Page 1319 - Hematology_ Basic Principles and Practice ( PDFDrive )

Chapter 71 Eosinophilia, Eosinophil-Associated Diseases, Eosinophilic Leukemias, and the Hypereosinophilic Syndromes 1165

prognosis is poor. Therefore, early allogeneic HSCT should be con- extensive knowledge about the pathogenesis of HE and HES etiolo-
sidered whenever possible. gies, and the advent of novel drugs such as PDGFR-targeting TKIs.
Notably, today, front-line therapy is largely dependent on the under-
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lying disease and the molecular targets detectable in neoplastic cells.
Organ-Restricted HE Syndromes In patients in whom eosinophils display mutated forms of PDGFRs,
imatinib is considered standard front-line therapy. By contrast, in
There are other clinical conditions and syndromes accompanied by patients with idiopathic HES (HES I) and those with HES L , cortico-
HE-related organ damage that cannot be classified (diagnosed) as steroids remain standard front-line therapy. However, there are also
typical HES. A special group of such disorders are organ-restricted patients in whom an initial staging and grading and/or molecular
inflammatory conditions, such as eosinophilic colitis, eosinophilic studies suggest that neither steroids nor imatinib will work. These
pneumonia, or eosinophilic esophagitis (see Table 71.4B). In these cases include, among others, patients with an advanced myeloid
patients, cytokine production and disease manifestations are typically neoplasm without a PDGFR mutation (e.g., AML-eo, MDS-eo, or
restricted to one single-organ system, in contrast to the classical forms SM-eo) and patients with rearranged FGFR genes. In many of these
of HES and most of the above-described specific syndromes. The cases, the primary treatment plan includes intensive chemotherapy
etiology of these organ-restricted HE syndromes remains largely and allogeneic HSCT.
unknown. In many instances, infectious or toxic agents or specific All in all, a number of different therapeutic approaches for the
allergens are felt to play a pathogenetic role. In addition, genetic or treatment of HES and of the underlying (eosinophil) disorder(s)
epigenetic factors may contribute to disease manifestations. Depend- detected in these patients are available. In the following sections,
ing on disease severity, suspected etiology, and presence of comorbidi- these treatment approaches are briefly reviewed and discussed.
ties, a treatment-plan is established. In many cases, corticosteroids are
prescribed. In those with suspected allergy, additional drugs, such as
antihistamines or leukotriene antagonists, have been recommended. Corticosteroids
The prognosis is variable and depends largely on the underlying etiol-
ogy and response to treatment. Most patients respond to corticoste- In patients with idiopathic HES (HES I ) and HES L , corticosteroids
roids. In some patients, an underlying (initially unrecognized) are considered standard front-line therapy. By contrast, in patients
systemic disease, infectious disease, or local tumor is diagnosed with HES R and HES N , corticosteroids should only be considered
during follow-up. In these patients, the prognosis and treatment as an adjunct to more specific treatment, in order to stop eosino-
depends on the type and stage of the underlying disease. phil activation and eosinophil recruitment as early as possible. In
patients with a (suspected) infection, diabetes mellitus, an ulcerative
TREATMENT ALGORITHM, TREATMENT OPTIONS GI tract disease, or arterial hypertension, corticosteroids should
be administered with caution and with recognition of potential
AND PROGNOSIS side effects and the related risk. In patients with HES I and HES L ,
corticosteroid therapy, usually in form of prednisone at 1 mg/kg/
When establishing the management plan for a patient with HE, day (initial dose) is usually effective in reducing eosinophil counts
several important questions have to be addressed. First, the final to normal levels, with overall response rates of >75% in HES I . In
diagnosis concerning the presence or absence of HES, and the pres- contrast, most patients with HES N do not respond to corticosteroid
ence and nature of the underlying disease, if present, has to be firmly therapy.
established. Second, it is important to decide whether the patient The mechanisms of action by which corticosteroids suppress HE
needs symptomatic or/and interventional therapy. In some of these in HES I and HES L patients are only partly understood. Steroids act
HE patients, a wait-and-watch strategy may be acceptable, whereas through specific corticosteroid receptors that are present in the
in other cases (when HES is diagnosed) specific therapy needs to be cytoplasm of eosinophils and eosinophil precursor cells, but also in
introduced quickly. Finally, the optimal treatment plan and most the cytoplasm of T lymphocytes and mast cells. It has also been
useful drugs need to be defined. The type of therapy varies depending described that steroids effectively block the production of various
on the underlying condition and the type of HES. 24 eosinotropic cytokines by T lymphocytes. In addition, corticosteroids
effectively counteract T-cell expansion. Based on these effects, corti-
costeroids may act directly and indirectly to block HE in HES
Primary Management and Algorithm patients, namely by (1) inducing growth inhibition and apoptosis of
eosinophils and their precursor cells, by (2) directly blocking eosino-
In many cases, treatment of HES is a straightforward approach. For phil recruitment and migration, and by (3) inhibiting the production
example, reactive HES is often managed (and resolved) quite easily and release of eosinophilopoietic cytokines by T lymphocytes and
by treating the underlying disease, such as a helminth infection or an other immune cells.
autoimmune disease. In cases with idiopathic HE or HES and those As mentioned earlier, long-term treatment with steroids is associ-
with advanced or aggressive disease, however, treatment should always ated with a risk of (severe) side effects. Therefore, steroids should be
be performed in collaboration with a specialized center and in an tapered down (and discontinued) whenever possible, especially in
interdisciplinary approach involving hematologists, immunologists, cases with HES R and HES N . However, in many patients with HES I ,
pathologists, and/or laboratory specialists, as needed. maintenance therapy with corticosteroids is required to control
In patients with HE US and HE F , it seems appropriate to follow the disease activity. In these patients, the steroid dose applied should be
patient without treatment provided there are no signs or symptoms reduced to a minimum. In fact, even though corticosteroids are
of eosinophil-related organ damage despite careful medical monitor- “natural” substances and very effective in reducing eosinophil counts
ing. However, both HE US and HE F must be regarded as provisional in HES I , chronic use of steroids is associated with the risk of serious
diagnoses, and in both conditions organ damage may develop over adverse events and long-term toxicity. Once reduction of the eosino-
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time. In addition, a hematologic or other underlying disease may be phil count to below 1500/mm and symptom control have been
detected during follow-up of these cases. In the reactive form of HES, achieved, the corticosteroid dose should be tapered. Increases in
it is important to define and to treat the underlying condition. eosinophil numbers on a prednisone dose greater than 10 mg daily
Additional symptomatic therapy, often in the form of corticosteroids, and/or reappearance of symptoms or signs of organ damage are
may be required to control eosinophil activation in these patients, indications for the addition of other agents to the steroid regimen. A
especially when eosinophil counts are high or/and cells undergo rapid number of different drugs may be useful as steroid-sparing agents in
lysis, which may occur during treatment with cytotoxic drugs. 24 patients with HES. These drugs include, among others, conventional
In the past, most patients with HES received corticosteroids as cytostatic agents such as HU or cyclophosphamide, IFN-α, and the
front-line therapy. However, this strategy has changed with more IL-5-targeting antibody mepolizumab. 25