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1.
Acta Haematol ; : 1-10, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38934131

RESUMO

INTRODUCTION: CMML is a rare neoplasm with overlapping myelodysplastic and myeloproliferative features whose only potential cure is allogeneic hematopoietic cell transplantation (allo-HCT). METHODS: This retrospective study examined 27 CMML patients with high-risk clinical features who underwent first allo-HCT at our institution between 2004 and 2022. RESULTS: Nineteen patients were diagnosed with the proliferative subtype (CMML-MPN) and 8 with the dysplastic subtype (CMML-MDS). Median OS was 15 months post-HCT (95% CI: 5-71); OS at 1, 3, and 5 years was 52%, 35%, and 35%, respectively. Compared to those with CMML-MPN, patients with CMML-MDS had longer OS (median, 8.6 vs. 0.9 years; p = 0.025), RFS (4.4 vs. 0.5 years; p = 0.021), and GVHD-free, relapse-free survival (GRFS, 9.4 vs. 3.4 months; p = 0.033) as well as lower 1-year NRM (13 vs. 47%; p = 0.043), with the statistical significance of this CMML subtype effect maintained in multivariable models. High-risk cytogenetics were associated with shorter GRFS in the univariable (median, 3.1 vs. 6.2 months; p = 0.013) and multivariable (HR = 4.88; p = 0.006) settings. CONCLUSIONS: Patients who underwent transplant for CMML-MDS experienced substantially better outcomes than those transplanted for CMML-MPN. Future studies are needed for transplantation optimization in CMML, especially CMML-MPN.

2.
Cytotherapy ; 25(4): 423-431, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36690537

RESUMO

BACKGROUND AIMS: In a previous pilot study of HLA-matched sibling donor hematopoietic cell transplantation (HCT), the authors determined the feasibility of day 4 versus day 5 granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood stem cell (PBSC) collection compared with a historical cohort. Given identified differences in the PBSC product (day 4 cohort with significantly lower infused total nucleated, mononuclear and CD3 cells compared with other collection cohorts), the authors performed a follow-up study to determine long-term post-HCT outcomes, including detailed characterization of chronic graft-versus-host disease (GVHD). METHODS: This was a prospective observational study, and the authors collected data on chronic GVHD, staging, sites of involvement and treatments. Performance status, incidence of relapse, overall survival and duration of immunosuppressive therapy (IST) were also evaluated. Data were examined retrospectively. To account for differences in length of follow-up among cohorts, the authors also determined performance status and chronic GVHD staging, sites and treatment at 2 years post-HCT. RESULTS: At 2 years post-HCT, the overall survival rate was 71.7% in the day 4 cohort compared with 61.5%, 52% and 56% in the day 5, 2-day and historical cohorts, respectively (P = 0.283). The cumulative incidence of chronic GVHD was 65.2% in the day 4 cohort versus 46.4% in the day 5 cohort, 51.1% in the 2-day cohort and 65% in the historical cohort (P = 0.26). There was no significant difference in the maximum overall stage of chronic GVHD (P = 0.513), median number of sites involved (P = 0.401) or cumulative incidence of discontinuation of IST (P = 0.32). Death from chronic GVHD was less common in the day 4 and day 5 cohorts compared with the 2-day and historical cohorts, though this did not reach statistical significance. CONCLUSIONS: The authors' preliminary results demonstrated that collection of allogeneic matched sibling donor PBSCs on day 4 of G-CSF was feasible, reduced donor exposure to growth factor and was associated with an initial cost savings. Importantly, the authors now demonstrate that transplantation of day 4 mobilized PBSCs is not associated with any adverse outcomes post-HCT, including late effects such as chronic GVHD. Further investigation of donor G-CSF collection algorithms is merited in other HCT settings, including unrelated and mismatched related donors.


Assuntos
Síndrome de Bronquiolite Obliterante , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Irmãos , Seguimentos , Estudos Retrospectivos , Projetos Piloto , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Fator Estimulador de Colônias de Granulócitos , Doença Crônica , Recidiva , Doadores de Sangue , Aloenxertos
3.
J Oncol Pharm Pract ; 25(2): 362-368, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29157146

RESUMO

BACKGROUND: Patients with gynecologic malignancies are at an increased risk for venous thromboembolism. National guidelines recommend treatment of an acute venous thromboembolism with low molecular weight heparin for 5-10 days followed by long-term secondary prophylaxis with low molecular weight heparin for at least six months. Non-vitamin K oral anticoagulants are not currently recommended to be used in cancer patients for the management of venous thromboembolism because robust data on their efficacy and safety have yet to become available in cancer patients. The objectives of this study were to determine the proportion of gynecologic oncology patients with venous thromboembolism using rivaroxaban compared to warfarin or low molecular weight heparin as well as compare the safety and efficacy of these anticoagulants. METHODS: This study was a retrospective pilot analysis of adult patients with gynecologic malignancies who received either rivaroxaban, warfarin or low molecular weight heparin for treatment of venous thromboembolism at Augusta University Medical Center from 1 July 2013 to 30 June 2015. Statistical comparisons between the enoxaparin and rivaroxaban group were made using T-tests and Chi-square or Fisher's exact tests, where appropriate. RESULTS: Out of the 49 patients, 37% (18) patients were on rivaroxaban, 53% (26) on enoxaparin, and 10% (5) on warfarin. Only one patient (4%) in the enoxaparin group experienced a recurrent deep vein thrombosis while there were no cases of recurrent venous thromboembolism in the rivaroxaban and warfarin group. The incidence of major bleeding was 17% (n = 2), 20% (n = 1), and 8% (n = 2) in patients receiving rivaroxaban, enoxaparin, and warfarin, respectively. The rate of switching to a different anticoagulant than originally prescribed was 42% (n = 14) in the enoxaparin arm, and 5.5% (n = 1) in the rivaroxaban arm. CONCLUSION: A high proportion of our gynecologic oncology patients received rivaroxaban for the management of venous thromboembolism. The sample size of this pilot analysis was too small to draw any conclusions regarding efficacy and safety of rivaroxaban compared with enoxaparin and warfarin. High rate of rivaroxaban use in gynecologic oncology patients at our institution highlights the need for larger, well-designed randomized controlled trials to confirm the safety and efficacy of its use in this population.


Assuntos
Enoxaparina/uso terapêutico , Inibidores do Fator Xa/uso terapêutico , Neoplasias dos Genitais Femininos/complicações , Rivaroxabana/uso terapêutico , Tromboembolia Venosa/tratamento farmacológico , Varfarina/uso terapêutico , Centros Médicos Acadêmicos , Adulto , Idoso , Anticoagulantes/uso terapêutico , Substituição de Medicamentos , Enoxaparina/efeitos adversos , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Projetos Piloto , Recidiva , Estudos Retrospectivos , Rivaroxabana/efeitos adversos , Prevenção Secundária , Tromboembolia Venosa/etiologia , Varfarina/efeitos adversos
4.
J Oncol Pharm Pract ; 25(2): 326-332, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29059026

RESUMO

BACKGROUND: Patients immediately post-hematopoietic cell transplantation are at high risk for bacteremia. Judicious prophylactic antimicrobial utilization must balance anticipated benefits (reduction infections) versus risk (bacterial resistance, Clostridium difficile) . OBJECTIVE: To compare infectious outcomes (primary: incidence bacteremia; secondary: febrile neutropenia, C. difficile, susceptibility of bacteremia, time to discharge and 30-day mortality) between hematopoietic cell transplantation who received fluoroquinolone prophylaxis to those who did not. METHODS: A local institutional review board-approved retrospective study was conducted on all hematopoietic cell transplantation patients ( n = 171) comparing those who received fluoroquinolone prophylaxis ( n = 105) to those who did not ( n = 66). Data included infectious outcomes and mortality for the first 30 days post-hematopoietic cell transplantation. Chi-squared was performed for categorical variables (GraphPad Software Inc., 2015). Secondary analysis compared outcomes within autologous and allogeneic sub-groups. RESULTS: Bacteremia was significantly lower for the overall cohort receiving fluoroquinolone (median duration eight days) versus those without fluoroquinolone (15.2% vs. 31.8%; P < 0.01). No difference was seen in C. difficile infection ( P = 0.81) or 30-day mortality (2.9% vs. 4.5%; P = 0.67). In the autologous sub-group ( n = 115), bacteremia was significantly lower in the fluoroquinolone cohort (8.5% vs. 27.3%; P = 0.0069), while no differences were seen in C. difficile infection ( P = 1) or 30-day mortality ( P = 1). In the allogeneic sub-group ( n = 56), there was no difference between those with and without fluoroquinolone in bacteremia (29.4% vs. 40.9%; P = 0.4) or C. difficile ( P = 0.72); however, there was a trend toward improved 30-day mortality (2.9% vs. 9.1%; P = 0.55). CONCLUSIONS: Fluoroquinolone prophylaxis reduces incidence of bacteremia in autologous hematopoietic cell transplantation without increasing C. difficile after hematopoietic cell transplantation.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Fluoroquinolonas/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Adolescente , Adulto , Idoso , Bacteriemia/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/mortalidade , Estudos Retrospectivos , Transplante Autólogo , Adulto Jovem
5.
Biol Blood Marrow Transplant ; 24(10): 2065-2071, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29906570

RESUMO

Evidence supports olanzapine for prophylaxis of chemotherapy-induced nausea/vomiting (CINV) for highly emetogenic chemotherapy; however, most studies focus on solid malignancies and single-day regimens. A randomized, double-blinded, placebo-controlled trial was conducted to compare the addition of olanzapine to triplet therapy (fosaprepitant, ondansetron, dexamethasone [FOND-O]) versus triplet therapy alone (FOND) in preventing CINV in hematology patients receiving single-day and multiple-day highly emetogenic chemotherapy and hematopoietic cell transplant (HCT) regimens (NCT02635984). The primary objective of this study was to compare complete response (CR; no emesis and minimal nausea, <25 mm on a 100-mm visual analog scale) during the overall assessment period (chemotherapy days plus 5 days after). Secondary objectives were the number of emesis, number of rescue medications, percent achieving minimal nausea, and percent achieving complete protection (CP; no emesis, rescue antiemetic, or significant nausea), all of which are reported as acute (chemotherapy days), delayed (5 days after chemotherapy), and overall phases. Olanzapine 10 mg or matching placebo were given on each chemotherapy day and 3 days after. Adults with hematologic malignancy receiving HCT regimens of melphalan, BEAM (carmustine, etoposide, cytarabine, melphalan), busulfan (Bu)/cyclophosphamide (Cy), Bu/fludarabine (Flu), Bu/melphalan, FluCy, FluCy-total body irradiation (TBI), etoposide-TBI, and ICE (ifosfamide, carboplatin, etoposide) or 7+3 chemotherapy regimens were included. An estimated 98 patients were required using alpha = .05 and 80% power. No significant differences existed in baseline characteristics between FOND-O (n = 51) and FOND (n = 50) arms. Mean duration of olanzapine was 7.7 days (range, 4 to 11). Discontinuation for possible adverse events occurred in 3 placebo and 0 olanzapine patients. CR was significantly higher for FOND-O in overall (55% versus 26%, P = .003) and delayed (60.8% versus 30%, P = .001) but not acute (P = .13) phases. Significantly more patients receiving FOND-O achieved no more than minimal nausea in overall (P = .001) and delayed phases (P = .0002), as well as fewer overall mean emesis counts (P = .005). CP rates were not different in any assessment phase (P ≥ .05 each). Within the HCT subgroup (n = 64), the CR, CP, and no significant nausea rates were significantly better for FONDO-O in overall and delayed phases (all P < .05). Analysis within the HCT subgroup revealed significant improvement in outcomes in delayed and overall phases with FOND-O in the autologous but not allogeneic cohort. Addition of olanzapine to an NK-1-based triplet antiemetic regimen significantly improved clinically relevant outcomes in the HCT population.


Assuntos
Antieméticos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Quimioterapia de Indução , Morfolinas/administração & dosagem , Náusea/tratamento farmacológico , Olanzapina/administração & dosagem , Ondansetron/administração & dosagem , Vômito/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carmustina/administração & dosagem , Carmustina/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Masculino , Melfalan/administração & dosagem , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Podofilotoxina/administração & dosagem , Podofilotoxina/efeitos adversos , Vômito/congênito
6.
Ann Pharmacother ; 51(12): 1090-1098, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28778132

RESUMO

OBJECTIVE: To review and summarize data on olaratumab, which was approved by the US Food and Drug Administration (FDA) in October 2016, in combination with doxorubicin, for the treatment of advanced soft tissue sarcoma. DATA SOURCES: A literature search using PubMed was conducted using the search terms olaratumab, IMC-3G3, and advanced soft tissue sarcoma from January 2005 to June 2017. STUDY SELECTION AND DATA EXTRACTION: The literature search was confined to human studies published in English. Trials of olaratumab for advanced soft tissue sarcomas were prioritized. DATA SYNTHESIS: Olaratumab is a human antiplatelet-derived growth factor receptor α monoclonal antibody. Its accelerated FDA approval was based on a phase II randomized trial of olaratumab plus doxorubicin (n = 66) versus doxorubicin monotherapy (n = 67) in patients with advanced soft tissue sarcoma. Olaratumab 15 mg/kg was administered intravenously (IV) on days 1 and 8 in combination with doxorubicin 75 mg/m2 IV on day 1 every 21 days for a total of 8 cycles compared to doxorubicin 75 mg/m2 IV monotherapy. The response rate was 18.2% with combination therapy versus 11.9% with monotherapy and median progression-free survival of 6.6 and 4.1 months, respectively. Additionally, overall survival was increased by 11.8 months in the olaratumab arm (26.5 months vs 14.7 months). Clinically relevant adverse effects in the olaratumab + doxorubicin arm included neutropenia (58%), mucositis (53%), nausea (73%), vomiting (45%), and diarrhea (34%). CONCLUSION: Olaratumab, in combination with doxorubicin, represents a novel treatment strategy for advanced soft tissue sarcoma and provides a significant survival advantage for this rare disease state with limited treatment options.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/uso terapêutico , Sarcoma/tratamento farmacológico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/economia , Anticorpos Monoclonais/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/economia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Doxorrubicina/efeitos adversos , Doxorrubicina/economia , Custos de Medicamentos , Humanos , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/antagonistas & inibidores , Sarcoma/economia , Sarcoma/metabolismo , Resultado do Tratamento
7.
Ann Pharmacother ; 51(2): 146-153, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27701080

RESUMO

OBJECTIVE: To review and summarize data on cobimetinib, which was approved by the US Food and Drug Administration (FDA) in November 2015 for use in combination with vemurafenib for unresectable or metastatic melanoma with a BRAFV600E or V600K mutation. DATA SOURCES: A literature search using PubMed was conducted using the terms cobimetinib, MEK inhibitor, and melanoma from January 2000 to June 2016. STUDY SELECTION AND DATA EXTRACTION: The literature search was confined to human studies published in English. Trials of cobimetinib for melanoma were prioritized. DATA SYNTHESIS: Cobimetinib is a reversible inhibitor of MEK1 and MEK2. Its FDA approval was based on a phase III, randomized trial of vemurafenib monotherapy (n = 248) or vemurafenib and cobimetinib (n = 247) in unresectable stage IIIC or IV melanoma with a BRAFV600 mutation. Cobimetinib was administered as 60 mg orally daily for 21 days/7 days off, whereas vemurafenib was administered as 960 mg twice daily. Vemurafenib and cobimetinib were associated with an objective response rate of 68%, and median progression-free survival of 9.9 months. The overall survival was not reached at the time of first interim analysis. Clinically relevant grade ≥3 adverse events were diarrhea (6%), rash (6%), photosensitivity (2%), elevated liver function tests (LFTs) (8%-12%), increased creatine kinase (11%), and retinal detachment (3%). CONCLUSION: Cobimetinib combined with vemurafenib is an alternative BRAF/MEK inhibitor therapy for unresectable or metastatic melanoma with BRAFV600 mutation. The role of cobimetinib in melanoma and other solid tumors is likely to expand as the results from ongoing studies become available.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Azetidinas/uso terapêutico , Indóis/uso terapêutico , Melanoma/tratamento farmacológico , Piperidinas/uso terapêutico , Sulfonamidas/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Azetidinas/administração & dosagem , Azetidinas/farmacocinética , Ensaios Clínicos como Assunto , Intervalo Livre de Doença , Humanos , Indóis/administração & dosagem , Indóis/farmacocinética , Melanoma/genética , Melanoma/patologia , Mutação , Piperidinas/administração & dosagem , Piperidinas/farmacocinética , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/genética , Sulfonamidas/administração & dosagem , Sulfonamidas/farmacocinética , Estados Unidos , United States Food and Drug Administration , Vemurafenib
8.
Ann Pharmacother ; 50(7): 541-7, 2016 07.
Artigo em Inglês | MEDLINE | ID: mdl-27091869

RESUMO

BACKGROUND: Acid suppressive therapy (AST)-namely, proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs)-is routinely prescribed to hospitalized patients for stress ulcer prophylaxis (SUP). OBJECTIVE: To identify the incidence of and indications for AST use in the hematology/oncology population as well as to identify the occurrence of the following PPI-associated adverse events: pneumonia and Clostridium difficile-associated diarrhea (CDAD). METHODS: A retrospective chart review was conducted on adult hematology/oncology patients admitted to any oncology service for ≥48 hours from October 1, 2014, to December 31, 2014. RESULTS: Of the 298 patients who met the inclusion criteria, 73% (n = 218) received an AST during admission. The most common indication for an AST was SUP (63%). The incidence of hospital-acquired pneumonia (HAP) was 10%, 0%, and 4% in patients who received a PPI, H2RA, and no AST, respectively (14/142 vs 0/70 vs 3/80; odds ratio [OR] for PPI vs no AST = 2.68; 95% CI = 0.75-9.63). The incidence of CDAD was 3%, 1.3%, and 1.2% in patients who received a PPI, H2RA, and no AST, respectively (4/142 vs 1/70 vs 1/80; OR for PPI vs H2RA = 1.92; 95% CI = 0.21-17.47). CONCLUSION: This is the first study to describe the incidence of and indications for AST use in the hospitalized hematology/oncology population. There was a high occurrence of AST use, particularly PPIs, in these patients at our institution. Additionally, there was a trend toward an increased risk of HAP and CDAD in patients who received AST during admission.


Assuntos
Diarreia/epidemiologia , Revisão de Uso de Medicamentos/estatística & dados numéricos , Antagonistas dos Receptores H2 da Histamina/efeitos adversos , Úlcera Péptica/prevenção & controle , Pneumonia/epidemiologia , Inibidores da Bomba de Prótons/efeitos adversos , Centros Médicos Acadêmicos/estatística & dados numéricos , Adulto , Clostridioides difficile/isolamento & purificação , Infecção Hospitalar/epidemiologia , Diarreia/induzido quimicamente , Diarreia/microbiologia , Feminino , Doenças Hematológicas/complicações , Doenças Hematológicas/tratamento farmacológico , Antagonistas dos Receptores H2 da Histamina/administração & dosagem , Antagonistas dos Receptores H2 da Histamina/uso terapêutico , Hospitalização , Humanos , Incidência , Masculino , Prontuários Médicos , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Razão de Chances , Úlcera Péptica/epidemiologia , Pneumonia/induzido quimicamente , Inibidores da Bomba de Prótons/administração & dosagem , Inibidores da Bomba de Prótons/uso terapêutico , Estudos Retrospectivos , Fatores de Risco
9.
Expert Opin Biol Ther ; 24(3): 139-146, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38481366

RESUMO

INTRODUCTION: The success of an allogeneic hematopoietic stem cell transplantation (alloHCT) is measured by cure from the underlying malignancy, immune reconstitution (IR), and freedom from graft-versus-host disease, without the continued need for immunosuppressive therapy. AREAS COVERED: Effective IR is critical to the success of alloHCT wherein poor IR can potentially increase the risk of infection and disease relapse. Different stem cell sources give rise to varying patterns of IR. Particularly with umbilical cord blood transplant, delayed IR is commonly seen with associated increased infection rates and non-relapse mortality, attributable to low CD34+ cell doses and predominance of naïve T cells in the graft. Recent FDA approval of omidubicel, an expanded cord blood graft, was granted due to rapid hematologic recovery and a reduced incidence of high-grade infections associated with improved IR. This review focuses on IR and infections seen with omidubicel and compares those to IR after alloHCT with other graft sources. EXPERT OPINION: Characteristics of omidubicel, such as ready availability, high infused CD34+ cell dose, and rapid hematologic and immune recovery improve upon the shortcomings of standard umbilical cord blood transplantation. We feel that the data support the emergence of omidubicel as an alternative donor product.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Humanos , Sangue Fetal , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Transplante Homólogo/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia
10.
Blood Adv ; 8(16): 4281-4293, 2024 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-38916866

RESUMO

ABSTRACT: We evaluate the impact of donor types on outcomes of hematopoietic cell transplantation (HCT) in myelofibrosis, using the Center for International Blood and Marrow Transplant Research registry data for HCTs done between 2013 and 2019. In all 1597 patients, the use of haploidentical donors increased from 3% in 2013 to 19% in 2019. In study-eligible 1032 patients who received peripheral blood grafts for chronic-phase myelofibrosis, 38% of recipients of haploidentical HCT were non-White/Caucasian. Matched sibling donor (MSD)-HCTs were associated with superior overall survival (OS) in the first 3 months (haploidentical hazard ratio [HR], 5.80 [95% confidence interval (CI), 2.52-13.35]; matched unrelated (MUD) HR, 4.50 [95% CI, 2.24-9.03]; mismatched unrelated HR, 5.13 [95% CI, 1.44-18.31]; P < .001). This difference in OS aligns with lower graft failure with MSD (haploidentical HR, 6.11 [95% CI, 2.98-12.54]; matched unrelated HR, 2.33 [95% CI, 1.20-4.51]; mismatched unrelated HR, 1.82 [95% CI, 0.58-5.72]). There was no significant difference in OS among haploidentical, MUD, and mismatched unrelated donor HCTs in the first 3 months. Donor type was not associated with differences in OS beyond 3 months after HCT, relapse, disease-free survival, or OS among patients who underwent HCT within 24 months of diagnosis. Patients who experienced graft failure had more advanced disease and commonly used nonmyeloablative conditioning. Although MSD-HCTs were superior, there is no significant difference in HCT outcomes from haploidentical and MUDs. These results establish haploidentical HCT with posttransplantation cyclophosphamide as a viable option in myelofibrosis, especially for ethnic minorities underrepresented in the donor registries.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária , Humanos , Mielofibrose Primária/terapia , Mielofibrose Primária/mortalidade , Transplante de Células-Tronco Hematopoéticas/métodos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Resultado do Tratamento , Condicionamento Pré-Transplante/métodos , Idoso , Doença Enxerto-Hospedeiro/etiologia , Doadores de Tecidos , Sistema de Registros , Doadores não Relacionados
12.
Cancers (Basel) ; 15(16)2023 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-37627136

RESUMO

Telemedicine has played an important role in delivering healthcare for primary care, chronic disease patients, and those with solid organ malignancies. However, its application in subspecialties such as hematologic malignancies, hematopoietic cell transplantation (HCT), or chimeric antigen receptor-T cell (CAR-T) therapy is not widespread since physical examination is a vital component in delivering care. During the COVID-19 pandemic, we widely used telemedicine, since protecting our immunocompromised patients became our top priority. The employment of HCT and CAR-T therapies continues to grow for high-risk hematologic malignancies, particularly in older and frail patients who must visit specialty centers for treatment access. Generally, HCT and CAR-T therapy care is highly complex, necessitating commitment from patients, caregivers, and a multidisciplinary team at specialty academic centers. All healthcare systems adapted to the crisis and implemented rapid changes during the COVID-19 public health emergency (PHE). Telemedicine, a vital modality for delivering healthcare in underserved areas, experienced rapid expansion, regardless of the geographic region, during the COVID-19 PHE. The data emerging from practices implemented during the PHE are propelling the field of telemedicine forward, particularly for specialties with complex medical treatments such as HCT and CAR-T therapy. In this review, we examine the current data on telemedicine in HCT and cellular therapy care models for the acute and long-term care of our patients.

13.
Ther Adv Hematol ; 14: 20406207231192146, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37664800

RESUMO

Umbilical cord blood (UCB) transplantation (CBT) has been an important alternative donor option for patients lacking matched related donor (MRD) or unrelated donor (URD) grafts. Only 30% of patients with high-risk hematologic malignancies have a human leukocyte antigen (HLA)-identical sibling; subjects without a MRD option are referred for HLA-matched URD selection, or utilize alternative donor sources such as HLA-mismatched URD, UCB, or haploidentical donor grafts. While CBT demonstrates an excellent graft-versus-leukemia (GVL) effect, use of UCB as a graft source is limited due to a lower cell dose that can result in delayed engraftment and an immature immune system with increased infectious risk as a consequence. Together, increased transplant related mortality (TRM) has been associated with UCB allografts. Omidubicel is an ex vivo expanded single cord blood product that has demonstrated rapid engraftment, improved immune reconstitution, and reduced infectious complications in clinical trials. Omidubicel has now been granted U.S. Food & Drug Administration approval to enhance neutrophil recovery and decrease infectious risk. This review will focus on CBT, benefits and barriers to using this alternative donor source, and finally the potential advancements with incorporation of omidubicel in the transplant setting for malignant and non-malignant diseases.

14.
Blood Adv ; 7(9): 1899-1909, 2023 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-36441905

RESUMO

Risk stratification in acute myeloid leukemia (AML) remains principle in survival prognostication and treatment selection. The 2022 European LeukemiaNet (ELN) recommendations were recently published, with notable updates to risk group assignment. The complexity of risk stratification and comparative outcomes between the 2022 and 2017 ELN guidelines remains unknown. This comparative analysis evaluated outcomes between the 2017 and 2022 ELN criteria in patients enrolled within the multicenter Beat AML cohort. Five hundred thirteen patients were included. Most patients had 1 or 2 ELN risk-defining abnormalities. In patients with ≥2 ELN risk-defining mutations, 44% (n = 132) had mutations spanning multiple ELN risk categories. Compared with ELN 2017 criteria, the updated ELN 2022 guidelines changed the assigned risk group in 15% of patients, including 10%, 26%, and 6% of patients categorized as being at ELN 2017 favorable-, intermediate-, and adverse-risk, respectively. The median overall survival across ELN 2022 favorable-, intermediate-, and adverse-risk groups was not reached, 16.8, and 9.7 months, respectively. The ELN 2022 guidelines more accurately stratified survival between patients with intermediate- or adverse-risk AML treated with induction chemotherapy compared with ELN 2017 guidelines. The updated ELN 2022 guidelines better stratify survival between patients with intermediate- or adverse-risk AML treated with induction chemotherapy. The increased complexity of risk stratification with inclusion of additional cytogenetic and molecular aberrations necessitates clinical workflows simplifying risk stratification.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/genética , Fatores de Risco , Mutação , Citogenética , Quimioterapia de Indução
15.
Clin Lymphoma Myeloma Leuk ; 22(12): e1033-e1049, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36192350

RESUMO

AML is a biologically and clinically heterogeneous disease that is associated with poor overall long-term survival. The expanding knowledge of genomic landscape in AML as well as advancements in molecular and chemical biology over the pathway in AML. After 40 years of stagnancy, the recent approval of numerous novel oral anti-leukemic agents for the treatment of AML has changed both the armamentarium of medications and treatment paradigms. These agents have unique clinical considerations in terms of administration, adverse effects, and monitoring parameters which may differ from clinician's historical expectations. Understanding the data, indication and clinical considerations for such novel oral anti-leukemic agents is paramount for clinicians caring patients with AML.


Assuntos
Antineoplásicos , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Antineoplásicos/efeitos adversos
16.
J Adv Pract Oncol ; 12(8): 810-832, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35295545

RESUMO

Chemotherapeutic agents and radiation therapy are associated with numerous potential adverse events (AEs). Many of these common AEs, namely chemotherapy- or radiation-induced nausea and vomiting, hypersensitivity reactions, and edema, can lead to deleterious outcomes (such as treatment nonadherence or cessation, or poor clinical outcomes) if not prevented appropriately. The occurrence and severity of these AEs can be prevented with the correct prescribing of prophylactic medications, often called "premedications." The advanced practitioner in hematology/oncology should have a good understanding of which chemotherapeutic agents are known to place patients at risk for these adverse events as well as be able to determine appropriate prophylactic medications to employ in the prevention of these adverse events. While several guidelines and literature exist regarding best practices for prophylaxis strategies, differences among guidelines and quality of data should be explored in order to accurately implement patient-specific recommendations. Herein, we review the existing literature for prophylaxis and summarize best practices.

17.
Hematol Rep ; 11(2): 7896, 2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31210917

RESUMO

Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia with high induction mortality in the general population despite evidence of high cure rates in the clinical trials. Aggressive supportive care is essential for ideal management of these patients. We conducted a survey to collect data on these important issues required for successful treatment/outcome of APL patients from two states (Michigan and Louisiana) due to their low one-year survival rate among the Surveillance, Epidemiology, and End Results registries. All eligible hospitals (253) were obtained from the Data Medicare online directory. Availability of ATRA, formulary process to obtain it, blood back availability and established treatment protocols for the management of APL patients were queried. Since most of the hospitals surveyed do not have a treatment protocol, we believe that outcome could be improved if a standardized and simplified set of treatment and supportive care guidelines are developed for all hospitals treating APL.

18.
J Pharm Pract ; 30(4): 400-405, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27432462

RESUMO

BACKGROUND: Etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin (EPOCH)-containing regimens are frequently utilized in non-Hodgkin's lymphoma, however, the incidence of febrile neutropenia (FN) in patients receiving inpatient versus outpatient EPOCH has not been described. Additionally, no comparisons have been made regarding financial implications of EPOCH administration in either setting. This study's primary objective was to compare hospital admissions for FN in patients receiving inpatient or outpatient EPOCH. METHODS: A single-center, institutional review board-approved review was conducted for adults receiving EPOCH beginning January 2010. Clinical and financial data were collected through chart review and the institution's financial department. Descriptive statistics were utilized for analysis. RESULTS: A total of 25 patients received 86 cycles of an EPOCH-containing regimen (61 [70.9%] inpatient). Five (8.2%) inpatient cycles resulted in an admission for FN compared to 4 (16%) outpatient cycles. Prophylactic antifungal and antiviral agents were prescribed more often after inpatient cycles (>80%) compared to outpatient cycles (<50%). Overall, 27 (31.4%) of 86 cycles did not receive granulocyte colony-stimulating factor support. Outpatient EPOCH administration was associated with a cost savings of approximately US$141 116 for both chemotherapy costs and hospital day avoidance. CONCLUSION: EPOCH-containing regimens can be safely administered in the outpatient setting, which may result in cost savings for healthcare institutions.


Assuntos
Assistência Ambulatorial/economia , Protocolos de Quimioterapia Combinada Antineoplásica/economia , Custos e Análise de Custo/normas , Hospitalização/economia , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/economia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/economia , Doxorrubicina/administração & dosagem , Doxorrubicina/economia , Esquema de Medicação , Etoposídeo/administração & dosagem , Etoposídeo/economia , Feminino , Humanos , Pacientes Internados , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais , Prednisona/administração & dosagem , Prednisona/economia , Estudos Prospectivos , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/economia
19.
Prehosp Disaster Med ; 21(3): 196-202, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16892885

RESUMO

The earthquake that occurred in Taiwan on 21 September 1999 killed >2,000 people and severely injured many survivors. Despite the large scale and sizeable impact of the event, a complete overview of its consequences and the causes of the inadequate rescue and treatment efforts is limited in the literature. This review examines the way different groups coped with the tragedy and points out the major mistakes made during the process. The effectiveness of Taiwan's emergency preparedness and disaster response system after the earthquake was analyzed. Problems encountered included: (1) an ineffective command center; (2) poor communication; (3) lack of cooperation between the civil government and the military; (4) delayed prehospital care; (5) overloading of hospitals beyond capacity; (6) inadequate staffing; and (7) mismanaged public health measures. The Taiwan Chi-Chi Earthquake experience demonstrates that precise disaster planning, the establishment of one designated central command, improved cooperation between central and local authorities, modern rescue equipment used by trained disaster specialists, rapid prehospital care, and medical personnel availability, as well earthquake-resistant buildings and infrastructure, are all necessary in order to improve disaster responses.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Humanos , Taiwan
20.
Pharmacotherapy ; 36(2): 218-29, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26890915

RESUMO

The prevention and treatment of chemotherapy-induced nausea and vomiting (CINV) continues to pose a challenge for clinicians. The development of 5-hydroxytryptamine (serotonin) antagonists and neurokinin-1 receptor antagonists (NK1 -RAs) have demonstrated significant improvements in acute and delayed CINV for highly and moderately emetogenic chemotherapy. Delayed and breakthrough CINV, however, continue to be difficult to manage despite available treatment agents. Randomized clinical trial data suggest that olanzapine, a second-generation thienobenzodiazepine, traditionally used in the treatment of manifestations of psychotic disorders, is an effective agent in these clinical settings. The short-term use of olanzapine has a favorable adverse event profile and was not associated with grade 3 or 4 toxicity in a phase III study. Olanzapine is recommended as an option within first-line prophylaxis for CINV in the National Comprehensive Cancer Network (NCCN) guidelines and is an option for treatment of refractory CINV in the Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology and NCCN guidelines.


Assuntos
Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Benzodiazepinas/uso terapêutico , Medicina Baseada em Evidências , Náusea/prevenção & controle , Antagonistas da Serotonina/uso terapêutico , Vômito/prevenção & controle , Antieméticos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Benzodiazepinas/efeitos adversos , Institutos de Câncer , Humanos , Agências Internacionais , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Olanzapina , Guias de Prática Clínica como Assunto , Antagonistas da Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Inibidores Seletivos de Recaptação de Serotonina/uso terapêutico , Sociedades Hospitalares , Sociedades Médicas , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
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