by Peter H. Wiernik, MD
Chairman of "Team Leukemia"
Our Lady of Mercy Cancer Center, New York Medical College, Bronx, New York, USA
(adapted from the Encyclopedia of Life Sciences, Macmillan Reference, Ltd.,In press, 2001)
The leukemias and lymphomas are neoplastic diseases of the blood and blood forming organs that are highly treatable and often curable. They cause bone marrow and immune system dysfunction, which renders the host highly susceptible to infection and bleeding. Often organ dysfunction secondary to tumor cell infiltration or tumor compression of vital structures may be apparent clinically. Tumor formation and organomegaly are more common with the lymphomas than with leukemias.
The major subtypes of leukemia are lymphoid and myeloid, which are further sub-classified into acute and chronic. Acute leukemias usually have a fulminant course if untreated and chronic leukemias are characteristically more indolent.
Acute lymphocytes take leukemia (ALL)
ALL occurs at all ages but is most frequently diagnosed during childhood. The cause is obscure in the vast majority of patients, but one rare form of the disease prevalent in Japan and the Caribbean, and known as the T-cell leukemia-lymphoma syndrome is caused by a retrovirus known as HTL. V I I I. Often there is a viral-like prodrome of fever, sore throat and lethargy that appears weeks before the diagnosis of ALL and completely resolves with symptomatic treatment.
Approximately 80% of ALL patients have B-ALL and the others, T-ALL. B-ALL cells are terminal deoxyneucleotidyl transferasepositive (TdT+) except in the most immunophenotypically mature cases, which are usually associated with a cytogenetic translocations involving chromosome 8. Earlier B-ALL associated with the Philadelphia chromosome is CD 34+, CD 10+, and CD 25+. Serial immunophenotypic studies by flow cytometry during remission are useful in detecting early relapse.
With modern treatment approximately 90% of children with ALL will obtain a complete clinical and hematologic remission and 60 to 75% will literally cured without serious longer-term complications of cure, but premature heart disease may develop years after treatment with potent drugs belonging to the anthracycline class DNA intercalators.
Acute myelocytic leukemia (AML)
AML is the most common acute leukemia in the immediate perinatal period, but the vast majority of cases occur in adults in which the incidence increases with each decade of life. AML occurs with roughly equal frequency throughout the world and its cause is in most patients is unknown. Exposure to ionizing radiation can be an etiologic factor as evidenced by the increased incidence in Japan after the atomic bomb blasts in which the incidence of ALL was directly related to the radiation dose received. Exposure to high concentrations of benzene in the air for prolonged periods of time has also been demonstrated to be a rare cause. Smoking is associated with a higher incidence of AML, possibly due to increased benzene exposure. Certain drugs used to treat cancer such as alkylating agents and topoisomerase II inhibitors have been associated with an increased incidence of AML in survivors.
Chronic lymphocytic leukemia (CLL)
CLL is the most common leukemia of older adults. While it is occasionally diagnosed in the fifth decade of life, incidence increases steadily with each succeeding decade. It is more common in males than females and rare in the Orient. Its cause is unknown, but many familial clusters have been reported which suggests that in some families at least, heredity may play a role. Most patients with
CLL have a B-cell disorder (B-CLL) and the minority have T-cell disease (T-CLL). Therefore, in the typical chronic lymphocytic leukemia patient, B cells accumulate in the blood as the disease progresses and the patient becomes progressively devoid of circulating T-cells. Monoclonality for surface Ig light chain is the strongest indication of B-cell malignancy.
Chronic myelocytic leukemia (CML)
The etiology of CML is unknown for most patients although it is clear that exposure to ionizing radiation and some chemicals (benzene) can cause the disease. This is a disease of adulthood.
Other related disorders
The myelodysplastic syndrome (MDS) includes a group of leukemia-like disorders that may be confused with ALL. Patients may give a history of prior chemotherapy treatment, radiation exposure, or exposure to benzene. MDS behaves much like a slowly evolving AML and occurs primarily in the elderly. MDS is more common than AML worldwide and is more common in males. Refractory anemia eventually requiring blood transfusion may be the only manifestation. However, when bone marrow cytogenetic aberrations are found, the disease usually progresses over a number of years to an acute leukemia, which is a generally refractory to treatment. Patients with MDS usually have pancytopenia, and circulating granulocytes often have abnormal morphology and some degree of immaturity.
The bone marrow is often hypocellular, and myeloblasts are not found in sufficient numbers to make a diagnosis of AML. Patients may survive for many years with supportive care alone.
Myeloid metaplasia and myelofibrosis is a syndrome usually diagnosed in middle-aged and elderly individuals, and this associated with massive hepatosplenomegaly. The white blood cell count is usually elevated but may be normal or low, and the differential white blood cell count demonstrates various degrees of granulocyte immaturity. However, blast cells are usually absent or few. Thrombocytopenia and anemia are common and are often severe. The bone marrow biopsy demonstrates extensive myelofibrosis and little normal hematopoiesis. The disease relentlessly progresses over 2 or 3 years and infection and/or hemorrhage are common causes of death.
Polycythemia vera (PV) is an uncommon myeloproliferative disorder in which marked erythrocytosia causes an unusually ruddy complexion. Haematocrits in the range of 60% at diagnosis are common. Then may also be a mature leukocytosis and thrombocytosis. Splenomegaly is common. The bone marrow examination shows extreme erythroid hyperplasia. Eventually the marrow becomes hypoplastic and virtually ceases to function, but it may be decades before this end stage is evident. Arterial and venous thrombosis, secondary to increase to blood viscosity, are major problems. This may be controlled by periodically bleeding the patient down to a haemocrit. PV may terminate in a refractory acute leukemia, especially if alkylating agents have been used to retard red cell production.
Primary thrombocytosis is a rare myeloproliferative disorder characterized by a substantially elevated blood platelet count and a bone marrow biopsy that demonstrates extreme megakaryocytosis. Clotting problems are common and abnormal platelet function may cause bleeding. Fortunately, platelet production is usually normalized by treatment, and patients may do well for many years. On rare occasion, the disease terminates as an acute leukemia, sometimes lymphoid.
Hairy cell leukemia (HCL) is a rare chronic B-cell disease that occurs more frequently in white males who are usually middle- aged, and may be confused with CLL. Initial findings usually include pancytopenia and splenomegaly. Examination of a blood smear reveals the presence of relatively mature lymphoid cells with unique, cytoplasmic projections. Such cells are found in the bone marrow, which may be difficult to aspirate. The leukaemic cells of HCL have tartrate-resistant phosphatase activity in the cytoplasm, which differentiates them from CLL cells. Patients with HCL often have severe granulocytopenia, and are highly susceptible to infection before treatment. New drugs cure a sizable fraction of patients.