HIV-Associated Burkitt Lymphoma: Good Efficacy and Tolerance of Intensive Chemotherapy Including CODOX-M/IVAC with or without Rituximab in the HAART Era.

Background. The outcome of HIV-associated non-Hodgkin lymphoma (NHL) has improved substantially in the highly active antiretroviral therapy (HAART) era. However, HIV-Burkitt lymphoma (BL), which accounts for up to 20% of HIV-NHL, has poor outcome with standard chemotherapy. Patients and Methods. We retrospectively reviewed HIV-BL treated in the HAART era with the Magrath regimen (CODOX-M/IVAC±R) at four Canadian centres. Results. Fourteen patients with HIV-BL received at least one CODOX-M/IVAC±R treatment. Median age at BL diagnosis was 45.5 years, CD4 count 375 cells/mL and HIV viral load (VL) <50 copies/mL. Patients received PCP prophylaxis and G-CSF, 13 received HAART with chemotherapy and 10 rituximab. There were 63 episodes of toxicity, none fatal, including: bacterial infection, n = 20; grade 3-4 hematologic toxicity, n = 14; febrile neutropenia, n = 7; oral thrush; and ifosfamide neurological toxicity, n = 1 each. At a median followup of 11.7 months, 12 (86%) patients are alive and in remission. All 10 patients who received HAART, chemotherapy, and rituximab are alive. CD4 counts and HIV VL 6 months following BL therapy completion (n = 5 patients) were >250 cells/mL and undetectable, respectively, in 4. Conclusion. Intensive chemotherapy with CODOX-M/IVAC±R yielded acceptable toxicity and good survival rates in patients with HIV-associated Burkitt lymphoma receiving HAART.

Improved survival in HIV-associated diffuse large B-cell lymphoma with the addition of rituximab to chemotherapy in patients receiving highly active antiretroviral therapy.

PURPOSE: Recent trials suggest serious toxicity in HIV-associated non-Hodgkin's lymphoma (NHL) with rituximab (R) and chemotherapy (CT), offsetting the benefit of rituximab. METHOD: We retrospectively reviewed experience with CHOP-R vs. CT in 40 patients with HIV-associated diffuse large B-cell lymphoma (DLBCL) diagnosed between December 1992 and February 2006, all of whom were treated with curative intent. RESULTS: In a univariate analysis, International Prognostic Index (IPI) score, prior AIDS, HAART, and rituximab were significant for overall survival (OS). In a multivariate analysis, IPI 0-1 (p < .02), no prior AIDS (p < .0002), and receiving CHOP-R (p < .01) were significant for improved OS, and HAART use (p < .09) retained a trend for improved OS. The hazard ratio (HR) for patients with high IPI receiving CHOP-R was 0.3 (95% CI 0.1-0.8). Patients without prior AIDS receiving CHOP-R had an HR of 0.5 (95% CI 0.1-1.7). The OS at 30 months in patients not receiving HAART was 0%. With HAART, OS was 33% for CT and 86% for CHOP-R; HR for CHOP-R was 0.4 (95% CI 0.1-1.2). Toxic deaths were 3 (33%) for CHOP-R and 6 (25%) for CT (p = ns); all toxic deaths with CHOP-R were in patients not receiving HAART. Rituximab-treated patients had a lower death rate from lymphoma (CHOP-R, 2 [16%] vs. CT, 15 [63%]; p < .04), and overall mortality (CHOP-R, 5 [42%] vs. CT, 21 [88%]; p < .01). CONCLUSION: These retrospective data suggest that fatal toxicity of rituximab in HIV-NHL is not increased provided HAART is used, that the addition of rituximab to CT improved outcome, and that further prospective trials investigating this issue are warranted.

Autologous blood and marrow transplantation in patients 60 years and older.

Although many hematologic malignancies are more common in older patients, autologous blood and marrow transplantation (ABMT) has traditionally been restricted to patients younger than 60 years because of concerns that older patients would be either unable to provide a graft or unable to tolerate the therapy. From June 1995 to May 1998, 30 patients > or = 60 years underwent ABMT at our institution for low-grade lymphoma (4 patients), relapsed intermediate-grade lymphoma (17 patients), or multiple myeloma (9 patients). The median patient age was 62.5 years (range 60-73). Pretransplantation conditioning regimens were CBV (cyclophosphamide, BCNU [carmustine], etoposide) or BEAM (carmustine, etoposide, cytarabine, melphalan) for intermediate-grade lymphoma patients and melphalan 140 mg/m2 + etoposide 60 mg/kg + total body irradiation 500 cGy for the others. The rescue product was bone marrow (BM; 4 patients), peripheral blood stem cells (PBSC; 23 patients), or BM+PBSC (3 patients). The median number of CD34+ cells/kg infused was 3.60 x 10(6) (range 0.53-31.0), by the International Society for Hematotherapy and Graft Engineering method. The treatment-related mortality at day 100 and at 6 months was 10% and 16.7%, respectively. The median days to neutrophil > 0.5 x 10(9)/L was 11 (range 9-25) and platelets > 20 x 10(9)/L was 16 (range 6-70). Three patients died of infection (days 26, 27, and 38), and 1 died of an intracranial hemorrhage related to persistent thrombocytopenia (day 130). Bearman regimen-related toxicity was moderate, with most toxicities < or = grade 2. Seven patients developed significant gut toxicity: 4 patients with Clostridium difficile colitis and 3 patients with neutropenic enterocolitis. Depressive symptoms and signs were noted in 4 patients. Three male patients developed decreased gonadal function after transplantation. These transplantations accounted for 997 patient days, of which 266 days (27%) were in the outpatient BMT program--a smaller percentage than in patients < 60 years (56%, P = .002). Twenty patients are alive 153 to > or = 1224 days after transplantation. ABMT in patients > or = 60 years of age is feasible. Further studies addressing supportive care particular to older patients and comparisons of ABMT with traditional approaches to multiple myeloma and relapsed non-Hodgkin's lymphoma in older patients are needed. Further work to identify elderly patients most likely to benefit from this approach is also required.