Page 1264 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

CHAPTER 92: Acute Leukemia 871

aPTT prolongation. FFP transfusion can give a significant fluid volume, intravenous fluids that do not contain potassium is critical for preventing
so attention should be paid to the patient’s overall clinical status during clinical consequences of TLS. Hydration targets in adults should be
plasma infusions and diuresis should match the additional fluid load. three to four times daily maintenance fluid requirements and urine
With severe hypofibrinogenemia (<1 g/L), cryoprecipitate or fibrinogen output of at least 100 mL/h. A trial of furosemide may also be helpful
49
concentrate should also be given. Plasma fibrinogen will increase on in maintaining urine output in volume repleted patients, although this is
average 100 mg/dL for every 3 g dose of fibrinogen administered as either controversial given the risk for further renal injury. It is critical to keep a
two cryoprecipitate pools (10 donor units) or as 3 g of fibrinogen con- close measurement of urine output during the initial treatment of acute
centrate. 16,34 The one exception to this is for patients with ALL who are leukemias while maintaining this degree of hydration as patients are at
hypofibrinogenemic following L-asparaginase therapy. These patients are high risk for pulmonary congestion and fluid overload. 40
at further increased risk of DIC and especially of thrombosis. In addition Historically, urinary alkalinization has been used for prevention of
to decreased fibrinogen levels, this patient group also tends to develop TLS. However, there is increasing evidence that systemic alkalinization
low levels of antithrombin-III which is also prothrombotic. Studies is both ineffective at preventing urate-induced nephropathy, and can
28
are underway investigating the use of antithrombin concentrates for the precipitate worsening renal function and TLS-associated electrolyte
management of DIC in this high-risk population. disturbances. The current recommendation is against routine systemic
alkalinization for treatment or prevention of TLS. 40
TUMOR LYSIS SYNDROME Hyperkalemia may be managed with a combination of intravenous
fluids, furosemide, the potassium-binder kayexalate, calcium gluconate, β -
2
Acute tumor lysis syndrome (TLS) is one of the oncologic emergencies agonists, and dialysis. In selecting the type of fluid to be administered, it is
that can evolve during the initial treatment of patients with newly diag- best to avoid preparations that contain additional potassium. Similarly, prior
nosed leukemias. TLS occurs when there is a high volume of malignant to initial treatment of a patient with new acute leukemia who has a signifi-
cells that die and release their intracellular contents (purines and electro- cant cell load, it is best to avoid overaggressive potassium repletion given the
lytes) into the bloodstream. The result is rapid development of hyperka- potassium load that will be entering the circulation with the start of therapy.
lemia, hypocalcemia, hyperphosphatemia, and hyperuricemia. Elevated Hyperuricemia can lead to urate crystal deposition in the renal
serum LDH levels are also noted. TLS can occur before the start of che- tubules, worsening renal function. In addition to intravenous hydration,
motherapy, and the highest risk period for clinical TLS extends through allopurinol, a xanthine oxidase inhibitor, or rasburicase, recombinant
the first 3 to 7 days of treatment. The formal definition of laboratory urate oxidase, may be used. Allopurinol can help prevent buildup of
TLS includes a 25% increase from baseline level of uric acid, potassium, urate crystals, but does not address what may already be deposited,
and phosphorous and serum calcium levels decrease by more than 25% while rasburicase rapidly decreases uric acid levels that are already
from baseline. Absolute value cutoffs are noted in Table 92-6. Clinical elevated. For patients deemed at high risk of TLS, including patients
TLS is the presence of laboratory TLS and the associated clinical com- with acute lymphoblastic leukemia and a WBC >100,000/µL or acute
plications as shown in Table 92-6. Risk factors for the development of myelocytic leukemia with a WBC >50,000/µL, rasburicase should be
TLS are related to both increased production and decreased clearance the treatment of choice. 11,40 Rare but potentially emergent side effects
of tumor lysis products including (1) cancer-specific factors of tumor of rasburicase include acute hemolysis in patients with glucose-6-phos-
bulk (in the case of leukemia, marrow and peripheral blood leukocyte phate dehydrogenase (G6PD) deficiency, hypersensitivity reaction, and
burden), cancer proliferation rate, and sensitivity to therapy and methemoglobinemia. In patients with these conditions, rasburicase
(2) patient-specific factors of chronic renal dysfunction and gout, should not be used. Hyperphosphatemia is treated with phosphate bind-
and clinical state at presentation including dehydration, low urine ers, low-phosphate diet, and hemodialysis.
output, and acute renal dysfunction. 14,27,38 A predictive model for devel-
opment of TLS has been developed and includes measurement of uric
acid, creatinine, LDH, WBC, gender, and history of chronic myelo- HYPERLEUKOCYTOSIS SYNDROME
monocytic leukemia prior to start of chemotherapy. 38 Hyperleukocytosis is defined as circulating blasts greater than 50,000/µL
Successful management of TLS is a function of reduction of tumor 5
burden (by chemotherapy or leukapheresis) and medical therapy tar- or 100,000/µL in patients with AML or ALL, respectively. Leukostasis
can occur at lower peripheral blast counts depending on unique char-
geted at normalizing electrolyte disturbances. Vigorous hydration with
acteristics of the individual leukemia clone. Consequences of elevated
white cell counts are a result of end-organ injury, typically of the CNS
TABLE 92-6 Detection and Management of Tumor Lysis Syndrome 55 and lungs. Patients may experience intracranial hemorrhage and CNS
symptoms of dizziness, confusion, lethargy, vision or hearing changes,
Electrolyte Measurement Symptoms Management
seizures, and loss of consciousness. Pulmonary symptoms and signs may
Hyperkalemia K >6 mmol/L Cardiac arrhythmias Kayexalate include dyspnea, cough, hypoxia, and respiratory failure and arrest.
+
7,37
(6 mEq/L) Myalgias Furosemide The mechanism is in part a result of leukocyte adhesion to endothelium,
Insulin + glucose endothelial injury, alteration in vascular integrity, and development of
β -agonist a prothrombotic milieu. The end result is microvascular injury and
7
2
IVF without K + occlusion and subsequent injury to the target organ.
+
Low K diet The risk of leukostasis varies by leukemia subtype, with AML carrying a
Hemodialysis higher risk for leukostasis than ALL. Between 5% and 29% of patients with
Hyperuricemia Uric acid >476 mmol/L Renal insufficiency/ Rasburicase AML present with WBC >50,000/µL depending on age of patient and sub-
(8 mg/dL) failure Allopurinol type of AML, and in a CALGB study of patients with AML under the age of
60, 12% had a WBC >100,000. Monocytic and myelomonocytic leukemia,
8
>1.45 mmol/L Renal insufficiency/ binders
Hyperphosphatemia P O 4 P O 4 inv16 (p13;q22), and AML with 11q23 rearrangements or FLT3-ITD tend
(4.5 mg/dL) failure Calcium toward higher WBC counts at presentation. 5,8,21 APL, especially the micro-
diet
Low P O 4 granular variant, can present with elevated WBC counts (>10,000/µL)
Hemodialysis
although it is less common. When patients with APL do present with
Hypocalcemia <1.75 mmol/L Cardiac arrhythmias Calcium elevated WBC counts, leukocytosis and the associated profound coagu-
(7 mg/dL) Seizures lopathy have an adverse prognosis. In ALL, T-cell subtype or the presence
56
Data from Tosi P, Barosi G, Lazzaro C, et al. Consensus conference on the management of tumor lysis of 11q23 is more likely to present with hyperleukocytosis. 5,26,58 With both
syndrome. Haematologica. December 2008;93(12):1877-1885. AML and ALL, a high WBC at presentation is a poor prognostic indicator.

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