Page 1494 - Williams Hematology ( PDFDrive )

1468 Part X: Malignant Myeloid Diseases Chapter 89: Chronic Myelogenous Leukemia and Related Disorders 1469

Treatment of eosinophilic leukemia and reviewed the literature regarding that
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Treatment of most patients with CMML has been unsatisfactory, and phenotypic designation. In 1975, Chusid and colleagues described 14
remissions of any duration are uncommon. The age and performance cases of hypereosinophilic syndrome, highlighted the frequency of sec-
status of the patient are considered in determining the intensity of treat- ondary cardiac and neurologic disorders, and suggested the existence of
ment. Cytarabine, either standard or low-dose, etoposide, hydroxyurea, a continuum of manifestations. Because some cases had clonal cytoge-
and other approaches used for the oligoblastic myelogenous leukemias netic abnormalities and hematologic findings compatible with a clonal
have been attempted, but with little success (Chap. 88). Decitabine and myeloid disease, the presence of eosinophilic leukemia was suspected in
5-azacytidine have been useful in a small proportion of patients. 905,906 this apparently heterogeneous group of patients.
One study of azacytidine treatment reported a complete response in 11 The relationship of blood eosinophilia to clonal myeloid diseases
percent, a partial response in 3 percent, and hematologic improvement is complex because the former can be reactive or represent acute eosin-
in 25 percent. The median survival of responders was 15 months com- ophilic leukemia, chronic eosinophilic leukemia, or eosinophilia asso-
pared to 12 months among nonresponders, a modest result. Unfor- ciated with a different category of disease, such as BCR-ABL1–positive
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tunately, although a particular approach may confer significant benefit CML, primary myelofibrosis, oligoblastic leukemia (MDS), or mastocy-
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in a small proportion of cases, determining which patients will respond tosis. Chronic eosinophilic leukemia is a BCR-ABL1–negative, clonal
is not possible, except by trial and error. An exception is the patient myeloid disease with a striking eosinophilia in the blood and marrow,
with a translocation involving PDGFR-β, which itself occurs in only often with clonal cytogenetic abnormalities that have features includ-
a small percentage of patients. In the case of PDGFR-β fusion genes ing, when present, cytogenetic findings that usually distinguish chronic
with several of the partner genes, imatinib 400 mg/day has resulted in eosinophilic leukemia from other clonal myeloid diseases that may have
normal blood counts, cytogenetic remissions, and, occasionally, molec- an associated eosinophilia, such as CMML. The phenotype of the eosin-
ular remission. 915–917,922,923 These fortunate patients probably will benefit ophilic variant of CMML overlaps somewhat with that of chronic eos-
from this treatment, as evidenced by prolonged remissions and survival, inophilic leukemia. However, the fusion gene associated with CMML
compared to other drug options, but the number of patients and dura- involves the PDGFR-β (see “Chronic Myelomonocytic Leukemia”
tion of followup do not permit quantitative estimates at this point. Allo- above), whereas in chronic eosinophilic leukemia the cytogenetic find-
geneic stem cell transplantation is an option for the small proportion ings are different and in some cases involve PDGFR-α. This definition
of younger patients with an appropriate matched-related or unrelated of chronic eosinophilic leukemia recognizes that, at the margins, clas-
donor. 924 sification may be arbitrary. Studies in cases with the FIP1L1–PDGFR-α
translocation were consistent with multilineage involvement, consistent
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Course and Prognosis with an origin in a pluripotential lymphohematopoietic cell. Another
Median survival in CMML is approximately 12 months, with a range from report found multilineage involvement but with a presumptive lesion in
approximately 1 to more than 60 months. Approximately 20 percent of a multipotential, not pluripotential, hematopoietic cell. 933
patients progress to frank AML. Arbitrary stratification of CMML into
types 1 (<5 percent blood myeloblasts) and 2 (5 to 20 percent blood mye- Signs and Symptoms
loblasts) based on the height of the blast count has been proposed, but Fever, cough, weakness, easy fatigability, dyspnea, abdominal pain,
distinguishing patients by whether, for example, they have 4 (type 1) or maculopapular rash, cardiac symptoms and signs of heart failure, and
8 percent blasts (type 2) on a marrow examination is of little use for a variety of neurologic manifestations ranging from peripheral neur-
care of an individual patient. Blast percentage may be a significant cor- opathy to cerebral encephalomalacia may occur, ranging from mild to
relate with outcome in any large group of patients with a clonal mye- severe in expression. Splenomegaly often is evident.
loid disease, and this factor among several others should guide therapy.
Clusters of prognostic variables have been used to stratify patients into Laboratory Findings
risk groups for survival duration. In general, the severity of the ane- Eosinophilia is a constant finding (see Chap. 62, Fig. 62–3). Anemia
mia, the cytogenetic risk category, and the height of the blast percentage usually but not always is present at the time of presentation. The leu-
are the most important. Other variables that may confer a shorter life kocyte count may be high-normal or more often elevated. Platelet
expectancy are height of the absolute lymphocyte count, high sponta- counts often are normal or mildly decreased. The marrow shows mye-
neous rates of myelomonocytic colony growth, higher total leukocyte locytic and eosinophilic hyperplasia and, occasionally, Charcot-Leyden
counts, higher LDH level, and larger spleen size. 925–927 These risk factors crystals. Mast cells, often spindle-shaped, may be increased. In the
for progression are validated in large groups of patients but the confi- FIP1L1–PDGFR-α type of chronic eosinophilic leukemia, which
dence intervals are not shown. In an individual patient the variability may make up approximately 14 percent of cases of primary eosino-
in outcome is great based on such variables; careful clinical observation philia not found to be reactive to another disease, marrow aggregates
for progression is most important. Unfortunately, at this time, unless of spindle-shaped mast cells are invariably found (see “Cytogenetic
the patient is a candidate for imatinib therapy or allogeneic stem cell Findings” below). 933,934 Megakaryocytes usually are present but may
transplantation, long-term salutary therapeutic effects are uncommon. appear dysmorphic. Reticulin fibrosis is common. Immunophenotyp-
ing and PCR do not show evidence of either a clonal T-cell population
CHRONIC EOSINOPHILIC LEUKEMIA or T-cell–receptor rearrangement. Pulmonary function studies may
provide evidence of fibrotic (restrictive) lung disease. Echocardiogra-
History and Definition phy may detect mural thrombi, thickening (fibrosis) of the ventricular
The recognition of eosinophilic lineage prominence in myelogenous wall, valvular dysfunction from papillary muscle, and chordae fibrosis.
leukemia dates to a case published in 1912. In 1968, the term hypereo- Magnetic resonance imaging can detect subendocardial fibrosis, thick-
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sinophilic syndrome was introduced to encompass a group of disorders ening of ventricles, and markedly reduced ventricular lumen volume.
with (1) prolonged exaggerated eosinophilia without an apparent cause, Serum immunoglobulin (Ig) E, vitamin B , and tryptase levels usually
12
(2) frequent cardiac and neurologic tissue damage, (3) a poor or tran- are elevated. Skin biopsy of lesions uncovers intense eosinophilic infil-
sient response to therapy, and (4) a progressive course and a high fatality trates. Neural or brain biopsy may disclose eosinophilic infiltrates, often
rate. Shortly thereafter, Benvenisti and Ultmann presented five cases perivascular, with microthrombi, axonal degeneration, and gliosis.
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