Page 1059 - Hematology_ Basic Principles and Practice ( PDFDrive )

942 Part VII Hematologic Malignancies

retrospective comparisons between patients with myeloid sarcoma the context in which it is delivered has become more refined. More
and those with AML suggest no significant differences in survival and significance is given to particular subsets of patients: a) patients unfit
a possible survival benefit with HSCT for all groups. 29 for standard chemotherapy (often but not always rightfully under-
stood as those over age 60 years) frequently receive lower intensity
therapies or are enrolled in clinical studies with novel agents (e.g.,
Central Nervous System Disease volasertib, vosaroxin, guadecitabine, venetoclax, SGN-CD33A); b)
more and more particular cytogenetic–molecular abnormalities are
CNS involvement occurs in less than 5% of patients with AML and amenable to targeted, often single-agent, approaches (e.g., FLT3
is therefore much rarer than in ALL. Consequently, there is no role inhibitors, IDH1/2 inhibitors, DOT1L inhibitors, multikinase
for CNS prophylaxis. Before HiDAC, inv(16) AML was associated inhibitors); c) addition of the FLT3 inhibitor midostaurin to standard
with a 30% incidence of CNS leukemia, particularly intracerebral induction therapy improves survival in FLT3 mutated AML;
masses. This particular problem has been virtually eliminated with d) CPX-351 improves survival in older patients with secondary AML;
the use of HiDAC but may still be noted in patients with inv(16) e) the studies of immunotherapy may open up new options. Response
AML in whom HiDAC is not delivered. In the presence of symptoms assessment extends beyond morphologic and cytogenetic remissions
suggestive of CNS disease, further workup should be pursued. and increasingly includes MRD measurements similar to what has
Symptoms are due to raised intracranial pressure, mass effect, or been happening in adult ALL. Molecular signatures and cellular
infiltration of cranial nerves. Whereas CT scan is a convenient modal- pathways that are abnormally activated or regulated in AML blasts
ity to rule out significant anatomic disruptions, it is not very sensitive are contributing to a more complex picture of the biology of AML
to detect more subtle signs of leptomeningeal disease, and, if concerns and, besides providing prognostic information, offer targets for drug
persist, a magnetic resonance image of any CNS structure where development.
disease is suspected should be obtained. Lumbar puncture is a crucial
component of the workup. Blasts in the cerebrospinal fluid may range
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