Hypereosinophilic syndrome: a multicenter, retrospective analysis of clinical characteristics and response to therapy.
BACKGROUND
Hypereosinophilic syndrome (HES) is a heterogeneous group of rare disorders defined by persistent blood eosinophilia > or =1.5 x 10(9)/L, absence of a secondary cause, and evidence of eosinophil-associated pathology. With the exception of a recent multicenter trial of mepolizumab (anti-IL-5 mAb), published therapeutic experience has been restricted to case reports and small case series.


OBJECTIVE
The purpose of the study was to collect and summarize baseline demographic, clinical, and laboratory characteristics in a large, diverse cohort of patients with HES and to review responses to treatment with conventional and novel therapies.


METHODS
Clinical and laboratory data from 188 patients with HES, seen between January 2001 and December 2006 at 11 institutions in the United States and Europe, were collected retrospectively by chart review.


RESULTS
Eighteen of 161 patients (11%) tested were Fip1-like 1-platelet-derived growth factor receptor alpha (FIP1L1-PDGFRA) mutation-positive, and 29 of 168 patients tested (17%) had a demonstrable aberrant or clonal T-cell population. Corticosteroid monotherapy induced complete or partial responses at 1 month in 85% (120/141) of patients with most remaining on maintenance doses (median, 10 mg prednisone equivalent daily for 2 months to 20 years). Hydroxyurea and IFN-alpha (used in 64 and 46 patients, respectively) were also effective, but their use was limited by toxicity. Imatinib (used in 68 patients) was more effective in patients with the FIP1L1-PDGFRA mutation (88%) than in those without (23%; P < .001).


CONCLUSIONS
This study, the largest clinical analysis of patients with HES to date, not only provides useful information for clinicians but also should stimulate prospective trials to optimize treatment of HES.
Ogbogu
Princess U
PU
National Institute of Allergy and Infectious Diseases, Laboratory of Parasitic Diseases, National Institutes of Health, Bethesda, MD 20892, USA. aklion@nih.gov
Bochner
Bruce S
BS
Butterfield
Joseph H
JH
Gleich
Gerald J
GJ
Huss-Marp
Johannes
J
Kahn
Jean Emmanuel
JE
Leiferman
Kristin M
KM
Nutman
Thomas B
TB
Pfab
Florian
F
Ring
Johannes
J
Rothenberg
Marc E
ME
Roufosse
Florence
F
Sajous
Marie-Helene
MH
Sheikh
Javed
J
Simon
Dagmar
D
Simon
Hans-Uwe
HU
Stein
Miguel L
ML
Wardlaw
Andrew
A
Weller
Peter F
PF
Klion
Amy D
AD
D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; D054414:Chemokine CCL17 / Q000097:blood; D002648:Child; D016572:Cyclosporine / Q000008:administration & dosage / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006801:Humans; D006918:Hydroxyurea / Q000008:administration & dosage / Q000627:therapeutic use; D017681:Hypereosinophilic Syndrome / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D015848:Interleukin-5 / Q000097:blood; D008297:Male; D008875:Middle Aged; D015514:Oncogene Proteins, Fusion / Q000276:immunology* / Q000378:metabolism; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000276:immunology* / Q000378:metabolism; D012189:Retrospective Studies; D053802:Tryptases / Q000097:blood; D055815:Young Adult; D039221:mRNA Cleavage and Polyadenylation Factors / Q000276:immunology* / Q000378:metabolism
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001549:Benzamides; C106230:CCL17 protein, human; D054414:Chemokine CCL17; C508599:IL5 protein, human; D016898:Interferon-alpha; D015848:Interleukin-5; D015514:Oncogene Proteins, Fusion; D010879:Piperazines; D011743:Pyrimidines; D039221:mRNA Cleavage and Polyadenylation Factors; C515492:reslizumab; D016572:Cyclosporine; D000068877:Imatinib Mesylate; C434107:mepolizumab; C479819:FIP1L1-PDGFRA fusion protein, human; D020796:Receptor, Platelet-Derived Growth Factor alpha; D053802:Tryptases; D006918:Hydroxyurea