Leukemia

Leukemia. It is a group of blood cancers that usually originate in the bone marrow and result in high numbers of abnormal white blood cells. These malignant cells, known as blasts, are not fully developed and crowd out healthy blood-forming cells, leading to complications. The disease is a major focus of research within global institutions like the National Cancer Institute and the World Health Organization.

Classification

The primary classification is based on the speed of progression and the type of blood cell affected. Acute leukemia progresses rapidly and involves immature cells, while chronic leukemia progresses more slowly and involves more mature cells. The main lineages are lymphoblastic leukemia, affecting lymphocytes, and myeloid leukemia, affecting myeloid cells. The French-American-British (FAB) classification system was historically significant, though contemporary diagnosis relies heavily on the World Health Organization classification of tumours of haematopoietic and lymphoid tissues. Specific entities include acute lymphoblastic leukemia, common in children, and chronic lymphocytic leukemia, frequently seen in adults in regions like North America.

Signs and symptoms

Common manifestations result from bone marrow failure and infiltration of organs by leukemic cells. Symptoms often include fatigue, fever, and frequent infections due to a lack of functional white blood cells. Pallor and dyspnea can occur from anemia, while petechiae and bleeding arise from thrombocytopenia. Organ infiltration may cause hepatomegaly, splenomegaly, and lymphadenopathy. Patients with certain types, like acute promyelocytic leukemia, are at high risk for life-threatening complications such as disseminated intravascular coagulation.

Causes and risk factors

The exact cause is often unknown but involves genetic mutations in hematopoietic stem cells. A well-established risk factor is exposure to high-dose ionizing radiation, as studied in survivors of the Atomic bombings of Hiroshima and Nagasaki. Certain chemical substances like benzene are also associated with increased risk. Genetic syndromes such as Down syndrome, Fanconi anemia, and Li-Fraumeni syndrome predispose individuals. Previous treatment with alkylating agents or topoisomerase inhibitor chemotherapy for other cancers can lead to therapy-related leukemia. The role of viruses is implicated in specific adult T-cell leukemia linked to HTLV-1.

Diagnosis

Diagnosis begins with a complete blood count and examination of a blood film on peripheral blood smear, which may show circulating blasts. The definitive test is bone marrow examination, typically an aspirate and biopsy performed at the posterior iliac crest. Flow cytometry is essential for immunophenotyping to determine the cell lineage. Cytogenetics, including karyotype analysis and fluorescence in situ hybridization, identifies chromosomal abnormalities like the Philadelphia chromosome. Polymerase chain reaction tests detect specific genetic mutations, such as in the NPM1 gene, which informs prognosis and treatment.

Treatment

Treatment strategies vary drastically by type, patient age, and genetic features. The mainstay for acute leukemias is intensive chemotherapy, often following protocols like those from the Berlin-Frankfurt-Münster group. Allogeneic stem cell transplantation is a potentially curative option for high-risk patients. Targeted therapy has revolutionized treatment; agents like imatinib for Philadelphia chromosome-positive disease and venetoclax for chronic lymphocytic leukemia are examples. Acute promyelocytic leukemia is uniquely treated with all-trans retinoic acid and arsenic trioxide. Supportive care includes blood transfusions and management of tumor lysis syndrome.

Prognosis

Prognosis is highly variable. In pediatric acute lymphoblastic leukemia, cure rates in developed countries can exceed 90% with modern protocols from cooperative groups like the Children's Oncology Group. Outcomes for acute myeloid leukemia are more heterogeneous and depend on factors like age and cytogenetics. The presence of mutations in genes like FLT3 often confers a poorer prognosis. For chronic leukemias, such as chronic myeloid leukemia, the advent of tyrosine kinase inhibitors has transformed the disease into a chronic condition for many, with survival approaching that of the general population. Ongoing research by entities like the European LeukemiaNet continues to refine prognostic models.