Annals of Oncology Advance Access published online on July 22, 2009
Annals of Oncology, doi:10.1093/annonc/mdp297
The frequency, manifestations, and duration of prolonged cytopenias after first-line fludarabine combination chemotherapy
1 Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre
2 Department of Medicine, University of Melbourne, Melbourne, Victoria, Australia
* Correspondence to: Assoc. Prof. J. F. Seymour, Division of Haematology and Medical Oncology, Peter MacCallum Cancer Centre, St Andrew's Place, East Melbourne 3001, Victoria, Australia. Tel: +61-3-9656-1111; Fax: +61-3-9656-1408; E-mail: john.seymour{at}petermac.org
Background: Fludarabine-based chemoimmunotherapy has well-recognised efficacy and short-term toxicity in the treatment of lymphoid malignancies. However, the presence and significance of prolonged cytopenias after completion of treatment have not been thoroughly quantified.
Methods: Sixty-one patients receiving initial therapy with fludarabine-based regimens were categorised according to the presence of post-treatment cytopenias (haemoglobin <110–130 g/l depending on sex and age, neutrophils <2.0 x 109/l, or platelets <140 x 109/l) lasting >3 months.
Results: Persistent cytopenias unrelated to persistent disease were found in 43% of patients. Cytopenias were associated with clinically important rates of infection and transfusion requirement (P = 0.03) and predicted for worse overall survival (61% versus 96% at 60 months, P = 0.05). Increasing age predicted for persistent cytopenias (P = 0.02), but the presence of pretreatment cytopenias and delivered dose intensity were not predictive. The median times to resolution of anaemia, neutropenia, and thrombocytopenia were 7, 9, and 10 months, respectively.
Conclusions: Cytopenias often persist >3 months after first-line fludarabine combination therapy and can lead to important clinical sequelae. Although cytopenias generally resolve over time, treating physicians should be aware of these factors when considering fludarabine combination chemotherapy and when documenting treatment response status in chronic lymphocytic leukaemia.
chemotherapy complications, FCR, fludarabine, post-chemotherapy cytopenias
Present address: Division of Blood and Marrow Transplantation, Department of Medicine, Stanford University, Stanford, CA, USA. Received for publication November 19, 2008. Revision received April 16, 2009. Accepted for publication April 27, 2009.