Page 1259 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

866 PART 7: Hematologic and Oncologic Disorders

The goal of this chapter is to alert the intensivist to specific issues TABLE 92-1 Initial Workup of a Patient with Suspected Acute Leukemia
unique to the management of patients with acute leukemias that can
directly impact the course of therapy in a medical ICU setting. We Lab/Study Panel Specific Tests
will focus on the diagnosis of leukemia and complications of patients Characterization of blood • CBC with differential
with newly diagnosed or relapsed acute leukemia including cytopenias, cell counts • Peripheral smear examination
tumor lysis syndrome, hyperleukocytosis, disseminated intravascular ◦ Blasts/immature cells
coagulation (DIC), and infections. Specific classification and prognostic ◦ Schistocytes
scoring for acute lymphoblastic and myeloid leukemias with special ◦ Attention for promyelocytes
attention to acute promyelocytic leukemia will be discussed as well as
the general organization and composition of the current standard treat- Bone marrow examination • Trephine bone marrow biopsy
ment protocols for each subtype of leukemia. Several biological and • Aspirate
chemotherapeutic drugs are infrequently used outside the treatment of ◦ Morphology
acute leukemias and therapy-associated side effects could directly affect ◦ Cytochemical staining (ie, MPO)
a patient’s acute management in an ICU setting. These will be specifi- ◦ Cytogenetics/karyotype
cally highlighted at the end of this chapter. ◦ Flow cytometry
◦ Specific molecular tests (ie, FLT3-IDT, NPM1, CEBPA)
DIC panel • PT and aPTT
ACUTE PRESENTATION AND DIFFERENTIAL DIAGNOSIS • Fibrinogen
Patients with acute leukemia typically present with a prodrome related • D-dimer
to progressive profound cytopenias (ie, neutropenia, anemia, and Tumor lysis panel • Potassium
thrombocytopenia), progressive fatigue, decreased exercise tolerance, • Lactate dehydrogenase (LDH)
petechiae and bleeding, and serious infections including pneumonia. • Phosphate
Acute leukemias can profoundly affect coagulation, causing significant • Uric acid
DIC, venous thromboembolism and bleeding. • Calcium
Initial evaluation of a patient with suspected acute leukemia should Liver function panel • Albumin
include a complete blood count with direct evaluation of the peripheral • AST/ ALT
smear for myeloblasts and lymphoblasts as well as for promyelocytes. • Alkaline phosphatase
Although there is often a profound leukocytosis consisting primarily of • Total and fractionated bilirubin
immature myeloid or lymphoid cells, it is not uncommon for the pre-
senting blood work to show pancytopenia, including leukopenia, with Complete metabolic panel • See tumor lysis panel above
minimal blasts in the peripheral blood smear. In these instances, careful • Sodium
examination of the cells present will often reveal dysplastic features in • BUN and serum creatinine
one or more cell lines. • Bicarbonate
In addition to a complete metabolic panel, lactate dehydrogenase • Glucose
(LDH) and uric acid levels, careful attention should be paid to coagula- Cardiac function • 12-lead ECG
tion measurements, including prothrombin time (PT), activated partial • Transthoracic echocardiogram
thromboplastin time (aPTT), D-dimer and fibrinogen levels. Presence
of promyelocytes and severe derangements in coagulation parameters
should alert the hematologist and critical care specialist to the poten- additional sites for translocation of endogenous organisms into the
tial diagnosis of acute promyelocytic leukemia (APL) and appropriate bloodstream. Clinical practice guidelines for antimicrobial use in neu-
measures, including rapid initiation of all-trans retinoic acid (ATRA) tropenic (ANC <500 cells/mm ) patients with cancer from the Infectious
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therapy and correction of coagulopathy, should occur (Table 92-1). Disease Society of America were recently updated. Patients with acute
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Initial examination should specifically be directed toward signs of leukemias are at increased risk for gram-negative enteric bacteria, gram-
infection (cellulitis, pneumonia, or sinusitis), bleeding or thrombosis, positive cocci and fungi, especially Candida and Aspergillus species.
and the presence of splenomegaly or hepatomegaly. Additional care Patients with ALL have abnormal lymphocyte populations, are exposed
should be paid to any symptom that is out of context for the patient’s to prolonged treatment with corticosteroids, and are thus at increased
prior health status (ie, nausea could connote CNS bleed, leukostasis, or risk for Pneumocystis, mycobacterial, and viral infections. Reactivation of
leukemic infiltration of the gastrointestinal tract). viruses such as cytomegalovirus, herpes zoster, and herpes simplex virus
When diagnosing the specific form of acute leukemia, the differential is also common in patients with prolonged leukopenia, and respiratory
diagnosis includes acute myelocytic leukemia (AML), myelodysplastic viruses such as respiratory syncytial virus and influenza are especially
syndrome (MDS), lymphoblastic leukemia (ALL), and blast-phase virulent and carry a high mortality in this patient population.
chronic myelocytic leukemia (CML). Myelofibrosis (MF) can also Management of infectious complications in patients with acute
present with cytopenias and elevated peripheral myeloblasts. In addi- leukemias is threefold: (1) appropriate prophylaxis against infections,
tion to the above blood work, direct examination of the bone marrow is (2) rapid treatment with empiric antibiotics followed by targeted therapy
required for diagnosis and classification of acute leukemia. Both aspirate at the onset of fever, and (3) use of granulocyte colony-stimulating factor
and trephine biopsy should be obtained from the bone marrow and (G-CSF) as appropriate to the point in therapy for the leukemia. Once
samples sent for morphology, cytogenetic analysis, flow cytometry, the induction chemotherapy is administered, prophylaxis against inva-
and specific molecular tests as detailed below. sive fungal infections should be started. The standard antifungal pro-
phylaxis has been with fluconazole, which offers good coverage against
INFECTIOUS COMPLICATIONS OF ACUTE LEUKEMIA many Candida species, but lacks activity against invasive mold infections
including aspergillosis, zygomycosis, and fusariosis. A seminal article in
Patients with acute leukemia are immunocompromised at presenta- the New England Journal of Medicine showed a decreased incidence of
tion resulting from impaired normal white cell maturation. Most Aspergillus infection as well as a survival benefit in neutropenic patients
chemotherapy regimens directed at these malignancies induce further with AML who were treated with posaconazole prophylaxis (200 mg
myelosuppression often lasting several weeks to a month at a time, and three times a day) when compared to fluconazole or itraconazole and is
frequently cause mucosal surface injury (ie, mucositis) which creates now an approved indication for this drug. Unfortunately, posaconazole
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