المؤلفون: Meg Wirth, Susan E. Krown, Ntokozo Ndlovu, Ethel Cesarman, Naftali Busakhala, Bongani Kaimila, Jeannette Y. Lee, Scot C. Remick, Ariela Noy, Robert M. Strother, Elson Mberi, Abrahams Omoding, Satish Gopal, Amy Chadburn

المصدر: JCO Global Oncology

مصطلحات موضوعية: Zimbabwe, Malawi, Cancer Research, Vincristine, medicine.medical_specialty, MEDLINE, law.invention, Special Series: Oncology Clinical Trials in Africa: The Landscape and Updates, 03 medical and health sciences, 0302 clinical medicine, Randomized controlled trial, law, Prednisone, Antineoplastic Combined Chemotherapy Protocols, medicine, Humans, Uganda, 030212 general & internal medicine, Intensive care medicine, Review Articles, Acquired Immunodeficiency Syndrome, Performance status, business.industry, medicine.disease, Kenya, Lymphoma, Clinical trial, Regimen, Oncology, 030220 oncology & carcinogenesis, Lymphoma, Large B-Cell, Diffuse, business, medicine.drug

الوصف: The purpose of this article is to describe lessons from the first lymphoma clinical trial conducted by the AIDS Malignancy Consortium (AMC) in sub-Saharan Africa (SSA). AMC-068 was a randomized phase II comparison of intravenous versus oral chemotherapy for HIV-positive diffuse large B-cell lymphoma. Opening in 2016, AMC-068 planned to enroll 90 patients (45 per arm) in Kenya, Malawi, Uganda, and Zimbabwe over 24 months and follow patients for 24 months to assess overall survival. In 2018, the study closed after screening 42 patients but enrolling only 7. Challenges occurred during protocol development, pre-activation, and postactivation. During protocol development (2011-2012), major obstacles were limited baseline data to inform study design; lack of consensus among investigators and approving bodies regarding appropriateness of the oral regimen and need for randomized comparison with cyclophosphamide, doxorubicin, vincristine, and prednisone; and heterogeneity across sites in local standards for diagnosis, staging, and treatment. During pre-activation (2012-2016), challenges included unexpected length and layers of regulatory approval across multiple countries, need to upgrade pathology capacity at sites, need to augment existing chemotherapy infusion capacity at sites, and procurement issues for drugs and supplies. Finally, during postactivation (2016-2018), challenges included long delays between symptom onset and screening entry for many patients, leading to compromised performance status and organ function; other patient characteristics that frequently led to exclusion, including high tumor proliferative index or other pathologic features that were disallowed; and costs of routine diagnostic procedures often being borne by patients, which also contributed to pre-enrollment delays. Lessons from AMC-068 are being applied to the design and conduct of new AMC lymphoma trials in SSA, and the study has contributed to a strong operational foundation that will support innovative clinical trials in the future.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d216567861e05fe5cdcd33ba070465eTest
https://doi.org/10.1200/go.20.00152Test

المؤلفون: Ethel Cesarman, Jeannette Y. Lee, Joseph A. Sparano, Juan Carlos Ramos, Ronald T. Mitsuyasu, Ariela Noy, William Wachsman, Amy Chadburn, David H. Henry, Richard F. Ambinder, Lawrence D. Kaplan, Lee Ratner, David M. Aboulafia

المصدر: Haematologica. 106:730-735

مصطلحات موضوعية: Oncology, Vincristine, medicine.medical_specialty, Cyclophosphamide, medicine.medical_treatment, Immunology, CHOP, Biochemistry, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, immune system diseases, Prednisone, hemic and lymphatic diseases, Internal medicine, medicine, EPOCH (chemotherapy), Etoposide, 030304 developmental biology, 0303 health sciences, Chemotherapy, business.industry, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, Non-Hodgkin's lymphoma, 030220 oncology & carcinogenesis, Rituximab, Primary effusion lymphoma, business, Diffuse large B-cell lymphoma, Burkitt's lymphoma, medicine.drug

الوصف: Introduction: Six cycles of rituximab plus infusional EPOCH is considered a preferred regimen for first-line treatment of HIV-associated diffuse large B-cell lymphoma (DLBCL), HHV8-positive DLBCL, and primary effusion lymphoma, and is among the preferred regimens for HIV-associated Burkitt's lymphoma in the 2019 NCCN guidelines. A phase III trial demonstrated non-inferiority of 4 cycles of R-CHOP (followed by 2 additional doses of rituximab) compared with 6 cycles of R-CHOP in immunocompetent patients with low-risk DLBCL (stage I-II, age 18-60 years, and an age-adjusted International Prognostic Index score of 0), indicating that de-escalation of treatment duration may be safely achieved without compromising curability in an appropriately selected patient population. Here we report the outcomes for patients with HIV-associated DLBCL and high-grade non-Hodgkin lymphoma (NHL) treated with 4-6 cycles of EPOCH plus rituximab based a response-adapted treatment strategy under a completed prospective clinical trial (AMC-034). Methods: One hundred-six patients with HIV-associated DLBCL or high-grade CD20-positive NHL enrolled at multiple centers across the U.S. 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 dose-adjusted EPOCH regimen tailored for HIV+ patients. 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. Results: Sixty-four of 106 patients (60%, 95% CI 50%, 70%) had a CR in both treatment arms; characteristics of entire population and CR proportions stratified by number of EPOCH treatment cycles were similar (Table 1).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%) due to failure to achieve a CR after 2 cycles (Table 2 and Figure 1). Time to disease progression and overall survival wer also similar for those treated with 4 or fewer cycles compared with 5-6 cycles (91% vs. 87%, and 78% vs. 90%, respectively) (Table 2 and Figure 1). Conclusion: A response-adapted strategy may permit a shorter treatment duration without compromising therapeutic efficacy in an appropriately selected population of patients with HIV-associated NHL, which merits further evaluation in additional prospective trials. Disclosures Noy: Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b1ccfd7428e208175c04d7633da58616Test
https://doi.org/10.3324/haematol.2019.243386Test

المؤلفون: David M. Aboulafia, Erin Reid, Juan Carlos Ramos, Frank Maldarelli, Ronald T. Mitsuyasu, David Looney, Ethel Cesarman, Jeannette Y. Lee, Sara Yahyaei, Ariela Noy, Richard F. Ambinder, David H. Henry, Joseph A. Sparano, William Wachsman

المصدر: Blood Advances. 2:3618-3626

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, Lymphoma, Clinical Trials and Observations, viruses, HIV Infections, APOBEC-3G Deaminase, Carboplatin, Bortezomib, chemistry.chemical_compound, 0302 clinical medicine, Recurrence, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Etoposide, Oncolytic Virotherapy, CD20, Ifosfamide, biology, virus diseases, Hematology, Middle Aged, Viral Load, 030220 oncology & carcinogenesis, Female, Rituximab, Viral load, medicine.drug, Adult, medicine.medical_specialty, 03 medical and health sciences, Internal medicine, medicine, Humans, Aged, business.industry, HIV, biochemical phenomena, metabolism, and nutrition, medicine.disease, 030104 developmental biology, chemistry, Leukocytes, Mononuclear, biology.protein, business

الوصف: 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/m2. 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.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8b18b66bf2a9693001611dd3c20dedc8Test
https://doi.org/10.1182/bloodadvances.2018022095Test

المؤلفون: Muhammad Junaid Tariq, Amina Chaudhry, Erin Reid, Paul Rubinstein, Amy Chadburn, Ethel Cesarman, Eshana Shah, Camille E. DeMarco

المصدر: Blood. 138:1447-1447

مصطلحات موضوعية: Pathology, medicine.medical_specialty, CD30, business.industry, Immunology, Cell Biology, Hematology, medicine.disease, Biochemistry, Acquired immunodeficiency syndrome (AIDS), immune system diseases, hemic and lymphatic diseases, medicine, business, Diffuse large B-cell lymphoma

الوصف: Introduction: AIDS-related Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, with a variable response to chemotherapy depending on, and not limited to, cell of origin, double/triple hit, or MYC/BCL-2 co-expression status. Similar to DLBCL, AIDS-related DLBCL (ARL) with non-germinal center histology or MYC expression reports poorer response to treatment. In the immunocompetent population CD30+ DLBCL defines a histology with improved survival, however, the characteristics and outcomes of ARL expressing CD30 are not well studied. Methods: We assessed 3 cohorts of ARL. The first cohort, consisted of of an immunohistochemistry tissue microarray (TMA) of 30 ARL patients, followed by two validation cohorts. The first validation was a TMA of 80 ARL, from the AIDS Cancer Specimen Resource. Both TMAs were stained for CD10, BCL6, MUM1, CD20, Ki67, EBER, MYC (by IHC) cut off at 40%, BCL2 (by IHC) cut off 50%, and CD30 (considered positive if any CD30 was expressed on the malignant cells). The third validation cohort was from the County Hospital AIDS Malignancy Project (CHAMP), a prospective database of patients with hematological malignancies and HIV. Of the 100 cases with ARL, only 25 cases were found to have CD30 staining performed, thus only those cases were included. In total, 135 patients diagnosed with ARL were assessed. Cell of origin and germinal (GCB) vs. non-germinal center (NGC) was determined by the Hans algorithm. Statistical differences between groups were analyzed by the fisher exact test. Survival data, when available, was estimated using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 135 ARL, 30% (n=41) were CD30+. Ninety-one% of the cohort was male. EBER was 23% positive in the entire cohort (n=29/126). EBER was positive in the CD30+ vs. CD30- population, 59% (N=17) vs 26% (p 80% was also higher in the CD30- vs the CD30+ cohort 75 vs.60%, (p=0.052). Myc, BCL2, and double expressor lymphomas were identified 59 vs. 57%, 59 vs. 57%, and 31 vs. 28%, respectively, in the CD30+ ARL vs. the CD30- population, none were statistically significant. Survival data was only obtained for 56 of the patients. In the patients treated in the combined anti-retroviral era (ART), there was no difference in survival in the CD30+ vs. CD30- population, 74% (n=18) vs. 84% (n=12) at 5 years (p=0.8). In the 15 patients treated in the early ART era, the OS at 5 years was 48% for the CD30+ vs. 52% (p=0.4), the rest were treated in the pre-ART era. Conclusion: CD30+ ARL in this cohort represents 30% of all ARL evaluated, and presents almost exclusively as a non-germinal center phenotype and has a strong correlation with EBV. While no differences in survival were identified in this study, possible due to the small numbers of patients assessed with survival data, historically, NGC ARL have been shown to have poorer outcomes, by 20-30% in studies with da-EPOCH. As such, the need for better therapies, potentially to overcome these poor prognostic factors, should be studied further. Figure 1 Figure 1. Disclosures Reid: ADC Therapeutics: Other: Serves as Principle Investigator, Research Funding; Aptose Biosciences: Other: Serves as Principle Investigator, Research Funding; Millennium Pharmaceuticals: Other: Serves as Principle Investigator, Research Funding; Xencor: Other: Serves as Principle Investigator.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::fbb0d0856718686526b72e3196093ce2Test
https://doi.org/10.1182/blood-2021-154030Test

المؤلفون: Naftali Busakhala, Satish Gopal, Meg Wirth, Joseph A. Sparano, Ronald T. Mitsuyasu, Jackson Orem, Ethel Cesarman, Samantha L. Vogt, Susan E. Krown, Warren Phipps, David S. Lakomy, Robert M. Strother, Margaret Borok, Lilie L. Lin, Carla J. Chibwesha, Lameck Chinula, Vikash Sewram, Elizabeth Y. Chiao, Ntokozo Ndlovu

المصدر: JCO Global Oncology

مصطلحات موضوعية: musculoskeletal diseases, Cancer Research, medicine.medical_specialty, Sub saharan, Capacity Building, Human immunodeficiency virus (HIV), HIV Infections, medicine.disease_cause, 03 medical and health sciences, Special Series: Oncology Clinical Trials in Africa: The Landscape and Updates, 0302 clinical medicine, Acquired immunodeficiency syndrome (AIDS), stomatognathic system, Neoplasms, Medicine, Humans, 030212 general & internal medicine, Intensive care medicine, Sarcoma, Kaposi, Africa South of the Sahara, business.industry, medicine.disease, Clinical trial, stomatognathic diseases, Oncology, 030220 oncology & carcinogenesis, Special Articles, Female, business

الوصف: PURPOSE The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research. METHODS All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives. RESULTS Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region. CONCLUSION As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::149ecd5b74e1038fca268c4d2a53db5aTest
http://europepmc.org/articles/PMC7392698Test

المؤلفون: Paul G. Rubinstein, Ronald T. Mitsuyasu, Ethel Cesarman, Amy Chadburn, Juan Carlos Ramos, Joseph A. Sparano, Lee Ratner, Page C. Moore, David M. Aboulafia, Adam A. Capoferri, Richard F. Ambinder, Ariela Noy, Lawrence D. Kaplan, Christine M. Durand, Robert A. Baiocchi, Erin Reid, Eric R. Siegel, Jeannette Y. Lee

المصدر: Blood. 136(11)

مصطلحات موضوعية: Oncology, Male, Herpesvirus 4, Human, Genes, myc, HIV Infections, Kaplan-Meier Estimate, Biochemistry, immune system diseases, hemic and lymphatic diseases, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Etoposide, Lymphoma, AIDS-Related, Vorinostat, Lymphoma, Non-Hodgkin, Hematology, Herpesviridae Infections, Middle Aged, Viral Load, Progression-Free Survival, Treatment Outcome, Vincristine, Herpesvirus 8, Human, Rituximab, Female, Primary effusion lymphoma, medicine.drug, Adult, medicine.medical_specialty, Neutropenia, Anti-HIV Agents, Immunology, Drug Administration Schedule, Internal medicine, medicine, Humans, EPOCH (chemotherapy), Cyclophosphamide, Aged, business.industry, Cell Biology, medicine.disease, Thrombocytopenia, Lymphoma, CD4 Lymphocyte Count, Histone Deacetylase Inhibitors, Doxorubicin, DNA, Viral, HIV-1, Prednisone, business, Diffuse large B-cell lymphoma, Plasmablastic lymphoma

الوصف: EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::f1b69e74841a7b7d4e60177622bd4479Test
https://pubmed.ncbi.nlm.nih.gov/32957115Test

المؤلفون: Lee Ratner, Ronald T. Mitsuyasu, Juan Carlos Ramos, David M. Aboulafia, Robert A. Baiocchi, Erin Reid, Ariela Noy, Lawrence D. Kaplan, Paul G. Rubinstein, Page C. Moore, Eric R. Siegel, Christine M. Durand, Joseph A. Sparano, Ethel Cesarman, Jeannette Y. Lee, Amy Chadburn, Adam A. Capoferri, Richard F. Ambinder

المصدر: Blood. 134:1588-1588

مصطلحات موضوعية: 0301 basic medicine, Oncology, medicine.medical_specialty, Immunology, Population, Biochemistry, 03 medical and health sciences, 0302 clinical medicine, International Prognostic Index, Internal medicine, medicine, Clinical endpoint, EPOCH (chemotherapy), education, education.field_of_study, business.industry, Cell Biology, Hematology, medicine.disease, Chemotherapy regimen, 030104 developmental biology, business, Diffuse large B-cell lymphoma, Febrile neutropenia, Plasmablastic lymphoma, 030215 immunology

الوصف: Introduction: EPOCH-based chemotherapy is considered a preferred first-line treatment for HIV-associated diffuse large B-cell lymphoma (DLBCL) and primary effusion lymphoma in the 2019 NCCN guidelines. We previously reported that adding the HDAC inhibitor vorinostat (VOR) to EPOCH had no impact on complete response (CR) rate, the primary trial endpoint, and similar 1-year survival rates (ASCO 2018, abstract 7573). Here, we report updated results from AMC075 and evaluate the impact of a DTI ≥15 days on clinical outcomes. A DTI ≥15 days has been shown to be associated with a better prognosis in an HIV-negative population treated with R-CHOP (Maurer et al. J Clin Oncol 2018; 36:1603-1610). We also look at the impact of allowing 1 cycle of systemic therapy given prior to study enrollment in order to circumvent logistical challenges in recruiting otherwise eligible trial subjects. Methods: Between 2012 and 2017 we conducted a randomized phase II study of EPOCH (with rituximab in CD20+ tumors) ± VOR 300 mg administered on days 1-5 of each cycle with HIV antiretroviral therapy in 90 participants with aggressive HIV-NHLs. Eligible patients had at least one of the following high-risk features or tumor characteristics: Age-adjusted International Prognostic Index (aa-IPI) of 2-3, Ki-67 ≥ 80%; activated B-cell (ABC) diffuse large B-cell lymphoma(DLBCL); or any other aggressive non-germinal center (non-GCB), non-Burkitt B-cell NHL. Patients who received 1 prior cycle of chemotherapy (CHOP-like or EPOCH) +/- rituximab were allowed to register. The primary endpoint was CR rate. Secondary objectives included determining adverse events, survival rates, and the effect of EPOCH +/- VOR on HIV viral reservoirs. We performed a post-hoc analysis evaluating the impact of time from DTI ≥15 days vs. Results: Of 86 evaluable patients, 64 had DLBCL (34 GCB-type and 27 ABC-type), 15 plasmablastic lymphoma (PBL), and 7 primary effusion lymphoma (PEL) [Table 1]. Fifty-one (59%) patients were treatment naïve, whereas 35 (41%) had been pre-treated with one cycle of CHOP-like or EPOCH prior to enrollment. Grade 4 neutropenia was more frequent for VOR-EPOCH than for EPOCH (47% vs. 20%), and also grade 4 thrombocytopenia more frequent for VOR-EPOCH (29% vs 2%). The two regimens had similar rates of febrile neutropenia (18% vs. 16%). CR rates were also comparable for the two regimens (68% vs. 74%) [1-sided P=0.72] (Table 1). Median HIV plasma RNA generally decreased in both arms. No significant differences were observed in T-cell subsets or size of the latent HIV reservoir between arms. Treatment outcomes did not differ significantly across NHL subtypes or EBV status (Table 1), nor with pre-protocol systemic therapy (Table 2). Overall CR rates were 45% in patients with CD4+ counts of 50-100 cells/mm3, 63% with 100-199 cells/mm3, and 85% in patients with >200 cells/mm3(Table 1). The 3-year overall survival rates for VOR-EPOCH was 70% and for EPOCH 77% (log-rank P=0.39), and 3-year event-free survival rates were 63% vs. 69%, respectively (log-rank P=0.32) [Figure 1]. Thirty-six patients (86% of n=42) with long DTI (≥15 days) had CR, compared to only 25 (57% of n=44) with short ( Conclusion: This prospective trial demonstrated that EPOCH-based chemotherapy was broadly efficacious against aggressive HIV-NHLs, including high risk subtypes (ABC DLBCL, PBL, and PEL). However, a 5-day course of VOR given with each chemotherapy cycle failed to improve outcomes. Consistent with prior reports in HIV-uninfected patients with DLBCL, a DTI of ≥15 days was associated with better clinical outcomes than a shorter DTI. A strategy of permitting pre-protocol therapy was useful in facilitating accrual and was used in about 40% of study participants without compromising clinical outcomes. Disclosures Baiocchi: Prelude: Consultancy. Noy:Janssen: Consultancy; Medscape: Honoraria; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. OffLabel Disclosure: Vorinostat is being tested in combination with chemotherapy for HIV-associated B-cell lymphoma

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::8bd22290649451647b993469702e48e8Test
https://doi.org/10.1182/blood-2019-129687Test

المؤلفون: Pierre Delobel, Herve Ghesquieres, François Boué, Elad Sharon, Amy Chadburn, Lionel Galicier, Nicolas Mounier, Milan Bimali, Erin Reid, Paul Coppo, Page C. Moore, Richard F. Ambinder, Paul G. Rubinstein, David H. Henry, Stefan K. Barta, Ethel Cesarman, Lee Ratner, Caroline Besson, Ariela Noy, Michelle A. Rudek, Juan Carlos Ramos

المصدر: Blood. 134:130-130

مصطلحات موضوعية: Oncology, medicine.medical_specialty, Chlorambucil, business.industry, Dacarbazine, Immunology, Phases of clinical research, Cell Biology, Hematology, Neutropenia, Bleomycin, medicine.disease, Biochemistry, Vinblastine, chemistry.chemical_compound, chemistry, Internal medicine, Medicine, Ritonavir, business, Brentuximab vedotin, medicine.drug

الوصف: Introduction: Patients (pts) with HIV have a 6-fold increased risk of developing classic Hodgkin lymphoma (cHL) over the general population. The outcome of frontline therapy for HIV-associated cHL (HIV-cHL) using doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) is similar to the non-HIV population. However, pts with advanced stage cHL continue to have a 30% chance of refractory/relapsed disease with ABVD. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate that selectively induces apoptosis of CD30+ cells. The FDA approved BV with AVD (BV-AVD) after the Echelon-1 (E1) study for advanced stage disease demonstrated improved modified progression free survival (mPFS) at 2 years compared with standard ABVD: 82% vs. 77%. Pts with HIV were excluded from both relapsed/refractory and frontline BV trials. Here we present the final results of the phase 2 trial of BV-AVD in previously untreated HIV-associated cHL, an AIDS Malignancy Consortium/LYSA collaboration (ClinicalTrials.gov ID: NCT01771107). Methods: Forty-one pts were treated on days 1 and 15 of 6, 28 day cycles, with 1.2mgs/kg of BV in combination with doxorubicin 25 mg/m2, vinblastine 6 mg/m2, and dacarbazine 375 mg/m2 (AVD). Eligibility criteria included untreated cHL stage II-IV, CD4 + T-cell counts ≥50 cells/mm3, and initiation of combined antiretroviral therapy (cART) at least 1 week prior to therapy. Ritonavir, zidovidine, cobisistat, and other strong CYP3A4 or P-glycoprotein inhibitors were excluded with a washout of at least 1 week being required. Hematopoietic growth factor was mandated. The primary objective was 2 year PFS. The sample size was based on providing an estimate of the PFS with a 95% CI +/- 10% under the assumption of a 2 year progression free survival (PFS) estimate of 85%. Secondary objectives included toxicity, effects on CD4/CD8 + T-cells, HIV-1 viral load, prognostic significance of post C2 and end of treatment PET-CT. Results: Forty-one pts (93% men) were treated with a median age of 48y (range 24-67). Pts presented with stage II (17%), III (27%), and IV (56%) disease. Two year PFS estimate in the overall population (N=41) was 86% (95% CI: .74, .98). The 2-year overall survival (OS) estimate was 92% (95% CI: 0.83, 1.0) with 3 deaths at the time of analysis, including 1 which was a treatment related death (Figure 1A). For pts with advanced disease (N=34), the 2-year PFS estimate was 87% (95% CI: 0.76, 0.99) with an OS estimate of 90% (95% CI: 0.8, 1.00) (Figure 1B). Safety profiles were quite similar to the BV-AVD arm in the E1 study of the pts who received growth factor. Neuropathy was higher in our study compared to E1, (49% vs. 29% for any grade, P=0.01; 9.8% vs. 5% for G3/4, p=0.06). G3 Neutropenia was greater in AMC 085 compared to E1 BV-AVD arm with growth factor: 57% vs. 29% (p Conclusions: BV-AVD in stage II-IV HIV-cHL was efficacious although neutropenia and neuropathy were increased compared to the non-HIV population. The 2-year PFS estimate was 86% for the entire cohort and 87% for advanced stage HIV-cHL. Major interactions with strong CYP3A4 inhibitors lead to toxicity and must be avoided. The etiology of the CD4 increase is under investigation and may have implications for future therapy. Disclosures Rudek: Cullinan Apollo: Research Funding; Taiho: Research Funding; RenovoRX: Research Funding; Celgene: Research Funding. Barta:Mundipharma: Honoraria; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Seattle Genetics: Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Mundipharma: Honoraria; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Noy:Medscape: Honoraria; Janssen: Consultancy; Prime Oncology: Honoraria; NIH: Research Funding; Pharamcyclics: Research Funding; Raphael Pharma: Research Funding. OffLabel Disclosure: Brentuximab Vedotin has been approved for the upfront treatment of advanced stage cHL in combination with AVD though not specifically approved for use in patients infected with HIV or stage 2 cHL.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e2b033a645174320da27439e405febf9Test
https://doi.org/10.1182/blood-2019-126787Test

المؤلفون: Ethel Cesarman

المصدر: Current Opinion in Oncology. 25:487-494

مصطلحات موضوعية: Cancer Research, Pathology, medicine.medical_specialty, business.industry, Incidence (epidemiology), Human immunodeficiency virus (HIV), Cancer, HIV Infections, Disease, medicine.disease, medicine.disease_cause, Antiretroviral therapy, Article, Lymphoma, Molecular Diagnostic Techniques, Oncology, Acquired immunodeficiency syndrome (AIDS), Biomarkers, Tumor, medicine, Humans, business, Pathological, Lymphoma, AIDS-Related

الوصف: Purpose of review HIV-infected individuals have a greatly increased risk of developing malignancies, even when HIV infection is successfully controlled with antiretrovirals. Non-Hodgkin's lymphoma is considered an AIDS-defining entity, and this disease is currently the most common type of cancer in HIV-infected individuals in the USA and Europe. Here, we describe the different types of lymphomas occurring in individuals with AIDS, and the most relevant pathologic features helpful for histologic and immunohistochemical diagnosis. Recent findings The incidence of some AIDS-related lymphoma subtypes has changed since the introduction of combined antiretroviral therapy, and some of the diagnostic methodologies have evolved. New biomarkers of disease have been identified, which may be useful for diagnosis. Summary Better pathological classification strategies and deeper molecular understanding of the different lymphoma subtypes that occur in people with AIDS will begin to allow the transition to more precise diagnosis and targeted treatments.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::34fa788fdbfc1d68024457fa7373309bTest
https://doi.org/10.1097/01.cco.0000432525.70099.a4Test

المؤلفون: Cheng Fu, Ryan Snodgrass, Andrea Gardner, Li Jiang, Ethel Cesarman, David Erickson

المصدر: PLoS ONE
PLoS ONE, Vol 11, Iss 1, p e0147636 (2016)

مصطلحات موضوعية: Pathology, Skin Neoplasms, Biopsy, Microfluidics, lcsh:Medicine, Artificial Gene Amplification and Extension, 02 engineering and technology, Polymerase Chain Reaction, law.invention, Kaposi Sarcoma, 0302 clinical medicine, law, Medicine and Health Sciences, lcsh:Science, Polymerase chain reaction, Skin, Gel Electrophoresis, Multidisciplinary, medicine.diagnostic_test, Sarcomas, Microfluidic Analytical Techniques, 021001 nanoscience & nanotechnology, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Herpesvirus 8, Human, Engineering and Technology, Sarcoma, Fluidics, Anatomy, 0210 nano-technology, Healthcare system, Research Article, Medical diagnostic, medicine.medical_specialty, Histology, Imaging Techniques, Equipment, Surgical and Invasive Medical Procedures, Biology, Research and Analysis Methods, Sensitivity and Specificity, Cell Line, 03 medical and health sciences, Electrophoretic Techniques, Fluorescence Imaging, medicine, Solar Energy, Humans, Molecular Biology Techniques, Device parameters, Kaposi's sarcoma, Sarcoma, Kaposi, Molecular Biology, Communication Equipment, lcsh:R, Reproducibility of Results, Biology and Life Sciences, Cancers and Neoplasms, medicine.disease, Virology, Energy infrastructure, lcsh:Q, Cell Phones

الوصف: Resource-limited settings present unique engineering challenges for medical diagnostics. Diagnosis is often needed for those unable to reach central healthcare systems, making portability and independence from traditional energy infrastructure essential device parameters. In 2014, our group presented a microfluidic device that performed a solar-powered variant of the polymerase chain reaction, which we called solar thermal PCR. In this work, we expand on our previous effort by presenting an integrated, portable, solar thermal PCR system targeted towards the diagnosis of Kaposi's sarcoma. We call this system KS-Detect, and we now report the system's performance as a diagnostic tool using pseudo-biopsy samples made from varying concentrations of human lymphoma cell lines positive for the KS herpesvirus (KSHV). KS-Detect achieved 83% sensitivity and 70% specificity at high (≥ 10%) KSHV+ cell concentrations when diagnosing pseudo-biopsy samples by smartphone image. Using histology, we confirm that our prepared pseudo-biopsies contain similar KSHV+ cell concentrations as human biopsies positive for KS. Through our testing of samples derived from human cell lines, we validate KS-Detect as a viable, portable KS diagnostic tool, and we identify critical engineering considerations for future solar-thermal PCR devices.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2e4194f8b552b2150ea7d5701f64e6c4Test
https://pubmed.ncbi.nlm.nih.gov/26799834Test