Physical Address
304 North Cardinal St.
Dorchester Center, MA 02124
Acute and chronic leukemias
KEY POINTS
-
Leukemias account for 0.3% to 1.2% of all malignancies with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) being the most common (one-third of all leukemia cases each).
-
Risk factors for leukemias are ill-defined, with the exception of a few well-documented risks, including exposure to alkylating agents or topoisomerase II inhibitors (AML) and ionizing radiation.
-
Prognosis differs for each of the four leukemia types based on age, cytogenetics, and molecular aberrations.
-
Treatment is disease-specific; for AML: cytarabine + anthracycline (7 + 3), with the addition of targeted agents, such as midostaurin ( FLT3 ) and gemtuzumab ozogamicin (CD33); for ALL multiagent cytotoxic chemotherapy regimens plus or minus BCR-ABL1 tyrosine kinase inhibitors (TKIs) or rituximab (CD20); for CLL Bruton tyrosine kinase (BTK) inhibitors, BCL2 inhibitors, and CD20-targeted monoclonal antibodies; and for chronic myeloid leukemia, BCR-ABL1 TKIs.
-
Cardiovascular risks include those of anthracycline exposure with the need for lifetime dose monitoring for acute lymphoblastic leukemia and AML.
-
QTc prolongation, pericardial effusions, and arterial occlusive events are the main concerns for BCR-ABL1 TKIs.
-
Atrial fibrillation and hypertension are the main CV concerns for BTK inhibitors.
-
Myelodysplastic syndromes and myeloproliferative neoplasms are unique myeloid entities that may have either treatment-related or disease-related risk for thrombosis necessitating antiplatelet and anticoagulation therapy.
-
Patients with clonal hematopoiesis of indeterminate potential have presumptive cancer related driver mutations increasing their risk for hematologic malignancy and all-cause mortality owing to accelerated cardiovascular disease (inflammatory milieu and endothelial dysfunction).
Introduction
Acute and chronic leukemias are characterized by unregulated cellular differentiation and proliferation occurring during specific phases in canonic hematopoiesis. Acute leukemias are caused by differentiation arrests occurring early during hematopoiesis, resulting in immature myeloid or lymphoid precursors, often called blasts, proliferating in an uncontrolled fashion. In contrast, chronic leukemias, in general, are a consequence of malignant cells developing later in hematopoiesis, resulting in relatively mature myeloid or lymphoid lineage cells that are unable to undergo routine cell death or apoptosis ( Fig. 49.1 ).
In 2020, 60,530 new cases of leukemia were estimated in the U.S., compromising approximately 3.5% of new cancer diagnoses. Of those, the incidence of acute and chronic leukemias is anticipated to be nearly equivalent, with the most prominent types being acute myeloid leukemia (AML; 34%) and chronic lymphocytic leukemia (CLL; 33%). More than 50% of acute lymphoblastic leukemia (ALL) cases are diagnosed in patients less than 20 years of age, making it the most common cancer in children. In contrast, AML, chronic myeloid leukemia (CML), and CLL occur most frequently in patients 65 to 74 years of age.
Prognosis
Prognosis in acute and chronic leukemias is highly dependent on the cytogenetic and molecular aberrations encountered. Cytogenetic aberrations can be analysed using metaphase cytogenetics, interphase fluorescence in situ hybridization and array-based genomic hybridization assays, whereas molecular abnormalities are identified using targeted next generation sequencing assays, including whole exome sequencing and in some cases fusion detection using fluorescence in situ hybridization and/or transcriptomic analysis (Q-PCR or RNA-seq). When appropriate, specific key cytogenetic features will be highlighted throughout the chapter.
Treatment strategies for acute myeloid and lymphoid malignancies
Acute myeloid leukemia
The mainstay of treatment in patients with minimal comorbidities remains aggressive chemotherapy with the goal of complete remission (CR), which is achieved in 60% to 70% of patients. Standard risk treatment includes a combination of anthracycline for 3 days and cytarabine continuous infusion for 7 days (7 + 3). Pretreatment evaluation with an echocardiogram is encouraged for baseline cardiac assessment, owing to the age of the population and cumulative anthracycline administration. In patients who achieve a CR, consolidation chemotherapy is generally with high-dose cytarabine over 3 to 5 days. Patients at intermediate or high risk are treated similarly, but should be evaluated early for allogeneic hematopoietic stem cell transplant (HSCT).
Some evidence suggests that patients with a favorable prognosis, such as core binding factor AML [(t8;21)(q22;22), inv(16)(p13q22)/t(6;16)(p13q22)], may benefit from the addition of gemtuzumab ozogamicin, a humanized CD33-directed monoclonal antibody-drug conjugate linked to a cytotoxic calicheamicin derivative. This is not thought to contribute to cardiotoxicity of traditional therapy, but does increase the risk for hepatic venoocclusive disease, especially in the context of planned allogeneic HSCT. In patients with FLT3 -mutated AML, midostaurin, a FLT3 inhibitor, is added on days 8 through 21 to induction and consolidation therapy with improvement in disease-free and overall survival (OS). Midostaurin is associated with moderate emetogenic potential and may cause nausea, vomiting, diarrhea and subsequent electrolyte derangements. Although evaluation of QTc in healthy individuals was unrevealing, QTc prolongation has occurred in more than 18% of patients with AML.
You're Reading a Preview
Become a Clinical Tree membership for Full access and enjoy Unlimited articles
If you are a member. Log in here