Somatic problems of HIV-Medicine: AIDS-related lymphomas

We followed 66 lymphoma -AIDS patients (pts): aggressive lymphomas were diagnosed in 48 pts (male — 35, female — 13, median age 32.5±1.2) and Hodgkin's lymphoma was established in 18 pts (male — 14, female — 4, median age 34.1±2.3). Median duration time from HIV exposure to the onset of lymphomas was 5 years (2—16 years). A part of pts was receiving HAART. 85 % of pts were drug users and association with HCV was shown in 60 % of them, with HCV and HBV- in 25 %. Sexual transmission was mentioned in 15 % of pts. «Immune status»: CD4 counts were from 50 to 500 (median 225) cells in mcL. Viral load was from 400 to 75000 (median 38000) copies in mcL. Histological diagnosis: diffuse large cell lymphomas — 60%, Burkitt lymphoma — 16%, follicular lymphoma — 12%, MALT-lymphomas-6%, T- cell lymphoma — 4%, primary CNS lymphoma — 2%. CHOP and CHOP-like courses had received 26 pts. Results: 3-year overall survival — 52%, 3-year disease free survival — 32%. Block therapy A-B-C of BFM — NHL— 90 and LB-M-04 with and without Mabthera had received 12 pts. Results: 3-year overall survival — 48%, 3-year disease free survival — 38%. After treatment CD4 count was 60 — 700 (median 316) cells in mcL, viral load 400 to 25000 (median 3000) copies in mcL. 75% of Hodgkin's lymphoma patients had III—IV stages of disease. Initial immune status: CD4 counts from 50 to 730 (median 363) cells in mcL, viral load — from 14000 to 150 000 (median 100 000) copies in mcL. Histological variants: mixed cellularity — 14 pts, lymphoid depletion — 3 pts, nodular sclerosis — 1 pt. Chemotherapy had received 11 pts: ABVD with or without radiotherapy — 8 pts, BEACOPP-escalated with or without radiotherapy — 3 pts. Complete 3-year remissions were achieved in 2 pts. Other pts are on therapy. After treatment CD4 counts were 184 — 900 (median 400) cells in mcL, viral load — 435000 (median 100 000) copies in mcL. Modern treatment approaches in lymphoma -AIDS pts can lead to complete remission, as well as in general non-HIV positive population.

1. Покровский В.В., Ермак Т.Н. , Беляева В.В. ВИЧ-инфекция. Клиника, диагностика, лечение. М., ГэотарМед; 2003.

2. Покровский В.И., Покровский В.В., Потекаев С.Н. и др. Первый случай СПИД у гражданина СССР. Тер арх 1988;(7): 10–4.

3. UNAIDS (1997b): HIV testing methods. UNAIDS Technical Update (UNAIDS Best Practice Collection: Technical Update). Geneva: UNAIDS, November 1997.

4. Cock K.M., Weiss H.A. The global epidemiology of HIV/AIDS. Trop Med Int Health 2000;5(7):3—9.

5. Mellors J.W., Munoz A.M., Giorgi J.V. et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997;126:946—54.

6. Lyles R.H., Munoz A., Yamashita T.E. et al. Natural history of HIV type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. J Infect Dis 2000;181:872—80.

7. Collins K.L., Chen B.K., Walker B.D., Baltimore D. HIV-1 protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998;391:397—401.

8. Кравченко А.В. Патогенетические механизмы нарушений системы гемостаза у больных ВИЧ-инфекцией. Эпидемиол и инфекцион болезни 2000;(3):45–9.

9. Moore R.D., Keruly J., Richman D.D. et al. Natural history of advanced HIV disease in patients treated with zidovudine. The Zidovudine Epidemiology Study Group. AIDS 1992;6:671—7.

10. Katz M.H., Schwarcz S.K., Kellogg T.A. et al. Impact of highly active antiretroviral treatment on HIV seroincidence among men who have sex with men: San Francisco. Am J Public Health 2002;92(3):388—94.

11. Hoffmann C., Rockstroh J.K., Kamps B.S. HIV Medicine 2006. Flying Publisher; 2006. p. 826.

12. Hoffman C., Kamps B.C. HIV Medicine 2005. Flying Publisher; 2005.

13. Goedert J.J., Cote T.R., Virgo P. et al. Spectrum of AIDS-associated malignant disorders. Lancet 1998;351:1833—9.

14. Clarke C.A., Glaser S.L. Epidemiological trends in HIV-associated lymphomas. Curr Opin Oncol 2001;13:354—9.

15. Straus D.J. Simplified prognostic indicators for AIDS-related lymphoma. Blood 2006;107(10):3819—20.

16. Little R.F., Gutierrez M., Jaffe E.S. et al. HIV-Associated non-Hodgkin lymphoma: incidence, presentation, and prognosis. JAMA 2001;285:1880—5.

17. Moore A.L., Youle M., Lipman M. et al. Raised viral load in patients with viral suppression on HAART: transient increase or treatment failure? AIDS 2002;16:615—8.

18. Levine A.M., Seneviratne L., Espina B.M. et al. Evolving characteristics of AIDS-related lymphoma. Blood 2000;96:4084—90.

19. Franceschi S., Dal Maso L., La Vecchia C. Advances in the epidemiology of HIV-associated non-Hodgkin's lymphoma and other lymphoid neoplasms. Int J Cancer 1999;83:481—5.

20. Aboulafia D.M., Pantanowitz L., Dezube B.J. AIDS-related non-Hodgkin lymphoma: still a problem in the era of HAART. AIDS 2004;14:605—17.

21. Matthews G.V., Bower M., Mandalia S. et al. Changes in AIDS-related lymphoma since the introduction of HAART. Blood 2000;96:2730—4.

22. Pauza C.D., Pyzalski R., Perlman S.B. et al. Positron emission tomography images of AIDS pathogenesis. Conf. Adv. AIDS Vaccine. 1997.

23. Antinori A., Cingolani A., Alba L. et al. Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to HAART. AIDS 2001;15:1483—91.

24. Besson C., Goubar A., Gabarre J. et al. Changes in AIDS-related lymphoma since the era of HAART. Blood 2001;98:2339—44.

25. Hoffmann C., Chow K.U., Wolf E. et al. Strong impact of highly active antiretroviral therapy on survival in patients with human immunodeficiency virusassociated Hodgkin's disease. Br J Haematol 2004;125(4):455—62.

26. Lim S.T., Karim R., Tulpule A. et al. Prognostic factors in HIV-related diffuse large-cell lymphoma: before versus after highly active antiretroviral therapy. J Clin Oncol 2005;23(33):8477—82.

27. Matthews G.V., Bower M., Mandalia S. et al. Changes in acquired immunodeficiency syndrome-related lymphoma since the introduction of highly active antiretroviral therapy. Blood 2000;96:2730—4.

28. Little R.F. AIDS-related nonHodgkin's lymphoma: etiology, epidemiology, and impact of highly active antiretroviral therapy. Leuk Lymphoma 2003;44(3):63—8.

29. Stebbing J., Gazzard B., Mandalia S. et al. Antiretroviral treatment regimens and immune parameters in the prevention of systemic AIDS-related non-Hodgkin's lymphoma. J Clin Oncol 2004;22(11):2177—83.

30. Spina M., Jaeger U., Sparana J.A. et al. Rituximab plus infusinal cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. Blood 2005;105(5):123—8.

31. Kaplan L.D., Lee J.Y., Ambinder R.F. et al. Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated nonHodgkin lymphoma: AIDS Malignancies Consortium Trial 010. Blood 2005;106:1538—43.

32. Gerard L., Galicier L., Maillard A. et al. Systemic non-Hodgkin lymphoma in HIV-infected patients with effective suppression of HIV replication: persistent occurrence but improved survival. J Acquir Immune Defic Syndr 2002;30(5):478—84.

33. Lim S.T., Karim R., Nathwani B.N. et al. AIDS-related Burkitt's lymphoma versus diffuse large cell lymphoma in the prehighly active antiretroviral therapy (HAART) and HAART eras: significant differences in survival with standard chemotherapy. J Clin Oncol 2005;23:4430—8.

34. Glaser S.L., Clarke C.A., Gulley M.L. et al. Population-based patterns of human immunodeficiency virus-related Hodgkin lymphoma in the Greate San Francisco Bay Area, 1988—1998. Cancer 2003;98(2):300—9.

35. Wang E.S., Straus D.J., TeruyaFeldstein J. Intensive chemotherapy with cyclophosphamide, doxorubicin, highdose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOXM/IVAC) for human immunodeficiency virus-associated Burkitt lymphoma. Cancer 2003;98:1196—205.

36. Oriol A., Ribera J.M., Esteve J. et al. Lack of influence of human immunodeficiency virus infection status in the response to therapy and survival of adult patients with mature B-cell lymphoma or leukemia. Results of the PETHEMALAL3/97 study. Haematologica 2003;88(4):445—53.

37. Kaplan L.D. Prognostic factors in the treatment of human immunodeficiency virus-associated non-Hodgkin's lymphoma: analysis of AIDS Clinical Trials Group protocol 142-low-dose versus standard-dose m-BACOD plus granulocytemacrophage colony-stimulating factor. National Institute of Allergy and Infectious Diseases. J Clin Oncol. 1998;16:3601—6.

38. Mounier N., Spina M., Gabarre J. et al. AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk adapted intensive chemotherapy. Blood 2006;107(10):3832—40.

39. Levine A.M. AIDS-related lymphoma. Semin Oncol Nurs 2006;22(2):80—9.

40. Hentrich M., Maretta L., Chow K.U. et al. Highly active antiretroviral therapy (HAART) improves survival in HIV-associated Hodgkin's disease: results of a multicenter study. Ann Oncol 2006;17(6):914—9.

41. Тишкевич О.А., Шахгильдян В.И., Пархоменко Ю.Г. Структура летальных исходов и патологическая анатомия у больных ВИЧ-инфекцией в Москве. Эпидемиол и инфекцион болезни 2004;4:42–6.

42. Пивник А.В., Коровушкин В.Г., Пархоменко Ю.Г. и др. Дифференциальная диагностика лимфаденопатий при ВИЧ/СПИД. Тер арх 2006;78(4):28–32.

43. Navarro W.H., Kaplan L.D. AIDSrelated lymphoproliferative disease. Blood 2006;107(1):13—20.

44. Барях Е.А., Звонков Е.Е., Кременецкая А.М. и др. Лечение Беркиттоподобной лимфомы у взрослых. Тер арх 2005;(7):53–8.

45. Барях Е.А., Кременецкая А.М., Кравченко С.К. и др. Новый короткий высокоинтенсивный протокол терапии лимфомы Беркитта у взрослых ЛБ-М-04: промежуточные результаты. Гематол и трансфузиол 2006;51(6):45–9.

46. Звонков Е.Е., Красильникова Б.Б., Махиня В.А. и др. Первый опыт модифицированной программы NHLBFM-90 у взрослых больных первичной диффузной В-крупноклеточной лимфосаркомой желудка с неблагоприятным прогнозом. Тер арх 2006;(7):38–46.

47. Bower M., Gazzard B., Mandalia S. et al. A prognostic index for systemic AIDSrelated non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med 2005;143:265—73.

48. Boue F., Gabarre J., Gisselbrecht C. et al. Phase II trial of CHOP plus rituximab in patients with HIV-associated nonHodgkin's lymphoma. J Clin Oncol 2006;24:4123—8.

49. Krishnan A., Molina A., Zaia J. et al. Durable remissions with autologous stem cell transplantation for high-risk HIV-associated lymphomas. Blood 2005;105(2):874—8.

50. Conti S., Masocco M., Pezzotti P. et al. Differential impact of combined antiretroviral therapy on the survival of Italian patients with specific AIDS-defining illnesses. J Acquir Immune Defic Syndr 2000;25:451–8.