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2.
Am J Transplant ; 16(5): 1492-502, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26608093

RESUMO

Nephropathy due to BK virus (BKV) infection is an evolving challenge in patients undergoing hematopoietic stem cell transplantation (HSCT). We hypothesized that BKV infection was a marker of kidney function decline and a poor prognostic factor in HSCT recipients who experience this complication. In this retrospective study, we analyzed all patients who underwent their first allogeneic HSCT at our institution between 2004 and 2012. We evaluated the incidence of persistent kidney function decline, which was defined as a confirmed reduction in estimated glomerular filtration rate of at least 25% from baseline using the Chronic Kidney Disease Epidemiology equation. Cox proportional hazard regression was used to model the cause-specific hazard of kidney function decline, and the Fine-Gray method was used to account for the competing risks of death. Among 2477 recipients of a first allogeneic HSCT, BK viruria was detected in 25% (n = 629) and kidney function decline in 944 (38.1%). On multivariate analysis, after adjusting for age, sex, acute graft-versus-host disease (GVHD), chronic GVHD, preparative conditioning regimen, and graft source, BK viruria remained a significant risk factor for kidney function decline (p < 0.001). In addition, patients with BKV infection and kidney function decline experienced worse overall survival. After allogeneic HSCT, BKV infection was strongly and independently associated with subsequent kidney function decline and worse patient survival after HSCT.


Assuntos
Vírus BK/patogenicidade , Doença Enxerto-Hospedeiro/mortalidade , Doenças Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Nefropatias/mortalidade , Infecções por Polyomavirus/mortalidade , Infecções Tumorais por Vírus/mortalidade , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Seguimentos , Taxa de Filtração Glomerular , Doença Enxerto-Hospedeiro/etiologia , Doenças Hematológicas/complicações , Doenças Hematológicas/terapia , Humanos , Lactente , Recém-Nascido , Nefropatias/virologia , Testes de Função Renal , Masculino , Pessoa de Meia-Idade , Infecções por Polyomavirus/virologia , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Transplante Homólogo , Infecções Tumorais por Vírus/virologia , Adulto Jovem
3.
Ann Oncol ; 26(12): 2490-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26416896

RESUMO

BACKGROUND: Cutaneous T-cell lymphomas (CTCLs) and its common variants mycosis fungoides (MF) and leukemic Sézary syndrome (SS) are rare extranodal non-Hodgkin's lymphomas. Patients who present with advanced disease and large-cell transformation (LCT) are incurable with standard treatments. In this article, we report the largest single-center experience with allogeneic stem-cell transplantation (SCT) for advanced CTCL. PATIENTS AND METHODS: This is a prospective case series of 47 CTCL patients who underwent allogeneic SCT after failure of standard therapy between July 2001 and September 2013. The Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS) curves. The method of Fine and Gray was used to fit regression models to the same covariates for these cumulative incidence data. RESULTS: The Kaplan-Meier estimates of OS and PFS at 4 years were 51% and 26%, respectively. There was no statistical difference in the OS in patients who had MF alone, SS, MF with LCT, or SS with LCT. PFS at 4 years was superior in patients who had SS versus those who did not (52.4% versus 9.9%; P = 0.02). The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and chronic GVHD were 40% and 28%, respectively. The cumulative nonrelapse mortality rate was 16.7% at 2 years. CONCLUSION: Allogeneic SCT may result in long-term remissions in a subset of patients with advanced CTCL. Although post-SCT relapse rates are high, many patients respond to immunomodulation and achieve durable remissions. CLINICALTRIALSGOV: NCT00506129.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Linfoma Cutâneo de Células T/diagnóstico , Linfoma Cutâneo de Células T/terapia , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/terapia , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Seguimentos , Transplante de Células-Tronco Hematopoéticas/tendências , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo/métodos , Transplante Homólogo/tendências , Adulto Jovem
4.
Transplant Cell Ther ; 29(3): 151-163, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36442770

RESUMO

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an increasingly recognized complication of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality. However, TA-TMA is a clinical diagnosis, and multiple criteria have been proposed without universal application. Although some patients have a self-resolving disease, others progress to multiorgan failure and/or death. Poor prognostic features also are not uniformly accepted. The lack of harmonization of diagnostic and prognostic markers has precluded multi-institutional studies to better understand incidence and outcomes. Even current interventional trials use different criteria, making it challenging to interpret the data. To address this urgent need, the American Society for Transplantation and Cellular Therapy, Center for International Bone Marrow Transplant Research, Asia-Pacific Blood and Marrow Transplantation, and European Society for Blood and Marrow Transplantation nominated representatives for an expert panel tasked with reaching consensus on diagnostic and prognostic criteria. The panel reviewed literature, generated consensus statements regarding diagnostic and prognostic features of TA-TMA using the Delphi method, and identified future directions of investigation. Consensus was reached on 4 key concepts: (1) TA-TMA can be diagnosed using clinical and laboratory criteria or tissue biopsy of kidney or gastrointestinal tissue; however, biopsy is not required; (2) consensus diagnostic criteria are proposed using the modified Jodele criteria with additional definitions of anemia and thrombocytopenia. TA-TMA is diagnosed when ≥4 of the following 7 features occur twice within 14 days: anemia, defined as failure to achieve transfusion independence despite neutrophil engraftment; hemoglobin decline by ≥1 g/dL or new-onset transfusion dependence; thrombocytopenia, defined as failure to achieve platelet engraftment, higher-than-expected transfusion needs, refractory to platelet transfusions, or ≥50% reduction in baseline platelet count after full platelet engraftment; lactate dehydrogenase (LDH) exceeding the upper limit of normal (ULN); schistocytes; hypertension; soluble C5b-9 (sC5b-9) exceeding the ULN; and proteinuria (≥1 mg/mg random urine protein-to-creatinine ratio [rUPCR]); (3) patients with any of the following features are at increased risk of nonrelapse mortality and should be stratified as high-risk TA-TMA: elevated sC5b-9, LDH ≥2 times the ULN, rUPCR ≥1 mg/mg, multiorgan dysfunction, concurrent grade II-IV acute graft-versus-host disease (GVHD), or infection (bacterial or viral); and (4) all allogeneic and pediatric autologous HCT recipients with neuroblastoma should be screened weekly for TA-TMA during the first 100 days post-HCT. Patients diagnosed with TA-TMA should be risk-stratified, and those with high-risk disease should be offered participation in a clinical trial for TA-TMA-directed therapy if available. We propose that these criteria and risk stratification features be used in data registries, prospective studies, and clinical practice across international settings. This harmonization will facilitate the investigation of TA-TMA across populations diverse in race, ethnicity, age, disease indications, and transplantation characteristics. As these criteria are widely used, we expect continued refinement as necessary. Efforts to identify more specific diagnostic and prognostic biomarkers are a top priority of the field. Finally, an investigation of the impact of TA-TMA-directed treatment, particularly in the setting of concurrent highly morbid complications, such as steroid-refractory GVHD and infection, is critically needed.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microangiopatias Trombóticas , Humanos , Criança , Prognóstico , Medula Óssea , Estudos Prospectivos , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/etiologia , Microangiopatias Trombóticas/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos
5.
Biol Blood Marrow Transplant ; 18(12): 1819-26, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22750645

RESUMO

We investigated the safety and early disease control data for i.v. busulfan (Bu) in combination with clofarabine (Clo) in patients with acute lymphoblastic leukemia undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients (median age, 36 years; range, 20-64 years) received a matched sibling (n = 24), syngeneic (n = 2), or matched unrelated donor transplant (n = 25) for acute lymphoblastic leukemia in first complete remission (n = 30), second complete remission (n = 13), or active disease (n = 8). More than one-half of the patients had a high-risk cytogenetic profile, as defined by the presence of t(9;22) (n = 17), t(4;11) (n = 3), or complex cytogenetics (n = 7). Clo 40 mg/m(2) was given once daily, with each dose followed by pharmacokinetically dosed Bu infused over 3 hours daily for 4 days, followed by hematopoietic SCT 2 days later. The Bu dose was based on drug clearance, as determined by the patient's response to a 32-mg/m(2) Bu test dose given 48 hours before the high-dose regimen. The target daily area under the receiver-operating characteristic curve was 5500 µM/min for patients age <60 years and 4000 µM/min for those age ≥60 years. The regimen was well tolerated, with a 100-day nonrelapse mortality rate of 6%. With a median follow-up of 14 months among surviving patients (range, 6-28 months), the 1-year overall survival, disease-free survival, and nonrelapse mortality rates were 67% (95% confidence interval [CI], 55%-83%), 54% (95% CI, 41%-71%), and 32% (95% CI, 16%-45%), respectively. For patients undergoing SCT in first remission, these respective rates were 74%, 64%, and 25%. Our data indicate that the combination of Clo and Bu provides effective disease control while maintaining a favorable safety profile.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/cirurgia , Nucleotídeos de Adenina/administração & dosagem , Nucleotídeos de Adenina/efeitos adversos , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Arabinonucleosídeos/administração & dosagem , Arabinonucleosídeos/efeitos adversos , Bussulfano/administração & dosagem , Bussulfano/efeitos adversos , Clofarabina , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Condicionamento Pré-Transplante/métodos , Adulto Jovem
6.
Ann Oncol ; 19(6): 1166-71, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18272911

RESUMO

PATIENTS AND METHODS: We present a retrospective analysis of 99 consecutive patients with relapsed non-Hodgkin's lymphomas who were older than 65 years at the time of high-dose chemotherapy and autologous progenitor cell transplantation. RESULTS: Median age at transplant was 68 years (range 65-82). Thirty-six percent of patients had a hematopoietic cell transplantation comorbidity index of >2 at the time of transplantation. The cumulative nonrelapse mortality was 8% [95% confidence interval (CI) 4-17] at 26 months and the 3-year overall survival (OS) was 61% (95% CI 49-71). On multivariate analysis, disease status at transplant and lactate dehydrogenase (LDH) > normal were significant predictors for OS (P = 0.002). Comorbidity index of >2 did not impact OS but did predict for higher risk of developing grade 3-5 toxicity (P = 0.006). Eight patients developed secondary myelodysplastic syndrome/acute myelogenous leukemia after transplantation (cumulative incidence 16%). CONCLUSIONS: Patients with relapsed lymphomas who are >65 years of age should be considered transplant candidates, particularly if they have chemosensitive disease and normal LDH levels at the time of transplantation. Patients with comorbidity index of >2 can also undergo transplantation with acceptable outcomes but may be at higher risk for developing toxicity.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Linfoma não Hodgkin/terapia , Recidiva Local de Neoplasia/terapia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Relação Dose-Resposta a Droga , Feminino , Humanos , Linfoma não Hodgkin/mortalidade , Masculino , Recidiva Local de Neoplasia/mortalidade , Prognóstico , Estudos Retrospectivos , Transplante Autólogo
7.
Bone Marrow Transplant ; 39(5): 279-83, 2007 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-17262062

RESUMO

Several clinical trials have shown the superiority of autologous stem cell transplantation over conventional dose therapy for patients with multiple myeloma. This treatment, however, is limited to younger patients (<65 years) owing to concerns about toxicity and treatment-related mortality (TRM) in older patients. We treated 26 elderly myeloma patients (>70 years), who received a preparative regimen of melphalan 200 mg/m2 (19 patients), melphalan 180 mg/m2 (six patients) or melphalan 140 mg/m2 (one patient). Twenty-two of the 26 patients were alive after a median follow-up of 25 months (range=8-74). Responses (complete+partial response) were seen in 20 patients (77%), five (19%) of which were complete responses. Median PFS was 24 months, whereas median OS has not been reached. Cumulative incidence of 100-day TRM was 0%. Three-year PFS and OS were 39% (range=16-61) and 65% (range=35-83), respectively. A low serum albumin (<3.5 g/dl) was associated with a shorter PFS (P=0.02). Patients with relapsed disease at transplant, and an interval of >12 months between diagnosis and autotransplant, had a shorter OS (P=0.0004 and 0.04). HDT and autologous transplant is safe and feasible in elderly myeloma patients.


Assuntos
Melfalan/administração & dosagem , Mieloma Múltiplo/terapia , Agonistas Mieloablativos/administração & dosagem , Transplante de Células-Tronco de Sangue Periférico , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Masculino , Mieloma Múltiplo/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Transplante Autólogo
8.
Bone Marrow Transplant ; 52(4): 580-587, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-27991894

RESUMO

We hypothesized that IV busulfan (Bu) dosing could be safely intensified through pharmacokinetic (PK-) dose guidance to minimize the inter-patient variability in systemic exposure (SE) associated with body-sized dosing, and that this should improve outcome of AML/MDS patients undergoing allogeneic stem cell transplantation. To test this hypothesis, we treated 218 patients (median age 50.7 years, male/female 50/50%) with fludarabine 40 mg/m2 once daily x4, each dose followed by IV Bu, randomized to 130 mg/m2 (N=107) or PK-guided to average daily SE, AUC of 6000 µM min (N=111), stratified for remission status and allo-grafting from HLA-matched donors. Toxicity and GvHD rates in the groups were similar; the risk of relapse or treatment-related mortality remained higher in the fixed-dose group throughout the 80-month observation period. Further, PK-guidance yielded safer disease control, leading to improved overall and PFS, most prominently in MDS patients and in AML patients not in remission at allogeneic stem cell transplantation. We conclude that AML/MDS patients receiving pretransplant conditioning treatment with our 4-day regimen may benefit significantly from PK-guided Bu dosing. This could be considered an alternative to fixed-dose delivery since it provides the benefit of precise dose delivery to a predetermined SE without increasing risk(s) of serious toxicity and/or GvHD.


Assuntos
Bussulfano/administração & dosagem , Monitoramento de Medicamentos/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Transplante Homólogo/métodos , Vidarabina/análogos & derivados , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Bussulfano/farmacocinética , Bussulfano/toxicidade , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Recidiva , Análise de Sobrevida , Condicionamento Pré-Transplante/mortalidade , Transplante Homólogo/mortalidade , Resultado do Tratamento , Vidarabina/administração & dosagem
9.
Bone Marrow Transplant ; 52(1): 28-33, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27595282

RESUMO

Bendamustine has shown a favorable safety profile when included in chemotherapy regimens for several types of lymphoma, including CLL. This study investigated the long-term effect of adding bendamustine to a conditioning regimen on survival, rate of engraftment, immune recovery and GvHD after allogeneic stem cell transplantation (alloSCT) in CLL patients. These outcomes were compared with the fludarabine, cyclophosphamide and rituximab (FCR) conditioning regimen. We reviewed the data for 89 CLL patients treated on three trials at our institution. Twenty-six (29%) patients received bendamustine, fludarabine and rituximab (BFR) and 63 (71%) received FCR. Patient characteristics were similar in both groups. Ten (38%) BFR-treated patients vs only two (3%) FCR-treated patients did not experience severe neutropenia (P=<0.001). The 3-year overall survival estimates for the BFR and FCR groups were 82 and 51% (P=0.03), and the 3-year PFS estimates were 63% and 27% (P=0.001), respectively. The 2-year treatment-related mortality was 8 and 23% and the incidence of grade 3 or 4 GvHD was 4% and 10%, respectively. This study is the first to report that addition of bendamustine to alloSCT conditioning for CLL patients is associated with improved survival and lower mortality, myelosuppression, and GvHD.


Assuntos
Cloridrato de Bendamustina/administração & dosagem , Leucemia Linfocítica Crônica de Células B/mortalidade , Leucemia Linfocítica Crônica de Células B/terapia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Rituximab/administração & dosagem , Taxa de Sobrevida , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados
10.
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
11.
J Clin Oncol ; 16(1): 63-9, 1998 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-9440724

RESUMO

PURPOSE: This study was performed to evaluate the outcome of high-dose chemotherapy and autologous transplantation in patients with diffuse B-cell large-cell lymphoma, and, specifically, to evaluate the impact of primary mediastinal localization on the outcome of high-dose chemotherapy. PATIENTS AND METHODS: A retrospective review was performed of all patients with diffuse large B-cell lymphoma who underwent autologous marrow or peripheral-blood stem-cell transplantation at our institution between January 1 986 and December 1995. RESULTS: Ninety patients were identified, of whom 31 (34%) had a primary mediastinal B-cell large-cell lymphoma (PML). Cumulative probabilities of disease-free survival, overall survival, and disease progression are 40% (95% confidence interval [CI], 29 to 51), 42% (95% CI, 31 to 53), and 52% (95% CI, 40 to 64), respectively. By univariate analysis, low lactate dehydrogenase (LDH) level and low Ann Arbor stage at transplant were associated with improved survival and disease-free survival. There was a trend for improved disease-free survival and survival for patients with PML. Multivariate stepwise Cox regression analysis showed that LDH level, Ann Arbor stage, and primary mediastinal localization were independent favorable prognostic factors for disease-free survival and survival. LDH level and Ann Arbor stage were also predictive for the risk of disease progression. CONCLUSION: Our results indicate that patients with PML may display an increased susceptibility to high-dose chemotherapy compared with other types of B-cell large-cell lymphoma. These findings, if confirmed, may have implications for the initial management of patients with PML.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Medula Óssea/métodos , Linfoma de Células B/terapia , Linfoma Difuso de Grandes Células B/terapia , Neoplasias do Mediastino/terapia , Adolescente , Adulto , Idoso , Carmustina/administração & dosagem , Terapia Combinada , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/patologia , Linfoma de Células B/radioterapia , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/patologia , Linfoma Difuso de Grandes Células B/radioterapia , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
12.
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
13.
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
14.
Bone Marrow Transplant ; 50(3): 420-6, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25531284

RESUMO

Diffuse alveolar hemorrhage (DAH) is a poorly understood complication of transplantation carrying a high mortality. Patients commonly deteriorate and require intensive care unit (ICU) admission. Treatment with high-dose steroids and aminocaproic acid (ACA) has been suggested. The current study examined 119 critically ill adult hematopoietic transplant patients treated for DAH. Patients were subdivided into low-, medium- and high-dose steroid groups with or without ACA. All groups had similar baseline characteristics and severity of illness scores. Primary objectives were 30, 60, 100 day, ICU and hospital mortality. Overall mortality (n=119) on day 100 was high at 85%. In the steroids and ACA cohort (n=82), there were no significant differences in 30, 60, 100, day, ICU and hospital mortality between the dosing groups. In the steroids only cohort (n=37), the low-dose steroid group had a lower ICU and hospital mortality (P=0.02). Adjunctive treatment with ACA did not produce differences in outcomes. In the multivariate analysis, medium- and high-dose steroids were associated with a higher ICU mortality (P=0.01) as compared with the low-dose group. Our data suggest that treatment strategies may need to be reanalyzed to avoid potentially unnecessary and potentially harmful therapies.


Assuntos
Ácido Aminocaproico/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/tratamento farmacológico , Pneumopatias/tratamento farmacológico , Alvéolos Pulmonares/irrigação sanguínea , Esteroides/administração & dosagem , Feminino , Transplante de Células-Tronco Hematopoéticas/métodos , Hemorragia/diagnóstico , Hemorragia/etiologia , Humanos , Pneumopatias/etiologia , Masculino , Pessoa de Meia-Idade , Alvéolos Pulmonares/efeitos dos fármacos , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos , Condicionamento Pré-Transplante/métodos
15.
Bone Marrow Transplant ; 50 Suppl 2: S55-62, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26039209

RESUMO

We are entering a very exciting era in umbilical cord blood transplantation (UCBT), where many of the associated formidable challenges may become treatable by ex vivo graft manipulation and/or adoptive immunotherapy utilizing specific cellular products. We envisage the use of double UCBT rather than single UCBT for most patients; this allows for greater ability to treat larger patients as well as to manipulate the graft. Ex vivo expansion and/or fucosylation of one cord will achieve more rapid engraftment, minimize the period of neutropenia and also give certainty that the other cord will provide long-term engraftment/immune reconstitution. The non-expanded (and future dominant) cord could be chosen for characteristics such as better HLA matching to minimize GvHD, or larger cell counts to enable part of the unit to be utilized for the development of specific cellular therapies such as the production of virus-specific T-cells or chimeric-antigen receptor T-cells which are reviewed in this study.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Facilitação Imunológica de Enxerto/métodos , Sobrevivência de Enxerto , Doença Enxerto-Hospedeiro/prevenção & controle , Engenharia Tecidual/métodos , Humanos
16.
Leukemia ; 29(11): 2126-33, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26293647

RESUMO

The aim of this work is to produce recommendations on the management of allogeneic stem cell transplantation (allo-SCT) in primary myelofibrosis (PMF). A comprehensive systematic review of articles released from 1999 to 2015 (January) was used as a source of scientific evidence. Recommendations were produced using a Delphi process involving a panel of 23 experts appointed by the European LeukemiaNet and European Blood and Marrow Transplantation Group. Key questions included patient selection, donor selection, pre-transplant management, conditioning regimen, post-transplant management, prevention and management of relapse after transplant. Patients with intermediate-2- or high-risk disease and age <70 years should be considered as candidates for allo-SCT. Patients with intermediate-1-risk disease and age <65 years should be considered as candidates if they present with either refractory, transfusion-dependent anemia, or a percentage of blasts in peripheral blood (PB) >2%, or adverse cytogenetics. Pre-transplant splenectomy should be decided on a case by case basis. Patients with intermediate-2- or high-risk disease lacking an human leukocyte antigen (HLA)-matched sibling or unrelated donor, should be enrolled in a protocol using HLA non-identical donors. PB was considered the most appropriate source of hematopoietic stem cells for HLA-matched sibling and unrelated donor transplants. The optimal intensity of the conditioning regimen still needs to be defined. Strategies such as discontinuation of immune-suppressive drugs, donor lymphocyte infusion or both were deemed appropriate to avoid clinical relapse. In conclusion, we provided consensus-based recommendations aimed to optimize allo-SCT in PMF. Unmet clinical needs were highlighted.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mielofibrose Primária/terapia , Seleção do Doador , Teste de Histocompatibilidade , Humanos , Mielofibrose Primária/mortalidade , Condicionamento Pré-Transplante , Transplante Homólogo
17.
Bone Marrow Transplant ; 16(5): 711-3, 1995 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-8547870

RESUMO

Chronic parvovirus B19 infection in the immunocompromised host may cause severe anaemia secondary to failure of erythropoiesis. This has been previously documented in patients with the Acquired Immune Deficiency Syndrome (AIDS), congenital immunodeficiencies and in children with acute lymphoblastic leukaemia during maintenance chemotherapy. We describe persistent parvovirus infection in a 14-year-old boy after HLA-matched sibling allogeneic bone marrow transplantation for acute lymphoblastic leukaemia in second remission.


Assuntos
Anemia Aplástica/terapia , Transplante de Medula Óssea/efeitos adversos , Eritema Infeccioso/terapia , Adolescente , Anemia Aplástica/etiologia , DNA Viral/análise , Eritema Infeccioso/etiologia , Humanos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Transplante Homólogo
18.
Bone Marrow Transplant ; 33(10): 1015-23, 2004 May.
Artigo em Inglês | MEDLINE | ID: mdl-15048145

RESUMO

Our purpose was to study the risk factors associated with disease progression after high-dose chemotherapy followed by autologous stem cell transplantation in patients with recurrent or refractory Hodgkin's lymphoma (HL). We analyzed the long-term outcome of 184 patients with recurrent or refractory HL who underwent autologous hematopoietic stem cell transplantation. At the time of transplantation, 82 patients were in first relapse or second remission, 46 patients were refractory to the primary induction chemotherapy, and 56 patients were beyond first relapse or second remission. In 64 patients, the disease had proved refractory to the chemotherapy regimen administered immediately prior to transplantation. The median follow-up of patients who were alive and free of disease at the time of this report was 8.9 years (range, 0.1-19.0 years). At 10 years, the overall and disease-free survival rates were 34% (95% CI 27-42) and 29% (95% CI 22-36) respectively. The major cause of treatment failure was disease relapse. Chemotherapy resistance prior to transplantation, advanced stage, and higher number of chemotherapy regimens administered prior to transplantation were adverse prognostic factors for disease progression. We conclude that autologous transplantation is an effective salvage treatment for recurrent HL.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença de Hodgkin/terapia , Doença Aguda , Adulto , Progressão da Doença , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro , Doença de Hodgkin/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Recidiva , Fatores de Risco , Fatores de Tempo , Transplante Homólogo , Resultado do Tratamento
19.
J Assoc Physicians India ; 40(3): 164-6, 1992 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1634481

RESUMO

Twenty healthy controls and 385 adult patients suffering from acute enteritis or gastroenteritis were enrolled for the study of Campylobacter Jejuni infection over a period of 2 years. Thirty five stool samples showed C jejuni on stool culture. The isolation rates were at peak in the monsoon season and from watery and bloody stool specimens. Pure C jejuni culture was obtained in 18 of 35 samples; the other 17 samples showed polymicrobial infection or infestation. Nine of 35 patients were treated with erythromycin 1 g in divided doses for 7 days. Repeat stool cultures did not grow C jejuni. There was no resistance to erythromycin therapy. C jejuni are fastidious organisms and require special medium and microaerophilic environment for culture.


Assuntos
Infecções por Campylobacter/epidemiologia , Campylobacter jejuni/isolamento & purificação , Enterite/microbiologia , Gastroenterite/microbiologia , Adolescente , Adulto , Infecções por Campylobacter/tratamento farmacológico , Diarreia/microbiologia , Enterite/epidemiologia , Eritromicina/uso terapêutico , Feminino , Gastroenterite/epidemiologia , Humanos , Índia/epidemiologia , Masculino
20.
J Assoc Physicians India ; 38 Suppl 1: 703-6, 1990 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-2092024

RESUMO

Helicobacter pylori is associated with 70-100% of peptic ulcers. Relapse of infection has been shown to cause recurrences of ulcers in a large number of studies. We diagnosed 137 cases of peptic ulcer (121 DU; 16 GU) during a 3 year period. Of these, 117 were positive for H pylori. Sixty six of the 117 cases staying in the vicinity of the Hospital were followed up for a minimum period of 3 months upto a maximum period of 3 years. In 91 examinations there was relapse of H pylori infection and ulcer recurrence was seen in 58 (63%), whereas ulcer recurred only in 6 out of 61 examinations where H pylori had not relapsed (10%). The difference was highly significant by Chi square test. (P less than 0.001).


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Úlcera Péptica/microbiologia , Adolescente , Adulto , Feminino , Seguimentos , Gastroscopia , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva
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