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1514 Part XI: Malignant Lymphoid Diseases Chapter 91: Acute Lymphoblastic Leukemia 1515

a primary lesion will be found by standard diagnostic studies. Dissemi- Infection Control
nated tumor cells often present in characteristic aggregates, and immu- Infections are common in febrile patients with newly diagnosed ALL.
nophenotypic characteristics of lymphoblasts are absent. Therefore, any patient presenting with fever, especially a patient with
neutropenia, should be given broad-spectrum antibiotics until infection
THERAPY is excluded. Remission induction therapy can increase susceptibility to
infection by exacerbating myelosuppression, immunosuppression, and
SUPPORTIVE CARE mucosal breakdown. At least 50 percent of patients undergoing induc-
tion therapy experience infections. Special precautions should be taken
Optimal management of patients with ALL requires careful attention to reduce the risk of infection during this critical phase of treatment,
to supportive care, including immediate treatment or prevention of including protective contact isolation and air filtration; elimination
metabolic and infectious complications (Chap. 24) and rational use of of contact with people with infections; refraining from eating certain
blood products (Chaps. 138 and 139). Other important supportive care food products, such as raw cheese, uncooked vegetables, or unpeeled
measures, such as use of indwelling catheters, amelioration of nausea fruits; and use of antiseptic mouthwash or sitz baths, especially for
and vomiting, pain control, and continuous psychosocial support for patients with mucositis. Good hand washing practices and the use of
the patient and family, are essential. alcohol-based cleansers are important. Administration of granulo-
cyte colony-stimulating factor can hasten recovery from neutropenia
Metabolic Complications and reduce the complications of intensive chemotherapy, but does not
Hyperuricemia and hyperphosphatemia with secondary hypocalcemia improve the EFS rate for children or adults. 101,102 One study suggested
are frequently encountered at diagnosis, even before chemotherapy is growth factor increased the risk of therapy-related acute myeloid leuke-
initiated, especially in patients with B-cell or T-cell ALL or precursor mia in the context of epipodophyllotoxin-based therapy. Intensified
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B-cell leukemia with high leukemic cell burden. Patients should be remission induction regimens, especially in combination with high-
98
given intravenous fluids; allopurinol or rasburicase (recombinant urate dose glucocorticoids, have resulted in an increased risk of disseminated
oxidase) to treat hyperuricemia; and a phosphate binder, such as alumi- fungal infection and death. Antifungal prophylaxis is commonly given.
num hydroxide, calcium carbonate (if the serum calcium concentration All nonallergic patients with ALL are given trimethoprim-
is low), lanthanum carbonate, or sevelamer to treat hyperphosphatemia. sulfamethoxazole, 2 to 3 days per week, as prophylactic therapy for
Allopurinol, a relatively inexpensive drug, is usually used if the uric acid Pneumocystis carinii (Pneumocystis jiroveci) pneumonia. Prophylaxis is
is less than 7 mg/dL. Allergic skin reactions occur in approximately 10 started after 2 weeks of remission induction and continues for several
percent, and allopurinol should be stopped as soon as the risk of hyperu- months after completion of all chemotherapy. Alternative treatments for
ricemia from the destruction of a large leukemic cell burden has passed. patients who cannot tolerate trimethoprim-sulfamethoxazole include
By inhibiting de novo purine synthesis in leukemic blast cells, allopu- aerosolized pentamidine, dapsone, and atovaquone. Live-virus vac-
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rinol can reduce the peripheral blast-cell count before chemotherapy. cines should not be administered during immunosuppressive therapy.
99
Allopurinol can decrease both the anabolism and catabolism of mercap- Siblings and other children who have frequent contact with patients
topurine by depleting intracellular phosphoribosyl pyrophosphate and can receive routine immunizations, including inactivated poliomyelitis
by inhibiting xanthine oxidase. If mercaptopurine and allopurinol are vaccine. Susceptible patients exposed to varicella virus should receive
given together orally, the dosage of mercaptopurine must be reduced. zoster immunoglobulin within 96 hours of exposure together with
Rasburicase works very rapidly and is extremely effective, espe- acyclovir. Such treatment usually prevents or mitigates the clinical man-
cially for very elevated uric acid levels (>7 mg/dL), often with one ifestations of varicella.
infusion (a far smaller dose than the manufacturer recommends). Ras-
buricase breaks down uric acid to allantoin, a readily excreted metab- Hematologic Support
olite that is five to 10 times more soluble than uric acid. Rasburicase is ALL and its treatment leads to pancytopenia. Hemorrhagic manifes-
more effective than allopurinol, and it facilitates phosphorus excretion, tations are common but usually are limited to the skin and mucous
partly because of rasburicase’s potent uricolytic effect (which obviates membranes. Although rare, bleeding in the CNS, lungs, or gastroin-
the need to alkalinize urine) and partly because of improved renal func- testinal tract can be life-threatening. Patients with extremely high leu-
tion with its use. However, rasburicase is contraindicated in patients kocyte counts (>400 × 10 /L) at diagnosis are more likely to develop
100
9
with glucose-6-dehydrogenase deficiency because hydrogen peroxide, a such complications. Coagulopathy attributable to disseminated intra-
70
by-product of uric acid breakdown, can cause methemoglobinemia or vascular coagulation, hepatic dysfunction, or chemotherapy is usually
hemolytic anemia. mild. Patients receiving l-asparaginase and a glucocorticoid have a
76
hypercoagulable state. Platelet transfusions should be given therapeuti-
Hyperleukocytosis cally for overt bleeding and may be used prophylactically when platelet
105
For patients with extreme leukocytosis (leukocyte count >400 × 10 /L), counts are less than 10 × 10 /L. Anticoagulants and antiplatelet agents
9
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either leukapheresis or exchange transfusion (in small children) can such as aspirin must be avoided. Children generally do not have active
be used to reduce the burden of leukemic cells. In theory, either treat- bleeding during remission induction therapy with prednisone, vincris-
ment should reduce the complications associated with leukostasis, tine, and l-asparaginase, even when platelet counts are less than 10 ×
9
but the short- and long-term benefits of the procedures are ques- 10 /L. A higher threshold for prophylactic platelet transfusions should
tionable. Emergency cranial irradiation, once advocated by some be considered for active toddlers and patients with fever or infection.
70
leukemia therapists, probably has no role in the treatment of these Transfusion of packed leukocyte-poor red cells is indicated in patients
patients. Preinduction therapy with low-dose glucocorticoids, with with anemia and marrow suppression but should be delayed until the
addition of vincristine and cyclophosphamide in cases of B-cell ALL, leukocyte count is reduced in patients with extreme hyperleukocyto-
is a favored means of ameliorating hyperleukocytosis. This method, sis. Transfusions should be given slowly in patients with profound but
when used in conjunction with urate oxidase, has largely eliminated chronic anemia to prevent development of congestive heart failure.
tumor lysis syndrome and the need for hemodialysis in patients with Granulocyte transfusions are rarely needed, but should be considered
mature B-cell ALL. for patients with absolute neutropenia and documented Gram-negative

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