Addition of fresh frozen plasma as a source of complement to rituximab in advanced chronic lymphocytic leukaemia

Abstract

A 59-year-old woman with a 12-year history of chronic lymphocytic leukaemia was sequentially treated with chlorambucil pulses, followed by ten cycles of fludarabine and cyclophosphamide for 5 years. Initially, protracted responses of up to 18 months were obtained of which the best was partial response according to the working group criteria of the National Cancer Institute. 1 Cheson BD Bennett JM Grever M et al. National Cancer Institute-sponsored Working Group guidelines for chronic lymphocytic leukemia: revised guidelines for diagnosis and treatment. Blood. 1996; 87: 4990-4997 PubMed Google Scholar However, during the final year of treatment the disease progressed, with severe malaise and marked B symptoms (eg, night sweats and weight loss) associated with massive lymphadenopathy and splenomegaly. Concentration of peripheral blood lymphocytes increased to 450×109/L and serum lactate dehydrogenase reached 2400 IU/L. This time the disease was resistant to regimens that contained fludarabine. Alemtuzumab was not yet approved for use in Israel at that time. The disease was also resistant to treatment with six cycles of rituximab combined with dose-modified cyclophosphamide, doxorubicin, vincristine, and prednisone-like chemotherapy (CHOP-R). Modest response was noted with the first four CHOP-R cycles, whereas two additional cycles yielded no lasting response. After the last cycle, complete blood count showed haemoglobin (Hb) concentration as 110 g/L, white blood cells (WBC) 180×109/L (92% lymphocytes), and platelets 200×109/L. However, within 8 weeks the patient deteriorated and showed no response to single agent rituximab. Her last blood count was Hb 90 g/L, WBC 458×109/L (450×109/L lymphocytes), and platelets 40×109/L. The patient was, therefore, assessed as having advanced and progressive disease, supported by the presence of massive peripheral lymph-node enlargement and hepatosplenomegaly (20 cm spleen confirmed by ultrasound). Peripheral blood smears, repeated immunophenotyping, and lymph node biopsy ruled out transformation into aggressive lymphoma (figure). Peripheral blood lymphocytes were positive for CD5, CD19, and CD23, and 40% were positive for CD38. They were negative for FMC7. The patient became catabolic and bed-ridden. She developed chronic culture-negative diarrhoea, which was diagnosed after colonoscopy and biopsy as specific involvement of the colon by chronic lymphocytic leukaemia. Allogeneic stem-cell transplantation was not feasible because no potential donor was available. (A) Bone marrow biopsy showing interstitial and nodular patterns of infiltration with small lymphocytes (arrow), characteristic of chronic lymphocytic leukaemia. (B) Lymph node biopsy showing diffuse nodal effacement and perinodal adipose tissue infiltration. Scattered small pale areas, representing proliferation centres, can also be seen (arrow), characteristic of lymph-node involvement by chronic lymphocytic leukaemia (haemotoxylin and eosin stain; ×40 magnification).