cancer cancer Hessamfar-Bonarek M et al. Int. J. Epidemiol. 2010;39:

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1 Hematopoietic Stem Cell Transplant in HIV- related lymphoma Song Zhao, MD PhD Hematology-Oncology Program University of Washington/FHCRC

2 Underlying Causes of Death in HIV-infected Adults cancer cancer Hessamfar-Bonarek M et al. Int. J. Epidemiol. 2010;39:

3 HIV-related ltd malignancies i Lymphomas* 10% Other Malignancies 30% No Malignancies 60% * About 70 to 90% of HIV-related lymphomas are highly aggressive.

4 Chemotherapy for HIV-related lymphoma Pre-HAART era Standard-dose dose therapy high risk of infection high treatment-related related mortality while no survival benefit Reduced-dose dose chemotherapy was adopted Post-HAART era - With advent of HAART and supportive care, high/standard- dose chemotherapies proved to be tolerable and resulted in complete remission and survival rates comparable to HIV- negative patients

5 Autologous HSCT in HIV-related Lymphomas Study No. of NHL No. of HL CD4+ count Viral load (copies per ml) Conditioning regimen NRM PFS OS Krishnan et al, 2005 Spitzer et al, 2008 Re et al, < 10,000 BEC, mean = TBI VP16/Cy 5% 85% at 32 months 15 5 > 50 < 110,000 BUCY 5% 49.5% at 6 months 19 (31) 8 (19) Mean= 218 Undetectable (78%) BEAM 0 75% at 44 months 85% at 32 months 74.4% at 6 months 75% at 44 months Balsalobre < 200 (80%) BEAM, % 5% at 61% at 32 et al, 2009 mean = TBI months 162 months months Krishnan et al, Mean = 154 < 50,000 BEC, TBI + VP16/Cy 72% at 60 70% at 60 1 yr months months

6 Common features among these studies Exclusion criteria Major organ dysfunction - LVEF < 50% - Renal insufficiency y( (CrCl < 60 or Cr > 2) - DLCO < 50% predicted - Abnormal LFTs CNS involvement HIV-specific criteria - Free of opportunistic infection within one year prior to HSCT - Must be on HAART at study entry

7 City of Hope Studies Single institution prospective study in 2005 & case-control control study in 2010 Eligibility - Fail to achieve CR after first line chemotherapy - Chemo-sensitive relapsed after 1 st CR - High risk NHL in 1 st CR HIV-specific criteria - First 5 patients CD4+ > Viral load < 10,000 /ml (2005) or < 50,000 /ml (2010) Prognostic factors (for better outcome) - Histology: DLBCL > non-dlbcl (overall survival) - Disease status at HSCT: CR/PR > Relapse/Induction failure (OS & PFS)

8 Italian Cooperative Group on AIDS and Tumors (GICAT) study Multi-institutional institutional prospective study in 2009 Intention-to ti to-treat treat t study: 50 enrolled, 27 underwent HSCT Eligibility - Fail to achieve CR after first line chemotherapy - High risk NHL in 1 st CR HIV-specific criteria: : CD4+ > 100 before 1 st line chemo in patients treated with HAART for > 6 months (HAART-responsive) Reasons of dropout: : early toxic death (2), chemo-resistant (10), refusal (1), failure of mobilization (6), early disease progression (4) Prognostic factors (for poor outcome) Marrow involvement (OS, PFS); Performance status ECOG 2 (OS); CD4+ < 100 (OS, PFS) Factors NOT significant for prognosis: Stage IV, HL vs NHL, systemic symptoms

9 European Group for Blood and Marrow Transplantation (EBMT) Study Multi-centric retrospective study Both chemosensitive (including relapse /progression if at least PR achieved after salvage tx) and chemo- resistant patients were included. HIV-specific criteria: None Prognostic factors for post-hsct relapse -Non-DLBCL (i.e. Burkitt, Plasmablastic, T cell) - Not in CR at HSCT - Use of > 2 pre-hsct treatment lines Median = 3 months

10 Autologous HSCT in HIV-related Lymphomas For fit, not profoundly immunocompromised patients with HIV-related dl lymphoma beyond first remission, salvage chemotherapy with HSCT should be considered as a standard option. HSCT candidates should at least show viral response to HAART Factors related to poorer HSCT outcome - not achieving CR/chemo-resistant disease -non-dlbcl histology

11 AllogeneicHSCT in HIV-infected patients

12 Allogeneic HSCT in HIV-infected patients

13 HIV Pathogenesis

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15 Acknowlegement Dr. Robert Richard Dr. Anthony Blau