Review Article

AIDS-Related Non-Hodgkin's Lymphoma in Sub-Saharan Africa: Current Status and Realities of Therapeutic Approach

Table 1

Summary of clinical data on the treatment of AIDS-related non-Hodgkin’s lymphoma (AR-NHL) in (A) sub-Saharan Africa presented in a hierarchal/strength of evidence approach and (B) the United States presented by year of report (most recent) of prospective clinical trials only. [Abbreviations used: Study/Year—trial number/study sponsor or group and year reported with AMC: AIDS Malignancy Consortium, CWRU: Case Western Reserve University, ECOG: Eastern Cooperative Oncology Group, NCI: National Cancer Institute, and ACTG: AIDS Clinical Trials Group; LD/SD: low dose/standard dose; Nos. Pts.: number patients; BL: Burkitt’s lymphoma; ORR: objective response rate (CR/PR): complete response/partial response; MST: median survival time, 1-yr : 1-year survival rate and OS: overall survival; and cART: combination antiretroviral therapy.].

Regimen (Study/Year) [Reference]Nos. Pts.ORR (CR/PR)SurvivalComment(s)

(A) Sub-Saharan Africa Data—Prospective trial (1) and key retrospective studies

Dose-modified oral chemo. (CWRU 2498/2009) [29]4978% (CR 58%/PR 20%)MST 12.3 mos.
(33% 1-yr)
Only published prospective treatment trial of AR-NHL in sub-Saharan Africa; conducted comparable HIV therapeutic era as ACTG 142 trial [45]; 6% treatment mortality rate.
Uganda Cancer Institute (NHL study/2011) [35]154
(32% HIV+)
No response data provided or types of chemotherapy.MST 61 days (13% 1-yr)Largest retrospective study on NHL including HIV(−) and HIV(+) cases ever reported with treatment and outcome data. Only 60% had acceptable clinical staging.
Stellenbosch University (NHL study/2010) [19]512
(4 HIV+)
Overall CR range 46–75% for all subtypes; chemotherapy regimens not reported.MST 10 mos. (50% 1-yr)Comprehensive retrospective study of spectrum lymphoproliferative disorders at a major private referral centre in Cape Town. Only 4 cases (<1%) were HIV(+). MST is for the 4 AR-NHL cases.
Uganda Cancer Institute (Pediatric BL study/2009) [34]228
(31% HIV+)
36% CR HIV(+)
41% CR HIV(−)
MST 11.8 mos. HIV(+) Not reached HIV(−)Comprehensive and largest retrospective study of pediatric BL in sub-Saharan Africa. No details on types of chemotherapy administered.
University of Nairobi (BL study/2001) [36]796
with 29 adult BL
(66% HIV+)
No response data reported or types of chemotherapy.MST 15 wks.Among earliest period prevalence and retrospective study that identified 3-fold increase in adult BL cases in the AIDS era. MST is for HIV(+) BL.

(B) United States Data—Select clinical trials

Concurrent R-EPOCH versus sequential R-EPOCH (AMC 034/2010 ) [53]48 concurrent
53 sequential
73% CR concurrent 55% CR sequential2-yr OS 70% concurrent versus 67% sequentialRandomized phase II trial of concurrent versus sequential rituximab with EPOCH chemotherapy; the primary efficacy endpoint of CR achieved only for the concurrent arm.
R-CHOP versus CHOP (AMC 010/2005) [49]15058% CR R-CHOP
47% CR CHOP
139 wks. OS R-CHOP 110 wks. OS CHOPRandomized trial among first to use rituximab; raised concern with higher infectious deaths on R-CHOP arm; not substantiated in future trials with rituximab.
Infusional CDE (ECOG E1494/2004) [48]9845% CR2-yr OS 43%Among largest studies of a highly active infusional regimen conducted during emergence of cART era.
Infusional EPOCH (NCI/2003) [47]3974% CR63% OS at 53 mos.Dose-adjusted (on basis of CD4+ lymphocyte count) chemotherapy regimen with interruption of cART amongst highest CR and survival reported at time.
LD and SD CHOP (AMC 005/2001) [46]40 LD
23 SD
30% CR LD
48% CR SD
Not reportedNot randomized; 2 consecutive treatment arms established feasibility of concurrent chemotherapy with cART. Median duration of response 9 mos. LD; not reached for SD CHOP.
LD versus SD m-BACOD (ACTG 142/1997) [45]98 LD
94 SD
41% CR LD
52% CR SD
35 wks. LD
31 wks. SD
Largest randomized clinical trial in AR-NHL ever conducted; established equivalence of LD versus SD in pre-cART era.