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1.
Hematol Oncol ; 35(4): 797-803, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27338621

RESUMO

The probability of achieving long term remission for patients with refractory acute leukaemia is very low. Allogeneic stem cell transplantation (SCT) is offered to these patients in order to improve their dismal outcome. We retrospectively analyzed 361 acute leukaemia patients, who underwent allogeneic SCT in the Hadassah's bone marrow transplantation department between the years 2005 and 2012 and identified 84 patients with active leukaemia at transplantation. Median age was 34 years. Sixty four patients were diagnosed with acute myeloid leukaemia (AML), 18 patients with acute lymphoblastic leukaemia and two with biphenotypic leukaemia. The majority of patients were diagnosed with de-novo AML and transplanted at relapse. In the surviving patients, median follow up was 15 months. One year OS was 20%. At time of last follow up, 13 patients were alive (15.5%): ten patients with AML and two patients with acute lymphoblastic leukaemia. In the univariate analysis, factors associated with significantly better overall survival were as follows: matched unrelated donor (p = 0.006), matched donor (p = 0.014) and occurrence of acute graft-versus-host disease (aGVHD) (p = 0.019). Karnofsky performance score at SCT and occurrence of cGVHD were found to be borderline significant. Only matched unrelated donor and aGVHD were found to affect overall survival significantly in the multivariate analysis. Other than performance score at SCT, none of the pretransplant patients' characteristics were found to influence survival. In conclusion, as none of the pretransplant characteristics were found to influence the ability to select the patients that will benefit from HSC transplantation, this work supports offering HSCT to all active leukaemia eligible patients with reasonable performance status. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Adulto Jovem
2.
Lancet ; 383(9915): 436-48, 2014 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-24161820

RESUMO

BACKGROUND: In chronic granulomatous disease allogeneic haemopoietic stem-cell transplantation (HSCT) in adolescents and young adults and patients with high-risk disease is complicated by graft-failure, graft-versus-host disease (GVHD), and transplant-related mortality. We examined the effect of a reduced-intensity conditioning regimen designed to enhance myeloid engraftment and reduce organ toxicity in these patients. METHODS: This prospective study was done at 16 centres in ten countries worldwide. Patients aged 0-40 years with chronic granulomatous disease were assessed and enrolled at the discretion of individual centres. Reduced-intensity conditioning consisted of high-dose fludarabine (30 mg/m(2) [infants <9 kg 1·2 mg/kg]; one dose per day on days -8 to -3), serotherapy (anti-thymocyte globulin [10 mg/kg, one dose per day on days -4 to -1; or thymoglobuline 2·5 mg/kg, one dose per day on days -5 to -3]; or low-dose alemtuzumab [<1 mg/kg on days -8 to -6]), and low-dose (50-72% of myeloablative dose) or targeted busulfan administration (recommended cumulative area under the curve: 45-65 mg/L × h). Busulfan was administered mainly intravenously and exceptionally orally from days -5 to -3. Intravenous busulfan was dosed according to weight-based recommendations and was administered in most centres (ten) twice daily over 4 h. Unmanipulated bone marrow or peripheral blood stem cells from HLA-matched related-donors or HLA-9/10 or HLA-10/10 matched unrelated-donors were infused. The primary endpoints were overall survival and event-free survival (EFS), probabilities of overall survival and EFS at 2 years, incidence of acute and chronic GVHD, achievement of at least 90% myeloid donor chimerism, and incidence of graft failure after at least 6 months of follow-up. FINDINGS: 56 patients (median age 12·7 years; IQR 6·8-17·3) with chronic granulomatous disease were enrolled from June 15, 2003, to Dec 15, 2012. 42 patients (75%) had high-risk features (ie, intractable infections and autoinflammation), 25 (45%) were adolescents and young adults (age 14-39 years). 21 HLA-matched related-donor and 35 HLA-matched unrelated-donor transplants were done. Median time to engraftment was 19 days (IQR 16-22) for neutrophils and 21 days (IQR 16-25) for platelets. At median follow-up of 21 months (IQR 13-35) overall survival was 93% (52 of 56) and EFS was 89% (50 of 56). The 2-year probability of overall survival was 96% (95% CI 86·46-99·09) and of EFS was 91% (79·78-96·17). Graft-failure occurred in 5% (three of 56) of patients. The cumulative incidence of acute GVHD of grade III-IV was 4% (two of 56) and of chronic graft-versus-host disease was 7% (four of 56). Stable (≥90%) myeloid donor chimerism was documented in 52 (93%) surviving patients. INTERPRETATION: This reduced-intensity conditioning regimen is safe and efficacious in high-risk patients with chronic granulomatous disease. FUNDING: None.


Assuntos
Doença Granulomatosa Crônica/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adolescente , Adulto , Alemtuzumab , Anticorpos Monoclonais Humanizados/administração & dosagem , Soro Antilinfocitário/administração & dosagem , Bussulfano/administração & dosagem , Criança , Pré-Escolar , Quimioterapia Combinada , Sobrevivência de Enxerto/efeitos dos fármacos , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA , Humanos , Imunossupressores/administração & dosagem , Lactente , Estudos Prospectivos , Quimeras de Transplante/fisiologia , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Adulto Jovem
3.
J Infect Dis ; 209(4): 557-61, 2014 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-23983215

RESUMO

We examined the rate, clinical impact, and risk factors of cytomegalovirus (CMV) drug resistance in 561 patients who underwent 616 hematopoietic stem cell transplantations (HSCTs) over 5 years. Drug resistance was exclusively identified in haploidentical (haplo)-HSCT recipients receiving preemptive therapy, among whom the rate was 14.5%. Resistance appeared after prolonged treatment (median, 70 days), was associated with higher preceding viral load (P < .001), and was the strongest predictor for disease by multivariate analysis. The high rate of drug resistance as interlinked with severe disease in haplo-HSCT recipients suggests the potential advantage of prophylactic over preemptive treatment in high-risk patients and highlights the need for better-tolerable anti-CMV drugs.


Assuntos
Antivirais/administração & dosagem , Infecções por Citomegalovirus/prevenção & controle , Citomegalovirus/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Análise de Variância , Distribuição de Qui-Quadrado , Criança , Citomegalovirus/genética , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Farmacorresistência Viral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Estudos Prospectivos
4.
Transpl Int ; 25(12): 1241-7, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22974004

RESUMO

Cyclosporine (CSA) is the most commonly used medication for GVHD prophylaxis. The initiation time varies from day -4 to day 0. Initially, we gave CSA starting on day -1. However, since 2003 we have changed CSA initiation timing policy in most of our protocols to day -4, to achieve stable and controlled pretransplant CSA levels. Here, we assessed if initiation time impact the outcome of allogeneic stem-cell transplantation (allo-SCT). Data of 261 patients who underwent allo-SCT for hematological malignancies from a fully matched donor, treated with CSA as a single agent for GVHD prophylaxis were prospectively collected. Patients were divided according to CSA initiation time and analyzed for outcome. The acute GVHD severity, cGVHD extent, GVHD-associated mortality were significantly lower in the CSA -4 group. There was no difference in the rate and timing of acute or chronic GVHD. Overall survival did not differ between the groups. We conclude that the initiation of CSA at day -4 reduced the severity of aGVHD, extent of cGVHD, and GVHD-associated mortality without impact on overall survival.


Assuntos
Ciclosporina/administração & dosagem , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Neoplasias Hematológicas/cirurgia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Vidarabina/uso terapêutico
5.
Biol Blood Marrow Transplant ; 17(9): 1282-8, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21220033

RESUMO

In the mid-1990s, we introduced a fludarabine (Flu)-based conditioning regimen for hematopoietic stem cell transplantation (HSCT) in patients with Fanconi anemia (FA).The aim of this study is to compare Flu-based conditioning to alternative regimens in patients with FA. Forty-one patients with FA (aged 0.5-31, median, 10.3 years) who underwent allogeneic HSCT were included in this retrospective study. Hospital records were reviewed for conditioning regimens, engraftment data, and toxicity. The median (range) follow-up was 32 (0.5-149) months. Flu-based conditioning regimens were used in 24 patients: 17 patients were treated with alternative conditioning regimens including a radiation-based regimen/cyclophosphamide and busulfan regimen. The disease-free survival (DFS) after Flu-based regimens is 83% (20/24) versus 35% (6/17) for the alternative regimens (P = .002). Toxicity was significantly lower in patients who received Flu-based conditioning (modified Bearman toxicity score [P = .001]). Seven patients received transplants from matched unrelated donors without irradiation (5 of whom are currently alive and well). All patients who survived are disease free and in good clinical condition. We conclude that a combination of fludarabine with antithymocyte globulin (ATG) and low-dose cyclophosphamide (Cy) and/or busulfan (Bu) is safe, demonstrates low rejection rates, and is well tolerated by FA patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Medula Óssea/métodos , Anemia de Fanconi/terapia , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Adolescente , Adulto , Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Criança , Pré-Escolar , Ciclofosfamida/uso terapêutico , Sobrevivência de Enxerto , Humanos , Lactente , Estudos Retrospectivos , Vidarabina/uso terapêutico , Adulto Jovem
6.
Haematologica ; 96(3): 472-6, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21109689

RESUMO

Mutations in the IL-2-inducible T-cell kinase gene have recently been shown to cause an autosomal recessive fatal Epstein Barr virus (EBV) associated lymphoproliferation. We report 3 cases from a single family who presented with EBV-positive B-cell proliferation diagnosed as Hodgkin's lymphoma. Single nucleotide polymorphism array-based genome-wide linkage analysis revealed IL-2-inducible T-cell kinase as a candidate gene for this disorder. All 3 patients harbored the same novel homozygous nonsense mutation C1764G which causes a premature stop-codon in the kinase domain. All cases were initially treated with chemotherapy. One patient remains in durable remission, the second patient subsequently developed severe hemophagocytic lymphohistiocytosis with multi-organ failure and died, and the third patient underwent a successful allogeneic bone marrow transplantation. IL-2-inducible T-cell kinase deficiency underlies a new primary immune deficiency which may account for part of the spectrum of Epstein Barr virus related lymphoproliferative disorders which can be successfully corrected by bone marrow transplantation.


Assuntos
Transplante de Medula Óssea/imunologia , Doença de Hodgkin/genética , Proteínas Tirosina Quinases/genética , Transplante Homólogo/imunologia , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Linfócitos B/imunologia , Linfócitos B/patologia , Pré-Escolar , Códon sem Sentido , Morte , Intervalo Livre de Doença , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Infecções por Vírus Epstein-Barr/imunologia , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/terapia , Feminino , Herpesvirus Humano 4/crescimento & desenvolvimento , Doença de Hodgkin/etiologia , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Doença de Hodgkin/terapia , Homozigoto , Humanos , Ativação Linfocitária/genética , Ativação Linfocitária/imunologia , Linfo-Histiocitose Hemofagocítica/mortalidade , Linfo-Histiocitose Hemofagocítica/patologia , Masculino , Linhagem , Proteínas Tirosina Quinases/imunologia , Indução de Remissão
7.
Pediatr Blood Cancer ; 57(4): 681-3, 2011 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-21618408

RESUMO

We report a successful umbilical cord blood transplantation (UCBT) in an 8-month male with Wiskott-Aldrich syndrome (WAS) and congenital cytomegalovirus (CMV) infection. The child presented at 3 months of age with symptomatic thrombocytopenia and CMV infection. Despite appropriate antiviral treatment no rise in the platelet count was observed. Genetic analysis confirmed the diagnosis of WAS. The clinical course was complicated by severe CMV retinitis with bilateral retinal hemorrhages and renal vasculitis. He underwent unrelated UCBT resulting in a rapid resolution of autoimmunity and thrombocytopenia.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Infecções por Citomegalovirus/congênito , Infecções por Citomegalovirus/cirurgia , Síndrome de Wiskott-Aldrich/cirurgia , Infecções por Citomegalovirus/fisiopatologia , Humanos , Lactente , Masculino , Transplante Homólogo , Síndrome de Wiskott-Aldrich/fisiopatologia
8.
Biol Blood Marrow Transplant ; 16(1): 62-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19733252

RESUMO

The aim of this study was to validate the 2005-2006 National Institutes of Health (NIH) scale for patient's self-reporting and clinical manifestations of oral chronic graft-versus-host disease (cGVHD). Numerical parameters of the NIH scale were analyzed for their construct validity (correlation of the NIH scale with numerical rating scale [NRS] for pain) and internal consistency reliability (correlation between different parameters of the same scale). Categoric parameters were analyzed by comparison between severity subgroups defined by the oral manifestation (lichenoid/erythema/ulceration). Analysis included data of 75 evaluations. The total NIH score and the NRS for pain were found to be moderately correlated (r=0.449). Cronbach's alpha reliability coefficient was .718. Strong correlations were found between the total NIH score and both erythema and ulceration scores (r=0.746 and r=0.926, respectively). The difference between the 2 "severe" subgroups (ie, lichenoid and erythema/ulceration) was significant (P=.025). The difference between the moderate-erythema/ulceration subgroup and the severe-lichenoid subgroup was nonsignificant (total NIH score and NRS for pain: P=.276 and .291, respectively). The correlation between the total NIH score and the NRS for pain is only moderate. The internal consistency reliability analysis yielded good reliability, especially for erythema and ulceration. Analysis of categoric parameters suggests that the NIH scale disproportionately differentiates between moderate-erythema/ulceration and severe-lichenoid cGVHD.


Assuntos
Doença Enxerto-Hospedeiro/classificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doenças da Boca/diagnóstico , Mucosa Bucal , Medicina Bucal/instrumentação , Dor/classificação , Índice de Gravidade de Doença , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/complicações , Doença Enxerto-Hospedeiro/fisiopatologia , Humanos , Israel , Masculino , Pessoa de Meia-Idade , Doenças da Boca/etiologia , National Institutes of Health (U.S.) , Úlceras Orais/etiologia , Dor/etiologia , Medição da Dor/métodos , Estatística como Assunto , Estados Unidos , Adulto Jovem
9.
Ann Hematol ; 89(3): 263-72, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19693502

RESUMO

The major cause of treatment failure following high-dose therapy with autologous stem cell transplantation (ASCT) for aggressive B cell non-Hodgkin's lymphoma (NHL) is persistent disease or recurrence. We describe our experience with the administration of rituximab post-ASCT, either as maintenance therapy or for the treatment of relapsed disease in patients with aggressive B cell NHL. Fifty-six patients achieved complete remission post-transplant, and 19 of them received maintenance with rituximab. Maintenance with rituximab resulted in statistically significant superior outcome in terms of progression free (PFS; p = 0.002) and overall survival (OS; p = 0.011). The median PFS and OS of patients in the maintenance arm has not been reached yet, while the median PFS and OS of patients in the control arm were 29 and 42 months, respectively. Fifty-four patients had disease progression or relapsed post-ASCT, and 15 of them received rituximab in combination with chemo- and/or radiotherapy in order to achieve disease remission. Therapeutic administration of rituximab resulted in statistically significant prolongation of OS (p = 0.021). The median OS of patients treated with rituximab was 17 months, while median OS of patients in the control group was 10 months. We consider that the results of our study are promising but need to be verified within large randomized trials.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma de Células B/terapia , Adolescente , Adulto , Idoso , Anticorpos Monoclonais Murinos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Terapia Combinada , Feminino , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Linfoma de Células B/mortalidade , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Rituximab , Prevenção Secundária , Análise de Sobrevida , Transplante Autólogo , Resultado do Tratamento , Adulto Jovem
10.
Pediatr Blood Cancer ; 54(2): 326-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19890904

RESUMO

We describe a 12-year-old boy male who presented with an expressive dysphasia after completion of treatment for unifocal Ewing sarcoma. CNS vasculitis was diagnosed by MRI/MRA and cerebral angiography. Extensive rheumatologic work-up failed to identify an underlying primary process. Restaging studies showed no evidence of tumor. Complete neurologic recovery was achieved on prednisone. Four months later the patient developed overt, extensive metastases, confirmed by biopsy to represent recurrent Ewing sarcoma. Despite intensive therapy the patient succumbed 6 months later. This case demonstrates the unique finding of isolated CNS vasculitis as a presenting sign of Ewing sarcoma.


Assuntos
Síndromes Paraneoplásicas do Sistema Nervoso/etiologia , Sarcoma de Ewing/complicações , Vasculite do Sistema Nervoso Central/etiologia , Afasia/etiologia , Angiografia Cerebral , Criança , Evolução Fatal , Humanos , Imageamento por Ressonância Magnética , Masculino , Recidiva , Sarcoma de Ewing/patologia
11.
Biol Blood Marrow Transplant ; 15(4): 483-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19285636

RESUMO

The failure of allogeneic stem cell transplant (allo-SCT) is cumbersome. We analyzed our experience in a second allo-SCT. Between the years 1981 and 2007, 144 patients underwent 2 or more allo-SCT. The first to second transplant interval ranged from 18 days to 13.25 years (median 98 days). The most frequent indications for the second SCT were activity of the basic disease (78), rejection (37), and engraftment failure (25). Twenty-nine of the 144 (20%) patients transplanted survived more then a year with treatment-related mortality of 45.5% as the leading cause of death. Interestingly, despite the low rate of graft-versus-host disease (GVHD) prophylaxis used, only 51 and 16 of the patients developed acute and chronic GVHD (aGVHD, cGVHD), respectively. Factors indicating higher likelihood for survival were nonmalignant disease, a nonrelapse indication for the second SCT, full HLA-matching, and the use of reduced-intensity conditioning (RIC). Age at transplantation, time interval between transplants, the development of GVHD, conditioning regimen, GVHD prophylaxis, or graft source were not shown to influence the prognosis. With a median follow-up of 4.5 years, 25 patients (17.2%) are alive, and 18 are disease-free. We conclude that although toxic, a second allo-SCT can lead to long-term survival.


Assuntos
Rejeição de Enxerto/mortalidade , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Doença Crônica , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo
12.
Cytotherapy ; 11(1): 61-7, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19191054

RESUMO

BACKGROUND AIMS: We have shown previously that alefacept is effective in acute steroid resistant/dependent and chronic extensive graft versus host disease (GvHD) with a protocol using timings similar to those used for psoriasis treatment. In this study, we describe the use of an alefacept induction (e.g. for 7 consecutive days) followed by a bi-weekly maintenance treatment in combination with tacrolimus for acute steroid resistant/dependent GvHD 1, 3. METHODS: Sixteen patients were treated in this cohort, most with refractory GvHD. The pre-treatment GvHD grade ranged from 2 to 4 (median 3), involving the skin 16, gut 11 and liver 5. RESULTS: Twelve out of the 16 patients showed a response. As with the first protocol, the response of GvHD in the skin was fastest. In contrast to our previous protocol, however, the gastro-intestinal (GI) GvHD response was faster (P=0.05 compared with the first cohort). A hepatic response was seen in 4/6 patients and was complete in three. All responses were durable, including mucocutaneous, gut and liver GvHD. In all responding patients we were able to decrease the steroid dose significantly and in seven it was completely withdrawn. CONCLUSION: Alefacept induction is safe in acute steroid resistant/dependent GvHD and may be more effective therapeutically than our previous alefacept protocol. We speculate that alefacept initiates an allo-versus-allo cellular effect through its Fc receptor.


Assuntos
Fármacos Dermatológicos/uso terapêutico , Doença Enxerto-Hospedeiro/tratamento farmacológico , Imunossupressores/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Tacrolimo/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Alefacept , Criança , Pré-Escolar , Protocolos Clínicos , Fármacos Dermatológicos/efeitos adversos , Quimioterapia Combinada , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/patologia , Humanos , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Proteínas Recombinantes de Fusão/efeitos adversos , Tacrolimo/efeitos adversos , Adulto Jovem
13.
Am J Hematol ; 84(3): 188-90, 2009 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-19105234

RESUMO

Acute myeloid leukemia (AML) is an extremely aggressive disease with a high relapse rate even after allogeneic hematopoietic stem cell transplantation (HSCT). We report the successful outcome of cell-mediated cytokine-activated immunotherapy in a high-risk pediatric AML patient who relapsed shortly after allogeneic HSCT. Donor lymphocyte infusion along with interferon induced a graft-versus-leukemia effect, presenting as a reversible episode of graft-versus-host disease, which led to stable complete donor chimerism and total eradication of AML for over 24 months, at the time of this report. The curative potential of immunotherapy in hematological malignancies is discussed.


Assuntos
Leucemia Mieloide Aguda/imunologia , Leucemia Mieloide Aguda/terapia , Transfusão de Linfócitos , Recidiva Local de Neoplasia/imunologia , Recidiva Local de Neoplasia/terapia , Criança , Doença Enxerto-Hospedeiro , Efeito Enxerto vs Leucemia , Transplante de Células-Tronco Hematopoéticas , Humanos , Fatores Imunológicos/administração & dosagem , Imunoterapia , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Masculino , Proteínas Recombinantes
14.
Clin Infect Dis ; 46(9): 1455-7, 2008 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-18419454

RESUMO

This is the first report of treatment of cytomegalovirus infection with artesunate, for a stem cell transplant recipient with a newly identified foscarnet-resistant and ganciclovir-resistant DNA polymerase L776M mutation. Artesunate treatment resulted in a 1.7-2.1-log reduction in viral load by treatment day 7, with a viral half-life of 0.9-1.9 days, indicating a highly effective block in viral replication.


Assuntos
Artemisininas/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Células-Tronco Hematopoéticas/métodos , Antivirais/farmacologia , Antivirais/uso terapêutico , Artemisininas/farmacologia , Artesunato , Criança , Citomegalovirus/efeitos dos fármacos , Infecções por Citomegalovirus/etiologia , Farmacorresistência Viral , Foscarnet/farmacologia , Foscarnet/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Resultado do Tratamento
15.
Biol Blood Marrow Transplant ; 14(4): 409-17, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-18342783

RESUMO

The effect of ABO-incompatibility on transplantation outcome remains a controversial issue, with many of the reported studies showing conflicting results. In this study, we evaluate: the association between ABO-incompatibility and myeloid engraftment; the incidence and severity of acute and chronic graft-versus-host disease (GVHD); non-relapse mortality (NRM); GVHD-associated mortality, relapse and overall survival (OS). Our study includes 221 patients with malignant diseases treated in the same institution with the same reduced intensity regimen. Other variables known to affect the transplantation outcome such as age, disease, disease risk, and donor characteristics were well-balanced between ABO-matched and ABO-mismatched transplants. Analysis of our data shows increased incidence of NRM during the first months after transplantation in the groups of patients with major and minor ABO-incompatibility. Although neither incidence nor severity of GVHD differed significantly among the different groups, we found increased mortality associated with GVHD in the major ABO-incompatible groups. Long-term OS and relapse rate were not different, although we observed a trend for decreased OS during the first year post transplantation in the group of patients with major ABO-incompatibility. Our study showed that ABO-incompatibility has an adverse impact on the transplantation outcome.


Assuntos
Sistema ABO de Grupos Sanguíneos , Incompatibilidade de Grupos Sanguíneos , Doença Enxerto-Hospedeiro/fisiopatologia , Neoplasias/terapia , Transplante de Células-Tronco/métodos , Adulto , Idoso , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Leucemia/terapia , Linfoma não Hodgkin/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Recidiva , Estudos Retrospectivos
16.
J Am Acad Dermatol ; 59(5): 781-4, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18723241

RESUMO

Toxoplasmosis is a rare and often fatal complication of hematopoietic stem cell transplantation (HSCT). The diagnosis of toxoplasmosis is usually made at autopsy because of the variety of systemic manifestations and the difficulty of diagnosis by serologic methods in the severely immunocompromised patient. Cutaneous toxoplasmosis in this setting is extremely rare and is difficult to diagnose with certainty because of the morphologic similarity of Toxoplasma gondii to other organisms, such as Leishmania and Histoplasma species. We report a patient who developed systemic toxoplasmosis, manifested as encephalitis and cutaneous lesions, after HSCT. Findings of a skin biopsy led to a tentative histologic diagnosis of toxoplasmosis, confirmed by polymerase chain reaction (PCR) examination of the skin biopsy and cerebrospinal fluid. This is, to our knowledge, the first report of cutaneous toxoplasmosis diagnosed by skin biopsy confirmed by PCR and sequencing. This disease may be more common than is generally appreciated in severely immunocompromised patients. PCR is a valuable adjunct to diagnosis.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Complicações Neoplásicas na Gravidez/terapia , Complicações Parasitárias na Gravidez/diagnóstico , Dermatopatias Parasitárias/diagnóstico , Toxoplasmose/diagnóstico , Adulto , Animais , Infecções por Citomegalovirus/diagnóstico , DNA de Protozoário/análise , Encefalite Viral/diagnóstico , Evolução Fatal , Feminino , Humanos , Hospedeiro Imunocomprometido , Leucemia Mieloide Aguda/terapia , Reação em Cadeia da Polimerase , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Dermatopatias Parasitárias/etiologia , Toxoplasma/genética , Toxoplasmose/líquido cefalorraquidiano , Toxoplasmose/etiologia
17.
Transpl Immunol ; 17(3): 198-202, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17331847

RESUMO

N-acetylcysteine (NAC) is a known antioxidant and induces modulation of glutathione cellular content effects. It has been suggested that in the context of stem cell transplantation (SCT), NAC can prevent and treat graft-vs.-host disease, veno-occlusive disease and idiopathic pneumonia syndrome. We investigated the possible effect of NAC on graft-vs.-leukemia effect (GVL) and lymphokine activated cells (LAK) activity in murine models. After 10 days of NAC treatment, the cytotoxic activity of the LAK cells did not significantly differ from LAK activity generated from spleen cells obtained from untreated controls. However, NAC mildly suppressed GVL (appearance of leukemia in 8/36 animals treated with NAC as compared to 0/20 in the SCT control group, p=0.023). In spite of this mild suppression of GVL, no negative effect on achievement of donor chimerism was seen. We conclude that NAC usage in SCT may be relatively safe with regard to the GVL effect, yet further clinical studies are warranted.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia/imunologia , Células Matadoras Ativadas por Linfocina/efeitos dos fármacos , Transferência Adotiva , Animais , Feminino , Masculino , Camundongos , Transplante de Células-Tronco
18.
Laryngoscope ; 117(1): 78-81, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17135980

RESUMO

OBJECTIVES/HYPOTHESIS: Sinonasal invasive aspergillosis (IA) is an aggressive fungal infection with high mortality rates. It commonly develops in immunocompromised patients, often after bone marrow transplantation (BMT). Aggressive surgical debridement by an external approach has been considered a central element of treatment. We describe our experience in endoscopic management of IA in BMT patients in a retrospective study. METHODS: Charts of BMT patients with IA in the past 5 years were reviewed. Demographic data, primary disease, comorbidities, signs and symptoms, blood test results, preparation for surgery, surgical technique, and outcome were recorded. RESULTS: Fourteen BMT patients, age ranging from 3 to 56 years, had sinonasal IA. The primary disease was acute myelogenous leukemia in 6, acute lymphoblastic leukemia in 3, chronic myeloblastic leukemia in one, severe combined immunodeficiency disease in 2, and myelodysplastic syndrome in 2 patients. Diagnosis was made by physical examination, biopsy, culture, and computed tomography scan. Treatment, including aggressive endoscopic debridement, a systemic antifungal medication, and local irrigations of amphotericin-B enabled eradication of IA in all patients. Seven patients required two or more operations. None required orbital exenteration or craniotomy. Six patients died of the primary illness or of comorbidities with no evidence of residual disease. Eight patients are alive. CONCLUSION: Early detection of IA in BMT patients enables aggressive treatment before the disease spreads into the orbit or brain. Proper preoperative preparation facilitates safe endoscopic surgery in patients with severe bleeding tendencies. Although sinonasal IA is lethal, endoscopic surgery is feasible and efficient, enabling excellent local control.


Assuntos
Aspergilose/cirurgia , Transplante de Medula Óssea/efeitos adversos , Endoscopia/métodos , Leucemia/complicações , Infecções Oportunistas/cirurgia , Doenças dos Seios Paranasais/cirurgia , Adulto , Aspergilose/etiologia , Criança , Pré-Escolar , Feminino , Humanos , Leucemia/terapia , Masculino , Pessoa de Meia-Idade , Infecções Oportunistas/etiologia , Doenças dos Seios Paranasais/etiologia , Doenças dos Seios Paranasais/microbiologia
19.
Haematologica ; 91(6): 852-5, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16769592

RESUMO

We describe our experience with the use of a single non-myeloablative preparative regimen in stem-cell transplantation (NST) in 37 heavily pretreated patients > or =55 years. The conditioning regimen consisted of fludarabine, low-dose busulfan, and antithymocyte globulin. Acute graft-versus-host disease (GVHD) grade III-IV and chronic GVHD developed in 15.6% and 44.4% of cases, respectively. With a median follow-up period of 22 (range 3-113) months, the 1-year overall survival and disease-free-survival were 55% and 53%, respectively, while the overall non-relapse mortality was 35%. In conclusion, reduced intensity stem cell transplantation is feasible and effective in patients > or =55 years. Age per se, should no longer be considered as a contra-indication to stem cell transplantation.


Assuntos
Transplante de Células-Tronco/métodos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Idoso , Intervalo Livre de Doença , Família , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/mortalidade , Análise de Sobrevida , Doadores de Tecidos , Transplante Homólogo/mortalidade
20.
Exp Hematol ; 33(6): 713-8, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15911096

RESUMO

OBJECTIVE: For recipients of haploidentically mismatched stem cell allografts, T-cell depletion is mandatory to prevent lethal graft-vs-host disease (GVHD). Prevention of GVHD can be accomplished by negative selection of T cells or positive selection of stem cells. Recently, a new method for positive selection of stem cells was introduced using monoclonal antibodies against CD133 antigen. We report five cases of successful application of immunomagnetic separation of CD133+ stem cells for haploidentically mismatched allogeneic stem cell transplantation. METHODS: Five patients with high-risk hematological malignancies, ages 7 to 63 years old (median, 17 years), underwent peripheral blood stem cell transplantation from haploidentically mismatched related donors. Conditioning protocol was tailored according to patient clinical situation and included combination of treosulfan/fludarabine/thiotepa/melphalan/Mabcampath. Two patients did not get thiotepa. One of them received a protocol that included infusion of 4.4 x 10(7) blood mononuclear cells from the donor (day -9), followed by a combination of fludarabine/cyclophosphamide/busulfex/MabCampath. Separation of CD133+ stem cells was done using CliniMACS with Miltenyi's CD133 reagent. RESULTS: The procedure was well tolerated by all patients. Early 3-lineage engraftment was documented and none exhibited immune-mediated rejection. Time to recovery of absolute neutrophils count above 0.5 x 10(9)/L and 1.0 x 10(9)/L was 10 to 15 days (median, 14) and 11 to 29 days (median, 15), respectively. Time for platelet recovery to values greater than 20 x 10(9)/L and greater than 50 x 10(9)/L ranged from 12 to 25 days (median, 13.5), and from 14 to 34 days (median, 16), respectively. Transplant-related mortality did not occur in any of the patients. CONCLUSION: Our successful pilot trial suggests that positive selection of CD133+ stem cells may be a useful method for safe transplantation with haploidentically mismatched stem cell allografts while avoiding lethal acute and chronic GVHD. Future studies will be required to assess the clinical benefits of stem cell purification with CD133+ in comparison with CD34+ stem cells.


Assuntos
Glicoproteínas/imunologia , Haplótipos , Peptídeos/imunologia , Transplante de Células-Tronco de Sangue Periférico , Antígeno AC133 , Adolescente , Adulto , Antígenos CD , Criança , Feminino , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo
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