Intensive Chemo for HIV+ Burkitt’s Lymphoma Patients

SAN FRANCISCO—HIV-positive patients with Burkitt’s lymphoma treated with intensive chemotherapy achieved high complete response rates similar to those without HIV infection, according to a retrospective review of 38 patients treated at Memorial Sloan-Kettering Cancer Center (MSKCC) between 1988 and 2000.

Lead author Eunice S. Wang, MD, discussed the results with ONI at a poster session of the 42^nd Annual Meeting of the American Society of Hematology (ASH). Dr. Wang is a hematology-oncology fellow at MSKCC.

Although previous experience had shown that high-dose chemotherapy does not usually work well in HIV-positive patients, Dr. Wang said, this study showed that intensive chemotherapy with CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, high-dose cytarabine) is appropriate for HIV-positive as well as HIV-negative patients.

Slightly more than half of the patients (21 or 56%) had received CODOX-M/IVAC. The complete response rate was 81% for CODOX-M/IVAC, compared with 47% for other chemotherapy regimens tested.

This benefit extended to both HIV-positive and HIV-negative patients: 5 of 7 HIV-positive patients (71%) and 11 of 14 HIV-negative patients (78%) treated with CODOX-M/IVAC achieved a complete response. Four HIV-positive patients (57%) and eleven HIV-negative patients (79%) remained disease-free at median follow-up of 34.5 months.

Although Burkitt’s lymphoma is responsible for only 1% to 2% of non-Hodgkin’s lymphoma (NHL) in adults, it accounts for 35% to 40% of NHL in those infected with HIV, Dr. Wang said. Moreover, the importance of Burkitt’s lymphoma among HIV-positive patients could rise as mortality from AIDS and AIDS-related opportunistic infections declines.

Benefits in Advanced Disease

The patients were predominantly male (71%). The age range was 19 to 66, with a mean age of 38.5. Fourteen patients were HIV positive, with Burkitt’s lymphoma being the AIDS-defining illness in six patients. Stage IV disease was present in 22 patients (58%), 16 with bone marrow and 9 with central nervous system (CNS) involvement.

Six of 11 patients (55%) with either CNS or bone marrow involvement achieved a complete response with CODOX-M/IVAC, as opposed to 0 of 7 patients receiving other treatment regimens, Dr. Wang said.

Stage IV patients and those with positive bone marrow experienced significantly improved 1-year event-free survival after treatment with CODOX-M/IVAC. HIV-negative patients had improved 1-year event-free survival with CODOX-M/IVAC, compared with other treatments. "A trend toward improved survival was noted in all patients treated with CODOX-M/IVAC," the researchers concluded.

Toxicity was similar in HIV-positive and HIV-negative patients. Treatment-related toxicity rates, however, were generally higher in patients receiving CODOX-M/IVAC.

Neutropenia occurred among 95% of the CODOX-M/IVAC patients and 65% of those receiving other chemotherapy regimens. For nadir fever, the rates were 91% for CODOX-M/IVAC vs 58% for other regimens. Infection was documented among 67% of those receiving CODOX-M/IVAC vs 29% of those receiving other treatments. Rates of sepsis (24%) and toxic death (less than 10%) were similar across treatment groups.

This study built on a report by McGrath and colleagues (J Clin Oncol 14:925-934, 1996) of 2-year event-free survival of 92% in adult and pediatric HIV-negative patients, with particularly impressive results in patients with bone marrow and/or CNS involvement.

David J. Straus, MD, of the MSKCC Lymphoma Service, told ONI that the MSKCC study essentially "confirmed those results." The MSKCC results are somewhat inferior because the MSKCC patient population included only adult oncology patients who, Dr. Wang said "have traditionally done less well."