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868 PART 7: Hematologic and Oncologic Disorders

ALL, but can also occur in patients with AML. Age, peripheral WBC with the return of normal neutrophil count. In instances of severe
count at presentation, detection of blasts in the CSF, and serum LDH typhlitis, G-CSF treatment may be indicated depending on the timing
are risk factors for CNS leukemia in ALL. Thus, CNS chemoprophy- of leukemia treatment.
laxis with intrathecal administration of preservative-free methotrexate
(12 mg/m up to a maximum of 15 mg total) and cytarabine (standard GENERAL FRAMEWORK FOR MANAGEMENT
2
and liposomal) are included in all major ALL chemotherapy regimens OF ACUTE LEUKEMIA
in a frequency that depends on the likelihood of active CNS disease.
30
Intrathecal methotrexate can cause an arachnoiditis, and is therefore Once the diagnosis of acute leukemia is made, and the subtype deter-
coadministered with hydrocortisone (50 mg). CNS chemoprophylaxis mined (AML vs ALL vs APL), rapid initiation of treatment with an appro-
has a positive effect on disease-free and overall survival for patients with priate regimen (Table 92-3) is indicated. Side effects and complications
ALL. Each time that intrathecal chemotherapy is administered, cerebro- from chemotherapies used in acute leukemia are included in Table 92-4.
spinal fluid should be sent for cytology. Leukemia treatment is generally divided into two to three phases, the
If headache and nausea or focal neurologic symptoms are present, first being induction of remission, followed by consolidation/intensification
dexamethasone (4 mg every 6 hours) can help rapidly alleviate signs and
symptoms of CNS edema or swelling. Additional treatment modalities
include intrathecal thio-TEPA, whole brain irradiation with 2400 cGy
in 12 fractions, local irradiation of spinal lesions, or systemic chemo- TABLE 92-3 Standard Induction Regimens for Acute Leukemias a
therapy with high-dose intravenous cytarabine or methotrexate, which Disease Regimens
can penetrate the blood-brain barrier.
ALL • Hyper-CVAD 31
SOLID ORGAN INFILTRATION ◦ Cytarabine, vincristine, adriamycin, dexamethasone
◦ Including imatinib or dasatinib if Ph
+42,54
As with the CNS, leukemia cells can infiltrate any solid organ, even with- • CALGB 5-Drug
out forming a solid tumor as in myeloid sarcomas. Frequently affected ◦ Daunorubicin, vincristine, prednisone, L-asparaginase, cyclophosphamide 32
organs include the liver, spleen, and kidneys. ALL and blast-phase CML AML • Cytarabine and daunorubicin or idarubicin (7 + 3) 59
more frequently than AML cause hepatosplenomegaly resulting from • Decitabine (elderly patients, or relapsed disease) 4
leukemic infiltration. Liver infiltration may produce signs of acute • High-dose cytarabine (HiDAC)
hepatitis (jaundice, tender hepatomegaly, and elevated serum trans- ◦ Most frequently used as consolidation therapy
aminases). Liver dysfunction will resolve with systemic chemotherapy, • Mitoxantrone and etoposide (MEC) 25,52 b
but does limit initial chemotherapy options. Fulminate liver failure can • Cytarabine and mitoxantrone b
also occur from portal venous thrombus formation and resultant Budd- • CLAG b 44
Chiari syndrome (either as a result of concurrent hypercoagulability or ◦ Cladribine, cytarabine, filgrastim
from leukemia cell thrombosis). Thrombectomy or thrombolysis should APL • AIDA 47
be considered as appropriate to the patient’s history, as this situation ◦ ATRA and idarubicin
can otherwise be rapidly lethal. Splenic infiltration and enlargement • ATRA + arsenic trioxide 17
can occur, and increases the risk of infarct, subcapsular hematoma, and
rupture. ALL and AML (especially “monoblastic” AML) can also infil- a Consolidation and maintenance phases may include additional chemotherapies.
trate the kidneys. Presenting signs include oliguric acute renal failure in b Induction for relapsed or refractory disease.
the absence of an obstructing lesion. Ultrasound evaluation may show
a homogeneous enlargement of both kidneys. Poor renal function can
place patients at greater risk of tumor lysis syndrome (ie, hyperkalemia
and hyperuricemia and associated complications). If retroperitoneal TABLE 92-4 Common and Most Severe Side Effects from Chemotherapies
a
lymphadenopathy is present, ureteral obstruction can also occur and Used in Treatment of Acute Leukemias
impair renal function and outflow. This is especially problematic when Drug Selected Side Effects
nephrotoxic chemotherapies are being administered. Appropriate inter- Anthracyclines (including Cardiac toxicity
vention including ureteral stenting should be performed to normalize daunorubicin, idarubicin, Hepatotoxicity (and hepatically cleared)
urinary tract outflow in these instances. and mitoxantrone) Pancytopenia
Nausea
NECROTIZING ENTEROCOLITIS (TYPHLITIS)
Cytarabine Nephrotoxic (and renally excreted)
Typhlitis or necrotizing enterocolitis of the terminal ileum, appendix, Cerebellar neurotoxicity (especially with concurrent renal failure)
and cecum is a frequent complication in patients experiencing pro- Pancytopenia
tracted chemotherapy-induced neutropenia. Symptoms include nausea Hepatic dysfunction
and emesis, jaundice, abdominal pain, watery and bloody diarrhea, and Mucositis
fever. The intestinal mucosa becomes ulcerated and ileus and bowel dila- Conjunctivitis (consider concurrent steroid-containing eye drops)
tion can occur. Enteric organisms infiltrate into the bowel wall and fluid, L-asparaginase and CNS irritation including seizure
electrolytes and plasma proteins are lost into the bowel lumen. Systemic PEG-asparaginase Hyperglycemia
bacteremia and sepsis, jaundice and hepatitis from portal seeding during Hypertriglyceridemia
bacteremia and bowel perforation may occur. Bowel thickening is fre- Nausea
quently seen on radiographic examination of the abdomen. Medical Pancreatitis
management consists of systemic administration of broad-spectrum Hypofibrinogenemia
antibiotics with gram-negative and anaerobic coverage. Serum electro- Decreased factors V, VII, IX
lytes and blood products should be aggressively repleted, and bowel rest Decreased protein C and antithrombin III
including nasogastric suction is appropriate. Medications that interfere Hepatotoxicity
with bowel function and motility should be avoided during this time Acute allergic reaction
frame to decrease the risk of ileus and further bowel distension and
perforation. In the absence of perforation, symptoms typically resolve (Continued)

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