Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 80
Filtrar
1.
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.

2.
Transplant Cell Ther ; 2021 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-34537419

RESUMO

In the coronavirus disease 19 (COVID-19) pandemic era, the number of haploidentical hematopoietic cell transplantations (HCTs) with peripheral blood (PB) grafts increased significantly compared with HCTs with bone marrow (BM) grafts, which may be associated with adverse outcomes. We compared outcomes of HCT in BM graft and PB graft recipients age ≥18 years with hematologic malignancies who underwent T cell- replete haploidentical HCT and received graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide, tacrolimus, and mycophenolate mofetil. Among the 264 patients, 180 (68%) received a BM graft and 84 (32%) received a PB graft. The median patient age was 50 years in both groups. The majority (n = 199; 75%) received reduced-intensity conditioning. The rate of acute leukemia or myelodysplastic syndrome was higher in the BM graft recipients compared with the PB graft recipients (85% [n = 152] versus 55% [n = 46]; P < .01). The median times to neutrophil and platelet engraftment and the incidence of grade II-IV and grade III-IV acute GVHD (aGVHD) were comparable in the 2 groups. Among the patients with grade II-IV aGVHD, the rate of steroid-refractory aGVHD was 9% (95% confidence interval [CI], 5% to 18%) in the BM group versus 32% (95% CI, 19% to 54%) in the PB group (hazard ratio [HR], 3.7, 95% CI, 1.5 to 9.3; P = .006). At 1 year post-HCT, the rate of chronic GVHD (cGVHD) was 8% (95% CI, 4% to 13%) in the BM group versus 22% (95% CI, 14% to 36%) in the PB group (HR, 3.0; 95% CI, 1.4-6.6; P = .005), and the rate of systemic therapy-requiring cGVHD was 2.5% (95% CI, 1% to 7%) versus 14% (95% CI, 7% to 27%), respectively (HR, 5.6; 95% CI, 1.7 to 18; P = .004). The PB group had a significantly higher risk of bacterial and viral infections, with no appreciable advantage in the duration of hospitalization, immune reconstitution, relapse, nonrelapse mortality, or survival. Our data suggest a benefit of the use of BM grafts over PB grafts for haplo-HCT.

3.
Clin Cancer Res ; 27(21): 5847-5856, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34380640

RESUMO

PURPOSE: To compare outcomes between patients with relapsed follicular lymphoma who received a nonmyeloablative allogeneic stem cell transplant (alloSCT) and those who received an autologous transplant (autoSCT). PATIENTS AND METHODS: We evaluated 194 patients with follicular lymphoma who received an alloSCT (n = 98) or autoSCT (n = 96) at MD Anderson Cancer Center (Houston, TX). The transplant type used was based on donor availability and by Medicare reimbursement guidelines. Patients who received an alloSCT were enrolled in four consecutive trials in which they received fludarabine, cyclophosphamide (or bendamustine), and rituximab conditioning. autoSCT patients received R-BEAM (rituximab, carmustine, etoposide, cytarabine, and melphalan). RESULTS: The median follow-up of survivors was 108 months for the alloSCT group and 102 months for the autoSCT group. Overall survival was significantly better for patients who received an alloSCT compared with those who received an autoSCT (62% vs. 46%; P = 0.048). Similarly, progression-free survival rates were 52% in patients who received an alloSCT and 31% in those who received an autoSCT (P < 0.001), and the 8-year relapse rates were 11% and 43%, respectively (P < 0.0001). Only three patients in the alloSCT group relapsed beyond 3.5 years. In the alloSCT group, the rates for grade 2 to 4 acute graft-versus-host disease (GVHD), grade 3 to 4 acute GVHD, and extensive chronic GVHD were 22%, 9%, and 38%, respectively. In the autoSCT group, the 8-year incidence of secondary myelodysplasia was 11%. Nonrelapse mortality was similar between the two groups (15% vs. 11% at 8 years; P = 0.27). CONCLUSIONS: This study shows that alloSCT is curative and confers superior survival compared with autoSCT in patients with follicular lymphoma.

4.
ACS Med Chem Lett ; 12(7): 1108-1115, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34267880

RESUMO

Cyclin-dependent kinase 9 (CDK9) is a serine/threonine kinase involved in the regulation of transcription elongation. An inhibition of CDK9 downregulates a number of short-lived proteins responsible for tumor maintenance and survival, including the antiapoptotic BCL-2 family member MCL-1. As pan-CDK inhibitors under development have faced dosing and toxicity challenges in the clinical setting, we generated selective CDK9 inhibitors that could be amenable to an oral administration. Here, we report the lead optimization of a series of azaindole-based inhibitors. To overcome early challenges with promiscuity and cardiovascular toxicity, carboxylates were introduced into the pharmacophore en route to compounds such as 14 and 16. These CDK9 inhibitors demonstrated a reduced toxicity, adequate pharmacokinetic properties, and a robust in vivo efficacy in mice upon oral dosing.

5.
Leukemia ; 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34312462

RESUMO

In this phase I/II clinical trial, we investigated the safety and efficacy of high doses of mb-IL21 ex vivo expanded donor-derived NK cells to decrease relapse in 25 patients with myeloid malignancies receiving haploidentical stem-cell transplantation (HSCT). Three doses of donor NK cells (1 × 105-1 × 108 cells/kg/dose) were administered on days -2, +7, and +28. Results were compared with an independent contemporaneously treated case-matched cohort of 160 patients from the CIBMTR database.After a median follow-up of 24 months, the 2-year relapse rate was 4% vs. 38% (p = 0.014), and disease-free survival (DFS) was 66% vs. 44% (p = 0.1) in the cases and controls, respectively. Only one relapse occurred in the study group, in a patient with the high level of donor-specific anti-HLA antibodies (DSA) presented before transplantation. The 2-year relapse and DFS in patients without DSA was 0% vs. 40% and 72% vs. 44%, respectively with HR for DFS in controls of 2.64 (p = 0.029). NK cells in recipient blood were increased at day +30 in a dose-dependent manner compared with historical controls, and had a proliferating, mature, highly cytotoxic, NKG2C+/KIR+ phenotype.Administration of donor-derived expanded NK cells after haploidentical transplantation was safe, associated with NK cell-dominant immune reconstitution early post-transplant, preserved T-cell reconstitution, and improved relapse and DFS. TRIAL REGISTRATION: NCT01904136 ( https://clinicaltrials.gov/ct2/show/NCT01904136 ).

6.
Transplant Cell Ther ; 27(11): 913.e1-913.e12, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34329753

RESUMO

Compared to reduced-intensity conditioning regimen, myeloablative conditioning (MAC) for hematopoietic stem cell transplantation (HCT) reduces relapse but is avoided in older patients because of higher non-relapse mortality (NRM). To meet the need for a myeloablative regimen for older patients, we developed a novel fludarabine and busulfan MAC regimen. We fractionated the dose of busulfan and gave it for 6 days over a 2-week period and demonstrated the feasibility and safety of this approach. However, the disease-specific efficacy of this regimen is not known. The purpose of this study was to estimate the efficacy of fractionated busulfan regimen by estimating diseases specific survival outcomes. The conditioning regimen consisted of busulfan and fludarabine. On days -13 and -12 before HCT, patients received 80 mg/m2 busulfan intravenously (IV) daily in an outpatient clinic. Additional chemotherapy was administered during inpatient treatment from day -6 through day -3, including fludarabine 40 mg/m2 and busulfan IV once daily. The dosing of busulfan was determined from pharmacokinetic analyses to achieve for the course a target area under the curve of 20,000 ± 12% µmol/min, which is close to the average exposure of myeloablative dose of busulfan. One hundred fifty patients with high-risk hematological malignancies up to 75 years were enrolled in this prospective phase II study. The objective was to evaluate NRM, relapse, survival, the rates of graft-versus-host disease (GVHD), and long-term complications. The median age of the patient population was 61 years (interquartile range, 55-67). The most common diagnoses were acute myeloid leukemia (AML; N = 59 [39.3%]), myelodysplastic syndrome (MDS; n = 29 [19.3%]), and myelofibrosis (MF; N = 22 [14.7%]). Most had an unrelated donor (n = 93 [62%]) and received peripheral blood graft (n = 110 [73.3%]). Over half had an HCT-specific comorbidity index of ≥3 (n = 79 [52.7%]). The median follow-up among survivors was 43.4 months (interquartile range, 38.9-50.4). In patients with AML in complete remission, MDS, and myelofibrosis, 3-year overall survival was 66.7% (95% confidence interval [CI], 50.2-88.5%), 43.6% (95% CI, 28.6-66.4%), and 59.1% (95% CI, 41.7-83.7%) respectively. The cumulative incidence of NRM was 22% (15.3%-28.7%), extensive chronic GVHD was 27% (95% CI, 20-34%), bronchiolitis obliterans was 4.7% (95% CI, 1.3-8.1%), and secondary malignancy was 8.7% (95% CI, 4.1-13.2%) at 3 years. Lengthening the duration of busulfan (fractionation) permits safe delivery of myeloablative conditioning in older patients, leading to prolonged survival. © 2021 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

7.
Transplant Cell Ther ; 27(5): 359-362, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965172

RESUMO

As an alternative stem cell source, cord blood (CB) has many advantages. However, delayed engraftment, lack of transferred immunity, and a significant incidence of acute graft-versus-host disease renders CB transplant (CBT) recipients at high risk of infectious complications. This guidance written by CBT and infectious disease experts outlines evidence-based recommendations for the prevention and treatment of opportunistic infections in adult patients undergoing CBT. Topics addressed include bacterial, fungal, viral, pneumocystis jirovcii and toxoplasmosis prophylaxis, suggested PCR monitoring for viruses, therapy for the most commonly encountered infections after CBT. We review key concepts including the recent important role of letermovir in the prevention of CMV reactivation. In instances where there is a paucity of data, practice recommendations are provided, including the duration of antimicrobial prophylaxis.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Infecções Oportunistas , Adulto , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Humanos , Infecções Oportunistas/tratamento farmacológico
8.
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
9.
Front Immunol ; 12: 675679, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33995420

RESUMO

Background: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.


Assuntos
Anticorpos Antivirais , Betacoronavirus/imunologia , COVID-19/terapia , Resfriado Comum/imunologia , Convalescença , Coronavirus Humano OC43/imunologia , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/mortalidade , Reações Cruzadas , Feminino , Humanos , Imunização Passiva , Masculino , Pessoa de Meia-Idade
10.
Transplant Cell Ther ; 27(8): 689-695, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34023569

RESUMO

Relapse after allogeneic hematopoietic cell transplantation (HCT) leads to poor survival in patients with acute myeloid leukemia (AML). A second HCT (HCT2) may achieve durable remission. To determine the outcomes of patients who received an HCT2 for relapsed AML and to evaluate the predictors of overall survival (OS) and progression-free survival (PFS). We retrospectively reviewed medical records of adult patients who underwent an HCT2 for relapsed AML at our institution during 2000 to 2019. Ninety-one patients were identified with a median age of 44 years (range 18-73) at HCT2. Donor types were HLA-identical sibling (n = 37 [41%]), HLA-matched-unrelated (n = 34 [37%]), haploidentical (n = 19 [21%]), and cord blood (n=1 [1%]). Donors were different at HCT2 in 53% of patients. The majority of patients received reduced intensity conditioning (n = 71 [78%]) and were in remission (n = 56 [61%]) at HCT2. The median remission duration after HCT1 was 8.4 months (range 1-70) and the median time between transplants was 14 months (range 3-73). The median follow-up of surviving patients after HCT2 was 66 months (range 2-171), with 32% alive at time of analysis. The most common cause of death was disease recurrence (n = 45 [73%]). At 2 years, the rates of OS, PFS, progression, and nonrelapse mortality were 36%, 27%, 42%, and 18%, respectively. The development of chronic graft-versus-host disease (GVHD) after first HCT and HCT comorbidity index (HCT-CI) ≥2 at HCT2 were associated with inferior PFS and OS after HCT2. A second HCT is feasible in selected patients with AML who have relapsed after HCT1. Long-term survival benefit is possible in patients without chronic GVHD after HCT1 and HCT-CI <2 at HCT2.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Humanos , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Estudos Retrospectivos , Condicionamento Pré-Transplante , Adulto Jovem
11.
Bone Marrow Transplant ; 56(8): 2005-2012, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33846563

RESUMO

Despite low nonrelapse mortality (NRM) at day 100 after allogeneic hematopoietic cell transplantation (HCT), NRM at 1 year remains substantial. In this study, we retrospectively analyzed 199 patients who were treated on a phase II clinical trial assessing safety and efficacy of myeloablative fractionated busulfan and fludarabine conditioning regimen for hematologic malignancies. The goal of the study was to identify factors associated with NRM occurring between days 101 and 365 post-HCT and generate a hypothesis for future studies to reduce the risk of NRM at 1 year. We found that a vast majority (83%) of patients who experienced NRM between days 101 and 365 had prior grade II-IV acute graft-versus-host disease (GVHD), which was the leading cause of death either by itself (33.3%) or complicated by infections (37.5%). In multivariate analysis, grade II-IV acute GVHD (hazard ratio (HR) 2.9, 95% confidence interval (CI) 1.3-6.6, p = 0.01) was the only significant predictor of NRM between days 101 and 365. Measures to reduce the risk of acute GVHD could lower the risk of NRM at 1 year and improve overall survival.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Bussulfano , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Estudos Retrospectivos , Análise de Sobrevida , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo
13.
J Clin Oncol ; 39(24): 2710-2719, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33929874

RESUMO

PURPOSE: BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS: We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS: Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION: Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.


Assuntos
Cistite/tratamento farmacológico , Transtornos Hemorrágicos/tratamento farmacológico , Linfócitos T Citotóxicos/metabolismo , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
14.
Transplant Cell Ther ; 27(3): 272.e1-272.e5, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33781539

RESUMO

Steroid-refractory (SR) lower gastrointestinal (LGI) acute graft-versus-host disease (aGVHD) has poor prognosis, and novel drugs are needed. We describe outcomes of patients with SR-LGI aGVHD treated with vedolizumab. The primary objective was to determine overall response rate (ORR) at days 14, 28, and 56. Secondary outcomes included overall survival (OS), non-relapse mortality and toxicities. Twenty patients, median age 46 years (range, 23-71), were included. All but 2 patients (90%) had grade 3 to 4 aGVHD (45% stage 4, 40% stage 3 LGI). Median time to vedolizumab was 21 days (range, 5-1031) and 13 days (range, 0-533) after diagnosis of LGI aGVHD and SR-LGI aGVHD, respectively. It was given as ≥3rd line (median 3; range 2-6) in 75% after failure of steroids, and additional treatments including ruxolitinib (n = 12) and others. Median follow-up was 17 months (range, 10-34). The days 14, 28 and 56 ORRs were 45% (9/20; complete response [CR] 25%), 35% (7/20; CR 20%), and 25% (5/20; CR 20%), respectively. Among ruxolitinib failures, it was 50% (6/12; CR 25%), 50% (6/12; CR 25%) and 25% (3/12; CR 16.7%), respectively. Fifteen patients died (14 GVHD, 1 leukemia relapse). The actuarial 6-month OS was 35% (95% confidence interval 16-55). No progressive multifocal leukoencephalopathy or infusion reaction occurred. Forty-four infection events (22 viral, 18 bacterial, and 4 fungal) were noted in 16 patients. Vedolizumab was well tolerated and demonstrated potential efficacy even after ruxolitinib failure for SR-LGI aGVHD. Yet the responses were suboptimal, and its use requires further investigation.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Anticorpos Monoclonais Humanizados , Doença Enxerto-Hospedeiro/tratamento farmacológico , Humanos , Trato Gastrointestinal Inferior , Pessoa de Meia-Idade , Esteroides/uso terapêutico
15.
Front Cardiovasc Med ; 8: 613625, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718445

RESUMO

Background: QT prolongation and torsades de pointes pose a major concern for cardiologists and oncologists. Although cancer patients are suspected to have prolonged QT intervals, this has not been investigated in a large population. The purpose of this study was to analyze the QT interval distribution in a cancer population and compare it to a non-cancer population in the same institution. Methods: The study was a retrospective review of 82,410 ECGs performed in cancer patients (51.8% women and 48.2% men) and 775 ECGs performed in normal stem cell donors (47.9% women and 52.1% men) from January 2009 to December 2013 at the University of Texas MD Anderson Cancer Center. Pharmacy prescription data was also collected and analyzed during the same time period. Correction of the QT interval for the heart rate was performed using the Bazett and Fridericia formulas. Results: After QT correction for heart rate by the Fridericia formula (QTcF), the mean and 99% percentile QTc for cancer patients were 414 and 473 ms, respectively. These were significantly longer than the normal stem cell donors, 407 and 458 ms, p < 0.001, respectively. Among the cancer patients, the QTc was longer in the inpatient setting when compared to both outpatient and emergency center areas. The most commonly prescribed QT prolonging medications identified were ondansetron and methadone. Conclusion: Our study demonstrates significantly longer QTc intervals in cancer patients, especially in the inpatient setting. Frequently prescribed QT prolonging medications such as antiemetics and analgesics may have a causative role in QT prolongation seen in our cancer hospital.

16.
medRxiv ; 2021 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-33758890

RESUMO

Background: COVID-19 Convalescent plasma (CCP) is safe and effective, particularly if given at an early stage of the disease. Our study aimed to identify an association between survival and specific antibodies found in CCP. Patients and Methods: Patients ≥18 years of age who were hospitalized with moderate to severe COVID-19 infection and received CCP at the MD Anderson Cancer Center between 4/30/2020 and 8/20/2020 were included in the study. We quantified the levels of anti-SARS-CoV-2 antibodies, as well as antibodies against antigens of other coronavirus strains, in the CCP units and compared antibody levels with patient outcomes. For each antibody, a Bayesian exponential survival time regression model including prognostic variables was fit, and the posterior probability of a beneficial effect (PBE) of higher antibody level on survival time was computed. Results: CCP was administered to 44 cancer patients. The median age was 60 years (range 37-84) and 19 (43%) were female. Twelve patients (27%) died of COVID-19-related complications. Higher levels of two non-SARS-CoV-2-specific antibodies, anti-HCoV-OC43 spike IgG and anti-HCoV-HKU1 spike IgG, had PBE = 1.00, and 4 SARS-CoV-2-specific antibodies had PBEs between 0.90 and 0.95. Other factors associated with better survival were shorter time to CCP administration, younger age, and female sex. Conclusions: Common cold coronavirus spike IgG antibodies anti-HCoV-OC43 and anti-HCoV-HKU1 may target a common domain for SARS-CoV-2 and other coronaviruses. They provide a promising therapeutic target for monoclonal antibody production.

18.
Cancer ; 127(10): 1598-1605, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33471943

RESUMO

BACKGROUND: A myeloablative conditioning regimen can be safely given to older patients and those with comorbidities without increasing nonrelapse mortality (NRM) by fractionating the dose of intravenous busulfan. How this approach compares in efficacy with traditional, nonfractionated, lower dose regimens is unknown. METHODS: Outcomes were compared in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome who received either myeloablative, fractionated busulfan (f-Bu) dosed to achieve an area under the curve of 20,000 µmol per minute (f-Bu20K) over 2 weeks (n = 84) or a standard, nonfractionated, lower busulfan dose regimen of 16,000 µmol per minute (Bu16K) over 4 days (n = 78). Both groups also received fludarabine 40 mg/m2 intravenously for 4 days. Graft-versus-host disease prophylaxis was tacrolimus and methotrexate. Patients in the Bu16K group who had unrelated donors also received antithymocyte globulin. The primary endpoint was progression-free survival. RESULTS: Roughly one-half of the patients were aged >65 years, approximately 40% had poor-risk cytogenetics, approximately 40% of those with AML were not in complete remission, and approximately 40% had a comorbidity index >3. At 2 years, progression-free survival was significantly improved in the f-Bu20K group compared with the Bu16K group (45% vs 24%, respectively; hazard ratio [HR], 0.6; 95% CI, 0.4-0.8; P = .004). This was because of a significant reduction in progression (34% vs 59%, respectively; HR, 0.5; 95% CI, 0.3-0.8; P = .003) without any increase in NRM (21% vs 15%, respectively; HR, 1.4; 95% CI, 0.7-3; P = .3), which resulted in improved overall survival (51% vs 31%, respectively; HR, 0.6; 95% CI, 0.3-0.9; P = .01). CONCLUSIONS: A myeloablative, fractionated busulfan regimen reduces relapse and improves survival without increasing NRM in older patients with AML and myelodysplastic syndrome.

19.
Br J Clin Pharmacol ; 87(6): 2414-2424, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32463929

RESUMO

Cancer immunotherapy has greatly advanced in recent years, with chimeric antigen receptor (CAR) T cells emerging as an innovative technology that harnesses the immune system to fight malignant diseases. These genetically engineered T-cells have shown encouraging results for B-cell lymphoid malignancies and are now being explored for other cancer types. However, this novel adoptive cell therapy is associated with a new spectrum of immune-mediated adverse events and toxicities. As CAR T cells recognize and engage tumour cells, cytokines are secreted and activate other immune cells, frequently leading to rapid development of cytokine release syndrome, which can result in acute deterioration of the patient's clinical condition. In many patients, cytokine release syndrome is mild and easy to manage, but others experience persistent fevers accompanied by hypotension and hypoxia, which require management with immune-modulatory agents. Another deleterious effect of cytokines released by effector cells is immune effector cell-associated neurotoxicity syndrome. This syndrome, caused by a disruption of the blood-brain barrier as a consequence of the immune process, can result in rapid deterioration in cognitive function. This is often associated with subtle changes in handwriting, often progressing to loss of memory and concentration and reduced ability to name objects or follow commands. In some cases, the neurological state is further compromised by seizures and in rare instances with fulminant life-threatening cerebral oedema. In this review, we discuss these toxicities, as well as other CAR T-cell-related immune phenomenon, and address their clinical manifestations, grading, and management options.


Assuntos
Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Síndrome da Liberação de Citocina , Humanos , Imunoterapia Adotiva/efeitos adversos , Receptores de Antígenos Quiméricos/genética , Linfócitos T
20.
Acta Haematol ; 144(1): 74-81, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-32604096

RESUMO

Acute myeloid leukemia (AML) patients not in remission and beyond first or second complete remission are considered allogeneic stem cell transplant (SCT) candidates. We present 361 patients who underwent SCT from matched related or unrelated donors between 2005 and 2013. The purpose was to identify a subgroup of patients with active disease at the time of transplant that benefit. Cox proportional hazards regression analysis was used for univariate and multivariate analyses to predict overall survival (OS). Variables considered were age, sex, SWOG cytogenetic risk group, bone marrow (BM) and peripheral blood (PB) blast percentage, regimen intensity, and type of AML. At a median of 26 months after transplantation, OS, progression-free survival (PFS), non-relapse mortality, and relapse rates were 26, 24, 23, and 48%, respectively. In a univariate analysis, risk cytogenetics (p < 0.001) and BM blasts >4% (p = 0.006) or any blasts in PB (p < 0.001) indicated worse OS. In a multivariate analysis, patients with <5% BM blasts or absence of circulating blasts and good or intermediate risk cytogenetics had significantly superior OS (46%), PFS (44%), and disease progression at 3 years. Based on these findings, patients not in remission with good or intermediate risk cytogenetics and low blast counts should be considered for SCT.


Assuntos
Medula Óssea/patologia , Aberrações Cromossômicas , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Adolescente , Adulto , Idoso , Biomarcadores Tumorais , Biópsia , Análise Citogenética , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Prognóstico , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...