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Prepublished online as a Blood First Edition Paper on January 30, 2003; DOI 10.1182/blood-2002-09-2856.
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Blood, 15 May 2003, Vol. 101, No. 10, pp. 3827-3834
CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS
Efficacy and safety of rituximab in type II mixed
cryoglobulinemia
Francesco Zaja,
Salvatore De Vita,
Cesare Mazzaro,
Stefania Sacco,
Daniela Damiani,
Ginevra De
Marchi,
Angela Michelutti,
Michele Baccarani,
Renato Fanin, and
Gianfranco Ferraccioli
From the Divisions of Hematology-Dipartimento
di Ricerche Mediche e Morfologiche and of Rheumatology-Dipartimento di
Patologia e Medicina Sperimentale e Clinica, University of Udine,
Italy; Department of Medicine, Hospital of Pordenone, Italy; Institute
of Hematology and Medical Oncology L. A. Seragnoli, University of
Bologna, Italy.
The best treatment of type II mixed cryoglobulinemia (MC) has still
to be defined. Antiviral treatment for the frequent underlying infectious trigger hepatitis C virus (HCV) may be ineffective, contraindicated, or not tolerated in a fraction of cases, whereas current immunosuppressive treatments may lead to relevant
complications. Selective B-cell blockade with rituximab was used in
this study, based on favorable results in preliminary experience.
Fifteen consecutive patients with type II MC (HCV-related in 12 of 15) were treated with rituximab, 375 mg/m2 intravenously weekly
for 4 weeks. Only medium- to low-dose steroids were allowed, if already
administered at the time of recruitment. All patients had active
disease, poorly controlled or difficult to manage with previous
treatments, including corticosteroids in all. Efficacy and safety of
rituximab therapy were evaluated in the following 6 months. The overall
follow-up after rituximab treatment ranged from 9 to 31 months.
Rituximab proved effective on skin vasculitis manifestations (ulcers,
purpura, or urticaria), subjective symptoms of peripheral neuropathy,
low-grade B-cell lymphoma, arthralgias, and fever. Nephritis of recent
onset went into remission in one case. Laboratory features, that is,
significantly decreased serum rheumatoid factor and cryoglobulins and
increased C4, were consistent with the clinical efficacy. Treatment was well tolerated, with no infectious complications. Thrombosis of retinal
artery or self-limiting panniculitis occurred in one patient each.
Rituximab may represent a safe and effective alternative to standard
immunosuppression in type II MC. Controlled studies are needed to
better define drug indications and the cost-efficacy profile in the
different systemic manifestations.

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