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1.
Am J Transplant ; 15(7): 1874-81, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25788003

RESUMO

Case reports describe significant norovirus gastroenteritis morbidity in immunocompromised patients. We evaluated norovirus pathogenesis in prospectively enrolled solid organ (SOT) and hematopoietic stem cell transplant (HSCT) patients with diarrhea who presented to Texas Children's Hospital and submitted stool for enteric testing. Noroviruses were detected by real-time reverse transcription polymerase chain reaction. Clinical outcomes of norovirus diarrhea and non-norovirus diarrhea patients, matched by transplanted organ type, were compared. Norovirus infection was identified in 25 (22%) of 116 patients, more frequently than other enteropathogens. Fifty percent of norovirus patients experienced diarrhea lasting ≥14 days, with median duration of 12.5 days (range 1-324 days); 29% developed diarrhea recurrence. Fifty-five percent of norovirus patients were hospitalized for diarrhea, with 27% requiring intensive care unit (ICU) admission. One HSCT recipient developed pneumatosis intestinalis. Three HSCT patients expired ≤6 months of norovirus diarrhea onset. Compared to non-norovirus diarrhea patients, norovirus patients experienced significantly more frequent ICU admission (27% vs. 0%, p = 0.02), greater serum creatinine rise (median 0.3 vs. 0.2 mg/dL, p = 0.01), and more weight loss (median 1.6 vs. 0.6 kg, p < 0.01). Noroviruses are an important cause of diarrhea in pediatric transplant patients and are associated with significant clinical complications.


Assuntos
Infecções por Caliciviridae/virologia , Diarreia/virologia , Transplante de Células-Tronco Hematopoéticas , Hospedeiro Imunocomprometido , Norovirus/isolamento & purificação , Transplante de Órgãos , Infecções por Caliciviridae/imunologia , Criança , Diarreia/diagnóstico , Diarreia/epidemiologia , Fezes/química , Fezes/virologia , Feminino , Seguimentos , Rejeição de Enxerto/etiologia , Sobrevivência de Enxerto , Humanos , Masculino , Prognóstico , Estudos Prospectivos , RNA Viral/genética , Fatores de Risco , Texas/epidemiologia , Transplantados
2.
Clin Exp Immunol ; 174(1): 89-96, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23763437

RESUMO

Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.


Assuntos
Aspergilose Broncopulmonar Alérgica/imunologia , Aspergilose Broncopulmonar Alérgica/terapia , Doença Granulomatosa Crônica/imunologia , Doença Granulomatosa Crônica/terapia , Imunoterapia Adotiva , Linfócitos T/imunologia , Linfócitos T/microbiologia , Animais , Aspergillus fumigatus/imunologia , Linhagem Celular , Células Cultivadas , Humanos , Imunoterapia Adotiva/métodos , Glicoproteínas de Membrana/deficiência , Glicoproteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , NADPH Oxidase 2 , NADPH Oxidases/deficiência , NADPH Oxidases/genética , Linfócitos T/patologia , Células Th1/imunologia , Células Th1/microbiologia , Células Th1/transplante
3.
Leuk Lymphoma ; 51(4): 664-70, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20367182

RESUMO

For patients with relapsed Hodgkin's lymphoma (HL), high dose chemotherapy with stem cell rescue (HDCT-SCT) may improve survival over chemotherapy alone. We assessed the outcomes of HDCT-SCT in 37 consecutive adolescent and young adult patients with relapsed HL whose malignancy was categorized based on sensitivity to chemotherapy. We determined whether current outcomes supported the use of HDCT-SCT in all of our patients or just those patients with lower-risk characteristics such as chemosensitivity. With a median follow-up of 6.5 years, the 2-year overall survival (OS) was 89% (95% CI: 62-97%) for the chemosensitive patients (n = 21), whereas for patients with resistant disease (n = 16), OS was 53% (95% CI: 25-74%). Both autologous and allogeneic transplants were well tolerated, with 100-day treatment-related mortality under 10%. Our data show encouraging outcomes for patients with chemosensitive relapsed HL who receive hematopoietic stem cell transplant (HSCT) and support the value of the procedure even when the disease is chemoresistant.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/terapia , Terapia de Salvação , Adolescente , Adulto , Criança , Seguimentos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/diagnóstico , Doença de Hodgkin/mortalidade , Humanos , Prognóstico , Estudos Retrospectivos , Terapia de Salvação/efeitos adversos , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
4.
Bone Marrow Transplant ; 37(6): 547-52, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16462757

RESUMO

Hemopoietic stem cell transplantation (SCT) with fully ablative conditioning is associated with an age-related increase in treatment-related mortality. It is therefore particularly unsuited to older individuals, who are most at risk of developing acute myeloid leukemia (AML). Reduced-intensity SCT (RISCT) may be of value in this group. We report 17 consecutive patients with high-risk AML whose median age was 58 years and who received stem cells from HLA-matched siblings (n=5), or alternative donors (n=12). We used lymphodepleting antibodies as a part of the reduced-intensity conditioning regimen to limit the risk of graft rejection and graft-versus-host disease (GVHD). All patients engrafted. One patient developed severe fatal GVHD, and two patients died of infection. At a median follow-up of 861 days (372-1957 days), seven patients are alive in remission, which includes two patients treated in relapse and five patients who lacked an MHC identical sibling donor. Both progression-free survival and overall survival are 40% (95% CI, 17-64%). Hence, RISCT using lymphodepleting antibodies may be of value for older patients with AML, even in those with active or high-risk disease, and even if they lack an MHC-identical sibling donor.


Assuntos
Soro Antilinfocitário/uso terapêutico , Imunossupressores/uso terapêutico , Leucemia Mieloide/terapia , Transplante de Células-Tronco , Doença Aguda , Adulto , Idoso , Feminino , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Infecções/epidemiologia , Complexo Principal de Histocompatibilidade , Masculino , Pessoa de Meia-Idade , Transplante de Células-Tronco/efeitos adversos , Fatores de Tempo , Quimeras de Transplante , Transplante Homólogo , Resultado do Tratamento
5.
Bone Marrow Transplant ; 36(11): 1001-8, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16184180

RESUMO

Infectious complications due to adenovirus are of increasing concern after allogeneic stem cell transplantation. Over the past 4 years, we have modified our conditioning regimens to use alemtuzumab in preference to anti-thymocyte globulin (ATG) for pediatric patients receiving stem cell transplants from alternate donors. Recent reports in adult studies implicate alemtuzumab as a risk factor for adenovirus infection. We therefore evaluated the incidence of adenovirus infection in pediatric patients receiving either ATG or alemtuzumab in their conditioning regimens. Of the 111 patients evaluated, a total of 54 patients received ATG and 57 patients received alemtuzumab. In total, 35/111 (32%) patients were infected by adenovirus, and 9/111 (8%) had adenovirus disease (AD). Adenovirus infection was greater in the alemtuzumab group than the ATG group (23/57 vs 12/54) (P=0.039) and disseminated AD was more frequent in the alemtuzumab group vs the ATG group (8/57 and 1/54 respectively) (P=0.032). The presence of Grade 3-4 graft-versus-host disease was a risk factor for adenovirus infection. Our findings highlight the fact that adenovirus infection is a frequent complication after stem cell transplantation from alternate donors in the pediatric population and that alemtuzumab increases the risk of infection compared to ATG. This work will help in identifying at-risk populations for our upcoming immunotherapy trial using adoptively transferred donor-derived adenovirus-specific cytotoxic T lymphocytes.


Assuntos
Infecções por Adenovirus Humanos/induzido quimicamente , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Soro Antilinfocitário/administração & dosagem , Transplante de Medula Óssea/efeitos adversos , Infecções por Adenovirus Humanos/etiologia , Adolescente , Alemtuzumab , Anticorpos Monoclonais/toxicidade , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/toxicidade , Transplante de Medula Óssea/métodos , Criança , Pré-Escolar , Doença Enxerto-Hospedeiro/complicações , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Incidência , Lactente , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo
6.
Bone Marrow Transplant ; 36(9): 797-802, 2005 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-16151431

RESUMO

We studied the incidence and recurrence of Cytomegalovirus (CMV) infection and reactivation in 38 recipients of Alemtuzumab reduced intensity conditioning-stem cell transplantation, and used CMV-HLA tetramer studies to discover if these events correlated with recovery of circulating CMV-specific CD8+ T cells (cytotoxic T lymphocyte (CTLs)). The cumulative incidence of CMV infection was 60% at 1 year (95% CI, 45-78%) with a median reactivation time of 24 days (range 5-95 days). All patients with CMV reactivation received Ganciclovir or Foscarnet, and only one developed CMV disease. More strikingly, only 8/21 patients had relapse of CMV antigenemia. Tetramer analysis in 13 patients showed that 11 reconstituted CMV CTLs (7/11 by day 30 and 10/11 by day 90). The development of CMV infection was accompanied by a >5-fold rise of CMV CTLs. Recurrence of CMV infection occurred only in the patients who failed to generate a CTL response to the virus. Hence, recipients of SCT using Alemtuzumab-RIC are initially profoundly immunosuppressed and have a high incidence of early CMV reactivation. However, in the majority of patients, infection is transient, and antiviral T cell reconstitution is rapid. Monitoring with CMV-specific CTLs may help identify the subset of patients at risk from recurrent infection or disease.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Anticorpos Antineoplásicos/administração & dosagem , Infecções por Citomegalovirus/imunologia , Neoplasias Hematológicas/terapia , Recuperação de Função Fisiológica/imunologia , Linfócitos T Citotóxicos/imunologia , Adulto , Idoso , Alemtuzumab , Anticorpos Monoclonais Humanizados , Antígenos Virais/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/tratamento farmacológico , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Doença Enxerto-Hospedeiro/virologia , Neoplasias Hematológicas/sangue , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Recuperação de Função Fisiológica/efeitos dos fármacos , Transplante de Células-Tronco , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Ativação Viral/efeitos dos fármacos , Ativação Viral/imunologia
7.
Bone Marrow Transplant ; 35(12): 1127-32, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15834432

RESUMO

Allogeneic hemopoietic stem cell transplantation (HSCT) is the only curative option for many patients with hematological malignancies. Since many of these patients lack HLA-identical sibling donors and are older or have comorbidity, a fully ablative HSCT is not feasible and an alternative approach is required. We studied 22 consecutive patients who could not have myeloablative conditioning because of comorbidity or age - 21/22 being over the age of 50 years (median 58 years range 20-70 years). A conditioning regimen consisting of fludarabine, total body radiation 450 cGy and alemtuzumab (CD52 mAb) was used for 15 patients. A second group of seven patients received CD45 monoclonal antibodies in addition. Unrelated donor stem cells were HLA matched (15 patients - 68%) or one locus mismatched (seven patients - 32%). In all, 16 patients had high-risk disease, including 12 with active malignancy at the time of transplant. With a median follow-up of 715 (216-1470) days, nonrelapse mortality, actuarial event-free and overall survival is 27, 45 and 45%, respectively. Hence the outcome of reduced intensity HSCT with lymphodepleting antibodies in older patients with intermediate/high-risk hematological malignancies appears comparable to that obtained with fully ablative transplantation in younger patients, even when these older recipients lack HLA-identical sibling donors.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antígenos CD/imunologia , Antígenos de Neoplasias/imunologia , Glicoproteínas/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Histocompatibilidade , Antígenos Comuns de Leucócito/imunologia , Condicionamento Pré-Transplante/métodos , Adulto , Distribuição por Idade , Idoso , Alemtuzumab , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Anticorpos Antineoplásicos/administração & dosagem , Antígeno CD52 , Terapia Combinada/efeitos adversos , Feminino , Sobrevivência de Enxerto , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/mortalidade , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/mortalidade , Teste de Histocompatibilidade , Humanos , Depleção Linfocítica/métodos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal Total
8.
Biol Blood Marrow Transplant ; 9(11): 698-705, 2003 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-14652853

RESUMO

Hemorrhagic cystitis (HC) is a well-documented adverse event experienced by patients undergoing hematopoietic stem cell transplantation. When severe, HC causes significant morbidity, leads to renal complications, prolongs hospitalization, increases health-care costs, and occasionally contributes to death. We retrospectively studied the medical records of 245 children undergoing an initial allogeneic bone marrow transplantation for malignant disease at St. Jude Children's Research Hospital between 1992 and 1999 to describe the clinical course of HC in all patients and to identify the risk factors for HC in this cohort. Conditioning regimens included cyclophosphamide, cytarabine, and total body irradiation. Grafts from unrelated or mismatched related donors were depleted of T lymphocytes, whereas matched sibling grafts were unmanipulated. All patients received cyclosporine as prophylaxis for graft-versus-host disease. Recipients of grafts from matched siblings also received pentoxifylline or short-course methotrexate. Severe HC developed in 27 patients (11.0%). The median duration of HC was 73 days (range, 5-619 days); 12 patients had ongoing HC at the time of death. In univariate analyses, patients were at increased risk of severe HC if they were male (P =.021) or had received T cell-depleted grafts (P =.017), grafts from unrelated donors (P =.021), a lower total nucleated cell dose (P =.032), or antithymocyte globulin (P =.0446). Multiple regression analysis revealed male sex (beta =.97; P =.027) and unrelated donor graft recipients (beta =.83; P =.039) to be significant factors.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Cistite/etiologia , Transtornos Hemorrágicos/etiologia , Doença Aguda , Adolescente , Adulto , Criança , Pré-Escolar , Doença Crônica , Família , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transtornos Hemorrágicos/epidemiologia , Humanos , Lactente , Doadores Vivos , Transfusão de Linfócitos , Pessoa de Meia-Idade , Neoplasias/tratamento farmacológico , Estudos Retrospectivos , Fatores de Risco , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento
9.
Bone Marrow Transplant ; 31(11): 981-6, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12774048

RESUMO

The histiocytoses are rare disorders of antigen-processing phagocytic or antigen-presenting cells. Allogeneic bone marrow transplantation (BMT) can be curative of these disorders. We report a series of five children with Langerhans cell histiocytosis (n=2) or hemophagocytic lymphohistiocytosis (n=3), who received allogeneic BMT with a total body irradiation (TBI)-containing regimen (TBI, cytarabine, and cyclophosphamide) at our institution between 1995 and 2000. One of these patients received busulfan, cyclophosphamide, and etoposide for the first of two BMTs. All grafts except one (a matched sibling-donor graft) were T-cell-depleted grafts from unrelated donors. All received cyclosporine graft-versus-host disease (GvHD) prophylaxis; the recipient of the matched sibling graft also received methotrexate. Three patients engrafted at a median of 24 days after transplantation. The patient who did not receive TBI experienced primary graft failure and recurrent disease. After the TBI-containing conditioning regimen was given, a second transplant engrafted on day +17. One patient with concurrent myelodysplastic syndrome died of toxicity on day +33 without evidence of engraftment. No acute or chronic GvHD was observed. Four patients survive disease-free, a median of 63 months after transplantation, all with Lansky performance scores of 100. We conclude that a conditioning regimen containing TBI but not etoposide is effective in allogeneic BMT for children with histiocytic diseases.


Assuntos
Transplante de Medula Óssea/estatística & dados numéricos , Histiocitose de Células de Langerhans/cirurgia , Condicionamento Pré-Transplante/métodos , Irradiação Corporal Total/métodos , Transplante de Medula Óssea/efeitos adversos , Criança , Seguimentos , Doença Enxerto-Hospedeiro/epidemiologia , Humanos , Depleção Linfocítica/métodos , Estudos Retrospectivos , Linfócitos T/imunologia , Fatores de Tempo , Resultado do Tratamento
10.
Bone Marrow Transplant ; 30(2): 125-30, 2002 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12132052

RESUMO

Prior studies suggest that patients undergoing hematopoietic stem cell transplantation (HSCT) for malignancy have nutritional needs that are greater than their estimated needs. To determine whether energy estimation equations accurately predict energy expenditure of pediatric patients undergoing HSCT, we prospectively compared the estimated energy expenditure (EEE) and measured energy expenditure (MEE) of 40 patients at four time-points. We also investigated whether energy requirements changed during the transplant period. MEE was determined by indirect calorimetry. Data from 34 patients (autologous HSCT = 10, allogeneic HSCT = 24) were sufficient for analysis. The World Health Organization equation adequately approximated MEE only on day 14 after HSCT. At all other time-points, measured energy expenditure was significantly less than estimated energy expenditure obtained by using the WHO equation (applicable to all patients), the Seashore equation (for patients <15 years of age; n = 19), or the Harris-Benedict equation (for patients > or =15 years of age; n = 15). The median measured energy expenditure varied significantly over the study period and was greatest on day 14 after HSCT. Until accurate equations have been identified for estimating these patients' needs, the use of indirect calorimetry may be medically warranted.


Assuntos
Metabolismo Energético , Transplante de Células-Tronco Hematopoéticas , Adolescente , Adulto , Calorimetria Indireta , Criança , Ingestão de Energia , Feminino , Neoplasias Hematológicas/fisiopatologia , Neoplasias Hematológicas/terapia , Humanos , Masculino , Modelos Teóricos , Estado Nutricional , Fatores de Tempo
11.
Bone Marrow Transplant ; 29(6): 515-7, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11960272

RESUMO

Guillain-Barré syndrome is a rare complication in the setting of hematopoietic stem cell transplantation. We report three children with T cell lymphoma/leukemia in whom this syndrome developed soon after they received unrelated donor transplants. The rapid onset of symptoms raises the concern that the bone marrow transplant conditioning regimen (ie, total body irradiation, cyclophosphamide and cytosine arabinoside) might have precipitated the clinical syndrome of ascending polyneuropathy. Although central nervous system toxicity has been well described with high-dose cytosine arabinoside therapy, peripheral neuropathy of the Guillain-Barré type has been reported only infrequently. We review possible factors contributing to the development of this syndrome in these three patients.


Assuntos
Síndrome de Guillain-Barré/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Adolescente , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Citarabina/efeitos adversos , Citarabina/uso terapêutico , Evolução Fatal , Síndrome de Guillain-Barré/induzido quimicamente , Síndrome de Guillain-Barré/tratamento farmacológico , Síndrome de Guillain-Barré/virologia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Leucemia de Células T/tratamento farmacológico , Leucemia de Células T/radioterapia , Leucemia de Células T/cirurgia , Leucemia de Células T/virologia , Linfoma de Células T/tratamento farmacológico , Linfoma de Células T/radioterapia , Linfoma de Células T/cirurgia , Masculino , Vírus da Parainfluenza 1 Humana/imunologia , Vírus da Parainfluenza 1 Humana/isolamento & purificação , Infecções por Respirovirus/complicações , Infecções por Respirovirus/diagnóstico , Infecções por Respirovirus/tratamento farmacológico , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos , Transplante Homólogo , Irradiação Corporal Total/efeitos adversos , Irradiação Corporal Total/métodos
12.
J Clin Oncol ; 19(11): 2804-11, 2001 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-11387351

RESUMO

PURPOSE: To develop more effective chemotherapy regimens for childhood acute myelogenous leukemia (AML). PATIENTS AND METHODS: Between June 1991 and December 1996, we administered the nucleoside analog 2-chlorodeoxyadenosine (2-CDA) to 73 children with primary AML and 20 children with secondary AML or myelodysplastic syndrome (MDS). Patients received one or two 5-day courses of 2-CDA (8.9 mg/m(2)/d) given by continuous infusion. All patients then received one to three courses of daunomycin, cytarabine, and etoposide (DAV) remission induction therapy. RESULTS: Seventy-two patients with primary AML were assessable for response. Their rate of complete remission (CR) was 24% after one course of 2-CDA, 40% after two courses of 2-CDA, and 78% after DAV therapy. Of the 57 patients who entered CR, 11 subsequently underwent allogeneic bone marrow transplantation (BMT), and 40 underwent autologous BMT. Twenty-nine patients remain in continuous CR after BMT. Two patients remain in CR after chemotherapy only. The 5-year event-free survival (EFS) estimate was 40% (SE = 0.080%). Patients with French-American-British (FAB) M5 AML had a higher rate of CR after treatment with 2-CDA (45% after one course and 70.6% after two courses) than did others (P =.002). In contrast, no patient with FAB M7 AML (n = 10) entered CR after treatment with 2-CDA. Similarly, no patient with primary MDS (n = 6) responded to 2-CDA. Seven patients with secondary AML or MDS (n = 14) had a partial response to one course of 2-CDA. CONCLUSION: This agent was well tolerated, and its toxicity was acceptable. Future trials should examine the effectiveness of 2-CDA given in combination with other agents effective against AML.


Assuntos
Antineoplásicos/farmacologia , Cladribina/farmacologia , Leucemia Mieloide Aguda/tratamento farmacológico , Síndromes Mielodisplásicas/tratamento farmacológico , Adolescente , Antineoplásicos/administração & dosagem , Transplante de Medula Óssea , Criança , Pré-Escolar , Cladribina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Recém-Nascido , Infusões Intravenosas , Masculino , Resultado do Tratamento
13.
Blood ; 95(4): 1502-5, 2000 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-10666232

RESUMO

After bone marrow transplantation (BMT) using T-cell-depleted marrow from an unrelated donor or HLA-mismatched related donor, the risk of developing lymphoproliferative disease associated with the Epstein-Barr virus (EBV) ranges from 1% to 25%. We have shown that administration of donor-derived EBV-specific cytotoxic T lymphocytes (CTL) is effective prophylaxis and treatment for this complication, and we routinely generate CTL for high-risk patients. However, EBV lymphoma can occur in recipients of matched-sibling transplants for whom CTL are unavailable or in patients for whom CTL administration is contraindicated. We report on 3 such patients, who were successfully and safely treated with rituximab, a CD20 monoclonal antibody. The patients remain disease free 7, 8, and 9 months, respectively, after therapy. We conclude that CD20 antibody may be a useful alternative treatment strategy in patients with EBV lymphoma after BMT. (Blood. 2000;95:1502-1505)


Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 4 , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Linfoma/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adolescente , Anticorpos Monoclonais Murinos , Antígenos CD20/imunologia , Transplante de Medula Óssea , Pré-Escolar , Intervalo Livre de Doença , Herpesvirus Humano 4/isolamento & purificação , Humanos , Imunofenotipagem , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Leucemia Mieloide Aguda/tratamento farmacológico , Linfócitos/imunologia , Linfoma/tratamento farmacológico , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Rituximab , Fatores de Tempo
14.
Bone Marrow Transplant ; 24(7): 735-9, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10516676

RESUMO

Twenty-one children who developed therapy-related acute myeloid leukemia after treatment for acute lymphoblastic leukemia received allogeneic bone marrow transplants between January 1990 and June 1997. All had previously received epipodophyllotoxin-containing regimens and 11 had cytogenetic abnormalities involving 11q23. Induction chemotherapy was given to 13 patients and eight patients went directly to BMT. Eleven received marrow from matched siblings, eight from matched unrelated donors and two from haploidentical family members. Conditioning regimens included cyclophosphamide (CY), cytarabine, and total body irradiation. Four patients are alive disease-free between 1118 and 1825 days post-BMT resulting in a 3-year DFS of 19%. Ten patients relapsed at a median of 150 days (range 30-664 days) post-BMT and all eventually died of disease. Seven patients died of regimen-related toxicity. The outlook for patients with therapy-related AML/MDS remains poor and more effective therapy is needed.


Assuntos
Transplante de Medula Óssea/métodos , Leucemia Mieloide Aguda/terapia , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Leucemia Linfoide/tratamento farmacológico , Leucemia Linfoide/terapia , Leucemia Mieloide Aguda/tratamento farmacológico , Masculino , Podofilotoxina/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Condicionamento Pré-Transplante , Resultado do Tratamento
15.
Bone Marrow Transplant ; 23(3): 277-82, 1999 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10084260

RESUMO

Retrospective analysis of 206 patients undergoing 215 consecutive bone marrow transplants (BMT) at St Jude Children's Research Hospital between November 1990 and December 1994 identified 6% (seven male, six female) with adenovirus infection. The affected patients had a median age of 7.9 years (range 3-24 years) at time of transplantation. Although transplants were performed for hematologic malignancies, solid tumors or nonmalignant conditions, only patients with hematologic malignancies had adenoviral infections. Adenovirus was first detected at a median of 54 days (range -4 to +333) after BMT. Adenovirus developed in eight of 69 (11.6%) patients receiving grafts from matched unrelated or mismatched related donors, in four of 52 (7.7%) receiving grafts from HLA-matched siblings, and in one of 93 (1.1%) receiving autografts. The most common manifestation of adenovirus infection was hemorrhagic cystitis, followed by gastroenteritis, pneumonitis and liver failure. The incidence of adenovirus infection in pediatric BMT patients at our institution is similar to that reported in adult patients. Using univariate analysis, use of total body irradiation and type of bone marrow graft were significant risk factors for adenovirus infection. Only use of total body irradiation remained as a factor on multiple logistic regression analysis.


Assuntos
Infecções por Adenoviridae/epidemiologia , Transplante de Medula Óssea/efeitos adversos , Infecções por Adenoviridae/etiologia , Infecções por Adenoviridae/transmissão , Adolescente , Adulto , Criança , Pré-Escolar , Cistite/epidemiologia , Cistite/etiologia , Feminino , Gastroenterite/epidemiologia , Gastroenterite/etiologia , Doença Enxerto-Hospedeiro/etiologia , Hemorragia/epidemiologia , Hemorragia/etiologia , Humanos , Hospedeiro Imunocomprometido , Terapia de Imunossupressão/efeitos adversos , Incidência , Falência Hepática/epidemiologia , Falência Hepática/etiologia , Masculino , Neoplasias/terapia , Pneumonia Viral/epidemiologia , Pneumonia Viral/etiologia , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Autólogo , Transplante Homólogo/efeitos adversos
16.
Blood ; 92(5): 1549-55, 1998 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-9716582

RESUMO

Epstein-Barr virus (EBV) causes potentially lethal immunoblastic lymphoma in up to 25% of children receiving bone marrow transplants from unrelated or HLA-mismatched donors. Because this complication appears to stem from a deficiency of EBV-specific cytotoxic T cells, we assessed the safety and efficacy of donor-derived polyclonal (CD4(+) and CD8(+)) T-cell lines as immunoprophylaxis and treatment for EBV-related lymphoma. Thirty-nine patients considered to be at high risk for EBV-induced lymphoma each received 2 to 4 intravenous infusions of donor-derived EBV-specific T lymphocytes, after they had received T-cell-depleted bone marrow from HLA-matched unrelated donors (n = 33) or mismatched family members (n = 6). The immunologic effects of this therapy were monitored during and after the infusions. Infused cells were identified by detection of the neo marker gene. EBV-specific T cells bearing the neo marker were identified in all but 1 of the patients. Serial analysis of DNA detected the marker gene for as long as 18 weeks in unmanipulated peripheral blood mononuclear cells and for as long as 38 months in regenerated lines of EBV-specific cytotoxic T cells. Six patients (15.5%) had greatly increased amounts of EBV-DNA on study entry (>2, 000 genome copies/10(6) mononuclear cells), indicating uncontrolled EBV replication, a complication that has had a high correlation with subsequent development of overt lymphoma. All of these patients showed 2 to 4 log decreases in viral DNA levels within 2 to 3 weeks after infusion and none developed lymphoma, confirming the antiviral activity of the donor-derived cells. There were no toxic effects that could be attributed to prophylactic T-cell therapy. Two additional patients who did not receive prophylaxis and developed overt immunoblastic lymphoma responded fully to T-cell infusion. Polyclonal donor-derived T-cell lines specific for EBV proteins can thus be used safely to prevent EBV-related immunoblastic lymphoma after allogeneic marrow transplantation and may also be effective in the treatment of established disease.


Assuntos
Transplante de Medula Óssea , Linfoma de Burkitt/prevenção & controle , Imunoterapia Adotiva , Linfócitos T Citotóxicos/imunologia , Adolescente , Adulto , Linfoma de Burkitt/terapia , Linfoma de Burkitt/virologia , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Marcadores Genéticos , Herpesvirus Humano 4/genética , Herpesvirus Humano 4/imunologia , Humanos , Lactente , Infusões Intravenosas , Masculino , Indução de Remissão
18.
Clin Radiol ; 52(12): 903-6, 1997 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-9413962

RESUMO

AIM: To describe the relationship between the resistance index of the common hepatic artery and liver function tests in children undergoing bone marrow transplantation. MATERIALS AND METHODS: We analysed prospectively the results of 106 Doppler ultrasound examinations of the common hepatic artery from 31 bone marrow transplant patients, 16 of whom had normal liver function. The aetiology of the liver dysfunction in the other 15 patients was veno-occlusive disease (n = 7), unknown (n = 3), hepatic graft-versus-host disease (n = 2), hepatitis (n = 2), or cholestasis (n = 1). We assessed the relationships between the hepatic arterial resistance index (HART) and the results of the serum glutamic-oxaloacetic transaminase (SGOT), serum glutamic-pyruvic transaminase (SGPT), alkaline phosphatase (ALK), lactate dehydrogenase (LDH) and serum albumin (ALB) assays and calculated HARI break-point values that might distinguish patients with liver disease from patients with the normal liver function. RESULTS: The significant break point (P < 0.05) of the HARI was 0.55 for SGOT, SGPT and ALK. LDH was associated with a break point of 0.53. Resistance indices for the common hepatic artery below the break-point values predicted liver dysfunction with specificities of 81%, 80%, 92% and 93%, respectively. There was no significant relationship between liver function tests and ALB levels. CONCLUSION: If below 0.55, the hepatic arterial resistance index is a non-invasive indicator of liver dysfunction in children undergoing bone marrow transplantation.


Assuntos
Transplante de Medula Óssea/efeitos adversos , Artéria Hepática/fisiopatologia , Hepatopatias/fisiopatologia , Resistência Vascular , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Artéria Hepática/diagnóstico por imagem , Humanos , Lactente , Leucemia/terapia , Hepatopatias/diagnóstico por imagem , Hepatopatias/etiologia , Testes de Função Hepática , Masculino , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia Doppler
19.
Lancet ; 350(9080): 767-71, 1997 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-9297996

RESUMO

BACKGROUND: For most conditions amenable to bone-marrow transplantation, grafts from HLA-matched but unrelated donors have yielded poorer results than those obtained from matched-sibling donors. We assessed this pattern in the light of improvements in donor selection and post-transplant supportive care. METHODS: We reviewed transplant outcome in 103 consecutive patients with childhood leukaemia who underwent allogeneic bone-marrow transplantation with HLA-matched sibling marrow (n = 52) or matched unrelated donor marrow (n = 51) between May, 1990, and March, 1996, at St Jude Children's Research Hospital. FINDINGS: Analysis of engraftment, frequency of procedure-related complications, and disease-free survival revealed no advantage from use of matched-sibling marrow. The 2-year disease-free survival estimate for standard-risk recipients of matched-sibling marrow was 81 [8.1]% compared with 73 [12.1]% in the unrelated donor marrow group (p = 0.77). In the high-risk category, patients with a matched-sibling donor had a 2-year disease-free survival of 31 [11.6]%, compared with 32 [15.1]% among recipients of matched unrelated donor marrow (p = 0.87). INTERPRETATION: We believe this improved result with unrelated donor marrow is a consequence of recent innovations in histocompatibility matching, prevention of graft-versus-host disease (GvHD), and antiviral prophylaxis. We suggest that such grafts can now be used in patients at both standard and high risk without compromising treatment outcome.


Assuntos
Transplante de Medula Óssea , Leucemia Mielogênica Crônica BCR-ABL Positiva/terapia , Leucemia Mieloide Aguda/terapia , Doadores Vivos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Criança , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Teste de Histocompatibilidade , Humanos , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mieloide Aguda/mortalidade , Masculino , Complicações Pós-Operatórias/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Fatores de Risco , Condicionamento Pré-Transplante , Resultado do Tratamento , Viroses/epidemiologia
20.
Leukemia ; 11(2): 206-11, 1997 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-9009082

RESUMO

To evaluate diagnostic criteria, disease characteristics, and the clinical course of pediatric myelodysplastic syndrome (MDS), we reviewed 327 consecutive cases diagnosed with de novo acute myeloid leukemia (AML) or MDS at St Jude Children's Research Hospital between February 1980 and January 1993. Among 49 cases with <30% marrow blasts (consistent with FAB criteria and common diagnostic practice for MDS), eight had karyotypes associated with de novo AML (four with t(8;21)(q22;q22) and one each with inv(16)(p13q22), t(11;17)(q23;q21), t(9;11)(p22;q13), and i(1)(ql0)). We termed these cases AML with a low blast count (AML-LBC) and compared their clinical and morphologic features with those of the remaining 41 cases. AML-LBC cases had little or no hematopoietic dysplasia. MDS cases consisted of refractory anemia (RA, n=6), RA with ring sideroblasts (n=2), RA with excess blasts (RAEB, n=4), RAEB in transformation (n=14), and chronic myelomonocytic leukemia (n=15). Most had moderate/severe or multilineage hematopoietic dysplasia, with significantly higher dysplasia scores than AML-LBC cases (P=0.007). Only 30% of patients with MDS achieved complete remission (CR) after two cycles of AML-directed therapy, compared with 88% of patients with AML-LBC (P=0.0001); MDS patients tended to experience prolonged severe cytopenias with chemotherapy. The 4-year survival for MDS patients was 23% +/- 7% (s.e.), vs 50% +/- 18% (s.e.) for AML-LBC (P=0.048). AML-LBC patients frequently had chloromas; none were seen in MDS patients. We conclude that the 30% blast threshold is ineffective for separation of AML and MDS in pediatric patients, and that genetic data should be included in this decision process. AML-LBC, defined by <30% blasts in bone marrow and cyto- (or molecular) genetic abnormalities associated with de novo AML, and characterized by absent or mild marrow dysplasia, is biologically and clinically distinct from MDS and should be treated as de novo AML. Outcome in pediatric MDS remains poor, and new treatment strategies are needed for these patients.


Assuntos
Leucemia Mieloide/diagnóstico , Síndromes Mielodisplásicas/diagnóstico , Doença Aguda , Adolescente , Medula Óssea/patologia , Contagem de Células , Criança , Pré-Escolar , Inversão Cromossômica , Diagnóstico Diferencial , Feminino , Humanos , Lactente , Leucemia Mielogênica Crônica BCR-ABL Positiva/sangue , Leucemia Mielogênica Crônica BCR-ABL Positiva/diagnóstico , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Leucemia Mielogênica Crônica BCR-ABL Positiva/mortalidade , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mieloide/sangue , Leucemia Mieloide/genética , Leucemia Mieloide/mortalidade , Leucemia Mieloide/patologia , Tábuas de Vida , Masculino , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/patologia , Cromossomo Filadélfia , Prognóstico , Translocação Genética , Resultado do Tratamento
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