RESUMO
BACKGROUND: The standard treatment for high-risk non-muscle invasive bladder tumors (NMIBT) is transurethral resection of the bladder and BCG instillations. However, responses are limited, and new therapeutic alternatives for these patients are required. The results of checkpoint inhibitors in advanced tumors have led to interest in the use of these molecules in NMIBT. METHODS: We conducted a search on PubMed using the terms «bladder cancer¼ and «check point inhibitors¼. We have used the search engines clinicaltrials.gov and clinicaltrialsregister.eu for the search of clinical trials. RESULTS: There are currently 5 trials in progress on BCG untreated patients. There are no results available. As for BCG non-responders, there are 15 ongoing trials, two of them with preliminary results: Keynote 057, with promising results with pembrolizumab, which has led the FDA to approve its use in January 2020, and SWOG S1605, which has shown similar results with atezolizumab. Other trials are using intravesical administration of these drugs, which is an attractive option if it is effective for cancer control. CONCLUSIONS: Checkpoint inhibitors offer a new possibility for patients who do not respond to BCG. These will probably be used in the future for previously BCG untreated patients. Preliminary data from clinical trials show promising results. A good understanding of these molecules by urologists and the creation of multidisciplinary teams are crucial in order to offer the best therapeutic alternatives to these patients.
Assuntos
Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Previsões , Humanos , Imunoterapia/tendências , Invasividade Neoplásica , Medição de Risco , Neoplasias da Bexiga Urinária/patologiaRESUMO
The impact of donor age in patients with acute myeloid leukemia and myelodysplastic syndrome who underwent allogeneic hematopoietic stem cell transplant (HSCT) remains unclear. In the current study, we evaluate 179 consecutive patients who received an HSCT, from January 2000 to January 2013, in our Institution. Most of the HSCT (91%) were HLA-matched. Patient and donor median age were 51 years (18-69) and 47 years (12-75) respectively, and 81 donors (45%) were older than 50 years. The median follow-up was 38 months (range 1-138), Kaplan-Meier estimated 3-year overall survival (OS) was 63% and disease free survival (DFS) was 56%. Interestingly, patients who received an HSCT from a donor older age (>50 y) showed a poorer OS (51% vs 73%; p=0.01), as well as a higher TRM (20% vs 8%; p=0.038) and higher relapse rate (28% vs 39%; p=0.03). In a stratified subanalysis, 3-year estimated OS was significantly lower among patients undergoing an HSCT from >50 years sibling donors compared to those receiving an HSCT from <50 years unrelated donor (54% vs 72%; p<0.001). In summary, we can conclude that receiving an HSCT from a donor over 50 years old is associated with poorer outcome in patients diagnosed with MDS and AML, and this information may be incorporated into the complex process of donor selection.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Doadores não Relacionados/estatística & dados numéricos , Adolescente , Adulto , Fatores Etários , Idoso , Criança , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Análise de Sobrevida , Transplante Homólogo , Resultado do Tratamento , Adulto JovemRESUMO
The benefit of azacitidine treatment in survival of high-risk myelodysplastic syndromes (MDS) patients compared with conventional care treatment (CCT) has not been established outside clinical trials. To assess its effectiveness, we compared overall survival (OS) between azacitidine and conventional treatment (CCT) in high-risk MDS patients, excluding those undergoing stem cell transplantation, submitted to the Spanish MDS registry from 2000 to 2013. Several Cox regression and competing risk models, considering azacitidine as a time-dependent covariate, were used to assess survival and acute myeloblastic leukemia (AML) progression. Among 821 patients included, 251 received azacitidine. Median survival was 13.4 (11.8-16) months for azacitidine-treated patients and 12.2 (11-14.1) for patients under CCT (P=0.41). In a multivariate model, age, International prognostic scoring system and lactate dehydrogenase were predictors of OS whereas azacitidine was not (adjusted odds ratio 1.08, 95% confidence interval 0.86-1.35, P=0.49). However, in patients with chromosome 7 abnormalities, a trend toward a better survival was observed in azacitidine-treated patients (median survival 13.3 (11-18) months) compared with CCT (median survival 8.6 (5-10.4) months, P=0.08). In conclusion, our data show that, in spite of a widespread use of azacitidine, there is a lack of improvement in survival over the years. Identification of predicting factors of response and survival is mandatory.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Azacitidina/uso terapêutico , Síndromes Mielodisplásicas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Progressão da Doença , Feminino , Seguimentos , Humanos , Incidência , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/etiologia , Masculino , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Prognóstico , Sistema de Registros , Espanha/epidemiologia , Resultado do TratamentoRESUMO
OBJECTIVES: The aim of the present clinical research is to analyze, in the light of the best scientific evidence, the performance and the cost of the main diagnostic tools for overactive bladder (OAB). METHODS: It is an exploratory transversal study in which 199 women diagnosed of OAB between 2006 and 2008 were selected and underwent to following prospective analyses: physical examination, urine analysis, micturition diary (MD) and urodynamic study (UDS). A percentage of 80% was assumed as highly sensitive and a diagnostic difference among tests of 10% would be considered clinically relevant. Tests' sensitivity for diagnosis of OAB was statistically established by two ways: isolated and combined. Besides, the direct and indirect costs of these tests performance were conducted. Cost-effectiveness study of clinical history (CH), MD and US for the diagnosis of OAB was performed. RESULTS: Overall sensitivity for OAB diagnosis is low for the 3 tests used in isolated way, whilst the combination of any two tests shows good overall sensitivity. The combination of CH and MD has appeared as the most cost-effective alternative to OAB diagnosis. CONCLUSIONS: For OAB diagnosis, CH-DM combination shows the same sensitivity than the association of either of them with the UDS, but unlike to these, it shows the lowest cost.
Assuntos
Análise Custo-Benefício , Bexiga Urinária Hiperativa/diagnóstico , Bexiga Urinária Hiperativa/economia , Micção , Urodinâmica , Idoso , Estudos Transversais , Técnicas e Procedimentos Diagnósticos/economia , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
OBJECTIVES: The incidence of neoplasms in renal transplant recipients is higher than in general population. The increasing age of donors and recipients also increases the risk of developing malignancies, including genitourinary. The aim of this study is to analyze clinical aspects and management of this complication. MATERIALS AND METHODS: We conducted a retrospective analysis of 1365 patients who underwent renal transplantation between 1977 and 2010 who were 44.6 ± 14.9 years old at the time of transplantation. The median follow-up was 95.6 months (range, 18.0-236.0). Data were analyzed for sex, age, time from transplant to diagnosis, location, clinical stage, immunosuppression, treatment, follow-up, and evolution. RESULTS: We diagnosed 25 de novo urologic neoplasms (25/1365; 1.8%) in 24 patients, with a median follow-up of 32 months (range, 12.5-51.8) from the diagnosis. Sixteen were male (66.7%) and 8 female (33.3%), with a median age at diagnosis of 59 years (range, 56.0-65.5). The median time between the transplant and the diagnosis of the malignancy was 69 months (range, 40.0-116.5). There were 11 renal cell carcinomas (RCC; 11/25; 44%), 8 in native kidney and 3 in renal allograft; 9 prostate cancers (PCa; 9/25; 36%), 8 localized and 1 metastatic; and 5 transitional cell carcinomas (TCC; 5/25; 20%), 3 in bladder and 2 in renal allograft pelvis. Treatments performed were similar to those used in the nontransplanted population. RCC were treated with radical nephrectomy when affecting the native kidney, partial nephrectomy when affecting the allograft, or immunotherapy when metastatic. Patients with localized PCa were treated with radical prostatectomy, radiotherapy, or androgenic deprivation if there were comorbidities, and those metastatic with hormonal deprivation. Bladder TCCs were treated with transurethral resection or radical cystectomy. Pelvis TCCs affecting the allograft were treated with radical nephroureterectomy of the allograft including bladder cuff and pelvic lymphadenectomy. CONCLUSIONS: There exists an increased incidence of urologic tumors in kidney transplant recipients. Conventional treatments of these tumors are technically feasible. The risk of developing these tumors remains even in the long term. Because of their suitability for curative treatments, it is advisable to perform periodic screening for urologic cancers to achieve an early diagnosis.
Assuntos
Carcinoma de Células Renais/complicações , Carcinoma de Células de Transição/complicações , Transplante de Rim/efeitos adversos , Neoplasias da Próstata/complicações , Insuficiência Renal/complicações , Neoplasias Urológicas/complicações , Adulto , Idoso , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células de Transição/diagnóstico , Feminino , Humanos , Imunossupressores/uso terapêutico , Rim/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/diagnóstico , Insuficiência Renal/diagnóstico , Estudos Retrospectivos , Risco , Neoplasias Urológicas/diagnósticoRESUMO
PRAME is a tumor associated antigen (TAA) of particular interest since it is widely expressed by lymphoid and myeloid malignancies. Several studies have associated high PRAME RNA levels with good prognosis in acute myeloid leukemia (AML). PRAME expression is regulated at the epigenetic level. For this reason inhibitors of DNA methylation, such as 5-azacytidine, can modulate the expression of this TAAs. In the current study we analyzed the effect of 5-azaC on the expression of PRAME in blasts versus CD34+ cells from healthy donors in an attempt to increase its expression, thus inducing a potential target for therapeutic strategies.
Assuntos
Antígenos CD34/metabolismo , Antígenos de Neoplasias/genética , Azacitidina/farmacologia , Leucemia Mieloide Aguda/genética , Células-Tronco/metabolismo , Antígenos de Neoplasias/metabolismo , Antimetabólitos Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Doadores de Sangue , Células da Medula Óssea/efeitos dos fármacos , Células da Medula Óssea/metabolismo , Células da Medula Óssea/patologia , Células Cultivadas , Ilhas de CpG/genética , Análise Citogenética , Epigênese Genética/efeitos dos fármacos , Epigênese Genética/fisiologia , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Saúde , Humanos , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/patologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/fisiologiaAssuntos
Anemia/tratamento farmacológico , Antineoplásicos Fitogênicos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Trombocitopenia/tratamento farmacológico , Vincristina/administração & dosagem , Adolescente , Anemia/etiologia , Criança , Feminino , Humanos , Transtornos Linfoproliferativos/complicações , Transtornos Linfoproliferativos/terapia , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco de Sangue Periférico/efeitos adversos , Estudos Retrospectivos , Trombocitopenia/etiologia , Transplante AutólogoRESUMO
We analysed the outcome of 92 consecutive unrelated donor haematopoietic cell transplantations (UD-HCTs) performed in Spain to treat adult patients with CML in the first chronic phase (1CP). Patients' and donors' median age was 32 (15-49) and 36 (22-56) years, respectively. In all, 73 pairs (79%) matched for A, B+/-C and DRB1+/-DQB1 loci and 19 had > or =1 mismatch. Their probability of survival and disease-free survival at 4 years were 50 and 46%, respectively. Pretransplant factors associated with a better survival were patient age <25 years (P=0.035), donor age < or =36 years (P=0.012), use of cyclosporine since day -7 (P=0.001), and matching 8/8, 9/10 or 10/10 loci at allele level (P=0.003). In multivariate analysis only donor age (P=0.003; RR=3.1 (95% CI: 1.3-7.1)) and degree of HLA-matching (P=0.009; RR: 7.7 (95% CI: 1.8-33)) maintained their significance. The addition of these two variables to the EBMT prognostic score allowed an adequate risk assessment for patients receiving a UD-HCT during 1CP. Our analysis shows that in patients with a young and fully allele-matched donor, UD-HCT should be considered in the initial therapeutic algorithm due to its excellent outcome (92% survival at 2 years).
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Doadores Vivos , Adolescente , Adulto , Fatores Etários , Intervalo Livre de Doença , Feminino , Antígenos HLA-DQ , Antígenos HLA-DR , Cadeias HLA-DRB1 , Teste de Histocompatibilidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Transplante HomólogoRESUMO
In order to analyze the outcome of patients with chronic myeloid leukemia (CML) who relapse after allogeneic stem cell transplantation (SCT), we investigated data from 107 patients reported to the Spanish Registry, GETH. In all, 93 (87%) patients were treated after relapse; 36 out of 49 that failed to achieve a response received a second relapse-treatment, and seven a third one. At the last follow-up, the number of patients in molecular or cytogenetic remission was 29 and 13, respectively. Overall survival and progression-free survival after relapse were 53.6% (95% CI: 42.9--64.2) and 52% (95% CI: 41-63) at 5 years, respectively. In multivariate analysis, survival was significantly related to CML phase at relapse (cytogenetic or chronic phase vs advanced phases) and time from transplant to relapse (<1 vs >or=1 year). Patients with no adverse factors had a better survival compared with patients with one or two adverse features (65 vs 35 vs 0%, respectively). We conclude that a significant proportion of CML patients that relapse after transplantation can regain complete and long-lasting remissions with one or more salvage therapies. Disease stage at relapse and time from transplant to relapse should be taken into account when comparing results of different salvage treatments.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Adolescente , Adulto , Feminino , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Recidiva , Indução de Remissão , Estudos Retrospectivos , Terapia de Salvação , Espanha , Análise de Sobrevida , Transplante Homólogo , Resultado do TratamentoRESUMO
In the present study, we analyze the efficacy of prophylaxis with meropenem in patients receiving a matched related donor allogeneic transplant. In total, 38 patients were sequentially treated with meropenem starting on the day of the first febrile episode (n=17, group A) vs prophylactic meropenem starting on the first day with <500/mm(3) granulocytes (n=21, group B), and maintained until resolution of fever or after granulocyte count >500/mm(3). Of these, 16 (94%) patients in group A developed fever as compared to 16 (76%) in group B (P=0.02). While only one patient in group A did not require first-line antibiotherapy, there were seven (33%) in group B who did not require it (P=0.01) since fever lasted less than 72 h. In addition, 52% patients in group B did not require second-line antibiotics as compared to 11% among patients in group A (P=0.04). In multivariate analysis prophylaxis with meropenem (HR=2.83, 95% CI (1-8.02); P=0.04) and disease status at transplant (HR for early stage=0.15, 95% CI (0.04-0.62); P=0.04) significantly influenced the development of fever. In conclusion, the current pilot study suggests that the use of prophylaxis with meropenem during the period of neutropenia in patients undergoing allogeneic transplantation favorably affects the morbidity of the procedure by reducing febrile episodes.
Assuntos
Infecções Bacterianas/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B/terapia , Leucemia Mieloide/terapia , Tienamicinas/administração & dosagem , Doença Aguda , Adulto , Infecções Bacterianas/epidemiologia , Doença Crônica , Estudos de Coortes , Feminino , Febre/epidemiologia , Febre/prevenção & controle , Humanos , Incidência , Masculino , Meropeném , Pessoa de Meia-Idade , Projetos PilotoRESUMO
Since graft-versus-leukemia (GVL) is the main weapon for disease eradication after reduced intensity conditioning (RIC) allogeneic SCT, the availability of sensitive and specific techniques to monitor changes in tumor load after transplant are especially helpful. These minimal residual disease techniques would allow an early intervention in the event of low tumor burden, for which immunotherapy is highly effective. Some authors have found an association between persistence of MRD, mixed chimerism and risk of relapse. Nevertheless, data from the literature remain contradictory and further correlations should be established, especially in RIC transplants. In this study we have analyzed the impact of MRD and chimerism monitoring on the outcome of 34 patients undergoing RIC allogeneic SCT who were considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions. At day +100 25 (75%) patients reached complete remission (CR), there were five (15%) partial responses and three patients progressed. Incidence of grade 2-4 aGVHD and extensive cGVHD were 35% and 58%, respectively. Sixteen percent of patients developing aGVHD relapsed as compared to 47% in those without aGVHD (P = 0.03) and also 10% of patients developing cGVHD relapsed as compared to 50% relapses in those without cGHVD (P = 0.03). Four patients (12%) died due to early (n = 1) and late (n = 3) transplant-related mortality. After a median follow-up of 15 months, 24 out of the 34 patients remain alive. Projected overall survival and disease-free survival at 3 years are 68% and 63%, respectively. Early chimerism analysis showed 67% of patients with complete chimerism (CC) in bone marrow (BM), 86% in peripheral blood (PB), 89% in granulocytes and 68% in T lymphocytes. On day +100, these figures were 68%, 79%, 90% and 73%, respectively, and on day +180 there were 83% patients with CC in BM, 100% in PB, 100% in granulocytes and 100% in T lymphocytes. We observed a trend to a higher incidence of relapse in patients with mixed chimerism (MC) as compared to patients with CC. MRD monitoring by flow cytometry and/or RT-PCR analysis was performed in 23 patients. MRD assessment on days +21 to +56 after transplant allowed identification of patients at risk of relapse. In this sense, seven out of 12 patients (58.3%) who had positive MRD on days +21 to +56 relapsed as compared to none out of 11 patients who had negative MRD (P = 0.002). Of the seven patients with criteria to monitor MRD who relapsed after transplant, all but one remained MRD positive until relapse. By contrast, 10 patients remained MRD negative and all of them are in continuous CR. In nine additional patients, persistence of MRD or mixed chimerism was observed after transplant and withdrawal of cyclosporin with or without DLI was performed. Only two out of these nine patients relapsed. MRD clearance was preceded by CC and GVHD. In conclusion, in our study we found that RIC allogeneic transplantation can be used in patients considered poor candidates for conventional transplantation due to advanced age or other concurrent medical conditions with both low toxicity and low transplant-related mortality. Simultaneous studies of both chimerism and MRD are a useful tool in order to predict risk of relapse in patients undergoing RIC transplants and so can be helpful for individualizing treatment strategies after transplant.
Assuntos
Sobrevivência de Enxerto , Transplante de Células-Tronco Hematopoéticas , Neoplasia Residual/diagnóstico , Condicionamento Pré-Transplante , Adulto , Idoso , Células Sanguíneas/patologia , Células da Medula Óssea/patologia , Intervalo Livre de Doença , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Terapia de Imunossupressão , Tábuas de Vida , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Neoplasia Residual/patologia , Células-Tronco Neoplásicas/patologia , Seleção de Pacientes , Indução de Remissão , Estudos Retrospectivos , Espanha/epidemiologia , Análise de Sobrevida , Taxa de Sobrevida , Transplante Autólogo/patologia , Transplante Homólogo/efeitos adversos , Transplante Homólogo/patologia , Resultado do TratamentoRESUMO
Early response to therapy is one of the most important prognostic factors in acute leukemia. It is hypothesized that early immunophenotypical evaluation may help identify patients at high risk for relapse from those who may remain in complete remission (CR). Using multiparametric flow cytometry, the level of minimal residual disease (MRD) was evaluated in the first bone marrow (BM) in morphologic CR obtained after induction treatment from 126 patients with acute myeloid leukemia (AML) who displayed aberrant phenotypes at diagnosis. Based on MRD level, 4 different risk categories were identified: 8 patients were at very low risk (fewer than 10(-4) cells), and none have relapsed thus far; 37 were at low risk (10(-4) to 10(-3) cells); and 64 were at intermediate risk (fewer than 10(-3) to 10(-2) cells), with 3-year cumulative relapse rates of 14% and 50%, respectively. The remaining 17 patients were in the high-risk group (more than 10(-2) residual aberrant cells) and had a 3-year relapse rate of 84% (P =.0001). MRD level not only influences relapse-free survival but also overall survival (P =.003). The adverse prognostic impact was also observed when M3 and non-M3 patients with AML were separately analyzed, and was associated with adverse cytogenetic subtypes, 2 or more cycles to achieve CR, and high white blood cell counts. Multivariate analysis showed that MRD level was the most powerful independent prognostic factor, followed by cytogenetics and number of cycles to achieve CR. In conclusion, immunophenotypical investigation of MRD in the first BM in mCR obtained after AML induction therapy provides important information for risk assessment in patients with AML.
Assuntos
Imunofenotipagem/métodos , Leucemia Mieloide/patologia , Doença Aguda , Adulto , Medula Óssea/patologia , Feminino , Citometria de Fluxo , Humanos , Leucemia Mieloide/mortalidade , Leucemia Mieloide/terapia , Masculino , Recidiva Local de Neoplasia , Neoplasia Residual , Fenótipo , Fatores de Risco , Taxa de SobrevidaRESUMO
We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.
Assuntos
Antivirais/uso terapêutico , Cistite/tratamento farmacológico , Citosina/uso terapêutico , Organofosfonatos , Compostos Organofosforados/uso terapêutico , Infecções por Polyomavirus/tratamento farmacológico , Infecções Tumorais por Vírus/tratamento farmacológico , Adolescente , Transplante de Medula Óssea/efeitos adversos , Transplante de Medula Óssea/métodos , Cidofovir , Cistite/complicações , Cistite/diagnóstico , Citosina/análogos & derivados , Hemorragia/etiologia , Humanos , Masculino , Polyomavirus/isolamento & purificação , Infecções por Polyomavirus/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Resultado do Tratamento , Infecções Tumorais por Vírus/diagnósticoRESUMO
We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day +21; bone marrow showed mixed chimaerism from day +21 to day +221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.
Assuntos
Anemia Sideroblástica/genética , Anemia Sideroblástica/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Anemia Sideroblástica/imunologia , Transfusão de Sangue , Ciclosporina/uso terapêutico , Seguimentos , Doença Enxerto-Hospedeiro/imunologia , Antígenos HLA/imunologia , Humanos , Imunossupressores/uso terapêutico , Masculino , Esteroides/uso terapêutico , Transplante HomólogoRESUMO
Patients with hypereosinophilic syndrome (HES) display a very heterogeneous clinical picture ranging from asymptomatic cases to very aggressive forms. We report a 38-year-old woman with progressive HES who developed severe myelofibrosis and was treated by allogeneic stem cell transplantation, using peripheral blood (PBSCT) instead of bone marrow as the source of progenitor cells, after conditioning with cytoxan and busulphan. To the best of our knowledge, this is the first case of HES with myelofibrosis treated with PBSCT. The patient remains alive 8 months post-PBSCT, and bone marrow fibrosis has significantly decreased following transplantation. Bone Marrow Transplantation (2000) 25, 217-218.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndrome Hipereosinofílica/complicações , Síndrome Hipereosinofílica/terapia , Mielofibrose Primária/complicações , Mielofibrose Primária/terapia , Adulto , Feminino , Humanos , Síndrome Hipereosinofílica/patologia , Mielofibrose Primária/patologia , Condicionamento Pré-Transplante , Resultado do TratamentoRESUMO
We report an unusual case of cerebral toxoplasmosis associated with Guillain-Barré syndrome (GBS) in a 25-year-old patient diagnosed with chronic myelogenous leukaemia (CML), who underwent a mismatched allogeneic peripheral stem cell transplantation (PSCT). On day +83 he started with fever, and 7 days later tremor, muscular weakness, diplopia, dysarthria, respiratory difficulty, and universal arreflexia appeared, compatible with GBS. As the patient had a positive cytomegalovirus (CMV) antigenemia, this was the aetiology suspected for his neurologic findings, but specific treatment failed to improve his clinical situation, and he died on day +123. Necropsy demonstrated cerebral toxoplasmosis and axonal degeneration of nerve roots compatible with the axonal form of GBS. Interestingly, the polymerase chain reaction (PCR) signal for Toxoplasma gondii in two different cerebrospinal fluid (CSF) samples had been negative. In addition, this case showed unique magnetic resonance imaging (MRI) abnormalities. We conclude that a negative PCR on CSF cannot exclude toxoplasmosis in a transplant patient, and we emphasise the importance of considering Toxoplasma as an aetiology of fever and neurological symptoms in the transplant setting.
Assuntos
Síndrome de Guillain-Barré/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Toxoplasmose Cerebral/diagnóstico , Adulto , Animais , Antígenos Virais/análise , Encéfalo/patologia , Citomegalovirus/isolamento & purificação , Evolução Fatal , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Imageamento por Ressonância Magnética , Masculino , Reação em Cadeia da Polimerase , Toxoplasma/isolamento & purificação , Toxoplasmose Cerebral/líquido cefalorraquidiano , Transplante HomólogoRESUMO
In the present review we analyse the current knowledge about the growth properties of AML progenitor cells and their relationship with other clinico-biological characteristics of the disease. Leukaemic colony forming unit L-CFU is considered to be the clonogenic cell in AML and more immature than the blast cell population. Our studies have shown that in leukaemic hematopoiesis colony forming cells can exist among both cell fractions CD34+ and CD34-. Optimal "in vitro" proliferation of L-CFU is dependent upon the addition of exogenous growth factors. However, it has been observed that leukaemic progenitor cells frequently display a certain degree of autonomous proliferation. In order to quantify the "in vitro" behaviour of L-CFU, we have explored 3 parameters: 1) plating efficiency (PE); 2) autonomous growth (AG); and 3) autonomous proliferative index (API) which was calculated as AG divided by PE and we have correlated them with other clinico-biological data. According to the FAB classification we could observe that patients with M3 subtype showed an higher PE than other AML subgroups and a significantly lower API. Regarding CD34 expression we observed that AG was enhanced in CD34+ cases and also in those showing a higher rh123 elimination. In order to determine whether PE could condition clinical evolution, we analysed this parameter in a large series of patients but failed to demonstrate any relationship. By contrast, we observed that patients who displayed a higher API showed a shorter survival than patients with lower API (18% vs 48% surviving at 3 years). We have also shown that abnormalities in the CFU-GM growth pattern could be associated with risk the of relapse in AML patients; a switch from normal to abnormal "in vitro" growth should alert us. But for the assessment of the real value of these analyses sequential follow-up studies are mandatory. In summary, cell culture studies contribute not only to a better understanding of leukaemic hematopoiesis but may also contribute to better disease monitoring.
Assuntos
Leucemia Mieloide Aguda/patologia , Antígenos CD34/análise , Divisão Celular , Humanos , Leucemia Mieloide Aguda/mortalidade , Células-Tronco Neoplásicas/fisiologia , Fenótipo , Prognóstico , RecidivaRESUMO
A Spanish National PBPC Donor Registry has recently been established for short- and long-term safety data collection in normal donors receiving rhG-CSF. To date, 466 donors have been included in the Registry. Median (range) dose and duration of rhG-CSF administration was 10 microg/kg/day (4-20) and 5 days (4-8), respectively. Donors underwent a median of two aphereses (range, 1-5). Adverse effects consisted mainly of bone pain (90.2%), headache (16.9%) and fever (6. 1%), but no donor discontinued rhG-CSF prematurely due to toxicity. Side-effects were more frequent in donors receiving >10 microg/kg/day than in those with lower doses (82.8% vs 61.8%; P = 0. 004). A significant decrease between baseline and post-apheresis platelet counts was the most important analytical finding (229 x 10(9)/l vs 140 x 10(9)/l; P < 0.0001), with a progressive reduction in platelet count with each apheresis procedure. One donor developed pneumothorax that required hospitalization due to central venous line placement. The mean CD34+ cell dose collected was 6.9 x 10(6)/kg (range, 1.3-36), with only 14 donors (2.9%) not achieving a minimum target of CD34+ cells of 2 x 10(6)/kg. No definitive information about potential long-term side effects is yet available. However, we hope this National Registry will serve as a useful basis for better monitoring of the efficiency and side-effects of cytokine administration in healthy people.