RESUMO
ABSTRACT Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.
Assuntos
Leucemia Promielocítica Aguda/terapia , Protocolos Clínicos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Consórcios de SaúdeRESUMO
Acute promyelocytic leukemia has good prognosis in view of the high complete remission and survival rates achieved with therapies containing all-trans retinoic acid or arsenic trioxide. However, there is a significant risk of death during induction due to hemorrhage secondary to disseminated intravascular coagulation. This has contributed to a gap in the prognosis of patients between developed and developing countries. The International Consortium on Acute Promyelocytic Leukemia was created in 2005 and proposed a treatment protocol based on daunorubicin and all-trans retinoic acid stratified by risk geared toward developing countries. Herein are presented the results from the first patient cohort treated in a single developing country hospital employing a slightly modified version of the International Consortium protocol in a real life setting. Twenty patients with acute promyelocytic leukemia were enrolled: 27.8% had low-risk, 55.6% intermediate risk and 16.7% high-risk. The complete remission rate was 94.4% after a median of 42 days. Both relapse rates and death rates were one patient (5.5%) each. No deaths were observed during consolidation. After a median follow-up of 29 months, the overall survival rate was 89.1%. Efficacy and safety of the International Consortium on Acute Promyelocytic Leukemia protocol has been reproduced in acute promyelocytic leukemia patients from a developing country.
RESUMO
BACKGROUND: Different criteria have been used to diagnose mixed-phenotype acute leukemia (MPAL), which has impacted the number of individuals diagnosed with this pathology. Better outcomes have been reported when using acute lymphoblastic leukemia (ALL)-type chemotherapy in the treatment of MPAL. METHODS: We compared the outcome of 4 groups of patients with MPAL. Group 1 included patients diagnosed using the 2008/2016 World Health Organization (WHO) classification; group 2 included patients diagnosed using the European Group for the Immunological Characterization of Leukemias (EGIL) criteria; group 3 included patients diagnosed using either the EGIL or the 2008/2016 WHO criteria; and group 4 was comprised of patients diagnosed with MPAL using the EGIL classification only. RESULTS: We found a significantly worse disease-free survival (groups 1-4) and overall survival (OS) (groups 2 and 3) when comparing MPAL patients to other acute leukemia (AL) patients. A significantly better OS was obtained in patients (groups 2-4) treated with ALL-type chemotherapy compared to acute myeloid leukemia (AML)-type regimens. CONCLUSION: In light of these results, and because a trend (P=0.06) was found with regard to a better OS in group 4 when compared to other AL patients, an argument can be made that the 2008/2016 WHO classification is underpowered to diagnose all MPAL cases, potentially resulting in the suboptimal treatment of some individuals with AL.
RESUMO
BACKGROUND: Patients with acute leukemia can express aberrant markers, defined as antigens that are normally restricted to a different lineage. The reported significance and frequency of these markers is inconclusive. We assessed the frequency and impact of aberrant markers in patients with acute leukemia in a referral institution in Mexico City. METHODS: We included 433 patients, diagnosed and treated between 2005 and 2015 in our institution. RESULTS: Aberrant markers were expressed in 128 patients (29.6%); CD13 and CD33 were the most frequent aberrant markers in patients with acute lymphoblastic leukemia, while CD7 and CD19 were the most frequent in patients with acute myeloid leukemia. In the univariate analysis, the group with aberrant markers had a lower disease-free survival when compared with the aberrant-free group (8 vs. 13 months) (p = 0.03). Aberrant expression of CD10, CD20, and CD33 correlated with a worse outcome in a statistically significant manner. In the multivariate analysis, male gender, lymphoid lineage, secondary leukemia, high risk at diagnosis, and the presence of aberrant markers had a significantly negative impact on disease-free survival. CONCLUSION: The use of more aggressive treatment strategies could be considered in patients with acute leukemia and an aberrant expression of CD10, CD20, and CD33.
Assuntos
Antígenos CD/sangue , Antígenos de Neoplasias/sangue , Leucemia Mieloide Aguda/sangue , Leucemia-Linfoma Linfoblástico de Células Precursoras/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Leucemia Aguda Bifenotípica/sangue , Masculino , México , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Fatores de Risco , Adulto JovemRESUMO
BACKGROUND: Myelodysplastic syndromes (MDS) are clonal diseases of hematopoietic cells. The International Prognostic Scoring System (IPSS) is the risk scale most employed in MDS. Cyclosporin A (CsA) has been used in the treatment of cytopenias in MDS. OBJECTIVE: To evaluate hematologic response and identify response predictive factors in adults with MDS treated with CsA. MATERIAL AND METHODS: Patients with MDS diagnosed according World Health Organization (WHO) classification were recruited from January 1997 to June 2012. All patients were classified with IPSS, IPSS revised (IPSS-R),WHO Prognostic Scoring System (WPSS), and WPSS revised (WPSS-R) risk scales. Cyclosporin A was administered orally at a dose of 5 mg/kg/day. Hematologic response was evaluated following the International Working Group for MDS (2006 version) criteria. RESULTS: Inclusion criteria were met by 32 patients. Median age was 56.5 years, with a median follow-up of 3.1 years. Hematologic response was 56.2% and erythrocyte independence transfusion was found in 42.9% of patients. Age,hemoglobin level, and WPSS at diagnosis were independent predictive factors for CsA response. Survival was longer in responder than in nonresponder CsA patients (p=0.06). CONCLUSIONS: Cyclosporin A induced hematologic response in >50% of patients with MDS aged <57 years, with Hb<8 g/dl and low WPSS at diagnosis.
Assuntos
Ciclosporina/uso terapêutico , Imunossupressores/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Administração Oral , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Ciclosporina/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: In Mexico, the frequency of thromboembolic events associated to paroxysmal nocturnal hemoglobinuria is 3%; a clone size > 50% in granulocytes has been associated with a higher risk of thromboembolic events. METHODS: Between 2001 and 2012, 40 patients with paroxysmal nocturnal hemoglobinuria were studied. In 12 cases anticoagulant, procoagulant, and fibrinolytic pathways were analyzed. RESULTS: Only two of 40 patients (5%) developed a thromboembolic event over a 25.5-year follow-up period. From 12 patients, 91.7% had a paroxysmal nocturnal hemoglobinuria clone > 50% in granulocytes and 83.3% a clone > 50 % in monocytes. Five of 12 cases had elevated FV levels and four showed increased FVIII, von Willebrand factor antigen, von Willebrand factor ristocetin cofactor activity and FX. Protein S and protein C were decreased in nine and three patients, respectively. Only antithrombin correlated positively with paroxysmal nocturnal hemoglobinuria clone size in monocytes (p = 0.0442), whereas von Willebrand factor ristocetin cofactor correlated negatively with lactic dehydrogenase levels (p = 0.0186). No statistically significant associations were recorded with all other factors. CONCLUSION: The low frequency of thromboembolic events in Mexican patients could partly be explained by the associations between anticoagulant system (antithrombin) with paroxysmal nocturnal hemoglobinuria monocyte clone size, and procoagulant system (von Willebrand factor ristocetin cofactor) with lactic dehydrogenase levels.
Assuntos
Anticoagulantes/metabolismo , Fatores de Coagulação Sanguínea/metabolismo , Hemoglobinúria Paroxística/complicações , Tromboembolia/epidemiologia , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Fibrinólise/fisiologia , Seguimentos , Hemoglobinúria Paroxística/fisiopatologia , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Tromboembolia/etiologia , Adulto JovemRESUMO
BACKGROUND: Laparoscopic splenectomy (LS) is considered the standard treatment for patients with refractory primary immune thrombocytopenia (ITP). PATIENTS AND METHODS: All patients with ITP who underwent LS during the last 17 years and who had a minimum follow-up of 1 year were included. Several perioperative variables such as age, platelet count, and duration of preoperative therapy were recorded and analyzed, looking for potential predictive variables of clinical response. RESULTS: In total, 150 patients were included: 108 (72%) women and 42 (28%) men, with a mean age of 37.3±15.8 years. In the evaluation 1 year after surgery, 133 (88.7%) patients had achieved complete response, 4 (2.7%) had a response, and in 13 (8.6%) there was no response. None of the analyzed preoperative variables was identified as a predictive factor of response at 1 year. Immediate responders after surgery (≥150,000 platelets/mL during the first week) had a higher platelet count and rate of complete response at 1 year (94.2%). CONCLUSIONS: LS has a high success rate in patients with refractory ITP. Potential predictive indicators of success remain to be determined.
Assuntos
Laparoscopia/métodos , Púrpura Trombocitopênica Idiopática/cirurgia , Esplenectomia/métodos , Trombocitopenia/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Laparoscopia/efeitos adversos , Masculino , Pessoa de Meia-Idade , Contagem de Plaquetas , Indução de Remissão , Esplenectomia/efeitos adversos , Resultado do TratamentoRESUMO
Mixed phenotype acute leukemia (MPAL) in adults represents nearly 2 to 5 % of all acute leukemia cases. There are two large studies throughout the world and only case reports and small series have been reported in Latin America. This study retrospectively analyses the clinical characteristics and survival of 27 patients with MPAL evaluated in three medical institutions of Mexico. All cases meet World Health Organization 2008 criteria; 70.3 % of patients had B lymphoid/myeloid lineage MPAL. Induction chemotherapy protocols included 7 + 3 hyper-CVAD, high-density schedules, and pediatric-like regimens such as New York II and total XI. Complete remission was achieved in 23/27 patients (85.2 %). Only one patient died due to chemotherapy-induced aplasia during remission induction (5.2 %). In 68 % of cases, we were able to administer maintenance therapy as a regimen in lymphoblastic leukemia. At the time of analysis, 70.4 % of the patients in the entire cohort had died mainly as result of disease progression (73.6 %). Disease-free survival was 13 months (95 % CI, 9.6-16.3 months) and overall survival was 14.8 months (95 % CI 13.4-16.27). Survival rates are low and standardized therapy for the management of this type of leukemia is still lacking. This is the largest series reported in Mexico and to the best of our knowledge in Latin America.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Imunofenotipagem , Leucemia Aguda Bifenotípica/diagnóstico , Leucemia Aguda Bifenotípica/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Leucemia Aguda Bifenotípica/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida/tendências , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: in Mexico published casuistry concerning hairy cell leukemia (HCL) is limited. OBJECTIVE: to describe the therapeutic response and survival of patients with HCL attended in a third level public institution. METHODS: patient's data with HCL diagnosis registered between January 1989 - December 2009 were analyzed. RESULTS: twenty three patients fulfilled HCL diagnosis criteria. Median age was 44 years (range 23-75 years) and median follow-up of the cohort was 1,877 days (range 1-8,462 days). First line treatment varied along time finding complete response (CR) and partial response (PR) rates of 77.3 and 18.2%, respectively. Of all therapeutic modalities employed cladribine induced the highest response rate. Survival at 1,877 days was 82.6%. At last follow-up 65.2% of patients remain alive, 13 in CR and 2 in PR; 4 died (CR = 2, PR = 1, active disease = 1) and 4 were lost during follow-up. CONCLUSION: this study which included more patients than previous single-institution Mexican series confirm the chronic clinical behavior of HCL and that purine analogs are corner stone in the treatment of patients suffering HCL.
Assuntos
Leucemia de Células Pilosas/mortalidade , Leucemia de Células Pilosas/terapia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Centros de Atenção Terciária , Adulto JovemRESUMO
INTRODUCTION: Acute myeloid leukemia (AML) comprises a group of diseases with different biologic characteristics; despite knowledge improvements, these are not reflected in long term survival. OBJECTIVE: To describe characteristics of adults with AML in a hospital of Mexico City, their treatment response, complications and to evaluate survival related factors. MATERIAL AND METHODS: Cohort study. Between January 2003 and July 2008, patients with AML diagnosis were included (except promyelocitic). Treatment protocols used: 3 + 7, high doses of cytarabine and autologous bone marrow transplant as consolidation therapy. RESULTS: 53 patients were included. Median age: 44 years (15-79). At diagnosis: tumor lysis syndrome in 4/ 53 (7.5%), 3/51 (5.9%) with altered liver function test and hyperleukocytosis in 8/53 (15.1%). 46 patients had available cytogenetic and this was successful in 28/46 (60.8%), 12/28 (42.8%) had adverse cytogenetic; 16/28 (57.1%) intermediate risk and none was favorable. There were 2 losses during follow up, 7 patients did not receive chemotherapy with curative intent and 1 died at diagnosis. 43 patients received 3 + 7, 13.9% died during aplasia, complete remission was achieved in 27/43 (62.7%) and 10/43 (23.2%) were refractory to treatment. A second induction attempt was required in 39.5% (17/43). Median disease free survival (DFS) was 491 days (366-615), with a median follow up of 993 days (105-1744). The median overall survival (OS) was 531 days (312-749). Aplasia related mortality decreased (p = 0.09) between the actual cohort (13.9%) and the historical cohort (37%). CONCLUSIONS: Long term survival in AML patients remains poor despite improvements in diagnosis, classification, and treatment. In our institution, it is required to improve induction protocols and cytogenetic analysis in order to adequately choose the group of patients that could be benefit from stem cell transplant.
Assuntos
Leucemia Mieloide Aguda , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de Tempo , Adulto JovemRESUMO
High P-glycoprotein-mediated multidrug resistance-1 (P-gp/MDR1) activity in lymphocytes from idiopathic thrombocytopenic purpura (ITP) patients may affect disease outcome. ITP treatment includes glucocorticoids that are substrates of P-gp; hence, P-gp functional activity and antigenic expression were assessed by flow cytometry in T and natural killer (NK) cells from ITP patients before and after prednisone therapy. Herein, patients' T and NK cells did not show increased MDR1 functional activity, whereas P-gp antigenic expression was significantly enhanced in both therapy-free and prednisone-treated patients. Prednisone treatment did not significantly modify the function and expression of MDR1 in T and NK cells of ITP patients.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Células Matadoras Naturais/efeitos dos fármacos , Prednisona/farmacologia , Prednisona/uso terapêutico , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Linfócitos T/efeitos dos fármacos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Adulto , Resistência a Múltiplos Medicamentos , Feminino , Humanos , Células Matadoras Naturais/metabolismo , Masculino , Pessoa de Meia-Idade , Púrpura Trombocitopênica Idiopática/metabolismo , Linfócitos T/metabolismoRESUMO
INTRODUCTION: Despite therapeutic advances, acute lymphoblastic leukemia (ALL) in adults remains a disease with poor long term outcome and survival rates. Developing countries lack of information about this disease. On the other hand, infections are frequent complications related to mortality and some research studies do not show accurate rates of septic shock or other related factors. OBJECTIVE: To describe characteristics of adults with acute lymphoblastic leukemia, response to treatment, complications and to evaluate further survival related factors and to compare our experience with other reports of literature. MATERIAL AND METHODS: Between September 2003 to November 2007, the entire cohort of patients with diagnosis of ALL was included. The treatment regimens used were MDACC HyperCVAD (HCVAD) and 0195 (institutional regimen). RESULTS: Of 40 patients included with the diagnosis of ALL, 92% was B phenotype and 8%, T phenotype, with a median age of 27 years. The median follow up was 28.5 months. Initially, 14% showed central nervous system infiltration; of 51% with available cytogenetics, 16.7% was Philadelphia chromosome positive. There were 36 patients who received treatment: 13 received HCVAD and 23 the 0195 protocol; 78% achieved global complete remission, 85% for the patients with HCVAD and 74% with 0195. The induction death rate was 2.8%. The median disease-free survival was 11.6 months (IC 95%, 2.5-20.8 months) and overall survival was 15 months (IC 95%, 10.6-19.4 months). In 95% of patients, no prophylactic antibiotic therapy was used and treatment related death was 8.4% (2.8% during induction and 5.6% during the rest of treatment). Factors associated with worse survival rate were hyperleukocytosis, T phenotype and lack of early complete remission. During induction, grade 3 to 4 non hematopoietic toxicity was 17%. Incidence of neutropenic febrile episodes was 61% and septic shock was 11%. CONCLUSIONS: With HCVAD, we observed worse complete remission, disease-free survival and overall survival rates compared with the original MDACC reports. Chemotherapy related death rates are similar to other early reports, despite prophylactic antibiotic was not used during myelosuppression.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Antibioticoprofilaxia/estatística & dados numéricos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos de Coortes , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Dexametasona/administração & dosagem , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Feminino , Humanos , Contagem de Leucócitos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Transfusão de Plaquetas , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida , Resultado do Tratamento , População Urbana , Vincristina/administração & dosagem , Vincristina/efeitos adversos , Adulto JovemRESUMO
Thalidomide, an immunomodulatory and antiangio genie agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenstróm macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.
La talidomida, agente inmunomodulador y antiangiogénico, es útil en el tratamiento de enfermedades hematologicas y oncológicas. Los efectos adversos asociados al uso de talidomida son múltiples e incluyen bradicardia sinusal que se presenta hasta en 6.8% de los casos. En el presente estudio se informa la frecuencia de bradicardia asociada al uso de talidomida en pacientes con enfermedades hematologicas atendidos en una sola institución. En un lapso de 34 meses se encontró que 33 pacientes con diversos padecimientos hematológicos (mieloma múltiple [MM], 20; síndrome mielodisplásico, ocho; macroglobulinemia de Waldenstróm, dos; linfoma no Hodgkin, dos; histiocitosis maligna, uno) recibieron tratamiento con talidomida. De ellos, cinco (15.1%) presentaron bradicardia, todos con MM. La dosis de talidomida al momento de la bradicardia fue de entre 100 a 300 mg por día y el tiempo que recibieron el fármaco antes del evento osciló entre uno y 18 meses. El electrocardiograma mostró bradicardia sinusal en todos los casos con frecuencia cardiaca (FC) de entre 32 a 48 latidos por minuto. Suspendida la talidomida la FC se normalizó en todos los enfermos en un tiempo que osciló entre 12 a 21 días. Ninguno de los pacientes falleció por esta complicación. Se concluye que: a) la bradicardia asociada a talidomida se identificó sólo en pacientes con MM, b) la frecuencia de bradicardia en nuestra serie fue superior a la informada en otras y c) en MM el tratamiento con talidomida debe prescribirse con precaución en aquellos pacientes con algún padecimiento cardiovascular de cualquier etiología.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Angiogênese/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Doenças Hematológicas/tratamento farmacológico , Talidomida/efeitos adversosRESUMO
Thalidomide, an immunomodulatory and antiangiogenic agent, is useful in the treatment of some hematologic and oncologic diseases. Up to 6.8% of thalidomide-treated patients present bradycardia. Herein the incidence of thalidomide-associated bradycardia in patients with hematologic diseases treated in a single institution is reported. In a 34-month period, 33 patients with different hematologic diseases (multiple myeloma [MM], 20; myelodysplastic syndrome, eight; Waldenström macroglobulinemia, two; non-Hodgkin's lymphoma, two; malignant histiocytosis, one) were treated with thalidomide. Of them, five (15.1%) had bradycardia, all with MM. Bradycardia was detected with a daily thalidomide dose ranging from 100 to 300 mg and the time patients received thalidomide before cardiac event went from one to 18 months. In all affected cases the electrocardiogram showed sinus bradycardia with cardiac frequency between 32 to 48 beats per minute. Time to normal cardiac beat recovery ranged from 12 to 21 days after thalidomide discontinuation. There were no fatalities due to thalidomide-associated bradycardia. It is concluded that: a) thalidomide-associated bradycardia was detected only in patients with MM, b) herein the incidence of bradycardia was higher as compared with other series, and c) in patients with MM thalidomide therapy must be prescribed with caution particularly in those with cardiovascular diseases of any etiology.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Bradicardia/induzido quimicamente , Bradicardia/epidemiologia , Doenças Hematológicas/tratamento farmacológico , Talidomida/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeAssuntos
Desenho de Fármacos , Inibidores Enzimáticos/farmacologia , Proteínas de Fusão bcr-abl/antagonistas & inibidores , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Benzamidas , Ensaios Clínicos como Assunto , Inibidores Enzimáticos/uso terapêutico , Proteínas de Fusão bcr-abl/genética , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Células-Tronco Hematopoéticas/enzimologia , Humanos , Mesilato de Imatinib , Leucemia Mielogênica Crônica BCR-ABL Positiva/enzimologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide de Fase Acelerada/tratamento farmacológico , Leucemia Mieloide de Fase Acelerada/terapia , Estudos Multicêntricos como Assunto , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/enzimologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/enzimologia , Proteínas de Fusão Oncogênica/antagonistas & inibidores , Cromossomo Filadélfia , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Pirimidinas/farmacologia , Pirimidinas/uso terapêutico , Ratos , Terapia de Salvação , Resultado do TratamentoRESUMO
OBJECTIVE: P-glycoprotein (P-gp) expression has been widely observed in normal and neoplastic cells. The physiologic role of P-gp involves hormone and metabolite secretion, bacterial product detoxification, and transport of several drugs to the extracellular space. Multidrug resistance-1 is characterized by drug extrusion through P-gp, reducing the intracellular levels of drugs and diminishing their pharmacological effects. Treatment of immune thrombocytopenic purpura (ITP) includes agents that are substrates of P-gp; hence, the objective of this study was to analyze the functional activity of P-gp in lymphocytes from patients with ITP. PATIENTS AND METHODS: 30 ITP patients (9 refractory, 5 dependent, 14 responders to treatment, and 2 with stable disease) and 25 healthy controls were studied. Peripheral blood mononuclear cells were isolated by gradient centrifugation and incubated with daunorubicin (a fluorescent drug extruded by P-gp). Functional activity of P-gp was analyzed by flow cytometry. Results were expressed as the percentage of lymphocytes able to extrude daunorubicin. RESULTS: ITP patients showed an increased number of lymphocytes with P-gp activity (mean=12.3%+/-16%) when compared to controls (mean=0.87%+/-0.72%) (p<0.05). P-gp function was higher in the refractory group (median=9.4%) than in the treatment-dependent (median=5.4%), responder (median=6.4%), and stable disease (median=5.2%) groups, although no statistical differences were found among them. CONCLUSION: Enhanced P-gp activity in ITP may be related to an unfavorable clinical outcome and poor response to treatment. Furthermore, P-gp function might affect therapeutic requirements for disease control.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Linfócitos/química , Púrpura Trombocitopênica Idiopática/patologia , Adolescente , Adulto , Idoso , Doenças Autoimunes/metabolismo , Doenças Autoimunes/patologia , Biomarcadores , Estudos de Casos e Controles , Daunorrubicina/farmacocinética , Feminino , Citometria de Fluxo , Humanos , Linfócitos/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Púrpura Trombocitopênica Idiopática/metabolismoRESUMO
BACKGROUND: Different flow cytometric methods have been developed to derive absolute CD34(+) cells in predicting transplant outcome. Two techniques for preparing cells for quantification of CD34(+) cells were compared. METHODS: Enumeration of CD34(+) cells in 16 samples of bone marrow (BM) and in 29 samples of mobilized peripheral blood stem cells (PBSC) obtained by leukapheresis was assessed simultaneously by single-platform (ProCOUNT kit) and dual-platform (Milan protocol) approaches within the first 3 h of collection. RESULTS: Absolute number of CD34(+) cells obtained in PBSC and BM using single- and dual-platform methods showed high determination coefficients as follows: for PBSC, slope = 1.0515 +/- 0.048, y-intercept = 88.638 +/- 52.45, and r(2) = 0.941, and for BM, slope = 1.0203 +/- 0.093, y-intercept = 122.25 +/- 20.65, and r(2) = 0.878. There were no statistically significant differences in absolute number of CD34(+) cells from PBSC between single-platform (mean 575/microL, range 70-3683/microL) and dual-platform (786/microL, range 51-3804/microL) assays. In contrast, absolute number of CD34(+) cells from BM was significantly lower (p = 0.0002) when enumerated by ProCount kit (135/microL, 14-758/microL) than with dual-platform method (260/microL, 74-889/microL). CONCLUSIONS: Both approaches can be used indistinctly to estimate absolute number of CD34(+) cells in PBSC but not in BM.
Assuntos
Antígenos CD34/análise , Células da Medula Óssea/citologia , Separação Celular/métodos , Citometria de Fluxo/métodos , Células-Tronco/fisiologia , Contagem de Células , Humanos , Estatística como AssuntoRESUMO
OBJECTIVE: To describe the frequency and compare the clinical characteristics, treatment response, survival and hematologic, immunophenotypic, cytogenetic, and histologic findings in adult patients with acute megakaryoblastic leukemia (AMegL) and megakaryocytic blast crisis of chronic myeloid leukemia (MegBC-CML). MATERIAL AND METHODS: The records of patients with AMegL and MegBC-CML attended in our institution between July 1993 and December 2000 were revised. Megakaryocytic lineage was established by the presence of one or more megakaryocyte/platelet associated antigens (CD41, CD42b, and CD61) in > 20% blast cells. RESULTS: In 90 months, 277 patients with acute leukemia were admitted and 25 with chronic myeloid leukemia (CML) in blast crisis (BC) were identified. Twelve of 125 patients (9.6%) with acute myeloid leukemia were AMegL and 32% of cases with CML-BC were MegBC-CML. Leukemic cells of patients with AMegL expressed more frequently CD15 antigen than blast cells of those with MegBC-CML (83% and 37.5%; p < 0.05). In contrast, blast cells expressing myeloperoxidase were present in 50% and 10% of cases with MegBC-CML and AMegL, respectively (p < 0.05). Only one patient in each group obtained remission. Although median survival in patients with AMegL was lower (70 days) than in those with MegBC-CML (175 days) the difference did not reach statistical significance. CONCLUSION: AMegL and MegBC-CML differ in some clinical and laboratory characteristics and are diseases with poor treatment response and short survival.