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Background: Brentuximab vedotin in combination with doxorubicin, vinblastine, and dacarbazine (AVD) is approved in the upfront setting for advanced stage classical Hodgkin lymphoma (cHL). People living with HIV have been excluded from these studies. We aimed to understand the activity and safety of brentuximab vedotin-AVD in people living with HIV diagnosed with Hodgkin lymphoma, while focusing on HIV disease parameters and antiretroviral therapy (ART) interactions., Methods: We present the phase 2 portion of a multicentre phase 1/2 study. Eligible patients were 18 years or older, had untreated stage II-IV HIV-associated cHL (HIV-cHL), a Karnofsky performance status of more than 30%, a CD4 + T-cell count of 50 cells per μL or more, were required to take ART, and were not on strong CYP3A4 or P-glycoprotein inhibitors. Patients were treated intravenously with 1·2 mg/kg of brentuximab vedotin (recommended phase 2 dose) with standard doses of AVD for six cycles on days 1 and 15 of a 28-day cycle. The primary endpoint of the phase 2 portion was 2-year progression-free survival (PFS), assessed in all eligible participants who began treatment. Accrual has been completed. This trial is registered at ClinicalTrials.gov, NCT01771107., Findings: Between March 8, 2013, and March 7, 2019, 41 patients received study therapy with a median follow up of 29 months (IQR 16-38). 34 (83%) of 41 patients presented with stage III-IV and seven (17%) with stage II unfavourable HIV-cHL. 37 (90%) of 41 patients completed therapy, all 37 of whom achieved complete response. The 2-year PFS was 87% (95% CI 71-94) and the overall survival was 92% (78-97). The most common grade 3 or worse adverse events were peripheral sensory neuropathy (four [10%] of 41 patients), neutropenia (18 [44%]), and febrile neutropenia (five [12%]). One treatment-related death was reported, due to infection., Interpretation: Brentuximab vedotin-AVD was highly active and had a tolerable adverse event rate in HIV-cHL and is an important therapeutic option for people with HIV-cHL. The complete reponse rate is encouraging and is possibly related to a unique aspect of HIV-cHL biology. Upcoming 5-year data will evaluate the sustainability of the outcomes obtained., Funding: National Institutes of Health and National Cancer Institute., Competing Interests: Declaration of interests AN has an MSK core grant National Institutes of Health (NIH) P30 CA008748 and NIH grant PO1 1568 G TA390. MAR is supported by the Johns Hopkins University Core Grant P30CA006973, contracts with Cullinan Apollo and RenovoRx, and is a founder and serves on the Board of Directors of Geminus Therapeutics. EGR is the co-chair of the National Comprehensive Cancer Network panel of Cancer in Persons With HIV and Kaposi Sarcoma, an unpaid position. PCM is supported by an MSK core grant (P30CA008748). PGR, AN, EGR, PCM, MB, JYL, RM, DHH, JCR, RFA, CD, MAR, AC, LR, and EC are supported in part by National Cancer Institute-sponsored AIDS Malignancy Consortium grant UM1CA121947 and UM1CA181255. RFA is supported by John Hopkins Cancer Center (5P30CA006973). CB and NM are supported in part by Lymphoma Study Association, and DC and YT are supported in part by the French Agency for Research on AIDS and Viral Hepatitis. DC also has contracts with Jansen and speaker bureau funding from Gilead and Pfizer. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We report a first in-depth comparison of immune reconstitution in patients with HIV-related lymphoma following autologous hematopoietic cell transplant (AHCT) recipients (n=37, lymphoma, BEAM conditioning), HIV(-) AHCT recipients (n=30, myeloma, melphalan conditioning) at 56, 180, and 365 days post-AHCT, and 71 healthy control subjects. Principal component analysis showed that immune cell composition in HIV(+) and HIV(-) AHCT recipients clustered away from healthy controls and from each other at each time point, but approached healthy controls over time. Unsupervised feature importance score analysis identified activated T cells, cytotoxic memory and effector T cells [higher in HIV(+)], and naïve and memory T helper cells [lower HIV(+)] as a having a significant impact on differences between HIV(+) AHCT recipient and healthy control lymphocyte composition (p<0.0033). HIV(+) AHCT recipients also demonstrated lower median absolute numbers of activated B cells and lower NK cell sub-populations, compared to healthy controls (p<0.0033) and HIV(-) AHCT recipients (p<0.006). HIV(+) patient T cells showed robust IFNγ production in response to HIV and EBV recall antigens. Overall, HIV(+) AHCT recipients, but not HIV(-) AHCT recipients, exhibited reconstitution of pro-inflammatory immune profiling that was consistent with that seen in patients with chronic HIV infection treated with antiretroviral regimens. Our results further support the use of AHCT in HIV(+) individuals with relapsed/refractory lymphoma., Competing Interests: PS, Seattle Genetics, Research funding. AK, Celgene, Consultancy, Speakers Bureau, Millennium/Takeda, Consultancy, Speakers Bureau, Onyx, Consultancy, Speakers Bureau, Janssen, Consultancy, Speakers Bureau. Hofmeister, Signal Genetics, Inc., Membership on an entity’s Board of Directors or advisory committees, Celgene, Research Funding; Arno Therapeutics, Inc., Research Funding, Incyte, Corp, Membership on an entity’s Board of Directors or advisory committees, Janssen, Pharmaceutical Companies of Johnson & Johnson, Research Funding, Karyopharm Therapeutics, Research Funding, Takeda Pharmaceutical Company, Research Funding, Teva, Membership on an entity’s Board of Directors or advisory committees. SF, Mustang Therapeutics, Other, Construct licensed by City of Hope. WN, Atara Biotherapeutics, employment, stock ownership. GL, Boehringer Ingelheim, Research Funding, Beckman Coulter, Research Funding, Stemline Therapeutics Inc., Research Funding, Genentech. RB, Prelude Therapeutics, Research Funding and Scientific Advisory Board, Viracta, Scientific Advisory Board. AN, Janssen, Membership on a Board or Advisory Committee; Medscape, Honoraria; Morphosys, Membership on a Board or Advisory Committee; Pharmacyclics, Research Funding, Honoraria; Rafael Pharma, Research Funding; Epizyme, Membership on a Board or Advisory Committee; Physician Education Resource, Consulting. MM and AMM are employed by EMMES Company. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Shindiapina, Pietrzak, Seweryn, McLaughlin, Zhang, Makowski, Ahmed, Schlotter, Pearson, Kitzler, Mozhenkova, Le-Rademacher, Little, Akpek, Ayala, Devine, Kaplan, Noy, Popat, Hsu, Morris, Mendizabal, Krishnan, Wachsman, Williams, Sharma, Hofmeister, Forman, Navarro, Alvarnas, Ambinder, Lozanski and Baiocchi.)

Four cycles of rituximab plus CHOP chemotherapy is as effective as 6 cycles in low-risk diffuse large B-cell lymphoma (DLBCL). Here we report a post-hoc analysis of a prospective clinical trial in patients with HIV-associated DLBCL and high-grade lymphoma treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy. 106 evaluable patients with HIV-associated DLBCL or high-grade CD20-positive non-Hodgkin's lymphoma were randomized to receive rituximab (375 mg/m2) given either concurrently prior to each infusional EPOCH cycle, or sequentially (weekly for 6 weeks) following completion of EPOCH. EPOCH consisted of a 96-hour IV infusion of etoposide, doxorubicin, and vincristine plus oral prednisone followed by IV bolus cyclophosphamide every 21 days for 4 to 6 cycles. Patients received 2 additional cycles of therapy after documentation of a complete response (CR) by computerized tomography after cycles 2 and 4. 64 of 106 evaluable patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms. The 2-year event-free survival (EFS) rates were similar in the 24 patients with CR who received 4 or fewer EPOCH cycles (78%, 95% confidence intervals [55%, 90%]) due to achieving a CR after 2 cycles, compared with those who received 5-6 cycles of EPOCH (85%, 95% CI 70%, 93%) because a CR was first documented after cycle 4. A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in patients with HIV-associated lymphoma treated with EPOCH plus rituximab, which merits further evaluation in additional prospective trials. Clinical Trials.gov identifier NCT00049036.

Burkitt lymphoma is a rare and aggressive non-Hodgkin lymphoma with three classifications: endemic, sporadic, and immunodeficiency-related. High-intensity chemotherapeutic regimens have considerably improved overall survival for patients with Burkitt lymphoma. In this Review of HIV-associated Burkitt lymphoma, we summarise expert opinion and provide general recommendations for the treatment of Burkitt lymphoma in patients with HIV on the basis of retrospective and prospective studies, taking into consideration immune status, CD4 cell counts, the presence of systemic disease, and the risk of CNS involvement or relapse. We also discuss the role of rituximab and antiretroviral therapy. We highlight the reasons behind the possible different mechanisms of lymphomagenesis in HIV-associated Burkitt lymphoma and endemic Burkitt lymphoma, which indicate that HIV might have either a direct or indirect oncogenic role in Burkitt lymphoma. We discuss the possible mechanisms by which HIV and HIV proteins could directly contribute to lymphomagenesis. Identifying these mechanisms might lead to the development of therapies that have fewer toxic effects than high-intensity chemotherapeutic regimens., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Despite widely available antiretroviral therapy, lymphoma remains the leading cause of death for human immunodeficiency virus (HIV)-infected persons in economically developed countries. Even a few months of drug interruptions can lead to drops in the CD4 cell count, HIV viremia, and an increased risk of lymphoma. Currently, good HIV control facilitates intensive therapies appropriate to the lymphoma, including autologous and even allogeneic hematopoietic stem cell transplantation. Nonetheless, HIV-related lymphomas have unique aspects, including pathogenetic differences driven by the presence of HIV and often coinfection with oncogenic viruses. Future therapies might exploit these differences. Lymphoma subtypes also differ in the HIV-infected population, and the disease has a higher propensity for advanced-stage, aggressive presentation and extranodal disease. Other unique aspects include the need to avoid potential interactions between antiretroviral therapy and chemotherapeutic agents and the need for HIV-specific supportive care such as infection prophylaxis. Overall, the care of these patients has progressed sufficiently that recent guidelines from the American Society of Clinical Oncology advocate the inclusion of HIV-infected patients alongside HIV-negative patients in cancer clinical trials when appropriate. This article examines HIV lymphoma and includes Burkitt lymphoma in the general population.

We set out to assess feasibility and safety of allogeneic hematopoietic cell transplant in 17 persons with HIV in a phase II prospective multicenter trial. The primary endpoint was 100-day nonrelapse mortality (NRM). Patients had an 8/8 HLA-matched related or at least a 7/8 HLA-matched unrelated donor. Indications for transplant were acute leukemia, myelodysplasia, and lymphoma. Conditioning was myeloablative or reduced intensity. There was no NRM at 100 days. The cumulative incidence of grades II to IV acute graft-versus-host disease (GVHD) was 41%. At 1 year, overall survival was 59%; deaths were from relapsed/progressive disease (n = 5), acute GVHD (n = 1), adult respiratory distress syndrome (n = 1), and liver failure (n = 1). In patients who achieved complete chimerism, cell-associated HIV DNA and inducible infectious virus in the blood were not detectable. Blood and Marrow Transplant Clinical Trials Network 0903/AIDS Malignancy Consortium 080 was registered at www.clinicaltrials.gov (no. NCT01410344)., (Copyright © 2019 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

HIV-associated lymphomas (HALs) have high rates of latent infection by gammaherpesviruses (GHVs). We hypothesized that proteasome inhibition would induce lytic activation of GHVs and inhibit HIV infectivity via preservation of cytidine deaminase APOBEC3G, improving lymphoma control. We tested this oncolytic and antiviral strategy by using bortezomib combined with ifosfamide, carboplatin, and etoposide (ICE) alone or with rituximab (ICE/R) in relapsed/refractory HAL. A 3+3 dose-escalation design was used with a 7-day lead-in period of single-agent bortezomib. Bortezomib was administered intravenously on days 1 and 8 of each cycle at 1 of 4 dose levels: 0.7, 1.0, 1.3, or 1.5 mg/m 2 ICE began day 8 of cycle 1 and day 1 of subsequent cycles. Rituximab was included on day 1 of cycles 2 to 6 for CD20 + lymphomas. Twenty-three patients were enrolled. The maximum tolerated dose of bortezomib was not reached. Grade 4 toxicities attributable to bortezomib were limited to myelosuppression. Responses occurred in 17 (77%) of 22 patients receiving any protocol therapy. The 1-year overall survival was 57%. After bortezomib alone, both patients with Kaposi sarcoma herpesvirus (KSHV)-positive lymphoma had more than a 1-log increase in KSHV viral load. In 12 patients with Epstein-Barr virus (EBV)-positive lymphoma, median values of EBV viral load increased. Undetectable HIV viremia at baseline in the majority of patients limited evaluation of HIV inhibition. APOBEC3G levels increased in 75% of evaluable patients. Bortezomib combined with ICE/R in patients with relapsed/refractory HAL is feasible with response and survival comparing favorably against previously reported second-line therapies. Changes in GHV viral loads and APOBEC3G levels trended as hypothesized. This trial was registered at www.clinicaltrials.gov as #NCT00598169.

People living with HIV (PLWH) are diagnosed with cancer at an increased rate over the general population and generally have a higher mortality due to delayed diagnoses, advanced cancer stage, comorbidities, immunosuppression, and cancer treatment disparities. Lack of guidelines and provider education has led to substandard cancer care being offered to PLWH. To fill that gap, the NCCN Guidelines for Cancer in PLWH were developed; they provide treatment recommendations for PLWH who develop non-small cell lung cancer, anal cancer, Hodgkin lymphoma, and cervical cancer. In addition, the NCCN Guidelines outline advice regarding HIV management during cancer therapy; drug-drug interactions between antiretroviral treatments and cancer therapies; and workup, radiation therapy, surgical management, and supportive care in PLWH who have cancer., (Copyright © 2018 by the National Comprehensive Cancer Network.)

Drug-drug interactions between cART and chemotherapy may impact HIV and lymphoma control or lead to increased toxicities. No prospective comparative data informs potential harms and benefits. In AMC034, HIV-associated high-grade B-cell NHL patients received DA-EPOCH with rituximab. cART was given with EPOCH or delayed until chemotherapy completion per investigator choice. Pharmacokinetic, immunological, and treatment effects of concurrent cART were evaluated. CD4 counts dropped during EPOCH in both groups but recovered to higher than baseline 6 months post-EPOCH only in the cART group. HIV viral load decreased during chemotherapy in the cART group but increased in the non-cART group. Incidence of grade ≥3 infectious, hematologic, or neurological toxicities was similar. Concurrent cART was not associated with 1-year EFS or OS. cART with EPOCH was well-tolerated and allowed for faster immune recovery. While we did not observe differences in outcome, the preponderance of evidence is in favor of combining cART with chemotherapy.

Introduction: Vorinostat (VOR), a histone deacetylase inhibitor, enhances the anti-tumor effects of rituximab (R) and cytotoxic chemotherapy, induces viral lytic expression and cell killing in Epstein-Barr virus-positive (EBV + ) or human herpesvirus-8-positive (HHV-8 + ) tumors, and reactivates latent human immunodeficiency virus (HIV) for possible eradication by combination antiretroviral therapy (cART)., Patients and Methods: We performed a phase I trial of VOR given with R-based infusional EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin hydrochloride) (n = 12) and cART in aggressive HIV-associated B-cell non-Hodgkin lymphoma (NHL) in order to identify safe dosing and schedule. VOR (300 or 400 mg) was given orally on days 1 to 5 with each cycle of R-EPOCH for 10 high-risk patients with diffuse large B-cell lymphoma (1 EBV + ), 1 EBV + /HHV-8 + primary effusion lymphoma, and 1 unclassifiable NHL. VOR was escalated from 300 to 400 mg using a standard 3 + 3 design based on dose-limiting toxicity observed in cycle 1 of R-EPOCH., Results: The recommended phase II dose of VOR was 300 mg, with dose-limiting toxicity in 2 of 6 patients at 400 mg (grade 4 thrombocytopenia, grade 4 neutropenia), and 1 of 6 treated at 300 mg (grade 4 sepsis from tooth abscess). Neither VOR, nor cART regimen, significantly altered chemotherapy steady-state concentrations. VOR chemotherapy did not negatively impact CD4+ cell counts or HIV viral loads, which decreased or remained undetectable in most patients during treatment. The response rate in high-risk patients with NHL treated with VOR(R)-EPOCH was 100% (complete 83% and partial 17%) with a 1-year event-free survival of 83% (95% confidence interval, 51.6%-97.9%)., Conclusion: VOR combined with R-EPOCH was tolerable and seemingly efficacious in patients with aggressive HIV-NHL., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose People with HIV are living longer as a result of effective antiretroviral therapy. Cancer has become a leading cause of morbidity and mortality in this patient population. However, studies of novel cancer therapeutics have historically excluded patients with HIV. Critical review of eligibility criteria related to HIV is required to accelerate development of and access to effective therapeutics for HIV-infected patients with cancer and make studies more generalizable to this patient population. Methods From January through April 2016, the HIV Working Group conducted a series of teleconferences; a review of 46 New Drug Applications from registration studies of unique agents studied in adults with cancer that led to the initial US Food and Drug Administration approval of that agent from 2011 to 2015; and a review of HIV-related eligibility criteria from National Cancer Institute-sponsored studies. Results were discussed and refined at a multistakeholder workshop held May 12, 2016. The HIV Working Group developed recommendations for eligibility criteria that focus on pharmacologic and immunologic considerations in this patient population and that balance patient safety, access to appropriate investigational agents, and study integrity. Results Exclusion of patients with HIV remains common in most studies of novel cancer agents. Models for HIV-related eligibility criteria in National Cancer Institute-sponsored studies are instructive. HIV infection itself should no longer be an exclusion criterion for most studies. Eligibility criteria related to HIV infection that address concurrent antiretroviral therapy and immune status should be designed in a manner that is appropriate for a given cancer. Conclusion Expanding clinical trial eligibility to be more inclusive of patients with HIV is justified in most cases and may accelerate the development of effective therapies in this area of unmet clinical need.

The toxicity of dose-intensive regimens used for Burkitt lymphoma prompted modification of cyclophosphamide, vincristine, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine (CODOX-M/IVAC) for HIV-positive patients. We added rituximab, reduced and/or rescheduled cyclophosphamide and methotrexate, capped vincristine, and used combination intrathecal chemotherapy. Antibiotic prophylaxis and growth factor support were required; highly active antiretroviral therapy (HAART) was discretionary. Thirteen AIDS Malignancy Consortium centers enrolled 34 patients from 2007 to 2010. Median age was 42 years (range, 19-55 years), 32 of 34 patients were high risk, 74% had stage III to IV BL and CD4 count of 195 cells per μL (range, 0-721 cells per μL), and 5 patients (15%) had CD4 <100 cells per μL. Twenty-six patients were receiving HAART; viral load was <100 copies per mL in 12 patients. Twenty-seven patients had at least one grade 3 to 5 toxicity, including 20 hematologic, 14 infectious, and 6 metabolic. None had grade 3 to 4 mucositis. Five patients did not complete treatments because of adverse events. Eleven patients died, including 1 treatment-related and 8 disease-related deaths. The 1-year progression-free survival was 69% (95% confidence interval [CI], 51%-82%) and overall survival was 72% (95% CI, 53%-84%); 2-year overall survival was 69% (95% CI, 50%-82%). Modifications of the CODOX-M/IVAC regimen resulted in a grade 3 to 4 toxicity rate of 79%, which was lower than that in the parent regimen (100%), without grade 3 to 4 mucositis. Despite a 68% protocol completion rate, the 1-year survival rate compares favorably with 2 studies that excluded HIV-positive patients. This trial was registered at http://clinicaltrials.gov as #NCT00392834., (© 2015 by The American Society of Hematology.)

Limited comparative data exist for the treatment of HIV-associated non-Hodgkin lymphoma. We analyzed pooled individual patient data for 1546 patients from 19 prospective clinical trials to assess treatment-specific factors (type of chemotherapy, rituximab, and concurrent combination antiretroviral [cART] use) and their influence on the outcomes complete response (CR), progression free survival (PFS), and overall survival (OS). In our analysis, rituximab was associated with a higher CR rate (odds ratio [OR] 2.89; P < .001), improved PFS (hazard ratio [HR] 0.50; P < .001), and OS (HR 0.51; P < .0001). Compared with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), initial therapy with more dose-intense regimens resulted in better CR rates (ACVBP [doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisolone]: OR 1.70; P < .04), PFS (ACVBP: HR 0.72; P = .049; "intensive regimens": HR 0.35; P < .001) and OS ("intensive regimens": HR 0.54; P < .001). Infusional etoposide, prednisone, infusional vincristine, infusional doxorubicin, and cyclophosphamide (EPOCH) was associated with significantly better OS in diffuse large B-cell lymphoma (HR 0.33; P = .03). Concurrent use of cART was associated with improved CR rates (OR 1.89; P = .005) and trended toward improved OS (HR 0.78; P = .07). These findings provide supporting evidence for current patterns of care where definitive evidence is unavailable.

Purpose: Infusional chemotherapy is efficacious in patients with AIDS-related lymphoma, but it may be difficult to administer. We studied standard agents with rituximab plus pegylated liposomal doxorubicin (DR-COP) in an attempt to provide a more practical approach to therapy while ascertaining rates of response, potential infectious complications, and prognostic role of biologic markers., Patients and Methods: We conducted a prospective, multi-institutional phase II trial, employing (day 1) pegylated liposomal doxorubicin 40 mg/m(2), rituximab 375 mg/m(2), cyclophosphamide 750 mg/m(2), vincristine 1.4 mg/m(2) (not > 2 mg), and prednisone 100 mg orally on days 1 through 5, with concomitant antiretroviral therapy., Results: In 40 evaluable patients, median CD4 cells was 114/μL (range, 5 to 1,026/μL), and median HIV-1 viral load (VL) was 25,000 copies/mL. High or intermediate/high age-adjusted International Prognostic Index was present in 28%. Overall response was 67.5%, with complete remission in 47.5% (95% CI, 31.5 to 63.9). Of 19 complete responders, 84% had extranodal disease, 47% had CD4 < 100/μL, and 47% had VL > 50,000 copies/mL; one relapsed. With 25.5-month median follow-up, 62% (95% CI, 44 to 75) of patients remain alive. Sixteen patients (40%) experienced 22 infections, with grade 4 in only two (5%). No patient died as a result of infection during treatment; one had opportunistic infection., Conclusion: Profound immunodeficiency and high HIV-1 viral load do not preclude attainment of complete response after DR-COP with highly active antiretroviral therapy. The regimen is tolerable, and use of rituximab was not associated with death as a result of infection during treatment. This approach may be useful in patients in whom the more intensive infusional regimens are impractical.

Purpose of Review: HIV-infected individuals remain at an increased risk for developing malignancies despite the use of combined antiretroviral therapy. Lymphomas comprise a large proportion of the malignancies that affect the HIV-infected population in developed countries. This review summarizes the recent progress made in HIV lymphoma research published in 2009 through January 2010., Recent Findings: The majority of investigation in this field has been in diffuse large B-cell lymphoma, with infusional therapy remaining promising. Rituximab likely improves complete response and possibly overall survival, but may be associated with increased infections in a subset of patients with very low CD4 cell counts. Risk factors associated with the development of lymphoma include low CD4 cell count and likely cumulative HIV viremia. Biologic insights have been realized regarding pathogenesis., Summary: Overall, the outcome for HIV lymphoma continues to improve as insights into the pathophysiology and treatment advance.

Central nervous system ( CNS) involvement is reportedly more common in acquired immunodeficiency syndrome ( AIDS)-related lymphomas ( ARL). We describe factors and outcomes associated with CNS involvement at baseline ( CNSB) and relapse ( CNSR) in 886 patients with newly diagnosed ARL. Of 886 patients, 800 received either intrathecal ( IT) therapy for CNSB or IT prophylaxis. CNSB was found in 13%. CNSB was not associated with reduced overall survival ( OS). There was no difference in the prevalence of CNSB between the pre-combination antiretroviral therapy ( cART) and cART eras. 5·3% of patients experienced CNSR at a median of 4·2 months after diagnosis (12% if CNSB; 4% if not). Median OS after CNSR was 1·6 months. On multivariate analysis, only CNSB [hazard ratio ( HR) 3·68, P = 0·005] and complete response to initial therapy ( HR 0·14, P < 0·0001) were significantly associated with CNSR. When restricted to patients without CNSB, IT CNS prophylaxis with 3 vs. 1 agent did not significantly impact the risk of CNSR. Despite IT CNS prophylaxis, 5% of patients experienced CNSR. Our data confirms that CNSR in ARL occurs early and has a poor outcome. Complete response to initial therapy was associated with a reduced frequency of CNSR. Although CNSB conferred an increased risk for CNSR, it did not impact OS. [ABSTRACT FROM AUTHOR]

Whether maintenance therapy adds value in the treatment of HIV-associated multicentric Castleman disease (HIV1MCD) is unknown. In this issue of Blood, Dalla Pria et al have analyzed a prospective cohort to advocate that it is not. [ABSTRACT FROM AUTHOR]

The article presents a study which evaluates the efficacy of a modified dose intensive CODOX-M/IVAC for HIV-associated burkitt lymphoma (BL). The predictive potential of the therapy in the expression of IRF4/MUM1 is outlined. Medications involved in the treatment modification are highlighted which include rituximab (R), cyclophosphamide and methotrexate.

We report the results of a phenotypic and functional analysis of immune reconstitution in HIV(+) patients treated with allogeneic hematopoietic stem cell transplant (allo-HSCT), in comparison with HIV(+) autologous transplant (auto-HSCT) recipients, HIV(-) auto-HSCT recipients and healthy controls (HCs). Blood samples were collected at days 56, 180 and 365 post-transplant from HIV(+) allo-ASCT recipients (n=17, BMT-CTN-0903/AMC-080 trial), HIV(+) auto-SCT recipients (n=36, BMT-CTN-0803/AMC-071 trial) and HIV(-) auto-SCT recipients (n=30, NCT00569309/OSU-07044 trial), and at 1 time point from 71 HCs. Five-color flow cytometry was performed on whole blood. Principal component analysis (PCA) examined global differences across 18 immune cell subsets between all subject cohorts. Wilcoxon rank-sum tests compared median absolute and proportionate cell counts. Feature importance score analysis (FIS) identified contributions of 100 immune cell populations to differences between HIV(+) cohorts and HCs. Functional responsiveness of HIV(+) allo-HSCT recipients' T cells to stimulation with CD3- and CD28-directed antibodies, NK cells to stimulation with IL-12+IL-18 and monocytes to stimulation with lipopolysaccharide (LPS) was assessed by mass cytometry on peripheral blood mononuclear cells (n=2) and compared to HCs (n=2). PCA showed that immunomes of HIV(+) allo-HSCT recipients and HIV(+) auto-HSCT recipients clustered together at all time points. HIV(-) auto-SCT recipients and HCs clustered together and away from the HIV(+) cohorts. FIS identified 13 cell subsets that defined the difference between HIV(+) allo-HSCT recipients (all visits) and HCs and 11 immune cell subsets that defined the difference between HIV(+) auto-HSCT recipients (all visits) and HCs; in each comparison, activated CD3+/HLA-DR+ T cells had the greatest impact on the difference between composite HIV(+) and HC immunomes. At 1 year, both HIV(+) transplant recipient cohorts had higher absolute numbers of activated T cells, effector T cells and CD8+ T cells than HCs and lower numbers of CD4+ T cells, naïve T cells, and activated NK cells compared to HCs (p<0.031). Mass cytometry analysis showed that IFNʏ production by CD8+ T cells was increased and there were expanded populations of CD4+/T-bet+ and CD8+/T-bet+ T cells co-expressing cytotoxic molecules granzyme B and perforin persisting in HIV(+) allo-HSCT recipients, but not in HCs at 1 year. NK cell function was preserved; monocytes showed enhanced production of TNFα upon stimulation with LPS in HIV(+) allo-HSCT recipients compared to HCs at 1 year post-HSCT. Chronic HIV infection confers pro-inflammatory immune characteristics on phenotypic and functional profiling of the cellular immunome of stem cell transplant recipients, irrespective of allogeneic or autologous stem cell donor source. [ABSTRACT FROM AUTHOR]