Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic leukemia.
OBJECTIVE
Patients with hypereosinophilic syndrome (HES) or chronic eosinophilic leukemia (CEL) that are refractory to standard therapies are difficult to manage and have significantly shortened life expectancy.


METHODS
CD52 is a surface glycoprotein highly expressed on eosinophils. We treated 11 patients with advanced HES/CEL with alemtuzumab, a humanized anti-CD52 monoclonal antibody. Alemtuzumab was administered, in general, first in escalating doses (5, 10, 30 mg i.v. on days 1-3), then at the tolerated dose thrice per week for a total of 12 doses. Patients with complete hematologic response (CHR; normal percent and absolute eosinophil count) were allowed to continue therapy once weekly as maintenance.


RESULTS
Ten patients (91%) achieved CHR after a median of 2 weeks (0.5-5 weeks) of therapy. Bone marrow eosinophilia resolved in four of seven evaluable patients. The median duration of CHR was 3 months (1.5-17+ months). Seven of the 10 CHR patients relapsed, five while off-therapy. Two patients achieved second CHR upon alemtuzumab rechallenge. Three patients experienced mild infusion-related symptoms, two developed cytomegalovirus reactivation requiring therapy, and one developed orbital lymphoma that was successfully treated.


CONCLUSIONS
Our limited experience suggests alemtuzumab to be a valuable therapy for advanced HES or CEL, refractory to standard therapies, and supports the clinical evaluation of alemtuzumab in a larger trial.
Verstovsek
Srdan
S
Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA. sverstov@mdanderson.org
Tefferi
Ayalew
A
Kantarjian
Hagop
H
Manshouri
Taghi
T
Luthra
Raja
R
Pardanani
Animesh
A
Quintás-Cardama
Alfonso
A
Ravandi
Farhad
F
Ault
Pat
P
Bueso-Ramos
Carlos
C
Cortes
Jorge E
JE
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074323:Alemtuzumab; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm / Q000008:administration & dosage / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D004334:Drug Administration Schedule; D004341:Drug Evaluation; D004804:Eosinophils; D005260:Female; D006801:Humans; D017681:Hypereosinophilic Syndrome / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D007958:Leukocyte Count; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000912:Antibodies, Neoplasm; D000074323:Alemtuzumab