history of hiv infection pre-haart era (up to 1996-1997) haart erahaart era (1997-...)
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History of HIV infectionHistory of HIV infection
• Pre-HAART era (up to 1996-1997)
• HAART eraHAART era (1997-...)
Impact of HAART on natural Impact of HAART on natural history of HIV infectionhistory of HIV infection
incidence opportunistic infections incidence Kaposi’s sarcoma incidence carcinoma of cervix incidence of primary CNS lymphoma incidence (significant in recent studies)
of the remaining NHL
• ↑ incidence Hodgkin’s lymphoma
Biggar, R. J. et al. J. Natl. Cancer Inst. 2007 99:962-972
Incidence of major AIDS-associated cancers by CD4 count category in persons with AIDS, by calendar-year period
Biggar RJ, et al. Blood 2006; 108: 3786-91
Incidence of HL and NHL by CD4 lymphocyte Incidence of HL and NHL by CD4 lymphocyte count at diagnosis of HIV infectioncount at diagnosis of HIV infection
HAART before lymphoma
N=31
No HAART before
lymphomaN=100
P
CNS involvement 1/31 25/100 0.008
PCNSL *1/31 13/100 0.108
Leptomeningeal spread in systemic NHL
0/30 12/87 0.023
CNS infiltration and HAARTCNS infiltration and HAART
JT Navarro et al. Haematologica 2008; 93: 149-150
Hodgkin’s (N=20)
Non Hodgkin’s (N=101)
Outcome of lymphomas in Pre-HAART eraICO-HGTP experience
Impact of HAART in response and Impact of HAART in response and survival in HIV-related lymphomassurvival in HIV-related lymphomas
HAART use HAART responseAuthor (yr) CR OS CR OS
Antinori (2001) + +Navarro (2001) + +Tam (2002) +Gerard (2002)* + +Navarro (2002) +Vaccher (2003) + +Hoffmann (2003) + +Ribera (2002)* + +Hoffmann (2004)* +Oriol (2005)** +Xicoy (2007)* +Ribera (2008) +
*Hodgkin’s lymphoma. **Burkitt’s lymphoma
Diffuse large-B-cell lymphoma
CHOP+ HAART(n=26, 0.60.2)
CHOP (n=44, 0.220.13)
P=0.002
HAART responders(n=15, 0.830.18)
HAART non-reesponders(n=10, 0.260.29)
P=0.015
JT Navarro, JM Ribera, A Oriol, et al. Br J Haematol 2001; 112: 909-915
Navarro JT, Ribera JM, Oriol A, et al. Leuk Lymphoma2002; 43: 1837-42
Burkitt’s lymphoma/leukemia
Response, 85±24%, n=7
No resp./No HAART, 27±22%, n= 11
P=0.04
A Oriol et al. Haematologica 2005; 90: 990-2
Hodgkin’s lymphoma
HAART n= 20, 83±15%.
No HAART n=25, 13±15%
P= 0.001
JM Ribera et al. AIDS 2002; 16: 1973-1976
Current approach of the treatment of HIV-related lymphomas in Spain
• Diffuse large B-cell lymphomas– CHOP– R-CHOP-21– R-CHOP-14– R-CHOP-21+ HDT/ASCT
• Burkitt’s lymphoma/leukemia– PETHEMA ALL3/97– BURKIMAB
• Hodgkin’s lymphoma– ABVD
Diffuse large B-cell lymphoma
CHOP
R-CHOP-21
R-CHOP-14
R-CHOP-21 + HDT/ASCT
Diffuse large B-cell lymphomaCHOP
CHOP+ HAART(n=26, 0.60.2)
CHOP (n=44, 0.220.13)
P=0.002
JT Navarro, JM Ribera, A Oriol, et al. Br J Haematol 2001; 112: 909-915
JT Navarro et al. Haematologica, 2005; 90: 704 - 706.
HIV+ and HAART vs. HIV-
ImmunochemotherapyImmunochemotherapy
Author (yr) Schedule N CR(%) DFS(%) OS(%)
Boue (2006) R-CHOP 61 77 69 75
Ribera (2008) R-CHOP 81 69 77 56
Kaplan (2005) R-CHOP** 99 58 45wk* 139wk*
Spina (2005) R-CDE 74 70*** 89*** 64***
*Median. **R-CHOP arm of the randomized study*** Better results than those from historic control with CDE (CR 45%, OS 38%)
Boue, F. et al. J Clin Oncol; 24:4123-4128 2006
R-CHOP (DLBCL & BL)
OS PFS
Spina, M. et al. Blood 2005;105:1891-1897
R-CDE
OS PFS
Ribera et al . Br J Haematol 2008; 140: 411-419
DFS OS
Diffuse large B-cell lymphomaRituximab+CHOP-21
LNH-VIHR-CHOP vs. CHOP
AMC010 StudyKaplan LD, et al. Blood 2005; 106: 1538-1543
AMC: Randomized Lymphoma Studies
Study Arm No. Median CD4
CR 1 YR EFS
AMC010 CHOP 51 154 47%
(22,62%)
50%
(39,61%)
AMC010 R-CHOP 99 128 58%
(47, 67%)
48%
(32,64%)
AMC034 EPOCHR 55 188 53%
(41,64%)
68%
(55,81%)
AMC034 R-EPOCH 51 196 69%
(56, 79%)
78%
(66,90%)
Sparano JA. Blood 2010; 115: 3008-16.
AMC 034 Study
AMC 034 Study