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1394 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1395

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poorer outcome as the time from diagnosis to treatment lengthens. than approximately 20 × 10 /L, as long as hydration is adequate and
9
Although remission rates are lower in older patients, a significant urine flow is high (>150 mL/h). The dermatitis may appear when anti-
proportion enter remission. Occasionally, very elderly patients refuse biotics are instituted. This concurrence may confound the decision to
treatment or are so ill from unrelated illnesses that treatment may be continue antibiotics. Thus, allopurinol should be discontinued after the
unreasonable. Age per se is not a contraindication to treatment, and risk of acute hyperuricosuria or tumor lysis has passed (usually 4 to
septuagenarians and octogenarians who are fit can enter remissions. 7 days). Recombinant urate oxidase (rasburicase) can be used to pre-
Treatment can be tailored to the decreased tolerance of older patients, vent urate-induced nephropathy. This preparation, although costly, can
some of whom have a smoldering course (see “Treatment of Older reduce plasma urate levels by approximately 80 percent within 4 hours
Patients” below). Associated problems, such as hemorrhagic manifesta- of the first drug dose. It is well tolerated, and the recommended dose
tions, severe anemia, or infections, should be treated in parallel. of rasburicase is 0.2 mg/kg daily for 5 to 7 days intravenously, although
shorter courses are usually effective. 580
Attention to decreasing pathogen exposure by assiduous hand
PREPARATION OF THE PATIENT washing and meticulous care of catheter and intravenous sites is impor-
9
Orientation of the patient and the family should provide them with an tant, especially when the total neutrophil count is less than 0.5 × 10 /L.
understanding of the disease, the treatment planned, and the adverse Care of the patient in a single room is advisable to provide privacy dur-
effects of treatment, as well as information about long-term prognosis to ing periods of intensive care and to help decrease the risk of exogenously
the extent this can be provided while awaiting cytogenetic and molecu- acquired infection until the neutrophil count recovers.
lar markers. Socioeconomic status and distance from the treatment cen-
ter have minimal effects on survival in AML, but impaired Karnofsky
577
performance status and instrumental activities of daily living score do REMISSION-INDUCTION THERAPY
impact outcomes. 578 Principles
Pretreatment laboratory examination should include blood cell The cytotoxic therapy of AML rests on two tenets: (1) two competing
counts, cytochemistry analysis and immunophenotyping of leukemic populations of cells are present in marrow—a normal polyclonal and a
cells from blood or marrow, marrow examination including cytogenetic leukemic monoclonal population; and (2) profound suppression of the
and molecular analyses to include FLT3 ITD, NPM-1, CEBPα, and KIT leukemic cells to the point they are inapparent in the marrow aspirate and
mutation status in CBF leukemias, if available. If these are not available, biopsy is required to permit restoration of polyclonal hematopoiesis. 581,582
they can performed later as required based on AML subtype from a Although these two principles hold in most cases, two deviations from
cryopreserved specimen. Blood chemistry studies, chest radiography, these guidelines are (1) the predisposition of patients with APL to
electrocardiogram, and determination of partial thromboplastin time, enter remission despite cellular posttherapy marrow and (2) the rare
583
prothrombin time, and fibrinogen level should be obtained. More presence of monoclonal hematopoiesis in some cases of AML during
extensive evaluation of coagulation factors should be made if (1) clot- remission (see “Results of Treatment” below). AML is a heterogeneous
ting times are abnormal, (2) bleeding is exaggerated for the level of the disease, and subgroups with different prognosis can be identified. In the
platelet count, or (3) APL or acute monocytic leukemia is the pheno- future, incorporation of knowledge about the biology of the particular
type. Early HLA typing is useful so that compatible platelet products AML subtype may be utilized for adapted therapies, but at present, all
can be provided if alloimmunization (Chap. 139) occurs and for patients subtypes of AML classified by cytogenetics or molecular changes with
who will become marrow transplantation candidates (Chap. 23). Herpes the exception of APL are approached similarly during induction, and
simplex virus and cytomegalovirus serotyping may be helpful, especially often induction therapy must be started before knowledge of cytoge-
if transplantation is a consideration. HIV and hepatitis serology is indi- netic and molecular factors is available. 584
cated in patients with appropriate risk factors, and patients should have The goal of induction therapy in AML is achievement of complete
a baseline cardiac scan to determine ejection fraction prior to adminis- remission (<2 percent blasts in the marrow), a neutrophil count greater
tration of an anthracycline antibiotic. than 1000/μL, and a platelet count greater than 100,000/μL. An Inter-
A peripherally inserted central catheter or a tunneled central national Working Group for Diagnosis, Standardization of Response
venous catheter should be placed. This access to the circulation facil- Criteria, Treatment Outcomes, and Reporting Standards has redefined
itates administration of chemotherapy, blood components, antibiotics, outcomes in an effort to standardize reporting and comparison of data
and other intravenous fluids and medications. It also permits sampling (see “Course and Prognosis: Results of Treatment: Definition of Remis-
blood for analysis without patient discomfort or concern about venous sion” below). Other treatment guidelines have been published. 586,587
585
access. Meticulous skin care at the catheter exit site is required to min- The majority of adults enter remission with standard induction therapy,
imize tunnel infections. Central venous catheters have become a major but for patients with high-risk disease, consideration can be given to an
source of infection during neutropenia, especially with Gram-positive experimental approach, and complete remission rates do not reach 100
organisms. In some patients with severe coagulopathy such as those percent, so clinical trial participation can be considered during induc-
579
with APL, a tunneled catheter may be best deferred to avoid significant tion chemotherapy. How durable a complete remission will be attained
bleeding or vessel activation during insertion. In those with neurologic in an individual patient often is difficult to predict at diagnosis. Gene-
symptoms, a head computed tomographic study or MRI followed by a expression profiling can separate some patients into prognostic groups
lumbar puncture should be obtained. Before procedures, adequate plate- that may indicate patients with a high risk of not responding to standard
let counts and control of coagulopathy should be achieved, if possible. approaches. 105
Therapy for hyperuricemia is required if (1) the pretreatment
uric acid level is greater than 7 mg/dL (0.4 mmol/L), (2) the marrow is
packed with blast cells, or (3) the blood blast cell count is moderately Cytotoxic Regimens
or markedly elevated. Allopurinol 300 mg/day orally should be given. Anthracycline Antibiotic or Anthraquinone and Cytarabine Current
Allopurinol can cause allergic dermatitis and should not be used if the standard induction treatment for non-APL AML involves drug regi-
uric acid level is less than 7 mg/dL and the total white cell count is less mens with two or more agents that include an anthracycline antibiotic

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