© 2007 European Society for Medical Oncology
letters to the editor |
Lymphoma and human immunodeficiency virus (HIV) infection: another favourable setting?
In his editorial ‘The treatment of lymphoma complicating autoimmune disease: two birds with one stone?’ T. R. Mikuls states that subjects with rheumatoid arthritis (RA) and non-Hodgkin's lymphoma (NHL) fare better than non-RA patients with NHL, as far as response to therapy is concerned [1, 2]. It is now a well-accepted notion that NHL developing in patients with HIV infection may be successfully treated with the very same regimens administered to their HIV-negative counterparts. What if they do better?Highly active antiretroviral therapy (HAART), often comprising a protease inhibitor (PI), is currently administered together with traditional full-dose chemotherapy, thus adding a new therapeutic tool [3, 4]. In fact, HAART not only causes in responding patients viral suppression and hence a rise in CD4 lymphocyte counts, thus controlling infection and re-establishing immune competence; it is also supposed to add to therapy by means of anti-angiogenic activity, at least when PIs are involved. HIV-related lymphomas are supposed to develop thanks to immune depression and loss of functional anti-tumour control.
We already know that HIV sustains inflammation in the vessel walls, in particular in the coronary tree, and suppression of HIV viral loads achieves in the short term what statins do in the long run, i.e. an improvement in inflammatory derangement of the arterial wall and a decrease in the rate of cardiovascular accidents [5]. What if HIV infection per se acts as an ongoing inflammatory stimulus, just as an autoimmune inflammatory condition does, driving in the long run to lymphoma development? Where is therefore the unique contribute of HAART to NHL management: in restoring immune control? In quenching a chronic inflammatory response through control of viral replication? In adding anti-angiogenesis to what chemotherapy already does?
Before the HAART era the fate of patients with HIV–NHL was very grim; since HAART's introduction, NHL has become a curable disease. Overlapping toxicities, mainly haematological and neurological, drug–drug interactions, opportunistic infections and comorbidities (one for all: chronic viral hepatitis is one of the most important and frequent comorbidities in HIV patients) all stand in the way of an uneventful course but are manageable or even preventable in expert hands. Aggressive histology, uncommon presentation and bone marrow depletion are always to be reckoned and dealt with, but nevertheless we have gained a confidence in the possibility to deal with these problems that but a few years ago was in the realm of the unthinkable.
Of course large numbers of patients, assembled in carefully constructed, multicentre clinical trials, are necessary to confirm what now is merely a whisper that all specialists dealing with these patients almost fear to voice, and many issues of uncertainty and concern still remain, such as the timing and schedule of follow-up, the salvage treatment in failure/relapse and the risk of a second neoplasm, to name only a few. And, obviously, the big question: is there a real gain in being HIV-positive and receiving HAART and, if so, why?
Infectious Diseases Department, E. O. Ospedali Galliera, Genova, Italy
* E-mail: marcello.feasi{at}galliera.it
References
1. Mikuls T. The treatment of lymphoma complicating autoimmune disease: two birds with one stone? Ann Oncol (2007) 18:615–618.
2. Mikuls T, Endo J, Puumala S, et al. Prospective study of survival outcomes in non-Hodgkin's lymphoma patients with rheumatoid arthritis. J Clin Oncol (2006) 24:1597–1602.
3. Oriol A, Ribera JM, Brunet S, et al. Influence of highly active antiretroviral therapy in the outcome of AIDS-related Burkitt's lymphoma or leukaemia: results of the PETHEMA-LAL3/97 study. Haematologica (2005) 90:990–992.
4. Navarro JT, Ribera JM, Oriol A, et al. Favorable impact of virological response to HAART on survival in patients with AIDS-related lymphoma. Leuk Lymphoma (2002) 43:1837–1842.[CrossRef][Web of Science][Medline]
5. Skiest DJ, Su Z, Havlir DV, et al. the AIDS Clinical Trials Group 5170 Study Team. Interruption of antiretroviral treatment in HIV-infected patients with preserved immune function is associated with a low rate of clinical progression: a prospective study by AIDS Clinical Trials Group 5170. The Journal of Infectious Diseases (2007) 195:1426–1436.[CrossRef][Web of Science][Medline]
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