Leukemia: Types and Treatment

What is leukemia?

Leukemia is a cancer of the blood or blood cells. There are a few types of leukemia. These types are classified by how quickly they progress (acute vs. chronic) and which cells they affect. Cells affected by leukemia are made in your bone marrow.

Bone marrow is a spongy area in the center of bones. Larger bones have more bone marrow. This means they make more cells. Larger bones are the femur (top part of the leg or thigh), the hip bones, and parts of the rib cage. There are some cells in the bone marrow that are still developing and are not yet mature. These cells are called “blasts.” Once the cell has matured, it moves out of the bone marrow and into the bloodstream. The body knows when more cells are needed and then makes them.

In leukemia, a certain type of blood cell does not work as it should (most often a white blood cell). The body makes too many of these cells. When looked at under a microscope, these cells look different than the healthy cells and do not work the way they should. The body keeps making these non-working cells, leaving little space for healthy cells. This imbalance of healthy and unhealthy cells causes symptoms of leukemia:

• Fever or chills.
• Fatigue and/or weakness that does not get better.
• Frequent or severe infections.
• Losing weight without trying.
• Swollen lymph nodes.
• Enlarged liver or spleen.
• Easy bleeding or bruising.
• Frequent nosebleeds.
• Tiny red spots on your skin (petechiae).
• Sweating a lot, especially at night.
• Bone pain or tenderness.

Most cancers are staged based on where the cancer started, how big the tumor is, and where it has spread (metastasized). Leukemia is a cancer of the blood and is not staged like most cancers. Most leukemias are classified into types instead of stages. When deciding treatment for your leukemia, your provider will look at:

• Blood cell counts.
• Your age.
• If your liver or spleen is larger than normal.
• If you have had any blood disorders or cancers in the past.
• Any gene mutations you may have.

What are the types of leukemia?

There are a few subtypes of leukemia, based on which cells are affected in the bone marrow. Some of them are staged and others are not.

Acute Lymphocytic Leukemia (ALL)

ALL is classified using the World Health Organization (WHO) system. ALL can affect B cells and T cells. You may hear your care team call your ALL by the changes seen in the genes and chromosomes. ALL is divided into several groups:

• B-cell ALL with certain gene or chromosome changes.
  • B-cell ALL with hypodiploidy (the leukemia cells have fewer than 44 chromosomes).
  • B-cell ALL with hyperdiploidy (the leukemia cells have more than 50 chromosomes).
  • B-cell ALL with a translocation between chromosomes 9 and 22 [t(9;22)] (the Philadelphia chromosome).
  • B-cell ALL with a translocation between chromosome 11 and another chromosome.
  • B-cell ALL with a translocation between chromosomes 12 and 21 [t(12;21)].
  • B-cell ALL with a translocation between chromosomes 1 and 19 [t(1;19].
  • B-cell ALL with a translocation between chromosomes 5 and 14 [t(5;14)].
  • B-cell ALL with amplification (too many copies) of a portion of chromosome 21 (iAMP21).
  • B-cell ALL with translocations involving certain tyrosine kinases or cytokine receptors (also known as “BCR-ABL1–like ALL”).
• B-cell ALL, not otherwise specified.

Acute Myelogenous Leukemia (AML)

AML may also be called acute myelocytic leukemia, acute granulocytic leukemia, or acute non-lymphocytic leukemia. Two systems that have been used to classify AML are the French-American-British (FAB) classification and the newer World Health Organization (WHO) classification. This article will focus on the World Health Organization (WHO) system:

• AML with certain genetic abnormalities (gene or chromosome changes)
  • AML with a translocation between chromosomes 8 and 21 [t(8;21)].
  • AML with a translocation or inversion in chromosome 16 [t(16;16) or inv(16)].
  • APL with the PML-RARA fusion gene.
  • AML with a translocation between chromosomes 9 and 11 [t(9;11)].
  • AML with a translocation between chromosomes 6 and 9 [t(6:9)].
  • AML with a translocation or inversion in chromosome 3 [t(3;3) or inv(3)].
  • AML (megakaryoblastic) with a translocation between chromosomes 1 and 22 [t(1:22)].
  • AML with the BCR-ABL1 (BCR-ABL) fusion gene.
  • AML with mutated NPM1 gene.
  • AML with biallelic mutations of the CEBPA gene (that is, mutations in both copies of the gene).
  • AML with mutated RUNX1 gene.
• AML with myelodysplasia-related changes.
• AML related to previous chemotherapy or radiation.
• AML not otherwise specified (This includes cases of AML that don’t fall into one of the above groups).
  • AML with minimal differentiation (FAB M0).
  • AML without maturation (FAB M1).
  • AML with maturation (FAB M2).
  • Acute myelomonocytic leukemia (FAB M4).
  • Acute monoblastic/monocytic leukemia (FAB M5).
  • Pure erythroid leukemia (FAB M6).
  • Acute megakaryoblastic leukemia (FAB M7).
  • Acute basophilic leukemia.
  • Acute panmyelosis with fibrosis.
  • Myeloid sarcoma (also known as granulocytic sarcoma or chloroma).
• Myeloid proliferations related to Down syndrome.
• Undifferentiated and biphenotypic acute leukemias are leukemias that have both lymphocytic and myeloid features. They are sometimes called mixed phenotype acute leukemias (MPALs). 

Chronic lymphocytic leukemia (CLL)

There are two different staging systems for CLL:

Rai Staging System- Based on results of blood tests (especially the number of white blood cells) and physical exam.

In each stage, there is lymphocytosis. Lymphocytosis is a higher-than-normal white blood cell (WBC) count. The extra WBCs are found in the blood and bone marrow.

• Stage 0: Lymphocytosis but no enlargement of lymph nodes, spleen, or liver, and red blood cell and platelet counts are almost normal.
• Stage I: Lymphocytosis with enlarged lymph nodes. The spleen and liver are not affected, and red blood cell and platelet counts are almost normal.
• Stage II: Lymphocytosis with an enlarged spleen and in some cases an enlarged liver. Lymph nodes may or may not be enlarged. Red blood cell and platelet counts are almost normal.
• Stage III: Lymphocytosis plus the lymph nodes, spleen or liver may or may not be enlarged. Red blood cell count is low, and platelets are near normal.
• Stage IV: Lymphocytosis plus enlarged lymph nodes, spleen, or liver. Red blood cell counts may be low or near normal and the platelet count is low.

Each stage is also put into a risk group that helps decide which treatments are best:

• Stage 0: Low risk.
• Stage I and II: Intermediate (middle) risk.
• Stage III and IV: High Risk.

Binet Staging System- Based on the number of affected lymphoid tissue groups and if you have anemia or thrombocytopenia.

The Binet system looks at lymphoid tissue, anemia, and thrombocytopenia. Lymphoid tissue groups include the neck lymph nodes, groin lymph nodes, underarm lymph nodes, spleen, and liver. 

• Stage A: Fewer than 2 areas of lymphoid tissue are enlarged, no anemia, and no thrombocytopenia.
• Stage B: 3 or more areas of enlarged lymphoid tissue, no anemia, and no thrombocytopenia.
• Stage C: Any number of lymphoid areas are enlarged, and anemia and thrombocytopenia are present.

Chronic myelogenous leukemia (CML)

CML is broken down into three phases. The phases are based mainly on the number of immature white blood cells (blasts) in the blood or bone marrow. There is no set system for CML, but common classifications (by the World Health Organization) are:

• Chronic: Less than 10% blasts in the blood or bone marrow. This phase often causes fairly mild symptoms, if any. Most patients are diagnosed in the chronic phase.
• Accelerated: 15% - 29% blasts in the blood. Basophils make up 20% and blasts and promyelocytes make up 30% or more of the blood. There are also very low platelet counts that are not caused by treatment. There are new chromosome changes in the leukemia cells with the Philadelphia chromosome. There may be symptoms such as fever, poor appetite, and weight loss.
• Blast (also called acute phase or blast crisis): 20% or more blast cells in the blood. This is the most aggressive phase of the disease. The blast cells have spread to tissues and organs outside the bone marrow. Symptoms may include fever, poor appetite, and weight loss. 

For more detailed information about the types of leukemia, visit our leukemia section at Oncolink.org.

How is leukemia treated?

Treatment for leukemia depends on many factors, such as your age and overall health, the type of leukemia you have, and whether it has spread to other parts of your body, including the central nervous system (CNS). Your treatment may include some or all of the following:

• Chemotherapy.
• Targeted therapy.
• Immunotherapy.
• Radiation therapy.
• Bone marrow transplant.
• CAR-T cell therapy.
• Clinical trials.

Talk with your care team about the subtype of leukemia you have, which stage or phase it is, and what the best treatment options are for you. For more information, read more about each leukemia subtype at OncoLink.org.