RESUMO
Lenalidomide (LEN) can induce red blood cell-transfusion independence (RBC-TI) in 60-70% of del(5q) myelodysplastic neoplasm (MDS) patients. Current recommendation is to continue LEN in responding patients until failure or progression, with likelihood of toxicity and a high cost for healthcare systems. This HARMONY Alliance study investigated the outcome of MDS del(5q) patients who discontinued LEN while RBC-transfusion independent. We enrolled 118 patients with IPSS-R low-intermediate risk. Seventy patients (59%) discontinued LEN for intolerance, 38 (32%) per their physician decision, nine (8%) per their own decision and one (1%) for unknown reasons. After a median follow-up of 49 months from discontinuation, 50/118 patients lost RBC-TI and 22/30 who underwent cytogenetic re-evaluation lost complete cytogenetic response. The median RBC-TI duration was 56 months. In multivariate analysis, RBC-TI duration after LEN discontinuation correlated with low transfusion burden before LEN therapy, treatment ≥ 12 LEN cycles, younger age and higher Hb level at LEN withdrawal. Forty-eight patients were re-treated with LEN for loss of response and 28 achieved again RBC-TI. These data show that stopping LEN therapy in MDS del(5q) patients who reached RBC-TI allows prolonged maintenance of TI in a large subset of patients.
RESUMO
Multiple myeloma (MM) patients complain of pain and stiffness limiting motility. To determine if patients can benefit from vertebroplasty, we assessed muscle activation and co-activation before and after surgery. Five patients with MM and five healthy controls performed sitting-to-standing and lifting tasks. Patients performed the task before and one month after surgery. Surface electromyography (sEMG) was recorded bilaterally over the erector spinae longissimus and rectus abdominis superior muscles to evaluate the trunk muscle activation and co-activation and their mean, maximum, and full width at half maximum were evaluated. Statistical analyses were performed to compare MM patients before and after the surgery, MM and healthy controls and to investigate any correlations between the muscle's parameters and the severity of pain in patients. The results reveal increased activations and co-activations after vertebroplasty as well as in comparison with healthy controls suggesting how MM patients try to control the trunk before and after vertebroplasty surgery. The findings confirm the beneficial effects of vertebral consolidation on the pain experienced by the patient, despite an overall increase in trunk muscle activation and co-activation. Therefore, it is important to provide patients with rehabilitation treatment early after surgery to facilitate the CNS to correctly stabilize the spine without overloading it with excessive co-activations.
Assuntos
Eletromiografia , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/fisiopatologia , Mieloma Múltiplo/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Vertebroplastia/métodos , Músculo Esquelético/fisiopatologia , Músculo Esquelético/cirurgia , Coluna Vertebral/cirurgia , Coluna Vertebral/fisiopatologia , Tronco/fisiopatologia , Tronco/cirurgia , Tronco/fisiologiaRESUMO
Multiple myeloma (MM) is an aggressive malignancy that shapes, during its progression, a pro-tumor microenvironment characterized by altered protein secretion and the gene expression of mesenchymal stem cells (MSCs). In turn, MSCs from MM patients can exert an high pro-tumor activity and play a strong immunosuppressive role. Here, we show, for the first time, greater cell mobility paralleled by the activation of FilaminA (FLNA) in MM-derived MSCs, when compared to healthy donor (HD)-derived MSCs. Moreover, we suggest the possible involvement of the IRE1a-FLNA axis in the control of the MSC migration process. In this way, IRE1a can be considered as a good target candidate for MM therapy, considering its pro-survival, pro-osteoclast and chemoresistance role in the MM microenvironment. Our results suggest that IRE1a downregulation could also interfere with the response of MSCs to MM stimuli, possibly preventing cell-cell adhesion-mediated drug resistance. In addition, further investigations harnessing IRE1a-FLNA interaction could improve the homing efficiency of MSC as cell product for advanced therapy applications.
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Filaminas , Células-Tronco Mesenquimais , Mieloma Múltiplo , Proteínas Serina-Treonina Quinases , Humanos , Movimento Celular , Células-Tronco Mesenquimais/metabolismo , Mieloma Múltiplo/patologia , Fosforilação , Microambiente Tumoral , Filaminas/metabolismo , Proteínas Serina-Treonina Quinases/metabolismoRESUMO
The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0-56.7), and the 18-month overall survival was 73.1% (95%CI:61.6-81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Linfoma de Células T Periférico , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células T Periférico/tratamento farmacológico , Transplante de Células-TroncoRESUMO
BACKGROUND: The hypomethylating agent Decitabine (DAC) is a valuable treatment option in acute myeloid leukemia (AML), particularly in elderly patients (pts) not suitable for intensive chemotherapy (CHT). However, limited data are available about efficacy and safety of DAC in clinical practice. PATIENTS AND METHODS: We retrospectively reviewed data of 104 AML pts treated with DAC in eight Italian Hematological Centers from 2015 to 2017. The objective of this study was to evaluate the efficacy and safety of DAC in older AML pts outside of clinical trial. Seventy-five (75%) pts received DAC as first line treatment (Cohort 1) and 29 pts as salvage therapy (Cohort 2). All pts received a DAC schedule of 20 mg/sqm IV for 5-days, every 28 days. The median age was 72.5 years (74 in cohort 1 and 66 in cohort 2) and 16% of pts had an ECOG performance status >2 at the start of DAC treatment (with non-significant difference in the two cohorts). The cumulative illness rating scale (CIRS) was > 6 in 27% of pts. Forty-five pts (43%) had secondary AML. Bone marrow blast count was > 30% in 64% of patients (67/104). In the relapsed cohort 17/29 (59%) patients were treated with DAC after conventional CHT, 5/29 (17%) after allo-SCT and 7/29 (24%) after azacitidine therapy. RESULTS: A total of 469 DAC cycles were given to the 104 pts with a median of 3 cycles (range 1-21) and 45/104 (43%) pts received > 4 cycles. The Overall Response Rate (ORR = Complete Remission-CR plus Partial Remission-PR) was 33%, significantly higher in Cohort 1 (42%) compared to Cohort 2 (14%) (p = 0.009). The median duration of response was 6 months (range 1-20). In Cohort 1 the best response (CR or PR) was obtained between 3th and 6th cycle. In multivariate Cox regression analysis, achievement of CR or PR (HR = 0.78; p = 0.0004), CIRS < 6 (HR = 0.9; p = 0.04) and complex karyotype (HR = 0.8; p = 0.03) were significant predictors of better overall survival (OS). Median OS from the start of DAC therapy was 11 months for the whole population with a significant OS advantage in Cohort 1 (median OS 12.7 mths vs 6.3 mths; p = 0.003); median OS was significantly longer in responders compared to non-responders (22.6 mths vs 5.7 mths; p < 0.0001). At the last follow-up, 56 patients (54%) are still alive and 48 (46%) are dead (71% due to disease progression). The most common toxicities were myelosuppression and documented infectious complications that occurred mainly during the first 4 cycles. CONCLUSION: These data confirm the efficacy (ORR 33%) and the acceptable safety profile of DAC in the real life management of AML in elderly pts unsuitable for intensive CHT, with a significant better performance in first line therapy (ORR 42%, median OS 12.7 mths). The efficacy of DAC, both in first line and as salvage therapy, may probably be improved with combined treatment strategies and/or with different DAC schedules that could increase its anti-leukemic effect.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Decitabina/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Decitabina/administração & dosagem , Decitabina/efeitos adversos , Feminino , Humanos , Itália , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Indução de Remissão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
We conducted a phase II study to assess activity and safety profile of bendamustine and rituximab in elderly patients with untreated diffuse large B-cell lymphoma (DLBCL) who were prospectively defined as frail using a simplified version of the Comprehensive Geriatric Assessment (CGA). Patients had to be over 70 years of age, with histologically confirmed DLBCL. Frail patients were those younger than 80 years with a frail profile at CGA or older than 80 years with an unfit profile. Treatment consisted of 4-6 courses of bendamustine [90 mg/m2 days (d)1-2] and rituximab (375 mg/m2 d1) administered every 28 days. Other main study end points were complete remission rate and the rate of extra-hematologic adverse events. Forty-nine patients were enrolled of whom 45 were confirmed eligible. Overall, 24 patients achieved a complete remission (53%; 95%CI: 38-68%) and the overall response rate was 62% (95%CI: 47-76%). The most frequent grade 3-4 adverse event was neutropenia (37.8%). Grade 3-4 extra-hematologic adverse events were observed in 7 patients (15.6%; 95%CI: 6.5-29.5%); the most frequent was grade 3 infection in 2 patients. With a median follow up of 33 months (range 1-52), the median progression-free survival was ten months (95%CI: 7-25). The study shows promising activity and manageable toxicity profile of BR combination as first-line therapy for patients with DLBCL who are prospectively defined as frail according to a simplified CGA, as adopted in this trial (clinicaltrials.gov identifier: 01990144).
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Cloridrato de Bendamustina/administração & dosagem , Idoso Fragilizado , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Rituximab/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia de Consolidação/métodos , Feminino , Humanos , Infecções/induzido quimicamente , Itália , Linfoma Difuso de Grandes Células B/mortalidade , Masculino , Neutropenia/induzido quimicamente , Indução de Remissão/métodos , Análise de Sobrevida , Resultado do TratamentoAssuntos
Preservação da Fertilidade , Sobreviventes , Adulto , Feminino , Fertilidade , Humanos , Infertilidade Feminina , Neoplasias , Adulto JovemRESUMO
Life expectancy has impressively increased over the past century and the US population over 65 years is rapidly growing, especially those over 80 years. In fact, persons older than 80 years have increased by more than 250% between the years 1960 and 2000, and it is expected that the population aged >75 years will triple by the year 2030. With the increase of the geriatric population, there is a need for the development and validation of treatment strategies for NHL for these patients. Therapy in elderly patients needs special attention because older patients usually suffered of several co-morbidities and their management represents a challenge for physicians. In fact, older patients treated for lymphoma may not tolerate the high-dose therapies used in younger patients and have increased risk of therapy-related toxicity as a result of age-related physiological changes and frequent co-morbidities. The widespread use of a comprehensive geriatric assessment tool might overcome the difficulty to run prospective clinical trial in elderly patients with lymphoma.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Humanos , Linfoma Difuso de Grandes Células B/diagnósticoRESUMO
This retrospective study of the thrombocythemia Italian registry (RIT) documented that 71 (30.6%) out of 232 ET patients experienced 88 cardiovascular adverse events (CV-AEs) during anagrelide treatment (522 pt-y). The rate of CV-AEs was: 24.1% for palpitations, 4.3% for angina, 3.5% for arterial hypertension, 3.0% for congestive heart failure, 1.8% for arrhythmia, 0.9% for AMI, 0.4% for pericardial effusion. CV-AEs led to treatment discontinuation in nine (3.9%) patients, while in the remaining cases they were managed by pharmacological intervention and/or patient life style improvement. CV-AEs had no relationship with patient characteristics (including older age). A significant relationship was found only with a higher anagrelide induction dose. In the absence of any agreed protocol, a cardiovascular instrumental evaluation (CV-IE) was performed in 102 (44%) patients before commencement of anagrelide (with higher rate after the anagrelide/Xagrid EMA approval of 2004), and in 84 (36%) patients during treatment. Patients with and without CV-IEs, who resulted completely balanced for all their characteristics, did not significantly differ in the occurrence of CV-AEs. In conclusion, this study on ET patients treated with anagrelide shows that CV-AEs, equally distributed in younger and older subjects, were mostly mild and easily manageable, allowing safe treatment continuation in the majority of cases. Moreover, routinely performing a CV-IE did not appear to anticipate the occurrence of CV-AEs.
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Doenças Cardiovasculares/epidemiologia , Quinazolinas/efeitos adversos , Quinazolinas/uso terapêutico , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/epidemiologia , Suspensão de Tratamento/estatística & dados numéricos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/induzido quimicamente , Criança , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/induzido quimicamente , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Inibidores da Agregação Plaquetária/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Quinazolinas/administração & dosagem , Estudos Retrospectivos , Adulto JovemRESUMO
We recently published a study aiming to verify the frequency of amyloid deposits in the bone marrow of patients with multiple myeloma (MM) who did not present any signs or symptoms of systemic amyloidosis, applying the Congo red technique on bone marrow smears obtained by aspiration from the posterior iliac spine. The results suggested that nearly 40% of patients affected by MM may have amyloid deposits in their bone marrow. Subsequently, this finding has not been confirmed by another study performed with histological specimens of bone marrow in a similar clinical setting. To explain this discrepancy, we performed a comparative study on the bone marrows of 36 patients affected by MM, evaluated by both cytological and histological techniques. The results of this study confirm the high frequency of amyloid deposits in the bone marrow of patients affected by MM when the analysis is made on cytological smears, and indicate that the presence of amyloid on marrow smears is confirmed by core biopsies simultaneously performed in only 25% of cases. Should further studies confirm our findings, cytological assessment could be considered a sensitive technique to detect bone marrow amyloid deposits.
Assuntos
Medula Óssea/patologia , Mieloma Múltiplo/patologia , Placa Amiloide/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/diagnóstico , Estudos RetrospectivosRESUMO
Pregnancy is a high-risk event in women with essential thrombocythemia (ET). This observational study evaluated pregnancy outcome in ET patients focusing on the potential impact of aspirin (ASA) or interferon alpha (IFN) treatment during pregnancy. We retrospectively analyzed 122 pregnancies in 92 women consecutively observed in the last 10 years in 17 centers of the Italian thrombocythemia registry (RIT). The live birth rate was 75.4% (92/122 pregnancies). The risk of spontaneous abortion was 2.5-fold higher than in the control population (P < 0.01). ASA did not affect the live birth rate (71/93, 76.3% vs. 21/29, 72.4%, P = 0.67). However, IFN treatment during pregnancy was associated with a better outcome than was management without IFN (live births 19/20, 95% vs. 73/102, 71.6%, P = 0.025), and this finding was supported by multivariate analysis (OR: 0.10; 95% CI: 0.013-0.846, P = 0.034). The JAK2 V617F mutation was associated with a poorer outcome (fetal losses JAK2 V617F positive 9/25, 36% vs. wild type 2/24, 8.3%, P = 0.037), and this association was still significant after multivariate analysis (OR: 6.19; 95% CI: 1.17-32.61; P = 0.038). No outcome concordance between first and second pregnancies was found (P = 0.30). Maternal complications occurred in 8% of cases. In this retrospective study, in consecutively observed pregnant ET patients, IFN treatment was associated with a higher live birth rate, while ASA treatment was not. In addition, the JAK2 V617F mutation was confirmed to be an adverse prognostic factor.
Assuntos
Complicações na Gravidez/epidemiologia , Resultado da Gravidez/epidemiologia , Trombocitemia Essencial/epidemiologia , Adolescente , Adulto , Aspirina/administração & dosagem , Aspirina/efeitos adversos , Aspirina/uso terapêutico , Feminino , Humanos , Interferon Tipo I/administração & dosagem , Interferon Tipo I/efeitos adversos , Interferon Tipo I/uso terapêutico , Itália/epidemiologia , Janus Quinase 2/genética , Pessoa de Meia-Idade , Análise Multivariada , Mutação , Paridade , Contagem de Plaquetas , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/etiologia , Complicações na Gravidez/genética , Complicações na Gravidez/prevenção & controle , Proteínas Recombinantes , Sistema de Registros , Estudos Retrospectivos , Trombocitemia Essencial/sangue , Trombocitemia Essencial/complicações , Trombocitemia Essencial/tratamento farmacológico , Trombocitemia Essencial/genética , Adulto JovemRESUMO
In this work, the effects of thalassemia, a blood disease quite diffuse in the Mediterranean sea region, have been investigated at single cell level using a Raman Tweezers system. By resonant excitation of hemoglobin Raman bands, we have examined the oxygenation capability of beta-thalassemic erythrocytes. A reduction of this fundamental erythrocyte function has been found. The measurements have been performed on a significant number of red blood cells; the relative statistical analysis is presented. Moreover, the response to photo-induced oxidative stress of diseased cells with respect to the normal ones has been analyzed. Finally, the deformability of thalassemic erythrocytes has been quantified by measuring the membrane shear modulus by using a double-trap system: the measurements have revealed an increase in membrane rigidity of more than 40%, giving evidence that the genetic defect associated to thalassemia, which manly relies on hemoglobin structure, also strongly affects the erythrocyte mechanical properties. Our results demonstrate that the developed set-up may have potential for the monitoring of blood diseases and their response to drug therapies.
Assuntos
Eritrócitos/patologia , Eritrócitos/fisiologia , Pinças Ópticas , Análise Espectral Raman/métodos , Talassemia/patologia , Talassemia/fisiopatologia , Células Cultivadas , Elasticidade , Humanos , Valores de Referência , Análise Espectral/métodos , Estresse MecânicoAssuntos
Fator de Transcrição GATA1/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Policitemia Vera/genética , Mielofibrose Primária/genética , Trombocitemia Essencial/genética , Adulto , Idoso , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Janus Quinase 2/genética , Masculino , Pessoa de Meia-Idade , Regulação para CimaRESUMO
The deformability of red blood cells flowing in microvessels is essential to maintain optimal blood circulation and to allow gas transfer between blood and tissues. Here, we report on an experimental methodology to investigate the deformability of RBCs flowing in microcapillaries having diameter close to the average cell size. The microcapillaries are placed in a rectangular flow cell, where a suspension of RBCs, properly diluted in albumin-additioned ACD, is fed through a syringe under the action of a liquid head in the physiological range. Video microscopy images of the flowing RBCs are acquired at high magnification and later processed by an automated image analysis macro. It was found that RBCs from healthy donors exhibit the classical parachute shape observed in vivo. Furthermore, all the data of healthy RBC velocity vs liquid head are well represented by the same linear regression, independently on the donor. Preliminary results on beta-thalassemia RBCs are also presented and show, on the average, a reduced velocity compared to healthy samples.
Assuntos
Deformação Eritrocítica/fisiologia , Eritrócitos/fisiologia , Hemorreologia/métodos , Velocidade do Fluxo Sanguíneo/fisiologia , Capilares/fisiologia , Tamanho Celular , Eritrócitos/ultraestrutura , Humanos , Interpretação de Imagem Assistida por Computador , Microscopia de Vídeo , Talassemia beta/sangueRESUMO
The accuracy of standard methods in estimating bulky lesions requires validation. We used clinical/computed tomography (CT) evaluation and power Doppler ultrasound (US) to detect bulky disease in 137 consecutive Hodgkin's lymphoma patients, and analyzed the prognostic relevance of each method. Bulky disease was detected by clinical/CT evaluation in 47% of the patients and by power Doppler US in 20%. After treatment, at multivariate analysis power Doppler US-selected bulky disease was the parameter that best correlated with freedom from treatment failure (p<0.001). Power Doppler US, a readily available imaging technique, provides a better prognostic classification by detecting true bulky disease more accurately.
Assuntos
Doença de Hodgkin/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Ultrassonografia Doppler/métodos , Adolescente , Adulto , Idoso , Erros de Diagnóstico , Feminino , Doença de Hodgkin/patologia , Humanos , Linfonodos/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X/normas , Ultrassonografia Doppler/normasRESUMO
Six patients with bone marrow micrometastases from solid cancers presented with increased numbers of circulating CD34+ cells; the CD34+ cell counts were very high in some cases. By contrast, no patient with metastatic cancer without bone marrow involvement showed raised numbers of circulating hemopoietic progenitors.
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Anemia Mielopática/metabolismo , Antígenos CD34/sangue , Adulto , Idoso , Antígenos de Diferenciação Mielomonocítica/metabolismo , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase NeoplásicaRESUMO
OBJECTIVES: In the past essential thrombocythemia was considered a disease of the elderly. At present, the number of young people suffering from this disease is growing, with a slightly higher frequency in females. We investigated the effects of interferon alfa therapy in these patients. STUDY DESIGN: We describe 9 pregnancies in 4 women affected by essential thrombocythemia. RESULTS: Four pregnancies were carried out without interferon alfa therapy, and resulted in 2 intrauterine deaths, 1 spontaneous abortion, and 1 neonatal death. Interferon alfa was given during another 5 pregnancies; among them, 2 ended in preterm deliveries with normal infants, and 3 in full-term deliveries. The literature is reviewed. CONCLUSION: Our cases and published series suggest that fetal outcome is improved by therapy, and that interferon alfa may be the best therapeutic option.
Assuntos
Interferon-alfa/uso terapêutico , Complicações Hematológicas na Gravidez/diagnóstico , Resultado da Gravidez , Trombocitemia Essencial/diagnóstico , Trombocitemia Essencial/tratamento farmacológico , Aborto Espontâneo , Adulto , Feminino , Morte Fetal , Seguimentos , Idade Gestacional , Humanos , Gravidez , Complicações Hematológicas na Gravidez/mortalidade , Medição de Risco , Índice de Gravidade de Doença , Trombocitemia Essencial/mortalidade , Resultado do TratamentoRESUMO
PURPOSE: The sensitivity of lymph node excisional biopsy requires validation. Power Doppler ultrasound (US) helps predict the malignant status of lymphadenopathies. We used power Doppler US to select for biopsy the lymph node most suspected of malignancy. PATIENTS AND METHODS: One hundred fifty-two patients having lymphadenopathies with clinical suspicion of lymphoma were divided into two well-matched groups and randomly assigned to undergo either standard or power Doppler US-directed lymph node excisional biopsy. RESULTS: Histology showed a malignancy in 64% of patients in the standard group (lymphoma, 49 patients; carcinoma, two patients) and in 87% of patients in the US-assisted group (lymphoma, 62 patients; carcinoma, one patient). There were significantly fewer biopsy-related complications in the assisted group than in the standard group. During the follow-up of the patients with lymph nodes reported as being reactive, 14 of 29 patients in the standard group were rebiopsied and were found to have lymphoma (13 patients) or carcinoma at the subsequent lymph node histology, whereas none of the patients in the assisted group (nine patients) required a second biopsy. Thus, biopsy provided false-negative results for malignancy in 21% of patients affected by lymphoma in the standard group and never in the assisted group (P <.01). CONCLUSION: Power Doppler US is an accurate tool for screening lymphadenopathies to be removed by excisional biopsy in patients with suspected lymphoma.
Assuntos
Carcinoma/diagnóstico , Doenças Linfáticas/etiologia , Doenças Linfáticas/patologia , Linfoma/diagnóstico , Ultrassonografia Doppler/métodos , Ultrassonografia de Intervenção/métodos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Biópsia/métodos , Carcinoma/patologia , Reações Falso-Negativas , Feminino , Humanos , Linfoma/patologia , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND AND OBJECTIVES: Chemotherapy can cause hepatitis flare-up through viral reactivation in patients who have had contact with hepatitis viruses. Few data are available on the genotype of the reactivated viruses. DESIGN AND METHODS: In 40 consecutive adult patients with indolent non-Hodgkin's lymphoma (NHL) receiving fludarabine-based front-line chemotherapy, we performed a prospective study on viral hepatitis reactivation and analyzed the genotype of the reactivated viruses. Before chemotherapy, 4 patients were healthy carriers of hepatitis B surface antigen (HBsAg), 2 had HB core antigen antibodies (anti-HBc), 6 anti-HBs and 6 anti-HCV; 22 were seronegative. RESULTS: Hepatitis flare-up occurred in the 4 HBsAg-positive patients and in 1 anti-HBc-positive patient at a median of 1 month (range 1-4) after chemotherapy, when the CD4/CD8 ratio was still inverted. HBV reactivation was documented in all 5 instances (HBV-DNA 2-8 x 10(6) copies/mL). Two of the 5 patients responded to lamivudine, whereas 1 died of acute liver failure and 2 had persistent severe hepatitis. HBV genome sequencing at hepatitis flare-up showed that deviation from the closest related published sequences was 1.0% and 1.1% in the 2 lamivudine-responsive patients, and 1.5%, 1.8% and 1.7% in the 3 lamivudine-resistant patients. The polymerase open reading frame (ORF) and the HBs ORF of lamivudine-resistant strains contained several novel amino acid substitutions. INTERPRETATION AND CONCLUSIONS: These results suggest that fludarabine treatment of HBV-infected patients is frequently associated with acute hepatitis due to viral reactivation, and that lamivudine may be less effective in this situation than in other settings of immunocompromised hosts because of the emergence of resistant mutant strains.