Human immunodeficiency virus-related lymphoma treatment with intensive combination chemotherapy. French-Italian Cooperative Group.
OBJECTIVE
An increased risk of high-grade non-Hodgkin's lymphoma is observed in patients who are seropositive for human immunodeficiency virus (HIV). Treatment of such patients is complicated by their underlying acquired immunodeficiency syndrome (AIDS). Intensive strategies such as those used in non-HIV-related lymphoma may be poorly tolerated. However, patients without severe AIDS may derive significant benefits from such an approach. In a prospective multicenter study, treatment outcomes were assessed in 141 cases of HIV-seropositive lymphomas submitted to aggressive chemotherapy.


METHODS
Adult patients with lymphoma with a performance status less than 3 and no active opportunistic infection were consecutively treated with three cycles of doxorubicin 75 mg/m2, cyclophosphamide 1,200 mg/m2, vindesine 2 mg/m2 for 2 days, bleomycin 10 mg for 2 days, and prednisolone 60 mg/m2 for 5 days (ACVB). This treatment was followed by a consolidation phase of high-dose methotrexate plus leucovorin, ifosfamide, etoposide, asparaginase, and cytarabine (LNH84). Central nervous system prophylaxis with intrathecal methotrexate was routinely used. Zidovudine maintenance therapy was started after chemotherapy. Ninety-three patients had high-grade lymphomas (59 Burkitt's type) and 48 had intermediate-grade lymphomas. Disseminated stage III-IV was present in 86 patients, meningeal involvement in 29, and bone marrow infiltration in 30; 62 patients had more than 2 extranodal localizations. Lactate dehydrogenase levels were above the normal value in 95 cases. The median CD4-positive lymphocyte count was 227 x 10(6)/L.


RESULTS
Eighty-nine patients (63%) achieved complete remission (CR) and 19 (13%) partial remission, whereas 13 did not respond and 20 (14%) died during the course of ACVB, 8 of them from progressive disease. With a median follow-up of 28 months, median survival and disease-free survival were 9 and 16 months, respectively. Median survival for nonresponders was 5 months; 23 patients died of opportunistic infections while in persistent CR. In multivariate analysis, four factors were strongly associated with shorter survival: (1) CD4 count less than 100 x 10(6)/L, (2) performance status greater than 1, (3) immunoblastic lymphoma, and (4) prior AIDS. In the absence of all risk factors, the probability of survival at 2 years was 50%.


CONCLUSIONS
In a selected group of HIV-related lymphomas, intensive chemotherapy with LNH84 is feasible and yields a high CR rate. Survival is short due to death from HIV-related infections; however, in a subgroup of patients without adverse prognostic factors, long-term remission was observed.
Gisselbrecht
C
C
Department of Hematology, Hôpital Saint Louis, Paris, France.
Oksenhendler
E
E
Tirelli
U
U
Lepage
E
E
Gabarre
J
J
Farcet
J P
JP
Gastaldi
R
R
Coiffier
B
B
Thyss
A
A
Raphael
M
M
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D005500:Follow-Up Studies; D006679:HIV Seropositivity / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D016483:Lymphoma, AIDS-Related / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011239:Prednisolone / Q000008:administration & dosage; D011446:Prospective Studies; D012008:Recurrence; D012074:Remission Induction; D015996:Survival Rate; D014751:Vindesine / Q000008:administration & dosage
D001761:Bleomycin; D004317:Doxorubicin; D003520:Cyclophosphamide; D011239:Prednisolone; D014751:Vindesine