1 / 39

Hematopoietic stem cell transplantation in HIV-infected patients

Chiara Cattaneo Hematology - ASST Spedali Civili Brescia, Italy. Hematopoietic stem cell transplantation in HIV-infected patients. HIV infections and hematological malignancies.

dorac
Download Presentation

Hematopoietic stem cell transplantation in HIV-infected patients

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  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

More Related