Addition of Fresh Frozen Plasma to Rituximab Induces a Major Clinical and Laboratory Response in Patients with Refractory Advanced CLL.
Authors: Klepfish Abraham , Schattner Amichay , Kotsianidis Iannis , Goldshtein Daniela , Ghoti Hussam , Patchenko Paulina , Rachmilewitz Eliezer 
Published: November 2019

Abstract
Rituximab (RTX) is a chimeric monoclonal antibody targeting the CD20 on B lymphocytes. It is effective in patients with B cell malignancies, but the response in CLL is inferior. We report 5 patients with advanced, therapy-resistant CLL, successfully treated by combining fresh frozen plasma (FFP) with standard-dose RTX. Patients. The patients’ data before treatment are summarized (Table1). Patient No.4, resistant only to Chlorambucil, had advanced disease and autoimmune hemolytic anemia with hemoglobin of 4gr/dL. Treatment. Treatment consisted of 2 units of FFP followed with standard-dose RTX: 375 mg/m2, repeated every 4–8 weeks.
Results and comments. Post-treatment data are summarized in table 2. A major improvement of symptoms, a significant reduction of lymph nodes and splenomegaly and correction of anemia and thrombocytopenia without inducing neutropenia has been achieved. The response was durable. Patient 1 died of E. coli sepsis 4 months after the last cycle. Treatment-related toxicity was minimal. Patient 2 developed a moderate tumor lysis syndrome and transient thrombocytopenia. He is now in un-maintained hematological remission for over 15 months. Complement-dependent cell lysis (CDC) is one of the major mechanisms of the cytoreductive effect of RTX. Following our observation of a rapid and dramatic response to a combination of FFP and RTX in a patient with advanced CLL with very high WBC counts, refractory to alkylating agents, to Fludarabine, and to RTX both alone and in combination with chemotherapy [Klepfish A. et al. Lancet Oncol.2007;8(4):361], four additional patients were treated with the same regimen with similar results. The mechanism of this phenomenon is still under investigation. It is possible, that providing FFP-derived complement enabled the response by correcting qualitative and quantitative abnormalities of the complement system reported in advanced CLL, consequently enhancing CDC by RTX. We suggest therefore, that adding FFP to RTX may provide a useful therapeutic option with minimal toxicity in patients with advanced CLL resistant to immuno-chemotherapy. A phase II clinical trial is now in progress.
Patients data before treatment Gender/Age Disease duration (yr) No of previous treatments B Symptoms Lymph count/mcl Hb(g/dl) / Plt/mcl LN / Spleen Other F/59 12 3 + RTX + 448,000 9.0 / 40,000 7cm / 20cm Bed ridden, diarrhea, colon involvement M/79 16 3 − 234,000 9.7 / 75,000 1.5cm / 22cm Resp. Infections M/70 11 3 + RTX − 169,000 6.4 / 13,000 6cm / Normal Resp. Infections M/76 8 1 + 163,000 9.7 / 70,000 2cm / 6cm BCM AIHA F/72 18 3 + RTX + 178,000 10.2 / 117,000 2.5cm / 7cm BCM COPD - severe Patients data after treatment No of cycles B symptoms Lymph/mcl Hb(gm) / Plt/mcl LN / Spleen Other Overall survival (mo) 4 - 38,200 11.1 / 92,000 2cm / 17cm Ambulatory, diarrhea resolved 7 5 - 900 13.0 / 128,000 Normal / 13cm Asymptomatic 20+ 5 - 3,200 11.0 / 58,000 3cm / 13cm Anemia 15+ 4 - 9,800 14.2 / 83,000 Normal / Normal Asymptomatic 4+ 2 - 74,300 14.7 / 140,000 Normal / 3cm BCM COPD 8+