Myelosuppression after frontline fludarabine, cyclophosphamide, and rituximab in patients with chronic lymphocytic leukemia: analysis of persistent and new-onset cytopenia.

Abstract

BACKGROUND:

The combination of fludarabine, cyclophosphamide, and rituximab (FCR) has produced improved response rates and a prolonged survival in patients with chronic lymphocytic leukemia (CLL). However, its therapeutic power is counterbalanced by significant hematologic toxicity. Persistent and new-onset cytopenia after the completion of FCR raise concern about disease recurrence, the development of therapy-related myeloid malignancies (TRMM), and infections.

METHODS:

A total of 207 patients with CLL who achieved complete response, complete response with incomplete bone marrow recovery, or nodular partial remission were analyzed after frontline FCR therapy.

RESULTS:

Three months after the completion of therapy, 35% of patients had developed grade 2 to 4 cytopenia (according to Common Terminology Criteria for Adverse Events [version 4.0]). Factors found to be associated with cytopenia at 3 months after therapy were older age, advanced Rai stage disease, and lower baseline blood counts. Moreover, patients with cytopenia were less likely to have completed 6 courses of therapy with FCR. At 6 months and 9 months after therapy, the prevalence of grade 2 to 4 cytopenia was 24% and 12%, respectively. No differences in progression-free survival and overall survival were noted between cytopenic and noncytopenic patients or between patients with persistent and new-onset cytopenia. The prevalence of TRMM was 2.3% and did not differ significantly between cytopenic and noncytopenic patients or between those with persistent and new-onset disease. Late infections were more common in patients who were cytopenic at 9 months (38%) and were mostly bacterial (67%).

CONCLUSIONS:

Cytopenia after the completion of therapy is a common complication of frontline FCR that improves over time, particularly for new-onset cases. The presence of persistent cytopenia (lasting up to 9 months after the completion of therapy) should not raise concern about CLL recurrence of the development of TRMM, but should encourage surveillance for bacterial infections for an additional 9 months.

• Authors: Paolo Strati, William Wierda, Jan Burger, Alessandra Ferrajoli, Constantine Tam, Susan Lerner, Michael J Keating, Susan O'Brien
• Journal: Cancer (Cancer) Vol. 119 Issue 21 Pg. 3805-11 (Nov 01 2013) ISSN: 1097-0142 [Electronic] United States
• PMID: 23943357 (Publication Type: Journal Article)
• Copyright: © 2013 American Cancer Society.

Chemical References

• Antibodies, Monoclonal, Murine-Derived
• Myeloablative Agonists
• Rituximab
• Cyclophosphamide
• Vidarabine
• fludarabine

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Murine-Derived (administration & dosage, adverse effects)
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, therapeutic use)
• Clinical Trials, Phase II as Topic (statistics & numerical data)
• Cyclophosphamide (administration & dosage, adverse effects)
• Female
• Humans
• Immune Tolerance (drug effects)
• Immunotherapy (adverse effects, methods)
• Leukemia, Lymphocytic, Chronic, B-Cell (blood, epidemiology, immunology, therapy)
• Male
• Middle Aged
• Myeloablative Agonists (adverse effects, therapeutic use)
• Neoadjuvant Therapy (adverse effects)
• Pancytopenia (blood, chemically induced, diagnosis, epidemiology)
• Retrospective Studies
• Rituximab
• Treatment Outcome
• Vidarabine (administration & dosage, adverse effects, analogs & derivatives)
• Young Adult