2‐Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic hypereosinophilic syndrome

Jabbour, Elias; Verstovšek, Srđan; Giles, Francis J.; Gandhi, Varsha; Cortes, Jorge; O’Brien, Susan; Plunkett, William; Jackson, C. Ellen; Kantarjian, Hagop M.; Andreeff, Michael

doi:10.1002/cncr.21186

Cited by 25 publications

(13 citation statements)

References 75 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hematologic benefit has been observed with second‐line and third‐line agents, including vincristine, cyclophosphamide, and etoposide . Responses to 2‐chlorodeoxyadenosine alone or in combination with cytarabine, and cyclosporine‐A have also been reported in HES, with a discontinuation rate of 82% with cyclosporine A in one series due to poor tolerance . Recently, dexpramipexole (an oral synthetic aminobenzothiazole) was incidentally found to decrease absolute eosinophil counts by an unknown mechanism in a phase 3 trial of amyotrophic lateral sclerosis.…”

Section: Risk‐adapted Therapymentioning

confidence: 99%

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

2019

View full text Add to dashboard Cite

Disease overview: The eosinophilias encompass a broad range of non-hematologic (secondary or reactive) and hematologic (primary or clonal) disorders with potential for end-organ damage.Diagnosis: Hypereosinophilia has generally been defined as a peripheral blood eosinophil count greater than 1.5 × 10 9 /L, and may be associated with tissue damage. After exclusion of secondary causes of eosinophilia, diagnostic evaluation of primary eosinophilias relies on a combination of various tests. They include morphologic review of the blood and marrow, standard cytogenetics, fluorescence in situ-hybridization, flow immunophenotyping, and T-cell clonality assessment to detect histopathologic or clonal evidence for an acute or chronic hematolymphoid neoplasm. Risk stratification: Disease prognosis relies on identifying the subtype of eosinophilia. After evaluation of secondary causes of eosinophilia, the 2016 World Health Organization endorses a semi-molecular classification scheme of disease subtypes. This includes the major category "myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA, PDGFRB, or FGFR1 or with PCM1-JAK2", and the MPN subtype, "chronic eosinophilic leukemia, not otherwise specified" (CEL, NOS). Lymphocyte-variant hypereosinophilia is an aberrant T-cell clone-driven reactive eosinophila, and idiopathic hypereosinophilic syndrome (HES) is a diagnosis of exclusion.Risk-adapted therapy: The goal of therapy is to mitigate eosinophil-mediated organ damage. For patients with milder forms of eosinophilia (eg, <1.5 × 10 9 /L) without symptoms or signs of organ involvement, a watch and wait approach with close-follow-up may be undertaken. Identification of rearranged PDGFRA or PDGFRB is critical because of the exquisite responsiveness of these diseases to imatinib. Corticosteroids are first-line therapy for patients with lymphocyte-variant hypereosinophilia and HES. Hydroxyurea and interferon-α have demonstrated efficacy as initial treatment and in steroid-refractory cases of HES. In addition to hydroxyurea, second line cytotoxic chemotherapy agents, and hematopoietic stem cell transplantation have been used for aggressive forms of HES and CEL, with outcomes reported for limited numbers of patients. The use of antibodies against interleukin-5 (IL-5) (mepolizumab), the IL-5 receptor (benralizumab), as well as other targets on eosinophils remains an active area of investigation.

show abstract

Section: Risk‐adapted Therapymentioning

confidence: 99%

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

2019

View full text Add to dashboard Cite

show abstract

“…83 Low-dose hydroxyurea (500 mg daily) has been reported to potentiate the effects of interferon-a without increasing toxicity in M-HES 84,85 and is a reasonable alternative to escalating the interferona dose in HES patients who demonstrate partial response to interferon-a alone. Cyclosporine, 16 alemtuzumab, 86,87 and 2-chlorodeoxyadenosine 88 have been used to treat small numbers of HES patients with some success but with considerable toxicity and are additional options for treatment-refractory patients. A variety of other agents have been used in the treatment of isolated cases of HES, but data are insufficient to recommend their routine use.…”

Section: Idiopathic Hesmentioning

confidence: 99%

How I treat hypereosinophilic syndromes

Klion

2015

Blood

208

126

View full text Add to dashboard Cite

Hypereosinophilic syndromes (HESs) are a group of rare disorders characterized by peripheral blood eosinophilia of 1.5 × 109/L or higher and evidence of end organ manifestations attributable to the eosinophilia and not otherwise explained in the clinical setting. HESs are pleomorphic in clinical presentation and can be idiopathic or associated with a variety of underlying conditions, including allergic, rheumatologic, infectious, and neoplastic disorders. Moreover, the etiology of the eosinophilia in HESs can be primary (myeloid), secondary (lymphocyte-driven), or unknown. Although corticosteroids remain the first-line therapy for most forms of HESs, the availability of an increasing number of novel therapeutic agents, including tyrosine kinase inhibitors and monoclonal antibodies, has necessarily altered the approach to treatment of HESs. This review presents an updated treatment-based approach to the classification of patients with presumed HES and discusses the roles of conventional and novel agents in the management of these patients.

show abstract

“…Other treatments are cyclosporin A (Zabel and Schlaak, 1991; Nadarajah et al , 1997). If signs of malignant transformation are diagnosed, the treatment lines specific for T‐cell lymphoma are proposed, with chemotherapy (cyclophosphamide, hydroxydoxorubicin, oncovin, prednisone; CHOP‐like regimen) (Granel et al , 2000), associated or not with monoclonal antibodies (Pitini et al , 2004; Sefcick et al , 2004), fludarabine, 2‐chlorodeoxyadenosine (2‐CdA) (Ueno et al , 1997; Jabbour et al , 2005). In resistant or recurrent cases, intensive high‐dose chemotherapy followed by HSCT can be used (Ueno et al , 2002).…”

Section: Hes Treatmentmentioning

confidence: 99%

Oral mucosa lesions in hypereosinophilic syndrome – an update

2008

View full text Add to dashboard Cite

Hypereosinophilic syndrome (HES) is a rare disorder characterized by persistent and marked eosinophilia. Some HES forms have a poor prognosis, either because of end-organ damage (particularly endomyocardial fibrosis), or because of associated myeloid leukemia or malignant T-cell lymphoma. Oral mucosa ulcerations can be early clinical signs in severe forms. They are discrete, round or oval, sometimes confluent ulcers or erosions, located on non-keratinized, unattached oral mucosa. In the last 15 years a better understanding of eosinophil biology has led to a new clinical classification of HES. The lymphocytic form is characterized by T-lymphocyte clonality, IL-5 production, and a possible progression to T-cell lymphoma. Oral lesions are more frequently associated with the myeloproliferative form, characterized by an increased risk of developing myeloid malignancies and a good response to a recent anti-tyrosine kinase therapy (imatinib mesylate). The target of imatinib is a novel kinase resulting from an 800-kb deletion on chromosome 4. Recently, the resulting FIP1L1-PDGFRalpha fusion gene was characterized as a marker of response to imatinib. Exclusion of other erosive ulcerative oral disease and early recognition of HES in patients with oral ulcerations, and precise characterization of the lymphocytic or myeloproliferative form are therefore important to rapidly initiate an effective therapy.

show abstract

2‐Chlorodeoxyadenosine and cytarabine combination therapy for idiopathic hypereosinophilic syndrome

Cited by 25 publications

References 75 publications

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

World Health Organization‐defined eosinophilic disorders: 2019 update on diagnosis, risk stratification, and management

How I treat hypereosinophilic syndromes

Oral mucosa lesions in hypereosinophilic syndrome – an update

Contact Info

Product

Resources

About