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CHAPTER 92: Acute Leukemia 867

is currently available only as an oral suspension that necessitates TABLE 92-2 Risk Stratification in Acute Myelogenous Leukemia by Cytogenetics 2,57
the ability of the patient to maintain good oral intake for optimal
absorption. This is difficult in patients with severe mucositis. Use of Risk group Cytogenetics
proton-pump inhibitors is necessary to decrease the risk of GI irritation Good risk t(15;17); acute promyelocytic leukemia
from the high-dose corticosteroids used in ALL regimens, but these t(8;21)
medications can further hinder posaconazole absorption. 12,33 Evidence inv(16)/t(16;16)
for the use of voriconazole prophylaxis in this patient group is not yet
definitive, but studies are underway using voriconazole for antifungal Intermediate risk t(9;11)
prophylaxis in hematopoietic stem cell transplant (SCT) recipients. Gain or loss of Y chromosome
33
Antiviral prophylaxis with acyclovir or valacyclovir is started in patients Normal cytogenetics
with acute leukemia undergoing induction or reinduction therapy and Adverse risk t(6;9)
continued until recovery of the WBC count or resolution of the muco- inv(3)/t(3;3)
sitis, whichever occurs later. Although there is debate about the risk 11a23 (MLL gene rearrangement)
of developing resistant organisms, there is increasing evidence to sup- Deletion of 5q
port the use of fluoroquinolone prophylaxis for high-risk patients with Monosomy 7
hematologic malignancies with expected durations of prolonged and Complex karyotype
profound neutropenia (ANC ≤100 cells/mm for >7 days). 13,20 Monosomal karyotype
3
Fever in the leukopenic patient (temperature ≥38.3°C) is considered
a medical emergency. Rapid collection of blood, urine and sputum
cultures, chest x-ray, and initiation of broad gram-negative coverage FLT3-TKD (tyrosine kinase domain) mutations. However, these are not
with agents that cover Pseudomonas aeruginosa are critical. Cefepime routinely included in diagnostic studies to date. 3
or carbapenem monotherapy or semisynthetic penicillin plus an amino-
glycoside can be considered for empiric treatment of neutropenic fever. DIAGNOSIS AND CLASSIFICATION OF
However, a 2010 Cochrane analysis suggested inferior outcomes with ACUTE LYMPHOBLASTIC LEUKEMIA
cefepime compared to carbapenem monotherapy, although the inci-
dence of Clostridium difficile infection was significantly increased with The classification of ALL is based on immunophenotype (ie, pro-B–,
routine carbapenem use. In considering an aminoglycoside-containing pre-B–, mature-B–, pro-T–, common-T–, and mature-T–cell lineage
regimen, baseline renal function and nephrotoxicity of concurrent che- and minimally differentiated ALL or ALL with myeloid markers). As
motherapy should be taken into account. with AML, there are many cytogenetic and molecular abnormalities
For patients who fail to defervesce with appropriately targeted anti- associated with ALL, the most important of which being the presence
bacterial agents, detailed radiographic pulmonary evaluation with of the BCR-ABL transgene [t(9;22)(q34;q11)]. It is especially important
computerized tomography should be performed. If fungal infection to recognize the presence of this transgene as treatment protocols for
is suspected, empiric antifungal therapy with voriconazole should be Philadelphia chromosome positive (Ph ) ALL now include a tyrosine
+
started. If the patient is hemodynamically stable, isolation and char- kinase inhibitor (imatinib or dasatinib) along with induction therapy. 42,54
33
acterization of the pathogen should be attempted by bronchoscopy Prognostic indicators for adult ALL include age >35 years, WBC
with bronchoalveolar lavage and biopsy or by CT-guided needle biopsy. >30,000 in B-cell ALL or >100,000 in T-cell ALL, time to complete
Granulocyte infusion is infrequently used, but G-CSF therapy may be remission (CR), immunophenotype, karyotype: t(9;22), BCR-ABL, CNS
considered depending on the clinical scenario and is best added under involvement, and persistence of minimal residual disease. As with
the guidance of a hematologic oncologist. AML, there are an increasing number of molecular markers that have
prognostic significance and continue to be an area of active clinical
research. Although the presence of the BCR-ABL transcript (ie, Ph ) is
+
DIAGNOSIS AND CLASSIFICATION still considered a poor-prognostic indicator, the addition of imatinib and
OF ACUTE MYELOGENOUS LEUKEMIA dasatinib to standard ALL regimens has significantly improved the prog-
nosis in this patient population to almost that of Ph ALL patients. 18,42,54
−
The classification of AML has moved away from the earlier morphologic
and cytochemistry based French-American-British (FAB) system. It
is now incorporated in the World Health Organization (WHO) sys- MYELOID SARCOMA
tem that includes morphology, immunophenotype, cytogenetics, and Although originating in the bone marrow, acute leukemias are systemic
molecular characterization of the leukemic clone and is useful for both diseases. Leukemia cells circulate in the bloodstream and are frequently
35
classification and prognosis. Risk stratification according to cytogenetics found on biopsy of nonhematopoietic tissues. When AML cells form a
is detailed in Table 92-2. It is worth noting that “normal cytogenetics” is solid mass, it is termed a myeloid sarcoma or chloroma. Myeloid sarco-
included in the intermediate risk group, but this is dependent on further mas are most frequently found in bone and subperiostium, lymph nodes,
molecular characterization that modifies prognosis. An increasingly and the gastrointestinal (GI) tract. Complications of myeloid sarcomas
9
important cytogenetic group is the monosomal karyotype which has an are similar to those encountered with a solid tumor interfering with
especially poor prognosis (3% overall survival at 4 years with chemo- the normal physiology of the involved organ. Special attention should
therapy alone) and is defined as two or more autosomal monosomies or be paid to these tumors within the spine as they can cause spinal cord
one autosomal monosomy and an additional chromosomal structural compression, and to those within the GI tract as intestinal and biliary
abnormality. 3,6,35 obstruction can occur. Granulocytic sarcomas may be treated with local
Well-established molecular studies that assist in risk stratification in irradiation, but are also responsive to and require treatment with
AML include FLT3-ITD (internal tandem duplication) (poor prognosis) systemic chemotherapy.
and NPM1 and CEBPA mutations (favorable prognosis). These are
especially helpful in determining prognosis in the “normal karyotype” CENTRAL NERVOUS SYSTEM LEUKEMIA
intermediate risk patient group. Presence of a poor-prognostic molecu-
lar marker in a patient with good-risk AML karyotype can alter the Acute leukemias can cause central nervous system (CNS) infiltration
decision to rapidly move toward stem cell transplant following induction with leukemic cells and may be observed as a lymphomatous mass
chemotherapy. There is increasing focus on identification of additional within the brain or spinal cord, or leptomeningeal infiltration with leu-
molecular changes that impact prognosis, including c-kit, DNMT3, and kemic cells which can be detected by MRI. These are most common with

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