Successful Induction of a Rapid Improvement of Both Clinical and Laboratory Parameters in a Patient with Advanced CLL by Combining Rituximab with Fresh Frozen Plasma as a Source for Complement. A Novel Therapeutic Approach?.
Authors: Klepfish Abraham , Ghoti H. , Rachmilewitz E.A. 
Published: October 2019

Abstract
Background
Chronic lymphocytic leukemia (CLL), a chronic proliferative disorder of mature-looking B-lymphocytes, is the most common leukemia in the Western world. Rituximab (RTX) is a chimeric IgG1 monoclonal antibody that specifically targets the CD20 surface antigen and induces the death of neoplastic B lymphocytes. The mechanisms proposed as causing this effect include complement-dependent cell lysis (CDC), apoptosis, and antibody-dependent cellular cytotoxicity. The response of CLL to RTX is inferior in comparison to other indolent B cell malignancies [Hillmen P. Semin Oncol.2004;31(1 Suppl 2):22]. Abnormalities in the complement system (low levels of complement components and properdin) have been reported in CLL patients, and their magnitude correlated with Rai stage of the disease [Schlesinger M. et al. Leukemia.1996;10:1509]. We report here an attempt to augment the RTX effect in a heavily pretreated patient with advanced CLL by adding complement present in fresh frozen plasma (FFP), which is a well known source of complement elements.
Case report
59 year-old woman diagnosed 12 years ago with CLL, was treated over the years with single agent cyclophosphamide (CTX), repeated cycles of fludarabine/CTX, and in the last 9 months - with 6 cycles of RTX combined with modified CHOP-like chemotherapy. Originally the response lasted for 18 months, but during the last 13 months the patient suffers from advanced disease, with malaise, B symptoms, massive lymphadenopathy, splenomegaly, lymphocytosis up to 450x109/l, and LDH up to 2,400 IU/l, in spite of the treatment. Peripheral smears, immunophenotyping and lymph node biopsy were still compatible with CLL. Endoscopic biopsy, performed because of culture-negative diarrhea, revealed involvement of the colon by CLL, with no evidence of infection. Treatment regimen consisted of 2 units of FFP followed by 400 mg/m2 of RTX on day 1, and 2 units of FFP followed by 270 mg/m2 of RTX on day 2. A dramatic response was manifested by improvement of ambulation, cessation of diarrhea, marked reduction of lymphadenopathy, as well as a decrease of lymphocyte count from 270 x109/mcl to 120 x109/mcl on day 2, and to 40x109/mcl on day 6, with decrease of LDH level from 2,400 IU/l to 1,200 IU/l.
The analysis of the complement system parameters prior to and following the treatment is currently being performed.
Comment
To the best of our knowledge, this is the first description of a case where successful induction of a dramatic and rapid improvement of both clinical and laboratory parameters in a patient with advanced CLL previously resistant to RTX-containing chemoimmuno-therapy, was achieved by combining RTX therapy with fresh frozen plasma as a source for complement. This observation has to be verified in additional patients in order to confirm the approach of potentiation of RTX effect by providing increased amount of complement in order to augment CDC.