Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.602
Filtrar
1.
Stem Cell Res Ther ; 12(1): 374, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215336

RESUMO

Adoptive cell therapy has received a great deal of interest in the treatment of advanced cancers that are resistant to traditional therapy. The tremendous success of chimeric antigen receptor (CAR)-engineered T (CAR-T) cells in the treatment of cancer, especially hematological cancers, has exposed CAR's potential. However, the toxicity and significant limitations of CAR-T cell immunotherapy prompted research into other immune cells as potential candidates for CAR engineering. NK cells are a major component of the innate immune system, especially for tumor immunosurveillance. They have a higher propensity for immunotherapy in hematologic malignancies because they can detect and eliminate cancerous cells more effectively. In comparison to CAR-T cells, CAR-NK cells can be prepared from allogeneic donors and are safer with a lower chance of cytokine release syndrome and graft-versus-host disease, as well as being a more efficient antitumor activity with high efficiency for off-the-shelf production. Moreover, CAR-NK cells may be modified to target various antigens while also increasing their expansion and survival in vivo. Extensive preclinical research has shown that NK cells can be effectively engineered to express CARs with substantial cytotoxic activity against both hematological and solid tumors, establishing evidence for potential clinical trials of CAR-NK cells. In this review, we discuss recent advances in CAR-NK cell engineering in a variety of hematological malignancies, as well as the main challenges that influence the outcomes of CAR-NK cell-based tumor immunotherapies.


Assuntos
Neoplasias Hematológicas , Receptores de Antígenos Quiméricos , Neoplasias Hematológicas/terapia , Humanos , Imunoterapia Adotiva , Células Matadoras Naturais , Receptores de Antígenos Quiméricos/genética , Linfócitos T
3.
J Immunother Cancer ; 9(6)2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34117116

RESUMO

SARS-CoV-2 is the virus responsible for the COVID-19 pandemic. COVID-19 has highly variable disease severity and a bimodal course characterized by acute respiratory viral infection followed by hyperinflammation in a subset of patients with severe disease. This immune dysregulation is characterized by lymphocytopenia, elevated levels of plasma cytokines and proliferative and exhausted T cells, among other dysfunctional cell types. Immunocompromised persons often fare worse in the context of acute respiratory infections, but preliminary data suggest this may not hold true for COVID-19. In this review, we explore the effect of SARS-CoV-2 infection on mortality in four populations with distinct forms of immunocompromise: (1) persons with hematological malignancies (HM) and hematopoietic stem cell transplant (HCT) recipients; (2) solid organ transplant recipients (SOTRs); (3) persons with rheumatological diseases; and (4) persons living with HIV (PLWH). For each population, key immunological defects are described and how these relate to the immune dysregulation in COVID-19. Next, outcomes including mortality after SARS-CoV-2 infection are described for each population, giving comparisons to the general population of age-matched and comorbidity-matched controls. In these four populations, iatrogenic or disease-related immunosuppression is not clearly associated with poor prognosis in HM, HCT, SOTR, rheumatological diseases, or HIV. However, certain individual immunosuppressants or disease states may be associated with harmful or beneficial effects, including harm from severe CD4 lymphocytopenia in PLWH and possible benefit to the calcineurin inhibitor ciclosporin in SOTRs, or tumor necrosis factor-α inhibitors in persons with rheumatic diseases. Lastly, insights gained from clinical and translational studies are explored as to the relevance for repurposing of immunosuppressive host-directed therapies for the treatment of hyperinflammation in COVID-19 in the general population.


Assuntos
COVID-19 , Reposicionamento de Medicamentos , Hospedeiro Imunocomprometido , Imunossupressores/uso terapêutico , Imunoterapia , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/terapia , Comorbidade , Reposicionamento de Medicamentos/métodos , Reposicionamento de Medicamentos/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/imunologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Hospedeiro Imunocomprometido/fisiologia , Imunoterapia/efeitos adversos , Imunoterapia/métodos , Imunoterapia/estatística & dados numéricos , Mortalidade , Pandemias , Prognóstico , Doenças Reumáticas/epidemiologia , SARS-CoV-2/fisiologia , Transplantados/estatística & dados numéricos
4.
BMJ Open ; 11(6): e046409, 2021 06 03.
Artigo em Inglês | MEDLINE | ID: mdl-34083339

RESUMO

INTRODUCTION: Older adults with cancer suffer from the combined effects of ageing, cancer disease and treatment side effects. The main treatment for patients with haematological malignancies is chemotherapy, associated with significant toxicities. Chemotherapy can alter patients' physical function and quality of life which are often already diminished in older patients due to ageing and comorbidities. It therefore seems essential to develop and to evaluate interventions capable of preventing physical and psychosocial decline and its consequences. Promoting physical activity is a promising approach to improve physical function and quality of life in older adults with cancer, but there are limited data on the feasibility of such interventions among older patients with haematological malignancies, concomitant to chemotherapy. METHODS AND ANALYSIS: OCAPI (OnCogeriatric and Individualized Physical Activity) is a single-arm, interdisciplinary, prospective, interventional, feasibility study. It is intended to include 40 patients (20 patients with acute myeloid leukaemia and 20 patients with non-Hodgkin's lymphoma) over 65 years in an individualised 6-month physical activity programme. The programme consists of individually supervised exercise sessions with an increasing volume of physical activity either at home and/or in a laminar airflow room (depending on the disease and treatment regimen) followed by unsupervised sessions and phone follow-ups. Patients will receive an activity tracker during the 6 months of the programme. Evaluations will take place at inclusion and at 3, 6 and 12 months to assess the feasibility of the programme and to explore potential changes in physical, psychosocial and clinical outcomes. The results will generate preliminary data to implement a larger randomised controlled trial. ETHICS AND DISSEMINATION: The study protocol was approved by the French ethics committee (Comité de protection des personnes Est I, N°ID-RCB 2019-A01231-56, 12 July 2019). All participants will have to sign and date an informed consent form. The findings will be disseminated in peer-reviewed journals and academic conferences. TRIAL REGISTRATION NUMBER: NCT04052126.


Assuntos
Neoplasias Hematológicas , Qualidade de Vida , Idoso , Exercício Físico , Estudos de Viabilidade , Neoplasias Hematológicas/terapia , Humanos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto
5.
Int J Mol Sci ; 22(11)2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34064196

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T-cells are changing the therapeutic landscape of hematologic malignancies. Severe side effects include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), but prolonged cytopenia has also been reported. The underlying mechanism for prolonged cytopenia is poorly understood so far. CASES: Severe pancytopenia with grade 2-3 anemia was marked 2-3 months after treatment. Laboratory evaluation revealed undetectable levels of haptoglobin with increased reticulocyte counts. Coomb's tests were negative, no schistocytes were detected on blood smear, and infectious causes were ruled out. Increased erythropoiesis without lymphoma infiltration was noted on bone marrow biopsy. A spontaneous increase in haptoglobin and hemoglobin levels was observed after several weeks. For one patient, peripheral CAR-T levels were monitored over time. We observed a decline at the same time as hemoglobin levels began to rise, implying a potential causality. CONCLUSION: To our knowledge, we describe the first two cases of Coombs-negative hemolytic anemia after CAR-T treatment for B-cell lymphoma. We encourage routine monitoring for hemolytic anemia after CAR-T treatment and also encourage further investigations on the underlying mechanism.


Assuntos
Anemia Hemolítica/etiologia , Terapia Baseada em Transplante de Células e Tecidos/efeitos adversos , Pancitopenia/etiologia , Receptores de Antígenos Quiméricos/imunologia , Feminino , Neoplasias Hematológicas/imunologia , Neoplasias Hematológicas/terapia , Humanos , Linfoma/genética , Masculino , Pessoa de Meia-Idade
7.
Artigo em Inglês | MEDLINE | ID: mdl-34064433

RESUMO

The physical environment of a treatment centre may impact the well-being of patients and their perceptions of care. Outpatients with haematological cancer may be in contact with the treatment centre over long periods and could be particularly affected. This study aimed to identify haematological cancer patients' perceptions of supportive design elements in the hospital they attended and associations with self-reported mood or well-being. Outpatients from three large metropolitan hospitals in Australia were mailed a self-report questionnaire and responded to statements about the treatment centre concerning their sense of control over the physical surroundings; access to social support; and access to positive distractions. Participants also reported whether they felt the overall environment affected their mood or wellbeing. Of the outpatients who returned the questionnaire (n = 165), almost one-quarter (24%) agreed that the physical environment of the hospital affected their mood or well-being. Patients who disagreed that the hospital was a comfortable temperature or agreed that waiting rooms were crowded had significantly higher odds of reporting that the treatment environment affected their mood or wellbeing. Implementing systems to reduce overcrowding in waiting rooms and increasing patient control over personal temperature in clinics may be the most effective strategies to improve patient wellbeing.


Assuntos
Neoplasias Hematológicas , Austrália , Neoplasias Hematológicas/terapia , Humanos , Percepção , Apoio Social , Inquéritos e Questionários
8.
Medicina (B Aires) ; 81(3): 396-400, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34137699

RESUMO

SARS-CoV-2 infection in patients with hematological malignancies and hematopoietic stem cell transplants (HSCT) can be severe and with significant mortality. We carried out a prospective and observational study to describe the clinical and epidemiological characteristics and outcome of SARS-CoV-2 infection in patients with hematological malignancies and HSCT. Twenty adult patients were included with a median age of 58 years and a median Charlson score of 3. Infections were community-acquired and nosocomial in 60% and 40%, respectively, and 30% of the patients had a history of contact with a SARS-CoV-2 infected person. Sixty-five percent had pulmonary infiltrates, mostly with a ground-glass pattern on CT scan. Almost half of the patients had a severe and critical illness, and a high proportion received convalescent plasma as treatment. Twenty percent and 15% had complications and hospital infections, respectively, and had prolonged hospitalization expressed as median days of it. The 30-day mortality was 10%. SARS-CoV-2 infection in our population had a considerable clinical and epidemiological impact.


Assuntos
COVID-19 , Neoplasias Hematológicas , Adulto , COVID-19/terapia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/terapia , Humanos , Imunização Passiva , Pessoa de Meia-Idade , Estudos Prospectivos , SARS-CoV-2
9.
Transl Behav Med ; 11(5): 1187-1197, 2021 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-34042962

RESUMO

The COVID-19 pandemic likely exacerbated caregiving challenges for caregivers of parents diagnosed with a blood cancer. Providing care during a public health crisis presents a complex web of uncertainties regarding cancer care, personal health, and COVID-19 risk. Identifying caregivers' uncertainty experiences during the COVID-19 pandemic can be a first step in learning where to direct resources or alter policies to ensure that they can not only perform their caregiver role but also cope in health-promoting ways. Using uncertainty management theory, this study explored how the pandemic has impacted adult child caregivers' experiences caring for a parent diagnosed with a blood cancer, as well as their experiences of uncertainty and uncertainty management. As part of a larger study on blood cancer caregivers' needs, a survey was administered from March 30 to June 1, 2020, to recruit caregivers through the Leukemia and Lymphoma Society. A qualitative and quantitative content analysis was conducted on open-ended responses from 84 caregivers. Caregivers described changes illustrating the complexity of providing care during a pandemic: (a) increased fears and uncertainty-related distress, b) reduced in-person care opportunities, (c) increased isolation, and (d) enhanced family communication. Caregivers with parents diagnosed with acute blood cancers used significantly more uncertainty management strategies and had more sources of uncertainty than caregivers with parents living with chronic blood cancer types. Findings highlight the need for supportive services to help caregivers manage uncertainty and improve their capacity to provide care in an unpredictable global health crisis. Such support may reduce poor psychosocial outcomes.


Assuntos
COVID-19 , Cuidadores/psicologia , Neoplasias Hematológicas/terapia , Adaptação Psicológica , Adulto , Humanos , Determinação de Necessidades de Cuidados de Saúde , Pandemias , Inquéritos e Questionários , Incerteza
10.
Transplant Cell Ther ; 27(5): 390.e1-390.e7, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965176

RESUMO

Databases were searched to identify studies published over the past 10 years that addressed the utility of patient-reported outcomes (PROs) in patients receiving chimeric antigen receptor (CAR) T cell therapy in patients with hematological malignancies. Among 280 records, three articles covering 206 patients were eligible. The data were prospectively collected at multiple time points. The compliance rates were 70% to 94%. There was an inverse relationship between fatigue and social function among adults. The quality of life (QoL) improvement and ability to complete PROs were linked to disease status. About 40% of adults reported at least some cognitive difficulties, with a detrimental impact on mental and physical health status. In adults, the most commonly reported cognitive impairment was memory difficulties. Depression was associated with cognitive difficulties. Younger adults were at higher risk of long-term poor mental health, anxiety, and depression. For pediatric and adolescent patients, emotional dysfunction improves over time. QoL status improved over time; yet, severe cytokine release syndrome and neurotoxicity caused delayed improvement. Information regarding whether the PROs were integrated into medical records and clinical guidelines is lacking. Utilizing PROs in patients on CAR T cell therapy seems feasible and informative. Studies utilizing larger sample sizes and using validated PRO tools at different time points remain unmet needs.


Assuntos
Neoplasias Hematológicas , Neoplasias , Receptores de Antígenos Quiméricos , Adolescente , Adulto , Terapia Baseada em Transplante de Células e Tecidos , Criança , Neoplasias Hematológicas/terapia , Humanos , Imunoterapia Adotiva , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida
11.
Ann Hematol ; 100(7): 1837-1847, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33948721

RESUMO

Despite the widespread use of rabbit anti-thymocyte globulin (ATG) to prevent acute and chronic graft-versus-host disease (aGVHD, cGVHD) after allogeneic hematopoietic cell transplantation (allo-HCT), convincing evidence about an optimal dose is lacking. We retrospectively evaluated the clinical impact of two different ATG doses (5 vs 6-7.5 mg/kg) in 395 adult patients undergoing HSCT from matched unrelated donors (MUD) at 3 Italian centers. Cumulative incidence of aGVHD and moderate-severe cGVHD did not differ in the 2 groups. We observed a trend toward prolonged overall survival (OS) and disease-free survival (DFS) with lower ATG dose (5-year OS and DFS 56.6% vs. 46.3%, p=0.052, and 46.8% vs. 38.6%, p=0.051, respectively) and no differences in relapse incidence and non-relapse mortality. However, a significantly increased infection-related mortality (IRM) was observed in patients who received a higher ATG dose (16.7% vs. 8.8% in the lower ATG group, p=0.019). Besides, graft and relapse-free survival (GRFS) was superior in the lower ATG group (5-year GRFS 43.1% vs. 32.4%, p=0.014). The negative impact of higher ATG dose on IRM and GRFS was confirmed by multivariate analysis. Our results suggest that ATG doses higher than 5 mg/kg are not required for MUD allo-HCT and seem associated with worse outcomes.


Assuntos
Soro Antilinfocitário/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adulto , Aloenxertos , Soro Antilinfocitário/administração & dosagem , Soro Antilinfocitário/efeitos adversos , Ciclosporina/uso terapêutico , Intervalo Livre de Doença , Relação Dose-Resposta Imunológica , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Histocompatibilidade , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Infecções/etiologia , Infecções/mortalidade , Estimativa de Kaplan-Meier , Masculino , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Modelos de Riscos Proporcionais , Recidiva , Estudos Retrospectivos , Linfócitos T/imunologia , Doadores não Relacionados
13.
Int Heart J ; 62(3): 575-583, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-33994498

RESUMO

Hematopoietic stem cell transplantation (HSCT) is occasionally associated with cardiac dysfunction during long-term follow-up. Global longitudinal strain (GLS) has emerged as an early predictor of cardiotoxicity associated with cancer therapy; however, the serial changes in GLS before and after HSCT have not been elucidated. To clarify the association between HSCT and GLS, we investigated serial changes in GLS before and after HSCT. We evaluated cardiac function before and 1, 3, and 6 months after HSCT in 38 consecutive HSCT patients enrolled in this study. Overall, GLS and left ventricular (LV) ejection fraction (EF) temporally decreased 1 month post-HSCT. LVEF completely recovered to baseline at 3 months after HSCT, whereas GLS partially recovered 6 months after HSCT. Except for five patients who died within 6 months, GLS values in the low EF group (LVEF ≤ 55% at 6 months post-HSCT, n = 6) were significantly and consistently lower than those in the normal EF group (LVEF > 55% at 6 months post-HSCT, n = 27) at any time during follow-up. These findings suggest that GLS before HSCT might be associated with a decrease in LVEF after HSCT in patients with hematologic malignancies. Further prospective and long-term data will be important for understanding the management of HSCT-associated cardiac dysfunction.


Assuntos
Cardiotoxicidade/fisiopatologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Contração Miocárdica , Adulto , Cardiotoxicidade/diagnóstico por imagem , Cardiotoxicidade/etiologia , Ecocardiografia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Cancer Epidemiol ; 72: 101929, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33819838

RESUMO

BACKGROUND: Numbers of patients who develop subsequent primary tumours have markedly increased recently. This study aimed to carry out a comprehensive analysis documenting the risk of incidence of subsequent haematological malignancies. METHODS: The Czech National Cancer Registry was the main data source, containing records of 126,822 haematological malignancies diagnosed in the period 1977-2016. Subsequent haematological malignancies were identified according to IACR rules. Joinpoint regression was employed to assess the time trends. The risk of development of subsequent haematological malignancy was evaluated by the standardised incidence ratio. The Kaplan-Meier curves were used to assess the differences in survival. RESULTS: Age-standardised incidence of subsequent haematological malignancies increased from 0.5 in 1977 to 9.1 in 2016. In 1992, there was a significant change in the trend: a sharp increase by 7.7 % annually was revealed thereafter. The risk of development of a haematological malignancy was approximately 1.5 times higher in persons with history of any cancer than in the general Czech population. Patients with haematological malignancies - mainly myelodysplastic syndromes, polycythaemia vera and non-Hodgkin lymphoma - were shown to be at the highest risk of developing a subsequent haematological malignancy. While the median survival following a first haematological malignancy was 2.3 years, it was only 1.1 years for subsequent haematological malignancies (p < 0.001). CONCLUSIONS: Our study identified the highest-risk diagnoses in terms of development of subsequent haematological malignancy. The results might be useful to set up correctly follow-up procedures from which cancer patients could benefit.


Assuntos
Neoplasias Hematológicas/epidemiologia , Segunda Neoplasia Primária/epidemiologia , Feminino , Neoplasias Hematológicas/terapia , Humanos , Incidência , Masculino , Sistema de Registros , Medição de Risco
16.
Biomed Pharmacother ; 139: 111573, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33894623

RESUMO

The incidence of hematological malignancies such as multiple myeloma, leukemia, and lymphoma has increased over time. Although bone marrow transplantation, immunotherapy and chemotherapy have led to significant improvements in efficacy, poor prognosis in elderly patients, recurrence and high mortality among hematological malignancies remain major challenges, and innovative therapeutic strategies should be explored. Besides directly lyse tumor cells, oncolytic viruses can activate immune responses or be engineered to express therapeutic factors to increase antitumor efficacy, and have gradually been recognized as an appealing approach for fighting cancers. An increasing number of studies have applied oncolytic viruses in hematological malignancies and made progress. In particular, strategies combining immunotherapy and oncolytic virotherapy are emerging. Various phase I clinical trials of oncolytic reovirus with lenalidomide or programmed death 1(PD-1) immune checkpoint inhibitors in multiple myeloma are ongoing. Moreover, preclinical studies of combinations with chimeric antigen receptor T (CAR-T) cells are underway. Thus, oncolytic virotherapy is expected to be a promising approach to cure hematological malignancies. This review summarizes progress in oncolytic virus research in hematological malignancies. After briefly reviewing the development and oncolytic mechanism of oncolytic viruses, we focus on delivery methods of oncolytic viruses, especially systemic delivery that is suitable for hematological tumors. We then discuss the main types of oncolytic viruses applied for hematological malignancies and related clinical trials. In addition, we present several ways to improve the antitumor efficacy of oncolytic viruses. Finally, we discuss current challenges and provide suggestions for future studies.


Assuntos
Neoplasias Hematológicas/terapia , Terapia Viral Oncolítica/métodos , Vírus Oncolíticos , Animais , Terapia Combinada , Humanos , Imunoterapia
18.
Transplant Cell Ther ; 27(6): 478.e1-478.e5, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33819481

RESUMO

Allogeneic stem cell transplantation from haploidentical donor using post-transplantation cyclophosphamide has been used to cure hematological diseases. Because of slow immunological reconstitution, there is an increased incidence of viral infection. The aim of our study was to prospectively evaluate the efficacy and the feasibility of a CD45RA+ depleted donor lymphocytes infusion (DLI) in terms of reduction of viral infection early after haploidentical transplantation. This a prospective single-center study. We enrolled 23 patients, of whom 19 were evaluable. Graft-versus-host disease (GVHD) prophylaxis was the same for all patients. The primary endpoint was 100-day cumulative incidence of viral infections. The primary endpoint was met, because the 100-day cumulative incidence of viral infection was 32%. The median time from transplantation to first CD45RA+ depleted DLI was 55 days (range, 46-63). 28% of patients had cytomegalovirus reactivation, no patients reactivated human herpesvirus-6; 1 patient developed BK virus related hemorrhagic cystitis. Most of the patients received the planned 3 infusions. Only 1 patient had development of grade 2 acute GVHD, and 2 patients had moderate chronic GVHD. All evaluable patients were off immunosuppressive therapy at last follow-up. The median follow-up was 12 months (range, 3-23), the 1-year overall survival and progression-free survival were 79% and 75%, respectively; the 100-day and 1-year non-relapse mortality were 5% and 12%, respectively. CD45RA+ depleted DLI are feasible in patients treated with haploidentical transplantation. The toxic profile is good with a low risk for development of both acute and chronic GVHD.


Assuntos
Neoplasias Hematológicas , Transplante Haploidêntico , Ciclofosfamida/uso terapêutico , Estudos de Viabilidade , Neoplasias Hematológicas/terapia , Humanos , Linfócitos , Estudos Prospectivos
19.
Transplant Cell Ther ; 27(2): 169.e1-169.e9, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33830028

RESUMO

TCRαß/CD19-depleted HCT has been used with excellent outcomes in pediatric patients with hematologic malignancies, and several studies have demonstrated rapid immune reconstitution in the nonmalignant setting. However, immune recovery following TCRαß/CD19-depleted hematopoietic cell transplantation (HCT) for malignancy remains incompletely elucidated. Furthermore, the majority of studies to date have used haploidentical and matched unrelated donors. Here we report results of immune reconstitution following TCRαß/CD19-depleted HCT for hematologic malignancy in 51 pediatric patients with hematologic malignancies, the majority of whom received grafts from unrelated donors. Grafts were from matched unrelated (n = 20), mismatched unrelated (n = 20), and haploidentical (n = 11) donors. The median CD34+ cell dose was 10.2 × 106/kg (range, 4.54 to 20 × 106/kg), and the median TCRαß+ cell dose was 2.53 × 104/kg (range, 0 to 44.9 × 104/kg). Conditioning was myeloablative with either busulfan or total body irradiation, cyclophosphamide, and thiotepa. Thirty-three patients also received rabbit antithymocyte globulin. No prophylactic post-transplantation immune suppression was routinely given. Forty-three patients received rituximab on day +1 for recipient positive Epstein-Barr virus serology. Forty-nine patients (96%) engrafted with a median time to neutrophil recovery of 13 days (range, 8 to 30 days). Thirty-seven patients (73%) are alive at a median follow-up of 25 months (range, 6 to 50 months). Nine patients (18%) developed grade II-IV acute graft-versus-host disease (GVHD), and 5 patients (11%) developed extensive chronic GVHD. Twenty-six patients (51%) experienced viral reactivation. T cell reconstitution was rapid with significant numbers of CD3+, CD4+, and CD8+ T cells present on first assessment at 4 months post-HCT, and significant numbers of naïve CD4+ T cells were present by 8 months post-HCT. Chronic GVHD was associated with delayed T cell recovery; however, T cell reconstitution was not affected by underlying diagnosis, donor source, TCRαß+ T cell dose, conditioning regimen, or use of antithymocyte globulin. B cell recovery mirrored T cell recovery, and i.v. Ig was discontinued at a median of 8 months (range, 4 to 22 months) post-HCT in patients alive and relapse-free at last follow-up. Immune reconstitution is rapid following TCRαß/CD19-depleted HCT in pediatric patients with hematologic malignancies. Donor graft source, haploidentical or unrelated, did not affect immune reconstitution. Viral reactivation is common in the first 100 days post-HCT, indicating that improved T cell defense is needed in the early post-HCT period.


Assuntos
Infecções por Vírus Epstein-Barr , Neoplasias Hematológicas , Transplante de Células-Tronco Hematopoéticas , Reconstituição Imune , Linfócitos T CD8-Positivos , Criança , Neoplasias Hematológicas/terapia , Herpesvirus Humano 4 , Humanos , Depleção Linfocítica , Recidiva Local de Neoplasia , Receptores de Antígenos de Linfócitos T alfa-beta , Condicionamento Pré-Transplante
20.
Transplant Cell Ther ; 27(4): 286-291, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33836867

RESUMO

For cord blood transplantation (CBT), appropriate patient and conditioning regimen selection is necessary to achieve long-term disease-free survival. This review aims to provide comprehensive guidelines on these issues using evidence from the literature and experience at dedicated CBT centers. Topics include patient and disease characteristics that make CBT a good or poor choice and a review of outcomes in commonly used conditioning regimens in CBT. This is accompanied with recommendations on regimen intensity based on disease, organ function, and patient performance status and age. In addition, the use of antithymocyte globulin in CBT is discussed, as is the choice of conditioning in aplastic anemia patients who have access to acceptable CB units.


Assuntos
Anemia Aplástica , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Neoplasias Hematológicas , Adulto , Anemia Aplástica/terapia , Neoplasias Hematológicas/terapia , Humanos , Seleção de Pacientes , Condicionamento Pré-Transplante
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...