Chapter 104. Acute and Chronic Myeloid Leukemia (Part 12)

Clinical PresentationSymptoms The clinical onset of the chronic phase is generally insidious. Accordingly, some patients are diagnosed while still asymptomatic, during health-screening tests; other patients present with fatigue, malaise, and weight loss or have symptoms resulting from splenic enlargement, such as early satiety and left upper quadrant pain or mass. Less common are features related to granulocyte or platelet dysfunction, such as infections, thrombosis, or bleeding. Occasionally, patients present with leukostatic manifestations due to severe leukocytosis or thrombosis such as vasoocclusive disease, cerebrovascular accidents, myocardial infarction,venous thrombosis, priapism, visual disturbances, and pulmonary insufficiency. Patients with p230BCR/ABL-positive CML have a...
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Chapter 104. Acute and Chronic Myeloid Leukemia (Part 12) Chapter 104. Acute and Chronic Myeloid Leukemia (Part 12) Clinical Presentation Symptoms The clinical onset of the chronic phase is generally insidious. Accordingly,some patients are diagnosed while still asymptomatic, during health-screeningtests; other patients present with fatigue, malaise, and weight loss or havesymptoms resulting from splenic enlargement, such as early satiety and left upperquadrant pain or mass. Less common are features related to granulocyte or plateletdysfunction, such as infections, thrombosis, or bleeding. Occasionally, patientspresent with leukostatic manifestations due to severe leukocytosis or thrombosissuch as vasoocclusive disease, cerebrovascular accidents, myocardial infarction,venous thrombosis, priapism, visual disturbances, and pulmonary insufficiency.Patients with p230BCR/ABL-positive CML have a more indolent course. Progression of CML is associated with worsening symptoms. Unexplainedfever, significant weight loss, increasing dose requirement of the drugs controllingthe disease, bone and joint pain, bleeding, thrombosis, and infections suggesttransformation into accelerated or blastic phases. Fewer than 10–15% of newlydiagnosed patients present with accelerated disease or with de novo blastic phaseCML. Physical Findings Minimal to moderate splenomegaly is the most common physical finding;mild hepatomegaly is found occasionally. Persistent splenomegaly despitecontinued therapy is a sign of disease acceleration. Lymphadenopathy andmyeloid sarcomas are unusual except late in the course of the disease; when theyare present, the prognosis is poor. Hematologic Findings Elevated white blood cell counts (WBCs), with increases in both immatureand mature granulocytes, are present at diagnosis. Usually observed in patients followed without treatment. Platelet counts are almost alwayselevated at diagnosis, and a mild degree of normocytic normochromic anemia ispresent. Leukocyte alkaline phosphatase is low in CML cells. Serum levels ofvitamin B12 and vitamin B12–binding proteins are elevated. Phagocytic functionsare usually normal at diagnosis and remain normal during the chronic phase.Histamine production secondary to basophilia is increased in later stages, causingpruritus, diarrhea, and flushing. At diagnosis, bone marrow cellularity is increased, with an increasedmyeloid to erythroid ratio. The marrow blast percentage is generally normal orslightly elevated. Marrow or blood basophilia, eosinophilia, and monocytosis maybe present. While collagen fibrosis in the marrow is unusual at presentation,significant degrees of reticulin stain–measured fibrosis are noted in about half ofthe patients. Disease acceleration is defined by the development of increasing degreesof anemia unaccounted for by bleeding or therapy; cytogenetic clonal evolution; orblood or marrow blasts between 10 and 20%, blood or marrow basophils ≥20%, orplatelet count Chromosomal Findings The cytogenetic hallmark of CML, found in 90–95% of patients, is thet(9;22)(q34;q11.2). Originally, this was recognized by the presence of a shortenedchromosome 22 (22q-), designated as the Philadelphia chromosome, that arisesfrom the reciprocal t(9;22). Some patients may have complex translocations(designated as variant translocations) involving three, four, or five chromosomes(usually including chromosomes 9 and 22). However, the molecular consequencesof these changes are similar to those resulting from the typical t(9;22). All patientsshould have evidence of the translocation molecularly or by cytogenetics or FISHto make a diagnosis of CML. Prognostic Factors The clinical outcome of patients with CML is variable. Before imatinibmesylate, death was expected in 10% of patients within 2 years and in about 20%yearly thereafter, and the median survival time was ~4 years. Therefore, severalprognostic models that identify different risk groups in CML were developed. Themost commonly used staging systems have been derived from multivariateanalyses of prognostic factors. The Sokal index identified percentage of circulatingblasts, spleen size, platelet count, age, and cytogenetic clonal evolution as the mostimportant prognostic indicators. This system was developed based onchemotherapy-treated patients. The Hasford system was developed on interferon(IFN) α–treated patients. It identified percentage of circulating blasts, spleen size,platelet count, age, and percentage of eosinophils and basophils as the mostimportant prognostic indicators. This system differs from the Sokal index byignoring clonal evolution and incorporating percentage of eosinophils andba ...