Leukemia is a cancer of the bone marrow and blood. The four major types of leukemia are acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL). Myelodisplastic syndrome (MDS) is a premalignant blood disorder that often develops into AML.
All leukemias originate in the bone marrow where a stem cell undergoes a mutation and becomes a leukemic cell. Once this leukemic cell mutates, it multiplies into billions of cells. These cells, called “leukemic blasts”, do not function normally but grow and survive better than normal cells. The presence of the leukemic blasts blocks the production of normal white blood cells which are key for a proper functioning of the immune system. As a result, the number of healthy white blood cells is usually lower than normal, severely affecting a patient’s immunoprotection.
Acute leukemias (AML and ALL) are rapidly progressing diseases whereas chronic leukemias (CML and CLL) usually progress more slowly, with patients having more functional cells for a longer period of time. The difference between those cancer types are also reflected in the differing drug approaches for each type of leukemia.
While people can get leukemia at different ages, it is most common in people over the age of sixty. The most common types of leukemia in adults are AML and CLL. ALL is the most common form of leukemia in children.
The aim of leukemia treatment is to achieve complete remission. This means that after treatment no sign of the disease remains, there are no detectable blasts in the bone marrow, and the patient returns to good health. In general, patients are considered cured after five years of complete remission. Patients with an acute leukemia (ALL and AML) need to start treatment as soon as possible after diagnosis as these diseases progress rapidly, ultimately leading to death.
First and second line treatments for leukemia include high doses of chemotherapy that may be combined with different drugs, such as cytarabine and anthracyclines. The initial phase of chemotherapy is called “induction therapy”. Induction therapy may involve the simultaneous use of multiple drugs or a planned sequence of treatments. The goal of induction therapy is to deplete blood and marrow of leukemic blast cells which will be checked by histopathology (i.e. microscopic examination of tissue). Generally, if blast cells are still evident after the first course of induction chemotherapy, a second course of the same chemotherapy is administered.
Most patients achieve initial remission. However, some patients have residual leukemic cells in their marrow even after intensive treatment. This is referred to as “refractory leukemia”. In other patients leukemic cells reappear. This is referred to as “relapsed leukemia”.
With refractory leukemia, approaches such as using drugs not used in the first course of treatment may be administered in an effort to induce remission. In relapsed patients, further prognosis and treatment will be influenced by the duration of the previous remission, the patient’s age and the cytogenetic findings in the leukemia.
HSCT is generally regarded as the most effective curative approach in post remission therapy for acute leukemia. During HSCT treatment, the bone marrow harboring the leukemic cells is completely destroyed and subsequently replaced with stem cells from a healthy donor.
This procedure is not without inherent risks. The four major risks and limitations that prevent HSCT from broader application are:
- opportunistic infections;
- cancer relapse; and
- limited matched donor availability.
Mitigating the risks associated with HSCT should allow broader use of this therapy for patients with blood cancers.
Recent developments in cell-based immunotherapy have resulted in approaches which may allow more patients with blood cancers to go into remission, including various CAR-T approaches. These patients will then be eligible for curative HSCT.