Abstract
Kaposi sarcoma (KS) herpesvirus-associated multicentric Castleman disease (KSHV-MCD) is a lymphoproliferative disorder, most commonly seen in HIV-infected patients, that has a high mortality if untreated. Concurrent KS is common. Although rituximab has reported activity in KSHV-MCD, its use is often associated with KS progression. Within a natural history study of KSHV-MCD, we prospectively evaluated rituximab 375 mg/m(2) combined with liposomal doxorubicin 20 mg/m(2) (R-Dox) every 3 weeks in 17 patients. Patients received a median of 4 cycles (range 3-9). All received antiretroviral therapy, 11 received consolidation interferon-α, and 6 received consolidation high-dose zidovudine with valganciclovir. Using NCI KSHV-MCD response criteria, major clinical and biochemical responses were attained in 94% and 88% of patients, respectively. With a median 58 months' potential follow-up, 3-year event-free survival was 69% and 3-year overall survival was 81%. During R-Dox therapy, cutaneous KS developed in 1 patient, whereas 5 of 6 patients with it had clinical improvement. R-Dox was associated with significant improvement in anemia and hypoalbuminemia. KSHV viral load, KSHV viral interleukin-6, C-reactive protein, human interleukin-6, and serum immunoglobulin free light chains decreased with therapy. R-Dox is effective in symptomatic KSHV-MCD and may be useful in patients with concurrent KS. This trial was registered at www.clinicaltrials.gov as #NCT00092222.
Publication types
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Clinical Trial
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Research Support, N.I.H., Intramural
MeSH terms
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Adult
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Anti-Retroviral Agents / administration & dosage
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Anti-Retroviral Agents / adverse effects
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Antibiotics, Antineoplastic / administration & dosage*
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Antibiotics, Antineoplastic / adverse effects
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Antibodies, Monoclonal, Murine-Derived / administration & dosage*
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Antibodies, Monoclonal, Murine-Derived / adverse effects
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C-Reactive Protein / metabolism
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Castleman Disease / blood
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Castleman Disease / complications
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Castleman Disease / drug therapy*
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Castleman Disease / mortality
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Disease-Free Survival
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Doxorubicin / administration & dosage
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Doxorubicin / adverse effects
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Doxorubicin / analogs & derivatives*
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Female
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Follow-Up Studies
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HIV Infections / blood
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HIV Infections / complications
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HIV Infections / drug therapy*
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HIV Infections / mortality
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Herpesviridae Infections / blood
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Herpesviridae Infections / complications
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Herpesviridae Infections / drug therapy*
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Herpesviridae Infections / mortality
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Herpesvirus 8, Human*
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Humans
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Interleukin-6 / blood
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Male
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Middle Aged
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Polyethylene Glycols / administration & dosage
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Polyethylene Glycols / adverse effects
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Prospective Studies
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Rituximab
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Survival Rate
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Viral Load
Substances
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Anti-Retroviral Agents
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Antibiotics, Antineoplastic
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Antibodies, Monoclonal, Murine-Derived
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IL6 protein, human
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Interleukin-6
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liposomal doxorubicin
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Polyethylene Glycols
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Rituximab
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Doxorubicin
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C-Reactive Protein
Supplementary concepts
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Multi-centric Castleman's Disease
Associated data
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ClinicalTrials.gov/NCT00092222