Hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone and highly active antiretroviral therapy for patients with acquired immunodeficiency syndrome‐related burkitt lymphoma/leukemia

Abstract

BACKGROUND Patients with acquired immunodeficiency syndrome (AIDS)‐associated lymphoma/leukemia have a poor prognosis and are frequently treated with low‐intensity therapy. The authors investigated the feasibility and efficacy of hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper‐CVAD), a dose‐intensive chemotherapy regimen, in patients with AIDS‐associated Burkitt lymphoma/leukemia, as well as the possible impact of highly active antiretroviral therapy (HAART) in these patients. METHODS Thirteen patients with AIDS‐associated Burkitt lymphoma (six patients) or leukemia (acute lymphoblastic leukemia; seven patients) were treated with hyper‐CVAD alternating with high‐dose methotrexate and ara‐C for a total of eight cycles. Nine patients received HAART from the start of induction chemotherapy (seven patients) or later in the course of chemotherapy (two patients). The median patient age was 43 years (range, 32–55). Nine patients were diagnosed with human immunodeficiency virus (HIV) infection at the time of diagnosis of Burkitt lymphoma/leukemia; the other 4 patients had been diagnosed with HIV infection for a median of 37 months (range, 18–137) prior to the diagnosis of Burkitt lymphoma/leukemia. The median absolute CD4 count from the 9 patients with evaluable counts was 77 cells/μL (range, 9–544); only one patient had a count > 200/μL. RESULTS Twelve patients (92%) achieved a complete remission (CR) and one achieved a partial response (PR). Eight patients continued in CR after a median of 31 months (range, 7–45) at the time of writing. Five patients were alive and in CR over two years later. The median survival was 12 months, with 48% of patients alive after 2 years. Six of seven patients who received HAART from the start of chemotherapy were alive and in CR after a median of 29 months (range, 7–45). The four patients who did not receive HAART died. The regimen was universally myelosuppressive, but the toxicity profiles, recoveries from myelosuppression, and incidences of infectious complications were similar to that of non‐HIV patients with Burkitt lymphoma/leukemia treated with the same regimen. CONCLUSIONS Hyper‐CVAD is an effective regimen for patients with AIDS‐associated Burkitt lymphoma/leukemia, with acceptable toxicity. The combination of hyper‐CVAD and HAART is associated with long‐term survival in patients with the two diseases, which, until recently, were both considered invariably fatal and almost futile to treat medically. Cancer 2002;94:1492–9. © 2002 American Cancer Society. DOI 10.1002/cncr.10365

Intensive chemotherapy with cyclophosphamide, doxorubicin, high‐dose methotrexate/ifosfamide, etoposide, and high‐dose cytarabine (CODOX‐M/IVAC) for human immunodeficiency virus–associated Burkitt lymphoma

“…Six of the 7 HIV-positive patients with BL who received HAART during chemotherapy were alive after a median period of 29 months, whereas 4 patients who did not receive HAART during the same chemotherapy died. 38 In summary, we have demonstrated that intensive chemotherapy with CODOX-M/IVAC can be administered safely to patients with HIV infection, that this regimen may abrogate poor prognostic features, and that the results are comparable with those observed in HIV-negative populations treated concomitantly. It should be emphasized that the current analysis was retrospective, nonrandomized, and included a relatively small number of patients.…”

“…37 The relatively good immune function possessed by patients with HIV-associated BL (independent of HAART) further suggests that this subset of patients may benefit from aggressive chemotherapy regimens that have acceptable toxicities. 6,27,28,31 Cortes et al 38 recently reported a retrospective study of 13 HIV-positive adult patients with BL who received intensive chemotherapy with hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper CVAD) alternating with high dose methatrexate and Ara-C from 1995 to 2000. Although they demonstrated an overall response rate of 92%, the median survival period was only 12 months.…”

Successful administration of aggressive chemotherapy concomitant to tuberculostatic and highly active antiretroviral therapy in a patient with AIDS‐related Burkitt's lymphoma

“…While an increasing number of patients with ARL are successfully treated with standard chemotherapies such as cyclophosphamide hydroxydoxorubicin, oncovin, prednisone (CHOP), there is little experience with more aggressive protocols [10]. Previous experience has shown very poor response rates in patients with AIDS-related Burkitt's lymphoma treated with CHOP [11]. Because of the aggressiveness of the lymphoma in our patient, we chose an intensive regimen, although the situation in our case was further complicated by concomitant tuberculosis.…”

The role of hematopoietic SCT in adult Burkitt lymphoma

“…12,16,17 Furthermore, these results seem to be reproducible in HIV þ patients. 18 The role of SCT in BL is not clear, and needs to be evaluated in the context of relatively favorable outcomes with modern intensive chemoimmunotherapeutic regimes.…”