RESUMO
BACKGROUND: The authors assessed the clinical utility of patient-reported symptom monitoring in the setting of newly diagnosed chronic myeloid leukemia (CML). The primary objective was to evaluate adherence to therapy. METHODS: The authors conducted an international prospective study that included patients with newly diagnosed, chronic-phase CML. Before clinical consultation, patients were provided a tablet computer to self-rate their symptoms, and the results were available in real time to each physician during the patient's visit. Adherence was assessed by pill count and with a validated self-reported questionnaire. The proportions of optimal responders at 3 and 6 months were assessed according to the European LeukemiaNet criteria. RESULTS: Between July 2020 and August 2021, 94 patients with a median age of 57 years were enrolled. Pill count adherence analysis indicated that 86 of 93 evaluable patients (92.5%) took at least 90% of prescribed tyrosine kinase inhibitor therapy during the 6-month observation period. The online platform was well accepted by patients and physicians. An optimal response was achieved by 69 of 79 patients (87.3%) at 3 months and by 61 of 81 patients (75.3%) at 6 months. CONCLUSIONS: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates (ClinicalTrials.gov identifier NCT04384848).
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Pessoa de Meia-Idade , Doença Crônica , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Adesão à Medicação , Medidas de Resultados Relatados pelo Paciente , Estudos ProspectivosRESUMO
While there is clear evidence to suggest poorer outcome associated with multi-hit (MH) TP53 mutation compared to single-hit (SH) in lower-risk myelodysplastic syndrome (MDS), data are conflicting in both higher-risk MDS and acute myeloid leukemia (AML). We conducted an indepth analysis utilizing data from 10 US academic institutions to study differences in molecular characteristics and outcomes of SH (n= 139) versus MH (n= 243) TP53MTAML. Complex cytogenetics (CG) were more common in MH compared to SH TP53MT AML (p <0.001); whereas ASXL1 (p= <0.001), RAS (p<0.001), splicing factor (p= 0.003), IDH1/2 (p= 0.001), FLT3 ITD (p= <0.001) and NPM1 (p= 0.005) mutations significantly clustered with SH TP53MT AML. Survival after excluding patients who received best supportive care alone was dismal but not significantly different between SH and MH (event free survival [EFS]: 3.0 vs 2.20 months, p= 0.22/ overall survival [OS]: 8.50 vs 7.53 months, respectively, p= 0.13). In multivariable analysis, IDH1 mutation and allogeneic hematopoietic stem cell transplantation (allo-HCT) as a time-dependent covariate were associated with superior EFS (HR; 0.44, 95% CI: 0.19-1.01, p= 0.05/ HR; 0.34, 95% CI: 0.18-0.62, p<0.001) and OS (HR; 0.24, 95% CI: 0.08-0.71, p= 0.01/ HR; 0.28, 95% CI: 0.16-0.47, p<0.001). While complex CG (HR; 1.56, 95% CI: 1.01-2.40, p= 0.04) retained unfavorable significance for OS. Our analysis suggests that unlike in MDS, multihit TP53MT is less relevant in independently predicting outcomes in patients with AML.
RESUMO
Venetoclax (VEN) combined with hypomethylating agents (HMAs) is the standard of care for the treatment of patients with newly diagnosed acute myeloid leukemia (AML) unfit for intensive chemotherapy. To date, real-world data published on HMAs plus VEN have been either single-center studies or using community-based electronic databases with limited details on mutational landscape, tolerability, and treatment patterns in elderly patients. Therefore, we conducted a multicenter retrospective study to assess the real-world experience of 204 elderly patients (≥75 years) with newly diagnosed AML treated with HMAs plus VEN from eight academic centers in the United States. Overall, 64 patients achieved complete remission (CR; 38%) and 43 CR with incomplete count recovery (CRi; 26%) for a CR/CRi rate of 64%, with a median duration of response of 14.2 months (95% CI: 9.43, 22.1). Among responders, 63 patients relapsed (59%) with median overall survival (OS) after relapse of 3.4 months (95% CI, 2.4, 6.7). Median OS for the entire population was 9.5 months (95% CI, 7.85-13.5), with OS significantly worse among patients with TP53-mutated AML (2.5 months) and improved in patients harboring NPM1, IDH1, and IDH2 mutations (13.5, 18.3, and 21.1 months, respectively). The 30-day and 60-day mortality rates were 9% and 19%, respectively. In conclusion, HMAs plus VEN yielded high response rates in elderly patients with newly diagnosed AML. The median OS was inferior to that reported in the VIALE-A trial. Outcomes are dismal after failure of HMAs plus VEN, representing an area of urgent unmet clinical need.
Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes , Leucemia Mieloide Aguda , Idoso , Humanos , Estudos Retrospectivos , Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Sulfonamidas/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêuticoRESUMO
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.
Assuntos
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 COVID-19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS-CoV-2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno-demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS-CoV-2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva-based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme-linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8-12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07-4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04-4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS-CoV-2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.
Assuntos
Vacinas contra COVID-19 , COVID-19 , Humanos , COVID-19/prevenção & controle , Pandemias , SARS-CoV-2 , Anticorpos Neutralizantes , Pessoal de Saúde , Imunoglobulina GRESUMO
For patients with optimally treated chronic myeloid leukemia (CML), discontinuation of tyrosine kinase inhibitor (TKI) therapy can lead to treatment-free remission. In previous trials, TKI discontinuation has been associated with increased musculoskeletal pain in some patients ("withdrawal syndrome"), based on physician-reported adverse events (AE). Patient-reported pain has not been described. The Life After Stopping TKI study was a 14-site prospective, non-randomized clinical trial of TKI discontinuation. We defined increased pain after discontinuation as: (i) a physician-reported pain AE, (ii) a 2-level increase in self-reported musculoskeletal pain (4-level single item), or (iii) initiation of a medication for pain. We plotted the trajectory of patient-reported pain over time using a piecewise mixed-effects ordinal logistic model. Within 3 months of discontinuation, 35 of 172 patients (20.3%) had a physician-reported pain AE, 22 of 172 (12.8%) had an increase in self-reported pain, and 18 of 154 (11.7%) initiated a pain medication. Agreement among these measures was limited; overall, 60 of 172 patients (34.9%) had increased pain. Three patients (1.7%) restarted a TKI because of pain. The modelpredicted trajectory showed an increase in pain in the first 3 months followed by a decrease, returning to baseline levels by 6 months and further decreasing after that. This trajectory was similar among patients who did and did not restart TKI, suggesting that resuming a TKI for withdrawal syndrome may be necessary for some, but other approaches to manage pain should be tried so that patients can remain in treatment-free remission when possible.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Dor Musculoesquelética , Médicos , Humanos , Estudos Prospectivos , Dor Musculoesquelética/induzido quimicamente , Dor Musculoesquelética/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêuticoRESUMO
Aim: Forty percent of patients with higher-risk myelodysplastic syndromes (HR-MDS) transform to acute myeloid leukemia (AML). Materials & methods: This retrospective study assessed the impact of HR-MDS transformation to AML on OS in a 6-month landmark analysis and the results were validated using a time-varying analysis. Results: The rate of AML transformation was 26.9% at 1 year. Patients who transformed to AML had a higher risk of death than patients who did not in the 6-month landmark analysis (HR: 1.82; p: 0.0072) and time-varying analysis at 1 year (HR: 2.85; p < 0.0001). Patients treated with azacitidine and decitabine in first-line therapy had similar results. Conclusion: HR-MDS transformation to AML is associated with inferior OS in patients with HR-MDS initiating first-line therapy.
Up to 40% of patients with higher-risk myelodysplastic syndromes (HR-MDS) could experience deterioration or progression to acute myeloid leukemia (AML), a type of blood cancer. We conducted a study to assess whether HR-MDS progression to AML had an unfavorable impact on patient life expectancy after initiating treatment for HR-MDS. Our study concluded that patients who experienced progression to AML had a higher chance of dying immediately after their progression to AML than patients who did not. Patients who received azacitidine and decitabine as their first treatment for HR-MDS had similar results.
Assuntos
Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Síndromes Mielodisplásicas/tratamento farmacológico , Estudos Retrospectivos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/epidemiologia , Azacitidina/uso terapêuticoRESUMO
Aim: We examined the preferences of adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) for benefits and risks of tyrosine kinase inhibitors combined with chemotherapy for first-line treatment. Methods: In a discrete choice experiment, 201 patients chose between hypothetical treatment alternatives with varied levels of remission duration and overall survival (OS), and risks of major cardiovascular (CV) events and myelosuppression. Results: Although OS was the most important attribute to patients with Ph+ ALL, they were willing to tolerate a 2.9% increase in CV risk for 1 additional month of OS. Older patients (>59 years) and patients not in remission were less likely to tolerate increased CV risk. Conclusion: Preferences and risk tolerance varied between patients, highlighting the importance of shared decision making when selecting treatments for Ph+ ALL.
Treatments differ in their potential benefits and side effects they may come with. Patients should be involved in deciding which treatments they receive. This is because patients may have different views than physicians on how the benefits and side effects of treatment would affect their quality of life. Additionally, patients may have different risk tolerances. This study shows how patients with a form of leukemia valued survival benefits and side effects of treatments, and the trade-offs that they were willing to make between these. On average, longer survival had most value to patients. They were willing to accept a higher risk of a major cardiovascular side effect (e.g., having a stroke) if the treatment would allow them to live longer. However, not all patients had the same opinion, and some groups of patients were less willing to accept risks to receive longer survival. By involving patients in treatment decisions, we can help ensure they receive treatments that match their personal preferences.
Assuntos
Preferência do Paciente , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Humanos , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
Indoleamine 2,3 dioxygenase (IDO), first discovered in the 1960s, is an enzyme that has become a highly investigated metabolic target in cancer research. IDO is the rate-limiting step in tryptophan metabolism catabolism into its byproducts - kynurenines. Both IDO and kynurenines have been implicated in altering the tumor microenvironment, allowing for a tolerogenesis by affecting T-cell maturation and proliferation, and more specifically by inducing differentiation into T regulatory cells. Two mechanisms have been suspected in creating this environment: tryptophan starvation and metabolite toxicity. IDO has been shown to be expressed not only in cancer cells but also in antigen-presenting cells. The exact mechanisms underlying the two different sites of expression have not been fully elucidated. To date, most literature has focused on the role of IDO in solid tumors; we provide a review of IDO and its impact on hematological malignancies - more specifically, acute myeloid leukemia. The pathophysiology of IDO will be discussed, including a summarization of the literature to date on how IDO expression effects prognosis and disease progression in acute myeloid leukemia, along with current IDO-specific therapeutics with future considerations.
Assuntos
Antineoplásicos/farmacologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Leucemia Mieloide Aguda/imunologia , Microambiente Tumoral/imunologia , Antineoplásicos/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/imunologia , Células Dendríticas/enzimologia , Células Dendríticas/imunologia , Progressão da Doença , Regulação Leucêmica da Expressão Gênica/imunologia , Humanos , Indolamina-Pirrol 2,3,-Dioxigenase/antagonistas & inibidores , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Cinurenina/metabolismo , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Prognóstico , Intervalo Livre de Progressão , Processamento de Proteína Pós-Traducional/imunologia , Taxa de Sobrevida , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo , Triptofano/metabolismo , Evasão Tumoral/efeitos dos fármacos , Evasão Tumoral/imunologia , Microambiente Tumoral/efeitos dos fármacos , Regulação para Cima/imunologiaRESUMO
Colorectal cancer (CRC) is a high burden disease with several genes involved in tumor progression. The aim of the present study was to identify, generate and clinically validate a novel gene signature to improve prediction of overall survival (OS) to effectively manage colorectal cancer. We explored The Cancer Genome Atlas (TCGA), COAD and READ datasets (597 samples) from The Protein Atlas (TPA) database to extract a total of 595 candidate genes. In parallel, we identified 29 genes with perturbations in > 6 cancers which are also affected in CRC. These genes were entered in cBioportal to generate a 17 gene panel with highest perturbations. For clinical validation, this gene panel was tested on the FFPE tissues of colorectal cancer patients (88 patients) using Nanostring analysis. Using multivariate analysis, a high prognostic score (composite 4 gene signature-DPP7/2, YWHAB, MCM4 and FBXO46) was found to be a significant predictor of poor prognosis in CRC patients (HR: 3.42, 95% CI: 1.71-7.94, p < 0.001 *) along with stage (HR: 4.56, 95% CI: 1.35-19.15, p = 0.01 *). The Kaplan-Meier analysis also segregated patients on the basis of prognostic score (log-rank test, p = 0.001 *). The external validation using GEO dataset (GSE38832, 122 patients) corroborated the prognostic score (HR: 2.7, 95% CI: 1.99-3.73, p < 0.001 *). Additionally, higher score was able to differentiate stage II and III patients (130 patients) on the basis of OS (HR: 2.5, 95% CI: 1.78-3.63, p < 0.001 *). Overall, our results identify a novel 4 gene prognostic signature that has clinical utility in colorectal cancer.
Assuntos
Biomarcadores Tumorais , Neoplasias Colorretais/genética , Neoplasias Colorretais/mortalidade , Transcriptoma , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Curva ROCRESUMO
BACKGROUND: To the authors' knowledge, the optimal frequency of monitoring after tyrosine kinase inhibitor (TKI) discontinuation in patients with chronic myeloid leukemia (CML) has not been established. Data regarding the discontinuation of second-generation TKIs used in first-line treatment or after the failure of first-line treatment with TKIs are limited. Herein, the authors report real-world experience with "reduced frequency" molecular monitoring in patients with CML in all phases who discontinued treatment with imatinib, dasatinib, or bosutinib. METHODS: The records of patients who discontinued TKIs were reviewed. Patients who discontinued TKIs were monitored prospectively on an intended schedule of monthly blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 for 3 months, quarterly for 12 months, and every 6 months thereafter until loss of major molecular response (MMR). After loss of MMR, the TKI that previously was discontinued was reinitiated. RESULTS: Between January 2010 and September 2015, a total of 24 patients in chronic (21 patients), accelerated (2 patients), and lymphoid blast (1 patient) phase discontinued imatinib (16 patients), dasatinib (5 patients), or bosutinib (3 patients) used in the front-line treatment or beyond. Blood quantitative reverse transcriptase-polymerase chain reaction for BCR-ABL1 was performed 1.3 ± 0.7 times within the first 3 months (24 patients) and 2.7 ± 1.4 times in the following 12 months (18 patients). With a median follow-up of 36.5 months (range, 3.2-67.4 months), the probabilities of treatment-free remission at 1 year and 2 years were 65.7% (95% confidence interval, 55.8%-75.6%) and 59.7% (95% confidence interval, 49.1%-70.3%), respectively. Loss of MMR was observed in 9 patients at a median of 2.8 months (range, 1.8-14.2 months) after discontinuation of TKIs. CONCLUSIONS: With the limitations of a small sample size, the results of the current study demonstrate that less frequent monitoring of BCR-ABL1 does not appear to affect outcomes, and that discontinuation of TKIs used as first-line treatment or beyond after resistance or intolerance to first-line treatment appears feasible. Cancer 2017;123:2482-88. © 2017 American Cancer Society.
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Desprescrições , Proteínas de Fusão bcr-abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Recidiva Local de Neoplasia/sangue , Inibidores de Proteínas Quinases/uso terapêutico , Conduta Expectante/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos de Anilina/uso terapêutico , Dasatinibe/uso terapêutico , Feminino , Humanos , Mesilato de Imatinib/uso terapêutico , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Nitrilas/uso terapêutico , Quinolinas/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Myelofibrosis (MF) is a chronic malignancy of the blood-forming system caused by hyperactivation of JAK2/STAT signaling pathway. Small-molecule inhibitors of JAK2 can variably ameliorate MF-related symptoms caused by chronic inflammation and hepatosplenomegaly. Anemia is a significant problem and adverse prognostic factor in over a third of MF patients and is often worsened by JAK2 inhibitors. The JAK1/2 inhibitor momelotinib unexpectedly resulted in reduction of anemia in MF patients during Phase I/II trials. Current Phase III trials will be the basis for seeking regulatory approval of momelotinib during 2017. Studies to determine how momelotinib improves anemia are underway, potentially leading to expanded momelotinib use and/or development of other targeted therapies for treating anemia in MF and related diseases.
Assuntos
Antineoplásicos/uso terapêutico , Benzamidas/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Inibidores de Proteínas Quinases/uso terapêutico , Pirimidinas/uso terapêutico , Anemia/etiologia , Antineoplásicos/farmacologia , Benzamidas/farmacologia , Ensaios Clínicos como Assunto , Descoberta de Drogas , Humanos , Janus Quinase 1/antagonistas & inibidores , Janus Quinase 2/antagonistas & inibidores , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/epidemiologia , Transtornos Mieloproliferativos/etiologia , Transtornos Mieloproliferativos/metabolismo , Mielofibrose Primária/epidemiologia , Mielofibrose Primária/etiologia , Mielofibrose Primária/metabolismo , Prognóstico , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Resultado do TratamentoRESUMO
Secondary failure of platelet recovery (SFPR) is a serious complication observed in approximately 20% of allogeneic hematopoietic stem cell transplant (HSCT) recipients. Although the standard therapeutic approach has been frequent platelet transfusions, romiplostim, a thrombopoietin receptor agonist, may have utility in treating SFPR. The primary objective of this single-center retrospective analysis was to assess effectiveness of romiplostim for SFPR and to evaluate patient factors which may influence clinical outcomes. The primary outcome measure of response was defined as achievement of platelet count ≥ 50 × 109/L without transfusions for ≥ 7 consecutive days. During the study period, 93 patients underwent HSCT and 13 (13.9%) received romiplostim for SFPR. Seven patients (53.8%) responded to romiplostim, requiring a median of three doses (range 1-6) to achieve independence from platelet transfusions. Disease relapse occurred in 38.5% of all patients, two responders and three nonresponders. Median survival post-HSCT was 753 days among responders and 266 days among nonresponders ( p = 0.0375). No serious adverse events were reported, and rates of graft-versus-host disease did not increase following administration of romiplostim. Thrombopoietin receptor agonists including romiplostim offer a treatment option for persistent thrombocytopenia following HSCT. Positive clinical response to romiplostim post-HSCT is associated with improved outcomes.
Assuntos
Plaquetas/efeitos dos fármacos , Doença Enxerto-Hospedeiro/tratamento farmacológico , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Trombopoetina/uso terapêutico , Adolescente , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/metabolismo , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas/métodos , Receptores de Trombopoetina/metabolismo , Estudos Retrospectivos , Trombocitopenia/tratamento farmacológico , Trombocitopenia/metabolismo , Adulto JovemRESUMO
PURPOSE: To assess the impact of single-dose fosaprepitant on nausea and emesis after BEAM and high-dose melphalan conditioning regimens for autologous hematopoietic stem cell transplantation. METHODS: In a single-center cohort study patients receiving melphalan containing hematopoietic stem cell transplantation regimens who received a one-time dose of 150 mg IV fosaprepitant (n = 56) were compared to a historical control (n = 70). RESULTS: The primary endpoint of no emesis from melphalan administration through five days afterward was 80% for the fosaprepitant group versus 66% in the control group (p = 0.068). Addition of fosaprepitant demonstrated significant improvement in emetic episodes per patient during the entire assessment period (p = 0.011) and days 1-5 after melphalan (p = 0.045). Fosaprepitant resulted in no substantial nausea during the entire assessment period in 37% of high-dose melphalan patients and 57% of BEAM patients. CONCLUSIONS: Further studies are suggested to investigate the optimal number and timing of doses of fosaprepitant in this setting.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Melfalan/efeitos adversos , Morfolinas/uso terapêutico , Náusea/prevenção & controle , Vômito/prevenção & controle , Idoso , Antieméticos/uso terapêutico , Antineoplásicos Alquilantes/administração & dosagem , Antineoplásicos Alquilantes/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Estudos de Coortes , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Podofilotoxina/administração & dosagem , Podofilotoxina/efeitos adversos , Estudos Prospectivos , Estudos Retrospectivos , Condicionamento Pré-Transplante/métodos , Vômito/induzido quimicamenteRESUMO
BACKGROUND: Flow cytometry (FC) is a commonly requested test in the workup of leukocytosis in community practices. The role of FC in chronic-phase chronic myeloid leukemia (CP-CML) is unknown. We hypothesized that finding aberrant cells with FC in CP-CML may predict early blast-phase (BP) transformation. METHODS: Results for FC performed at the time of diagnosis for adult and pediatric patients with CP-CML who were referred to our institution were reviewed, and they were correlated with outcomes. RESULTS: FC was performed at the time of diagnosis for 110 of 233 patients (47%) with CP-CML. Aberrant populations, representing a median of 2% (range, 0.3%-15%), were detected with FC in 30% of patients (33 of 110): 2 of these 33 patients expressed lymphoid markers, and 31 expressed aberrant myeloid markers. Patients received imatinib (85%), dasatinib (12%), or nilotinib (3%) as their first-line treatment. With a median follow-up of 43 months (range, 2-113 months), chronic myeloid leukemia transformed to BP in 5 of the 33 patients. The 2 patients with lymphoid markers and the 3 of 31 patients with aberrant myeloid markers experienced a transformation to lymphoid BP at a median of 11 months (range, 4-72 months) after the initiation of tyrosine kinase inhibitor therapy. Although both cases with detectable lymphoid markers rapidly progressed to lymphoid BP, the positive predictive value of BP transformation by the detection of myeloid aberrant cells with FC was only 10% (3 of 31). CONCLUSIONS: In contrast to aberrant myeloid markers, the detection of lymphoid markers by FC at the time of the diagnosis of CP-CML appears to be associated with early progression to lymphoid BP.
Assuntos
Crise Blástica/imunologia , Crise Blástica/patologia , Imunofenotipagem/métodos , Leucemia Mieloide de Fase Crônica/imunologia , Leucemia Mieloide de Fase Crônica/patologia , Adulto , Criança , Feminino , Citometria de Fluxo/métodos , Humanos , Masculino , Valor Preditivo dos TestesRESUMO
The introduction of tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). Each approved TKI has its own risk-benefit profile, and patients have choices across lines of therapy. Identifying the initial and subsequent treatment that will lead to the best possible outcome for individual patients is challenging. In this review, we summarize data for each approved TKI across lines of therapy in patients with CML in chronic phase, highlighting elements of each agent's safety and efficacy profile that may impact patient selection, and provide insights into individualized treatment sequencing decision-making aimed at optimizing patient outcomes.
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Background/Objectives: High-dose chemotherapy (HD-CHT) followed by autologous stem cell transplantation (ASCT) remains the gold standard for eligible multiple myeloma (MM) patients, even amidst evolving therapeutic options. Clinical trials have demonstrated ASCT's efficacy in MM, including its potential as salvage therapy after prolonged remission. Peripheral blood stem cells (PBSCs) are now the primary source of hematopoietic stem cells for ASCT. Collecting additional PBSCs post-initial myeloablative conditioning is challenging, leading many centers to adopt the practice of collecting and storing excess PBSCs during initial therapy to support tandem transplants or salvage treatments. The use of salvage ASCT may diminish in the face of novel, highly effective treatments like bispecific antibodies and cellular therapies for relapsed/refractory MM (RRMM). Despite available stored PBSC grafts, salvage ASCTs are underutilized due to various factors, including declining performance status and therapy-related comorbidities. A cost utilization analysis from 2013 revealed that roughly 70% of patients had unused PBSC products in prolonged cryopreservation, costing a significant portion of total ASCT expenses. The average cost for collecting, cryopreserving, and storing PBSCs exceeded $20,000 per person, with more than $6700 spent on unused PBSCs for a second ASCT. A more recent analysis from 2016 underscored the declining need for salvage ASCT, with less than 10% of patients using stored PBSC grafts over a decade. Methods: To address the dilemma of whether backup stem cells remain necessary for myeloma patients, the study investigated strategies to reduce the financial burden of PBSC collection, processing, and storage. It evaluated MM patients undergoing frontline ASCT from January 2012 to June 2022, excluding those with planned tandem transplants and those who had a single ASCT with no stored cells. Discussion: Among the 240 patients studied, the median age at PBSC collection was 61. Notably, only 7% underwent salvage ASCT, with nearly 90% of salvage ASCT recipients being ≤ 61 years old at the time of initial ASCT. The study revealed a decreasing trend in salvage ASCT use with increasing age, suggesting that PBSC collection for a single transplant among elderly patients (>60 years old) could be a cost-effective alternative. Most transplant centers aimed to collect 10 × 106 CD34 + cells/kg, with patients over 65 often requiring multiple collection days. Shifting towards single-transplant collections among the elderly could reduce costs and resource requirements. Additionally, the study recommended implementing strategies for excess PBSC disposal or repurposing on the collection day to avoid additional storage costs. In summary, the decreasing utilization of salvage ASCT in MM, alongside financial considerations, underscores the need for revised stem cell collection policies. Conclusions: The study advocates considering single-transplant PBSC collections for elderly patients and efficient management of excess PBSCs to optimize resource utilization.
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Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF-AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF-AML. We included 200 patients with CBF-AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow-up for the whole cohort was 2.5 years. Three-year overall survival (OS) was 70% and 3-year event-free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3-year EFS of 50% compared to those treated with IC alone who experienced a 3-year EFS of 47%, with no statistically significant difference (p = 0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (p = 0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3-year EFS of 85% compared to those with IC with or without GO (p = 0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF-AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.