RESUMO
BACKGROUND: The degree of immunosuppression required for adequate graft-versus-host disease (GVHD) prevention, while keeping an adequate graft-versus-leukemia effect, in children with acute leukemia has not been established. We report the results of a retrospective comparison of cyclosporine levels and relapse rate in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS: Patients <21 y/o with ALL in remission who underwent TBI-based hematopoietic cell transplantation from related or unrelated donors between 2008 and 2021 were included. Cyclosporine levels were measured twice a week and we calculated the area under the curve (AUC) from D0 to D + 7, D + 14, and D + 21. RESULTS: We included 76 patients. There was a trend towards a lower incidence of relapse in patients with a mean AUC < 200 ng/ml at D + 21 (HR = 0.41; p = .08). The 5-year relapse rate was 26.9% for patients with a mean AUC < 200 ng/ml at D + 21 and 43.9% for patients with a mean AUC≥200 ng/ml at D + 21. Relapse protection was restricted to relapses happening after D + 120 (HR = 0.21; p = .04). CONCLUSIONS: Our results show evidence that pediatric patients with ALL might benefit from lower cyclosporine levels between D0 and D + 21 without a detectable increase in GVHD. Large prospective studies comparing different cyclosporine levels are awaited.
Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Adolescente , Criança , Doença Crônica , Ciclosporina/uso terapêutico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicações , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Estudos Prospectivos , Recidiva , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante HomólogoRESUMO
The choice of alternative donors for HCT for patients without an HLA-matched related donor depends on several factors. We compared major HCT outcomes in 212 consecutive children transplanted at 11 centers in Brazil for acute leukemia or MDS from an HLA-matched unrelated donor (MUD, n = 95), mismatched unrelated donor (MMUD, n = 47) or unrelated umbilical cord blood (UCB, n = 70). Most had ALL (61%), bone marrow (57%) as the graft source and 95% received a MAC regimen. The 3-year OS probability were 57, 55, and 37% after HCT from MUD, MMUD, and UCB, respectively (HR 1.68, 95%CI 1.07-2.63; P = .02). In comparison with MUD, OS was similar after transplantation of a ≥ 6/8 HLA-matched or a high cell dose (>5 × 107 TNC/kg) CB unit (HR 1.41, 95%CI 0.88-2.27; P = .15). NRM was higher for UCB (HR 3.90, 95%CI 1.43-10.7; P = .01) but not for MMUD (HR 1.03, 95%CI 0.53-2.00; P > .20). Advanced disease (HR 2.05, 95%CI 1.26-3.33; P < .001) and UCB with high probability of being < 6/8 HLA-matched (HR 5.34, 95%CI 2.0-13.9; P < .001) were associated with higher mortality. Relapse and acute GVHD were similar among groups, while PGF was higher among UCB transplants (P = .002) and chronic GVHD among MMUD group (HR 2.88, 95% CI 1.05-7.88; P = .04). Our results suggest that in Brazil HCT outcomes performed with MMUD and MUD donors were comparable, while with UCB units < 6/8 HLA-matched were associated with higher NRM for children with acute leukemia or MDS.
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Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Brasil/epidemiologia , Criança , Feminino , Sobrevivência de Enxerto , Humanos , Incidência , Leucemia Mieloide Aguda/epidemiologia , Masculino , Síndromes Mielodisplásicas/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Pediatric myelodysplastic syndrome (MDS) is an uncommon disease and little is known about the molecular alterations of its development and evolution to acute myeloid leukemia (AML). The Enhancer of Zeste Homolog 2 (EZH2) is the catalytic subunit of Polycomb repressive complex 2 (PCR2). It is a histone methyltransferase, that targets lysine 27 of histone 3. This methylated H3-K27 is usually associated with the silencing of genes that are involved in fundamental cellular processes, such as cell proliferation and differentiation. There are only few studies showing the status of EZH2 expression in patients with MDS and they were performed in adult MDS patients. The aim of this study was to analyze the EZH2 expression in pediatric patients with MDS and its association with karyotypes and evolution to acute myeloid leukemia (AML). We conducted the first study of EZH2 expression in pediatric patients with MDS. Considering the EZH2 expression levels in 42 patients and 17 healthy pediatric donors, it was possible to define three groups of expression in patients: low, intermediate, and high. The intermediate level encompassed patients with normal karyotypes, low level included patients with monosomy 7 and del(7q) and high level included patients with trisomy 8 and del(11q) (p < 0.0001). Comparing the leukemic evolution, the low expression group presented disease evolution in 100% (8/8) of the cases, the intermediate expression group showed disease evolution in 4.34% (1/23) and in the high expression group, 63.63% (7/11) patients showed evolution from MDS to AML (p < 0.0001). It is important to note that low and high EZH2 expression are associated with leukemic evolution, however low expression showed a stronger association with evolution from MDS to AML than the high expression. Our results suggest a scale of measure for EZH2 expression in pediatric MDS, where aberrant EZH2 expression may be a potential biomarker of disease evolution.
Assuntos
Biomarcadores Tumorais/biossíntese , Proteína Potenciadora do Homólogo 2 de Zeste/biossíntese , Regulação Leucêmica da Expressão Gênica , Leucemia Mieloide Aguda/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas de Neoplasias/biossíntese , Adolescente , Biomarcadores Tumorais/genética , Criança , Pré-Escolar , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Feminino , Humanos , Lactente , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/patologia , Masculino , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/patologia , Proteínas de Neoplasias/genéticaRESUMO
BACKGROUND: This paper describes the transmission of hepatitis A virus (HAV) to two blood recipients from a healthy donor that later presented to the blood bank with jaundice. METHODS: The RNA of HAV was detected by qualitative nested reverse transcription polymerase chain reaction (nested RT-PCR) and quantified by real-time RT-PCR. HAV RNA samples were genotyped by direct sequencing of PCR products. A sequence from a fragment of 168 bp from the VP1/2A HAV region was used to construct a phylogenetic tree. CASE REPORT: A 31-year-old male donor accepted for donation of a whole blood unit returned to the blood bank with clinical jaundice 20 days after donation. His serological and NAT tests were negative for HBV and HCV. Serological tests for HAV IgM and IgG were negative on donation sample but positive on follow-up sample, confirming donor's HAV acute infection. Both recipients of red blood cells (R1) and platelet concentrate (R2) from the same implicated donation were HAV IgM-negative and IgG-positive. Qualitative PCR was positive on samples from all three individuals and phylogenetic analysis of viruses proved HAV transmission to the two recipients of blood products. HAV viral load on donor follow-up sample and the platelet recipient was 1.3 and 1.5 × 10(3) IU/ml, respectively. The RBC recipient, also infected by HCV, was undergoing bone marrow transplantation and died from fulminant hepatitis, 26 days after the implicated HAV transfusion. CONCLUSION: The blood donor, a garbage collector, spontaneously returned to the blood bank when developing jaundice. This highlights the importance of donor education to immediately report to blood banks of any signs and symptoms related to infectious disease developed after blood donation. The fact that one immunocompromised patient with HCV infection died from fulminant hepatitis after receiving a HAV-contaminated platelet transfusion underpins the importance of a HAV vaccination program for these group of patients.
RESUMO
OBJECTIVES: The objective of this study was to compare the major transplant outcomes between patients receiving hematopoietic stem cell transplantation (HSCT) from bone marrow (BM) or peripheral blood stem cells (PBSC). METHODS: All consecutive HSCT patients using BM or PBSC from an HLA-matched related donors for haematological malignancies after high intensity conditioning at seven Brazilian transplant centres between January 2008 and December 2009 were retrospectively evaluated. RESULTS: In the study period, 334 patients were treated in the centres and included in the evaluation. The cumulative incidence of grades II-IV and III-IV acute graft-versus-host disease (GVHD) at one year was 36.7% and 9.7% for BM recipients and 34.4% and 15.1% for PBSC recipients, respectively (not statistically different). The cumulative incidence of chronic GVHD at three years was 53.7% and 79.8% (HR 1.93; 95% CI 1.38-2.69, P < 0.001) for BM and PBSC, respectively. Median overall survival was 2.85 and 2.39 years for BM and PBSC recipients, respectively (HR 1.19; 95% CI, 0.84-1.68, P = 0.34). CONCLUSIONS: Our results confirm previous findings of increased chronic GVHD incidence in patients receiving PBSC when compared to patients receiving BM as the graft source in HSCT. Acute GVHD incidence, progression-free survival and overall survival were not different between the groups.
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Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco de Sangue Periférico , Doadores de Tecidos , Adolescente , Adulto , Idoso , Aloenxertos , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/etiologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHODS: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.
Assuntos
Doença Enxerto-Hospedeiro/classificação , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , TutoriaRESUMO
BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76%) met the criteria of overlap syndrome and eight (24%) the classic subcategory. The overall severity of disease was moderate in 21 (62%) and severe in 13 (38%) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75%. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.
RESUMO
BACKGROUND: The lack of standardization of clinical diagnostic criteria, classification and severity scores of chronic graft-versus-host disease led the National Institutes of Health to propose consensus criteria for the purpose of clinical trials. METHOD: Here we describe a one-day workshop model conducted by the Chronic Graft-versus-Host Disease Brazil-Seattle Consortium Study Group to train investigators interested in participating in multicenter clinical trials in Brazil. Workshop participants included eight transplant physicians, one dermatologist, two dentists, three physical therapists and one psychologist from five institutions. Workshop participants evaluated nine patients with varying degrees of severity of mucocutaneous lesions and other manifestations of the disease followed by a training session to review and discuss the issues encountered with the evaluation and scoring of patients and in the methods used to evaluate grip strength and the 2-minute walk test. RESULTS: Most participants had difficulties in rating the percentage of each type of mucocutaneous lesion and thought 20 minutes was insufficient to evaluate and record the scores of each patient using the National Institutes of Health criteria and other cutaneous assessments. Several specific areas of difficulties encountered by the evaluators were: 1) determining the percentage of erythema in movable and non-movable sclerosis, 2) whether to score all cutaneous findings in a particular area or just the dominant lesion; 3) clarification of the definition of poikiloderma in chronic graft-versus-host disease; 4) discrepant interpretation of the mouth score and 5) clarification on the methodology used for the evaluation of grip strength and the 2-minute walk tests. CONCLUSIONS: Results of this workshop support the need to train investigators participating in clinical trials on chronic graft-versus-host disease.
RESUMO
BACKGROUND: New criteria for the diagnosis and classification of chronic graft-versus-host disease were developed in 2005 for the purpose of clinical trials with a consensus sponsored by the National Institute of Health. OBJECTIVES: The aim of this study is to present the results of a multicenter pilot study performed by the Brazil-Seattle chronic graft-versus-host disease consortium to determine the feasibility of using these criteria in five Brazilian centers. METHODS: The study was performed after translation of the consensus criteria into Portuguese and training. A total of 34 patients with National Institute of Health chronic graft-versus-host disease were enrolled in the pilot study between June 2006 and May 2009. RESULTS: Of the 34 patients, 26 (76 percent) met the criteria of overlap syndrome and eight (24 percent) the classic subcategory. The overall severity of disease was moderate in 21 (62 percent) and severe in 13 (38 percent) patients. The median time from transplant to onset of chronic graft-versus-host disease was 5.9 months (Range: 3 - 16 months); the median time for the overlap syndrome subcategory was 5.9 months (Range: 3 - 10 months) and for the classic subcategory, it was 7.3 months (Range: 3 - 16 months). At a median follow up of 16.5 months (Range: 4 - 39 months), overall survival was 75 percent. CONCLUSIONS: It was feasible to use the National Institute of Health consensus criteria for the diagnosis and scoring of chronic graft-versus-host disease in a Brazilian prospective multicenter study. More importantly, a collaborative hematopoietic cell transplantation network was established in Brazil offering new opportunities for future clinical trials in chronic graft-versus-host disease and in other areas of research involving hematopoietic stem cell transplantation.
Assuntos
Humanos , Conferências para Desenvolvimento de Consenso de NIH como Assunto , Ensaio Clínico , Transplante de Células-Tronco Hematopoéticas , Doença Enxerto-HospedeiroRESUMO
A falta de critérios diagnósticos padronizados, amplamente utilizados, pode comprometer tanto a avaliação real da incidência da doença contra hospedeiro crônica bem como a correlação de sua gravidade com a taxa de mortalidade pós-transplante. Na I Reunião de Diretrizes da Sociedade Brasileira de Transplante de Medula Óssea, realizada em junho de 2009, o Grupo de Estudos de DECH Brasil - Seattle (GEDECH), baseado na realidade dos Centros brasileiros, apresentou as recomendações para diagnóstico, classificação, profilaxia e tratamento da doença enxerto contra hospedeiro crônica propostas pelo National Institutes of Health. Estas propostas incluíram padronização das características utilizadas no diagnóstico e ferramentas para a pontuação dos órgãos envolvidos e avaliação global da gravidade a serem utilizados em estudos clínicos da doença enxerto contra hospedeiro crônica. Estes critérios são úteis para uma melhor análise da incidência desta doença, além de poder avaliar a gravidade do comprometimento de um órgão ou sítio envolvido e a influência na mortalidade tardia do transplante. A profilaxia e os tratamentos propostos para esta importante complicação dos transplantes de células-tronco hematopoéticas foram discutidos e graduados de acordo com níveis de evidência estabelecidos pelo National Institutes of Health.
The lack of widely-used standardized diagnostic criteria may impair both the true evaluation of chronic graft-versus-host disease and the correlation of its severity with transplant-related mortality. At the I Consensus of the Brazilian Society of Bone Marrow Transplantation - SBTMO that took place in June 2009, the Group of GVHD Studies Brazil-Seattle (GEDECH), presented the guidelines for diagnosis, classification, prophylaxis and treatment of chronic GVHD as proposed by the National Institutes of Health and based on the reality in Brazilian Centers. These proposals, including standardization of features used in diagnosis and tools to score involved organs and to assess the overall severity, should be used in clinical studies of chronic graft-versus-host disease. These criteria are useful to better analyze the incidence of this disease, in addition to evaluate the extension of the involvement of organs or the site affected and its influence on late transplantation mortality. Prophylaxis and treatment proposed for this important complication of hematopoietic stem cell transplantations were discussed and graded according to the levels of evidence established by the National Institutes of Health.
Assuntos
Humanos , Transplante de Medula Óssea , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-HospedeiroRESUMO
O agrupamento de obesidade central, hipertensão arterial, hiperglicemia e dislipidemia, conhecido como síndrome metabólica (SM), está associado com aumento no risco de diabetes mellitus tipo 2 e doença cardiovascular. Estudos sugerem maior freqüência desta síndrome em sobreviventes do transplante de células precursoras hematopoéticas (TCPH), porém a prevalência de SM e de resistência insulínica (RI), bem como fatores associados ao seu desenvolvimento permanecem mal definidos nesta população. Objetivos.Comparar a prevalência de SM e de RI em mulheres submetidas ou não ao TCPH; identificar possíveis fatores de risco para SM e RI e avaliar o efeito da terapia hormonal sobre a prevalência destas condições em receptoras de TCPH. Métodos. Cento e treze receptoras de TCPH e 48 controles, entre 18 e 65 anos, foram avaliadas em estudo de corte transversal realizado no Centro de Transplante de Medula Óssea do Instituto Nacional do Câncer, Rio de Janeiro, de junho de 2005 a maio de 2008. As variáveis analisadas foram: componentes da síndrome metabólica conforme os critérios do NCEP-ATPIII e resistência insulínica pelo índice do modelo homeostático para insulino-resistência (HOMA-IR) (dependentes), e tipo dotransplante, doença do enxerto-contra-o-hospedeiro, hipotireoidismo, hipogonadismo, terapia hormonal, uso de imunossupressores, idade, idade ao transplante, tempo pós-transplante, diagnóstico de SM pré-TCPH, regime de condicionamento, cor, status menopausal, tabagismo, índice de massa corpórea, dieta, atividade física e história familiar de doença cardiovascular (independentes). Resultados. A idade mediana foi 36,9 anos, e 30 anos ao transplante. Foram 77 transplantes alogênicos, 2 singênicos e 34 autólogos. Não houve diferença significativa na prevalência de SM entre receptoras de transplante (22,1%) e controles (20,8%). Entretanto, a prevalência de RI foi significativamente maior entre pacientes (20%) que nos controles (6,5%). Os componentes mais frequentes foram hipertensão arterial (36,2%) e obesidade central (32,7%). A SM foi mais prevalente nas mulheres com idade superior a 30 anos ao transplante. Os diagnósticos de SM pré-TCPH e obesidade estiveram significativamente ssociados à SM e à RI, porém hiperinsulinemia e hipogonadismo estiveram relacionados significativamente apenas com SM. O uso de terapia hormonal reduziu em 75% o risco de SM, mas a redução no risco de RI não foi significativa. Conclusões. A prevalência de RI foi significativamente maior entre receptoras de TCPH. Diagnóstico de SM pré-TCPH, obesidade, hiperinsulinemia e hipogonadismo foram preditores independentes de SM. Os únicos preditores independentes de RI oram diagnóstico de SM pré-TCPH e obesidade. Novos estudos serão necessários para definir qual a melhor terapia hormonal para a prevenção destes distúrbios metabólicos em receptoras de TCPH.
Introduction. The clustering of central obesity, arterial hypertension, hyperglycemia and dyslipidemia, known as the metabolic syndrome (MS), is associated with an increased risk for type 2 diabetes mellitus and cardiovascular disease. Studies suggest a higher frequency of this syndrome in survivors of hematopoietic stem cell transplantation (HSCT); however, the prevalence of MS and insulin resistance (IR), as well as of the factors associated with its development, remains ill-defined. Objectives. To compare the prevalence of MS and of IR in women submitted or not to HSCT; to identify possible risk factors for MS and IR and to evaluate the effect of hormone therapy on the risk of these conditions in HSCT recipients. Methods. One hundred and thirteen HSCT recipients and 48 controls, between 18 and 65 years old, were evaluated in a cross-sectional study carried out at Centro de Transplante de Medula Óssea, in Instituto Nacional de Câncer, Rio de Janeiro, Brazil, from June 2005 to May 2008. The variables analyzed were: MS components on the basis of the NCEP-ATPIII criteria and insulin resistance by the homeostasis model assessment insulin resistance index (HOMAIR) (dependents), and transplant type, graft-versus-host disease, hypothyroidism, hypogonadism, hormone therapy, immunosuppressor use, age, age at transplant, time since transplant, MS diagnosis before HSCT, conditioning regimen, race, menopausal status, smoking habits, body mass index, diet, physical activity and family history of cardiovascular disease (independents). Results. The median age was 36.9 years, and 30 years at transplant. There were 77 allogeneic, two syngeneic and 34 autologous transplants. There was no significant difference in the prevalence of MS between transplant recipients (22.1%) and controls (20.8%). However, the prevalence of IR was significantly higher among patients (20%) than controls (6.5%). The most frequent components were arterial hypertension (36.2%) and central obesity (32.7%). MS was more prevalent among women older than 30 years at transplant. MS diagnosis before HSCT and obesity were significantly associated with MS and IR. However, hyperinsulinemia and hypogonadism were significantly related only with MS. Hormone therapy decreased by 75% the risk of MS, but the risk reduction for IR was not significant. Conclusions. The prevalence of IR was significantly higher among HSCT recipients. MS diagnosis before HSCT, obesity, hyperinsulinemia and hypogonadism were independent predictors of MS. Only obesity and MS diagnosis before HSCT were independent predictors of IR. Further studies will be necessary to define the best hormone therapy for prevention of these metabolic disorders in HSCT recipients.
Assuntos
Feminino , Humanos , Transplante de Células-Tronco Hematopoéticas , Síndrome Metabólica/epidemiologia , Condicionamento Pré-Transplante , Prevalência , Fatores de RiscoRESUMO
CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. DESIGN AND SETTING: Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. METHODS: Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. RESULTS: Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5%). Among these, 23 (82.3%) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. CONCLUSION: In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.
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Aberrações Cromossômicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Adolescente , Adulto , Brasil/epidemiologia , Feminino , Humanos , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Condicionamento Pré-TransplanteRESUMO
A 13-year-old boy with hypocellular primary myelodysplastic syndrome, classified as refractory cytopenia, underwent umbilical cord blood transplantation. Cytogenetic analysis revealed two rare biclonal chromosomal aberrations, del(17)(p12) and del(11)(q23). Cytogenetic analysis was a valuable tool in diagnosis, in clinical decision-making, and in treatment and follow-up. To our knowledge, this is the first reported case of cytogenetic biclonality involving chromosomes 17 and 11.
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Síndromes Mielodisplásicas/genética , Adolescente , Aberrações Cromossômicas , Bandeamento Cromossômico , Deleção Cromossômica , Análise Citogenética , Citogenética , Sangue Fetal/metabolismo , Deleção de Genes , Humanos , Hibridização in Situ Fluorescente , Masculino , Transplante de Células-Tronco , TransplanteRESUMO
CONTEXT AND OBJECTIVE: Following hematopoietic stem cell transplantation (HSCT), karyotyping is a valuable tool for monitoring engraftment and disease status. Few studies have examined the prognostic significance of karyotypes in patients who underwent HSCT for chronic myeloid leukemia (CML). The objective of this study was to evaluate the significance of pretransplantation cytogenetic status in relation to outcomes following HSCT in CML patients. DESIGN AND SETTING: Case series study at Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brazil. METHODS: Cytogenetic analysis was performed by G banding on 39 patients treated with HSCT. RESULTS: Thirty-one patients were in the chronic phase and eight were in the accelerated phase. Prior to HSCT, additional chromosomal abnormalities on the Philadelphia (Ph) chromosome were found in 11 patients. The most frequent additional abnormality was a double Ph, which was observed in four cases. Following HSCT, full chimeras were observed in 31 patients (79.5 percent). Among these, 23 (82.3 percent) had presented Ph as the sole abnormality. Mixed chimeras were observed in seven patients, of which three had additional abnormalities. Only one case did not present any cytogenetic response. Five patients presented cytogenetic relapse associated with clinical relapse following HSCT. Twenty-seven patients are still alive and present complete hematological and cytogenetic remission. CONCLUSION: In our study, the presence of additional abnormalities was not associated with worse outcome and relapse risk. Also, no differences in survival rates were observed. Our study supports the view that classical cytogenetic analysis remains an important tool regarding HSCT outcome.
RESUMO CONTEXTO E OBJETIVO: Após o transplante de células tronco-hematopoéticas (TCTH), o cariótipo é uma ferramenta valiosa para monitorar o status do enxerto e da doença. Poucos estudos investigaram o significado prognóstico do cariótipo nos pacientes que se submeteram ao TCTH para leucemia mielóide crônica (LMC). O objetivo desse estudo foi verificar o significado dos achados citogenéticos pré-TCTH em pacientes portadores de LMC. TIPO DE ESTUDO E LOCAL: Série de casos. Instituto Nacional do Câncer (INCA), Rio de Janeiro, Brasil. METODOLOGIA: Foram realizados estudos citogenéticos por bandeamento G em 39 pacientes submetidos ao TCTH. RESULTADOS: Trinta e um pacientes estavam em fase crônica e oito em fase acelerada. Pré-TCTH, alterações cromossômicas adicionais ao cromossomo Philadelphia (Ph) foram observadas em 11 pacientes. A mais freqüente foi o duplo Ph observado em quatro casos. Após o TCTH, quimerismo total foi observado em 31 pacientes (79,5 por cento). Desses, 23 (82,3 por cento) apresentavam somente o cromossomo Ph. Quimerismo misto foi observado em sete pacientes, sendo três com alterações adicionais ao Ph. Um caso não apresentou resposta ao TCTH. Recaída citogenética associada com recaída clínica foi observada em cinco pacientes. Após o TCTH, 27 pacientes permanecem vivos e com remissão clínica e citogenética. CONCLUSÃO: Em nosso estudo a presença de alterações cromossômicas adicionais ao Ph, prévias ao TCTH, não foi associada com pior evolução, com risco de recaída, bem como não foi observada diferença entre as taxas de sobrevida. Nosso estudo sugere que a citogenética clássica permanece uma grande ferramenta no monitoramento do TCTH.
Assuntos
Adolescente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Aberrações Cromossômicas , Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Cromossomo Filadélfia , Brasil/epidemiologia , Cariotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Prognóstico , Análise de Sobrevida , Condicionamento Pré-TransplanteRESUMO
Serial assays of qualitative (multiplex and nested) and quantitative PCR were carried out for detecting and estimating the level of BCR-ABL transcripts in 39 CML patients following bone marrow transplantation. Seven of these patients, who received donor lymphocyte infusions (DLIs) following to relapse, were also monitored. Quantitative estimates of BCR-ABL transcripts were obtained by co-amplification with a competitor sequence. Estimates of ABL transcripts were used, an internal control and the ratio BCR-ABL/ABL was thus estimated for evaluating the kinetics of residual clones. Twenty four patients were followed shortly after BMT; two of these patients were in cytogenetic relapse coexisting with very high BCR-ABL levels while other 22 were in clinical, haematologic and cytogenetic remission 2-42 months after BMT. In this latter group, seven patients showed a favourable clinical-haematological progression in association with molecular remission while in 14 patients quantitative PCR assays indicated molecular relapse that was not associated with an early cytogenetic-haematologic relapse. BCR-ABL/ABL levels could not be correlated with presence of GVHD in 24 patients after BMT. In all seven patients treated with DLI, high levels of transcripts were detected at least 4 months before the appearance of clinical haematological relapse. Following DLI, five of these patients showed decreasing transcript levels from 2 to 5 logs between 4 and 12 months. In eight other patients studied long after BMT, five showed molecular relapse up to 117 months post-BMT and only one showed cytogenetic relapse. Our findings indicated that quantitative estimates of BCR-ABL transcripts were valuable for monitoring minimal residual disease in each patient.