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1396 Part X: Malignant Myeloid Diseases Chapter 88: Acute Myelogenous Leukemia 1397

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greater than 100 mL/h/m . Cytoreduction therapy can be initiated with without coagulation abnormalities, anticoagulant use, sepsis, or other
hydroxyurea 1.5 to 2.5 g orally every 6 hours (total dose 6 to 10 g/day) complications usually can maintain hemostasis with platelet counts of
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for approximately 36 hours. Appropriate remission-induction therapy 5 to 10 × 10 /L. Initially, random donor platelets can be used, although
should be initiated as soon as possible after the leukocyte count has single-donor platelets or HLA-matched platelets may be preferable
been decreased significantly. Simultaneous leukapheresis can decrease products and should be tried if random-donor platelets do not raise the
blast cell concentration by approximately 30 percent within several platelet count significantly A no-prophylaxis platelet-transfusion strat-
hours 331,630,631 without contributing to uric acid or cellular phosphate egy for blood cancers has been examined, but data support the need
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release. Leukapheresis may improve acute disturbances resulting from for prophylactic platelet transfusions. Family members may be effec-
the vascular effects of blast cells, but the procedure may not alter the tive donors, if allogeneic HSC transplantation is not being considered
long-term outcome with current therapeutic programs. 339,340,630 Inhaled (Chap. 139). There are data that fever should result in increasing the
nitric oxide may improve the hypoxemia related to hyperleukocytosis. 631 platelet count used as a transfusion threshold, and there is some sugges-
Antibiotic Therapy Pancytopenia is worsened or induced shortly tion that higher hemoglobin values protect against bleeding related to
after treatment is instituted. Absolute neutrophil counts less than thrombocytopenia. 646
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100/μL (0.1 × 10 /L) are expected and are a sign of effective drug action. All red cell and platelet products should be depleted of leukocytes,
The patient usually becomes febrile (>38°C), often with associated rig- and all products, including granulocytes for transfusions, should be
ors. Cultures of urine, blood, nasopharynx, and, if available, sputum irradiated to prevent transfusion-associated graft-versus-host disease
should be obtained. Because the inflammatory response is blunted by (GVHD) in this immunosuppressed population (Chaps. 138 and 139).
severe neutropenia and monocytopenia, evidence of exudates on phys- Granulocyte transfusion should not be used prophylactically for
ical examination or imaging studies may be minimal or absent. Anti- neutropenia but may be used in patients with high fever, rigors, and
biotics should be started immediately after cultures are obtained. bacteremia unresponsive to antibiotics, with blood fungal infections, or
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Chapter 24 describes antibiotic usage in the setting of intensive chemo- with septic shock. G-CSF administration to a volunteer donor increases
therapy. Infections remain a major cause of therapy-associated morbid- neutrophil yield fourfold and results in posttransfusion blood neu-
ity and mortality. 633,634 Gram-positive bacterial isolates now outnumber trophil increments for more than 24 hours after transfusion. There is
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Gram-negative organisms. Cultures are often negative, but if fever still ambiguity about the usefulness of this approach. GM-CSF admin-
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and other signs are present, antibiotic therapy should be continued until istration may be warranted for treatment of major fungal infections
neutrophil recovery. (Chap. 24).
Some centers use prophylactic antibacterial, antifungal, and/or Jehovah’s Witnesses and others who refuse blood product support
antiviral antibiotics, whereas other centers do not. Antifungal prophy- can survive tailored chemotherapy. In general, phlebotomy is mini-
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laxis can consist of low-dose amphotericin or azoles such as fluconazole, mized, and antifibrinolytics, hematinics, and growth factors are used to
itraconazole, posaconazole, or voriconazole. 635,636 In a randomized study support such patients during severe cytopenias.
in patients undergoing induction therapy, posaconazole was more Therapy for Hypofibrinogenemic Hemorrhage Patients with
effective in preventing invasive fungal infections than fluconazole or itra- evidence of intravascular coagulation (Chap. 129) or exaggerated pri-
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conazole. Voriconazole was not included in the comparison. Acyclo- mary fibrinolysis (Chap. 135) should be considered for platelet and
vir, valacyclovir, or famciclovir prophylaxis during remission-induction fresh-frozen plasma administration before antileukemic therapy is
therapy of patients with AML does not affect the duration of fever or started. Infusion of cryoprecipitate can be used for fibrinogen levels
the need for antibiotics. The incidence of bacteremia is not reduced, under approximately 125 mg/dL. If the findings are equivocal, patients
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but acute oral infections are less severe. Liposomal amphotericin, the should be monitored closely with measurements of fibrinogen levels,
caspofungins and azoles are available for treatment of established fungal fibrin(ogen) degradation products, D-dimer assay, and coagulation
infections. Some centers use outpatient supportive therapy, including times. Intravascular coagulation or primary fibrinolysis may occur in
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oral antimicrobials, immediately after induction therapy administration patients with APL and acute monocytic leukemia, but also may occur in
in adult AML. 640 occasional patients with other AML subtypes.
Hematopoietic Growth Factors to Treat Cytopenias Cytokine Management of Central Nervous System Disease CNS disease
therapy as an adjunctive treatment for AML remains controversial. occurs in approximately one in 50 cases at presentation. Prophylac-
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GM-CSF and G-CSF accelerate neutrophil recovery; neither GM-CSF tic therapy usually is not indicated, but examination of the spinal fluid
nor G-CSF reproducibly decreases major morbidity or mortality. How- after remission should be considered in (1) monocytic subtypes,
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ever, one study has shown decreased mortality from fungal infections in (2) cases with extramedullary disease, (3) cases with inversion 16
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older patients. Use of cytokines during periods of cytopenia following and t(8;21) 263,266 cytogenetics, (4) CD7- and CD56-positive (neural-cell
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induction therapy is safe, and nearly all trials have shown a modestly adhesion molecule) immunophenotypes, and (5) patients who pres-
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reduced duration of severe neutropenia with a variable effect on the ent with very high blood blast cell counts. In these situations, the risk of
incidence of severe infections, antibiotic usage, and duration of hospi- meningeal leukemia or a brain myeloid sarcoma is heightened, but pro-
tal stays. Although no increase in relapse has been noted when growth phylactic intrathecal chemotherapy is not recommended if high-dose
factors are started after completion of chemotherapy, no consistent cytarabine is used for consolidation. Patients who present with neuro-
enhancement of remission, event-free survival, or overall survival has logic symptoms should have a head computed tomogram or MRI to rule
been noted. Therefore, the cost-effectiveness and clinical effectiveness out hemorrhage or mass effect. If negative, a lumbar puncture should
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of growth factor usage is doubtful. Also, growth factor usage can cloud be performed. Treatment of meningeal leukemia can include high-dose
marrow interpretation when used during induction. intravenous cytarabine (which penetrates the blood–brain barrier),
Component Transfusion Therapy Red cell transfusions should intrathecal methotrexate, intrathecal cytarabine, cranial radiation, or
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be used to keep the hemoglobin level greater than 7.0 g/dL, or higher chemotherapy and radiation in combination. If CNS leukemia is pres-
in special cases (e.g., symptomatic coronary artery disease; Chap. 138). ent, intrathecal therapy is often given twice per week until blasts are
Platelet transfusions should be used for hemorrhagic manifestations cleared, and then once per week for 4 to 6 weeks. This therapy can be
related to thrombocytopenia and prophylactically if necessary to main- accomplished via the lumbar puncture route or through placement of
tain the platelet count between 5 × 10 /L and 10 × 10 /L. Patients an Ommaya reservoir. If there is a mass present, radiation or high-dose
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