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References
1. Lewden C, May T, Rosenthal E, et al. Changes in causes of death among adults infected by HIV between 2000 and 2005: The "Mortalite 2000 and 2005" surveys (ANRS EN19 and Mortavic). J Acquir Immune Defic Syndr. 2008;48(5):590-598.
2. Barta SK, Dunleavy K, Mounier N. Diffuse large B-cell lymphoma. Hentrich M, Barta SK (eds.). HIV-associated Hematological Malignancies. Springer International Publishing; 2016.
3. Dunleavy K, Wilson WH. How I treat HIV- associated lymphoma. Blood. 2012; 119(14):3245-3255.
4. Brunnberg U, Hentrich M, Hoffmann C, Wolf T, Hubel K. HIV-Associated Malignant Lymphoma. Oncol Res Treat. 2017;40(3):82-87.
5. ReA,MichieliM,CasariS,etal.High-dose therapy and autologous peripheral blood stem cell transplantation as salvage treat- ment for AIDS-related lymphoma: long- term results of the Italian Cooperative Group on AIDS and Tumors (GICAT) study with analysis of prognostic factors. Blood. 2009;114(7):1306-1313.
6. Pfreundschuh M, Kuhnt E, Trumper L, et al. CHOP-like chemotherapy with or without rituximab in young patients with good- prognosis diffuse large-B-cell lymphoma: 6- year results of an open-label randomised study of the MabThera International Trial (MInT) Group. Lancet Oncol. 2011; 12(11):1013-1022.
7. Feugier P, Van Hoof A, Sebban C, et al. Long-term results of the R-CHOP study in the treatment of elderly patients with dif- fuse large B-cell lymphoma: a study by the Groupe d'Etude des Lymphomes de l'Adulte. J Clin Oncol. 2005;23(18):4117- 4126.
multicenter trial. Blood. 2014;124(26):3870-
3879.
11. Dunleavy K, Pittaluga S, Shovlin M, et al.
Low-intensity therapy in adults with Burkitt's lymphoma. N Engl J Med. 2013; 369(20):1915-1925.
12. Ribrag V, Koscielny S, Bosq J, et al. Rituximab and dose-dense chemotherapy for adults with Burkitt's lymphoma: a ran- domised, controlled, open-label, phase 3 trial. Lancet. 2016;387(10036):2402-2411.
13. Cheson BD, Horning SJ, Coiffier B, et al. Report of an international workshop to standardize response criteria for non- Hodgkin's lymphomas. NCI Sponsored International Working Group. J Clin Oncol. 1999;17(4):1244.
14. Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-
haematologica | 2018; 103(5)
8. Rovira J, Valera A, Colomo L, et al.
Prognosis of patients with diffuse large B
cell lymphoma not reaching complete
response or relapsing after frontline chemotherapy or immunochemotherapy.
Ann Hematol. 2015;94(5):803-812. 586.
9. Montoto S, Noy A, Ribera JM. Burkitt lym- phoma. Hentrich M, Barta SK (eds): HIV- associated Hematological Malignancies. Springer International Publishing; 2016.
10. Hoelzer D, Walewski J, Dohner H, et al. Improved outcome of adult Burkitt lym- phoma/leukemia with rituximab and chemotherapy: report of a large prospective
15. Hudis CA, Barlow WE, Costantino JP, et al. Proposal for standardized definitions for efficacy end points in adjuvant breast can- cer trials: the STEEP system. J Clin Oncol. 2007;25(15):2127-2132.
16. Schommers P, Wyen C, Hentrich M, et al. Poor outcome of HIV-infected patients with plasmablastic lymphoma: results from
Relapses in AIDS-related lymphomas
between patients who have achieved a CR (12%) to those observed in DLBCL and BL. The inferior OS of the small patient group of PBL may at least in part be explained by 3 late deaths 4-7 years after first diagnosis that were unre- lated to lymphoma: one case of sepsis due to pneumonia and 2 cases of secondary malignancies (lung cancer and oral cavity cancer).
AIDS-related lymphoma patients with an intermediate and high IPI had higher relapse rates and a lower 5yRFS than those with a low IPI in univariate analysis. The lack of significance in the multivariate analysis was somewhat surprising as previous studies have demonstrated strong prognostic relevance of the IPI in ARL.17,18 Whether patients with HIV-related DLBCL and intermediate or high IPI may benefit from more intensive treatments such as the CHOEP regimen, as has been shown in the HIV- negative setting, remains to be seen.19,20
Previous studies have shown that concomitant cART was associated with improved CR rates and a trend toward improved OS.21 Our results also support a concur- rent use of cART as it was associated with better 5yRFS. Several cART regimens with a good safety and tolerability profile and low interaction potential are now available, strongly arguing for a simultaneous cART during ARL chemotherapy.4
The use of R-CHOP-based regimens showed signifi- cantly less treatment delays and reductions, as compared to the GMALL protocol. However, the majority of patients with BL (84%) received chemotherapy according to the GMALL-protocol which resulted in significantly lower relapse rates compared to R-CHOP-based regimens (Figure 3E and F). Notably, treatment delays and a reduced chemotherapy intensity appeared to have no impact on the relapse-rate in GMALL-treated BL, while, at least in the univariate analysis, a reduced number of chemothera- py cycles was associated with lower 5yRFS. Thus, our data indicate that HIV-infected patients with BL should be
treated with the planned number of intensive chemother- apy cycles.3,8 By contrast, reduced relative dose intensity did not negatively impact 5yRFS in patients treated with R-CHOP-based regimens for DLBCL. This finding does not correspond to data reported in HIV-negative DLBCL and warrants further investigation.22,23
It is important to note that this analysis focuses on patients in first CR, and that factors that predict RFS were not necessarily associated with initial treatment response.
Our study has several limitations. First, given the uncon- trolled design selection biases cannot be ruled out. Second, the analysis of risk factors associated with outcome is more exploratory in nature. Given the relatively low num- ber of patients in some of the selected subgroups, the sta- tistical power of the analysis is limited and does not allow any firm conclusions to be drawn. Notably, data on poten- tial risk factors for lymphoma relapse such as adherence to ART or cumulative viremia between CR and relapse are not available.24 Nevertheless, if a CR has been reached, the relapse rate was low regardless of whether the CR was achieved with or without dose reduction and whether rit- uximab was used or not. Fourth, CRs were not generally confirmed by negative positron emission tomography (PET) scans as recommended by current guidelines for HIV-negative lymphomas.14,25 However, the role of PET- scanning in HIV-lymphoma remains controversial as the rate of false positive results appears to be higher than in the HIV-negative setting.26,27 Finally, the number of patients with ARL, not further classified, may have been lowered by reference pathology services which, in turn, may have slightly altered our findings.
In conclusion, both CR rates and relapse rates observed in the German HIV-related Lymphoma Cohort Study are similar to those reported in HIV-negative NHL. These data add to the growing body of evidence showing that treat- ment outcomes compare favorably with those in patients with NHL and no HIV infection.
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