Assuntos
Acetamidas/uso terapêutico , Antibacterianos/uso terapêutico , Artrite/tratamento farmacológico , Mieloma Múltiplo/complicações , Oxazolidinonas/uso terapêutico , Infecções Relacionadas à Prótese/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Artrite/microbiologia , Humanos , Linezolida , Masculino , Pessoa de Meia-Idade , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/microbiologia , Resultado do TratamentoRESUMO
The implication of MLL gene rearrangements in the prognosis of acute myeloblastic leukemia is an issue of considerable current interest. We report a case of a young man who initially presented with a pancytopenia and went on to develop a highly-aggressive acute myeloblastic leukemia. At this time, the karyotypic study revealed trisomy 8, a t(9;11) was demonstrated by fluorescence in situ hybridization (FISH) and the MLL/AF4 rearrangement by reverse transcriptase-polymerase chain reaction (RT-PCR).
Assuntos
Cromossomos Humanos Par 11/genética , Cromossomos Humanos Par 8/genética , Cromossomos Humanos Par 9/genética , Leucemia Monocítica Aguda/genética , Pancitopenia/patologia , Proto-Oncogenes , Fatores de Transcrição , Trissomia , Adulto , Southern Blotting , Análise Citogenética , DNA de Neoplasias/genética , Proteínas de Ligação a DNA/genética , Histona-Lisina N-Metiltransferase , Humanos , Hibridização in Situ Fluorescente , Cariotipagem , Leucemia Monocítica Aguda/patologia , Masculino , Proteína de Leucina Linfoide-Mieloide , Proteínas Nucleares/genética , Proteínas de Fusão Oncogênica/genética , Pancitopenia/genética , Translocação GenéticaRESUMO
BACKGROUND: The Philadelphia chromosome (Ph') is originated by the t(9;22) which determines the rearrangement BCR/ABL. This rearrangement has been associated with an unfavourable prognosis in patients diagnosed with adult acute lymphoblastic leukaemia (ALL). PATIENTS AND METHODS: The BCR/ABL gene (p210 and p190) was prospectively studied by nested RT-PCR in 17 adult patients diagnosed with ALL BCR/ABL-positive cases were monitored by RT-PCR and cytogenetic techniques over the treatment period (LAL-93 AR protocol). RESULTS: BCR/ABL mRNA was detected in 8 out the 17 patients studied (47%). The Ph' chromosome was detected in 4 cases. Follow-up was completed in 6 out of the 8 BCR/ABL positive cases. PCR only became negative in one patient. The 5 patients with persistently positive BCR/ABL relapsed, whereas the case which became negative was still in complete remission after 24 months follow-up. In 3 out of the 4 Ph' positive patients, the karyotype was normal after induction therapy. CONCLUSIONS: This study clearly demonstrates the usefulness of molecular analysis in the diagnosis and follow-up of ALL compared with conventional cytogenetic techniques. The importance of molecular analysis to assess the efficacy of the treatment used has been emphasized and the poor evolution of BCR/ABL-positive patients has been confirmed.
Assuntos
Genes abl/genética , Proteínas Oncogênicas/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Southern Blotting , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Cromossomo Filadélfia , Estudos Prospectivos , Proteínas Proto-Oncogênicas c-bcr , Recidiva , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodosRESUMO
Chronic myelogenous leukemia (CML) is a myelo-proliferative disorder which, after a chronic phase which lasts an average of 3 years, evolves into an acute disease which is resistant to chemotherapy. Nevertheless, a few studies have reported cases in which partial or complete hematologic, cytogenetic and/or molecular remission of the disease were observed either spontaneously or after non intensive chemotherapy, with or without medullar aplasia. Some of these patients later relapsed into a blast crisis. We report a case of CML with clinical and hematologic remission for 19 years after two cycles of busulphan not causing medullar aplasia, negative for the BCR/ABL gene by Southern blot but with the gene's mRNA detectable by hot start nested RT-PCR.
Assuntos
Biomarcadores Tumorais/sangue , Proteínas de Fusão bcr-abl/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto , Biomarcadores Tumorais/genética , Southern Blotting , Bussulfano/uso terapêutico , Feminino , Proteínas de Fusão bcr-abl/genética , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Neoplasia Residual , RNA Mensageiro/sangue , RNA Neoplásico/sangue , Indução de Remissão , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: To value the usefulness of the bcl-2 rearrangement analysis by PCR in the study of the minimal residual disease in patients with follicular non-Hodgkin's B cell lymphoma (NHL) submitted to peripheral blood stem-cell transplantation (PSCT). PATIENTS AND METHOD: The study was done on 12 patients diagnosed with low grade B-cell NHL, who were entered in a program of myeloablative chemotherapy followed by rescue with progenitor cells obtained from peripheral blood. At the time of peripheral stem-cells (PSC) harvesting, 8 patients did not present medullar infiltration and four of them presented medullar infiltration according to conventional histological criteria. The study was done on DNA from samples taken from bone marrow and cells taken in the apheresis. The DNA samples were studied by PCR to determine the existence of the bcl-2 rearrangement. RESULTS: At the time of apheresis, 8 patients did not present medullar infiltration according to conventional histological criteria but 7 of them presented bcl-2/JH rearrangement. Most patients studied (10 out of 12) showed bcl-2/JH rearrangement (minimal residual disease) in apheresis products. However, in 2 of these 10 patients, such rearrangement was negative in the bone marrow samples obtained 3-6 and 12 months after transplantation. CONCLUSION: In some patients with follicular NHL submitted to PSCT, the bcl-2/JH rearrangement had negativized after transplantation, this implies that the tumoral cells present in apheresis products lost their clonogenic capacity and were not able to subsist in vivo and that the myeloablative polychemotherapy schedules are able to eradicate the t(14; 18) translocation bearing cells or, at least, to decrease their number in bone marrow to levels below those of PCR detection.
Assuntos
Rearranjo Gênico , Genes bcl-2 , Transplante de Células-Tronco Hematopoéticas , Linfoma Folicular/genética , Linfoma Folicular/terapia , Adulto , Feminino , Humanos , Linfoma Folicular/sangue , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
We assessed the ability of granulocyte colony-stimulating factor (G-CSF) to mobilize peripheral blood stem cells (PBSC), the efficacy of PBSC infusion in the rescue of hematopoiesis after high-dose chemotherapy in 22 adult patients with hematological malignancies, and the long-term quality of engraftment. Bolus subcutaneous injections of G-CSF (12 micrograms/kg/day) were administered for 6 days. A median of three leukaphereses resulted in the collection of a median of 5.45 X 10(8) mononuclear cells/kg, 4.52 X 10(6) CD34+ cells/kg, and 3.97 X 10(4) CFU-GM/kg. G-CSF (5 micrograms/kg daily) was administered after PBSC infusion until granulocyte recovery. The median time to attain a neutrophil level > 0.5 X 10(9)/L and a platelet count > 20 X 10(9)/ L was 11 days. The median follow-up in 17 survivors was 23.8 months. These patients have maintained a complete and stable graft and some of them with neoplastic recurrence tolerated further chemotherapy. These results confirm that mobilization of PBSC by G-CSF can be performed on an outpatient setting and used in heavily pretreated patients. G-CSF mobilized PBSC transplantation provides early and complete engraftment in most patients.
Assuntos
Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma/terapia , Mieloma Múltiplo/terapia , Adulto , Antineoplásicos/uso terapêutico , Terapia Combinada , Feminino , Hematopoese , Humanos , Masculino , Pessoa de Meia-Idade , Transplante AutólogoRESUMO
We describe a family with an inherited fragile chromosome 16 with the concurrence of a constitutional chromosome abnormality, together with neoplastic pathology within the family. The following findings should be pointed out: in relation to the constitutional chromosome pathology, of the proband's 3 children, the eldest daughter was a carrier of the fragile 16, the same as the father, and the second child, a son, had Down syndrome (trisomy 21). Regarding the tumoral pathology of this family, one of the proband's daughters died in childhood from acute lymphoblastic leukemia, whereas the proband developed two different malignant hematologic disorders: a follicular lymphoma and an acute nonlymphocytic leukemia (M5 type). Moreover, two independent acquired chromosome disorders coexisted in the proband; each of these was related to one of the respective hematologic disorders.
Assuntos
Aberrações Cromossômicas , Fragilidade Cromossômica , Cromossomos Humanos Par 16 , Leucemia Mieloide Aguda/genética , Linfoma Folicular/genética , Idoso , Feminino , Humanos , Cariotipagem , Masculino , Translocação GenéticaRESUMO
OBJECTIVE: To ascertain the etiology and outcome of episodes of bacteremia and fungemia over a three-year period (1990-1992) in patients with hematological malignancies. DESIGN: Retrospective study. SETTING: Hematology service of a 1,500-bed Spanish university hospital. RESULTS: Of a total of 178 episodes of significant bacteremia or fungemia in 101 patients, 53% affected patients with acute leukemia. Gram-positive microorganisms were found to be the cause in 70% of the monomicrobial episodes. The most frequently isolated microorganism was coagulase-negative Staphylococcus (35%), followed by Staphylococcus aureus (11%). Most blood-stream infections occurred during an episode of neutropenia (59%). A total of 34 patients died during hospitalization; in 14, infection was the cause of death. CONCLUSIONS: A marked increase in the incidence of bacteremias caused by gram-positive microorganisms has been observed in our hospital over the last 10 years, especially in patients with hematological malignancies. The mortality due to bacteremia is similar to that found by other authors in series of bacteremia in hematological patients, and we have not found significant differences in the mortality due to bacteremia between neutropenic and non-neutropenic patients (Infect Control Hosp Epidemiol 1994;15:101-104).
Assuntos
Bacteriemia/etiologia , Infecção Hospitalar/etiologia , Fungemia/etiologia , Infecções por Bactérias Gram-Positivas/etiologia , Controle de Infecções , Leucemia/complicações , Linfoma/complicações , Neutropenia/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle , Causas de Morte , Distribuição de Qui-Quadrado , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Feminino , Fungemia/epidemiologia , Fungemia/prevenção & controle , Infecções por Bactérias Gram-Positivas/epidemiologia , Infecções por Bactérias Gram-Positivas/prevenção & controle , Mortalidade Hospitalar , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Neutropenia/epidemiologia , Prognóstico , Estudos RetrospectivosRESUMO
A novel alpha-thalassemia-1 deletion of 14-15.4 kb that removes the alpha-2, alpha-1, theta-1 genes and pseudo-alpha-1 genes, has been detected in a father and 2 of his children from northern Spain.
Assuntos
Cromossomos Humanos Par 16 , Deleção de Genes , Globinas/genética , Mutação , Talassemia alfa/genética , Adulto , Southern Blotting , Criança , Feminino , Frequência do Gene , Heterozigoto , Humanos , Masculino , Polimorfismo de Fragmento de Restrição , Prevalência , Pseudogenes , Espanha/epidemiologia , Talassemia alfa/epidemiologiaRESUMO
BACKGROUND: The rearrangement of the bcr/abl gene constitutes the molecular substrate of the Philadelphia chromosome (Ph'). The aim of this study was to analyze the usefulness of bcr/abl rearrangement in the diagnosis and evolution of chronic myeloid leukemia (CML). METHODS: The rearrangement of the bcr/abl gene was studied in 81 cases of which 34 corresponded to patients with CML (29 Ph' positive chromosome, 2 Ph' negative chromosome and 3 without karyotype), 2 patients with Ph' positive acute lymphoblastic leukemia, 15 patients with chronic myeloproliferative syndromes different from CML and 30 controls. Of the patients with CML, 6 were reevaluated when a blastic crisis was developed, 2 after receiving interferon treatment and 1 following allogeneic bone marrow transplantation. The technique used was that of Southern blotting using the restriction enzymes Bgl II and BamHI and the transprobe. RESULTS: Rearrangement of the bcr/abl gene was observed in all the patients with CML except in one with Ph' negative chromosome. In the remaining cases bcr/abl rearrangement was not observed. CONCLUSIONS: The Southern blotting technique for the study of the bcr/abl gene rearrangement is a sensitive and specific method in the diagnosis of chronic myeloid leukemia constituting a valid alternative to chromosomic study when this cannot be carried out or is not conclusive. It may also be used for the control of treatment in chronic myeloid leukemia.
Assuntos
Rearranjo Gênico , Genes abl/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Crise Blástica/diagnóstico , Crise Blástica/genética , Southern Blotting , Criança , DNA de Neoplasias/análise , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/diagnóstico , Leucemia Mieloide Crônica Atípica BCR-ABL Negativa/genética , Masculino , Pessoa de Meia-Idade , Sensibilidade e Especificidade , Talassemia alfa/diagnóstico , Talassemia alfa/genéticaRESUMO
We have identified the case of a 9-months-old girl with heterozygotic thalassemia and triplication of alpha genes of globin (alpha alpha alpha 3.7). Molecular defect of thalassemia was a mutation without sense of 39 codon. Patient's phenotype was an intermediate thalassemia with moderate splenomegaly and marked unbalance on the globin chains. This is the first case of intermediate thalassemia, through this mechanism, described in Spain.
Assuntos
Genes , Hemoglobina A/genética , Talassemia/genética , Talassemia beta/genética , Feminino , Heterozigoto , Humanos , Lactente , Mutação , Espanha , Talassemia/etiologiaRESUMO
PURPOSE: To determine the incidence of a second malignancy in patients with Hodgkin's disease (HD) diagnosed and treated in the same hospital. PATIENTS AND METHODS: A retrospective study was performed on 99 patients diagnosed and treated for HD in the Hospital San Carlos, in Madrid, between January 1976 and december 1987. The clinical records were revised; the diagnosis and staging followed the Rye and Ann Arbor criteria, and the treatment included radiation therapy (RT), chemotherapy (CT), or a combination of both. The diagnosis of the second malignancy was based upon clinical, analytical, radiological and histological records. RESULTS: The median age in the series was 31 years (16-82) and the M/F ratio was 61/38. The stage distribution was: I-9; II-29; III-31, and IV-30. Twenty-six patients received RT alone, 59 were treated with CT, and 14 received RT plus CT. A second neoplasm was found in 6 patients (6%), of whom 4 developed a myelodysplastic syndrome (MDS) and 2 a solid tumour. All the patients who had MDS had received MOPP or C-MOPP chemotherapy, associated in two of them with extensive RT. Both patients with solid tumour had been given CT+RT. The median time of presentation of the second malignancy since the diagnosis od HD was 89 months (48-174) for MDS and 120 months for the solid tumours. The four MDS patients have died, 2 for ANLL-M5, one for SRA and the remainder for cerebral haemorrhage, not yet evolved into acute leukaemia. The two patients which solid tumours are alive and seemingly in complete remission at 12 and 10 months, respectively, of the diagnosis of the second malignancy. CONCLUSIONS: 1) All the patients with second neoplasms had been previously treated with CT (MOPP or C-MOPP) or CT+RT. 2) Non-Hodgkin's lymphoma has not appeared in any of the patients in this series. 3) An endless follow-up of patients with HD seems important in order to achieve an early diagnosis of other malignant complications which, although in case of MDS have poor prognosis, in case of solid tumours may do well with adequate treatment.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma Papilar/etiologia , Carcinoma de Células Escamosas/etiologia , Doença de Hodgkin/terapia , Leucemia Monocítica Aguda/etiologia , Neoplasias Pulmonares/etiologia , Síndromes Mielodisplásicas/etiologia , Neoplasias Induzidas por Radiação/epidemiologia , Segunda Neoplasia Primária/etiologia , Radioterapia/efeitos adversos , Neoplasias da Glândula Tireoide/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Feminino , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/radioterapia , Humanos , Incidência , Masculino , Mecloretamina/administração & dosagem , Mecloretamina/efeitos adversos , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/etiologia , Segunda Neoplasia Primária/epidemiologia , Prednisona/administração & dosagem , Prednisona/efeitos adversos , Procarbazina/administração & dosagem , Procarbazina/efeitos adversos , Estudos Retrospectivos , Vincristina/administração & dosagem , Vincristina/efeitos adversosRESUMO
We report three cases of ANLL and one case of ALL in which we found chromosome abnormalities not previously described. The first patient had a (9;11;16)(p22;q23;p13) translocation in the relapse after bone marrow transplantation. In the second case, a secondary leukemia following a Wilms' tumor, there was a single chromosome anomaly, an inversion of chromosome 13. The third case also presented an isochromosome 13q. In the fourth patient we observed a translocation between two achrocentric chromosomes, as in the third patient, but not of the Robertsonian type: t(21;21)(q22.1;q22.5).
Assuntos
Aberrações Cromossômicas/genética , Leucemia Mieloide Aguda/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Adolescente , Idoso , Bandeamento Cromossômico , Transtornos Cromossômicos , Inversão Cromossômica , Cromossomos Humanos Par 13 , Cromossomos Humanos Par 21 , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Translocação GenéticaRESUMO
A case is presented of a female patient initially diagnosed of acute lymphoblastic leukemia who was treated achieving complete remission. Twenty six months later and while in remission of her leukemia, she presented an abdominal mass the histological study of which showed infiltration due to Hodgkin disease. She was treated with chemotherapy type MOPP and complete remission was achieved. Four months after completing treatment she presented pancytopenia in peripheral blood. A bone marrow study was performed observing a blastoid infiltration with morphological and cytochemical characteristics of acute non-lymphoblastic M-5 leukemia. The possible common origin of the three clinical pictures is discussed given the recent findings regarding the origin of Reed-Sternberg cell.
Assuntos
Doença de Hodgkin/diagnóstico , Leucemia Mieloide Aguda/diagnóstico , Segunda Neoplasia Primária , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Feminino , Doença de Hodgkin/tratamento farmacológico , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Indução de Remissão , Fatores de TempoRESUMO
The coagulation abnormalities in 20 cases of acute promyelocytic leukemia (APL) treated at a single institution were reviewed. A remarkably uniform picture of defibrination and increased FDPs with well-preserved levels of other coagulation factors including AT-III was seen. Our data, together with those available in the literature, do not support DIC as the underlying mechanism of bleeding but seem rather to point to increased proteolysis as the cause.
Assuntos
Transtornos da Coagulação Sanguínea/etiologia , Fibrina/metabolismo , Fibrinólise/fisiologia , Hemorragia/etiologia , Leucemia Promielocítica Aguda/fisiopatologia , Adulto , Feminino , Humanos , Leucemia Promielocítica Aguda/complicações , Masculino , Estudos RetrospectivosRESUMO
Sixty patients diagnosed of acute myeloblastic leukaemia (AML) on whom a chromosomal study was performed at diagnosis were evaluated. Their median age was 43 years (range: 8-89). Normal karyotype was present in 59% of the cases, it being abnormal in the remaining 41%. Chromosomal alterations appeared in 64% of the patients with M-4 morphology, in 43% of M-5, 40% of those with M-1, 33% of the M-2, and in 14% of the cases with M-3 morphology. The two patients with M-6 had abnormal karyotype. No correlations could be established between normal or abnormal karyotype and the clinical or laboratory data. Structural alterations were commonest amongst the patients with abnormal karyotype. Such alterations included t(8; 21), t(9; 22); t(7; 22), del 11q23, inv 16 (p13;q22), plus multiple major abnormalities in the M-6 patients. A strikingly low incidence of t(15; 17) was found in the acute promyelocytic leukaemia cases. Two chromosomal alterations not previously reported in AML were found in this series, namely, inv 13 (p11;q32) and t(21;1) (q22;q22). The finding of an abnormal karyotype had no unfavourable influence on the complete remission (CR) rate, which reached 65% of the patients with normal karyotype and 81% of those with abnormal karyotype. No differences were found in the duration of CR in this connection (80 and 77 weeks, respectively). Despite the lack of definite prognostic significance, the study of the karyotype appears as an important information in the diagnosis of AML.
Assuntos
Aberrações Cromossômicas , Leucemia Mieloide Aguda/genética , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/classificação , Leucemia Mieloide Aguda/tratamento farmacológico , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Prognóstico , Indução de RemissãoRESUMO
We prospectively evaluated the infective complications in 279 neutropenic episodes which developed during the treatment of 79 patients with malignant hemopathies over a 35 month period. In 150 episodes (53.73%) infections were detected: one infection in 121 episodes and two in 29 episodes. Overall 179 infections were detected. 75 of them (41.89%) were considered as possible, 57 (31.84%) were microbiologically documented with bacteremia/fungemia 24 (13.40%) were clinically documented, and 23 (12.84%) were microbiologically documented without bacteremia/fungemia. The portal of entry could not be identified in 121 infections (67.59%), 26 (14.76%) originated in the skin and soft tissues, 14 (7.82%) in the lung, 7 (3.91%) in the oropharynx, 5 (2.79%) in a catheter, and 6 (3.33%) were of miscellaneous origin. Of 80 microbiologically documented infections, 39 (48.75%) were due to gram-negative bacteria, 23 (28.75%) to gram-positive bacteria, 12 (15%) to fungi, and 6 (7.5%) to polymicrobial flora. The overall mortality rate was 4.3%. It was 8% for episodes complicated by infection and 0 in episodes of neutropenia without infection.