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Hematopoietic stem cell transplantation in HIV-infected patients

Explore the efficacy and safety of hematopoietic stem cell transplantation in HIV-infected patients with hematological malignancies. Discover the impact of treatment modalities like autologous and allogeneic stem cell transplantation on outcomes and immune reconstitution.

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Hematopoietic stem cell transplantation in HIV-infected patients

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  1. Chiara Cattaneo Hematology - ASST Spedali Civili Brescia, Italy Hematopoietic stem cell transplantationin HIV-infected patients

  2. HIV infections and hematological malignancies • HIV-infected patients still have a risk of developing non-Hodgkin lymphoma (NHL) 24.2 times greater than does the general population • The risk of Hodgkin lymphoma (HL) is increased nearly 15-fold • Patients with HIV also remain at increased risk of acute leukemia,myelodysplastic syndromes andmyeloma Alvarnas Blood 2017

  3. HAART: impact on cancer epidemiology Non HodgkinLymphoma Non AIDS definingcancer CobucciJ Infect Public Health 2015

  4. Chemotherapy in HIV-pos patients: feasibility Standard chemotherapy • Standard chemotherapyfeasible • Welltolerated • Fewinfectiousevents • High Dose chemotherapy + • Autologousstemcelltransplantation • Allogeneicstemcelltransplantation Navarro Br J Haematol 2001

  5. Hematopoietic stem cell transplantation in HIV-infected patients • Autologous SCT (ASCT) • Lymphoprolipherative disesases • Salvage treatment • First line treatment • Acute Leukemia • Myeloma • Allogeneic SCT • HIV cure

  6. Hematopoietic stem cell transplantation in HIV-infected patients • Autologous SCT (ASCT) • Lymphoprolipherativedisesases • Salvage treatment • First line treatment • Acute Leukemia • Myeloma • Allogeneic SCT • HIV cure

  7. 16 relapsed/refractory HIV-ly • 8 NHL • 8 HL • 10 ptsreceivedtransplant • Promptengrafment • Acceptabletoxicity • 7 CR out of 9 evaluablepts

  8. Efficacy of ASCT in relapsed/refractory HIV-related ly

  9. Toxicity of ASCT in relapsed/refractory HIV-related ly

  10. The GICAT experience Relapsed/refractory HIV-Ly Re Blood 2009

  11. EBMT retrospectivestudy: 53 patients within each cohort • 66% non-Hodgkin lymphoma and 34% Hodgkin lymphoma Non relapse mortalitywithin the 1st year after ASCT: 8% (HIV-ly group) vs 2% (HIV-neg group) (NS)

  12. ‘Patients with HIV-related lymphomas should not be precluded from participating in AHCT clinical trials’

  13. Immune reconstitution after ASCT:no differences between HIV-pos and HIV-neg Thymicfunctionrecovery Simonelli ClinInfectDis 2010

  14. B- and T-cell recovery HIV-pos HIV-pos HIV-pos HIV-pos and HIV-neglymphomaundergoing ASCT Bertoli Sci Rep 2016

  15. Retrospectivemulticenterstudy (10 European centers) • Success (collection ≥2 x 10^6 CD34/kg) vs Failure (<2 x 10^6 CD34/kg) • 113/155 (73%) succesfulmobilization • Optimalyeld(≥5 x 10^6 CD34/kg) 74/155 (48%)

  16. ASCT as 1st line • High risk non HodgkinLymphoma • 20 DLCL • 6 Plasmablastic • 1 Anaplastic ITT (27 pts) Transplantedpts (16 pts) Re Bone MarrowTransplant 2018

  17. ASCT outcome according to disease status 62 HIV-ly (Brescia) Re ASH 2018

  18. A particular setting:plasmablastic lymphoma • HIV-associated • Frequentoralcavityinvolvement • CD20 neg • Poorprognosis Transplantedpts (n=10) Entirecohort (n=20) Cattaneo LeukLymphoma 2014 Al-MalkiBiol Blood MarrowTransplant 2014

  19. Acute leukemia in HIV-pos patients • About 2-fold risk increase than general population • Sporadic reports/ retrospective studies for HIV-AML • Intensive chemotherapy feasible and high percentage of remission, but limited survival • Low CD4 count predictive of poor response Median OS: 11 months Sutton Br J Haematol 2001 Aboulafia AIDS 2002 Evans leukLymph 2012 Hagiwara AIDS 2013

  20. Acute leukemia in HIV-positive patients: the REL’sexperience (1994-2011) • 14 HIV-AL/HR-MDS pts • 3 patients received only palliative care • Induction treatment: 9 pts • 3 ASCT • 3 AlloSCT • 1 front-line allogeneic stem cell transplantation • 1 azacytidine (HR-MDS) Pagani SIE 2013

  21. REL study: outcome of HIV-pos AL 3-y survival 20% Pagani SIE 2013

  22. REL study: toxicity of HIV-pos AL • 2 Toxicdeaths • 1 induction • 1 alloSCT

  23. Multiple myeloma in HIV-pos patients • HIV-infected patients have increased risks for plasma cell disorders • Incidence of monoclonal gammopathy: 3.8% to 26% (vs 3.2% HIV-neg population) • SIRs for MM range between 2.6 and 5 in different epidemiological studies CokerBiomark res 2013

  24. MM in HIV-pos: ASCT • Few data in literature, mainlysporadic • Feasible • Japaneseregistry: similar OS in HIV-pos and HIV-negpts 5-y OS: HIV-pos 61% vs HIV-neg 63% YoshinagaBiol Blood MarrowTransplant 2018

  25. Hematopoietic stem cell transplantation in HIV-infected patients • Autologous SCT (ASCT) • Lymphoprolipherativedisesases • Salvage treatment • First line treatment • Acute Leukemia • Myeloma • Allogeneic SCT • HIV cure

  26. AlloSCT in HIV-pos patients: data from the CIBMTR • 23 patients (1987-2003) • 10 Non HodgkinLymphoma • 7 Acute Leukemia • 2 ChronicMyelogenousLeukemia • 1 Severe Aplastic Anemia • 1 Erytrocyteinheriteddisorders 2-y OS: 30% †17 pts only 1 disease relapse GuptaBiol Blood Bone MarrowTransplant 2009

  27. AlloSCT in HIV-pos patients: impact of HAART HAART pts 25-years experience (1983-2008) HütterClinExpImmunol. 2011

  28. AlloSCT in HIV-infected patients: the spanish experience • 1999-2018 • 22 high risk HM • All patients cART • NRM 14% at 12mo • Relapse 24% at 24mo • Grade II-IV aGvHD: 40% • 68% of patients with infectious complications  viral infections as the most frequent cause Median OS and EFS: 46% Kwon AIDS 2019

  29. Allogeneic hematopoietic cell transplant (alloHCT) for hematologic malignancies in human immunodeficiency virus infected (HIV) patients (pts): Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0903)/AIDS Malignancy Consortium (AMC-080) trialAmbinder RF, et al. J Clin Oncol 2017; 35(15 suppl): 7006 First prospective cooperative group trial of matched related or unrelated allogeneic alloSCT (cART-treatable HIV infection and standard indication for Allo) • 17 pts (2012-2015): acute myeloid leukemia (9), acute lymphoblastic leukemia (2), myelodisplasia (2) or lymphoma (4) • Full ablative (8) or reduced-intensity alloHCT (investigator’s discretion); cART not interrupted • NRM at 100 days (primary endpoint): 0% • At 100 days: 13 CR; 4 Rel/PD (8 complete chimerism) • Grade II-IV GVHD 41%; Infections in 11 pts (3 gr 2; 8 gr 3) • 1 year OS 57% (median follow-up 24 ms) • Cause of death: disease relapse (5), aGVHD (1), liver failure (1), ARDS (1) AlloSCT should be considered for HIV patients with treatable HIV-infection with standard indications for alloSCT

  30. Hematopoietic stem cell transplantation in HIV-infected patients • Autologous SCT (ASCT) • Lymphoprolipherativedisesases • Salvage treatment • First line treatment • Acute Leukemia • Myeloma • Allogeneic SCT • HIV cure

  31. Blocking chemokine coreceptors Kiem Cell Stemcell 2012

  32. BERLIN PATIENT • 40-year-old HIV-AML patient • AlloSCTat first and second relapse • Stem cells from a donor who was homozygous for CCR5 delta32

  33. LONDON PATIENT • HIV-Hodgkinlymphomapatient • Reducedintensityregimen • CCR5Δ32/Δ32 donor • Antiretroviral therapy interrupted 16 months after transplantation • HIV-1 remission maintained over a further 18 months

  34. Gene therapy for HIV cure gene-modified autologous hematopoietic stem cells Kiem Cell Stemcell 2012

  35. Conclusions (I) • High dose therapy and autologousstemcelltransplantationfeasibleand welltoleratedin the HAART era • HIV-relatedlymphomaand otherhematologicalmalignancies • Similaroutcometo HIV-negativepatients

  36. Conclusions (II) • Selected HIV-infected patients with hematologic malignancies for alloHSCTwhen indicated, in expert centers • Homozygous for CCR5 D32 preferreddonors HIV cure • Gene therapyas a future approach for HIV-cure

  37. Thanks to… Alessandro Re Chiara Pagani Giuseppe Rossi Hematology ASST-Spedali Civili Brescia

  38. Acute myeloid leukemia in HIV-positive patients: the REL’s experience Pagani SIE 2013

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