Filgrastim and alemtuzumab (Campath-1H) for refractory chronic lymphocytic leukemia

• Published in: Leukemia Vol. 19; no. 7; pp. 1207 - 1210
• Main Authors: LIN, T. S, FLINN, I. W, LUCAS, M. S, PORCU, P, SICKLER, J, MORAN, M. E, LUCAS, D. M, HEEREMA, N. A, GREVER, M. R, BYRD, J. C
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 01-07-2005; Nature Publishing Group
• Subjects: Aged; Alemtuzumab; Antibodies, Monoclonal - administration & dosage; Antibodies, Monoclonal - adverse effects; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm - administration & dosage; Antibodies, Neoplasm - adverse effects; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Chronic infection; Chronic lymphocytic leukemia; Clinical trials; Cytomegalovirus; Dose-Response Relationship, Drug; Etiology; Female; Fever; Filgrastim; Fludarabine; Ganciclovir; Granulocyte colony-stimulating factor; Granulocyte Colony-Stimulating Factor - administration & dosage; Granulocyte Colony-Stimulating Factor - adverse effects; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemia, Lymphocytic, Chronic, B-Cell - drug therapy; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymph nodes; Lymphatic leukemia; Male; Medical sciences; Middle Aged; Monoclonal antibodies; Neutropenia; Neutropenia - chemically induced; Patients; Pneumonia; Recombinant Proteins; Recurrence; Survival Rate; Therapy; Time Factors; Toxicity; Cytomegalovirus; Treatment resistance; CLL; Hematology; Herpesviridae; Cytokine; Malignant hemopathy; Alemtuzumab; Monoclonal antibody; Betaherpesvirinae; CMV; G-CSF; Filgrastim; Infection; Virus; Chronic; Granulocyte colony stimulating factor; Chronic lymphocytic leukemia; Lymphoproliferative syndrome; Viral disease; CAMPATH
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/sj.leu.2403782

Alemtuzumab (anti-CD52; Campath-1H) is effective in fludarabine-refractory chronic lymphocytic leukemia (CLL), but is associated with infection and early onset neutropenia. To reduce toxicity, filgrastim (G-CSF) was administered concurrently with alemtuzumab. In total, 14 CLL patients (median age 59) with a median of 3.5 prior regimens (range 1--12) received i.v. alemtuzumab, stepped up from 3 to 30 mg the first week, then 30 mg thrice weekly for 12 weeks. Filgrastim 5 microg/kg was administered daily 5 days before and throughout alemtuzumab therapy. Six patients developed cytomegalovirus (CMV) reactivation 3--6 weeks into treatment; six patients developed fever, three neutropenia, and one pneumonia. The patient with CMV pneumonia died; ganciclovir cleared CMV in the other patients. Five patients developed early neutropenia (weeks 2--5). Four patients developed delayed neutropenia (weeks 10--13) unassociated with CMV reactivation. Nine patients ceased therapy because of infectious and hematologic toxicity. Five partial responses were noted, all in patients with lymph nodes>cm, lasting a median of 6.5 months (range 5--13). Filgrastim and alemtuzumab were given concurrently with manageable infusion toxicity and clinical activity, but the efficacy of this regimen was limited by delayed neutropenia of unclear etiology and CMV reactivation. Filgrastrim should not be administered prophylactically during alemtuzumab therapy outside clinical trials.