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1.
Blood ; 141(3): 295-308, 2023 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-36260765

RESUMO

We designed a prospective, observational study enrolling patients presenting for treatment of acute myeloid leukemia (AML) at 13 institutions to analyze associations between hematopoietic cell transplantation (HCT) and survival, quality of life (QOL), and function in: the entire cohort, those aged ≥65 years, those with high comorbidity burden, intermediate cytogenetic risk, adverse cytogenetic risk, and first complete remission with or without measurable residual disease. Patient were assessed 8 times over 2 years. Time-dependent regression models were used. Among 692 patients that were evaluable, 46% received HCT with a 2-year survival of 58%. In unadjusted models, HCT was associated with reduced risks of mortality most of the subgroups. However, after accounting for covariates associated with increased mortality (age, comorbidity burden, disease risks, frailty, impaired QOL, depression, and impaired function), the associations between HCT and longer survival disappeared in most subgroups. Although function, social life, performance status, and depressive symptoms were better for those selected for HCT, these health advantages were lost after receiving HCT. Recipients and nonrecipients of HCT similarly ranked and expected cure as main goal of therapy, whereas physicians had greater expectations for cure than the former. Accounting for health impairments negates survival benefits from HCT for AML, suggesting that the unadjusted observed benefit is mostly owing to selection of the healthier candidates. Considering patients' overall expectations of cure but also the QOL burdens of HCT motivate the need for randomized trials to identify the best candidates for HCT. This trial was registered at www.clinicaltrials.gov as #NCT01929408.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Idoso , Qualidade de Vida , Estudos Prospectivos , Indução de Remissão , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos
2.
Blood ; 138(5): 387-400, 2021 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-34351368

RESUMO

Less-intensive induction therapies are increasingly used in older patients with acute myeloid leukemia (AML). Using an AML composite model (AML-CM) assigning higher scores to older age, increased comorbidity burdens, and adverse cytogenetic risks, we defined 3 distinct prognostic groups and compared outcomes after less-intensive vs intensive induction therapies in a multicenter retrospective cohort (n = 1292) treated at 6 institutions from 2008 to 2012 and a prospective cohort (n = 695) treated at 13 institutions from 2013 to 2017. Prospective study included impacts of Karnofsky performance status (KPS), quality of life (QOL), and physician perception of cure. In the retrospective cohort, recipients of less-intensive therapies were older and had more comorbidities, more adverse cytogenetics, and worse KPS. Less-intensive therapies were associated with higher risks of mortality in AML-CM scores of 4 to 6, 7 to 9, and ≥10. Results were independent of allogeneic transplantation and similar in those age 70 to 79 years. In the prospective cohort, the 2 groups were similar in baseline QOL, geriatric assessment, and patient outcome preferences. Higher mortality risks were seen after less-intensive therapies. However, in models adjusted for age, physician-assigned KPS, and chance of cure, mortality risks and QOL were similar. Less-intensive therapy recipients had shorter length of hospitalization (LOH). Our study questions the survival and QOL benefits (except LOH) of less-intensive therapies in patients with AML, including those age 70 to 79 years or with high comorbidity burdens. A randomized trial in older/medically infirm patients is required to better assess the value of less-intensive and intensive therapies or their combination. This trial was registered at www.clinicaltrials.gov as #NCT01929408.


Assuntos
Cuidados Críticos , Leucemia Mieloide Aguda , Qualidade de Vida , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida
3.
Br J Haematol ; 183(4): 601-607, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30596402

RESUMO

We sought to develop a safe and effective outpatient salvage regimen by replacing ifosfamide within the (R)ICE (rituximab, ifosfomide, carboplatin, etoposide) regimen with bendamustine (T(R)EC) via a multicentre phase I/II study for patients with relapsed or refractory diffuse large B cell lymphoma (DLBCL) and classic Hodgkin lymphoma (HL). Therapy consisted of 60-120 mg/m2 per day bendamustine on days 1 and 2 in combination with carboplatin, etoposide and rituximab (only for CD20+ lymphoma) used in the (R)ICE regimen for up to 2 cycles. The objectives were to define a maximally tolerated dose (MTD) of bendamustine, determine safety and toxicity, assess efficacy, and evaluate impact on stem cell collection. Forty-eight patients were treated of which 71% had refractory disease. No dose-limiting toxicities were observed. The recommended phase II dose of bendamustine was 120 mg/m2 per day on days 1 and 2. Response rates were 85% (70% complete response, CR) in HL, and 65% (40% CR) in DLBCL. Stem cell collection was successful in 30 of 32 patients. The most common non-haematological toxicities ≥grade 3 were febrile neutropenia (8%) and dehydration (8%). The T(R)EC regimen safely yields high response rates, successfully mobilizes peripheral blood stem cells and compares favourably to RICE, offering an effective outpatient treatment option for patients with relapsed or refractory DLBCL and HL.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cloridrato de Bendamustina/administração & dosagem , Cloridrato de Bendamustina/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Desidratação/induzido quimicamente , Desidratação/epidemiologia , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Neutropenia Febril/induzido quimicamente , Neutropenia Febril/epidemiologia , Feminino , Humanos , Linfoma Difuso de Grandes Células B/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recidiva , Rituximab/administração & dosagem , Rituximab/efeitos adversos
4.
Transplantation ; 85(1): 22-8, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18192907

RESUMO

BACKGROUND: Posttransplantation thrombotic microangiopathy (PTMA) is a complication of allogeneic hematopoietic stem cell transplantation (HSCT). However, limited autopsy data are available, and it remains unclear whether PTMA is a discrete clinical and pathologic entity. The aims of this autopsy study were to determine the correlation between clinical and pathologic diagnosis of PTMA, to define the precise morphologic spectrum of PTMA, and to seek for potential etiologic factors. METHODS: The study included 20 consecutive patients with HSCT autopsied at the University of Oklahoma, between 1994 and 2005. Applying strict clinical-laboratory criteria, 6 patients were diagnosed clinically with PTMA and treated with plasma exchange. Clinical variables, including underlying disease, conditioning regimen, stem cell donor status, duration and serum level of cyclosporine, infections, and acute graft versus host disease were compared statistically in patients with histologic signs of PTMA (n=8) with those without PTMA (n=12). RESULTS: PTMA was verified histologically in all 6 patients with a clinical diagnosis of PTMA but only 2 of the 14 patients who were not clinically diagnosed had histologic evidence of PTMA (P<0.0001). Kidneys were affected in all 8 patients with PTMA, and limited extrarenal involvement by PTMA was observed in 3 of these 8 patients. No statistically significant differences in relevant clinical and morphologic variables were identified between the PTMA and non-PTMA groups. CONCLUSIONS: This study documents a strong correlation between the clinical and morphologic diagnosis of PTMA. The kidney is the primary target of PTMA, with dominant glomerular and arteriolar involvement. The etiology is likely to be multifactorial.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Trombose/etiologia , Adolescente , Adulto , Autopsia , Criança , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/patologia , Humanos , Rim/irrigação sanguínea , Rim/patologia , Masculino , Pessoa de Meia-Idade , Trombose/diagnóstico , Trombose/patologia , Transplante Homólogo/efeitos adversos
5.
Cancer Genet Cytogenet ; 169(1): 73-5, 2006 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-16875941

RESUMO

Aplastic anemia is a rare, serious disease characterized by hypocellular bone marrow and pancytopenia in the peripheral blood. Most cases are acquired, idiopathic, and without gross cytogenetic abnormalities. A few chromosome abnormalities have recurred among a small subset of patients, most commonly trisomy 8 and monosomy 7. Some of these chromosome abnormalities have prognostic and therapeutic significance, although for most the clinical relevance is not known. We present the case of a 40-year-old man with idiopathic severe aplastic anemia in bone marrow cells with trisomy of the whole long arm of chromosome 1 due to an unbalanced translocation between chromosomes 1 and 15 at breakpoints of q10 and 15q10. This clonal abnormality (which, to our knowledge, has not been previously reported in a patient with aplastic anemia) suggests that genes on 1q may be involved in marrow aplasia.


Assuntos
Anemia Aplástica/genética , Cromossomos Humanos Par 1 , Trissomia , Adulto , Feminino , Humanos , Cariotipagem
6.
Int J Hematol ; 81(2): 119-25, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15765779

RESUMO

We define chronic refractory immune thrombocytopenic purpura (ITP) as ITP with persistent thrombocytopenia following treatment with glucocorticoids and splenectomy. Chronic refractory ITP is uncommon, occurring in fewer than 10% of all adult patients with ITP diagnoses. The goal of treatment is only to achieve a safe platelet count with minimal treatment-related risk. A safe platelet count may be considered to be as low as 10,000/microL, because the risk for major bleeding in otherwise healthy subjects is great only when the platelet count is less than 10,000/microL. Observation without specific treatment is appropriate for patients with moderate thrombocytopenia and no clinically important bleeding symptoms. For patients with chronic refractory ITP who require treatment, there is no consensus for what therapies to use or the sequence in which to use them. For patients with severe and symptomatic thrombocytopenia, the use of anti-CD20 (rituximab) and immunosuppressive agents, alone or in combination, may be most effective. The mechanism of all current therapies is to decrease the accelerated platelet destruction brought about by immunosuppression. An alternative approach, the stimulation of platelet production with thrombopoietic agents, has been successful in investigational studies and may provide a new management option.


Assuntos
Púrpura Trombocitopênica Idiopática/terapia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Doença Crônica , Quimioterapia Combinada , Hemorragia/etiologia , Hemorragia/mortalidade , Humanos , Imunossupressores/uso terapêutico , Prognóstico , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/mortalidade , Rituximab , Esplenectomia
7.
Laryngoscope ; 118(8): 1357-61, 2008 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-18528311

RESUMO

OBJECTIVES/HYPOTHESIS: To assess the efficacy of paclitaxel, ifosfamide, and cisplatinum induction chemotherapy plus concurrent chemoradiation in the treatment of stage III and IV base of tongue cancer. STUDY DESIGN: Subgroup analysis of patients with base of tongue cancer enrolled in a single-institution prospective phase II trial, evaluating an organ-preservation approach in the treatment of locally advanced head and neck cancer. METHODS: Eighteen patients with tumors ranging from stage T2-T4, any N, or M0 were treated with a protocol of induction chemotherapy, with Taxol, ifosfamide, cisplatin every 21 days for up to three cycles. If the primary tumor exhibited a complete or partial response, patients were treated with radiation and weekly taxol and carboplatin for 7 weeks. Surgery was used for those with less than partial response or disease progression. Neck dissection was performed in cases with clinical or radiological evidence of persistent disease in the neck 6 to 8 weeks after completion of treatment. RESULTS: Sixteen patients were male and two were female; the average age was 55 years (range, 43-65). Fifteen patients had stage IV disease and three had stage III disease. Of the 18 patients initially enrolled, 17 patients had a complete response. All 17 patients had no evidence of loco-regional disease at a median follow-up of 29.6 months. Only 1 of them developed distant metastases 30 months after completion of treatment. Three patients required permanent percutaneous endoscopic gastrostomy tubes because of severe dysphagia associated with concurrent chemoradiation. CONCLUSIONS: The treatment regimen studied is remarkably effective in stage III and IV base of tongue cancer with 100% of patients completing the protocol alive to date. Although some patients required persistent percutaneous endoscopic gastrostomy use, no patient experienced significant enough toxicity during the protocol to delay or withdraw from treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Neoplasias da Língua/tratamento farmacológico , Neoplasias da Língua/radioterapia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/secundário , Carcinoma de Células Escamosas/cirurgia , Cisplatino/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Ifosfamida/administração & dosagem , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Doenças do Sistema Nervoso/induzido quimicamente , Paclitaxel/administração & dosagem , Radioterapia Adjuvante , Taxa de Sobrevida , Neoplasias da Língua/mortalidade , Neoplasias da Língua/patologia , Neoplasias da Língua/cirurgia
8.
Curr Opin Oncol ; 19(2): 148-54, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17272988

RESUMO

PURPOSE OF REVIEW: The aim of this article is to assess the current understanding and uncertainties about the evaluation and management of thrombotic microangiopathy that occurs following allogeneic hematopoietic stem cell transplantation. RECENT FINDINGS: Current data may not be sufficient to establish posttransplantation thrombotic microangiopathy as a discrete clinical or pathologic entity, distinct from other well recognized transplant-related complications. Analysis of case series of posttransplantation thrombotic microangiopathy illustrates uncertainties regarding incidence, risk factors, diagnosis, treatment, and survival. These studies have suggested the lack of efficacy of plasma exchange treatment and have identified other transplant-related complications, such as acute graft-versus-host disease and opportunistic infections, as the predominant causes of death in patients who had been diagnosed with posttransplantation thrombotic microangiopathy. Recently consensus diagnostic criteria were proposed by two independent groups to provide more uniform identification of patients with posttransplantation thrombotic microangiopathy; these criteria may result in a clearer definition of this syndrome. SUMMARY: Posttransplantation thrombotic microangiopathy remains a diagnostic and therapeutic challenge. Further studies are required to determine if it is a specific entity and to define its relation to other transplant-related complications.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Púrpura Trombocitopênica Trombótica/etiologia , Transplante Homólogo/efeitos adversos , Humanos , Prognóstico , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Fatores de Risco
9.
J Oncol Pharm Pract ; 13(2): 69-75, 2007 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17873106

RESUMO

OBJECTIVE: The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT(3))antagonists in revolutionizing the management of platinum-based chemotherapy-induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT(3) antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting cleary endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest. METHODS: Data for patients (n=159) receiving platinum-based chemotherapy regimens were retrospectively collected . Patients getting 5-HT(3) antagonists without steriods or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered , number of cycles, and Eastern Cooperative Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of > or = grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic eficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity. RESULTS: A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron ( n=157), granisetron ( n=81), and ondansetron ( n=131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p=0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p=0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting ( p= 0.15 and p=0.63, respectively). However, complete nausea control was signinficantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p<0.05). CONCLUSION: No significant difference exists in the antiemetic efficacy of the three 5-HT(3) antagonists studied in controlling CINV when administered in combination with dexamethasone. Choicce of antiemetic regimen should therefore be based on drug cost.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Náusea , Antagonistas do Receptor 5-HT3 de Serotonina , Vômito , Doença Aguda , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antieméticos/administração & dosagem , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Dexametasona/administração & dosagem , Dexametasona/farmacologia , Dexametasona/uso terapêutico , Feminino , Granisetron/farmacologia , Granisetron/uso terapêutico , Humanos , Indóis/farmacologia , Indóis/uso terapêutico , Masculino , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/tratamento farmacológico , Ondansetron/farmacologia , Ondansetron/uso terapêutico , Compostos de Platina/administração & dosagem , Quinolizinas/farmacologia , Quinolizinas/uso terapêutico , Estudos Retrospectivos , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
10.
J Clin Apher ; 21(1): 49-56, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16619232

RESUMO

The rationale for immunosuppressive therapy of thrombotic thrombocytopenic purpura (TTP) was established by observations that TTP may be caused by autoantibodies to ADAMTS13. Patients with high-titer autoantibodies to ADAMTS13 may have a higher mortality, and survivors may require prolonged plasma exchange therapy in spite of adjunctive glucocorticoid treatment. More intensive immunosuppressive therapy with rituximab may provide benefit for many of these patients. The Transfusion Medicine/Hemostasis Clinical Trials Network is developing a randomized, clinical trial to test the hypothesis that addition of rituximab to standard treatment of TTP with plasma exchange and glucocorticoids will decrease initial treatment failure rates as well as subsequent relapses over the following 3 years. To provide the background data for this clinical trial, a systematic review of all published reports on rituximab treatment of immune-mediated disorders was performed. Twelve articles have reported 27 patients treated with rituximab for TTP, with benefit described in 25 (93%) of the patients. Additional reports have described rituximab treatment of 37 other immune-mediated disorders, with clinical response in most patients. These observations from small uncontrolled case series provide the background and rationale for a randomized clinical trial to establish the role of rituximab in the management of patients with TTP.


Assuntos
Anticorpos Monoclonais , Ensaios Clínicos como Assunto , Púrpura Trombocitopênica Trombótica , Humanos , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais Murinos , Protocolos Clínicos , Glucocorticoides/uso terapêutico , Doenças do Sistema Imunitário/tratamento farmacológico , Terapia de Imunossupressão/métodos , Troca Plasmática , Púrpura Trombocitopênica Trombótica/tratamento farmacológico , Projetos de Pesquisa , Rituximab , Ensaios Clínicos Controlados Aleatórios como Assunto
11.
Blood ; 104(9): 2623-34, 2004 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-15217831

RESUMO

Splenectomy has been a standard treatment for adult patients with idiopathic thrombocytopenic purpura (ITP) for more than 50 years. However, the durability of responses, the ability to predict who will respond, and the frequency of surgical complications with splenectomy all remain uncertain. To better interpret current knowledge we systematically identified and reviewed all 135 case series, 1966 to 2004, that described 15 or more consecutive patients who had splenectomy for ITP and that had data for 1 of these 3 outcomes. Complete response was defined as a normal platelet count following splenectomy and for the duration of follow-up with no additional treatment. Forty-seven case series reported complete response in 1731 (66%) of 2623 adult patients with follow-up for 1 to 153 months; complete response rates did not correlate with duration of follow-up (r = -0.103, P = .49). None of 12 preoperative characteristics that have been reported consistently predicted response to splenectomy. Mortality was 1.0% (48 of 4955 patients) with laparotomy and 0.2% (3 of 1301 patients) with laparoscopy. Complication rates were 12.9% (318 of 2465) with laparotomy and 9.6% (88 of 921 patients) with laparoscopic splenectomy. Although the risk of surgery is an important consideration, splenectomy provides a high frequency of durable responses for adult patients with ITP.


Assuntos
Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/efeitos adversos , Adulto , Humanos , MEDLINE , Contagem de Plaquetas , Complicações Pós-Operatórias , Prognóstico , Púrpura Trombocitopênica Idiopática/complicações , Esplenectomia/estatística & dados numéricos
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