Assuntos
Biomarcadores/sangue , Eritropoetina/sangue , Síndromes Mielodisplásicas/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Diferenciação Celular , Células Precursoras Eritroides/patologia , Feminino , Hematínicos/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológicoRESUMO
BACKGROUND: Adequate gluten-free diet (GFD) is the only treatment for coeliac disease (CD). However, no agreement has been reached on either how and when to assess patient adherence to GFD or its effectiveness on villous atrophy. AIM: To assess, in a prospective study, patient adherence to and efficacy of GFD on histological recovery after 1-year of GFD. METHODS: Between 2009 and 2012, we enrolled 65 consecutive newly-diagnosed adult patients (median age 38 years, 18-70) with biopsy-proven atrophic CD. Patients were re-evaluated after 1 year of GFD with duodenal histology, serological assays, symptoms and a dietary interview based on a validated questionnaire. Complete histological recovery was defined as the absence of villous atrophy and ≤30/100 intraepithelial lymphocytes. RESULTS: Overall, 81.5% of patients had adequate adherence (ADA) to GFD, whereas 18.5% had an inadequate adherence (IADA); 66% of ADA patients and no IADA patients achieved complete histological recovery (P < 0.00001). Among ADA patients, antibody seroconversion and symptoms were not significantly different between patients who achieved complete histological recovery and those who achieved partial histological recovery with P = 0.309 and P = 0.197, respectively. Multivariate analysis showed that Marsh 3C was a risk factor for incomplete histological recovery in ADA patients (OR 8.74, 95% CI: 1.87-40.83). CONCLUSIONS: This study shows that complete histological recovery after 1-year of GFD in adult patients, who are assessed as adherent to the GFD, can be obtained in 66% of patients. Patients with severe histological damage at diagnosis are at risk for incomplete histological recovery 1 year later.
Assuntos
Doença Celíaca/dietoterapia , Dieta Livre de Glúten , Duodeno/patologia , Adulto , Atrofia/dietoterapia , Atrofia/patologia , Biópsia , Doença Celíaca/patologia , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Systemic non-Hodgkin lymphomas are often accompanied by cutaneous manifestations, which are not always looked out for. Nevertheless, these alterations can be very important because their presence is lied to the clinical behaviour of the underlying malignancy, with an early recognition being fundamental. The aim of this study was to make order in this topic and propose a preliminary classification of the cutaneous manifestations associated with non-Hodgkin lymphomas. We performed a retrospective chart review of 62 haematological patients affected by non-Hodgkin systemic lymphomas with dermatological manifestations, who were evaluated from January 2007 to December 2011, and combined these results with a systematic review of Pub medical literature from 1937 to 2011 on this topic. A preliminary classification of these manifestations has been proposed, dividing them in specific and non-specific ones, along with a description of the clinical features and those cases observed in our department. A preliminary approach has been proposed for the study of these manifestations that could be helpful in understanding the biological behaviour and aid early recognition of a flare up in systemic non-Hodgkin lymphomas.
Assuntos
Linfoma de Células B/complicações , Linfoma de Células T/complicações , Síndromes Paraneoplásicas/classificação , Dermatopatias/classificação , Dermatopatias/etiologia , Adulto , Idoso , Feminino , Humanos , Linfoma de Células B/patologia , Linfoma de Células T/patologia , Masculino , Pessoa de Meia-Idade , Síndromes Paraneoplásicas/etiologia , Estudos Retrospectivos , Dermatopatias Infecciosas/etiologia , Neoplasias Cutâneas/etiologia , Adulto JovemRESUMO
AIM: In the elderly, prevalence of bleeding- and/or iron malabsorption-related gastrointestinal (GI) causes of iron deficiency anemia (IDA) has not been addressed yet. The aim of this study was to assess the occurrence of malabsorptive diseases and bleeding lesions of the upper and lower GI tract in early (65-74 year-old) and late (over 75 year-old) elderly group compared with adult (50-64 year-old) outpatients. METHODS: The study enrolled 136 consecutive adult (N.=31), early (N.=48) and late elderly (N.=57) IDA outpatients who were referred to the Gastroenterology Department for IDA evaluation and underwent gastroscopy/histology and colonoscopy. RESULTS: Bleeding lesions were significantly less frequent in adult patients than in elderly patients (29% vs. 49.5%, P=0.0252). The most common bleeding lesions were large hiatal hernia (14.7%) and colon cancer (12.5%). Iron malabsorption diseases (Hp-related pangastritis, atrophic body gastritis and celiac disease) were more frequent in the adult group than in the early elderly group (80.6% vs. 56.2%, P=0.0367). In elderly patients, the observed prevalence of bleeding and iron malabsorption IDA causes was similar, whereas in adult patients iron malabsoptive diseases were more frequently detected (P<0.0001). The occurrence of concomitant IDA causes was not different among the three age-groups. CONCLUSION: In the early and late elderly, almost half of GI IDA causes are related to bleeding lesions which are more frequently observed respect to the adult patients. Iron malabsorption diseases affect almost 60% of early and late elderly groups. As for adult patients, an accurate upper and lower endoscopical/histological evaluation diagnoses IDA causes in the vast majority of the elderly outpatients.
Assuntos
Anemia Ferropriva/diagnóstico , Anemia Ferropriva/etiologia , Hemorragia Gastrointestinal/diagnóstico , Hemorragia Gastrointestinal/etiologia , Trato Gastrointestinal Inferior/patologia , Pacientes Ambulatoriais , Trato Gastrointestinal Superior/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia Ferropriva/complicações , Anemia Ferropriva/epidemiologia , Feminino , Humanos , Itália/epidemiologia , Síndromes de Malabsorção/complicações , Síndromes de Malabsorção/etiologia , Masculino , Pessoa de Meia-Idade , Pacientes Ambulatoriais/estatística & dados numéricos , Prevalência , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Improved treatment have modified survival outcome in patients with diffuse large B-cell lymphoma (DLBCL) and altered the importance of previously recognized prognostic markers. DESIGN AND METHODS: To evaluate International Prognostic Index (IPI) score before and after rituximab introduction and to validate the absolute lymphocyte count (ALC)/revised International Prognostic Index (R-IPI) model, we carried out a retrospective analysis on a total of 831 patients with DLBCL. RESULTS: Our results show that IPI lost its discriminating power with the introduction of rituximab. The analysis of our second set allowed us to validate the ALC/R-IPI model. The R-IPI and ALC/R-IPI could still be used for designing clinical trials, but both have difficulty recognizing a high percentage of poor prognosis patients, though it remains an important goal of a good prognostic model considering the modest impact of salvage treatments on survival. CONCLUSIONS: A new model on the basis of significant variables in the rituximab era and built on a large database of patients treated with rituximab is urgently needed. As prognostic models are changing with the efficacy and mechanisms of action of treatment utilized, looking for a new prognostic score is a never-ending story in which researchers are trying to hit a continuously moving target.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Modelos Estatísticos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais Murinos , Feminino , Seguimentos , Humanos , Contagem de Linfócitos , Linfoma Difuso de Grandes Células B/mortalidade , Linfoma Difuso de Grandes Células B/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Rituximab , Taxa de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Iron-deficiency anaemia (IDA) is common in premenopausal women and menorrhagia is often considered responsible. Aim To evaluate prospectively the occurrence of bleeding and iron malabsorption related gastrointestinal (GI) diseases likely responsible of IDA in premenopausal women regardless of their menstrual flow. METHODS: One hundred and eighty-seven premenopausal women [median age 39 (20-56) years] irrespective of their menstrual flow underwent gastroscopy with gastric and duodenal biopsies and faecal occult blood test (FOBT). Patients over 50 years, positive 1st degree family history for colonic cancer and/or positive FOBT underwent colonoscopy too. RESULTS: Menorrhagia was present in 67.4% of premenopausal women. A possible GI cause of IDA was found in 129/187 patients; in 65.2% the cause of IDA was possibly related to iron malabsorption diseases. GI bleeding as a cause of IDA was found in seven patients. An exclusive GI cause of IDA was found in 26.7% of premenopausal women, whereas a possible GI cause was observed in 34.2% of menorrhagic premenopausal women. The main risk factor for the presence of likely GI causes was the presence of upper GI symptoms (OR 5.2: 95% CI = 1.6-16.4). CONCLUSIONS: Most premenopausal women had a possible upper GI cause of IDA because of diseases related to iron malabsorption. Menorrhagia and a GI cause coexist in one-third of women with iron-deficiency anaemia.
Assuntos
Anemia Ferropriva/etiologia , Síndromes de Malabsorção/complicações , Menorragia/complicações , Menstruação/fisiologia , Sangue Oculto , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Ferritinas/sangue , Gastroscopia , Humanos , Pessoa de Meia-Idade , Pré-Menopausa/fisiologia , Estudos Prospectivos , Fatores de Risco , Saúde da MulherRESUMO
The aim of the study was to evaluate the antileukemic effectiveness and toxicity of high-dose hydroxyurea (HHY) and to assess its acute toxicity. Between August 1997 and October 1998, 12 consecutive adult patients (>18 years) with high-risk acute myeloid leukemia (AML) (four patients in first early relapse, seven patients with secondary AML, and one patient with de novo AML concomitant to a lymphoproliferative disorder) were enrolled to receive a single course of HY (100 mg/kg per day) until bone marrow aplasia or for a maximum of 30 days. Of the 12 patients, 5 (41.6%) achieved complete remission (CR), 1 achieved partial remission (PR), 4 were resistant to treatment, and 2 died during induction from infection. No patient with relapsed AML achieved CR, while it was achieved by five of eight patients with secondary AML at diagnosis; five of six MDR1+ patients achieved CR. As concerns follow-up of the CR patients, one did not receive any further treatment and died in CR from pulmonary aspergillosis, and one with a concomitant chronic lymphocytic leukemia (CLL) received two courses of FLAG (fludarabine, cytarabine, granulocyte colony-stimulating factor) regimen with disappearance of the clonal Ig rearrangement, but relapsed after 11 months and died from pneumonia. The remaining three patients were consolidated with two courses of high-dose cytosine arabinoside (AraC), followed by peripheral blood stem cell transplantation (PBSCT) in one patient. One of them relapsed after 3 months, while the other two are still in continuous complete remission (CCR) after 16 and 28 months, respectively. This study has demonstrated the safety and efficacy of HHY in inducing CR in AML patients with unfavorable prognosis. Despite the small number of patients, these encouraging results warrant further studies.
Assuntos
Antineoplásicos/efeitos adversos , Hidroxiureia/administração & dosagem , Leucemia Mieloide/tratamento farmacológico , Adulto , Antineoplásicos/uso terapêutico , Transplante de Medula Óssea , Análise Citogenética , Relação Dose-Resposta a Droga , Feminino , Expressão Gênica , Genes MDR , Humanos , Hidroxiureia/efeitos adversos , Hibridização in Situ Fluorescente , Leucemia Mieloide/genética , Leucemia Mieloide/mortalidade , Leucemia Mieloide/cirurgia , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/etiologia , Transtornos Linfoproliferativos/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Recidiva Local de Neoplasia , Prognóstico , Indução de Remissão , Resultado do TratamentoRESUMO
Between January 1985 and December 1992, 104 consecutive patients with symptomatic myelofibrosis with myeloid metaplasia (MMM) [splenic enlargement >5 cm and/or transfusional requirement or Hb < 10 g/dl and/or white blood cell (WBC) count >20 x 10(9)/l and/or platelets >1.0 x 10(9)/l] received low-dose Melphalan (2.5 mg/3 times/week) to evaluate the efficacy and toxicity of this approach. Among 99 evaluable patients, 66 (66.7%) achieved a response after a median time of 6.7 months: 26 (26.3%) had a normalization of all clinical and haematological parameters (complete response, CR) and 40 (40.4%) showed an improvement >50% (partial response, PR). Thirty-three patients (33.3%) were resistant. Reversible haematological toxicity was the most common complication. Median durations of CR and PR were 28.4 and 26 months respectively: median survival of CR + PR patients was 71.2 months (95%CI: 33.8-108.7) versus 36.5 months (95%CI: 24.5-48.5) for the non-responders (log-rank test, P =0.002). In the multivariate analysis, the following variables were significantly associated with a shorter survival: anaemia [hazard risk (HR) = 2.7], WBC count >20 x 10(9)/l (HR = 2.4) and not achieving any type of response, either partial or complete (HR = 3.9). In conclusion, Melphalan could be a promising first-line option for MMM patients with clinical or haematological symptoms requiring treatment.
Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Melfalan/uso terapêutico , Mielofibrose Primária/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anemia/complicações , Feminino , Seguimentos , Humanos , Contagem de Leucócitos , Masculino , Pessoa de Meia-Idade , Mielofibrose Primária/sangue , Prognóstico , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVES: Spontaneous remission (SR) in de novo myelodysplastic syndromes (MDS) is a rare event, which has been so far described only in children with monosomy 7. The phenomenon is extremely heterogeneous, perhaps depending on different pathogeneses of the disease. DESIGN AND METHODS: We retrospectively evaluated the outcome of 564 consecutive adult patients with primary MDS diagnosed at our Institution in a 12-year period. SR was defined as an unexpected improvement lasting more than 1 year without concomitant treatments other than vitamins or low-dose steroids (in patients with platelets < 50 x 10(9)/L). RESULTS: Nine cases of SR were observed in 3 males and 6 females (median age 38.7 years). At diagnosis, all patients had Hb levels < 10 g/dL and 8/9 required packed red cell transfusions. The median time from diagnosis to SR was 18 months (range 4-46) and all patients had normalization of peripheral blood parameters: in 2 out of 3 patients with karyotypic abnormalities at onset, a cytogenetic remission was documented. The median duration of SR was 56 months; 5 patients are still in SR and 4 patients have relapsed (1 as MDS and 3 as acute myeloid leukemia). INTERPRETATION AND CONCLUSIONS: SR is a rare (less than 2% in our experience) but possible event also in adult MDS patients. It should be kept in mind in the evaluation of experimental treatments for MDS in which very low rates of complete responses are expected.
Assuntos
Síndromes Mielodisplásicas/diagnóstico , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Remissão Espontânea , Estudos RetrospectivosRESUMO
Erythropoietin (EPO) is a glycoprotein synthesized by the kidney, which has a stimulating effect on bone marrow erythroid precursors. It has been identified many years ago, but its clinical use has been developed only since 1985 with the introduction of recombinant molecle (rHuEPO). In the past decade, rHuEPO has been employed in neoplastic as well as in chronic inflammatory diseases associated with anemia, that recognizes a multifactorial pathogenesis: defective endogenous EPO production, impaired erythroid proliferation due to excessive release of inflammatory cytokines, intrinsic abnormalities of erythroid precursors, reticulo-endothelial blockage with reduced erythroid uptake of iron. Anemia of neoplastic diseases, moreover, may be induced or worsened by marrow toxicity of chemotherapy. The efficacy of rHuEPO in these conditions is still unclear.
Assuntos
Eritropoetina/uso terapêutico , Doenças Hematológicas/tratamento farmacológico , HumanosRESUMO
We have shown previously that the antitumor drug, hydroxyurea (HU) is able to induce dose-dependent increases in plasma corticosterone levels in the rat. The drug was administered early in the morning, when the levels of circulating glucocorticoids are low in this species. Normally, in humans under physiological conditions, cortisol levels are elevated early in the morning, to which a sharp decrease follows between 09:00 and 11:00 hours. In a group of healthy volunteers, HU significantly attenuated the decrease in cortisol levels occurring between 09:00 and 11:00 hours with respect to the same subjects receiving placebo. Given the different circadian rhythms of the two species, such an effect of HU in man appeared to be the counterpart of the increase in serum corticosterone occurring in the rat. In the present study, we have attempted to ascertain whether HU is also able to influence adrenocortical function in patients with acute and chronic myeloproliferative disorders undergoing treatments with high doses of the drug. We found that the rate of decline in circulating cortisol observed in patients during the time interval 09:00-11:00 hours was overlapping to that previously found in healthy volunteers treated with HU. In patients, serum cortisol was still elevated at 15:00 hours, since average hormone levels were near to the upper normal limit of the assay. However, in the absence of a control group treated with placebo, we could not draw any clear-cut conclusion as to whether HU was able to modify significantly the pattern of cortisol release in the study population.
Assuntos
Antineoplásicos/farmacologia , Hidrocortisona/sangue , Hidroxiureia/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Transtornos Mieloproliferativos/tratamento farmacológico , Adulto , Idoso , Estudos de Casos e Controles , Doença Crônica , Interações Medicamentosas , Feminino , Humanos , Leucemia Mieloide Aguda/sangue , Masculino , Pessoa de Meia-Idade , Transtornos Mieloproliferativos/sangueRESUMO
To evaluate the addition of a third drug to standard induction chemotherapy in patients with MDS-AML, 23 patients (males/females 13/10, median age 54.3 years, range 24-74 years, median MDS duration 9.8 months, range 2-39 months) who received a standard 2-drugs induction were compared with 23 patients (males/females 11/12, median age 45.6 months, range 21-60 years, median MDS duration 8.3 months, range 2-29 months) who received an intensified 3-drugs induction with etoposide. CR rate, median CR duration and median OS were similar in both groups (48% vs 56%, 4.8 vs 5.9 months, 6.5 vs 7.0 months respectively). Among responding patients, all but one, who underwent allogeneic bone marrow transplantation, relapsed. In conclusion, addition of a third drug (etoposide) does not seem to significantly improve the poor prognosis of MDS-AML patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas , Adulto , Idoso , Citarabina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Infusões Intravenosas , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/patologia , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Indução de RemissãoRESUMO
OBJECTIVES: The purpose of this study has been to investigate by ultrasonographic methods the flow velocities of cerebral arteries because increased blood viscosity due to haematocrit elevation can cause neurological symptoms in polycythaemia vera patients, because of the resulting decrease in cerebral flow. SUBJECTS AND DESIGN: Twenty newly diagnosed patients, with haemoglobin values of > 18 g dl-1 and/or an haematocrit of > 50%, were examined by transcranial Doppler. Recordings were performed in basal conditions and after pharmacological and/or phlebotomic treatment, when haematocrit values were < or = 50%. Blood velocities were evaluated in middle (MCA), anterior (ACA), posterior (PCA) cerebral arteries and in the basilar (BA) artery. RESULTS: Basal recordings showed decreased velocities (MCA: 39.40 +/- 9.34 cm s-1; ACA: 34.05 +/- 10.25 cm s-1; PCA: 31.46 +/- 5.97 cm s-1; and BA: 27.47 +/- 7.42 cm s-1); pre- and post-treatment value differences observed in MCA, ACA and BA were highly significant (P < 0.001). CONCLUSIONS: A decrease in cerebral flow could be a risk for multifocal micro-ischaemic cerebral infarctions leading, after several years, to a multi-infarct dementia; an early reduction in erythrocyte burden should be very useful in polycythaemic patients in preventing lacunar lesions.
Assuntos
Circulação Cerebrovascular/fisiologia , Policitemia Vera/diagnóstico por imagem , Policitemia Vera/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Velocidade do Fluxo Sanguíneo/fisiologia , Viscosidade Sanguínea/fisiologia , Feminino , Hematócrito , Humanos , Masculino , Pessoa de Meia-Idade , Policitemia Vera/sangue , Ultrassonografia Doppler TranscranianaRESUMO
A total of 74 patients with poor risk AML (median age 36.7 years, range 4.5-60.6) received a single course of a regimen including mitoxantrone (6 mg/m2 intravenous bolus daily, days 1 to 6), etoposide (80 mg/m2 intravenous over 1 h, daily, days 1 to 6) and intermediate-dose Ara-C (1 g/m2 over 6 h, daily days 1 to 6). 28 patients had failed initial remission induction with daunorubicin and conventional doses of Ara-C, 16 patients had secondary AML and 30 patients had relapsed from initial remission (five within six months, 15 over six months and ten after autologous or allogeneic bone marrow transplantation). Overall 41/74 patients (55%) achieved complete remission, 26 (35%) had resistant disease and seven (10%) died of infection during marrow hypoplasia. A 4-day course of the same regimen was given as consolidation to patients in complete remission. Subsequent antileukemic therapy was individualized. Profound myelosuppression and pancytopenia were universal resulting in fever or documented infections in almost 100% of patient; major hemorrhagic complications occurred in 39% of patients. Extrahematologic toxicity was mild to moderate consisting mostly of nausea and vomiting, oral mucositis and transient liver and cardiac dysfunction. We conclude that the MEC combination chemotherapy program seems to be an effective antileukemic regimen for secondary and advanced AML, with acceptable toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Criança , Pré-Escolar , Cisplatino/administração & dosagem , Esquema de Medicação , Etoposídeo/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mitoxantrona/administração & dosagem , Risco , Resultado do TratamentoRESUMO
BACKGROUND: It has recently been demonstrated that erythropoietin increases hemoglobin levels in anemia secondary to chronic renal failure. Some recent experiences have suggested a possible role in the treatment of anemia in patients with myelodysplastic syndrome (MDS). METHODS AND RESULTS: From April, 1990 to March, 1991, 16 patients (11 males and 5 females, median age 58.5 years) affected by low-risk myelodysplastic syndromes (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and reduce transfusional requirement. All patients received high doses of rHuEPO (400 U/Kg s.c. twice weekly for 3 months). A partial response, defined as a stable increase in Hb levels > 1g/dL and/or a reduction in transfusional need > 50% lasting at least 3 months, was achieved by 5/16 patients. Those who responded received an additional course of treatment with rHuEPO at an increased dosage (600 U/Kg twice weekly for 3 months), and one of these five showed a progressive rise in Hb level up to normalization, while the other 4 remained stable. The treatment was well tolerated and no adverse reactions were observed. CONCLUSIONS: These results suggest that some patients with MDS may benefit from rHuEPO treatment.
Assuntos
Eritropoetina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Transfusão de Sangue , Terapia Combinada , Avaliação de Medicamentos , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/terapia , Projetos Piloto , Proteínas Recombinantes/uso terapêutico , Resultado do TratamentoRESUMO
It has been recently demonstrated that erythropoietin increases the haemoglobin levels in anemia secondary to chronic renal failure. Moreover some recent experiences also suggested a possible role in the treatment of MDS. From April 1990 to April 1992, 23 patients (16 males and 7 females, median age 63.5 years) affected with low risk myelodysplastic syndrome (MDS) were treated with recombinant human erythropoietin (rHuEPO) to ameliorate Hb levels and transfusional requirement. All patients received high doses of rHuEPO (800 U/Kg weekly s.c. in 2-3 divided doses, for 3 months). A complete remission, defined as stable normalization of Hb level, was achieved in 1/23 patients. This patient had refractory anemia, by FAB criteria. A partial response, defined as stable increase of Hb levels > or = 1 g/dl and/or reduction of transfusional requirement > or = 50% lasting at least 3 months, was achieved in 7/23 patients. Patients with a partial response received rHuEPO at increased dosages (1200 U/Kg weekly s.c. 2-3 times): 1/7 achieved a complete response, 4/7 remained stable and 2/7 decreased to pre-therapy Hb value. These results suggest that rHuEPO may be a promising therapeutic tool for some MDS patients.
Assuntos
Eritropoetina/uso terapêutico , Fatores Imunológicos/uso terapêutico , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , Terapia Combinada , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Proteínas Recombinantes/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
We report the clinical, hematologic, cytogenetic, and molecular characteristics of 13 patients with Philadelphia-negative (Ph-), bcr-negative atypical chronic myelogenous leukemia (CML). In the majority of cases, the phenotypic features at presentation resembled those of typical CML. However, these patients presented with a higher median age, lower median hemoglobin levels, and lower leukocyte and platelet counts than patients with Ph-positive CML. Cytogenetic analysis showed an abnormal karyotype in only one case. Southern blot investigation, using probes exploring the entire M-bcr region, demonstrated the absence of genomic bcr-abl rearrangements. The assessment of clonality in five patients (study of X-methylation patterns in females heterozygous at the DXS255 locus) indicated the proliferation of a monoclonal cell population. Disease evolution was mostly characterized by bone marrow failure, extramedullary infiltrates, and poor response to chemotherapy, without evidence of overt acute transformation. Our observations suggest that some hematologic and clinical features and the modalities of disease progression are presently the most helpful factors in distinguishing these bcr/abl-negative patients from those with typical bcr+CML. The differences existing also with chronic myelomonocytic leukemia (CMMoL), allow the consideration of ph-/bcr- CML as a separate entity, the nature of which remains to be elucidated.
Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Translocação Genética/genética , Citogenética , DNA de Neoplasias/análise , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/fisiopatologia , Indução de Remissão , Análise de SobrevidaRESUMO
A case of acute nonlymphocytic leukemia after radiochemotherapy for Hodgkin's disease, with a rearrangement of 6p23 region, is described. This chromosome change, which has been previously reported in secondary leukemias or myelodysplastic syndromes, was an isolated karyotypic anomaly in our case, which strongly supports the nonrandom involvement of chromosome 6p in induced leukemias.
Assuntos
Cromossomos Humanos Par 6 , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Leucemia Mieloide Aguda/genética , Translocação Genética , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Cariotipagem , Leucemia Mieloide Aguda/induzido quimicamente , Leucemia Mieloide Aguda/etiologia , Leucemia Induzida por Radiação/genéticaRESUMO
Granulocyte-macrophage colony-stimulating factor, (GM-CSF) was given at 8 micrograms/kg daily by continuous i.v. infusion for 72 h to six patients with acute myeloid leukemia (AML) in expansion and one with chronic myeloid leukemia in blastic crisis to determine whether it was possible to augment the proliferative activity of the neoplastic population. The percentage of marrow blasts in S phase (labeling index, LI) was increased in five patients (1.3-, 1.5-, 1.9-, 2.3- and 3.2-fold change). The increase in LI was similar 24 and 48 h after beginning GM-CSF. The RNA Index also increased in patients who showed an increased LI, suggesting that GM-CSF had recruited quiescent neoplastic cells into the cell cycle. Forty eight hours after beginning GM-CSF, chemotherapy was started. The fate of S phase cells, labeled in vivo with bromodeoxyuridine (BrdU) immediately before cytostatic treatment, was monitored. BrdU positive cells were identified by fluorescent antibody for up to 28 days. A preferential killing of BrdU (S phase) cells was observed in 5/7 patients who obtained a complete remission, whereas this was not apparent in the two patients who achieved only a partial remission. Chemotherapy induced a rapid and profound aplasia; its duration, however, was not significantly different from that observed in historical controls. GM-CSF may have a potential role in the treatment of AML, as this study shows that it recruits leukemic cells into the cell cycle without adversely prolonging aplasia after cycle-specific therapy.