High Dose Rituxan Restores Immunoglobulins

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Serum globulins as marker of immune restoration after treatment with

high-dose rituximab for chronic lymphocytic leukemia.

Doru T andrescu and H Wiernik

Med Oncol, January 5, 2008; . Abstract

Comprehensive Cancer Center, Our Lady of Mercy Medical Center, New

York Medical College, 600 East 233rd Street, Bronx, NY, 10466, USA,

mddoru@....

An important biological alteration in chronic lymphocytic leukemia

(CLL) is the dysregulation of immunoglobulin production, as a

consequence of complex and yet incompletely understood interactions

between plasma cells and the neoplastic B-cell clone. As a result,

most patients develop severe hypogammaglobulinemia during the course

of the disease. Fourteen patients were analyzed retrospectively for

changes in globulins produced by antineoplastic treatments. During

maximum response to fludarabine, chlorambucil, and overall rituximab,

the mean levels of globulins were 2.500, 2.752, and 3.018 g/dl. The

mean increase in globulins during clinical response to individual

treatments compared to pre-treatment values were 0.050 g/dl for

fludarabine, 0.302 g/dl for chlorambucil, 0.267 g/dl for low-dose

rituximab, and 0.346 g/dl for high-dose rituximab. Overall, treatment

with rituximab produced an average increase in globulins at clinical

response of 11.6%, which increased further to 17.3% at maximum

clinical response. Serum globulins increased significantly compared

with pre-treatment values at maximum clinical response to rituximab

overall (P = 0.001) and high-dose rituximab (P = 0.001), but no

statistical significance occurred in the cases of fludarabine (P =

0.5), chlorambucil/prednisone (P = 0.14), and low-dose rituximab (P =

0.07). Serum globulins levels correlate with disease status (complete

responders versus partial responders and stable disease groups), but

not with peripheral neoplastic load. Therefore, although rituximab is

efficient in decreasing the tumor burden, additional mechanisms may

be involved in relieving suppressive effects on immunoglobulin-

producing cells, which especially manifest at high doses of the

agent. Use of high doses of rituximab in CLL can avoid T-cell

dysfunction and neutropenia, and is associated with humoral

immunorestorative effects.

PMID: 18176848