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3.
Transplant Cell Ther ; 27(3): 243.e1-243.e6, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33781521

RESUMO

Numerous genetic abnormalities affect treatment outcomes in multiple myeloma. The role of coexistent trisomy or hyperdiploidy and high-risk cytogenetic abnormalities (CGAs) is not well defined. We assessed the influence of overlapping genetic abnormalities in patients who received frontline autologous stem cell transplantation. A total of 491 consecutive patients between January 2009 and January 2016 were identified. High-risk CGAs included del(17p), t(4;14), t(14;16), and gain 1q21 by fluorescence in situ hybridization and del(13) by conventional cytogenetics. Thirty-two percent had a trisomy, 27% had a high-risk CGA, and 11% had both. Among patients with any trisomy, 3-year progression-free survival (PFS) and overall survival (OS) were 60% and 90%, respectively, compared to 25% and 65%, respectively, for patients with any high-risk CGA. Patients with co-existent trisomy and high-risk CGAs had 3-year PFS and OS of 43% and 89%, respectively, whereas those with isolated high-risk CGAs without trisomy had 3-year PFS and OS of 13% and 49%, respectively. The PFS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 1.1 to 3.3; P = .02) and OS (HR, 4.5; 95% CI, 1.5 to 13; P = .006) were worse for high-risk CGAs without versus those with concurrent trisomies. Our findings suggest a protective impact of trisomies in patients with high-risk CGAs and a potential need for revised risk stratification assessments to account for overlapping genetic abnormalities.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Hibridização in Situ Fluorescente , Mieloma Múltiplo/genética , Transplante Autólogo , Resultado do Tratamento
5.
Leuk Lymphoma ; 61(13): 3101-3111, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32723196

RESUMO

The long-term impact of Autologous hematopietic stem cell transplantation (ASCT) on renal function, and the impact of renal function on progression-free survival (PFS) and overall survival (OS) in patients with multiple myeloma are not known. We retrospectively reviewed the records of 885 patients at our institution. We used linear mixed effect models to study the change in estimated glomerular filtration rate (eGFR) and a joint model approach to assess associations between the eGFR, PFS and OS. Sensitivity analyses were conducted at days 0, 100, 180, and 365 post-SCT. eGFR post-ASCT was significantly lower than at day 0 but stabilized at approximately 80 mL/min/1.73 m2. There was no association between eGFR and PFS or OS.; However, relapsed disease and ISS stage were associated with shorter PFS and OS. This data suggests that although there is a modest decline in eGFR post-ASCT, it is not associated with an adverse impact on PFS or OS. KEY POINTS Advanced MM stage at diagnosis was associated with reduced eGFR at all stages of chronic kidney disease. eGFR was not associated with PFS or OS in any of the analyses, but disease-related factors prior to ASCT were all associated with reduced eGFR, PFS and OS. ASCT did not adversely impact kidney function and mitigated the risk of CKD on outcomes in MM.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Intervalo Livre de Doença , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante de Células-Tronco , Transplante Autólogo , Resultado do Tratamento
7.
Clin Cancer Res ; 25(22): 6781-6787, 2019 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-31481508

RESUMO

PURPOSE: Patients with multiple myeloma with t(11;14) have been considered to have standard-risk disease. However, several recent reports have shown contradictory results. We identified 95 patients with multiple myeloma with t(11;14) on FISH studies, who underwent upfront autologous hematopoietic stem cell transplant (auto-HCT) at our center. We compared their outcome with a group of standard-risk patients with multiple myeloma who had diploid cytogenetics by both conventional cytogenetics (CC) and FISH (n = 287). EXPERIMENTAL DESIGN: To reduce the bias between the groups, we performed a 1:1 propensity score matching technique for analysis. A total of 160 patients, 80 in each group, were identified. Patients in the 2 groups were matched for age, International staging system stage at diagnosis, serum creatinine at presentation, disease status at auto-HCT, type of preparative regimens, dose of melphalan used for conditioning, and induction and maintenance regimens. RESULTS: Patients in t(11;14) group had a post auto-HCT overall response rate (ORR) of 97.5% (78/80), compared with 100% (80/80) in the standard-risk control group (P = 0.50). Complete response rate in the t(11;14) group was 35% (28/80), compared with 45% (36/80) in the standard-risk control group (P = 0.26). The 4-year PFS rates were 40.8% (95% CI, 29.6%-56.1%) and 51.1% (95% CI, 39.4%-66.3%) in the t(11;14) and standard-risk control groups, respectively (P = 0.14). The 4-year OS rates were 74.9% (95% CI, 63.3%-88.7%) and 88.3% (95% CI, 80.4%-97.0%) in the t(11;14) and standard-risk control groups, respectively (P = 0.17). Also, patients with t(11;14) with concurrent cytogenetics had significantly poor PFS and OS compared with a propensity matched standard-risk control group. CONCLUSIONS: Our study confirms that t(11;14) multiple myeloma undergoing upfront autologous transplantation had similar outcomes as patients with multiple myeloma with normal cytogenetic and FISH studies. Existence of additional genomic aberrations by CC or FISH was associated with a worse outcome.


Assuntos
Cromossomos Humanos Par 11 , Cromossomos Humanos Par 14 , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Translocação Genética , Idoso , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Estadiamento de Neoplasias , Prognóstico , Pontuação de Propensão , Indução de Remissão , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
9.
Lancet Haematol ; 6(5): e266-e275, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30910541

RESUMO

BACKGROUND: Retrospective studies suggest that conditioning therapy with busulfan plus melphalan could result in longer progression-free survival compared with melphalan alone in patients with multiple myeloma undergoing autologous haemopoietic cell transplantation (auto-HCT). We aimed to test this hypothesis in a randomised trial. METHODS: The primary objective of the study was to compare progression-free survival with conditioning of busulfan plus melphalan with melphalan alone in patients with multiple myeloma. Patients with newly diagnosed multiple myeloma who were eligible for cell transplantation, aged 70 years or younger, with at least stable disease, were randomly assigned (1:1) to treatment. Patients received either busulfan plus melphalan, with a test dose of busulfan 32 mg/m2 followed by pharmacokinetically adjusted doses on days -7, -6, -5, and -4 to achieve a target daily area under the curve (AUC) of 5000 mmol-minute and melphalan 70 mg/m2 per day on days -2 and -1 (total melphalan dose 140 mg/m2), or a melphalan dose of 200 mg/m2 on day -2. Randomisation was performed via a Clinical Trial Conduct Website at the University of Texas MD Anderson Cancer Center. The accrual is complete and final results are presented here. The study is registered with ClinicalTrials.gov, number NCT01413178. FINDINGS: Between Oct 12, 2011, and March 22, 2017, 205 patients were assessed for eligibility and randomly assigned to treatment. The primary analysis of progression-free survival was measured in 202 patients who received treatment: 104 patients in the busulfan plus melphalan group and 98 patients in the melphalan alone group. 90 days after auto-HCT, 102 (98%) of 104 patients given busulfan plus melphalan and 95 (97%) of 98 patients given melphalan alone achieved partial response or better. The median follow-up in the busulfan plus melphalan group was 22·6 months (IQR 15·2-47·1) and 20·2 months (IQR 8·8-46·6) in the melphalan alone group. Median progression-free survival was 64·7 months (32·9-64·7) with busulfan plus melphalan versus 43·5 months (19·9-not estimated) with melphalan alone (hazard ratio 0·53 [95% CI 0·30-0·91]; p=0·022). There were no treatment-related deaths by day 100 in either group. Grade 2-3 mucositis was observed in 77 (74%) of 104 patients in the busulfan plus melphalan group versus 14 (14%) of 98 patients in the melphalan alone group. INTERPRETATION: These findings, if confirmed in other ongoing studies, suggest that busulfan plus melphalan could replace melphalan alone as the conditioning regimen for auto-HCT in patients with newly diagnosed myeloma. FUNDING: This study was funded in part by the National Institutes of Health (NIH) through MD Anderson's Cancer Center Support Grant (CA016672).


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo/terapia , Condicionamento Pré-Transplante , Adulto , Idoso , Bussulfano/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Estimativa de Kaplan-Meier , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Gradação de Tumores , Condicionamento Pré-Transplante/métodos , Transplante Autólogo , Resultado do Tratamento
10.
Leuk Lymphoma ; 60(2): 442-452, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30032678

RESUMO

The aim of our study was to determine the impact of high-risk disease (HRD) and MRD on outcomes in myeloma patients receiving bortezomib-based induction followed by autologous hematopoietic stem cell transplant (auto-HSCT). HRD included t(4:14), t(14;16), del 17p, del 1p and/or amplification 1q by cytogenetics/FISH; all others were standard-risk disease (SRD). A subset of 165 newly diagnosed myeloma patients in a 2:1 ratio of HRD:SRD was generated using propensity score based nearest neighbor matching. Multiparametric flow cytometry (MFC) was used to detect MRD after auto-HSCT in select patients. MRD+ status at 3 months post auto-HSCT (hazard ratio (HR = 4.23, p = .028) and HRD (HR = 1.72, p = .026) were associated with a shorter PFS. Similarly, MRD+ 3 months post auto-HSCT (HR = 6.93, p = .08) and HRD (HR = 3.54, p < .001) and were associated with a shorter OS. Despite bortezomib-based induction, upfront auto-HSCT, and use of maintenance therapy, PFS and OS remained worse in MRD+ and HRD patients.


Assuntos
Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Neoplasia Residual/diagnóstico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Aberrações Cromossômicas , Terapia Combinada , Análise Citogenética , Feminino , Citometria de Fluxo , Predisposição Genética para Doença , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/etiologia , Mieloma Múltiplo/terapia , Prognóstico , Transplante Autólogo , Resultado do Tratamento
13.
Leuk Lymphoma ; 59(8): 1905-1912, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29295650

RESUMO

High-dose melphalan (HDM) followed by autologous hematopoietic cell transplantation (auto-HCT) remains the standard-of-care therapy for multiple myeloma (MM) even with the availability of proteasome inhibitors and immunomodulatory drugs. Gastrointestinal (GI) toxicity is the main cause of morbidity after HDM. Amifostine, a cytoprotective agent, may reduce HDM-associated GI toxicity. We conducted a case control study comparing HDM + auto-HCT with or without amifostine for MM patients. One hundred and seven patients treated at University Hospitals Cleveland Medical Center who received pre-transplant amifostine were compared to 114 patients treated at MD Anderson Cancer Center without use of this agent. Amifostine 740 mg/m2 was administered as a bolus infusion at 24 h and 15 min before HDM. Patients' characteristics were similar in both the groups. Amifostine therapy was well tolerated without any significant adverse effects. Grade II or greater oral mucositis (27.1% vs 47.4%; p = .002), nausea (31.8% vs. 86.0%; p = .0001), vomiting (18.7% vs. 52.6%; p = .0001) and diarrhea (56.1% vs. 72.7%; p = .006) occurred less frequently in the amifostine-treated group. There was no discernable effect of amifostine on engraftment, progression-free or overall survival. Our results indicate that amifostine decreases GI toxicity while preserving anti-myeloma efficacy of HDM and auto-HCT.


Assuntos
Amifostina/administração & dosagem , Gastroenteropatias/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Adulto , Idoso , Estudos de Casos e Controles , Terapia Combinada , Diarreia/etiologia , Diarreia/prevenção & controle , Intervalo Livre de Doença , Feminino , Gastroenteropatias/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Melfalan/efeitos adversos , Pessoa de Meia-Idade , Náusea/etiologia , Náusea/prevenção & controle , Transplante Autólogo , Vômito/etiologia , Vômito/prevenção & controle
15.
Lancet Haematol ; 4(6): e283-e292, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28522110

RESUMO

BACKGROUND: High-dose melphalan is of little benefit as a regimen for patients with relapsed or refractory myeloma undergoing an autologous stem-cell transplant (ASCT). The poor performance of single-agent melphalan in this setting prompted us to study a new high-dose combination of infused gemcitabine, busulfan, and melphalan. METHODS: We did a phase 2 trial at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). We enrolled patients with primary refractory or relapsed myeloma who had received treatment with bortezomib, an immunomodulatory drug, or both, or who were receiving a salvage ASCT. Gemcitabine was infused at 1875 mg/m2 for 3 h for 2 days, followed by busulfan (target area under the curve 4000 µmol/L per min per day for 4 days) and melphalan (60 mg/m2 per day for 2 days). The primary endpoint of this trial was to establish the proportion of patients with measurable disease at ASCT receiving gemcitabine, busulfan, and melphalan who achieved stringent complete remission in accordance with the International Myeloma Working Group criteria. We then retrospectively compared the patients in this study with all other concurrent patients at the MD Anderson Cancer Center who were eligible for this trial but declined to participate or had no financial coverage for ASCT in a clinical trial and instead received melphalan at 200 mg/m2 intravenously over 30 min on 1 day, followed by ASCT (control group). To compare survival outcomes, we used a statistical algorithm to select a subset of patients from this control cohort who were matched in a 1-2:1 ratio with the patients in the gemcitabine, busulfan, and melphalan group by sex, age, disease status, refractory to both proteasome inhibitors and immunomodulatory imide drugs, time from diagnosis to ASCT, and cytogenetic risk. All analyses were per protocol. This is the final analysis of the clinical trial, which is registered at ClinicalTrials.gov, number NCT01237951. FINDINGS: Between Nov 30, 2010, and Dec 11, 2013, we enrolled 74 patients into the gemcitabine, busulfan, and melphalan trial. In these patients, median age was 58 years (IQR 51-62), median number of previous lines of therapy was two (2-5), 38 patients had high-risk cytogenetics, 17 were unresponsive to all previous treatments, and 32 were receiving a salvage ASCT. We identified 184 patients for the concurrent control cohort. The study patients and the concurrent controls received similar post-ASCT maintenance. Among patients with measurable disease at ASCT, 16 of 65 patients (24·6%, 95% CI 14·2-35·0) in the gemcitabine, busulfan, and melphalan group had stringent complete remission compared with 22 of 174 patients (12·6%, 10·1-15·1) in the concurrent control group (p=0·040). Median follow-up time was 36 months (IQR 30-46) in the patients receiving gemcitabine, busulfan, and melphalan and 34 months (25-53) in the matched control subset (n=111). With respect to the secondary survival endpoints, the gemcitabine, busulfan, and melphalan cohort had significantly longer median progression-free survival than the matched control cohort (15·1 months [95% CI 8·7-22·1] vs 9·3 months [8·0-10·7]) with a significantly reduced risk of progression or death (HR 0·55, 95% CI 0·38-0·81, log-rank p=0·030), as well as significantly longer median overall survival (37·5 months [26-not reached] vs 23·0 months [16·6-30·5]) and a lower risk of death (HR 0·60, 0·34-0·84, log-rank p=0·0092). For only the patients treated with gemcitabine, busulfan, and melphalan, grade 3 or worse adverse events included grade 3 mucositis (12 patients), grade 3 dermatitis (five patients), grade 3 aminotransferase elevation (seven patients), grade 3 diarrhoea (two patients), and three treatment-related deaths. One death was cardiac sudden death and two were due to sepsis. INTERPRETATION: Gemcitabine, busulfan, and melphalan is a comparatively safe and active regimen for ASCT in patients with refractory or relapsed myeloma. Better outcomes were achieved in patients who received this regimen than in a concurrent matched cohort receiving melphalan, although this will need to be confirmed in a prospective, randomised trial. FUNDING: Otsuka Pharmaceutical Development & Commercialization and US National Cancer Institute.


Assuntos
Bussulfano/uso terapêutico , Desoxicitidina/análogos & derivados , Melfalan/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Transplante de Células-Tronco , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/cirurgia , Análise de Sobrevida , Transplante Autólogo , Falha de Tratamento
16.
Cancer ; 123(18): 3568-3575, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28513828

RESUMO

BACKGROUND: Despite the introduction of effective, novel agents, the outcome of patients with refractory multiple myeloma remains poor, particularly those who are refractory to both proteasome inhibitors (PIs) and immunomodulatory agents (IMiDs). Limited data are available on the role of autologous hematopoietic stem cell transplantation in this population. METHODS: Patients with refractory myeloma who underwent first autologous hematopoietic stem cell transplantation (auto-HCT) between March 2000 and October 2015 were retrospectively analyzed. Those who had primary refractory disease and those with relapsed and refractory disease were included. Disease that was refractory to at least 1 PI and at least 1 IMiD was classified as double-refractory multiple myeloma (DR-MM). RESULTS: In total, 233 patients were identified, including 105 (45%) classified with DR-MM and 128 (55%) classified with nondouble-refractory myeloma (NDR-MM). At a median follow-up of 42 months for surviving patients, at least a partial response was observed in 188 patients (81%; 83 patients in the DR-MM group [79%] and 105 patients in the NDR-MM [82%]; P = .77). A near complete response or better was observed in 52 patients (22%; 25 patients in the DR-MM group [24%] and 27 patients in the NDR-MM group [21%]; P = .77). The median progression-free survival was 17.6 months (14.4 months in the DR-MM group and 18.2 months in the NDR-MM group), and the 2-year progression-free survival rate was 38% (35% in the DR-MM group and 40% in the NDR-MM group; P = .40). The median overall survival was 48 months (38.9 months in the DR-MM group and 56.6 months in the NDR-MM group), and the 2-year overall survival rate was 74% (71% in the DR-MM group and 76% in the NDR-MM group; P = .27). CONCLUSIONS: The current findings indicate that auto-HCT is an effective and safe therapy in patients with refractory multiple myeloma, including those who are refractory to IMiDs and PIs. Cancer 2017;123:3568-75. © 2017 American Cancer Society.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Causas de Morte , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/terapia , Adulto , Fatores Etários , Idoso , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Imunossupressores/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/patologia , Análise Multivariada , Prognóstico , Inibidores de Proteassoma/uso terapêutico , Indução de Remissão , Estudos Retrospectivos , Medição de Risco , Fatores Sexuais , Análise de Sobrevida , Transplante Autólogo , Falha de Tratamento , Resultado do Tratamento , Estados Unidos
17.
Biol Blood Marrow Transplant ; 22(12): 2159-2164, 2016 12.
Artigo em Inglês | MEDLINE | ID: mdl-27638366

RESUMO

The gain/amplification of the CKS1B gene on chromosome 1q21 region is associated with a poor outcome in patients with multiple myeloma (MM). However, there are limited data on the outcome of patients with CKS1B amplification after a single high-dose chemotherapy and autologous hematopoietic stem cell transplantation (auto-HCT). We retrospectively evaluated the outcome of patients with CKS1B amplification who received an auto-HCT between June 2012 and July 2014 at our institution. We identified 58 patients with MM and CKS1B gene amplification detected by fluorescent in situ hybridization (FISH). We compared their outcomes with a propensity score-matched control group of 58 patients without CKS1B amplification who were treated at approximately the same time. The primary objective was to compare the progression-free (PFS) and overall survival (OS) between the CKS1B and the control groups. Stratified log-rank test with the matched pairs as strata and double robust estimation under the Cox model were used to assess the effect of CKS1B gene amplification on PFS or OS in the matched cohort. Patients in the CKS1B and control groups were well matched for age, gender, disease status, year of auto-HCT, response to pretransplantation therapy, and baseline hemoglobin level. In both groups, 57% patients were in first remission and 43% had relapsed disease at auto-HCT. Twenty-seven (47%) patients with CKS1B amplification had concurrent monosomy 13 or 13q deletion; 6 (10%) by conventional cytogenetics only, 16 (28%) by FISH only, and 5 (9%) by both. Median follow-up after auto-HCT was 25.4 months. The median PFS of the CKS1B and the control groups were 15.0 months and 33.0 months (P = .002), respectively. The median OS have not been reached yet. The 2-year OS rates in the CKS1B and the control groups were 62% and 91% (P = .02), respectively. In conclusion, Patients with CKS1B amplification are more likely to have additional high-risk cytogenetic abnormalities and a shorter PFS and OS after an auto-HCT.


Assuntos
Quinases relacionadas a CDC2 e CDC28/genética , Amplificação de Genes , Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/genética , Mieloma Múltiplo/terapia , Adulto , Idoso , Estudos de Casos e Controles , Aberrações Cromossômicas , Cromossomos Humanos Par 13/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
18.
Am J Hematol ; 91(10): E442-7, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27420405

RESUMO

TP53 gene deletion is associated with poor outcomes in multiple myeloma (MM). We report the outcomes of patients with MM with and without TP53 deletion who underwent immunomodulatory drug (IMiD) and/or proteasome inhibitor (PI) induction followed by autologous hematopoietic stem cell transplant (auto-HCT). We identified 34 patients with MM and TP53 deletion who underwent IMiD and/or PI induction followed by auto-HCT at our institution during 2008-2014. We compared their outcomes with those of control patients (n = 111) with MM without TP53 deletion. Median age at auto-HCT was 59 years in the TP53-deletion group and 58 years in the control group (P = 0.4). Twenty-one patients (62%) with TP53 deletion and 69 controls (62%) achieved at least partial remission before auto-HCT (P = 0.97). Twenty-three patients (68%) with TP53 deletion and 47 controls (42%) had relapsed disease at auto-HCT (P = 0.01). Median progression-free survival was 8 months for patients with TP53 deletion and 28 months for controls (P < 0.001). Median overall survival was 21 months for patients with TP53 deletion and 56 months for controls (P < 0.001). On multivariate analysis of both groups, TP53 deletion (hazard ratio 3.4, 95% confidence interval 1.9-5.8, P < 0.001) and relapsed disease at auto-HCT (hazard ratio 2.0, 95% confidence interval 1.2-3.4, P = 0.008) were associated with a higher risk of earlier progression. In MM patients treated with PI and/or IMiD drugs, and auto-HCT, TP53 deletion and relapsed disease at the time of auto-HCT are independent predictors of progression. Novel approaches should be evaluated in this high-risk population. Am. J. Hematol. 91:E442-E447, 2016. © 2016 Wiley Periodicals, Inc.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Mieloma Múltiplo/terapia , Proteína Supressora de Tumor p53/genética , Adulto , Idoso , Progressão da Doença , Intervalo Livre de Doença , Feminino , Deleção de Genes , Humanos , Fatores Imunológicos/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/genética , Mieloma Múltiplo/mortalidade , Inibidores de Proteassoma/uso terapêutico , Recidiva , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento
19.
Cancer ; 112(9): 2052-9, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18338809

RESUMO

BACKGROUND: Few data exist regarding techniques, indications, and outcomes for sentinel lymph node biopsy in pediatric patients with sarcomas and carcinomas. METHODS: A retrospective 10-year review was conducted, with Institutional Review Board waiver, of the pathology, lymphoscintigraphy, and clinical records for all pediatric patients selected to undergo sentinel lymph node biopsy at a major cancer center. RESULTS: Thirty-one sentinel lymph node biopsies were performed in 30 pediatric patients (median age, 12 years; range, 2-21 years). With the administration of technetium 99m sulfur colloid, sentinel lymph nodes were identified preoperatively in 30 of 31 cases, and intraoperatively in the remaining case. Radiotracer alone was used in 13 of 31 cases but was supplemented with isosulfan blue dye in the remaining 18 cases. There were no complications. Positive sentinel lymph nodes occurred in 1 of 9 patients with rhabdomyosarcoma and in 2 of 5 patients with breast cancer, and in both of these diseases the sentinel lymph node results helped guide treatment decisions. No other patients had positive sentinel lymph nodes, and among those with nonrhabdomyosarcoma soft-tissue sarcomas there were no lymph node basin recurrences despite a lack of lymph node basin irradiation or formal lymph node dissection. The median follow-up was 48 months (range, 0-111 months). CONCLUSIONS: Sentinel lymph node biopsy for pediatric soft-tissue tumors can be performed safely, and the results can alter treatment decisions both for children with rhabdomyosarcoma and adolescents with breast cancer. In patients with nonrhabdomyosarcoma soft-tissue sarcoma, we observed no positive sentinel lymph nodes and no lymph node basin recurrences; these data should prompt the prospective study of sentinel lymph node biopsy as a modality that might help guide the administration or withholding of regional therapy among pediatric patients with nonrhabdomyosarcoma soft-tissue sarcoma.


Assuntos
Carcinoma/patologia , Sarcoma/patologia , Biópsia de Linfonodo Sentinela , Adolescente , Adulto , Neoplasias da Mama/patologia , Criança , Pré-Escolar , Feminino , Humanos , Linfografia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Rabdomiossarcoma/patologia , Sarcoma Alveolar de Partes Moles/patologia , Sarcoma de Células Claras/patologia
20.
J Am Acad Dermatol ; 58(1): 142-8, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18029055

RESUMO

BACKGROUND: Complete surgical excision for lentigo maligna (LM) and LM melanoma (LMM) in the head and neck region may be challenging because of potential significant subclinical extension. OBJECTIVE: We sought to review clinical and histologic features of LM and LMM and determine surgical margin necessary for complete excision. METHODS: We conducted a retrospective study of 117 LM and LMM cases treated with a staged margin-controlled excision technique with rush paraffin-embedded sections. RESULTS: The mean total surgical margin required for excision of LM was 7.1 mm and was 10.3 mm for LMM. Of the tumors diagnosed as LM on initial biopsy specimen, 16% were found to have unsuspected invasion. Total surgical margin was associated with initial clinical lesion diameter. LIMITATIONS: Retrospective and single-institution experience are limitations. CONCLUSION: This study corroborates that the standard excision margins for LM and LMM are often inadequate and occult invasive melanoma occurs in LM. An excision technique with permanent sections using a team of dermatopathology and surgery that carefully examines the central tumor and the surgical margins is reliable for the treatment of LM and LMM.


Assuntos
Neoplasias de Cabeça e Pescoço/cirurgia , Sarda Melanótica de Hutchinson/cirurgia , Melanoma/cirurgia , Neoplasias Primárias Múltiplas/cirurgia , Neoplasias Cutâneas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Sarda Melanótica de Hutchinson/patologia , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Primárias Múltiplas/patologia , Estudos Retrospectivos , Neoplasias Cutâneas/patologia , Procedimentos Cirúrgicos Operatórios/métodos
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