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1.
Blood Adv ; 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35008100

RESUMO

Secondary central nervous system large B-cell lymphoma (SCNSL) is rare with a generally poor prognosis. There is limited data about the role of autologous stem cell transplantation (ASCT) in these high-risk patients. We explored in this study treatment outcomes and prognostic factors for patients with SCNSL who underwent ASCT. We included all consecutive patients who underwent ASCT at our institution. Primary endpoints were progression free survival (PFS) and overall survival (OS). One-hundred two patients were identified. Median age at transplant was 56 (range, 21-71) years. With a median follow-up of 56 (range, 1-256) months, the median PFS and OS were 40 and 88 months, respectively. The 4-year PFS and OS were 48% and 57%, respectively. In univariate analysis, complete remission (CR) at transplant, prior lines of therapy (≤2), normal LDH, and parenchymal involvement were significantly associated with improved PFS. For OS, only CR at transplant and ≤2 prior lines of therapy were associated with improved survival. On multivariable analysis for PFS, CR at transplant (HR 0.278, 95% CI: 0.153-0.506; p=<0.0001) and ≤ 2 prior lines of therapy (HR 0.485, 95% CI: 0.274-0.859; p=0.0131) were significantly associated with superior PFS. Similarly, CR at transplant (HR 0.352, 95% CI: 0.186-0.663; p=0.0013) and ≤ 2 prior lines of therapy (HR 0.476, 95% CI: 0.257-0.882; p=0.0183) were associated with improved survival. In the largest single center study, our findings indicate that ASCT is associated with durable responses and prolonged survival in patients with SCNSL. Patients in CR at transplant and those received less than two lines of therapy have particularly excellent outcomes.

2.
Blood Adv ; 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35015825

RESUMO

About 70% of patients with large B-cell lymphoma (LBCL) treated with axicabtagene ciloleucel (axi-cel) who achieve a partial response (PR) or a stable disease (SD) on day 30 (D30) PET-CT scan progress, but predictive factors of progression are unknown. This a retrospective study of patients with LBCL treated with axi-cel at MD Anderson Cancer Center between 01/2018 and 02/2021. Among 50 patients with D30 PR/SD, 13 (26%) converted to complete response (CR). Among 95 patients with D30 CR, 72 (76%) remained in CR. On univariate analysis, the only day -5 characteristic associated with conversion from D30 PR/SD to subsequent CR was a higher platelet count (p=0.05). The only D30 factor associated with conversion from D30 PR/SD to subsequent CR was lower D30 SUVmax (p<0.001), and all patients with and D30 SUVmax ≥10 progressed. After a median follow-up of 12 months, no significant difference in median progression-free survival was observed when comparing patients who converted from D30 PR/SD to subsequent CR to those who had been in CR since D30 (p=0.19). Novel predictive and prognostic markers based on tissue biopsy and non-invasive diagnostic assays are needed to more effectively identify these patients and characterize the biology of their residual disease.

3.
Hematol Oncol ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34763367

RESUMO

Waldenström macroglobulinemia (WM) is a rare B-cell lymphoproliferative malignancy. Autologous hematopoietic cell transplantation (auto-HCT) is considered in a subset of WM patients with relapsed disease. While registry data has shown a benefit for auto-HCT in relapsed WM, there is a paucity of data on outcomes of patients relapsing after auto-HCT. Eligibility criteria included adult patients with relapsed/refractory WM who underwent auto-HCT between 2007 and 2017. The primary endpoint was post-relapse overall survival (PR-OS). Secondary endpoints were to identify factors prognostic of PR-OS. Of the 48 patients with WM who underwent auto-HCT, 22 (46%) experienced relapse following auto-HCT. Median PR-OS of relapsed WM patients after auto-HCT (n = 22) was not reached (NR) (95% confidence interval [CI]: 17.5 months-NR). Among patients who relapsed <1 year versus ≥1 year from auto-HCT, the median PR-OS was 18.4 months (95%CI: 0.8-NR) months and NR (95%CI: 17.5-NR), respectively (p = 0.06). Of note, disease status at the time of transplant, CR/VGPR versus partial remission did not appear to impact PR-OS. The median PR-OS was significantly longer in patients who received ibrutinib in the post-transplant setting compared to those who did not (NR vs. 18.4 months, 95%CI: 9.1-NR, p = 0.02). On univariable analysis, the presence of complex karyotype (RR = 4.87, 95% CI = 1.22-19.53) and a higher number of prior lines of therapy (RR = 1.81, 95% CI = 1.23-2.67) were associated with a significantly higher risk of relapse. This is the only study to date that evaluated outcomes of WM patients who relapsed following auto-HCT and provides a benchmark for future trials evaluating survival following auto-HCT relapse.

4.
Haematologica ; 2021 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-34758610

RESUMO

Standard of care (SOC) chimeric antigen receptor (CAR) T-cell therapies such as axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) are associated with multisystem toxicities. There is limited information available about cardiovascular (CV) events associated with SOC axi-cel or tisa-cel. Patients with CV comorbidities, organ dysfunction, or lower performance status were often excluded in the clinical trials leading to their FDA approval. An improved understanding of CV toxicities in the real-world setting will better inform therapy selection and management of patients receiving these cellular therapies. Here, we retrospectively reviewed the characteristics and outcomes of adult patients with relapsed/refractory large B-cell lymphoma treated with SOC axi-cel or tisa-cel. Among the 165 patients evaluated, 27 (16%) developed at least one 30-day Major adverse CV event (MACE). Cumulatively, these patients experienced 21 arrhythmias, 4 exacerbations of heart failure/cardiomyopathy, 4 cerebrovascular accidents, 3 myocardial infarctions (MI), and one patient died due to MI. Factors significantly associated with an increased risk of 30-d MACE included age ≥60 years, an earlier start of cytokine release syndrome (CRS), CRS ≥ grade 3, long duration of CRS, and use of tocilizumab. After a median follow-up time of 16.2 months (range 14.3-19.1), the occurrence of 30-d MACE was not significantly associated with progression-free survival (PFS) or with overall survival (OS). Our results suggest that the occurrence of 30-d MACE is more frequent among patients who are elderly, with early, severe, and prolonged CRS. However, with limited followup, larger prospective studies are needed, and multidisciplinary management of these patients is recommended.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34782260

RESUMO

Aggressive B-cell lymphomas including diffuse large B-cell lymphoma make up the majority of non-Hodgkin's lymphoma globally. While more than half of these patients can be cured with modern chemoimmunotherapy regimens, the outcomes of relapsed or refractory disease continue to be very poor. Despite significant developments in targeted cancer therapies and immuno-oncology, the attainability of a cure remained an elusive goal outside of incorporating high doses of chemotherapy followed by hematopoietic stem cell transplantation, for patients who have chemosensitive disease. The development of chimeric antigen receptor T-cell therapy changed that paradigm and introduced a new field of therapeutic possibilities for these patients. In this review, we will discuss the current state of this therapeutic modality in B-cell lymphomas and provide opinions on where future efforts need to focus in order to further improve their clinical utility.

6.
Semin Oncol Nurs ; 37(6): 151216, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34629213

RESUMO

OBJECTIVES: There is little research on the patient experience of symptom burden from CAR T-cell therapy, and no validated measure specific to the symptoms of CAR T-cell therapy currently exists. The purpose of this study was to identify symptoms experienced and to determine the content domain for a patient-reported outcome (PRO) measuring symptom burden for patients who had received standard of care CAR T-cell therapy for advanced B-cell lymphoid malignancies. DATA SOURCES: Semi-structured qualitative interviews were conducted with a sample of 21 patients who had received CAR T-cell therapy. Content analysis was used to define the symptom burden content domain. CONCLUSION: Sixty-two percent of patients were interviewed within 3 months of therapy; 81.0% experienced cytokine release syndrome and 28.6% experienced neurotoxicity. Content analysis found 31 symptoms related to disease and treatment. The most common disease-related symptom identified by patients was pain (43%). The most common symptoms identified by patients as related to CAR T-cell therapy included fatigue (tiredness) (62%), lack of appetite (29%), headache (29%), chills or feeling cold (24%), and feeling confused (24%). The qualitative analysis also confirmed that symptoms interfere with daily activities, work, walking, relationships with others, mood, and enjoyment of life. IMPLICATIONS FOR NURSING PRACTICE: Patients who receive standard CAR T-cell therapy experience numerous symptoms related to disease and CAR T-cell therapy, including symptoms related to the T-cell infusion. Symptoms may result in interference with daily activities, relationships, treatment adherence, and mood. Oncology nurses should be aware of and assess symptom related to CAR T-cell therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-34629467

RESUMO

Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN) is an aggressive hematological malignancy; however, some patients achieve durable remission with allogeneic hematopoietic cell transplantation (allo-HCT). We report on all 17 patients with BPDCN who underwent allo-HCT at our center between 2000 and 2020. The median age was 39 (18-67) years. All (n = 16, 94%), except one patient, had systemic disease involving bone marrow and/or other organs. Ten patients (59%) were in first complete remission (CR1) at allo-HCT. The donor source was matched related or unrelated in ten (59%) and alternate donor in seven (41%) patients. Five (31%) patients developed acute graft-versus-host disease (GVHD), all grade I-II. The cumulative incidence (CI) of chronic GVHD at five-year was 34%. The CI of non-relapse mortality at one-year was 29%. Progression-free survival (PFS) rates at two-year and five-year were 49% (95% CI = 22-71%) and 39% (95% CI = 14-64%), respectively. The two-year and five-year overall survival (OS) rates were 65% (95% CI = 38-82%) and 40% (95% CI = 12-68%), respectively. The five-year rate for both PFS and OS was 80% in CR1 patients versus 0% in patients not in CR1. In conclusion, allo-HCT provides long-lasting remissions in BPDCN patients, particularly when performed in CR1.

8.
Cancer Epidemiol ; 75: 102044, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34597882

RESUMO

PURPOSE: The population of adolescent and young adult (AYA, ages 15-39 years) diffuse large B-cell lymphoma (DLBCL) survivors is growing, however long-term overall survival patterns and disparities are largely unknown. METHODS: The current study utilized the Surveillance, Epidemiology, and End Results (SEER) registry to assess the impact of race/ethnicity, sex, socioeconomic status, and rurality on long-term survival in 5-year DLBCL survivors using an accelerated failure time model. RESULTS: Included were 4767 5-year survivors of AYA DLBCL diagnosed between the years 1980 and 2009 with a median follow-up time of 13.4 years. Non-Hispanic Black survivors had significantly worse long-term survival than non-Hispanic White survivors (Survival Time Ratio (STR): 0.53, p < 0.0001). Male sex (STR: 0.57, p < 0.0001) and older age at diagnosis were also associated with reduced long-term survival. There was no evidence that survival disparities improved over time. CONCLUSIONS: Racial disparities persist well into survivorship among AYA DLBCL survivors. Studies investigating specific factors associated with survival disparities are urgently needed to better address these disparities.

9.
Blood Adv ; 2021 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-34673903

RESUMO

Allogeneic transplant (alloHCT) and chimeric antigen receptor modified (CAR) T-cell therapy are potentially cuarative options of diffuse large B-cell lymphoma (DLBCL) relapsing after an autologous (auto) HCT. While the Center for International Blood and Marrow Transplant Research (CIBMTR) prognostic model can predict outcomes of alloHCT in DLBCL after autoHCT failure, corresponding models of CAR-T treatment in similar patient populations are not available. In this noncomparative registry analysis we report outcomes of DLBCL patients (≥18 years), undergoing a reduced intensity alloHCT or CAR-T therapy during 2012-2019, after a prior auto-HCT failure, and apply CIBMTR prognostic model to CAR-T recipients. 584 patients were included. The 1-year relapse, non-relapse mortality, overall survival (OS) and progression-free survival (PFS) for CAR-T treatment after autoHCT failure were were 39.5%, 4.8%, 73.4% and 55.7%, respectively. The corresponding rates in alloHCT cohort were 26.2%, 20.0%, 65.6% and 53.8%, respectively. The 1-year OS of alloHCT recipients classified as low-, intermediate- and high/very high-risk groups according to the CIBMTR prognostic score was 73.3%, 59.9%, and 46.3, respectively (p=0.002). The corresponding rates for low-, intermediate- and high/very high-risk CAR-T patients were 88.4%, 76.4%, and 52.8%, respectively (p<0.001). This registry analysis shows that both CAR-T and alloHCT can provide durable remissions in subset of DLBCL patients relapsing after a prior autoHCT. The simple, CIBMTR prognostic score can be used to identify patients at high risk of treatment failure after either procedure. Evaluation of novel relapse mitigations strategies after cellular immunotherapies are warranted in these high risk patients.

10.
Transplant Cell Ther ; 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34474166

RESUMO

Each year, more than 8000 allogeneic stem cell transplantations (allo-SCT) are performed in the United States, with approximately 30% of these patients age ≥60 years. Allo-SCT recipients are at increased risk for developing human papillomavirus (HPV)-related precancer or second malignancy. It is important to evaluate HPV-related precancer or second malignancy among allo-SCT recipients to develop or enhance screening and preventive practice guidelines to improve patients' survival and quality of life. In this retrospective matched case-control study, we estimated the cumulative incidence of HPV-related precancer or second malignancy in both male and female Medicare beneficiaries who underwent allo-SCT and compared it with the cumulative incidence in non-SCT controls and noncancer controls. Hematologic cancer patients age ≥18 years who underwent allo-SCT between 2002 and 2011 were matched 1:5 to non-SCT controls and to noncancer controls by age, sex, race/ethnicity, and duration of follow-up. Proportions of HPV-related precancer or second malignancy were estimated and compared between cases and controls using the chi-square test and logistic regression. Kaplan-Meier cumulative incidences were estimated and compared using log-rank tests. We identified 700 allo-SCT cases (median age, 64 years; median follow-up post-transplantation, 4.3 years) matched with 3159 non-SCT controls and 3302 noncancer controls. Approximately 3.7% of allo-SCT cases developed HPV-related precancer or second malignancy post-transplantation, compared with 1.9% of the non-SCT controls and 1.1% of the noncancer controls. The odds ratio of developing HPV-related precancer or second malignancy of allo-SCT cases compared with non-SCT controls and noncancer controls was 2.0 (95% confidence interval [CI], 1.25 to 3.18) and 3.5 (95% CI, 2.1 to 5.8), respectively. Both allo-SCT cases and non-SCT controls had significantly higher proportions and odds of developing HPV-related precancer or second malignancy compared with noncancer controls. The 5-year cumulative incidence in allo-SCT cases was 5%, compared with 2.1% in non-SCT controls and 1.2% in noncancer controls. The cumulative incidence of HPV-related precancer or second malignancy was statistically significantly higher in the allo-SCT than in either of the 2 matched control groups, and the non-SCT controls had a higher cumulative incidence of HPV-related precancer or second malignancy than the noncancer controls. The allo-SCT cases were at increased risk of developing HPV-related precancer or second malignancy compared with the non-SCT controls and noncancer controls. Routine screening of HPV-related precancer or second malignancy in allo-SCT recipients is needed to help prevent HPV-related precancer or second malignancy. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

11.
Bone Marrow Transplant ; 56(12): 2911-2921, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34413469

RESUMO

Autologous (auto-) or allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities for mantle cell lymphoma (MCL). Recently, chimeric antigen receptor (CAR) T-cell therapy received approval for MCL; however, its exact place and sequence in relation to HCT is unclear. The ASTCT, CIBMTR, and the EBMT, jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-, allo-HCT, and CAR T-cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated; in the first-line setting auto-HCT consolidation represents standard-of-care in eligible patients, whereas there is no clear role of allo-HCT or CAR T-cell therapy, outside of a clinical trial. In the R/R setting, the preferential option is CAR T-cell therapy especially in MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T-cell therapy has failed or is not feasible. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.

12.
Transplant Cell Ther ; 27(9): 720-728, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34452722

RESUMO

Autologous (auto-) and allogeneic (allo-) hematopoietic cell transplantation (HCT) are accepted treatment modalities in contemporary treatment algorithms for mantle cell lymphoma (MCL). Chimeric antigen receptor (CAR) T cell therapy recently received approval for MCL; however, its exact place and sequence in relation to HCT remain unclear. The American Society of Transplantation and Cellular Therapy, Center of International Blood and Marrow Transplant Research, and the European Society for Blood and Marrow Transplantation jointly convened an expert panel to formulate consensus recommendations for role, timing, and sequencing of auto-HCT, allo-HCT, and CAR T cell therapy for patients with newly diagnosed and relapsed/refractory (R/R) MCL. The RAND-modified Delphi method was used to generate consensus statements. Seventeen consensus statements were generated, with a few key statements as follows: in the first line setting, auto-HCT consolidation represents standard of care in eligible patients, whereas there is no clear role of allo-HCT or CAR T cell therapy outside of clinical trials. In the R/R setting, the preferential option is CAR T cell therapy, especially in patients with MCL failing or intolerant to at least one Bruton's tyrosine kinase inhibitor, while allo-HCT is recommended if CAR T cell therapy fails or is infeasible. Several recommendations were based on expert opinion, where the panel developed consensus statements for important real-world clinical scenarios to guide clinical practice. In the absence of contemporary evidence-based data, the panel found RAND-modified Delphi methodology effective in providing a formal framework for developing consensus recommendations for the timing and sequence of cellular therapies for MCL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Célula do Manto , Adulto , Medula Óssea , Humanos , Linfoma de Célula do Manto/terapia , Recidiva Local de Neoplasia , Condicionamento Pré-Transplante , Estados Unidos
13.
Transplant Cell Ther ; 27(11): 930.e1-930.e10, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34265479

RESUMO

Chimeric antigen receptor (CAR) T cell therapy is being increasingly used to treat patients with advanced hematologic malignancies; however, the symptoms related to standard of care CAR T cell therapy during the first year after treatment have not been assessed using patient-reported outcome (PRO) measurements. This study aimed to quantify patients' perspectives of symptom burden and functional status using PROs during the first year after CAR T cell therapy for hematologic malignancies, especially in patients who experienced grade 2-4 toxicities. Sixty patients were enrolled in this observational cross-sectional study at any time during their first 12 months post-treatment. All 60 had received CAR T cell therapy as standard of care at MD Anderson Cancer Center in 2019. PROs were measured using the MD Anderson Symptom Inventory (MDASI), the PROs Measurement Information System 29 (PROMIS-29), the global health tool EQ5D-5L, and the single-item health-related quality of life scale (HRQoL). Twenty-two additional symptoms related to CAR T cell therapy, as identified by an expert panel, were also evaluated. CAR T cell therapy-related toxicities were rated according to the ASTCT consensus grading criteria. The majority of patients (52 of 60; 87%) received axicabtagene ciloleucel (Yescarta). One-third of the patients developed grade 2-4 cytokine release syndrome or neurotoxicity. The first 90 days after infusion represented the most symptomatic period, in which >10% of patients rated 18 symptoms as severe (ie, MDASI symptom score of 7 to 10 on scale of 0 to 10), strongly indicating the need for effective symptom management. Physical functioning, measured by interference on the "general activity" item on the MDASI and this domain on the PROMIS-29, were significantly worse in patients who underwent therapy during the first 30 days compared with those who underwent therapy over 90 days (all P < .05 with the Hochberg step-up procedure), whereas the EQ5D-5L and single-item HRQoL did not detect such differences. Compared with patients who had mild cytokine release syndrome or neurotoxicity (grade 0-1), patients who developed grade 2-4 toxicities persistently reported multiple severe symptoms after 30 days following therapy (all P < .05). Furthermore, although using a different recall period, patient-reported scores on several PROMIS-29 domains were significantly correlated with the scores of corresponding MDASI symptom items. This real-world quantitative PRO symptoms study provides evidence of unique profiles of the physical, psychological, and cognitive symptom burden in patients undergoing CAR T cell therapy that varies within the first year after infusion and demonstrates differences among PRO measurement scales. These results support the need for validation of fit-for-purpose PRO measurements for routinely monitoring symptom and toxicity burdens in CAR T cell therapy care settings.

14.
Blood Adv ; 5(14): 2799-2806, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34264268

RESUMO

The Endothelial Activation and Stress Index (EASIX) score, defined as [(creatinine × lactate dehydrogenase [LDH])/platelets], is a marker of endothelial activation that has been validated in the allogeneic hematopoietic stem cell transplant setting. Endothelial activation is one of the mechanisms driving immune-mediated toxicities in patients treated with chimeric antigen receptor-T (CAR-T)-cell therapy. This study's objective was to evaluate the association between EASIX and other laboratory parameters collected before lymphodepletion and the subsequent onset of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) those patients. Toxicity data were collected prospectively on 171 patients treated with axicabtagene ciloleucel (axi-cel) for large B-cell lymphoma (LBCL). CRS grades 2 to 4 were diagnosed in 81 (47%) patients and ICANS grades 2 to 4 in 84 (49%). EASIX combined with ferritin (EASIX-F) identified 3 risk groups with CRS grades 2 to 4 cumulative incidence of 74% (hazards ratio [HR], 4.8; 95% confidence interval [CI], 2.1-11; P < .001), 49% (HR, 2.3; 95% CI, 1.02-5; P = .04), and 23% (reference), respectively. EASIX combined with CRP and ferritin (EASIX-FC) identified 3 risk groups with an ICANS grade 2 to 4 cumulative incidence of 74% (HR, 3.6; 95% CI, 1.9-6.9; P < .001), 51% (HR, 2.1; 95% CI, 1.1-3.9; P = .025), and 29% (reference). Our results indicate that common laboratory parameters before lymphodepletion correlate with CAR-T-related toxicities and can help support clinical decisions, such as preemptive toxicity management, hospitalization length, and proper setting for CAR-T administration.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Síndrome da Liberação de Citocina , Ferritinas , Humanos
15.
Cancer Epidemiol Biomarkers Prev ; 30(9): 1717-1725, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34244160

RESUMO

BACKGROUND: Although there are growing numbers of adolescent and young adult (AYA) Hodgkin lymphoma (HL) survivors, long-term overall survival (OS) patterns and disparities in this population are underreported. The aim of the current study was to assess the impact of race/ethnicity, socioeconomic status (SES), rurality, diagnosis age, sex, and HL stage over time on long-term survival in AYA HL survivors. METHODS: The authors used the Surveillance, Epidemiology, and End Results (SEER) registry to identify survivors of HL diagnosed as AYAs (ages 15-39 years) between the years 1980 and 2009 and who were alive 5 years after diagnosis. An accelerated failure time model was used to estimate survival over time and compare survival between groups. RESULTS: There were 15,899 5-year survivors of AYA HL identified, with a median follow-up of 14.4 years and range up to 33.9 years from diagnosis. Non-Hispanic black survivors had inferior survival compared with non-Hispanic white survivors [survival time ratio (STR): 0.71, P = 0.002]. Male survivors, older age at diagnosis, those diagnosed at higher stages, and those living in areas of higher SES deprivation had unfavorable long-term survival. There was no evidence of racial or sex-based survival disparities changing over time. CONCLUSIONS: Racial, SES, and sex-based disparities persist well into survivorship among AYA HL survivors. IMPACT: Disparities in long-term survival among AYA HL survivors show no evidence of improving over time. Studies investigating specific factors associated with survival disparities are needed to identify opportunities for intervention.

16.
JAMA Oncol ; 7(7): 993-1003, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-33956047

RESUMO

Importance: Primary central nervous system lymphoma (PCNSL) requires induction and consolidation to achieve potential cure. High-dose therapy and autologous hematopoietic cell transplant (AHCT) is an accepted and effective consolidation strategy for PCNSL, but no consensus exists on the optimal conditioning regimens. Objective: To assess the outcomes in patients with PCNSL undergoing AHCT with the 3 most commonly used conditioning regimens: thiotepa/busulfan/cyclophosphamide (TBC), thiotepa/carmustine (TT-BCNU), and carmustine/etoposide/cytarabine/melphalan (BEAM). Design, Setting, and Participants: This observational cohort study used registry data from the Center for International Blood and Marrow Transplant Research registry. The Center is a working group of more than 380 transplantation centers worldwide that contributed detailed data on HCT to a statistical center at the Medical College of Wisconsin, Milwaukee. The participant data were from 603 adult patients with PCNSL who underwent AHCT as initial, or subsequent, consolidation between January 2010 and December 2018. Patients were excluded if they had a non-Hodgkin lymphoma subtype other than diffuse large B-cell lymphoma, systemic non-Hodgkin lymphoma, or HIV; received an uncommon conditioning regimen; or were not in partial remission or complete remission prior to AHCT. Statistical analysis was performed from July 5, 2020, to March 1, 2021. Interventions: Patients received 1 of 3 conditioning regimens: TBC (n = 263), TT-BCNU (n = 275), and BEAM (n = 65). Main Outcomes and Measures: The primary outcome was progression-free survival. Secondary outcomes included hematopoietic recovery, incidence of relapse, nonrelapse mortality, and overall survival. Results: Of 603 patients, the mean age was 57 (range, 19-77) years and 318 (53%) were male. The 3-year adjusted progression-free survival rates were higher in the TBC cohort (75%) and TT-BCNU cohort (76%) compared with the BEAM cohort (58%) (P = .03) owing to a higher relapse risk in the BEAM cohort (hazard ratio [HR], 4.34; 95% CI, 2.45-7.70; P < .001). In a multivariable regression analysis, compared with the TBC cohort, patients who received TT-BCNU had a higher relapse risk (HR, 1.79; 95% CI, 1.07-2.98; P = .03), lower risk of nonrelapse mortality (NRM) (HR, 0.50; 95% CI, 0.29-0.87; P = .01), and similar risk of all-cause mortality more than 6 months after HCT (HR, 1.54; 95% CI, 0.93-2.55; P = .10). Age of 60 years or older, Karnofsky performance status less than 90, and an HCT-comorbidity index greater than or equal to 3 were associated with lower rates of survival across all 3 cohorts. Subgroup analyses demonstrated that patients aged 60 years and older had considerably higher NRM with TBC. Conclusions and Relevance: In this cohort study, thiotepa-based conditioning regimen was associated with higher rates of survival compared with BEAM, despite higher rates of early toxic effects and NRM; these findings may assist clinicians in choosing between TBC or TT-BCNU based on patient and disease characteristics.

17.
Leuk Lymphoma ; 62(10): 2400-2407, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-33942701

RESUMO

This study aimed to assess the prognostic value of baseline disease distribution for patients with the secondary central nervous system (CNS) diffuse large B-cell lymphoma (DLBCL) treated with chemotherapy and radiation (RT). 44 patients with secondary CNS DLBCL were reviewed. Twenty patients had leptomeningeal disease (LMD), and 24 had localized/targetable disease (LTD). Of 8 patients who received stem cell transplantation (SCT) after RT, 6 had LTD with a complete or partial response after RT. Median time to CNS relapse after RT was 10.1 months; 3/24 patients with LTD and 5/15 with LMD had CNS relapse. The median overall survival (OS) was 8 and 20 months for patients with LMD and LTD, respectively (p = 0.20). On multivariable analysis, LTD, receipt of SCT, and response after RT were associated with better OS and CNS-disease-free survival. Patients with localized secondary CNS DLBCL may benefit from RT serving as a bridge to SCT.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma Difuso de Grandes Células B , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Sistema Nervoso Central , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Neoplasias do Sistema Nervoso Central/terapia , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/terapia , Recidiva Local de Neoplasia , Prognóstico , Estudos Retrospectivos
18.
Haematologica ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33951890

RESUMO

High-dose chemotherapy and autologous stem-cell transplant (HDC/ASCT) is standard treatment of chemosensitive relapsed classical Hodgkin lymphoma (cHL), although outcomes of high-risk relapse (HRR) patients remain suboptimal. We retrospectively analyzed all HRR cHL patients treated with HDC/ASCT at our institution between 01/01/2005-12/31/2019. HRR criteria included primary refractory disease/relapse within 1 year, extranodal extension, B symptoms, requiring > 1 salvage line, or PET+ disease at ASCT. All patients met the same ASCT eligibility criteria. We treated 501 patients with BEAM (N=146), BuMel (N=38), GemBuMel (N=189) and vorinostat/GemBuMel (N=128). The GemBuMel and vorinostat/GemBuMel cohorts had more HRR criteria and more patients with PET+ disease at ASCT. Pre-ASCT BV, anti-PD1, PET-negative disease at ASCT, and maintenance BV increased over time. BEAM and BuMel predominated in earlier years (2005-2007), GemBuMel and BEAM in middle years (2008-2015), and vorinostat/GemBuMel and BEAM in later years (2016-2019). Median follow-up is 50 months (6-186). Outcomes improved over time, with 2-year PFS/OS rates of 58%/82% (2005-2007), 59%/83% (2008-2011), 71%/94% (2012-2015) and 86%/99% (2016-2019) (P.

19.
Transplant Cell Ther ; 27(5): 404.e1-404.e5, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965178

RESUMO

The cell of origin (COO) classification into germinal center B cell (GCB) and non-GCB types has been shown to predict survival outcomes in newly diagnosed diffuse large B cell lymphoma (DLBCL). In the relapsed/refractory (R/R) setting, there is building evidence that COO does not predict prognosis after high-dose chemotherapy and autologous stem cell transplantation (auto-SCT). The present analysis aimed to compare survival outcomes based on COO classification in R/R DLBCL patients who underwent auto-SCT. This retrospective study included adult patients with R/R DLBCL who underwent auto-SCT at MD Anderson Cancer Center between January 2007 and December 2016. The Hans algorithm using CD10, BCL6, and MUM1 markers was used to classify patients by COO. A total of 122 patients with DLBCL (71 GCB, 51 non-GCB) were included in the analysis. There were no significant differences in patient characteristics between the 2 groups, except for older median age in the GCB cohort (64 years versus 58 years; P < .004). The median overall survival (OS) time was 68.5 (95% confidence interval [CI], 51.3 to not reached) months for the total population, 68.5 (95% CI, 44.8 to not reached) for GCB, and not reached for non-GCB. The 3-year OS rate was 0.659 (95% CI, 0.575 to 0.755) for the total population, 0.653 (95% CI, 0.547 to 0.779) for GCB, and 0.666 (95% CI, 0.537 to 0.824) for non-GCB. When adjusted for age and other factors of interest, no statistically significant associations for OS or progression-free survival were observed between the 2 cohorts. Our results confirm that COO loses its prognostic potential in patients with R/R DLBCL who receive high-dose chemotherapy followed by auto-SCT and both GCB and non-GCB types of DLBCL derive similar benefit from auto-SCT. Younger age, female sex, and pretransplantation disease status were associated with better OS.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma Difuso de Grandes Células B , Adulto , Feminino , Centro Germinativo , Humanos , Linfoma Difuso de Grandes Células B/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Autólogo
20.
Transplant Cell Ther ; 27(5): 430.e1-430.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965187

RESUMO

Prolonged thrombocytopenia occurs in up to 37% of patients after hematopoietic stem cell transplantation (HSCT) and is associated with adverse prognosis and increased risk of bleeding. Eltrombopag, a thrombopoietin receptor agonist, can increase platelet counts in thrombocytopenic patients. We conducted a phase II study, adaptively randomizing patients at ≥35 days post-HSCT to receive placebo or eltrombopag at a platelet count ≤20,000/µL for 7 days or platelet transfusion-dependent and a neutrophil count ≥1500/µL. Sixty patients were randomized to eltrombopag (n = 42) or placebo (n = 18) and received at least 1 dose. Fifteen patients (36%) in the eltrombopag arm achieved a platelet count of ≥30,000/µL, compared with 5 patients (28%) in the placebo arm, with a posterior probability of 0.75. (The protocol required this probability to be >0.975 to declare a winner; thus, the results are inconclusive.) However, 9 patients (21%) in the eltrombopag arm achieved a platelet count of ≥50,000/µL, compared with no patients in the placebo arm (P = .046). The overall survival, progression-free survival, relapse rate, and nonrelapse mortality were similar in the 2 arms. In conclusion, compared with placebo, treatment with eltrombopag led to a higher percentage of patients achieving a platelet count of ≥50,000/µL in patients with persistent thrombocytopenia after HSCT.


Assuntos
Recidiva Local de Neoplasia , Trombocitopenia , Benzoatos/uso terapêutico , Humanos , Hidrazinas/uso terapêutico , Pirazóis , Trombocitopenia/tratamento farmacológico
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