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Epstein-Peterson ZD, Gurumurthi A, Horwitz SM. New treatments for adult T-cell leukemia/lymphoma. Leuk Res 2025; 149:107642. [PMID: 39847921 DOI: 10.1016/j.leukres.2025.107642] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/12/2024] [Revised: 12/18/2024] [Accepted: 01/02/2025] [Indexed: 01/25/2025]
Abstract
Adult T cell leukemia lymphoma (ATL) is a mature T cell neoplasm caused by human T-cell lymphotropic virus type 1 (HTLV-1). ATL is endemic in specific geographic regions of the world closely related to areas with high prevalence of HLTV-1 infection, including Southwestern Japan, the Caribbean Basin, Central Africa, South America, Northern and Central Australia. HLTV-1 is primarily transmitted through breastmilk in asymptomatic carriers with a long latency period before transformation into ATL in 3 - 5 % of carriers after acquisition of multiple leukemogenic mutations. The Shimoyama classification established by the Japanese Lymphoma Study Group more than three decades ago remains clinically relevant and practical for guiding treatment. Due to the rarity of this illness, prospective, large prospective clinical are challenging to perform and treatment recommendations are based upon limited evidence. Aggressive disease subtypes have median survival ranging in months and the only curative therapy remains achieving deep remission with induction therapy followed by consolidative allogeneic transplantation. The prognosis for relapsed disease remains dismal due to chemo-refractoriness and limited therapeutic options. Herein, we review the current landscape of novel therapeutic agents with a focus on relapsed and refractory ATL including their mechanisms of action, resistance, and clinical efficacy.
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Affiliation(s)
- Zachary D Epstein-Peterson
- Lymphoma Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St., New York, NY 10021, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA
| | - Ashwath Gurumurthi
- Lymphoma Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St., New York, NY 10021, USA
| | - Steven M Horwitz
- Lymphoma Service, Division of Hematologic Malignancies, Department of Medicine, Memorial Sloan Kettering Cancer Center, 530 E 74th St., New York, NY 10021, USA; Department of Medicine, Weill Cornell Medical College, 1300 York Ave, New York, NY 10065, USA.
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Straining R, Foss F, Schiffer M, Amin K, Agarwal S, Isufi I, Huntington S, Kothari S, Seropian S, Girardi M, Sethi T. Real World Data on Efficacy and Safety of EPOCH in T-Cell Lymphoma. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2025; 25:e96-e102. [PMID: 39368885 DOI: 10.1016/j.clml.2024.09.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/26/2024] [Revised: 08/31/2024] [Accepted: 09/06/2024] [Indexed: 10/07/2024]
Abstract
BACKGROUND T-cell lymphomas are a heterogeneous group of lymphoid malignancies with poor outcomes. Frontline multiagent chemotherapy options include CHOP (prednisone, vincristine, cyclophosphamide, and doxorubicin), brentuximab-CHP, CHOEP, and EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin). PATIENTS AND METHODS We report our single institution data for safety and efficacy of EPOCH in 38 patients with aggressive T-cell lymphoma including both peripheral T cell lymphoma (PTCL) and cutaneous T-cell lymphoma (CTCL). RESULTS Eighteen patients received EPOCH as first-line and 21 in the relapsed/refractory (R/R) setting. In 36 evaluable patients, the overall response rate (ORR) was 77% (95% CI, 61%-89%) with 19 (53%) patients achieving complete response (CR) (95% CI, 36%-69%). The ORR in first line and R/R settings were 80% (95% CI, 46%-94%) and 75% (95% CI, 52%-90%), respectively. Response rate was similar in African American versus Caucasian patients but was higher in CD30 negative versus positive patients. Most common grade 3/4 adverse events included cytopenias. CONCLUSIONS Overall, EPOCH was well tolerated with high response rates in first line and R/R setting.
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Affiliation(s)
| | - Francine Foss
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT.
| | - Molly Schiffer
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT
| | - Kejal Amin
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT
| | - Sonal Agarwal
- Department of Pharmacy, Yale New Haven Hospital, New Haven, CT
| | - Iris Isufi
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT
| | - Scott Huntington
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT
| | - Shalin Kothari
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT
| | - Stuart Seropian
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT
| | - Michael Girardi
- Department of Dermatology, Yale University School of Medicine, New Haven, CT
| | - Tarsheen Sethi
- Department of Internal Medicine, Section of Hematology, Yale University School of Medicine, New Haven, CT
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Braunstein Z, Brammer JE. Maintenance Therapy Post-Stem Cell Transplantation for Patients with T-Cell Lymphomas. Curr Hematol Malig Rep 2024; 19:276-284. [PMID: 39425756 PMCID: PMC11568030 DOI: 10.1007/s11899-024-00743-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/19/2024] [Indexed: 10/21/2024]
Abstract
PURPOSE OF REVIEW Given the poor outcomes for peripheral T-cell lymphomas (PTCL), stem cell transplant (SCT) remains an important therapeutic approach. Post-SCT relapse is common and maintenance therapy post-SCT is increasingly being utilized. Here we review the use of post-SCT maintenance therapy for PTCL patients. RECENT FINDINGS Maintenance therapy is increasingly utilized to decrease post-SCT relapse and improve outcomes in PTCL. Ongoing and completed post-SCT maintenance trials utilizing agents such as romidepsin, brentuximab vedotin, duvelisib, and pembrolizumab have shown efficacy in decreasing relapse. Further, additional agents with efficacy in PTCL have emerged that may inform future maintenance approaches. Maintenance therapy is a promising approach to maintain response after SCT in PTCL. While several trials are ongoing to evaluate maintenance therapy in PTCL, current data suggests this may be an effective method to decrease post-SCT relapse.
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Affiliation(s)
- Zachary Braunstein
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, 2121 Kenny Road, Room 7168, Columbus, OH, 43210, USA
| | - Jonathan E Brammer
- Division of Hematology, Department of Internal Medicine, James Comprehensive Cancer Center, The Ohio State University Wexner Medical Center, 2121 Kenny Road, Room 7168, Columbus, OH, 43210, USA.
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O'Connor OA, Ma H, Chan JYS, Kim SJ, Yoon SE, Kim WS. Peripheral T-cell lymphoma: From biology to practice to the future. Cancer Treat Rev 2024; 129:102793. [PMID: 39002211 DOI: 10.1016/j.ctrv.2024.102793] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2024] [Revised: 06/23/2024] [Accepted: 06/24/2024] [Indexed: 07/15/2024]
Abstract
Recent advancements in comprehending peripheral T-cell lymphomas (PTCLs) validate and broaden our perspective, highlighting their diverse nature and the varying molecular mechanisms underlying the entities. Based on a comprehensive accumulated understanding, the PTCLs currently overcome the most challenging features of any disease: rarity, incredible heterogeneity, and a lack of any established standard of care. The treatments deployed in the front-line are extrapolated from regimens developed for other diseases. The recent approval of the three drugs brentuximab vedotin (BV), pralatrexate, and belinostat for patients with relapsed or refractory disease has provided clues about pathophysiology and future directions, though challenges satisfying post-marketing requirements (PMR) for those accelerated approvals have led to one of those drugs being withdrawn and put the other two in jeopardy. Edits of the front-line regimens, often called CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-plus approaches, look more like CHOP-minus strategies, as the toxicity of five-drug regimens often reduces the dose intensity of the added 'novel' drug, nullifying any hope of an advance. The turmoil in the field produced by the aforementioned, coupled with an ever-changing classification, has left the field uncertain about the path forward. Despite these challenges, empiric findings from studies of novel drug approaches, coupled with a logic emerging from studies of PTCL lymphomagenesis, have begun to illuminate, albeit faintly for some, a potential direction. The empiric finding that drugs targeting the discrete components of the PTCL epigenome, coupled with the description of multiple mutations in genes that govern epigenetic biology, offers, at the very least, an opportunity to finally be hypothesis-driven. The most recent recognition that the only combination of drugs shown to markedly improve progression-free survival (PFS) in patients with relapsed disease is one based on dual targeting of different and discrete components of that epigenetic biology has established a possibility that circumnavigating chemotherapy addition studies is both plausible, feasible, and likely the best prospect for a quantum advance in this disease. Herein, we analyze PTCL through a 2025 lens, highlighting and underscoring walls that have impeded progress. We will critically explore all the clues and the panoramic view of PTCL research.
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Affiliation(s)
- Owen A O'Connor
- University of Virginia Comprehensive Cancer Center, Charlottesville, VA, United States
| | - Helen Ma
- VA Long Beach Healthcare System, Long Beach, CA, United States; University of California-Irvine, Orange, CA, United States
| | | | - Seok Jin Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Sang Eun Yoon
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Won Seog Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
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Zhang YS, Kong DT, Zhang M, Liu XY. Monomorphic epitropic intestinal T-cell lymphoma presenting with intestinal perforation. Asian J Surg 2024; 47:2494-2495. [PMID: 38296683 DOI: 10.1016/j.asjsur.2024.01.091] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2023] [Accepted: 01/19/2024] [Indexed: 02/02/2024] Open
Affiliation(s)
- Yong-Sheng Zhang
- Department of Gastroenterology, Sishui People's Hospital, Jining, Shandong Province, China
| | - De-Tong Kong
- Department of General Surgery, Sishui People's Hospital, Jining, Shandong Province, China
| | - Min Zhang
- Department of Painless Endoscopy, Sishui People's Hospital, Jining, Shandong Province, China
| | - Xiang-Yu Liu
- Department of Gastroenterology, Jining No. 1 People's Hospital, Jining, 272000, Shandong Province, China.
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Galligan D, Williamson S, Myers J, Chen AI, Hayes-Lattin B, Okada C, Spurgeon S, Maziarz R, Schachter L. Long-term Outcomes After Hematopoietic Cell Transplant in Peripheral T-Cell Lymphoma - The Oregon Health and Science University Experience. CLINICAL LYMPHOMA, MYELOMA & LEUKEMIA 2023; 23:874-881. [PMID: 37741763 DOI: 10.1016/j.clml.2023.08.010] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/04/2023] [Revised: 08/04/2023] [Accepted: 08/11/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Peripheral T-cell lymphomas (PTCL) are a group of aggressive malignancies with inferior outcomes compared to B-cell non-Hodgkin lymphoma (NHL). Both allogeneic and autologous hematopoietic cell transplantation (HCT) are commonly employed for consolidation and salvage. MATERIALS AND METHODS We conducted a single-center review of all adult PTCL patients at OHSU who received HCT from 1991 to 2020 with responses assed by CIBMTR criteria. RESULTS 88 patients (autoHCT = 52, alloHCT = 36) were identified from the internal registry of ∼3800 autoHCT & alloHCT recipients in that time period. Median OS after autoHCT and alloHCT were 7.0 and 2.6 years. Median PFS after autoHCT and alloHCT was 3.9 vs 1.1 years. Post-HCT median OS for ALCL, AITL, and PTCL NOS were 14.9, 3.9, and 3.4 years, respectively. Median PFS after autoHCT performed while in CR vs. not in CR was 3.4 vs 4.2 years (P = 0.86); for alloHCT in CR vs. not CR 2.4 vs 0.7 years (P = 0.28). 1-year non-relapse mortality (NRM) for autoHCT and alloHCT were 6.1% and 22.2% (P = 0.2). 10/88 patients developed secondary malignancies including 4 skin cancers, 3 new lymphomas, and 2 MDS. CONCLUSION Our experience with HCT for PTCL shows that HCT has acceptable toxicities and relatively long disease remissions. AutoHCT was most frequently utilized as planned remission consolidation while alloHCT was most often used late during salvage. Differences in response between autoHCT and alloHCT likely reflect differences in clinical setting and underlying disease natural history and biology.
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Affiliation(s)
| | | | - Jessie Myers
- Oregon Health and Science University, Portland, OR
| | - Andy I Chen
- Oregon Health and Science University, Portland, OR
| | | | - Craig Okada
- Oregon Health and Science University, Portland, OR
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Shen CQ, He GQ, Wan Z, Lin C, Yang X, Lu XX, Zhu YP, Gao J, Guo X. "Sandwich" protocol based on modified SMILE regimen for children with newly extranodal NK/T cell lymphoma, nasal type: a single-arm, single-center clinical study. Ann Hematol 2023; 102:3143-3152. [PMID: 37486391 PMCID: PMC10567983 DOI: 10.1007/s00277-023-05375-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 07/14/2023] [Indexed: 07/25/2023]
Abstract
Extranodal NK/T-cell lymphoma, nasal type (ENKTL), which is a rare form of mature T/NK cell lymphoma in children, currently lacks a standardized first-line treatment approach. However, a treatment protocol known as the "sandwich" regimen has been used in children newly diagnosed with ENKTL. This protocol combines the administration of methotrexate, ifosfamide, etoposide, pegaspargase, and dexamethasone (referred to as SMILE) with the addition of radiotherapy (RT). From September 2017 to December 2020, a total of five patients were included in the study, consisting of three males and two females. The median age of onset was 10.6 years (range, 9.8 to 14.0 years). Among the patients, four had nasal/nasopharyngeal disease at stage II, while one patient had extra nasal disease involving the skin at stage IV. The median EBV-DNA level in plasma was 1.68 × 103 copies/ml (range, 0.44 to 21.1 × 103copies/ml). All the patients had good overall response after 2 cycles of chemotherapy and radiotherapy, including 4 of the patients who had a complete response and 1 of the patients with partial remission. The patient with stage IV received allogeneic hematopoietic stem cell transplantation after the EBV-DNA level was elevated again during treatment. One patient in the low-risk group experienced grade 4 oral mucositis, while no other severe complications or treatment-related deaths were observed. The median follow-up period was 22 months (range, 5 to 57 months). All five patients successfully completed their treatment, with four patients achieving event-free survival, and one patient was lost to follow-up. The median OS time and EFS time was 33 months (range: 18-57 months) and 20 months (range: 5-47 months), respectively. The sandwich protocol has demonstrated a high response rate, good tolerance to chemotherapy, and no treatment-related fatalities. However, further confirmation is necessary through additional clinical studies involving larger sample sizes. Clinical trial registration number: Due to modified SMILE regimens with sandwiched radiotherapy yielded promising outcomes in children ENKTL, we have carried out a phase II multicenter clinical trial (ChiCTR220005954) for children ENKTL in China to further verify the efficacy and safety.
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Affiliation(s)
- Cheng-Qi Shen
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Guo-Qian He
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Zhi Wan
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Chao Lin
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Xue Yang
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Xiao-Xi Lu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
- NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, 610041, China
| | - Yi-Ping Zhu
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China
| | - Ju Gao
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China.
- NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, 610041, China.
| | - Xia Guo
- Department of Pediatrics, West China Second University Hospital, Sichuan University, Section 3, South Renmin Road, Chengdu, 610041, China.
- NHC Key Laboratory of Chronobiology, Sichuan University, Chengdu, 610041, China.
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8
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Lucero OM, Lee JA, Bowman J, Johnson K, Sapparapu G, Thomas JK, Fan G, Chang BH, Thiel-Klare K, Eide CA, Okada C, Palazzolo M, Lind E, Kosaka Y, Druker BJ, Lydon N, Bowers PM. Patient-Specific Targeting of the T-Cell Receptor Variable Region as a Therapeutic Strategy in Clonal T-Cell Diseases. Clin Cancer Res 2023; 29:4230-4241. [PMID: 37199721 PMCID: PMC10592575 DOI: 10.1158/1078-0432.ccr-22-0906] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Revised: 01/31/2023] [Accepted: 05/16/2023] [Indexed: 05/19/2023]
Abstract
PURPOSE Targeted therapeutics are a goal of medicine. Methods for targeting T-cell lymphoma lack specificity for the malignant cell, leading to elimination of healthy cells. The T-cell receptor (TCR) is designed for antigen recognition. T-cell malignancies expand from a single clone that expresses one of 48 TCR variable beta (Vβ) genes, providing a distinct therapeutic target. We hypothesized that a mAb that is exclusive to a specific Vβ would eliminate the malignant clone while having minimal effects on healthy T cells. EXPERIMENTAL DESIGN We identified a patient with large granular T-cell leukemia and sequenced his circulating T-cell population, 95% of which expressed Vβ13.3. We developed a panel of anti-Vβ13.3 antibodies to test for binding and elimination of the malignant T-cell clone. RESULTS Therapeutic antibody candidates bound the malignant clone with high affinity. Antibodies killed engineered cell lines expressing the patient TCR Vβ13.3 by antibody-dependent cellular cytotoxicity and TCR-mediated activation-induced cell death, and exhibited specific killing of patient malignant T cells in combination with exogenous natural killer cells. EL4 cells expressing the patient's TCR Vβ13.3 were also killed by antibody administration in an in vivo murine model. CONCLUSIONS This approach serves as an outline for development of therapeutics that can treat clonal T-cell-based malignancies and potentially other T-cell-mediated diseases. See related commentary by Varma and Diefenbach, p. 4024.
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Affiliation(s)
- Olivia M Lucero
- Department of Dermatology, Oregon Health & Science University, Portland, Oregon
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
| | - Ji-Ann Lee
- Clinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Jenna Bowman
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon
| | - Kara Johnson
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon
| | - Gopal Sapparapu
- Clinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California
| | - John K Thomas
- Clinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Guang Fan
- Department of Pathology and Clinical Laboratory Medicine, Oregon Health & Science University, Portland, Oregon
| | - Bill H Chang
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Pediatric Hematology and Oncology, Oregon Health & Science University, Portland, Oregon
| | - Karina Thiel-Klare
- Division of Pediatric Hematology and Oncology, Oregon Health & Science University, Portland, Oregon
| | - Christopher A Eide
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon
| | - Craig Okada
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon
| | - Mike Palazzolo
- Clinical and Translational Science Institute, David Geffen School of Medicine, University of California, Los Angeles, California
| | - Evan Lind
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Department of Molecular Microbiology and Immunology, Oregon Health & Science University, Portland, Oregon
- Department of Cell, Developmental, and Cancer Biology, Oregon Health & Science University, Portland, Oregon
| | - Yoko Kosaka
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Pediatric Hematology and Oncology, Oregon Health & Science University, Portland, Oregon
| | - Brian J Druker
- Knight Cancer Institute, Oregon Health & Science University, Portland, Oregon
- Division of Hematology and Medical Oncology, Oregon Health & Science University, Portland, Oregon
- VB Therapeutics LLC, Jackson, Wyoming
| | | | - Peter M Bowers
- Therapeutic Antibody Laboratory, Department of Pulmonology and Critical Care, David Geffen School of Medicine, Los Angeles, California
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Abreu Rocha C, Drummond Borges M, Santos GM, Sousa M, Teixeira T. Itchy Skin: A Challenging Differential Diagnosis Between Mycosis Fungoides and Sézary Syndrome. Cureus 2023; 15:e46427. [PMID: 37927614 PMCID: PMC10621883 DOI: 10.7759/cureus.46427] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/02/2023] [Indexed: 11/07/2023] Open
Abstract
Primary cutaneous lymphomas represent a diverse spectrum of T-cell and B-cell lymphomas with their primary skin manifestation. Among these, mycosis fungoides (MF) and Sézary syndrome (SS) represent classic forms of cutaneous T-cell lymphomas (CTCLs). This report details the case of a 67-year-old female who presented with longstanding pruritic skin lesions, initially misdiagnosed and managed as eczema. The diagnostic process ultimately revealed the presence of Sézary cells in the peripheral blood smear (PBS). The SS diagnosis was confirmed based on CD4 positivity and CD7 negativity as determined by flow cytometry. The disease was staged as IVA1 (T2N0M1B2). The patient exhibited partial improvement with oral corticosteroid therapy. This report underscores the critical importance of integrating clinical evaluation and blood findings to distinguish between MF and SS. The progression of a circulating clone signals a poor prognosis, requiring surveillance and consideration of targeted therapies to enhance patient outcomes and improve their quality of life. Early detection remains paramount in the management of these rare cutaneous lymphomas, which are associated with unique therapeutic challenges.
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Affiliation(s)
- Cláudia Abreu Rocha
- Family Medicine, Centro de Saúde de Machico, Serviço de Saúde da Região Autónoma da Madeira (SESARAM), Madeira Island, PRT
| | - Margarida Drummond Borges
- Family Medicine, Centro de Saúde de Machico, Serviço de Saúde da Região Autónoma da Madeira (SESARAM), Madeira Island, PRT
| | - Guida Maria Santos
- Family Medicine, Centro de Saúde do Caniço, Serviço de Saúde da Região Autónoma da Madeira (SESARAM), Madeira Island, PRT
| | - Miriam Sousa
- Pathology, Hospital Central do Funchal, Madeira Island, PRT
| | - Tânia Teixeira
- Family Medicine, Centro de Saúde de Machico, Serviço de Saúde da Região Autónoma da Madeira (SESARAM), Madeira Island, PRT
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10
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Kim SJ, Jo JC, Yoon DH, Yang DH, Yoon SE, Lee GW, Kong JH, Park Y, Kang KW, Lee HS, Oh SY, Shin HJ, Lee WS, Choi YS, Jeong SH, Kim MK, Kang HJ, Yi JH, Lim SN, Yhim HY, Do YR, Yun HJ, Eom HS, Lee MH, Suh C, Kim WS. Comparison of first-line treatment with CHOP versus ICED in patients with peripheral T-cell lymphoma eligible for upfront autologous stem cell transplantation. Front Oncol 2023; 13:1230629. [PMID: 37675232 PMCID: PMC10477982 DOI: 10.3389/fonc.2023.1230629] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Accepted: 07/31/2023] [Indexed: 09/08/2023] Open
Abstract
Introduction Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL. Methods We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles. Results Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS. Discussion In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL.
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Affiliation(s)
- Seok Jin Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Jae-Cheol Jo
- Department of Hematology and Oncology, Ulsan University Hospital, University of Ulsan College of Medicine, Ulsan, Republic of Korea
| | - Dok Hyun Yoon
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Deok-Hwan Yang
- Department of Internal Medicine, Chonnam National University Hwasun Hospital, Chonnam National University Medical School, Gwangju, Republic of Korea
| | - Sang Eun Yoon
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
| | - Gyeong-Won Lee
- Division of Hematology and Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Changwon, Republic of Korea
| | - Jee Hyun Kong
- Department of Hematology-oncology, Division of Internal Medicine, Wonju Severance Christian Hospital, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea
- Cancer of Evidence Based Medicine, Institute of Convergence Science, Yonsei University, Seoul, Republic of Korea
| | - Yong Park
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Ka-Won Kang
- Department of Internal Medicine, Korea University College of Medicine, Korea University Anam Hospital, Seoul, Republic of Korea
| | - Ho-Sup Lee
- Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Republic of Korea
| | - Sung Yong Oh
- Department of Internal Medicine, Dong-A University Medical Center, Busan, Republic of Korea
| | - Ho-Jin Shin
- Department of Internal Medicine, Pusan National University Hospital, Busan, Republic of Korea
| | - Won Sik Lee
- Department of Internal Medicine, Inje University Busan Paik Hospital, Busan, Republic of Korea
| | - Yoon Seok Choi
- Division of Hematology-Oncology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Seong Hyun Jeong
- Division of Hematology-Oncology, Department of Internal Medicine, Ajou University School of Medicine, Suwon, Republic of Korea
| | - Min Kyoung Kim
- Department of Internal Medicine, Yeungnam University College of Medicine, Daegu, Republic of Korea
| | - Hye Jin Kang
- Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Republic of Korea
| | - Jun Ho Yi
- Department Internal Medicine, Chung-Ang University Hospital, Seoul, Republic of Korea
| | - Sung-Nam Lim
- Department of Internal Medicine, Haeundae Baek Hospital, Busan, Republic of Korea
| | - Ho-Young Yhim
- Department of Internal Medicine, Jeonbuk National University Medical School, Research Institute of Clinical Medicine of Jeonbuk National University-Biomedical Research Institute of Jeonbuk National University Hospital, Jeonju, Republic of Korea
| | - Young Rok Do
- Department of Internal Medicine, Dongsan Medical Center, Daegu, Republic of Korea
| | - Hwan Jung Yun
- Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Republic of Korea
| | - Hyeon-Seok Eom
- Hematology-Oncology Clinic, National Cancer Center, Go-Yang, Republic of Korea
| | - Mark Hong Lee
- Division of Hematology-Oncology, Department of Internal Medicine, Konkuk University Medical Center, Seoul, Republic of Korea
| | - Cheolwon Suh
- Department of Oncology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Won Seog Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
- Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea
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11
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Subramanian K, Martinez J, Castellanos SH, Ivanidze J, Nagar H, Nicholson S, Youn T, Nauseef JT, Tagawa S, Osborne JR. Complex implementation factors demonstrated when evaluating cost-effectiveness and monitoring racial disparities associated with [ 18F]DCFPyL PET/CT in prostate cancer men. Sci Rep 2023; 13:8321. [PMID: 37221397 DOI: 10.1038/s41598-023-35567-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/10/2022] [Accepted: 05/20/2023] [Indexed: 05/25/2023] Open
Abstract
Prostate cancer (PC) staging with conventional imaging often includes multiparametric magnetic resonance (MR) of the prostate, computed tomography (CT) of the chest, abdomen, and pelvis, and whole-body bone scintigraphy. The recent development of highly sensitive and specific prostate specific membrane antigen (PSMA) positron emission tomography (PET) has suggested that prior imaging techniques may be insufficiently sensitive or specific, particularly when evaluating small pathologic lesions. As PSMA PET/CT is considered to be superior for multiple clinical indications, it is being deployed as the new multidisciplinary standard-of-care. Given this, we performed a cost-effectiveness analysis of [18F]DCFPyL PSMA PET/CT imaging in the evaluation of PC relative to conventional imaging and anti-3-[18F]FACBC (18F-Fluciclovine) PET/CT. We also conducted a single institution review of PSMA PET/CT scans performed primarily for research indications from January 2018 to October 2021. Our snapshot of this period of time in our catchment demonstrated that PSMA PET/CT imaging was disproportionately accessed by men of European ancestry (EA) and those residing in zip codes associated with a higher median household income. The cost-effectiveness analysis demonstrated that [18F]DCFPyL PET/CT should be considered as an alternative to anti-3-[18F]FACBC PET/CT and standard of care imaging for prostate cancer staging. [18F]DCFPyL PET/CT is a new imaging modality to evaluate PC patients with higher sensitivity and specificity in detecting disease than other prostate specific imaging studies. Despite this, access may be inequitable. This discrepancy will need to be addressed proactively as the distribution network of the radiotracer includes both academic and non-academic sites nationwide.
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Affiliation(s)
- Kritika Subramanian
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA.
| | - Juana Martinez
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Sandra Huicochea Castellanos
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Jana Ivanidze
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Himanshu Nagar
- Department of Radiation Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Sean Nicholson
- Department of Policy Analysis and Management, Sloan, Cornell Institute for Public Affairs, New York, NY, USA
| | - Trisha Youn
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
| | - Jones T Nauseef
- Department of Medical Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Scott Tagawa
- Department of Medical Oncology, Weill Cornell Medicine, New York, NY, USA
| | - Joseph R Osborne
- Division of Molecular Imaging and Therapeutics, Department of Radiology, Weill Cornell Medicine, New York, NY, USA
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12
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Mafra A, Laversanne M, Gospodarowicz M, Klinger P, De Paula Silva N, Piñeros M, Steliarova-Foucher E, Bray F, Znaor A. Global patterns of non-Hodgkin lymphoma in 2020. Int J Cancer 2022; 151:1474-1481. [PMID: 35695282 DOI: 10.1002/ijc.34163] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 04/29/2022] [Accepted: 05/10/2022] [Indexed: 11/11/2022]
Abstract
We evaluated the global patterns of non-Hodgkin lymphoma (NHL) in 2020 using the estimates of NHL incidence and mortality in 185 countries that are part of the GLOBOCAN 2020 database, developed by the International Agency for Research on Cancer (IARC). As well as new cases and deaths of NHL, corresponding age-standardized (world) rates (ASR) of incidence and mortality per 100 000 person-years were derived by country and world region. In 2020, an estimated 544 000 new cases of NHL were diagnosed worldwide, and approximately 260 000 people died from the disease. Eastern Asia accounted for a quarter (24.9%) of all cases, followed by Northern America (15.1%) and South-Central Asia (9.7%). Incidence rates were higher in men than in women, with similar geographical patterns. While the incidence rates were highest in Australia and New Zealand, Northern America, Northern Europe and Western Europe (>10/100 000 for both sexes combined), the highest mortality rates (>3/100 000) were found in regions in Africa, Western Asia and Oceania. The large variations and the disproportionately higher mortality in low- and middle-income countries can be related to the underlying prevalence and distribution of risk factors, and to the level of access to diagnostic and treatment facilities.
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Affiliation(s)
- Allini Mafra
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Mathieu Laversanne
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Mary Gospodarowicz
- Radiation Oncology, University of Toronto, Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
| | - Paulo Klinger
- Department of Hematology and Cell Therapy, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, University of São Paulo, São Paulo, Brazil
| | - Neimar De Paula Silva
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Marion Piñeros
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | | | - Freddie Bray
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
| | - Ariana Znaor
- Cancer Surveillance Branch, International Agency for Research on Cancer, Lyon, France
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13
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Impact of autologous stem cell transplantation on survival outcomes in patients with peripheral T cell lymphoma. Transfus Apher Sci 2022; 61:103514. [DOI: 10.1016/j.transci.2022.103514] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2022] [Revised: 07/07/2022] [Accepted: 07/22/2022] [Indexed: 11/19/2022]
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14
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Recent Advances in the Management of Relapsed and Refractory Peripheral T-Cell Lymphomas. J Pers Med 2022; 12:jpm12060964. [PMID: 35743749 PMCID: PMC9225101 DOI: 10.3390/jpm12060964] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2022] [Revised: 05/31/2022] [Accepted: 06/07/2022] [Indexed: 11/16/2022] Open
Abstract
Peripheral T-cell lymphomas (PTCLs) are a group of heterogeneous lymphomas with poor overall prognosis, particularly in the setting of relapsed/refractory PTCL. Given the limited efficacy of current therapies, several different novel therapies encompassing multiple different mechanisms of action have been evaluated for relapsed and refractory PTCLs. In this review, we explore the current standard of care for relapsed/refractory PTCL, and evaluate in depth novel and emerging therapies, their scientific basis, and current trials for relapsed/refractory PTCL.
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15
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Gao LM, Zhang YH, Shi X, Liu Y, Wang J, Zhang WY, Liu WP. The Role of PD-L1 Expression in Prediction and Stratification of Recurrent or Refractory Extranodal Natural Killer/T-Cell Lymphoma. Front Oncol 2022; 12:821918. [PMID: 35619907 PMCID: PMC9128790 DOI: 10.3389/fonc.2022.821918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2021] [Accepted: 03/29/2022] [Indexed: 02/05/2023] Open
Abstract
Background and Aims The clinical outcome of relapsed and refractory (RR) extranodal natural killer/T-cell lymphoma (ENKTL) is poor. It is necessary to identify RR patients in ENKTL and find novel therapeutic targets to improve the prognosis of patients with RR ENKTL. Methods A total of 189 ENKTL patients with effective clinical characteristics were enrolled. Paraffin specimens were collected for PD-L1 expression identification. Kaplan-Meier curve analysis was performed for survival analysis. Whole exome sequencing (WES) was performed for identifying the mutational characterization of RR and effective treatment (ET) patients. Results Univariate and multivariate Cox proportional hazards regression analysis showed that negative PD-L1 expression (HR = 1.132, 95% CI = 0.739-1.734, P = 0.036) was an independent predictor of poor prognosis in patients with ENKTL. The overall survival (OS) of PD-L1 positive patients was significantly higher than that of PD-L1 negative patients (P = 0.009). Then, we added PD-L1 expression as a risk factor to the model of Prognostic Index of Natural Killer Lymphoma (PINK), and named as PINK+PD-L1. The PINK+PD-L1 model can significantly distinguish RR patients, ET patients, and the whole cohort. Moreover, our data showed that PD-L1 expression was lower than 25% in most RR patients, suggesting that RR subtypes may be associated with low expression of PD-L1 (P = 0.019). According to the whole exome sequencing (WES), we found that the mutation frequencies of JAK-STAT (P = 0.001), PI3K-AKT (P = 0.02) and NF-kappa B (P < 0.001) pathways in RR patients were significantly higher than those in ET patients. Conclusion Patients tend to show RR when PD-L1 expression is lower than 25%. The model of PINK+PD-L1 can stratify the risk of different groups and predict OS in ENKTL patients. The mutational profile of ENKTL patients with RR is different from that of patients with ET.
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Affiliation(s)
- Li-Min Gao
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Yue-Hua Zhang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Xiaoliang Shi
- Department of Medical Product, OrigiMed, Inc., Shanghai, China
| | - Yang Liu
- Department of Medical Product, OrigiMed, Inc., Shanghai, China
| | - Junwei Wang
- Department of Medical Product, OrigiMed, Inc., Shanghai, China
| | - Wen-Yan Zhang
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
| | - Wei-Ping Liu
- Department of Pathology, West China Hospital of Sichuan University, Chengdu, China
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16
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Sibon D. Peripheral T-Cell Lymphomas: Therapeutic Approaches. Cancers (Basel) 2022; 14:cancers14092332. [PMID: 35565460 PMCID: PMC9104854 DOI: 10.3390/cancers14092332] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 05/04/2022] [Indexed: 11/21/2022] Open
Abstract
Simple Summary Peripheral T-cell lymphomas are a group of rare cancers of T cells or natural killer cells, most often with a poor prognosis. In recent years, significant progress has been made through the development of more specific therapies. This review aims to provide an up-to-date overview of current treatments in nodal PTCL. Abstract Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of rare neoplasms of mature T cells or natural killer (NK) cell. PTCLs usually have an aggressive course and a poor outcome. In recent years, significant progress has been made in the knowledge of the molecular lymphomagenesis of PTCLs, and through the development of new, more specific therapeutic molecules, one can hope in the coming years for more personalized medicine and improved patient prognosis. This review aims to provide an up-to-date overview of the current therapeutic approaches in nodal PTCLs.
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Affiliation(s)
- David Sibon
- Lymphoid Malignancies Department, Henri Mondor University Hospital, AP-HP, 94000 Créteil, France;
- Faculty of Medicine and Health, Campus Henri Mondor, Paris-Est Créteil University, 94000 Créteil, France
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17
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Lei T, Chang Y, Zhang L, Zhang M. The Effect of Chronic Rhinosinusitis on the Staging and Prognosis of Extranodal Natural Killer/T-Cell Lymphoma: A Single-Center Retrospective Analysis. Front Oncol 2022; 12:878559. [PMID: 35449572 PMCID: PMC9016184 DOI: 10.3389/fonc.2022.878559] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2022] [Accepted: 03/03/2022] [Indexed: 11/25/2022] Open
Abstract
Clinically, extranodal natural killer/T-cell lymphoma (ENKTL) patients frequently had a history of chronic rhinosinusitis (CRS) before onset, and the correlation between the two diseases has not been systematically reported at present. In this study, we applied the method-retrospective analysis-to explore the relationship between CRS and ENKTL. We collected clinical data and the length of CRS history before onset in 214 patients diagnosed with ENKTL and found that the length of CRS history was correlated with the stage of 182 ENKTL patients whose primary sites were upper aerodigestive tract (UAT) (χ 2 = 21.317, p = 0.046, n = 182); the Spearman correlation coefficient was 0.162 (p = 0.029). There was no significant difference in stage of the non-UAT-ENKTL patients (χ 2 = 18.910, p = 0.091, n = 32). The COX multivariate regression analysis showed that CRS history was an independent prognostic predictor for PFS of the UAT-ENKTL patients (p = 0.004), and patients without CRS had significantly better PFS than the more than 15 years CRS history group (p = 0.001). Our findings suggested that we should not ignore the existence of chronic inflammation of the nasal cavity in ENKTL patients. It is better to treat CRS as soon as possible in clinical practice to reduce the possibility of the occurrence or progression of UAT-ENKTL.
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18
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Genetic profiling and biomarkers in peripheral T-cell lymphomas: current role in the diagnostic work-up. Mod Pathol 2022; 35:306-318. [PMID: 34584212 DOI: 10.1038/s41379-021-00937-0] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/06/2021] [Revised: 09/15/2021] [Accepted: 09/16/2021] [Indexed: 11/08/2022]
Abstract
Peripheral T-cell lymphomas are a heterogeneous, and usually aggressive, group of mature T-cell neoplasms with overlapping clinical, morphologic and immunologic features. A large subset of these neoplasms remains unclassifiable with current diagnostic methods ("not otherwise specified"). Genetic profiling and other molecular tools have emerged as widely applied and transformative technologies for discerning the biology of lymphomas and other hematopoietic neoplasms. Although the application of these technologies to peripheral T-cell lymphomas has lagged behind B-cell lymphomas and other cancers, molecular profiling has provided novel prognostic and diagnostic markers as well as an opportunity to understand the biologic mechanisms involved in the pathogenesis of these neoplasms. Some biomarkers are more prevalent in specific T-cell lymphoma subsets and are being used currently in the diagnosis and/or risk stratification of patients with peripheral T-cell lymphomas. Other biomarkers, while promising, need to be validated in larger clinical studies. In this review, we present a summary of our current understanding of the molecular profiles of the major types of peripheral T-cell lymphoma. We particularly focus on the use of biomarkers, including those that can be detected by conventional immunohistochemical studies and those that contribute to the diagnosis, classification, or risk stratification of these neoplasms.
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19
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Sethi T, Montanari F, Foss F. Safety considerations with the current treatments for peripheral T-cell lymphoma. Expert Opin Drug Saf 2022; 21:653-660. [PMID: 35129014 DOI: 10.1080/14740338.2022.2036120] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/04/2022]
Abstract
INTRODUCTION Peripheral T-Cell Lymphomas (PTCL) constitute a heterogeneous group of aggressive T - and natural killer (NK)-cell disorders and are associated with a poor prognosis. Frontline treatments often consist of anthracycline-based combination chemotherapy with the exception of NK-T cell lymphomas, where such combinations are ineffective due to the presence of P-glycoprotein which leads to multidrug resistance. Infectious and immune mediated side effects might be more pronounced in or unique to T-cell lymphomas due to the selection of agents which target multiple T-cell subtypes and also an immunocompromised state induced by the lymphomas themselves. AREAS COVERED This review provides a comprehensive overview of safety considerations of treatment regimens used for peripheral T-cell lymphomas. We cover regimens used in both frontline and relapsed settings including combination chemotherapy, single agent chemotherapies and immunotherapies. EXPERT OPINION Treatment of T-cell lymphomas often requires sequencing of several therapies due to lower efficacy of available treatment regimens in curing the disease compared to that seen in B-cell non-Hodgkin lymphomas. In addition, certain complications are more common in T-cell lymphomas due to their unique immunobiology. An understanding of these salient aspects is important for all providers who treat patients with this challenging disease group.
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Affiliation(s)
- Tarsheen Sethi
- Hematology and Stem Cell Therapy, Yale University School of Medicine, New Haven
| | - Francesca Montanari
- Hematology and Stem Cell Therapy, Yale University School of Medicine, New Haven
| | - Francine Foss
- Hematology and Stem Cell Therapy, Yale University School of Medicine, New Haven
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20
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Honda T, Yamaoka M, Terao YM, Hasegawa D, Kumamoto T, Takagi M, Yoshida K, Ogawa S, Goto H, Akiyama M. Successful treatment of hepatosplenic T-cell lymphoma with fludarabine, high-dose cytarabine and subsequent unrelated umbilical cord blood transplantation. Int J Hematol 2022; 115:140-145. [PMID: 34591292 DOI: 10.1007/s12185-021-03229-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Revised: 09/21/2021] [Accepted: 09/26/2021] [Indexed: 11/30/2022]
Abstract
Hepatosplenic T-cell lymphoma (HSTCL) is a rare subtype of peripheral T-cell lymphoma that occurs most often in adolescents and young adults and is rare in children. Because of the aggressive clinical course, resistance to conventional chemotherapy and poor prognosis of HSTCL, an effective treatment has not been established. We report the case of a 3-year-old girl with HSTCL presenting with trilineage myelodysplasia. Although the HSTCL was refractory to conventional chemotherapy, remission was achieved with salvage chemotherapy that included fludarabine and cytarabine, which were shown to be effective in the drug sensitivity assay. After undergoing umbilical cord blood transplantation with a conditioning regimen consisting of etoposide, cyclophosphamide and total body irradiation, the patient has remained in complete remission for 8 years. Single-nucleotide polymorphism array analysis revealed heterozygous deletions of PAX5 (9p), ETV6 (12p) and homozygous deletions of CDKN2A (9p). Exome analysis showed a heterozygous nonsense c.2961C>G (p.Tyr987Ter) variant of the KMT2C gene. To improve the poor prognosis of HSTCL, the chemotherapeutic regimen can be selected for each patient on the basis of drug sensitivity and molecular genetic characteristics.
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Affiliation(s)
- Takaya Honda
- Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Masayoshi Yamaoka
- Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Yoko Mikami Terao
- Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan
| | - Daisuke Hasegawa
- Department of Pediatrics, St. Luke's International Hospital, Tokyo, Japan
| | - Tadashi Kumamoto
- Department of Pediatric Oncology, National Cancer Center Hospital, Tokyo, Japan
| | - Masatoshi Takagi
- Department of Pediatrics and Developmental Biology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo, Japan
| | - Kenichi Yoshida
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
| | - Seishi Ogawa
- Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
- Institute for the Advanced Study of Human Biology, Kyoto University, Kyoto, Japan
- Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institute, Stockholm, Sweden
| | - Hiroaki Goto
- Division of Hematology/Oncology, Kanagawa Children's Medical Center, Yokohama, Japan
| | - Masaharu Akiyama
- Department of Pediatrics, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo, 105-8461, Japan.
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21
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Nosaka K, Crawford B, Yi J, Kuan W, Matsumoto T, Takahashi T. Systematic review of survival outcomes for relapsed or refractory adult T-cell leukemia-lymphoma. Eur J Haematol 2021; 108:212-222. [PMID: 34862665 PMCID: PMC9299810 DOI: 10.1111/ejh.13728] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/30/2021] [Revised: 11/18/2021] [Accepted: 11/19/2021] [Indexed: 01/06/2023]
Abstract
Introduction Adult T‐cell leukemia‐lymphoma (ATL) is a mature T‐cell lymphoproliferative neoplasm caused by human T‐cell leukemia virus type‐1 infection. There is no standard treatment for relapsed or refractory (r/r) ATL, and clinical outcomes are poor. This systematic review examined the survival outcomes for r/r ATL treated with various systemic therapies. Methods EMBASE and PubMed were searched for studies on r/r ATL, published between January 2010 and January 2020. The main outcome of interest was overall survival (OS). Median OS and an exploratory 30% OS time were assessed based on published data and Kaplan‐Meier curves. Results There were 21 unique treatment subgroups (from 14 studies), that met the eligibility criteria. Nine subgroups were mogamulizumab treatment, two were mogamulizumab prior to allogenic hematopoietic stem cell transplantation (allo‐HSCT), five were allo‐HSCT, and five were other chemotherapy. Respectively, the median OS and 30% OS varied considerably in range for mogamulizumab treatment (2.2–17.6 months and 8.7–27.1 months), allo‐HSCT (3.8–6.2 months and 7.5–19.8 months), and other chemotherapy arms (4.1–20.3 months and 7.1–17.0 months). Conclusion Mogamulizumab was the most frequently studied treatment regimen and can potentially provide longer survival compared with chemotherapy alone. Future comparisons with synthetic or historical control arms may enable clearer insights into treatment efficacy.
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Affiliation(s)
- Kisato Nosaka
- Cancer Center, Kumamoto University Hospital, Kumamoto, Japan
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22
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Ma Y, Li Y, Ma A, Li H. Is the Scope of Costs Considered in Budget Impact Analyses for Anticancer Drugs Rational? A Systematic Review and Comparative Study. Front Public Health 2021; 9:777199. [PMID: 34805082 PMCID: PMC8602071 DOI: 10.3389/fpubh.2021.777199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2021] [Accepted: 10/14/2021] [Indexed: 12/24/2022] Open
Abstract
Background: With the increasing disease burden of cancer worldwide, more and more anticancer drugs have been approved in many countries, and the results of budget impact analyses (BIAs) have become important evidence for related reimbursement decisions. Objectives: We systematically reviewed whether BIAs for anticancer drugs consider the scope of costs rationally and compared the results of different cost scopes to provide suggestions for future analyses and decision-making. Methods: Eligible BIAs published in PubMed, Embase, Web of Science, and the Cochrane Library from 2016 to 2021 were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We extracted 15 terms from the included studies and analyzed how they considered the scope of costs. In addition, a budget impact model was developed for the introduction of geptanolimab to China's National Reimbursement Drug List to enable a comparison of two cost-scope scenarios. Results: A total of 29 studies were included in the systematic review. All 29 studies considered the costs of anticancer drugs, and 25 (86%) also considered condition-related costs, but only 11 (38%) considered subsequent treatment costs. In the comparative study, the predicted budget impacts from 2022 to 2024 were significantly impacted by subsequent treatment costs, with annual differences between the two cost-scope scenarios of $39,546,664, $65,866,161, and $86,577,386, respectively. Conclusions: The scope of costs considered in some existing BIAs for anticancer drugs are not rational. The variations between different cost scopes in terms of budget impact were significant. Thus, BIAs for anticancer drugs should consider a rational scope of costs that adheres to BIA guidelines. Researchers and decision-makers should pay more attention to the scope of costs to achieve better-quality BIAs for anticancer drugs and enhance reimbursement decision-making.
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Affiliation(s)
- Yue Ma
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.,Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China
| | - Yuxin Li
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.,Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China
| | - Aixia Ma
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.,Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China
| | - Hongchao Li
- School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.,Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China
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Cencini E, Fabbri A, Mecacci B, Bocchia M. Role of lenalidomide in the treatment of peripheral T-cell non-Hodgkin lymphomas. World J Clin Oncol 2021; 12:882-896. [PMID: 34733611 PMCID: PMC8546656 DOI: 10.5306/wjco.v12.i10.882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/05/2021] [Revised: 07/07/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
T-cell lymphomas (TCLs) represent a group of lymphoid neoplasms characterized by an aggressive clinical course, even after an anthracycline-containing regimen. Novel agents for patients with relapsed/refractory TCL are urgently needed. Lenalidomide is an oral drug with immunomodulatory, antiangiogenic and direct antineoplastic effects. These peculiar mechanisms of action make TCL an attractive target for lenalidomide. We have identified five clinical trials in which lenalidomide monotherapy was investigated to treat TCL, including cutaneous TCL (CTCL) and adult T-cell lymphoma/leukemia (ATLL). In the ATLL-002 study, the overall response rate (ORR) was 42% and median progression-free survival (PFS) and overall survival were 3.8 mo and 20.3 mo, respectively. In a phase II trial for CTCL, ORR was 28% and median PFS and overall survival were 8 mo and 43 mo, respectively. For nodal peripheral TCL, ORR was between 10% and 43% in three clinical trials, with a median PFS of about 4 mo, even if some patients had a durable response. Overall toxicity is manageable and grade 3-4 events are mainly hematological and reversible. Combination strategies did not improve PFS. In conclusion, lenalidomide could represent a suitable treatment option for relapsed/refractory TCL, especially for neoplasms with a T-follicular helper origin, such as angioimmunoblastic TCL.
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Affiliation(s)
- Emanuele Cencini
- Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena 53100, Italy
| | - Alberto Fabbri
- Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena 53100, Italy
| | - Bianca Mecacci
- Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena 53100, Italy
| | - Monica Bocchia
- Unit of Hematology, Azienda Ospedaliera Universitaria Senese and University of Siena, Siena 53100, Italy
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Kim J, Cho J, Byeon S, Kim WS, Kim SJ. Comparison of first-line treatments of peripheral T-cell lymphoma according to regimen: A systematic review and meta-analysis. Hematol Oncol 2021; 39:664-673. [PMID: 34487565 DOI: 10.1002/hon.2924] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/23/2021] [Accepted: 08/27/2021] [Indexed: 12/17/2022]
Abstract
Peripheral T-cell lymphomas (PTCLs) are known to have an aggressive clinical course and grave prognosis. Several recommended first-line treatment regimens are available, but identification of the superior treatment remain elusive. We conducted a systematic review and meta-analysis to determine which study-level factors and group of regimens affect survival outcomes. The MEDLINE, Embase, and Cochrane databases were searched from inception to January 2021, and phase II or III clinical studies evaluating the efficacy of chemotherapy regimens were included. Random effects models were used to estimate 3-year overall survival rate, complete remission rate, and subgroup differences. Meta-regressions were carried out with adjustments for relevant covariates. Overall, 34 cohorts from 28 studies comprising 1424 PTCL patients were included in the pooled analysis. Chemotherapy regimens were divided into four groups: cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP), CHOP plus etoposide, gemcitabine-based, and others. The pooled 3-year overall survival rate was 0.49 (95% confidence interval [CI] 0.43-0.54) for CHOP, 0.61 (95% CI 0.52-0.70) for CHOP plus etoposide, 0.39 (95% CI 0.30-0.47) for gemcitabine-based, and 0.61 (95% CI 0.44-0.78) for others. CHOP plus etoposide was significantly better than CHOP, with the latter used as a reference (coefficient of 0.11; p = 0.035), with adjustment for the proportion of International Prognostic Index score 4-5 in meta-regression analysis. Although grossly divided groups were pooled and analyzed, among four regimen groups for frontline PTCL treatment CHOP plus etoposide showed better survival than CHOP.
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Affiliation(s)
- Jinchul Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Hematology-Oncology, Inha University College of Medicine and Hospital, Incheon, Korea
| | - Jinhyun Cho
- Department of Hematology-Oncology, Inha University College of Medicine and Hospital, Incheon, Korea
| | - Seonggyu Byeon
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea
| | - Won Seog Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea
| | - Seok Jin Kim
- Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.,Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea
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Bron D, De Leval L, Michiels S, Wittnebel S. Hepatosplenic T-cell lymphoma: treatment challenges. Curr Opin Oncol 2021; 33:406-411. [PMID: 34409955 DOI: 10.1097/cco.0000000000000775] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
PURPOSE OF REVIEW Hepatosplenic lymphoma (HSTCL) is a rare T-cell malignancy occurring in young males, associated with immune deficiency in 20% of the cases which, despite aggressive treatments, has a poor survival. Specific recommendations for first-line treatment remain debatable. RECENT FINDINGS Published data covering case reports or series of HSTCL concur that allogeneic stem cell transplant should be proposed as a consolidation after response to chemotherapy in all patients eligible for transplant. In the light of two recent clinical examples, we also confirm that specific chemotherapy and a first-line consolidation with allogeneic transplantation when a donor is available to represent a treatment of choice these rare and distinctive lymphomas. Recent molecular studies are summarized in this review and suggest potential targets for new therapeutic strategies. SUMMARY Major progresses have been achieved in improving the outcome of HSTCL l patients using intensive chemotherapy and allogeneic transplantation.
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Affiliation(s)
- Dominique Bron
- Department of Hematology, Institut Jules Bordet (ULB), Brussels, Belgium
| | - Laurence De Leval
- Institute of Pathology, Lausanne University Hospital and Lausanne University, Lausanne, Switzerland
| | - Sandra Michiels
- Department of Hematology, Institut Jules Bordet (ULB), Brussels, Belgium
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Zain JM, Hanona P. Aggressive T-cell lymphomas: 2021 Updates on diagnosis, risk stratification and management. Am J Hematol 2021; 96:1027-1046. [PMID: 34111312 DOI: 10.1002/ajh.26270] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Accepted: 06/08/2021] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Aggressive T-cell lymphomas continue to have a poor prognosis. There are over 27 different subtypes of peripheral T-cell lymphoma (PTCL), and we are now beginning to understand the differences between the various subtypes beyond histologic variations. MOLECULAR PATHOGENESIS OF VARIOUS SUBTYPES OF PTCL Gene expression profiling (GEP) can help in diagnosis and prognostication of various subtypes including PTCL-nos and anaplastic large cell lymphoma (ALCL). In addition, mutational analysis is now being incorporated in clinical trials of novel agents to evaluate various biomarkers of response to allow better therapeutic choices for patients. TARGETED THERAPIES There are many targeted agents currently in various stages of clinical trials for PTCL that take advantage of the differential expression of specific proteins or receptors in PTCL tumors. This includes the CD30 directed antibody drug conjugate brentuximab vedotin. Other notable targets are CD25, CCR4, inhibition of PI3kinase - m TOR and JAK/STAT pathways. The ALK inhibitors are promising for ALK expressing tumors. IMMUNOTHERAPIES Allogeneic stem cell transplant continues to be the curative therapy for most aggressive subtypes of PTCL. The use of checkpoint inhibitors in the treatment of PTCL is still controversial. The most promising results have been seen in cases of extranodal natural killer cell/T-cell (ENK/T) lymphomas and cutaneous T-cell lymphomas (CTCL). Bispecific antibody based treatments as well as CAR-T cell based therapies are in clinical trials.
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Affiliation(s)
- Jasmine M. Zain
- Department of Hematology/Hematopoietic Cell Transplantation City of Hope Medical Center Duarte California USA
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The importance of genomic predictors for clinical outcome of hematological malignancies. BLOOD SCIENCE 2021; 3:93-95. [PMID: 35402837 PMCID: PMC8974908 DOI: 10.1097/bs9.0000000000000075] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2021] [Accepted: 04/21/2021] [Indexed: 12/17/2022] Open
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