem Cell Transplantation

Stem cell transplantation, particularly allogeneic transplantation (which uses cells from a compatible donor), remains the definitive curative strategy for high-risk patients. The procedure replaces the diseased bone marrow with healthy donor stem cells. These cells can rebuild a fully functional immune system, one that recognizes and eliminates any residual leukemia cells. This process is known as the graft-versus-leukemia (GvL) effect.

Lifestyle and Supportive Care During Treatment

The success of leukemia therapy depends not only on the drugs used, but on the overall wellbeing of the patient:

• Nutrition: A balanced diet that is safe from a microbiological standpoint is essential during periods of immunosuppression, to minimize infection risk.
• Physical activity: Even gentle exercise, like walks or low-impact gymnastics, significantly helps combat cancer-related fatigue and improves psychological resilience during treatment.
• Psychological support: Addressing the emotional and mental health impact of a leukemia diagnosis is now recognized as an integral part of modern care protocols.

Management of complications is highly effective today. Transfusion support addresses anemia and hemorrhagic risk; prophylactic antibiotics and antifungals prevent life-threatening infections during periods of bone marrow suppression. Oral care, including the prevention and treatment of mucositis, is also a critical component of supportive management.

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Frequently Asked Questions

What is leukemia?

Leukemia is the collective term for a group of cancers that originate in the blood-forming cells of the bone marrow. Rather than a single disease, it encompasses multiple subtypes that differ in their behavior, speed of progression, and the type of blood cell affected.

What causes leukemia?

Unfortunately, in the majority of patients the precise cause is unknown. Identified risk factors include:

• Prior chemotherapy or radiation therapy
• Family history and inherited genetic abnormalities (e.g., Down syndrome, Fanconi anemia)
• Exposure to specific environmental pollutants (e.g., benzene)
• Tobacco smoking

What are the most common symptoms of leukemia?

The most frequent symptoms include:

• Fever and chills
• Persistent fatigue and weakness
• Frequent infections
• Unexplained weight loss
• Swollen lymph nodes, spleen, or liver
• Unexplained bleeding or bruising
• Petechiae (tiny red or purple spots on the skin)
• Night sweats
• Bone or joint pain

How is leukemia diagnosed?

Diagnosis typically involves:

• Physical examination: checking for lymph node enlargement, spleen or liver swelling
• Blood tests (often the first abnormality detected, sometimes incidentally during routine check-ups)
• Bone marrow biopsy and aspiration: the definitive diagnostic test
• Advanced molecular and genetic testing: to characterize the specific subtype and guide treatment
• Additional tests as needed: lumbar puncture, CT scan, ultrasound, PET scan

How is leukemia treated?

Treatment is planned by a multidisciplinary team and tailored to the specific leukemia type and the patient’s individual characteristics. It may include:

• Chemotherapy
• Targeted molecular therapy (e.g., tyrosine kinase inhibitors)
• Immunotherapy (e.g., monoclonal antibodies, bispecific antibodies)
• CAR-T cell therapy
• Radiation therapy
• Stem cell (bone marrow) transplantation
• Watchful waiting (for selected asymptomatic chronic leukemias)

What is the survival rate for leukemia?

Survival rates vary enormously depending on the type of leukemia, the patient’s age, and overall health. Considering all leukemia types together:

• In children with lymphoid leukemias (ALL), the 5-year survival rate is approximately 90%.
• In adults, the overall 5-year survival rate across all leukemia types is approximately 45%. However, this figure hides significant variation. Outcomes range from near-normal life expectancy in well-controlled CML to more challenging results in some AML subtypes.

Prognosis has improved substantially in recent years thanks to targeted therapies and immunotherapy.

How does leukemia cause death?

Death from leukemia can result from several causes, often in combination:

• Hemorrhage (e.g., hemorrhagic stroke caused by severe thrombocytopenia)
• Complications of severe anemia
• Serious infections (e.g., pneumonia, sepsis) caused by immune system failure
• Organ failure when the body can no longer sustain vital functions

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Sources and Bibliography

• National Cancer Institute (NCI) – Leukemia
• AIRC – Leucemia (Italian Association for Cancer Research)
• Greaves M. A causal mechanism for childhood acute lymphoblastic leukaemia. Nature Reviews Cancer. 2018;18(8):471–484.
• Döhner H, et al. Diagnosis and management of AML in adults: 2022 ELN recommendations. Blood. 2022;140(12):1345–1377.
• Sanz MA, et al. Management of acute promyelocytic leukemia: updated recommendations from the European LeukemiaNet. Blood. 2019;133(15):1630–1643.
• American Society of Hematology (ASH). Leukemia resources.
• Canadian Virtual Hospice. Understanding dying from leukemia.