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