Leukemia is a cancer of the blood and bone marrow, the soft material in the center of most bones. Leukemias are named for how quickly the disease develops and gets worse. Acute leukemia is a fast-growing cancer that usually gets worse quickly. Chronic leukemia is a slower-growing cancer that gets worse gradually over time. Leukemia is also named for the type of blood cell that is affected. Leukemia that starts in myeloid cells—the pathway that leads to red blood cells, platelets (cells that clot the blood), or white blood cells known as granulocytes—is called myeloid (or myelogenous/myeloblastic) leukemia. Leukemia that starts in lymphoid cells—which make different types of white blood cells—is called lymphocytic or lymphoblastic leukemia.
There are four main types of leukemia:
- Acute myeloid leukemia (AML)
- Acute lymphocytic leukemia (ALL)
- Chronic myeloid leukemia (CML)
- Chronic lymphocytic leukemia (CLL)
Leukemia occurs most often in adults older than 55 years, but it is the most common cancer in children younger than 15 years. Among adults, the most common types are CLL (35%) and AML (32%). Among children and teens, ALL is the most common, accounting for 75% of pediatric leukemia cases.
In the U.S., over 60,140 new cases of leukemia are expected in 2016, and more than 24,400 deaths will occur. Survival rates vary substantially by leukemia subtype, ranging from a current 5-year relative survival rate of 26.6% for patients diagnosed with AML, to 82.6% for those with CLL. In 2013, there were an estimated 333,975 people living with leukemia in the United States.
Chemotherapy drugs, alone or in combination, are used to treat most types of leukemia. Some leukemia patients may require a hematopoietic stem cell transplant (HSCT) to fully eradicate their disease. In this procedure, high-dose chemotherapy, with or without radiation, is first used to eliminate the patient’s diseased bone marrow. Then bone marrow stem cells from an immunologically matched donor (or from the patient’s own body) are given back to the patient. The transplanted stem cells then grow and repopulate the person’s bone marrow and blood with healthy cells.
Several targeted drugs (e.g., imatinib [Gleevec®], dasatinib [Sprycel®]) are effective for treating CML because they attack cells with the Philadelphia chromosome, the genetic abnormality that is the hallmark of this type of leukemia. Some of these drugs are also FDA-approved to treat a type of ALL involving the same genetic defect. For CLL that is CD20-positive, the monoclonal antibodies rituximab (Rituxan®), ofatumumab (Arzerra®), or obinutuzumab (Gazyva®) can be used in combination with chemotherapy as an initial treatment or as a treatment after disease has recurred. For CLL that is CD52-positive, the monoclonal antibody alemtuzumab (Campath®) may be used.
In 2014, the immunotherapy blinatumomab (Blincyto®) was approved for the treatment of Philadelphia chromosome-negative precursor B cell ALL that is refractory or has recurred. Blincyto is a special type of monoclonal antibody called a bispecific T cell engager (BiTE), consisting of two monoclonal antibodies joined together. One end of the BiTE binds to a molecule on T cells, and the other end binds to a molecule called CD19 on cancer cells; by bringing the two together, the BiTE facilitates cancer cell killing. In addition to its FDA-approved use for Philadelphia chromosome-negative ALL, Blincyto is also being tested in patients with Philadelphia chromosome-positive ALL, where it has also shown promise.
Gemtuzumab ozogamacin (MylotargTM), an anti-CD33 antibody-drug conjugate, is approved for CD33-positive acute myeloid leukemia (AML) in both adults and children who have relapsed as well as in newly diagnosed adults, while the combination of rituximab, an anti-CD20 targeted antibody, and hyaluronidase (Rituxan HycelaTM) has been approved for chronic lymphocytic leukemia (CLL). Most recently, tisagenlecleucel—a CAR T cell immunotherapy targeting the CD19 protein—was approved for children and young adults with ALL.
For those patients who relapse, or are not cured by existing approaches, newer treatments are badly needed.