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Journal of Clinical Oncology, Vol 23, No 33 (November 20), 2005: pp. 8540-8541 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.03.0205
In Reply:Division of Hematology, University of Southern California/Norris Cancer Hospital, Los Angeles, CA
Department of Medical Oncology National Cancer Center, Singapore, Singapore In their letter, Stebbing et al analyzed prognostic factors in 215 patients with AIDS-related lymphoma (ARL). In multivariate analyses of these patients, the four clinical features found to be independently associated with decreased survival were a prior AIDS diagnosis, Burkitt’s lymphoma (BL) histology, a CD4 cell count at diagnosis of less than 100/mm3, and International Prognostic Index high risk disease. By adding the weightings for each of these variables, the authors proposed a prognostic scoring system, which can be used to identify patients for specific treatment approaches. While Burkitt’s lymphoma was a poor prognostic factor in their group as a whole and in the patients treated in the pre–highly active antiretroviral therapy (HAART) era, BL histology was not found to be a significant factor in the HAART-treated patients, a result divergent from our own1 and from other recently published studies.2,3 It is extremely difficult to decipher the actual reasons for the discrepancy between Stebbing’s data and our own, especially since we are not provided with many of the important details related to the characteristics of his cohort or the factors that were considered in his multivariate analyses. While he references an article recently published,4 that analysis concerned a group of 111 patients with systemic AIDS lymphoma, all of whom were treated in the HAART era.4 In contrast, the current letter deals with 215 patients, representing the full cohort of ARL patients treated at Chelsea and Westminister from 1986 onwards, apparently including the 111 individuals treated in the era of HAART, and also those treated before the availability of HAART. The first issue related to Stebbing’s prognostic model, which may explain our divergent results, relates to the fact that many of the patients considered in Stebbing’s analyses never received therapy for their underlying lymphoma. As treatment would clearly impact on outcome and prognosis, it would be important to evaluate the treatment regimens that were used in the patients who were included. According to the publication,4 10.8% of patients included in Stebbing’s HAART treated group were never treated for their underlying lymphoma with curative intent. Rather, these individuals received local radiation alone or best supportive care.4 It would be inappropriate to include individuals who were never treated for their malignant disease in a study in which prognostic factors for survival were being analyzed, unless, of course, treatment type or results of therapy were included in the factors being analyzed. This was apparently not the case. The issue becomes even more difficult when we try to decipher how many patients in the pre-HAART era were left untreated for their lymphoma. This information is not provided in Stebbing’s letter, and these patients were not included in the published article.4 Based on other publications from the Chelsea and Westminister group, however, it is likely that a significant number of the individuals included in the current analysis were never treated with curative intent.5,6 Thus, the Chelsea-Westminister group recently recounted their data regarding leptomeningeal disease in patients with ARL, employing the same cohort.5 In that publication, which included a total of 176 patients comprising their full database of ARL at the time, the authors stated that a total of 84 (48% of the total group) with adverse prognostic features received therapy with palliative intent.5 One can assume, therefore, that many of the patients treated in the pre-HAART era as well as at least 10.8% diagnosed in the HAART era, did not, in fact, receive either optimal or specific therapy for their lymphomatous disease, yet were included in the analyses which sought to determine prognostic factors for survival. In our own study of 363 patients, we analyzed prognostic factors in patients treated in pre-HAART versus HAART eras, and specifically evaluated those patients who actually received chemotherapy with curative intent. We found that lack of receipt of a complete remission and CD4 cells less than 100/mm3 were statistically associated with decreased survival on multivariate analysis in the pre-HAART era, while lack of complete remission and BL histology were significant predictors of poor prognosis in the HAART era. We believe that the divergent results between our data and those of the Chelsea-Westminister group in terms of the importance of histologic type may have been lost by their inclusion of patients who received palliative chemotherapy or supportive therapy alone in their prognostic model. A further potential explanation for the divergent results between Stebbing’s current report and our own concerns the fact that patients diagnosed in both pre-HAART and HAART eras are included in their prognostic model. In addition, the authors defined the HAART era as commencing on January 1, 1996, but failed to provide full information on the proportion of patients who actually did receive HAART.4 Considering the impact of HAART in improving the survival of patients with AIDS,6 it is surprising that HAART use did not feature as an important prognostic factor in their study. Furthermore, since HAART is now employed routinely in patients with ARL, either concomitant or subsequent to chemotherapy, the clinical relevance of the proposed prognostic scoring system in Stebbing’s 215 patients, in whom approximately half did not receive HAART, is likely to be limited. The finding by Stebbing et al that a pathologic subtype of BL is an independent poor prognostic factor for survival for the entire cohort of patients as well as for patients in the pre-HAART but not the HAART era is difficult to understand, as they readily admit. It is certainly possible that this unexpected result could simply reflect the fact that the prognostic model employed included a proportion of patients who were never treated with curative intent, as well as those who did not receive HAART, leading to results that are divergent from other published data,2,3 including our own.1 As we demonstrated, the survival of patients with HIV-diffuse large-cell lymphoma has improved substantially in the HAART era, along with CD4 cell count, while survival of similarly treated patients with HIV BL has remained poor. The current practice of using the same regimen for both groups of patients should be re-evaluated.1 Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Lim ST, Karim R, Nathwani BN, et al: AIDS-related Burkitt’s lymphoma versus diffuse large-cell lymphoma in the pre-highly active antiretroviral therapy (HAART) and HAART eras: Significant differences in survival with standard chemotherapy. J Clin Oncol 23:4430-4438, 2005
2. Spina M, Jaeger U, Sparano JA, et al: Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: Pooled results from 3 phase 2 trials. Blood 105:1891-1897, 2005
3. Kaplan LD, Lee JY, Ambinder RF, 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 non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood 106:1538-1543, 2005
4. Bower M, Gazzard B, Mandalia S: A prognostic index for systemic AIDS-related non-Hodgkin lymphoma treated in the era of highly active antiretroviral therapy. Ann Intern Med 143:265-273, 2005 5. Sarker D, Thirlwell C, Nelson M: Leptomeningeal disease in AIDS-related non-Hodgkin’s lymphoma. AIDS 17:861-865, 2003[CrossRef][Medline] 6. Palella FJ Jr., Delaney KM, Moorman AC, et al: Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection: HIV Outpatient Study Investigators. N Engl J Med 338:853-860, 1998
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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