Safety and Efficacy of Rituximab for Treatment of Multicentric Castleman Disease in Malawi

Inclusion Criteria: 1. Newly diagnosed or previously treated subjects with KSHV-associated MCD that is pathologically confirmed by characteristic histologic features and latency-associated nuclear antigen (LANA) positivity by Immunohistochemistry (IHC). 2. Age is greater than or equal 18 years old at time of consent. 3. Can provide informed consent. 4. HIV-infected or HIV-uninfected. 5. If HIV-infected, must be on or willing to start antiretroviral therapy including lamivudine or tenofovir. 6. Willing to comply with study visits. 7. MCD treatment indicated based on the presence of a symptomatic MCD flare, defined as the presence of each of the following three criteria: 1. Fever (subjective or objective) 2. Lymphadenopathy or hepatosplenomegaly 3. At least one of the following signs or symptoms attributable to MCD by the local study investigator: * Weight loss \>5% * Malaise * Anemia (Hemoglobin \<10 g/dL) within the past 4 weeks * Thrombocytopenia (Platelets \<100 x 103/mL) NOTE: If only two of the three criteria are present, but the provider feels treatment is indicated for a symptomatic MCD flare, this will be allowed after communication with the study principal investigator (PI). Subjects with low hemoglobin within the past 4 weeks that have since received a blood transfusion are still eligible for participation. The subject's pre-transfusion hemoglobin value will be considered when determining risk classification. 8. Females of childbearing potential must have a negative urine pregnancy test within three days prior to registration. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months. Documentation of postmenopausal status must be provided. 9. Females must agree to abstain from breastfeeding during therapy and for 6 months after the completion of therapy. 10. Females of childbearing potential must be willing to abstain from heterosexual activity or to use two forms of effective methods of contraception from the time of informed consent until 12 months after treatment discontinuation. The two contraception methods can be comprised of two barrier methods, a barrier method plus a hormonal method, or an intrauterine device that meets \<1% failure rate for protection from pregnancy in the product label. 11. Male subjects with female partners must have had a prior vasectomy or agree to use an adequate method of contraception (i.e., double barrier method: condom plus spermicidal agent) starting with the first dose of study therapy through 6 months after the last dose of study therapy. 12. More than 7 days without corticosteroid use prior to starting the treatment. Exclusion Criteria: 1. Symptomatic, extensive-stage KS (T1 by the AIDS Clinical Trials Group (ACTG) staging system; T1 includes ulceration or edema from KS, raised or non-hard palate oral lesions, or any visceral involvement) requiring urgent treatment, to avoid potential rituximab-induced KS worsening. 2. Previous rituximab use for MCD. 3. Second active malignancy requiring systemic therapy. 4. If HIV negative and a) hepatitis B virus surface antigen positive or b) a combination of HepB core antibody positive and HepB surface antibody negative (indicative of chronic infection) unless on tenofovir or lamivudine. All HIV-infected patients must be on tenofovir or lamivudine as part of the inclusion criteria. 5. Active infection requiring systemic therapy. 6. Treatment with any investigational drug within 28 days prior to registration. 7. More than 7 days of corticosteroids immediately prior to enrollment. If the subject is taking corticosteroids for more than 7 days, they require a 7 day washout period before enrollment. 8. Bilirubin \>3 mg/dL. 9. Creatinine clearance \<30 ml/min by Cockcroft-Gault formula. 10. ECOG performance status \>3. 11. Pregnant or breastfeeding (Note: Breast milk cannot be stored for future use while the mother is being treated in the study).