Page 1435 - Williams Hematology ( PDFDrive )

1410 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1411

intensification therapy. Studies are under way to examine the effects of in serious ventricular and valvular disturbances years after therapy in
using fludarabine in the regimen (Medical Research Council 15 Trial). some patients. Periodic evaluation of cardiac status by ultrasonography
Autologous stem cell transplantation has not improved outcome should be undertaken in long-term survivors. 1106 Cardiomyopathy and
compared to current intensive chemotherapy treatment regimens. 1095 heart failure can occur 10 to 15 years after therapy. Two approaches that
Allogeneic stem cell transplantation from a histocompatible sibling may ameliorate the cardiomyopathic effect of anthracycline antibiotics
should be considered in children in first remission with a donor and are the use of these agents in liposome encapsulated preparations 1107 and
poor prognostic indicators or in children who relapse. 1095 Trials have the use of dexrazoxane. Either approach may reduce the cardiotoxicity
shown good results of allogeneic transplantation in first remission; of anthracycline antibiotics. 1108
event-free survival was better in childhood AML with those allografted
than with those who underwent autografting. 1096 Children younger than Hepatitis
age 2 years previously had a very poor prognosis. They tend to present Hepatitis may occur in multiply transfused patients and usually is mild,
with myelomonocytic or monocytic leukemia with high blast counts but persistent hepatitis can develop, although hepatitis viruses A and B
and CNS involvement. The t(9;11) abnormality has a more favorable infection are not increased above the expected incidence in the general
prognosis. Intensive multidrug regimens have resulted in 3-year surviv- population. Hepatitis caused by type A virus is nearly nonexistent early
als approaching 70 percent of all infants treated. Thus, most infants can in the course of AML. Cases of type B hepatitis can occur infrequently
be successfully treated with intensive chemotherapy or allogeneic stem in patients who are carriers of the B virus and in whom chemother-
cell transplantation. 1097,1098 Cord blood may be a suitable allograft option apy and transient immunosuppression reactivate the virus. 1109–1111 These
for children with AML who lack an acceptably matched unrelated mar- rare cases of fibrosing cholestatic hepatitis can be fulminant. Screening
row donor. 1099 blood products for hepatitis virus C has markedly decreased the risk of
Growth failure, neurocognitive abnormalities, endocrine deficien- hepatitis C. 1112 Reactivation of carriers of the C virus after chemotherapy
cies, and cardiac abnormalities are found in children treated at a young is unusual. 1113 Medication induced chemical hepatitis or cholestasis can
age. 1100 The occurrence of a second malignancy in cured children is occur but is usually reversible. Iron overload in the multiply transfused
approximately 10-fold greater than expected in a matched population survival may lead to later liver abnormalities.
by age. 1101 Indefinite followup of children in remission or believed to
be cured is important to assess developmental and intellectual progress Systemic Candidiasis Syndrome
and to evaluate long-term adverse events. The syndrome is manifested by fever, abdominal pain, and hepatomegaly.
Increased serum alkaline phosphatase activity often is noted. Blood
cultures are often negative. Abdominal ultrasonography, computed
NONHEMATOPOIETIC ADVERSE EFFECTS OF tomography, and MRI show characteristic hepatic lesions: circular
TREATMENT areas of decreased attenuation of liver and often spleen, kidney, lung,
1114
Skin Rashes or paraspinal muscles by imaging. Ultrasonography reveals multiple
hypoechogenic areas with a bull’s-eye appearance. Laparoscopic-guided
More than 50 percent of patients with AML develop skin lesions dur- liver biopsy reveals yellow nodules on the liver surface, which on micro-
ing remission-induction or remission-consolidation therapy. The rash scopic examination are large granulomas with Candida and pseudohy-
may be on the trunk and extremities. The rash usually is maculopapu- phae. Cure of this infection is possible with long-term (2 to 10 months)
lar initially but can become hemorrhagic in patients who have throm- antifungals. Hepatosplenic candidiasis is seen much less frequently
bocytopenia. Allopurinol, trimethoprim-sulfamethoxazole, and other when azoles are used for fungal prophylaxis.
β-lactam antibiotics are commonly implicated causes. Use of multi-
ple drugs enhances the probability of skin reactivity of patients. 1102 Neutropenic Enterocolitis
Cytostatic therapy coupled with the effects of leukemia predisposes Necrotizing inflammation of the cecum with secondary infection can
patients to an increased frequency of allergic dermatitis.
occur in patients with acute leukemia on intensive chemotherapy.
233
Bacteremia may occur. Right lower abdominal pain and fever can sim-
Cardiac Toxicity ulate appendicitis. The diagnosis can be confirmed by sonography or
Alterations in cardiac function, especially left ventricular and intraven- computerized tomographic scanning in which a characteristic mucosal
tricular septal diastolic wall motion abnormalities, occur frequently in thickening and polypoid appearance are evident. 1115,1116 Management
patients after they are exposed to the anthracycline antibiotics, daunoru- includes bowel rest, nasogastric suction, fluids, and antibiotics. Par-
bicin, or doxorubicin. 1103 The risk of serious cardiac effects is correlated enteral alimentation is sometimes used but is generally not helpful. 1117
with increasing dose of anthracycline antibiotic, increasing patient age, Restoration of the neutrophil count after chemotherapy is an important
and presence of underlying heart disease. Adverse effects include elec- feature of resolution. In the absence of resolution, right hemicolectomy
trocardiographic changes, such as prolonged QT interval, myocarditis, should be considered but is a last resort in neutropenic patients, usually
pericarditis, myocardial infarction, and congestive heart failure. The imposed if hemodynamic stability is lost. 233
incidence of congestive heart failure is dose related and ranges from
approximately 5 percent at doses of 550 mg/m to greater than 30 per- Thromboembolic Disease
2
cent at doses of 600 mg/m . The frequency and long-term sequelae Although bleeding is associated with AML, thrombotic complications
2 1104
increase as anthracycline dose increases. However, even lower doses of can also occur; up to 10 percent in APL and up to 3 percent in other
these agents exert negative effects on cardiac myocytes. Measurement AML subtypes. 1118 Management can be difficult because of thrombocy-
of heart wall behavior, valvular competence, and ejection fraction by topenia. Central lines may contribute to this incidence. 1119 Thrombotic
ultrasonography can assist in assessing the risk of proceeding with thrombocytopenic purpura has also been reported in patients in remis-
anthracycline treatment in patients with or without pretreatment heart sion of AML during consolidation chemotherapy. 1120 Patients with AML
disease. 1105,1106 In younger patients, transient abnormalities, although undergoing allogeneic stem cell transplantation also may develop post-
frequent, often improve after therapy is completed. Increased long- transplantation thrombotic thrombocytopenic purpura, which rarely
term remissions in children and younger adults have led to an increase responds to plasmapheresis.

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