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Blood, 15 November 2006, Vol. 108, No. 10, pp. 3621-3622.

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CORRESPONDENCE

To the editor:

HAART- and AIDS-related lymphomas

Previous studies have shown improvement in the remission rate, prognosis, and survival of patients with AIDS-related lymphomas (ARLs) with highly active antiretroviral therapy (HAART).1-5 In the pre-HAART era, low-dose chemotherapy was the preferred regimen because of a higher risk of infection and hematologic toxicity.6 With the availability of HAART, administration of standard chemotherapy has become feasible as infectious complications have been reduced.1-5

The study on AIDS-related lymphoma by Mounier et al7 is certainly a step forward in understanding the impact of HAART in the management of ARL. The patients in the study were stratified into 3 risk groups based on their HIV score, and low-dose versus high-dose chemotherapy was administered in each group. The authors concluded that the intensity of the chemotherapy regimen did not affect the overall survival in each group. However, we think it would have been more interesting had the authors specified the number of patients that were enrolled into the low-dose chemotherapy and the high-dose chemotherapy arms based on their International Prognostic Index (IPI) score. This information would have potentially impacted the results of the study. For example, it is possible that there was a greater number of patients with a lower IPI score in the less-intensive chemotherapy group compared with those in the high-dose chemotherapy group, thereby giving the false perception of "no difference" in overall survival irrespective of the type of chemotherapy regimen used. As in the case of non-HIV patients with high-grade non-Hodgkin lymphoma, we believe that the IPI score rather than the type of chemotherapy regimen used may be affecting the survival rate of ARL patients. The same argument would hold good for the type/grade of lymphomas.

In addition, this study has shown improved response rates (partial response [PR] and complete response [CR]) with high-dose chemotherapy when compared with low-dose chemotherapy. However, this did not translate into improved overall survival rates. Therefore, it would have been interesting to know the cause of death in these patients over the period of study, whether they died from the progression of the disease, infections related to chemotherapy, or HIV-related complications.

Jaswinder Singh, Ashok K. Malani, Siddhartha Ganguly, and Suman Kambhampati

Correspondence: Ashok K. Malani, 902 N Riverside Rd, Suite # 200, St Joseph, MO 64507; e-mail: drmalani{at}yahoo.com.

Footnotes

The authors declare no competing financial interests.

References

  1. Ratner L, Lee J, Tang S, et al. AIDS Malignancy Consortium: chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J Clin Oncol. 2001;19: 2171-2178.[Abstract/Free Full Text]

  2. Antinori A, Cingolani A, Alba L, et al. Better response to chemotherapy and prolonged survival in AIDS-related lymphomas responding to highly active antiretroviral therapy. AIDS. 2001;15: 1483-1491.[CrossRef][Medline] [Order article via Infotrieve]

  3. 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: 478-484.[Medline] [Order article via Infotrieve]

  4. Hoffmann C, Wolf E, Fatkenheuer G, et al. Response to highly active antiretroviral therapy strongly predicts outcome in patients with AIDS-related lymphoma. AIDS. 2003;17: 1521-1529.[CrossRef][Medline] [Order article via Infotrieve]

  5. Vaccher E, Spina M, Talamini R, et al. Improvement of systemic human immunodeficiency virus-related non-Hodgkin lymphoma outcome in the era of highly active antiretroviral therapy. Clin Infect Dis. 2003;37: 1556-1564.[CrossRef][Medline] [Order article via Infotrieve]

  6. Kaplan LD, Straus DJ, Testa MA, et al. Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection: National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N Engl J Med. 1997;336: 1641-1648.[Abstract/Free Full Text]

  7. 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: 3832-3840.[Abstract/Free Full Text]


 

Response:

AIDS-related lymphoma

The suggestion by Singh et al to include the number of patients randomized in the low-dose chemotherapy arm and the high-dose chemotherapy arm based on their International Prognostic Index (IPI) score is interesting, since it would affect the survival results. The multivariate model failed to detect interaction between IPI and treatment within strata, but investigated that problem. In the low-risk group, 45% of patients had an IPI score of 0-1 in the control arm versus 55% in the high-dose arm (P = .38); in the intermediate-risk group, 39% versus 43% (P = .12); and in the high-risk group, 30% versus 24% (P = .44).

The same argument would hold good for the pathologic subtype. Again, the multivariate model failed to detect interaction with pathologic subtype and treatment within strata. In addition, the small sample size of each subset prevented us from making any conclusion.

Concerning the question of the cause of death, the database is not precise enough but we are able to draw some conclusions. In all risk groups, the leading cause of death was lymphoma (n = 214; 66%). In the low-risk group, death was due to lymphoma in 77 patients (67%), infection in 28 (24%), and toxicity or several factors in 11 patients (9%). There was no difference between ACVBP (doxorubicin, cyclophosphamide, vindesine, bleomycin, and prednisolone) and CHOP (doxorubicin, cyclophosphamide, vincristine, and prednisolone) treatment groups. In the intermediate-risk group, death was due to lymphoma in 46 patients (75%) on low-dose CHOP (Ld-CHOP) and 35 (54%) on CHOP (P = .003) and to infection in 11 (18%) and 20 patients (31%) in these groups, respectively. In the high-risk group, death was due to lymphoma in 56 patients (71%), infection in 16 (20%), and toxicity or several factors in 7 (9%). There was no difference between Ld-CHOP or vincristine and steroids (VS). There seems to be a trade-off between efficacy and toxicity, with more deaths due to infection on CHOP than Ld-CHOP (31% vs 18%). However, this hypothesis needs to be confirmed by competing risk analysis of the cause of death. If death due to infection on CHOP was early in the course of the trial, while subjects were on therapy and their absolute neutrophil count (ANC) was depressed, then the subject could not die due to lymphoma.

Nicolas Mounier

Correspondence: Nicolas Mounier, Department of Onco-Hematology, Centre Hospitalier Universitaire l'Archet, 151 route Saint Antoine-Ginestière,Nice, 06200 France; e-mail: mounier.n{at}chu-nice.fr.

The author declares no competing financial interests.


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Related Article in Blood Online:

AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy
Nicolas Mounier, Michele Spina, Jean Gabarre, Martine Raphael, Giuliano Rizzardini, Jean-Baptiste Golfier, Emanuela Vaccher, Antonino Carbone, Bertrand Coiffier, Guido Chichino, Andre Bosly, Umberto Tirelli, and Christian Gisselbrecht, for the French-Italian cooperative group
Blood 2006 107: 3832-3840. [Abstract] [Full Text] [PDF]




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