RESUMO
Acquired aplastic anemia (AA) is a rare heterogeneous disorder characterized by pancytopenia and hypoplastic bone marrow. The incidence is 2-3 per million population per year in the Western world, but 3 times higher in East Asia. Survival in severe aplastic anemia (SAA) has improved significantly due to advances in hematopoietic stem cell transplantation (HSCT), immunosuppressive therapy, biologic agents, and supportive care. In SAA, HSCT from a matched sibling donor (MSD) is the first-line treatment. If a MSD is not available, options include immunosuppressive therapy (IST), matched unrelated donor, or haploidentical HSCT. The purpose of this guideline is to provide health care professionals with clear guidance on the diagnosis and management of pediatric patients with AA. A preliminary evidence-based document prepared by a group of pediatric hematologists of the Bone Marrow Failure Study Group of the Italian Association of Pediatric Hemato-Oncology (AIEOP) was discussed, modified and approved during a series of consensus conferences that started online during COVID 19 and continued in the following years, according to procedures previously validated by the AIEOP Board of Directors.
Assuntos
Anemia Aplástica , Transplante de Células-Tronco Hematopoéticas , Anemia Aplástica/terapia , Anemia Aplástica/diagnóstico , Anemia Aplástica/etiologia , Humanos , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Itália , COVID-19/diagnóstico , Imunossupressores/uso terapêutico , SARS-CoV-2RESUMO
The objective of the study was to evaluate the incidence, characteristics, treatment and outcome of acute megakaryoblastic leukemia (AMeL) in patients enrolled in GIMEMA trials. Between 1982 and 1999, 3603 new consecutive cases of AML aged over 15 years were admitted to GIMEMA trials. Of them, 24 were AMeL. The incidence of AMeL among AML patients enrolled in GIMEMA trials was 0.6% (24/3603). Diagnosis was based on morphological criteria. Out of 11 cytogenetic studies performed two presented chromosome 3 abnormalities. Twelve patients (50%) reached a CR, five (21%) died in induction and seven (27%) were unresponsive. The median duration of CR was 35 weeks (range 10-441). Seven patients underwent transplantation procedures (1 BMT, 4 aBMT, 2 aPBSCT). Four patients died in CR due to chemotherapy-related complications. Comparing the CR rate between AMeL and the other cases of AML enrolled in GIMEMA trials, no differences were observed. These results were mirrored for different age groups. The median survival was 40 weeks. At present, after a follow-up of a minimum of 2 years, only two patients are alive in CR, all the others having died. A 5-year Kaplan-Meier curve shows a disease-free survival of 17% and an actuarial overall survival of 10%. AMeL is a rare form of AML. The CR duration and the overall survival in this group of patients are very poor, even if similar to those observed in other AML. Furthermore, a high number of deaths in CR were observed. On the basis of these data, a specific therapeutic approach, possibly with innovative treatments, should be evaluated.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea , Leucemia Megacarioblástica Aguda/terapia , Adolescente , Adulto , Idoso , Criança , Terapia Combinada , Análise Citogenética , Feminino , Humanos , Imunofenotipagem , Leucemia Megacarioblástica Aguda/mortalidade , Leucemia Megacarioblástica Aguda/patologia , Pessoa de Meia-Idade , Indução de Remissão , Taxa de Sobrevida , Resultado do TratamentoRESUMO
We describe a single center experience of 41 consecutive patients with poor prognosis acute myeloid leukemia (AML) who received a single course of FLAG regimen consisting of Fludarabine 30 mg/m2/day plus Cytarabine 2 gr/m2/day (days 1-5) and G-CSF 5 mg/Kg/day (from day 0 to polymorphonuclear recovery) as salvage therapy. Eleven patients were primarily refractory to previous chemotherapy, 10 patients were in first relapse, 2 patients in second relapse and 7 patients in relapse after transplants. Eleven cases were defined as secondary AML (diagnosis of AML made after a preexisting diagnosis of myelodysplastic syndrome). The median age was 52.6 years (range 16-72); 29 patients were males and 12 females. Overall, 23 (56%) patients reached complete remission (CR), 3 patients died of infection (2) or hemorrhage (1) during induction, and 15 (36%) patients had resistant disease. The highest CR rates (80%) were obtained in relapsed cases; de novo and secondary AML registered 60% and 45% of CR rates, respectively. Patients achieving CR received a second FLAG course as consolidation and were submitted to an individualized program post-remission therapy, depending on the age and performance status. Hematological and non hematological toxicities were acceptable. In conclusion, our data confirm that FLAG is a an high effective treatment for poor prognosis AML and in young patients allows intensive post remissional therapy including allogeneic BMT.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide/tratamento farmacológico , Vidarabina/análogos & derivados , Doença Aguda , Adolescente , Adulto , Fatores Etários , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Estudos de Coortes , Citarabina/administração & dosagem , Citarabina/toxicidade , Intervalo Livre de Doença , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/toxicidade , Humanos , Infecções/etiologia , Infecções/mortalidade , Leucemia Mieloide/complicações , Leucemia Mieloide/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Terapia de Salvação , Fatores Sexuais , Vidarabina/administração & dosagem , Vidarabina/toxicidadeAssuntos
Doença de Gaucher/diagnóstico , Doença de Gaucher/imunologia , Adolescente , Linfócitos B/classificação , Linfócitos B/citologia , Medula Óssea/patologia , Citometria de Fluxo , Doença de Gaucher/patologia , Humanos , Imunofenotipagem , Ativação Linfocitária , Masculino , Células-Tronco/classificação , Células-Tronco/citologiaRESUMO
Low levels of factor X (F.X) were detected in a 4-year-old boy who experienced acute lymphoblastic leukemia and bleeding manifestations. Laboratory data suggested the presence of a dysfunctional F.X molecule. Two novel F.X gene mutations were identified in the proband that was double heterozygous for both: a microdeletion (delC556) in exon VI resulting in a frameshift leading to a termination codon at position 226. This deletion was found in six family members with reduced F.X antigen and activity levels. A second mutation characterised by a G(1344)-->C transversion in exon VIII was detected in the proband resulting in a Lys(408)-->Asn substitution. This latter mutation was present in several asymptomatic family members from the paternal and the maternal side. The proband's sister was homozygous for the Lys(408)-->Asn substitution and exhibited low F.X activity with a normal antigen level. The naturally occurring F.X Lys(408)-->Asn (F.X(K408N)) variant was isolated from plasma of either homozygous or double heterozygous individuals. NH(2)-terminal sequencing of the heavy chain of F.X(K408N) failed to show any sequence abnormality in patients who were also carriers of the delC556, suggesting that this latter lesion accounted for the lack of F.X synthesis. Purified F.X Lys(408)-->Asn had an identical behaviour to normal F.X as judged by SDS-PAGE and immunoblotting. Clotting assay using purified F.X(K408N) and F.X-deficient plasma resulted in a laboratory phenotype similar to that observed in a homozygous subject for F.X Lys(408)-->Asn substitution. This is the first characterisation of a naturally occurring F.X variant with a mutation at the COOH-terminal end of the molecule.
Assuntos
Deficiência do Fator X/genética , Fator X/genética , Mutação , Sequência de Aminoácidos , Substituição de Aminoácidos , Sequência de Bases , Pré-Escolar , Códon de Terminação/genética , DNA/genética , Análise Mutacional de DNA , Deficiência do Fator X/sangue , Deficiência do Fator X/complicações , Feminino , Mutação da Fase de Leitura , Variação Genética , Genótipo , Heterozigoto , Homozigoto , Humanos , Itália , Masculino , Mutação de Sentido Incorreto , Linhagem , Fenótipo , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Deleção de SequênciaRESUMO
Sixty-one adults aged <55 years with acute lymphoblastic leukaemia (ALL) in first bone marrow relapse were enrolled in an Italian cooperative study (ALL R-87 protocol) from 12 GIMEMA Institutions. The treatment programme consisted of: (1) an induction phase with intermediate-dose cytarabine (IDARA-C 1 g/m2, 6 h daily infusion x 6 d) plus idarubicin (IDA; 5 mg/m2/d x 6 d) and prednisone (40 mg/m2/d x 21 d), (2) a consolidation phase followed by (3) bone marrow transplant (BMT). Median first complete remission (CR) duration was 8.5 months (range 1-54 months). 34/61 patients achieved CR (56%); 24 (39%) failed to respond and three (5%) died during induction. Most responders (24 patients) could not enter the BMT programme; 15 relapsed early (median time to relapse 2 months); nine were withdrawn due to toxicity and one died in CR of infection. Nine of the 34 CRs underwent BMT (five autologous and four allogeneic). Three of the four allotransplanted patients are alive in continuous CR at 22, 43 and 63 months; only one of the five who underwent an autologous BMT is alive in CR at 46 months. The estimated disease-free survival (DFS +/- SE) at 36 months was 0.16 +/- 0.08 for all responders. Univariate analysis showed that previous therapy was the only prognostic factor influencing DFS. The estimated probabilities of event-free survival (EFS +/- SE) and survival +/- SE at 37 months were 0.09 +/- 0.04 and 0.10 +/- 0.04, respectively. The EFS was significantly better in patients with a preceding CR > or = 24 months, compared to those with a shorter first remission. Our results confirm the tolerance and efficacy of IDARA-C plus IDA in inducing CR in poor-risk adult ALL. Even though the number of transplanted patients was small, allogeneic BMT seems to give a real opportunity of cure in this category of patients.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Transplante de Medula Óssea/mortalidade , Terapia Combinada/mortalidade , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Feminino , Humanos , Idarubicina/administração & dosagem , Idarubicina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Estudos Prospectivos , Recidiva , Análise de Sobrevida , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND AND OBJECTIVE: The prognostic significance of CD34 antigen expression in acute lymphoblastic leukemias (ALL), especially in adult patients, is still not well established. In the present report we analyzed a series of biological and clinical findings from 128 ALL patients in order to evaluate the possible clinical significance of this marker. METHODS: The clinical and biological significance of CD34 expression, an early marker of hemopoietic cells, was analyzed by flow cytometry in a series of 128 patients affected by ALL, including 78 adults and 50 children under 15 years old. RESULTS: Overall, 68.7% of patients showed significant ( > 10%) CD34 expression. There was no difference between CD34+ and CD34- ALL with respect to age, sex, FAB morphology, hepatosplenomegaly, Plt count, Hb level, DNA index, P-170 expression. CD34+ ALL displayed a significantly lower frequency of extramedullary involvement, a lower LDH level and lower WBC count, lower proliferative activity (as evaluated by the Ki67 monoclonal antibody) than CD34- ALL. CD34 expression was also associated with early phenotypes in both B- and T-ALL, co-expression of myeloid antigens, and the presence of the Ph1 chromosome. Due to a different distribution of prognostic factors investigated, DFS and OS were both significantly better in CD34+ than in CD34- childhood ALL, whereas no statistical difference was found in adults. Multivariate analyses confirmed these data in children. INTERPRETATION AND CONCLUSIONS: Expression of the CD34 antigen is a positive prognostic factor in childhood ALL. In adult ALL the presence of this marker on leukemic cell does not seem to influence the clinical outcome of these patients.
Assuntos
Antígenos CD34/biossíntese , Antígenos de Neoplasias/biossíntese , Regulação Leucêmica da Expressão Gênica , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/genética , Antígenos de Neoplasias/genética , Biomarcadores Tumorais , Divisão Celular , Criança , Pré-Escolar , DNA de Neoplasias/análise , Intervalo Livre de Doença , Feminino , Células-Tronco Hematopoéticas/imunologia , Células-Tronco Hematopoéticas/patologia , Humanos , Imunofenotipagem , Lactente , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/imunologia , Células-Tronco Neoplásicas/patologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
Clinical and biological parameters were retrospectively reviewed in 34 cases of T-lineage acute lymphoblastic leukemia (T-ALL), classified as "early" (20 cases) or "late" (14 cases) subgroups, according to the degree of blast cell differentiation, assessed by immunophenotyping. In "early" T-ALL, age, co-expression of "immature" (CD34 and HLA-Dr) or myeloid (My+) antigens, proliferative activity (as evaluated by Ki67 monoclonal antibody), and expression of the "multidrug-resistance" (MDR) phenotype (as determined by C-219 monoclonal antibody) were significantly higher, while WBC count and expression of CDl0 were significantly lower, than in "late" T-ALL. Furthermore, although no statistically significant difference was found between the two groups, "late" T-ALL more frequently displayed a greater extramedullary tumor mass ("lymphoma-like" syndrome), LI FAB morphology and a normal karyotype. A single patient, with "late" T-ALL, also showed positivity for TCR gamma/delta chains, specific monoclonal antibodies. On the whole, 30 patients (88.2%) achieved complete remission: 16(80%) were "early" and 14(100%) "late" T-ALL. No statistical difference was found between the two groups with respect to disease free survival (42% vs 54% at six years), whereas median overall survival was significantly shorter in "early" T-ALL (23 months vs median not yet reached at six years for "late" T-ALL, p < 0.05). We conclude that "early" and "late" T-ALL show clinical and biological differences, that could perhaps justify differential therapeutic approaches.
Assuntos
Leucemia-Linfoma de Células T do Adulto/classificação , Células-Tronco Neoplásicas/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Diferenciação Celular , Criança , Pré-Escolar , Aberrações Cromossômicas , Intervalo Livre de Doença , Feminino , Humanos , Imunofenotipagem , Leucemia-Linfoma de Células T do Adulto/tratamento farmacológico , Leucemia-Linfoma de Células T do Adulto/genética , Leucemia-Linfoma de Células T do Adulto/mortalidade , Leucemia-Linfoma de Células T do Adulto/patologia , Contagem de Leucócitos , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/análise , Células-Tronco Neoplásicas/química , Prognóstico , Indução de Remissão , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
We describe the case of an infant with immune thrombocytopenia whose bone marrow showed an increased percentage of CD10/TdT-positive lymphoid cells that resembled the onset of an acute lymphoproliferative disorder. Genotypic analysis of bone marrow, however, failed to reveal the malignant origin of these B cell precursors. After 8 months of follow-up, the child is alive and well, and shows a chronic form of ITP. Although a relation between this B cell proliferation and the onset of ITP cannot be excluded, it is important to consider this atypical pattern as a benign hematologic condition.
Assuntos
Medula Óssea/imunologia , DNA Nucleotidilexotransferase/análise , Neprilisina/análise , Trombocitopenia/imunologia , Medula Óssea/enzimologia , Feminino , Humanos , Lactente , Trombocitopenia/enzimologiaRESUMO
One hundred and forty-seven patients aged < 55 years with advanced acute lymphoblastic leukaemia (ALL) were enrolled in an Italian cooperative study (ALL R-87). This protocol consists of an induction phase with idarubicin (IDA) plus intermediate-dose cytarabine (IDARA-C), followed by a consolidation phase and bone marrow transplant (BMT). Complete remission (CR) was achieved in 97/147 patients (66%) with a CR rate of 77% in children versus 51% in adults (P < 0.01). 48 responders (50%) underwent BMT. Probability of event-free survival (EFS +/- SE) was 10.2 +/- 3.1% at 56 months. EFS was 14.3 +/- 4.51% at 56 months for children versus 3.8 +/- 3.41% at 37 months for adults (P < 0.0001). Among patients treated in first relapse, EFS was 14.2 +/-7.79% for patients with CR > 18 months verus 6.6 +/- 3.17% for those with CR < 18 months (P < 0.0001). Projected disease-free survival (DFS +/- SE) was 15.4 +/- 4.61% at 55 months for all responders and 43.3 +/- 14.34% at 52 months for allografted patients. Projected overall probability of survival +/- SE for all patients was 18.8 +/- 4.13% at 56 months. This study confirms the efficacy of IDA plus IDARA-C in poor-risk. ALL patients. A more intensive post-remission therapy or alternative approach must be designed to improve long-term results.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Fatores Etários , Transplante de Medula Óssea , Criança , Pré-Escolar , Terapia Combinada , Citarabina/administração & dosagem , Feminino , Seguimentos , Humanos , Idarubicina/administração & dosagem , Lactente , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Prognóstico , Estudos Prospectivos , RecidivaRESUMO
Cerebrospinal fluid thymidine kinase (CSF-TK) was measured at diagnosis in 62 patients with acute lymphoblastic leukemia (ALL) without initial neurological manifestations, who achieved a complete remission after chemotherapy. During the follow-up period, 10 patients developed central nervous system (CNS) involvement. At the onset of the disease mean CSF-TK levels in these subjects were found to be significantly higher than those observed in patients without subsequent CNS complications. In particular, 7/10 (70%) of these patients who presented CSF-TK levels above the upper limit of normal (1.4 U/microliters) had evidence of a neurological relapse, while 49/52 (94.2%) of subjects with presenting CSF-TK levels of up to 1.4 U/microliters did not develop a neurological leukemic disease (p < 0.00001). The white blood cell count at diagnosis was significantly increased, but not directly correlated to CSF-TK levels, in the group with CNS involvement, while age, serum thymidine kinase levels and lactic dehydrogenase, FAB classification or immunophenotype were not different in patients with or without neurological relapse. In conclusion, increased levels of CSF-TK at presentation correlate with a high risk of subsequent CNS involvement in patients with responsive ALL.
Assuntos
Biomarcadores Tumorais/líquido cefalorraquidiano , Meninges/patologia , Proteínas de Neoplasias/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Timidina Quinase/líquido cefalorraquidiano , Adolescente , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Terapia Combinada , Irradiação Craniana , Feminino , Humanos , Injeções Espinhais , Infiltração Leucêmica/tratamento farmacológico , Infiltração Leucêmica/enzimologia , Infiltração Leucêmica/radioterapia , Contagem de Leucócitos , Masculino , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/radioterapia , Valor Preditivo dos Testes , Prognóstico , Indução de Remissão , Fatores de Risco , Fatores de TempoAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Idoso , Asparaginase/administração & dosagem , Protocolos Clínicos , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Prognóstico , Vincristina/administração & dosagemRESUMO
255 patients with acute non-lymphoid leukaemia (ANLL), observed between October 1984 and June 1987, entered a chemotherapy regimen consisting of induction therapy with cytarabine in combination with idarubicin (IDA/ARA) or daunorubicin (DNR/ARA), followed by consolidation with four courses of IDA + ARA plus 6-thioguanine (6-TG) or DNR + ARA + 6-TG and a 6 month maintenance therapy with 6-TG and ARA. The median age was 62 years (range 55-78 years) and 33 were aged more than 70 years. The treatment groups were comparable for median age, FAB type, performance status and initial blood counts. 249 patients were randomised, 124 to the IDA/ARA arm and 125 to the DNR/ARA arm. Complete remission was achieved in 50 patients (40%) on the IDA/ARA treatment program and 49 patients (39%) on DNR/ARA. No definite differences were found between patients receiving IDA/ARA and those treated with DNR/ARA as far as complete response (CR), overall survival, failure free and relapse free survival are concerned. 74% of the complete responders in the IDA/ARA arm and 51% in the DNR/ARA arm achieved CR after a single course of treatment. Resistant leukaemia was observed in 13.7% of the patients in the IDA/ARA arm and in 31.2% in the DNR/ARA one, whereas hypoplastic death occurred in 29% and 14.4%, respectively. In conclusion, our data failed to show any advantage of idarubicin over daunorubicin even though there is some evidence that IDA, despite the higher toxicity, is more rapid in eradicating leukaemia as proved by the higher CR rate obtained after one course of induction.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Feminino , Humanos , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Tioguanina/administração & dosagemRESUMO
P-glycoprotein (P-170) is the phenotypic marker of tumoral cells that show the phenomenon of multidrug resistance (MDR). Using an immunocytochemical approach, we employed the monoclonal antibody C219 (which recognizes an epitope of such a glycoprotein) to evaluate in cytologic samples the expression of P-170 on neoplastic cells from 52 patients affected by different hematologic malignancies and its eventual correlation to clinical outcome. Longitudinal studies were also performed in 14 patients. Results obtained demonstrated that a) the so-called "MDR phenotype" may be heterogeneously represented (from less than 1 to 100% of positive cells) in hemopoietic tumors at diagnosis (without exposure to pharmacologic agents), as well as during the course of the disease, although a more substantial presence of P-170 occurred in treated patients. There was no correlation between neoplastic kinetic activity (such as expression of Ki 67 recognized nuclear proliferation-associated antigen) and P-170-positive cells. b) Percentage of positive cells as well as intensity of staining seemed to be important in determining MDR; in general, there was a strong correlation between expression of P-170 in more than 20% of neoplastic cells and a lack of response to chemotherapy. However, some false-positive and false-negative cases were observed. c) The detection of scattered P-170-positive cells may predict a pharmacologic selection of intrinsic or mutant-resistant clones.
Assuntos
Antineoplásicos/metabolismo , Leucemia/metabolismo , Glicoproteínas de Membrana/biossíntese , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Resistência a Medicamentos , Humanos , Imuno-Histoquímica , Estudos Longitudinais , Fenótipo , Valor Preditivo dos TestesAssuntos
Doenças Autoimunes/tratamento farmacológico , Isquemia Encefálica/etiologia , Ciclosporinas/uso terapêutico , Infarto do Miocárdio/etiologia , Púrpura Trombocitopênica/tratamento farmacológico , Idoso , Arteriosclerose/complicações , Doenças Autoimunes/complicações , Ciclosporinas/farmacologia , Feminino , Humanos , Megacariócitos/patologia , Contagem de Plaquetas/efeitos dos fármacos , Púrpura Trombocitopênica/complicações , Púrpura Trombocitopênica/patologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Citarabina/administração & dosagem , Daunorrubicina/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Itália/epidemiologia , Leucemia Mieloide Aguda/mortalidade , Tábuas de Vida , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Indução de Remissão , Taxa de Sobrevida , Tioguanina/administração & dosagemAssuntos
Leucemia Mieloide Aguda/enzimologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/enzimologia , Timidina Quinase/líquido cefalorraquidiano , Humanos , Leucemia Mieloide Aguda/líquido cefalorraquidiano , Leucemia-Linfoma Linfoblástico de Células Precursoras/líquido cefalorraquidianoRESUMO
Levels of Thymidine Kinase (TK) in cerebrospinal fluid (CSF) were longitudinally evaluated in 68 patients with acute leukemia. Values significantly above the normal range were found in all cases with meningeal involvement (in two subjects before the cytological evidence of leukemic cells in CSF). Such high levels decreased until normal values after an effective treatment. Two patients with multiple cerebral neoplastic nodules without infiltration of meninges showed normal CSF-TK values. No false positive cases were observed. Both kinetic activity and mass of leukemic cells appeared to influence CSF-TK levels. Thus, CSF-TK appears to be a promising marker in diagnosing and monitoring meningeal disease in the course of acute leukemia.
Assuntos
Leucemia/líquido cefalorraquidiano , Neoplasias Meníngeas/líquido cefalorraquidiano , Timidina Quinase/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Ensaios Enzimáticos Clínicos , Humanos , Leucemia/enzimologia , Neoplasias Meníngeas/enzimologiaRESUMO
Cerebrospinal fluid beta-2-microglobulin (CSF-beta 2m) was measured longitudinally in 48 patients affected by acute lymphoblastic leukemia (ALL). Thirteen developed a central nervous system (CNS) involvement during the course of the disease; although moderately higher mean CSF-beta 2m levels were found in these subjects, no significant statistical differences were observed in comparison with patients without this complication and compared with the control group. No correlations were found between beta 2m and other biochemical parameters in CSF. Furthermore, CSF-beta 2m levels appeared to be influenced by previous combined chemoradiotherapeutic treatment for CNS prophylaxis, presence of meningeal non-neoplastic infiltrates, patients' ages, amount of CSF blasts, and their immunological phenotype. In particular, only clearly B-committed leukemic cells, when tested, showed a strong surface expression of beta 2m, as demonstrated by immunocytochemical detection of this protein on cell membrane. However, in specific cases, CSF beta 2m measurement and CSF/serum beta 2m ratio were helpful in diagnosing and monitoring isolated CNS disease. Such findings suggest that CSF-beta 2m assay may be a useful tool in the management of CNS involvement in the course of ALL in only selected patients, as several factors can modify the outcome.