Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia

Srdan Verstovsek, AyalewTefferi, Hagop Kantarjian, Taghi Manshouri, Raja Luthra, Animesh D Pardanani, Alfonso Quintás-Cardama, Farhad Ravandi, Pat Ault, Carlos Bueso-Ramos, Jorge E. Cortes

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

Purpose: 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. Experimental Design: 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.

Original languageEnglish (US)
Pages (from-to)368-373
Number of pages6
JournalClinical Cancer Research
Volume15
Issue number1
DOIs
StatePublished - Jan 1 2009

Fingerprint

Hypereosinophilic Syndrome
Therapeutics
Eosinophils
alemtuzumab
Pdgfra-Associated Chronic Eosinophilic Leukemia
Membrane Glycoproteins
Eosinophilia
Life Expectancy
Cytomegalovirus
Research Design
Bone Marrow
Monoclonal Antibodies
Maintenance

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Verstovsek, S., AyalewTefferi, Kantarjian, H., Manshouri, T., Luthra, R., Pardanani, A. D., ... Cortes, J. E. (2009). Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia. Clinical Cancer Research, 15(1), 368-373. https://doi.org/10.1158/1078-0432.CCR-08-1302

Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia. / Verstovsek, Srdan; AyalewTefferi; Kantarjian, Hagop; Manshouri, Taghi; Luthra, Raja; Pardanani, Animesh D; Quintás-Cardama, Alfonso; Ravandi, Farhad; Ault, Pat; Bueso-Ramos, Carlos; Cortes, Jorge E.

In: Clinical Cancer Research, Vol. 15, No. 1, 01.01.2009, p. 368-373.

Research output: Contribution to journalArticle

Verstovsek, S, AyalewTefferi, Kantarjian, H, Manshouri, T, Luthra, R, Pardanani, AD, Quintás-Cardama, A, Ravandi, F, Ault, P, Bueso-Ramos, C & Cortes, JE 2009, 'Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia', Clinical Cancer Research, vol. 15, no. 1, pp. 368-373. https://doi.org/10.1158/1078-0432.CCR-08-1302
Verstovsek, Srdan ; AyalewTefferi ; Kantarjian, Hagop ; Manshouri, Taghi ; Luthra, Raja ; Pardanani, Animesh D ; Quintás-Cardama, Alfonso ; Ravandi, Farhad ; Ault, Pat ; Bueso-Ramos, Carlos ; Cortes, Jorge E. / Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia. In: Clinical Cancer Research. 2009 ; Vol. 15, No. 1. pp. 368-373.
@article{dbc0d471b2564e4e89e32dc888160247,
title = "Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia",
abstract = "Purpose: 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. Experimental Design: 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.",
author = "Srdan Verstovsek and AyalewTefferi and Hagop Kantarjian and Taghi Manshouri and Raja Luthra and Pardanani, {Animesh D} and Alfonso Quint{\'a}s-Cardama and Farhad Ravandi and Pat Ault and Carlos Bueso-Ramos and Cortes, {Jorge E.}",
year = "2009",
month = "1",
day = "1",
doi = "10.1158/1078-0432.CCR-08-1302",
language = "English (US)",
volume = "15",
pages = "368--373",
journal = "Clinical Cancer Research",
issn = "1078-0432",
publisher = "American Association for Cancer Research Inc.",
number = "1",

}

TY - JOUR

T1 - Alemtuzumab therapy for hypereosinophilic syndrome and chronic eosinophilic Leukemia

AU - Verstovsek, Srdan

AU - AyalewTefferi,

AU - Kantarjian, Hagop

AU - Manshouri, Taghi

AU - Luthra, Raja

AU - Pardanani, Animesh D

AU - Quintás-Cardama, Alfonso

AU - Ravandi, Farhad

AU - Ault, Pat

AU - Bueso-Ramos, Carlos

AU - Cortes, Jorge E.

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Purpose: 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. Experimental Design: 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.

AB - Purpose: 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. Experimental Design: 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.

UR - http://www.scopus.com/inward/record.url?scp=58949090059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58949090059&partnerID=8YFLogxK

U2 - 10.1158/1078-0432.CCR-08-1302

DO - 10.1158/1078-0432.CCR-08-1302

M3 - Article

C2 - 19118067

AN - SCOPUS:58949090059

VL - 15

SP - 368

EP - 373

JO - Clinical Cancer Research

JF - Clinical Cancer Research

SN - 1078-0432

IS - 1

ER -