Reply to A. Messori et al.
Authors: Jorge Castillo
Journal: American Journal of Hematology (2013)

We thank Messori and collaborators for their comment on our previously published study 1 and appreciate the opportunity to expand on the discussion of therapies in patients with HIV-associated non-Hodgkin lymphoma (NHL). In their correspondence, Messori and colleagues have performed a meta-regression analysis to evaluate the trend in the 2-year overall survival (OS) rate reported in prospective studies on patients with HIV-associated NHL between the years 1995 and 2004 2. They report an improvement in the 2-year OS, from 42.8% in 1995 to 68.8% in 2004, which represents a 26% absolute and a 60% relative improvement in 2-year OS in patients with HIV-associated NHL. They also report a median 2-year OS of 61% in patients treated with rituximab-containing regimens versus 48% in patients treated with chemotherapy alone. There are mounting data in the literature showing an improvement in response rates and survival in patients with HIV-associated NHL who are treated with rituximab in combination with chemotherapy. The correspondence by Messori and colleagues certainly adds to that body of evidence by means of a meta-regression analysis. Meta-regression indeed provides a more “granular” feeling to an otherwise categorical meta-analysis. Such “granularity” is clearly exemplified by the figure provided in their article. However, meta-regression analyses have inherent problems and caveats. In this specific example, Messori and colleagues used the middle point of the enrollment interval as a representative point in time for the whole group. By using this approach, it is easy to fall into ecological fallacy, in which any inference about the individual is estimated based on the result of the group but might not represent the actual individual. As an example, a study enrolling patients between the years 1990 and 1999 will be assigned as year 1995 without having into account the potential differences in therapy that took place during that interval as it is likely that practices changed between 1990 and 1999. Additionally, meta-regression analyses do not address other weaknesses of categorical meta-analyses such as missing data and lack of adjustment for other potential important factors. These two aspects, not surprisingly, go hand in hand. For example, it is likely that the addition of appropriate antibiotic prophylaxis, growth factor support and use of intrathecal chemotherapy to decrease central nervous system involvement, in addition to rituximab, have partially improved the outcome; however, this will be unlikely to be evaluated without patient-level data. A recent study presented in abstract format at the 2012 American Society of Hematology Annual Meeting attempts to address this issue by analyzing patient-level data on 1,546 patients with HIV-associated NHL from 19 studies 3. Preliminary results show an improvement on response and survival rates in patients treated with rituximab and chemotherapy. A final peer-reviewed publication is eagerly expected. Jorge Castillo The Warren Alpert Medical School, Division of Hematology and Oncology, Rhode Island Hospital/The Miriam Hospital, Providence, Rhode Island