Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study

Durand, Christine M.; Capoferri, Adam A.; Redd, Andrew D.; Zahurak, Marianna; Rosenbloom, Daniel I. S.; Cash, Ayla; Avery, Robin K.; Bolaños-Meade, Javier; Bollard, Catherine M.; Bullen, C. Korin; Flexner, Charles; Fuchs, Ephraim J.; Gallant, Joel E.; Gladstone, Doug E; Gocke, Christopher D.; Jones, Richard J.; Kasamon, Yvette L.; Lai, Jun; Levis, Mark J.; Luznik, Leo; Marr, Kieren A.; McHugh, Holly; Steinke, Seema Mehta; Pham, Paul A.; Pohlmeyer, Christopher W.; Pratz, Keith W.; Shoham, Shmuel; Wagner‐Johnston, Nina D.; Xu, Daniel; Siliciano, Janet D.; Quinn, Thomas C.; Siliciano, Robert F.; Ambinder, Richard F.

doi:10.1016/s2352-3018(20)30073-4

Cited by 16 publications

(15 citation statements)

References 32 publications

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“…Several studies have reported similar outcomes in HIV-infected patients and the general population when treated with salvage therapy followed by autologous stem cell transplantation [81][82][83]. Moreover, two patients with cHL have been reported in a prospective clinical trial of allogeneic bone marrow transplantation for patients with HIV and hematological malignancies [84].…”

Section: Treatment and Prognosismentioning

confidence: 84%

Hodgkin Lymphoma in People Living with HIV

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et al. 2021

Cancers

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Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While the incidence of aggressive forms of non-Hodgkin lymphoma decreased after the advent of cART, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein–Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching that of the general population. In this regard, effective cART during chemotherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug–drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the optimal treatment of PLWH with HL. In this article the authors review and update the epidemiological, clinical and biological aspects of HL presenting in PLWH with special emphasis on advances in prognosis and the factors that have contributed to it.

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Section: Treatment and Prognosismentioning

confidence: 84%

Hodgkin Lymphoma in People Living with HIV

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Cancers

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“…These results contrast with GvHD developing shortly after transplant with T-cell replete HSCs in ART-suppressed SHIV-infected rhesus macaques [45] or uninfected MCMs [46]. Although we performed transplants with cells from sex and MHC-matched donors, our strategy to limit post-transplant GvHD could broaden donor pools, allowing for more extensive MHC-mismatches, similar to a recent human study [47].…”

Section: Discussionmentioning

confidence: 91%

MHC-matched allogeneic bone marrow transplants fail to eliminate SHIV-infected cells from ART-suppressed Mauritian cynomolgus macaques

Weinfurter

D'Souza

Matschke

et al. 2021

Preprint

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Objective: Allogeneic hematopoietic stem cell transplants (allo-HSCTs) in antiretroviral therapy (ART) suppressed individuals can significantly reduce human immunodeficiency virus (HIV) latent reservoirs and lead to prolonged ART-free remission. The mechanisms reducing the reservoir size are not fully understood but may include pre-transplant conditioning regimens, ART-mediated protection of donor cells, and graft-versus-host responses. Design: We modeled allo-HSCT in four ART-suppressed simian-human immunodeficiency virus (SHIV)-infected Mauritian cynomolgus macaques (MCMs) to examine the role of transplant mediated factors in eliminating SHIV latently infected cells. Methods: SHIV-infected MCMs started ART 6-16 weeks post-infection. After 3-6 weeks on ART, the MCMs received myeloablative conditioning and MHC-matched bone marrow depleted of α/β T cells. The MCMs were treated with GvH disease (GvHD) prophylaxis consisting of cyclophosphamide and tacrolimus and maintained daily ART post-transplant. One MCM was removed from ART 74 days post-transplant, while the remaining three MCMs continued ART until their necropsies. Viral reservoirs were measured in the peripheral blood and lymph nodes pre- and post-transplant and tissues at necropsy. Results: The treatment regimen induced profound lymphocyte depletion without causing severe GvHD, producing undetectable viral loads post-transplant. However, SHIV-harboring cells persisted in lymphoid and non-lymphoid tissues, resulting in a rapid viral rebound in the ART withdrawn MCM. Conclusions: Our results indicate that myeloablative conditioning and maintaining ART through the peri-transplant period alone are insufficient for eradicating latent reservoirs early after transplant. They also suggest that GvH responses mediated by α/β T cells are likely necessary to kill HIV latently infected cells following allo-HSCTs.

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“…Several studies have reported similar outcomes in HIV-infected and general population treated with salvage therapy followed by autologous stem cell transplantation [82][83][84]. Moreover, 2 patients with cHL have been reported in a prospective clinical trial of allogeneic bone marrow transplantation for patients with HIV and hematological malignancies [85].…”

Section: Treatment and Prognosismentioning

confidence: 81%

Hodgkin Lymphoma in People Living With HIV

Navarro¹,

Moltó²,

Tapia³

et al. 2021

Preprint

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Despite widespread use of combined antiretroviral therapy (cART) and increased life expectancy in people living with HIV (PLWH), HIV-related lymphomas (HRL) remain a leading cause of cancer morbidity and mortality for PLWH, even in patients optimally treated with cART. While incidence of aggressive forms of non-Hodgkin lymphoma decreased after cART advent, incidence of Hodgkin lymphoma (HL) has increased among PLWH in recent decades. The coinfection of Epstein Barr virus plays a crucial role in the pathogenesis of HL in the HIV setting. Currently, PLWH with HRL, including HL, are treated similarly to HIV-negative patients and, importantly, the prognosis of HL in PLWH is approaching to that of the general population. In this regard, effective chem-otherapy is strongly recommended since it has been shown to improve survival rates in all lymphoma subtypes, including HL. As a consequence, interdisciplinary collaboration between HIV specialists and hemato-oncologists for the management of potential drug-drug interactions and overlapping toxicities between antiretroviral and antineoplastic drugs is crucial for the op-timal treatment of PLWH with HL. In this article the authors review and update the epidemio-logical, clinical and biological aspects of HL presenting in PLWH with special emphasis in the improvement on prognosis and the factors that have contributed to it.

show abstract

Allogeneic bone marrow transplantation with post-transplant cyclophosphamide for patients with HIV and haematological malignancies: a feasibility study

Cited by 16 publications

References 32 publications

Hodgkin Lymphoma in People Living with HIV

Hodgkin Lymphoma in People Living with HIV

MHC-matched allogeneic bone marrow transplants fail to eliminate SHIV-infected cells from ART-suppressed Mauritian cynomolgus macaques

Hodgkin Lymphoma in People Living With HIV

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