Leukemia (peds)

Background

• Most common cancer in children (33% of all malignancies)
• ALL
  • 3/4 of pediatric leukemias
  • 5-year survival 75%-80%
  • Peak incidence 3-5yr old
• AML
  • 1/5 of pediatric leukemias
  • Worse prognosis
  • More complications (more intense chemo tx required)

Diagnosis

• Signs/symptoms due to bone marrow infiltration and failure
  • Pallor, fatigue, easy bleeding, fever, infection
  • Bone/joint pain
  • Hepatomegaly or splenomegaly

Work-Up

• CBC
  • If suggestive complete blood count (CBC) with manual differential count.

coagulation profile for unexplained bleeding. If the CBC suggests the diagnosis of leukemia, draw serum electrolytes, blood urea nitrogen, creatinine, calcium, phosphate, magnesium, uric acid, liver function studies including lactate dehydrogenase, coagulation studies, a type and screen, and a chest radiograph, at a minimum

Although almost all children with leukemia have some form of hematologic abnormality (rarely the CBC can be normal), including an elevated or depressed white cell count, very few have the extremely elevated WBC thought to be the typical presentation of leukemia

With AML, the management goals are the same, but it is more difficult to induce remission while managing the adverse effects of therapy. Improved survival rates have been produced by increasingly intense induction regimens. Complete remission may be as high as 80% to 90%, with overall survival approaching 60%. Survival is less because many children may not survive the treatment regimen

DDx

A partial differential diagnosis of children with suspicious hematologic presentations (i.e., marrow suppression) includes aplastic anemia, profound iron deficiency anemia (commonly noted in toddlers with excessive milk intake), viral infections [Epstein-Barr virus, cytomegalovirus (CMV), parvovirus B19], immune thrombocytopenia, and rheumatologic diseases. A good rule of thumb is that leukemias will involve more than one cell line, whereas these other conditions are usually restricted to a single cell line.

Treatment

ANEMIA

Life-threatening hemorrhage or rapidly consumptive coagulopathy requires transfusion and factor replacement. The general goals of transfusion therapy are to raise the Hb level to >8 to 10 grams/dL, depending on the child's condition, and the platelet count to >50,000–100,000/m

THROMBOCYTOPENIA Bleeding in patients with leukemia is most likely due to thrombocytopenia. but the risk of spontaneous intracranial hemorrhage is extremely low until the platelet count dips to <5000/mL3. Most protocols reserve prophylactic platelet transfusions in asymptomatic patients to platelet counts <10,000/mL3 in the absence of other bleeding risk factors. Invasive procedures require a platelet count >50,000/mL3,10 and the platelet count should exceed 50,000-100,000/mL3 for surgeries or procedures with bleeding risks

Platelet transfusions are usually given according to either of the following guidelines: 0.1 unit/kg results in a 30,000–50,000/mL3 increase

DIC is commonly associated with AML. Some subtypes are known to release a procoagulant tissue factor that can lead to a life-threatening consumptive coagulopathy. ED treatment is replacement of platelets, depleted coagulation factors, fibrinogen with fresh frozen plasma (FFP) and cryoprecipitate, because FFP contains little fibrinogen

Generally, 10 cc/kg of PRBCs is expected to raise the Hb level 3 grams/dL in a patient without active hemorrhage.

The clinician ordering blood products (PRBCs and platelets) is faced with several product choices: irradiated, leukocyte reduced, and CMV seronegative (Table 136-3). Consult with the pediatric oncologist for specific directions before administering blood products.

Leukodepletion by the blood bank effectively prevents CMV transmission (by reducing the load of transfused white blood cells 99.9%, to <5 x 106/L).14 However, it is conservatively recommended that infants <1 year of age still receive CMV-negative blood products. In addition, any patient who might need a bone marrow transplant in the future should receive CMV-negative blood. By reducing transfusion of donor white blood cells, leukodepletion will reduce febrile transfusion reactions and platelet alloimmunization rates as noted above.11 Most blood banks routinely provide leukocyte-depleted PRBCs in this situation.

Finally, irradiation of blood products is recommended for profoundly immunosuppressed individuals (e.g., severe immunodeficiency, high-dose chemotherapy, post–bone marrow transplant). Alloreactive lymphocytes found in units of PRBCs and platelets are capable of causing transfusion-associated graft-versus-host-disease, which may be rapidly fatal. (Note that leukoreduction as described above does not prevent transfusion-associated graft-versus-host-disease and is not a substitute for irradiation). Many pediatric cancer centers will transfuse only irradiated blood to all oncology patients.

Hyperleukocytosis is considered to be present when the WBC is >100,000/mL3. Clinically significant hyperleukocytosis occurs with WBCs >200,000/mL3 in AML and >300,000/mL3 in ALL

In the cerebral circulation, symptoms and signs include headache, mental status changes, visual changes, seizures, and stroke (ischemic and hemorrhagic), while in the pulmonary circulation, leukostasis can cause dyspnea, hypoxemia, and respiratory failure.

ED management of hyperleukocytosis consists of aggressive IV hydration, urinary alkalinization, and administration of allopurinol for tumor lysis syndrome (see discussion in Tumor Lysis Syndrome below and Table 136-4). Avoid treatments that increase blood viscosity such as diuretics and PRBC transfusion. Platelets do not increase blood viscosity and should be administered for levels <20,000/mL3 to decrease the risk of cerebral hemorrhage. Leukapheresis is a temporizing measure until definitive antileukemic therapy can be given.

Table 136-4 Initial Management of Leukocytosis/Tumor Lysis Syndrome

Labs (repeat every 4–8 h)

 Complete blood count
 Electrolytes
 Renal function studies
 Calcium, phosphate, magnesium
 Uric acid
 Urinalysis
 ECG

IV fluids

 5% dextrose/0.25% sodium chloride solution
 Bicarbonate 40–80 mEq/L
 Run at two to four times maintenance
 Goals
   Maintain urinary output at 100 cc/m2

   Maintain urine pH 7–7.5 (avoid higher)
   Maintain urine specific gravity <1.010

Specific therapies if indicated

 Allopurinol, 100 milligrams/m2 to prevent uropathy

 Calcium gluconate (for symptomatic hypocalcemia)
 Glucose/insulin/bicarbonate/calcium (for hyperkalemia)
 Rasburicase, 0.2 milligram/kg (to prevent uropathy from excess urate)

Source

Tintinalli