How I treat patients with HIV-related hematological malignancies using hematopoietic cell transplantation

Abstract

Hematopoietic cell transplantation (HCT) has now been shown to be safe and effective for selected HIV-infected patients with hematological malignancies. Autologous HCT is now the standard of care for patients with HIV-related lymphomas who otherwise meet standard transplant criteria. Limited data also support use of allogeneic HCT (alloHCT) in selected HIV-infected patients who meet standard transplant criteria. We recommend enrolling patients in clinical trials that offer access to CCR5Δ32 homozygous donors, if available. HIV-infected patients requiring HCT may also be considered for participation in trials evaluating the activity of gene-modified hematopoietic stem cells in conferring resistance to HIV infection. To be considered for HCT, patients must have HIV infection that is responsive to combination antiretroviral therapy (cART). Careful planning for the peri-HCT management of the cART can avoid risk of significant drug interactions and development of cART-resistant HIV. In general, we recommend against the use of boosted proteasome inhibitors and nonnucleotide reverse transcriptase inhibitors in the cART regimen, in favor of nucleoside reverse transcriptase inhibitors and integrase inhibitors (without cobicistat). After HCT, patients must be closely monitored for development of opportunistic infections (OI), such as cytomegalovirus. Prevention of OI should include prophylactic and pre-emptive antimicrobials.

Evolving Paradigms in HIV Malignancies: Review of Ongoing Clinical Trials

“…40 However, more research is needed to address several themes in HIVAM. Future trials should focus on not only testing safety and efficacy of cutting-edge immunotherapy and targeted treat ments being used in the general cancer population, but also improving the gaps in knowledge and practice for cancer screening and treatment, especially in low-resource regions.…”

“…Additional important considerations include identifying novel therapies for virally mediated tumors that disproportionally present in PLWH, treating persons with HIVAM and advanced immunosuppression, and optimizing co-management of both diseases in ART-naïve persons and those receiving care in settings where supportive therapies for hematologic toxicities and infections are limited. 40 …”

Acute Myeloid Leukemia in Patients Living with HIV Infection: Several Questions, Fewer Answers

“…As in the general HIV-negative population receiving alloHSCT, malignancy relapse remained the main cause of treatment failure, with 6-month and 1-year OS were 82.4% and 58.8%, respectively [82]. Although clinical evidence for alloHSCT in PLWH is globally limited, mainly resulting from case reports and small retrospective case series, as recently reviewed elsewhere [80], alloHSCT could actually be a reasonable and potentially curative option for selected patients, with well-controlled HIV infection, who otherwise meet standard criteria for transplant eligibility [79][80][81]. Detailed information so far available from the literature on the use of alloHSCT in HIV-infected patients with AML in the ART era is summarized in Table 4 [36,37,54,[81][82][83][84][85][86][87][88][89][90][91][92][93][94][95].…”

“…Since the 1980s, alloHSCT has been suggested as a possible treatment option to eradicate HIV infection, but this strategy was highly unsuccessful, because HIV replication was not affected during conditioning therapy in the absence of antiviral treatment and donor lymphoid cells arising after engraftment were persistently susceptible to HIV infection [77]. Furthermore, in the pre-ART era, the survival outcomes of alloHSCT performed to treat hematological malignancies were poor, mainly due to extremely high infection-related mortality rates [78,79]. After the introduction of ART, leading to advances in HIV management, survival outcomes in PLWH undergoing alloHSCT have significantly improved, resulting similar to those obtained for subjects without HIV infection [78][79][80][81].…”

“…Furthermore, in the pre-ART era, the survival outcomes of alloHSCT performed to treat hematological malignancies were poor, mainly due to extremely high infection-related mortality rates [78,79]. After the introduction of ART, leading to advances in HIV management, survival outcomes in PLWH undergoing alloHSCT have significantly improved, resulting similar to those obtained for subjects without HIV infection [78][79][80][81]. Notwithstanding, there still was general reluctance to routinely use alloHSCT in PLWH, mainly because of basal immunosuppression with presumptive high risk of opportunistic infections, complex drug-drug interactions, increase in conditioning regimens-related toxicities, and risk of delayed engraftment, potentially resulting in higher transplant-related mortality (TRM) [80].…”