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1.
Biol Blood Marrow Transplant ; 26(8): e177-e182, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32438042

RESUMO

Hematopoietic cell transplantation (HCT) is a well-established treatment to control and/or cure many malignant and nonmalignant diseases involving the hematopoietic system and some solid tumors. We report information about HCT procedures performed in the United States in 2018 and analyze trends and outcomes of HCT as reported to the Center for International Blood and Marrow Transplant Research (CIBMTR). Overall, compared with 2017, the number of allogeneic HCTs performed in the United States increased by 1%, and the number of autologous HCTs decreased by 5%. Key findings are fewer autologous HCTs performed for non-Hodgkin lymphoma and increasing numbers of haploidentical HCTs, nearly all of which use post-transplantation cyclophosphamide for graft-versus-host disease prophylaxis. There is a continuing increase in HCT in adults age >70 years, particularly for acute myelogenous leukemia and myelodysplastic syndromes. Survival rates by disease, disease stage, donor type, and age are presented. This report, prepared annually by the CIBMTR, provides a snapshot of current transplant activity in the United States.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Adulto , Idoso , Ciclofosfamida , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Leucemia Mieloide Aguda/terapia , Doadores de Tecidos , Condicionamento Pré-Transplante , Estados Unidos
2.
Blood ; 118(17): 4732-9, 2011 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-21868572

RESUMO

Studies of haploidentical hematopoietic stem cell transplantation (HSCT) have identified threshold doses of T cells below which severe GVHD is usually absent. However, little is known regarding optimal T-cell dosing as it relates to engraftment, immune reconstitution, and relapse. To begin to address this question, we developed a 2-step myeloablative approach to haploidentical HSCT in which 27 patients conditioned with total body irradiation (TBI) were given a fixed dose of donor T cells (HSCT step 1), followed by cyclophosphamide (CY) for T-cell tolerization. A CD34-selected HSC product (HSCT step 2) was infused after CY. A dose of 2 × 10(8)/kg of T cells resulted in consistent engraftment, immune reconstitution, and acceptable rates of GVHD. Cumulative incidences of grade III-IV GVHD, nonrelapse mortality (NRM), and relapse-related mortality were 7.4%, 22.2%, and 29.6%, respectively. With a follow-up of 28-56 months, the 3-year probability of overall survival for the whole cohort is 48% and 75% in patients without disease at HSCT. In the context of CY tolerization, a high, fixed dose of haploidentical T cells was associated with encouraging outcomes, especially in good-risk patients, and can serve as the basis for further exploration and optimization of this 2-step approach. This study is registered at www.clinicaltrials.gov as NCT00429143.


Assuntos
Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Agonistas Mieloablativos/uso terapêutico , Linfócitos T/citologia , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Calibragem , Contagem de Células , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Haplótipos , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/mortalidade , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/normas , Humanos , Masculino , Pessoa de Meia-Idade , Agonistas Mieloablativos/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo , Adulto Jovem
3.
Biol Blood Marrow Transplant ; 15(12): 1609-19, 2009 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19744572

RESUMO

Although allogeneic hematopoietic progenitor cell transplant (HPCT) is curative therapy for many disorders, it is associated with significant morbidity and mortality, which can be related to graft-versus-host disease (GVHD) and the immunosuppressive measures required for its prevention and/or treatment. Whether the immunosuppression is pharmacologic or secondary to graft manipulation, the graft recipient is left at increased risk of the threatening opportunistic infection. Refractory viral diseases in the immunocompromised host have been treated by infusion of virus-specific lymphotyces and by unmanipulated donor lymphocyte infusion (DLI) therapy. L-leucyl-L-leucine methyl ester (LLME) is a compound that induces programmed cell death of natural killer (NK) cells, monocytes, granulocytes, most CD8(+) T cells, and a small fraction of CD4(+) T cells. We have undertaken a study of the use of LLME-treated DLI following T cell-depleted allogeneic HPCT, specifically to aid with immune reconstitution. In this ongoing clinical trial, we have demonstrated the rapid emergence of virus-specific responses following LLME DLI with minimal associated GVHD. This paper examines the pace of immune recovery and the rapid development of antiviral responses in 6 patients who developed viral infections during the time period immediately preceding or coincident with the administration of the LLME DLI.


Assuntos
Dipeptídeos/uso terapêutico , Doença Enxerto-Hospedeiro/imunologia , Transplante de Células-Tronco Hematopoéticas/métodos , Transfusão de Linfócitos/métodos , Subpopulações de Linfócitos T/efeitos dos fármacos , Subpopulações de Linfócitos T/transplante , Adulto , Idoso , Estudos de Coortes , Citometria de Fluxo , Doença Enxerto-Hospedeiro/prevenção & controle , Humanos , Masculino , Pessoa de Meia-Idade , Subpopulações de Linfócitos T/citologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante , Adulto Jovem
5.
Semin Oncol ; 31(6 Suppl 18): 67-73, 2004 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-15726527

RESUMO

Planning therapy for acute myelogenous leukemia (AML) is difficult because of the heterogeneous nature of the disease and varying patient age at presentation. Cytogenetics and patient age at the time of diagnosis are two major factors determining treatment outcome in AML. Patients with poor-risk cytogenetics have much lower complete remission rates than other groups. In addition, AML in patients greater than 55 to 60 years of age often exhibits a resistant phenotype, more akin to secondary AML or AML arising from myelodysplastic syndromes. This group is also characterized by lower complete remission rates, and often requires the delivery of intensive therapy to a patient population that is the least likely to tolerate it. At the Jefferson Health System (Philadelphia, PA), we wished to develop a regimen that was maximally intensive to treat stubborn disease, but gentle enough to be given to all patients regardless of age. Toward this end, 33 patients received a maximal dose of the cytoprotective agent, amifostine, before each infusion of idarubicin in the "7 + 3" regimen, escalating the dose of idarubicin in a phase I fashion to a maximum dose of 24 mg/m2 . The data indicate that the addition of amifostine to "7 + 3" AML induction therapy enables a substantial escalation of the idarubicin dose through the 21-mg/m2 dose level, without a concomitant increase in side effects, thus providing a regimen that is both intensive and applicable to patients of all ages. Currently, phase II studies are ongoing on a national basis to evaluate the efficacy of this regimen.


Assuntos
Amifostina/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idarubicina/administração & dosagem , Leucemia Mieloide Aguda/tratamento farmacológico , Adulto , Idoso , Amifostina/efeitos adversos , Medula Óssea/efeitos dos fármacos , Citoproteção , Feminino , Humanos , Idarubicina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida
6.
Biol Blood Marrow Transplant ; 13(1): 74-81, 2007 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17222755

RESUMO

Invasive adenovirus (AdV) disease is fatal in >50% of allogeneic hematopoietic stem cell transplant (SCT) recipients. Treatment with cidofovir may improve outcomes based on in vitro susceptibility data and case reports. Six consecutive cases of invasive AdV disease treated with cidofovir were reviewed among 84 allogeneic adult SCT recipients (incidence, 7.1%). Cidofovir was administered intravenously at 5 mg/kg per dose (1-7 doses). All patients received intravenous immune globulin. Blood AdV DNA levels (viral loads, VLs) were monitored with a real-time quantitative polymerase chain reaction assay. Published reports of cidofovir treatment of AdV disease in SCT recipients were critically reviewed. The primary manifestations of AdV disease were hepatitis (n = 3), colitis (n = 2), and nephritis (n = 1). All patients had detectable AdV VLs, with peak values from 5 x 10(5) to 2 x 10(8) copies/mL. All patients received CD34+ selected grafts (n = 3) and/or had graft-versus-host disease (n = 4) and had CD4 counts <100 cells/mm3. Only 1 of 5 patients (20%) who received >or=2 doses of cidofovir died with active AdV disease. Four patients exhibited improvement within days of treatment with cidofovir as documented by clinical criteria and declines in AdV VLs (without a change in immunosuppression). In contrast, 1 patient treated late after onset of AdV disease died after 1 dose of cidofovir. In our review of 70 published cases treated with >or=2 doses of cidofovir, 13 (19%) died from AdV disease. In conclusion, early treatment of AdV disease with cidofovir inhibits viral replication in vivo and reduces mortality in allogeneic SCT recipients compared with historical data.


Assuntos
Infecções por Adenovirus Humanos/tratamento farmacológico , Antivirais/uso terapêutico , Citosina/análogos & derivados , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Organofosfonatos/uso terapêutico , Infecções por Adenovirus Humanos/etiologia , Adulto , Idoso , Contagem de Linfócito CD4 , Cidofovir , Colite/tratamento farmacológico , Colite/virologia , Citosina/uso terapêutico , Feminino , Hepatite Viral Humana/tratamento farmacológico , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Fatores Imunológicos/uso terapêutico , Masculino , Nefrite/tratamento farmacológico , Nefrite/virologia , Transplante Homólogo , Carga Viral
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