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T-cell/histiocyte-rich large B-cell lymphoma (THRLBCL) is a rare histologic variant of LBCL. Limited data regarding CD19-directed chimeric antigen receptor T-cell (CART) therapy in relapsed/refractory (R/R) THRLBCL suggest poor efficacy. We investigated CART outcomes for R/R THRLBCL through the CIBMTR registry. A total of 58 adult patients with R/R THRLBCL who received commercial CD19-CART between 2018-2022 were identified. Most patients (67%) had early relapse of disease (45% primary refractory) with a median of 3 (range: 1-7) prior therapies and were treated with Axicabtagene ciloleucel (69%). At median follow-up of 23 months post-CART, 2-year overall and progression-free survival were 42% (95% CI: 27-57) and 29% (95% CI: 17-43), respectively. In univariable analysis, poor performance status pre-CART was associated with higher mortality (HR 2.35, 95%CI 1.02-5.5). The 2-year cumulative incidences of relapse/progression and non-relapse mortality were 69% and 2%, respectively. Grade ≥3 CRS and ICANS occurred in 7% and 15% of patients, respectively. In this largest analysis of CD19-CART for R/R THRLBCL, approximately 30% of patients were alive and progression-free 2 years post-CART. Despite a high incidence of progression (69% at 2 years), these results suggest a subset of patients with R/R THRLBCL may have durable responses with CART.
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Neoplasias do Sistema Nervoso Central , Imunoterapia Adotiva , Linfoma de Célula do Manto , Humanos , Linfoma de Célula do Manto/terapia , Linfoma de Célula do Manto/patologia , Imunoterapia Adotiva/métodos , Neoplasias do Sistema Nervoso Central/terapia , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Receptores de Antígenos Quiméricos , Resultado do TratamentoRESUMO
Outcomes are poor for patients with relapsed and/or refractory (R/R) large B-cell lymphoma (LBCL) post chimeric antigen receptor T-cell (CAR-T) therapy. Two CD19-directed therapies, tafasitamab- cxix plus lenalidomide (tafa-len) and loncastuximab tesirine (loncaT) are approved in R/R LBCL. The efficacy of these CD19 directed therapies in patients who relapse after CD19 directed CAR-T (CD19-CART) therapy is not well understood. We conducted a multi-center study of patients with R/R LBCL that received either tafa-len or loncaT at any timepoint for R/R disease after CD19-CART therapy. Fifty-three patients were included in this study with the median follow up of 56 (9.1-199) weeks from CAR-T infusion. Median number of systemic therapies pre-CAR-T therapy was 3 (range: 1-6); axicabtagene ciloleucel was the most utilized CAR-T product (n = 32,60%). Median time from CAR-T therapy to tafa-len or loncaT was 7.3 (1.2-38.2) months with median number of lines of therapy between CAR-T therapy and these regimens of 1 (0-5). Combined overall response rate and complete response rates were 27% and 10%, respectively. Median duration of response was 13.3 (2.1-56.7) weeks. In this real-world study, the use of currently approved CD19-directed therapies to treat R/R LBCL after CD19-CAR-T therapy showed limited clinical activity and duration of responses.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Humanos , Antígenos CD19 , Terapia Baseada em Transplante de Células e Tecidos , Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Receptores de Antígenos Quiméricos/uso terapêuticoRESUMO
Over the past decade, the treatment landscape of chronic lymphocytic leukemia (CLL) has dramatically changed, shifting from cytotoxic chemotherapy to targeted therapies. Bruton's tyrosine kinase (BTK) inhibitors have revolutionized the treatment of CLL and are increasingly applied in many other malignancies. However, ibrutinib, the first BTK inhibitor approved, is associated with serious toxicities, including atrial fibrillation in up to 38% of patients, ventricular arrhythmias, and other cardiovascular toxicities. Emerging data suggest several newer BTK inhibitors (eg, acalabrutinib, zanubrutinib) are still associated with cardiotoxic risks. This review examines the current state of evidence, including incidence rates, risk factors, mechanisms, and management strategies of cardiovascular toxicities with BTK inhibitors and other CLL therapies. We specifically focus on atrial fibrillation, ventricular arrhythmias/sudden death, hypertension, heart failure, bleeding, and stroke. We also touch on other emerging BTK therapies (eg, pirtobrutinib). Finally, we highlight key unanswered questions and future directions of research.
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Thiotepa/carmustine (TT-BCNU) is a commonly used autologous transplant (ASCT) conditioning regimen for primary DLBCL of the CNS (PCNSL). The total thiotepa dose varies among TT-BCNU recipients, with some centers administering a total dose of 20 mg/kg, while others using 10 mg/kg. We retrospectively assessed the impact of thiotepa dose intensity on ASCT outcomes in 218 adult PCNSL patients who underwent a first ASCT with TT-BCNU conditioning and received either a total thiotepa dose of 10 mg/kg (TT-10 group; N = 90), or 20 mg/kg (TT-20 group; N = 128). The median follow-up of survivors was 22 months. The cumulative incidence of 1-year non-relapse mortality (NRM) for TT-10 and TT-20 cohorts were 6% (95%CI = 2-12%) vs. 4% (95%CI = 1-8%), respectively (p = 0.66). The 3-year cumulative incidence of relapse (15% vs. 13%; p = 0.67), progression-free survival (PFS) (71% vs. 80%; p = 0.25) and overall survival (OS) (79% vs. 83%; p = 0.56) were similar in the TT-10 and TT-20 groups, respectively. On multivariate analysis compared to TT-10, the TT-20 cohort was not associated with significantly different risk of NRM (Hazard ration [HR] = 0.77; p = 0.64), relapse/progression (HR = 0.87; p = 0.74), PFS (HR = 0.80; p = 0.48) or OS (HR = 1.10; p = 0.80). In conclusion thiotepa dose-intensity in TT-BCNU conditioning does not impact ASCT outcomes of PCNSL patients.
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Neoplasias do Sistema Nervoso Central , Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Adulto , Humanos , Tiotepa/uso terapêutico , Carmustina/uso terapêutico , Autoenxertos/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Estudos Retrospectivos , Recidiva Local de Neoplasia , Transplante Autólogo , Sistema Nervoso Central/patologia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Recidiva , Protocolos de Quimioterapia Combinada AntineoplásicaRESUMO
Autologous hematopoietic cell transplantation (auto-HCT) has long been the standard approach for patients with relapsed/refractory (R/R) chemosensitive diffuse large B cell lymphoma (DLBCL). However, the advent of chimeric antigen receptor (CAR) T cell therapy has caused a paradigm shift in the management of R/R DLBCL patients, especially with the recent approval of CD19-directed CAR-T therapy in the second-line setting in high-risk groups (primary refractory and early relapse [≤12 months]). Consensus on the contemporary role, optimal timing, and sequencing of HCT and cellular therapies in DLBCL is lacking; therefore, the American Society of Transplantation and Cellular Therapy (ASTCT) Committee on Practice Guidelines undertook this project to formulate consensus recommendations to address this unmet need. The RAND-modified Delphi method was used to generate 20 consensus statements with a few key statements as follows: (1) in the first-line setting, there is no role for auto-HCT consolidation for patients achieving complete remission (CR) following R-CHOP (rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone) or similar therapy in non-double-hit/triple-hit cases (DHL/THL) and in DHL/THL cases receiving intensive induction therapies, but auto-HCT may be considered in eligible patients receiving R-CHOP or similar therapies in DHL/THL cases; (2) auto-HCT consolidation with thiotepa-based conditioning is standard of care for eligible patients with primary central nervous system lymphoma achieving CR with first-line therapy; and (3) in the primary refractory and early relapse setting, the preferred option is CAR-T therapy, whereas in late relapse (>12 months), consolidation with auto-HCT is recommended for patients achieving chemosensitivity to salvage therapy (complete or partial response), and CAR-T therapy is recommended for those not achieving remission. These clinical practice recommendations will serve as a tool to guide clinicians managing patients with newly diagnosed and R/R DLBCL.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Linfoma não Hodgkin , Receptores de Antígenos Quiméricos , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Rituximab/uso terapêutico , Linfoma não Hodgkin/tratamento farmacológico , Ciclofosfamida/uso terapêutico , Vincristina/uso terapêutico , Prednisona/uso terapêutico , Doxorrubicina/uso terapêutico , RecidivaRESUMO
OBJECTIVE: Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. METHODS: Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. RESULTS: Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. CONCLUSION: Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.
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COVID-19 , Neoplasias Hematológicas , Humanos , Vacinas contra COVID-19 , Imunoglobulina G , SARS-CoV-2 , Formação de Anticorpos , COVID-19/prevenção & controle , VacinaçãoRESUMO
BTK (Bruton's tyrosine kinase) inhibitors are highly effective front-line therapy for CLL (chronic lymphocytic leukemia) due to high response rates and prolonged progression-free survival, even in patients with high-risk disease features. They are also generally well tolerated, with the newer BTK inhibitors demonstrating better tolerability than ibrutinib while maintaining efficacy. Adverse effects such as bleeding or infections are usually manageable with supportive care or dose adjustments. Orally administered BTK inhibitors do not require intensive or inpatient monitoring and improve quality-of-life outcomes. Moreover, the established activity of venetoclax in the setting of BTK inhibitor failure is also reassuring as a salvage option. Nevertheless, the advantage of venetoclax as a time-limited treatment option is substantial, despite its inferior progression-free survival, since these patients can get another challenge with a reasonable chance of success. BTK inhibitors after venetoclax may be effective, but long-term data is limited. Given these reasons, BTK inhibitors remain the preferred treatment option as initial therapy for patients with CLL, especially those with del17p or TP53 mutations.
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Leucemia Linfocítica Crônica de Células B , Humanos , Tirosina Quinase da Agamaglobulinemia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Importance: Ibrutinib has been associated with serious cardiotoxic arrhythmias. In preclinical models, these events are paralleled or proceeded by diffuse myocardial injury (inflammation and fibrosis). Yet whether this is seen in patients or has implications for future cardiotoxic risk is unknown. Objective: To assess the incidence and outcomes of myocardial injury among patients with ibrutinib-related cardiotoxicity. Design, Setting, and Participants: This cohort study included consecutive patients treated with ibrutinib from 2012 to 2019, phenotyped using cardiovascular magnetic resonance (CMR) from a large US Comprehensive Cancer Center registry. Exposures: Ibrutinib treatment for cancer control. Main Outcomes and Measures: The primary outcome was the presence of late gadolinium enhancement (LGE) fibrosis. The secondary outcome was the occurrence of major adverse cardiac events (MACE), defined as atrial fibrillation, heart failure, symptomatic ventricular arrhythmias, and sudden death of probable or definite ibrutinib association after CMR. We also assessed parametric-mapping subclinical fibrosis (native-T1, extracellular volume fraction) and inflammation/edema (max-T2) measures. Cardiovascular magnetic resonance measures were compared with those obtained in similar consecutive patients with cancer without ibrutinib treatment (pretreatment controls). Observed measures were also compared with similar-aged broad population rates (general-population controls) and a broader pool of cardiovascular disease (CVD) risk-matched cancer controls. Multivariable regression was used to assess the association between CMR measures and MACE. Results: Overall, 49 patients treated with ibrutinib were identified, including 33 imaged after treatment initiation (mean [SD] age, 65 [10] years, 9 [27%] with hypertension, and 23 [69.7%] with index-arrhythmias); median duration of ibrutinib-use was 14 months. The mean (SD) pretreatment native T1 was 977.0 (73.0) ms, max-T2 56.5 (4.0) ms, and 4 (13.3%) had LGE. Posttreatment initiation, mean (SD) native T1 was 1033.7 (48.2) ms, max-T2 61.5 (4.8) ms, and 17 (54.8%) had LGE (P < .001, P = .01, and P < .001, respectively, pre- vs post-ibrutinib treatment). Native T12SDs was elevated in 9 (28.6%), and max-T22SDs in 21 (63.0%), respectively. Cardiovascular magnetic resonance measures were highest in those with suspected toxic effects (P = .01 and P = .01, respectively). There was no association between traditional CVD-risk or cancer-treatment status and abnormal CMR measures. Among those without traditional CVD, 16 (58.6%) had LGE vs 38 (13.3%) in matched-controls (relative-risk, 4.8; P < .001). Over a median follow-up of 19 months, 13 (39.4%) experienced MACE. In multivariable models inclusive of traditional CVD risk factors, LGE (hazard ratio [HR], 4.9; P = .04), and native-T12SDs (HR, 3.3; P = .05) associated with higher risks of MACE. Conclusions and Relevance: In this cohort study, myocardial injury was common in ibrutinib users, and its presence was associated with higher cardiotoxic risk.
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Meios de Contraste , Miocárdio , Humanos , Idoso , Miocárdio/patologia , Estudos de Coortes , Cardiotoxicidade/etiologia , Imagem Cinética por Ressonância Magnética , Gadolínio , Imageamento por Ressonância Magnética/métodos , Fibrose , Inflamação , Valor Preditivo dos Testes , Função Ventricular Esquerda , Prognóstico , Volume SistólicoRESUMO
Vitamin C is an essential vitamin that acts as a co-factor for many enzymes involved in epigenetic regulation in humans. Low vitamin C levels in hematopoietic stem cells (HSC) promote self-renewal and vitamin C supplementation retards leukaemogenesis in vitamin C-deficient mouse models. Studies on vitamin C levels in patients with myeloid malignancies are limited. We thus conducted a retrospective analysis on a prospective cohort of patients with myeloid malignancies on whom plasma vitamin C levels were measured serially at diagnosis and during treatment. Baseline characteristics including hematological indices, cytogenetics, and molecular mutations are described in this cohort. Among 64 patients included in our study, 11 patients (17%) had low vitamin C levels. We noted a younger age at diagnosis for patients with myeloid malignancies who had low plasma vitamin C levels. Patients with low plasma vitamin C levels were more likely to have acute myeloid leukemia compared to other myeloid malignancies. Low vitamin C levels were associated with ASXL1 mutations. Our study calls for further multi-institutional studies to understand the relevance of low plasma vitamin C level in myeloid neoplasms, the role of vitamin C deficiency in leukemogenesis, and the potential benefit of vitamin C supplementation.
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Deficiência de Ácido Ascórbico , Leucemia Mieloide Aguda , Transtornos Mieloproliferativos , Camundongos , Animais , Humanos , Epigênese Genética , Estudos Prospectivos , Estudos Retrospectivos , Transtornos Mieloproliferativos/genética , Mutação , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Ácido Ascórbico , Deficiência de Ácido Ascórbico/complicações , Deficiência de Ácido Ascórbico/genéticaAssuntos
Linfoma de Zona Marginal Tipo Células B , Recidiva Local de Neoplasia , Humanos , Recidiva Local de Neoplasia/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Intervalo Livre de Doença , Doença CrônicaRESUMO
PURPOSE: Primary cutaneous T-cell lymphomas (CTCLs) are radiosensitive tumors with variable and often relapsing courses. Local disease can be treated with low-dose focal palliative radiation therapy (RT), though little data supports the use of a specific dose. This study assesses clinical outcomes after focal RT to a total dose of 4 Gy, 8 Gy, or 12 Gy. METHODS AND MATERIALS: An International Review Board-approved, retrospective, single-institution study was performed of 225 lesions in 41 patients with primary CTCL treated with low-dose focal RT from 2015 to 2020. Patient, tumor, and treatment characteristics were reviewed. The primary outcome was freedom from treatment failure (FFTF), defined as time to requiring local retreatment, and secondary outcomes included response rates and toxicities. RESULTS: Of the 225 lesions, 90 received 4 Gy, 106 received 8 Gy, and 29 received 12 Gy. Lesions treated with 12 Gy (96%) or 8 Gy (92%) had a significantly higher 1-year FFTF compared with 4 Gy (77%) (P = .034). Overall response rate and complete response rate were not significantly different between different doses (P = .117), though there was a trend toward higher overall response rate at initial assessment with 8 Gy versus 4 Gy (91.5% vs 82.2%, P = .057). Toxicity was low, with 7.1% of lesions having grade 2 or higher radiation dermatitis. CONCLUSIONS: In primary CTCL lesions treated with focal palliative RT, a dose response was noted favoring 8 to 12 Gy, with 1-year FFTF rates over 90%. However, 4 Gy resulted in substantially better outcomes than previously reported, with 77% requiring no further treatment at 1 year and comparable response rates to higher doses. While our data substantiates 8 to 12 Gy as the standard of care, it also suggests that 4 Gy should be considered an acceptable alternative in situations with concern for radiation toxicities, such as with fragile or heavily pretreated skin.
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Linfoma Cutâneo de Células T , Humanos , Dosagem Radioterapêutica , Estudos Retrospectivos , Falha de Tratamento , Linfoma Cutâneo de Células T/radioterapiaRESUMO
Chimeric antigen receptor T-cell (CAR T) therapy is a revolutionary personalized therapy that has significantly impacted the treatment of patients with hematologic malignancies refractory to other therapies. Cytokine release syndrome (CRS) is a major side effect of CAR T therapy that can occur in 70-90% of patients, with roughly 40% of patients at grade 2 or higher. CRS can cause an intense inflammatory state leading to cardiovascular complications, including troponin elevation, arrhythmias, hemodynamic instability, and depressed left ventricular systolic function. There are currently no standardized guidelines for the management of cardiovascular complications due to CAR T therapy, but systematic practice patterns are emerging. In this review, we contextualize the history and indications of CAR T cell therapy, side effects related to this treatment, strategies to optimize the cardiovascular health prior to CAR T and the management of cardiovascular complications related to CRS. We analyze the existing data and discuss potential future approaches.
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Ibrutinib is effective in the treatment of relapsed/refractory (R/R) marginal zone lymphoma (MZL) with an overall response rate (ORR) of 48%. However, factors associated with response (or lack thereof) to ibrutinib in R/R MZL in clinical practice are largely unknown. To answer this question, we performed a multicenter (25 US centers) cohort study and divided the study population into three groups: "ibrutinib responders"-patients who achieved complete or partial response (CR/PR) to ibrutinib; "stable disease (SD)"; and "primary progressors (PP)"-patients with progression of disease as their best response to ibrutinib. One hundred and nineteen patients met the eligibility criteria with 58%/17% ORR/CR, 29% with SD, and 13% with PP. The median PFS and OS were 29 and 71.4 months, respectively, with no difference in PFS or OS based on the ibrutinib line of therapy or type of therapy before ibrutinib. Patients with complex cytogenetics had an inferior PFS (HR = 3.08, 95% CI 1.23-7.67, p = 0.02), while those with both complex cytogenetics (HR = 3.00, 95% CI 1.03-8.68, p = 0.04) and PP (HR = 13.94, 95% CI 5.17-37.62, p < 0.001) had inferior OS. Only primary refractory disease to first-line therapy predicted a higher probability of PP to ibrutinib (RR = 3.77, 95% CI 1.15-12.33, p = 0.03). In this largest study to date evaluating outcomes of R/R MZL treated with ibrutinib, we show that patients with primary refractory disease and those with PP on ibrutinib are very high-risk subsets and need to be prioritized for experimental therapies.
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Linfoma de Zona Marginal Tipo Células B , Adenina/análogos & derivados , Estudos de Coortes , Humanos , Linfoma de Zona Marginal Tipo Células B/tratamento farmacológico , Linfoma de Zona Marginal Tipo Células B/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Piperidinas , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Resultado do TratamentoRESUMO
Bruton's tyrosine kinase inhibitors (BTKis) have altered the treatment landscape for chronic lymphocytic leukemia (CLL) by offering effective and well-tolerated therapeutic options. However, since the approval of ibrutinib, concern has risen regarding the risk of cardiovascular (CV) adverse events, including atrial fibrillation (AF), hypertension, and heart failure. Newer BTKis appear to have lower CV risks, but data are limited. It is important to understand the risks posed by BTKis and how those risks interact with individual patients, and we convened a panel of physicians with expertise in CLL and CV toxicities in oncology to develop evidence-based consensus recommendations for community hematologists and oncologists. Care providers should thoroughly assess a patient's CV risk level before treatment initiation, including established CV diseases and risk factors, and perform investigations dependent on preexisting diseases and risk factors, including an electrocardiogram (ECG). For patients with high CV risk, BTKi treatment is often appropriate in consultation with a multidisciplinary team (MDT), and more selective BTKis, including acalabrutinib and zanubrutinib, are preferred. BTKi treatment should generally be avoided in patients with a history of heart failure. Ibrutinib should be avoided in patients with a history of ventricular arrhythmias, but the risk of newer drugs is not yet known. Finally, an MDT is crucial to help manage emerging toxicities with the goal of maintaining BTKi therapy, if possible. Optimizing heart failure, arrhythmia, and hypertension control will likely improve tolerance and maintenance of BTKi therapy. However, additional studies are needed to identify the most optimal strategy for these drugs.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Hipertensão , Leucemia Linfocítica Crônica de Células B , Tirosina Quinase da Agamaglobulinemia , Doenças Cardiovasculares/induzido quimicamente , Fatores de Risco de Doenças Cardíacas , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Hipertensão/induzido quimicamente , Leucemia Linfocítica Crônica de Células B/complicações , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Fatores de RiscoRESUMO
Background: This study analyzes sociodemographic barriers for primary CNS lymphoma (PCNSL) treatment and outcomes at a public safety-net hospital versus a private tertiary academic institution. We hypothesized that these barriers would lead to access disparities and poorer outcomes in the safety-net population. Methods: We reviewed records of PCNSL patients from 2007-2020 (n = 95) at a public safety-net hospital (n = 33) and a private academic center (n = 62) staffed by the same university. Demographics, treatment patterns, and outcomes were analyzed. Results: Patients at the safety-net hospital were significantly younger, more commonly Black or Hispanic, and had a higher prevalence of HIV/AIDS. They were significantly less likely to receive induction chemotherapy (67% vs 86%, P = .003) or consolidation autologous stem cell transplantation (0% vs. 47%, P = .001), but received more whole-brain radiation therapy (35% vs 16%, P = .001). Younger age and receiving any consolidation therapy were associated with improved progression-free (PFS, P = .001) and overall survival (OS, P = .001). Hospital location had no statistical impact on PFS (P = .725) or OS (P = .226) on an age-adjusted analysis. Conclusions: Our study shows significant differences in treatment patterns for PCNSL between a public safety-net hospital and an academic cancer center. A significant survival difference was not demonstrated, which is likely multifactorial, but likely was positively impacted by the shared multidisciplinary care delivery between the institutions. As personalized therapies for PCNSL are being developed, equitable access including clinical trials should be advocated for resource-limited settings.
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Data for outcomes after autologous hematopoietic cell transplantation (auto-HCT) in diffuse large B-cell lymphoma (DLBCL) patients ≥70 years are limited. Auto-HCT is feasible in older DLBCL patients. Using the Center for International Blood and Marrow Transplant Research database, we compared outcomes of auto-HCT in DLBCL patients aged 60 to 69 years (n = 363) versus ≥70 years (n = 103) between 2008 and 2019. Non-relapse mortality (NRM), relapse/progression (REL), progression-free survival (PFS), and overall survival (OS) were modeled using Cox proportional hazards models. All patients received BEAM conditioning (carmustine, etoposide, cytosine arabinoside and melphalan). On univariate analysis, in the 60 to 69 years versus ≥70 years cohorts, 100-day NRM was 3% versus 4%, 5-year REL was 47% versus 45%, 5-year PFS 40% versus 38% and 5-year OS 55% versus 41%, respectively. On multivariate analysis, patients ≥70 had no significant difference in NRM (hazard ratio [HR] 1.43, 95% confidence interval [CI] 0.85-2.39), REL (HR 1.11, 95% CI 0.79-1.56), PFS (HR 1.23, 95% CI 0.92-1.63) compared to patients 60 to 69 years. Patients ≥70 years had a higher mortality (HR 1.39, 95% CI 1.05-1.85, p=0.02), likely because of inferior post-relapse OS in this cohort (HR 1.82, 95% CI 1.27-2.61, P = .001). DLBCL was the major cause of death in both cohorts (62% versus 59%). Older patients should not be denied auto-HCT solely on the basis of chronological age.
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Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Idoso , Humanos , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia , Condicionamento Pré-Transplante , Transplante AutólogoRESUMO
OBJECTIVES: Diagnosis of high-grade B-cell lymphoma with MYC and BCL2 or BCL6 rearrangements (double-/triple-hit lymphoma [DTHL]) appears to mandate fluorescence in situ hybridization (FISH) testing for all large B-cell lymphoma (LBCL). Given the low incidence of DTHL, we aimed to identify flow cytometry (FC) and immunohistochemistry (IHC) features of DTHL that could be used to develop an optimal screening strategy. This combined FC-IHC approach has not yet been studied. METHODS: We compared features of 40 cases of DTHL and 39 cases of diffuse LBCL (DLBCL) without MYC rearrangement. RESULTS: Bright CD38 expression (CD38bright) by FC, high MYC expression (≥55%), and double-expressor phenotype by IHC were significantly associated with DTHL. The biomarker combining FC and IHC, CD38bright and/or MYC ≥55%, was superior to FC and IHC markers alone in predicting DTHL. Restricting FISH testing to approximately 25% of LBCL based on CD38brightand/or MYC ≥55% would detect approximately 95% of DTHL-BCL2 and approximately 75% of DHL-BCL6. CONCLUSIONS: Our study demonstrated that the novel biomarker of CD38bright and/or MYC ≥55% is highly predictive of DTHL. Awareness of the advantages and limitations of this screening strategy would facilitate development of a rational diagnostic workflow to provide high-quality patient care.
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ADP-Ribosil Ciclase 1/sangue , Linfoma Difuso de Grandes Células B , Glicoproteínas de Membrana/sangue , Proteínas Proto-Oncogênicas c-myc/sangue , Biomarcadores Tumorais/genética , Rearranjo Gênico , Humanos , Hibridização in Situ Fluorescente , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/patologia , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteínas Proto-Oncogênicas c-bcl-6/genética , Proteínas Proto-Oncogênicas c-myc/genéticaRESUMO
INTRODUCTION: The development of Bruton