title: Rituximab plus liposomal doxorubicin in HIV-infected patients with KSHV-associated multicentric Castleman disease.
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.
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Thomas S
authors.initials: TS
authors.lastname: Uldrick
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Mark N
authors.initials: MN
authors.lastname: Polizzotto
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Karen
authors.initials: K
authors.lastname: Aleman
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Wyvill
authors.affiliation: AIDS and Cancer Virus Program, Viral Oncology Section, Leidos-Frederick, National Cancer Institute, Frederick, MD; and.
authors.forename: Vickie
authors.initials: V
authors.lastname: Marshall
authors.affiliation: AIDS and Cancer Virus Program, Viral Oncology Section, Leidos-Frederick, National Cancer Institute, Frederick, MD; and.
authors.forename: Denise
authors.initials: D
authors.lastname: Whitby
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Victoria
authors.initials: V
authors.lastname: Wang
authors.affiliation: Laboratory of Pathology and.
authors.forename: Stefania
authors.initials: S
authors.lastname: Pittaluga
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Deirdre
authors.initials: D
authors.lastname: O'Mahony
authors.affiliation: Biostatistics and Data Management Section, Center for Cancer Research, National Cancer Institute, Bethesda, MD.
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Richard F
authors.initials: RF
authors.lastname: Little
authors.affiliation: HIV & AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD;
authors.forename: Robert
authors.initials: R
authors.lastname: Yarchoan
mesh_terms: D000328:Adult; D044966:Anti-Retroviral Agents / Q000008:administration & dosage / Q000009:adverse effects; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage* / Q000009:adverse effects; D002097:C-Reactive Protein / Q000378:metabolism; D005871:Castleman Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D005260:Female; D005500:Follow-Up Studies; D015658:HIV Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006566:Herpesviridae Infections / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D019288:Herpesvirus 8, Human; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D000069283:Rituximab; D015996:Survival Rate; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D000903:Antibiotics, Antineoplastic; D058846:Antibodies, Monoclonal, Murine-Derived; C508600:IL6 protein, human; D015850:Interleukin-6; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D000069283:Rituximab; D004317:Doxorubicin; D002097:C-Reactive Protein