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ABSTRACT: Recent studies demonstrating the feasibility of outpatient chimeric antigen receptor (CAR)-modified T-cell therapy administration are either restricted to CARs with 41BB costimulatory domains or use intensive at-home monitoring. We report outcomes of outpatient administration of all commercially available CD19- and B-cell maturation antigen (BCMA)-directed CAR T-cell therapy using a strategy of no remote at-home monitoring and an early cytokine release syndrome (CRS) intervention strategy. Patients with hematologic malignancies who received CAR T-cell therapy in the outpatient setting during 2022 to 2023 were included. Patients were seen daily in the cancer center day hospital for the first 7 to 10 days and then twice weekly through day 30. The primary end point was to determine 3-, 7-, and 30-day post-CAR T-cell infusion hospitalizations. Early CRS intervention involved administering tocilizumab as an outpatient for grade ≥1 CRS. Fifty-eight patients received outpatient CAR T-cell infusion (33 myeloma, 24 lymphoma, and 1 acute lymphoblastic leukemia). Of these, 17 (41%), 16 (38%), and 9 patients (21%) were admitted between days 0 to 3, 4 to 7, and 8 to 30 after CAR T-cell infusion, respectively. The most common reason for admission was CAR T-cell-related toxicities (33/42). Hospitalization was prevented in 15 of 35 patients who received tocilizumab for CRS as an outpatient. The nonrelapse mortality rates were 1.7% at 1 month and 3.4% at 6 months. In conclusion, we demonstrate that the administration of commercial CAR T-cell therapies in an outpatient setting is safe and feasible without intensive remote monitoring using an early CRS intervention strategy.
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Imunoterapia Adotiva , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Feminino , Pessoa de Meia-Idade , Masculino , Adulto , Idoso , Síndrome da Liberação de Citocina/etiologia , Síndrome da Liberação de Citocina/terapia , Pacientes Ambulatoriais , Neoplasias Hematológicas/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Resultado do Tratamento , Anticorpos Monoclonais Humanizados/uso terapêuticoRESUMO
ABSTRACT: Progression of myeloproliferative neoplasms (MPNs) to accelerated or blast phase is associated with poor survival outcomes. Since 2017 there have been several therapies approved for use in acute myeloid leukemia (AML); these therapies have been incorporated into the management of accelerated/blast-phase MPNs (MPN-AP/BP). We performed a multicenter analysis to investigate outcomes of patients diagnosed with MPN-AP/BP in 2017 or later. In total, 202 patients were identified; median overall survival (OS) was 0.86 years. We also analyzed patients based on first-line treatment; the 3 most common approaches were intensive chemotherapy (n = 65), DNA methyltransferase inhibitor (DNMTi)-based regimens (n = 65), and DNMTi + venetoclax-based regimens (n = 54). Median OS was not significantly different by treatment type. In addition, we evaluated response by 2017 European LeukemiaNet AML criteria and 2012 MPN-BP criteria in an effort to understand the association of response with survival outcomes. We also analyzed outcomes in 65 patients that received allogeneic hematopoietic stem cell transplant (allo-HSCT); median OS was 2.30 years from time of allo-HSCT. Our study demonstrates that survival among patients with MPN-AP/BP is limited in the absence of allo-HSCT even in the current era of therapeutics and underscores the urgent need for new agents and approaches.
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Transtornos Mieloproliferativos , Humanos , Transtornos Mieloproliferativos/terapia , Transtornos Mieloproliferativos/mortalidade , Transtornos Mieloproliferativos/tratamento farmacológico , Feminino , Pessoa de Meia-Idade , Masculino , Idoso , Adulto , Resultado do Tratamento , Transplante de Células-Tronco Hematopoéticas , Idoso de 80 Anos ou mais , Crise Blástica/terapia , Crise Blástica/mortalidade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute's surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information. Our results showed that median OS significantly improved over time [7.8 years (2000-2005), 9.1 years (2006-2013), and not reached (2014-2018) (p < 0.001)]. Compared to diagnosis in 2014-2018, diagnosis in earlier periods was associated with higher mortality risk (2000-2005-HR 1.32, 95 % CI 1.28-1.37, p < 0.001: 2006-2013-HR 1.09, 95 % CI 1.06-1.13, p < 0.001). Lower mortality risk was seen in patients age < 85 years whereas median household income of <$75000 was associated with higher mortality. Our study provides real-world data suggesting a possible multifactorial contribution to improvement in survival, including availability of novel agents, better monitoring, and supportive care. They also show discrepancies in overall survival for CLL/SLL patients due to socioeconomic status and demographic factors.
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Leucemia Linfocítica Crônica de Células B , Programa de SEER , Humanos , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/epidemiologia , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto , Sistema de Registros , Taxa de Sobrevida , Estados Unidos/epidemiologia , Resultado do TratamentoRESUMO
Disease relapse remains a major barrier to success after allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic neoplasms (MDS). While certain high risk genomic alterations are associated with increased risk of relapse, there is a lack of clinically applicable tools to analyze the downstream cellular events that are associated with relapse. We hypothesized that unique proteomic signatures in MDS patients undergoing allo-HCT could serve as a tool to understand this aspect and predict relapse. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified 52 MDS patients who underwent allo-HCT and analyzed their proteomic profile from pretransplant blood samples in a matched case-control design. Twenty-six patients without disease relapse after allo-HCT (controls) were matched with 26 patients who experienced relapse (cases). Proteomics assessment was conducted using the Slow Off-rate Modified Aptamers (SOMAmer) based assay. In gene set enrichment analysis, we noted that expression in the hallmark complement, and hallmark allograft rejection pathways were statistically enriched among patients who had disease relapse post-transplant. In addition, correlation analyses showed that methylation array probes in cis- and transcription regulatory elements of immune pathway genes were modulated and differentially sensitize the immune response. These findings suggest that proteomic analysis could serve as a novel tool for prediction of relapse after allo-HCT in MDS.
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Allogeneic hematopoietic cell transplantation (alloHCT) provides cure for older patients with acute myeloid leukemia (AML); however, disease relapse remains a major concern. Based on recent data suggesting that younger donor age confers the greatest benefit for alloHCT with matched unrelated donors (MUDs), we attempted to answer a practical question: which donor type provides the best outcomes when an older patient with AML has a matched sibling donor (MSD, also older) versus the best MUD? This retrospective cohort registry study accessed data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients with AML age ≥ 50 years undergoing alloHCT from older MSDs (age ≥ 50 years) or younger MUDs (age ≤ 35 years) between 2011 and 2018. The study included common allograft types, conditioning regimens, and graft-versus-host disease (GVHD) prophylaxis. The primary outcome was relapse risk. Secondary outcomes included nonrelapse mortality (NRM), GVHD, disease-free survival (DFS), and overall survival. Among 4684 eligible patients, 1736 underwent alloHCT with an older MSD (median donor age, 60 years), and 2948 underwent alloHCT from a younger MUD (median donor age, 25 years). In multivariable analysis, compared to older MSDs, the use of younger MUDs conferred a decreased relapse risk (hazard ratio [HR], .86; P = .005) and a significantly lower adjusted 5-year cumulative incidence of relapse (35% versus 41%; P = .003), but was associated with an increased risk for chronic GVHD (HR, 1.18; 95% confidence interval [CI], 1.08 to 1.29; P = .0002) and greater NRM only in the earlier period of 2011 to 2015 (HR, 1.24; P = .016). The corresponding NRM rates were significantly lower in the more recent period of 2016 to 2018 (HR, .78; P = .017). The adjusted 5-year DFS probability was 44% (95% CI, 42% to 46%) with an alloHCT from younger MUDs compared to 41% (95% CI, 38% to 43%) with older MSDs (P = .04). In summary, for older patients with AML undergoing alloHCT, the use of younger MUDs is associated with decreased relapse risk and improved DFS compared with the use of older MSDs.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Idoso , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Leucemia Mieloide Aguda/terapia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , RecidivaRESUMO
The availability of novel targeted agents has revolutionized the management of chronic lymphocytic leukemia (CLL). Both B-cell lymphoma 2 (BCL2) and Bruton tyrosine kinase (BTK) inhibitors are highly effective agents for CLL treatment. Several clinical trials have demonstrated the efficacy and safety of these agents in the management of newly diagnosed and relapsed/refractory CLL. This has led to two broad approaches in the frontline management of CLL, namely venetoclax-based time-limited therapy versus BTK inhibitor-based continuous therapy. In this review, we discussed why we consider venetoclax-based therapy as a suitable frontline option for patients with CLL.
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Antineoplásicos , Leucemia Linfocítica Crônica de Células B , Linfoma de Células B , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas/uso terapêuticoRESUMO
Allogeneic hematopoietic cell transplantation (allo-HCT) is a potentially curative treatment for acute myeloid leukemia (AML) and acute lymphoblastic leukemia (ALL). While many factors influence the outcomes of allo-HCT, the independent impact of donor-recipient ABO mismatching remains unclear. Using the Center for International Blood and Marrow Transplant Research (CIBMTR) database, we identified patients aged ≥18 years with AML or ALL who underwent allo-HCT between 2008 and 2018. Our objectives were to analyze the outcomes of allo-HCT based on the donor-recipient ABO status (match, minor mismatch, major mismatch, bidirectional mismatch). Among 4946 eligible patients, 2741 patients (55.4%) were ABO matched, 1030 patients (20.8%) had a minor ABO mismatch, 899 patients (18.1%) had a major ABO mismatch, and 276 patients (5.6%) had a bidirectional ABO mismatch. In multivariable analyses, compared to ABO matched allo-HCT, the presence of a major ABO mismatch was associated with worse overall survival (HR 1.16, 95% CI 1.05-1.29; p = 0.005), inferior platelet engraftment (HR 0.83, 95% CI 0.77-0.90; p < 0.001), and higher primary graft failure (HR 1.60, 95% CI 1.12-2.30, p = 0.01). Relapse, acute graft versus host disease (GVHD) grades III-IV and chronic GVHD were not significantly associated with ABO status. While donor age was not significantly associated with outcomes, older recipient age was associated with worse survival and non-relapse mortality. Our study demonstrates that donor-recipient ABO status is independently associated with survival and other post-transplantation outcomes in acute leukemia. This underscores the importance of considering the ABO status in donor selection algorithms and its impact in acute leukemia.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Adolescente , Adulto , Leucemia Mieloide Aguda/terapia , Transplante de Medula Óssea , Medula Óssea , Doença Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Doença Enxerto-Hospedeiro/etiologia , Estudos Retrospectivos , Condicionamento Pré-TransplanteRESUMO
BACKGROUND: Although the clinical outcomes of patients with TP53-mutated acute myeloid leukemia (AML) are dismal, subsets of patients eligible for curative-intent therapies may fare better. Because racial disparities are known to affect outcome in hematologic malignancies, the authors sought to explore disparities among patients with TP53-mutated AML. METHODS: A multicenter, retrospective study was conducted in a cohort of 340 patients who had TP53-mutated AML (275 non-Hispanic White [NHW] and 65 non-Hispanic Black [NHB]) to analyze differences in treatment and outcome among NHW and NHB patients. RESULTS: The median patient age was comparable between NHW and NHB patients (p = .76). A higher proportion of NHB patients had therapy-related AML (31% vs. 20%; p = .08) and had co-mutations (74% vs. 61%; p = .06). A higher proportion of NHW patients received intensive chemotherapy compared with NHB patients (47% vs. 31%; p = .02). Conversely, a higher proportion of NHB patients received low-intensity chemotherapy (9% vs. 5.5%; p = .02) or best supportive care (22% vs. 7%; p < .001). The complete response rate (including complete responses with or without complete count recovery) was 31% versus 24.5% (p = .39) in NHW and NHB patients, respectively. Only 5% of NHB patients received allogeneic stem cell transplantation compared with 15.5% of NHW patients (p = .02). The proportion of patients who were event-free (18.5% vs. 8.5%; p = .49) or who remained alive (24.9% vs. 8.3%; p = .13) at 18 months was numerically higher in NHW versus NHB patients, respectively, but was not statistically significant. CONCLUSIONS: The current study highlights disparities between NHW and NHB patients with TP53-mutated AML. Efforts are warranted to eliminate treatment disparities in minority populations.
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Disparidades em Assistência à Saúde , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética , População Branca/genética , População Negra/genéticaRESUMO
The management of chronic myeloid leukemia (CML) has remarkably changed in the last 20 years with the availability of tyrosine kinase inhibitors (TKI). Most patients with chronic phase CML now have a life expectancy like that of age matched controls. Understanding the practical aspects of choosing the appropriate TKI, monitoring response and side-effects are key to long term success. Currently, treatment cessation is also an option in patients achieving sustained deep molecular response. Novel agents are needed in patients with lack of response to TKI and in those with advanced disease.
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IMPORTANCE: Matched sibling donors (MSDs) are preferred for allogeneic hematopoietic cell transplantation (allo-HCT) in myelodysplastic syndrome even if they are older. However, whether older MSDs or younger human leukocyte antigen-matched unrelated donors (MUDs) are associated with better outcomes remains unclear. OBJECTIVE: To investigate whether allo-HCT for myelodysplastic syndrome using younger MUDs would be associated with improved disease-free survival and less relapse compared with older MSDs. DESIGN, SETTING, AND PARTICIPANTS: This retrospective cohort study assessed data reported to the Center for International Blood and Marrow Transplant Research database from 1761 adults 50 years or older with myelodysplastic syndrome who underwent allo-HCT using an older MSD or younger MUD between January 1, 2011, and December 31, 2017, with a median follow-up of 48 months. Data analysis was performed from January 8, 2019, to December 30, 2020. INTERVENTIONS/EXPOSURES: Allo-HCT from an older MSD (donor age ≥50 years) or a younger MUD (donor age ≤35 years). MAIN OUTCOMES AND MEASURES: The primary outcome was disease-free survival. Secondary outcomes were overall survival, relapse, nonrelapse mortality, acute graft-vs-host disease (GVHD), chronic GVHD, and GVHD-free relapse-free survival. RESULTS: Of 1761 patients (1162 [66%] male; median [range] age, 64.9 [50.2-77.6] years in the MSD cohort and 66.5 [50.4-80.9] years in MUD cohort), 646 underwent allo-HCT with an older MSD and 1115 with a younger MUD. In multivariable analysis, the rate of disease-free survival was significantly lower in allo-HCTs with older MSDs compared with younger MUDs (hazard ratio [HR], 1.17; 95% CI, 1.02-1.34; P = .02), whereas the difference in overall survival rate of allo-HCT with younger MUDs vs older MSDs was not statistically significant (HR, 1.13; 95% CI, 0.98-1.29; P = .07). Allo-HCT with older MSDs was associated with significantly higher relapse (HR, 1.62; 95% CI, 1.32-1.97; P < .001), lower nonrelapse mortality (HR, 0.76; 95% CI, 0.59-0.96; P = .02), lower acute GVHD (HR, 0.52; 95% CI, 0.42-0.65; P < .001), chronic GVHD (HR, 0.77; 95% CI, 0.64-0.92; P = .005), and a lower rate of GVHD-free relapse-free survival beyond 12 months after allo-HCT (HR, 1.42; 95% CI, 1.02-1.98; P = .04). CONCLUSIONS AND RELEVANCE: This cohort study found higher disease-free survival and lower relapse for allo-HCT in myelodysplastic syndrome using younger MUDs compared with older MSDs. The risk of nonrelapse mortality and GVHD was lower with older MSDs. These results suggest that the use of younger MUDs should be considered in the donor selection algorithm for myelodysplastic syndrome, in which it is pivotal to minimize relapse given limited treatment options for managing relapsed disease.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Adulto , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Recidiva Local de Neoplasia , Estudos Retrospectivos , Irmãos , Condicionamento Pré-Transplante/métodos , Doadores não RelacionadosRESUMO
We compared the outcomes of salvage chemotherapy in 146 patients with relapsed (57.5%) or refractory (42.5%) AML who received CLAG-M (51%), MEC (39%) or CLAG (10%). Minimal residual disease (MRD) was assessed by flow cytometry. Bivariate, Kaplan-Meier, and Cox regression analyses were conducted. Complete remission (CR) rate of 46% (CLAG-M 54% versus MEC/CLAG 40%, p = .045) was observed with MRD-negative CR of 33% (CLAG-M 39% versus MEC/CLAG 22%, p = .042). Median overall survival (OS) was 9.7 months; the longest OS occurred with CLAG-M (13.3, 95%CI 2.4-24.3) versus MEC (6.9, 95%CI 2.9-10.9) or CLAG (6.2, 95%CI 2.4-12.6) (p = .025). When adjusted for age, gender, relapsed/refractory AML, poor risk AML, MRD, chemotherapy and transplant, CLAG-M (HR 0.63, 95% CI 0.40-0.98, p = .042), MRD-negativity (HR 0.15, 95% CI 0.07-0.30, p < .001) and transplant (HR 0.22, 95% CI 0.13-0.39, p < .001) were associated with higher OS. Our findings confirm that CLAG-M is a reasonable salvage regimen for RR-AML followed by transplant.
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Citarabina , Leucemia Mieloide Aguda , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cladribina/uso terapêutico , Citarabina/uso terapêutico , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasia Residual , Prognóstico , Indução de Remissão , Terapia de SalvaçãoRESUMO
OBJECTIVE: To determine whether the population level outcomes of pediatric acute promyelocytic leukemia have improved over time. STUDY DESIGN: We conducted a retrospective analysis of the Surveillance Epidemiology and End Results database for patients with acute promyelocytic leukemia, up to 20 years of age, diagnosed between 1976 and 2016 and actively followed. Patients were stratified based on their period of diagnosis (1976-1989, 1990-1999, 2000-2009, 2010-2016) to assess the temporal trends in overall survival and early mortality. RESULTS: A total of 553 patients with a median age of 15 years (range, 0-20 years) were included. The 5-year overall survival increased significantly over time (by 22.6% from 1976 to 1989; by 59.2% from 1990 to 1999; by 77.7% from 2000 to 2009; and by 88.9% from 2010 to 2016; P < .001). Early mortality showed an improvement over time in the most recent cohort (by 14% from 1976 to 1989; by 13.5% from1990 to 1999; by 13.3% 2000 to 2009; and by 7.2% from 2010 to 2016) after adjusting for other demographic characteristics in a logistic regression model. On multivariate analysis of overall survival, diagnosis in the earlier time periods was associated with higher mortality as compared with the 2010-2016 period. Age, sex, and race/ethnicity were not significant predictors of overall survival. CONCLUSIONS: Outcomes of pediatric acute promyelocytic leukemia have continued to improve over time at the population level.
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Etnicidade , Leucemia Promielocítica Aguda/etnologia , Programa de SEER , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Morbidade/tendências , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Estados Unidos/epidemiologia , Adulto JovemAssuntos
Antitrombinas/administração & dosagem , Asparaginase/administração & dosagem , Polietilenoglicóis/administração & dosagem , Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombose Venosa , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Trombose Venosa/tratamento farmacológico , Trombose Venosa/etiologiaRESUMO
BACKGROUND: Outcomes of acute promyelocytic leukemia (APL) have significantly improved with the availability of targeted agents. It remains unclear whether the population-level outcomes of APL have improved over time. METHODS: Using the SEER database, we identified patients aged ≥20 years with pathologically confirmed APL diagnosed in 2000 through 2014 and who were actively followed. Patients were stratified by diagnosis period into 3 groups (2000-2004, 2005-2009, and 2010-2014) to assess the temporal trends in overall survival (OS), cause-specific survival (CSS), and other outcomes. RESULTS: A total of 2,962 patients with a median age of 48 years (range, 20-96 years) were included. Hispanic patients constituted 21.5% of the cohort and the largest proportion (47.9%) of uninsured patients. The incidence of APL was 0.33 cases per 100,000 population per year. Incidence varied significantly by age, sex, race/ethnicity, and diagnosis period. Survival was significantly higher for patients diagnosed in 2010 through 2014 compared with those diagnosed in 2005 through 2009 and in 2000 through 2004 (4-year OS, 73.4% vs 65.6% vs 57.3%, respectively; 4-year CSS, 78.3% vs 70.8% vs 60.8%, respectively). Early mortality improved significantly over time (2000-2004, 25.3%; 2005-2009, 20.6%; 2010-2014, 17.1%) and was higher in men and Hispanic patients. According to multivariate analysis, diagnosis before 2010 and unmarried status were associated with a higher mortality risk. Uninsured patients had a significantly higher early mortality without a significant difference in post-30-day CSS. No significant changes were noted in risk of secondary malignancies. CONCLUSIONS: Population-level outcomes of APL have continued to improve over time. However, significant discrepancies in disease outcomes continue to exist, highlighting the need for more research.
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Biomarcadores Tumorais/análise , Leucemia Promielocítica Aguda/terapia , Segunda Neoplasia Primária/epidemiologia , Cuidados Paliativos/métodos , Terapia de Salvação/métodos , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/antagonistas & inibidores , Feminino , Seguimentos , Humanos , Incidência , Estimativa de Kaplan-Meier , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Terapia de Alvo Molecular/métodos , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Programa de SEER/estatística & dados numéricos , Fatores Sexuais , Estados Unidos/epidemiologia , Adulto JovemRESUMO
BACKGROUND: Advanced-stage Hodgkin lymphoma (HL) is a curable malignancy, although outcomes remain poor in certain patients. It remains unclear if recent advances have improved their population-level survival over time. MATERIALS AND METHODS: Using the Surveillance, Epidemiology, and End Results database, we identified patients aged ≥18 years with stage III or IV classical HL as the first primary malignancy, diagnosed between 2000 and 2014 and treated with chemotherapy. Patients were stratified by date of diagnosis into three groups (2000-2004, 2005-2009, 2010-2014) to assess the trends in overall survival (OS). RESULTS: A total of 9,042 patients with a median age of 41 years were included. The use of frontline radiation therapy decreased in each period (21.3% [2000-2004] vs. 15.5% [2005-2009] vs. 10.7% [2010-2014]; p < .001). Three-year OS was significantly higher for patients diagnosed between 2010 and 2014 (81.8%) and 2005 and 2009 (80.6%) compared with 2000 and 2004 (78.5%; p = .0008 and .02, respectively). Whereas outcomes were poorest in the age >60 cohort, similar improvements were also seen in 3-year OS over the three time periods within this patient population. On multivariate analysis, diagnosis in the earlier period and minority race were associated with higher mortality. Females and married patients had significantly lower mortality risk. CONCLUSION: Survival of patients with advanced-stage HL has continued to improve over time, suggesting the impact of evolving treatment approaches. Three-year OS in the contemporary period remains inadequate at 81.8%, highlighting the need for continued research to improve their outcomes. IMPLICATIONS FOR PRACTICE: This article evaluates contemporary outcomes for advanced-stage Hodgkin lymphoma (HL) in the U.S. using the Surveillance, Epidemiology, and End Results database. Although overall survival (OS) has improved in each 5-year period since 2000, the 3-year OS from 2010 to 2014 remains inadequate at 81.8% and is limited by patient demographics. New therapies are indicated to improve clinical outcomes in advanced-stage HL.
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Quimiorradioterapia/mortalidade , Doença de Hodgkin/mortalidade , Programa de SEER/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Adulto JovemRESUMO
The cure rate for several solid tumour malignancies including breast cancers, head and neck cancers, bone cancers, and sarcoma has improved remarkably with the advent of neoadjuvant and adjuvant therapies. Unfortunately, exposure to chemotherapy or radiation as a part of these treatments exposes patients to the risk of subsequent myeloid malignancies. Therapy related myeloid malignancies have certain characteristic findings. They typically arise within 10 years of treatment exposure, they are seen in younger patients, and the greatest risk is in patients who receive therapy with alkylating agents or topoisomerase II inhibitors. Solid tumours whose therapies utilize these agents at higher doses, namely bone/soft tissue cancers, testicular cancer, anal cancer, and brain tumours, appear to be the groups at highest risk for T-MN. Beyond these patients, emerging populations diagnosed with T-MN include prior platinum exposure, and patients requiring G-CSF support with chemotherapy.
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Neoplasias Hematológicas , Transtornos Mieloproliferativos , Segunda Neoplasia Primária , Quimioterapia Adjuvante/efeitos adversos , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Neoplasias Hematológicas/induzido quimicamente , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Transtornos Mieloproliferativos/induzido quimicamente , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/patologia , Transtornos Mieloproliferativos/terapia , Segunda Neoplasia Primária/metabolismo , Segunda Neoplasia Primária/patologia , Segunda Neoplasia Primária/terapia , Platina/efeitos adversos , Platina/uso terapêutico , Fatores de Risco , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêuticoRESUMO
PURPOSE OF REVIEW: Chronic myeloid leukemia (CML) patients treated with tyrosine kinase inhibitors (TKI) have near-normal life expectancy. However, lifelong TKI therapy is associated with reduced quality of life and significant economic burden. Currently, the management of CML is shifting from continuous TKI therapy towards the goal of TKI cessation which is discussed in this review. RECENT FINDINGS: Several studies in the last decade have demonstrated the feasibility and safety of TKI discontinuation in selected patients with CML who achieve deep and sustained molecular response with TKI. This has moved prime-time into clinical practice although open questions remain in terms of understanding the disease biology that leads to successful TKI cessation in some patients while not in others. Cessation of TKI for CML patients is a feasible approach. Ongoing research aims to find out optimal strategies to sustain ongoing treatment-free remission (TFR) and increase the number of patients who achieve TFR.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Indução de Remissão/métodos , HumanosRESUMO
Allogeneic hematopoietic cell transplantation (allo-HCT) with reduced-intensity conditioning (RIC) is commonly performed as an inpatient procedure. The feasibility and outcomes of RIC allo-HCT in the outpatient setting is not known. We performed a single-center retrospective cohort study of patients aged ≥ 18years with hematologic malignancies who underwent RIC allo-HCT either in the inpatient or outpatient setting. Donor types included HLA-matched sibling and well-matched unrelated donors. The objectives were to compare the survival, complications, charges, and incidences of relapse, nonrelapse mortality (NRM), and acute and chronic graft-versus-host disease (GVHD) between the 2 groups. Between 2014 and 2017, 151 eligible patients were included, with 116 undergoing RIC allo-HCT in the inpatient setting and 35 patients undergoing RIC allo-HCT in the outpatient setting. Baseline characteristics were comparable between the 2 groups except for a higher proportion of patients with myeloma in the outpatient cohort (inpatient 15.5% versus outpatient 37.1%). The cumulative incidence of grades II to IV acute GVHD (inpatient 25.2% versus outpatient 25.7%), grades III to IV acute GVHD (inpatient 10.4% versus outpatient 8.5%), chronic GVHD (inpatient 38.3% versus outpatient 51.6%), NRM at 1 year (inpatient 10.8% versus outpatient 3.2%), and relapse (inpatient 24.8% versus outpatient 33.2%) did not significantly differ between the 2 cohorts. One-year progression-free survival (inpatient 64.4% versus outpatient 63.6%, Pâ¯=â¯.39) and overall survival (inpatient 73.8% versus outpatient 82.8%, Pâ¯=â¯.93) were also not significantly different between the 2 groups. The proportion of patients who developed neutropenic fever (inpatient 25.8% versus outpatient 8.5%, Pâ¯=â¯.03) and mucositis (inpatient 50.8% versus outpatient 8.5%, P < .001) and who required total parenteral nutrition (inpatient 20.6% versus outpatient 5.7%, Pâ¯=â¯.04) were more frequent in the inpatient cohort. About 51.5% of the outpatient cohort never required hospital admission in the first 100days. Outpatient HCT resulted in significantly lower charges than inpatient HCT in the first 100days (median charges: inpatient $339,621 versus outpatient $247,334; P < .001). On multivariate analysis the site of the HCT (outpatient versus inpatient) was not a significant predictor of either overall or progression-free survival. Outpatient RIC allo-HCT is feasible and safe with daily outpatient evaluation and aggressive supportive care resulting in outcomes comparable with those who received the transplant in the inpatient setting.