We prospectively studied a further modification of the CODOX-M/IVAC regimen previously reported in 14 HIV-negative patients,19 after noting that the various BL regimens had not been prospectively compared. Patients and methods Eligibility This research protocol was approved by each sites institutional review boards and all participants gave written informed consent. because of adverse events. Eleven patients died, including 1 treatment-related and 8 disease-related deaths. The 1-year progression-free survival was 69% (95% confidence interval [CI], 51%-82%) and overall survival was 72% (95% CI, 53%-84%); 2-year overall survival was 69% (95% CI, 50%-82%). Modifications of the CODOX-M/IVAC regimen resulted in a grade 3 to 4 4 toxicity rate of 79%, which was lower than that Beloranib in the parent regimen (100%), without grade 3 to 4 4 mucositis. Despite a 68% protocol completion rate, the 1-year survival rate compares favorably with 2 studies that excluded HIV-positive patients. This trial was registered at http://clinicaltrials.gov as #”type”:”clinical-trial”,”attrs”:”text”:”NCT00392834″,”term_id”:”NCT00392834″NCT00392834. Introduction Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma (NHL) characterized by obligate gene expression driving a nearly 100% growth phase fraction. BL accounts for 1% to 2% of adult NHL but is more common in children and adolescents. Most patients present with advanced disease involving multiple extranodal sites. Historically, BL was one of the first cancers to respond to chemotherapy,1 but early relapses occurred, often in the central nervous system (CNS) with rapid disease progression.2 Cure rates of 50% to 60% were achieved in early-stage patients with high-dose cyclophosphamide, antimetabolites, and prophylactic intrathecal (IT) chemotherapy. However, only 20% of patients with bone marrow or CNS involvement achieved durable responses.3-5 In 1996, Magrath et al6 reported a 92% 2-year event-free survival (EFS) rate in HIV-negative adult and pediatric patients after intensive chemotherapy with cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC). Results were particularly impressive in patients with bone marrow and/or CNS involvement, with an 80% 2-year disease-free survival rate. Although inferior to the Magrath report, an international multicenter phase 2 study demonstrated a 2-year EFS of 65% and 2-year overall cure rate of 72.8%, with excellent results even in high-risk patients stratified by the International Prognostic Index.6,7 Other regimens that incorporate high-dose cytarabine and methotrexate and intensive IT prophylaxis have also been similarly successful.8,9 In Beloranib contrast to BL in the general population, BL comprised 25% to 40% of HIV-associated NHL before the era of highly active antiretroviral therapy (HAART).10-12 BL was more recently estimated at 10%, although this study included 31% NHL unspecified.13 Patients with HIV-BL closely resemble the general BL population in terms of stage, marrow involvement (33% to 35%), CNS involvement (17% to 19%),14 and histology.15 Prior to HAART, combination chemotherapy was less successful for patients with HIV-associated NHL than for HIV-negative patients with similar NHL histopathology. Early deaths were often the result of opportunistic infection.16 However, improved immune function in the HAART era has led to a reevaluation of full-dose chemotherapy. Moreover, HIV-positive patients with BL and preserved immune function may benefit from more aggressive chemotherapeutic approaches with acceptable toxicities.3 Finally, retrospective analyses suggest that HAART era HIV-positive BL patients do poorly with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) Clike regimens,17 but may do well with intensive regimens.18 Nonetheless, because of the perceived risk of increased hematologic and infectious complications, many patients with HIV-associated BL continue to be treated with CHOP and other moderate-dose chemotherapy despite inferiority in HIV-negative BL patients. The AIDS Malignancy Consortium 048 (AMC 048; Rituximab and Combination Chemotherapy in Treating Patients With Newly Diagnosed, HIV-Associated Burkitts Lymphoma) trial, which to the best of our knowledge was the first dedicated Beloranib phase 2 clinical therapeutic study in HIV-associated BL, sought to determine Rabbit Polyclonal to CHML whether intensive therapy was feasible and appropriate in the HAART era. We prospectively studied a further modification of the CODOX-M/IVAC regimen previously reported in 14 HIV-negative patients,19 after noting that the various BL regimens had not been prospectively compared. Patients and methods Eligibility This research protocol was approved by each sites institutional review boards and all Beloranib participants gave written informed consent. Patients with documented HIV infection and newly diagnosed untreated BL or atypical BL per Beloranib World Health Organization criteria20 were.