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1.
J Clin Oncol ; 39(24): 2710-2719, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-33929874

RESUMO

PURPOSE: BK virus-associated hemorrhagic cystitis (BKV-HC) is a common complication of allogenic hematopoietic stem cell transplantation (AHSCT), particularly in recipients of alternative donor transplants, which are being performed in increasing numbers. BKV-HC typically results in painful hematuria, urinary obstruction, and renal dysfunction, without a definitive therapeutic option. METHODS: We performed a clinical trial (ClinicalTrials.gov identifier: NCT02479698) to assess the feasibility, safety, and efficacy of administering most closely HLA-matched third-party BKV-specific cytotoxic T lymphocytes (CTLs), generated from 26 healthy donors and banked for off-the-shelf use. The cells were infused into 59 patients who developed BKV-HC following AHSCT. Comprehensive clinical assessments and correlative studies were performed. RESULTS: Response to BKV-CTL infusion was rapid; the day 14 overall response rate was 67.7% (40 of 59 evaluable patients), which increased to 81.6% among evaluable patients at day 45 (40 of 49 evaluable patients). No patient lost a previously achieved response. There were no cases of de novo grade 3 or 4 graft-versus-host disease, graft failure, or infusion-related toxicities. BKV-CTLs were identified in patient blood samples up to 3 months postinfusion and their in vivo expansion predicted for clinical response. A matched-pair analysis revealed that, compared with standard of care, after accounting for prognostic covariate effects, treatment with BKV-CTLs resulted in higher probabilities of response at all follow-up timepoints as well as significantly lower transfusion requirement. CONCLUSION: Off-the-shelf BKV-CTLs are a safe and effective therapy for the management of patients with BKV-HC after AHSCT.


Assuntos
Cistite/tratamento farmacológico , Transtornos Hemorrágicos/tratamento farmacológico , Linfócitos T Citotóxicos/metabolismo , Alotransplante de Tecidos Compostos Vascularizados/efeitos adversos , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
2.
J Immunother Cancer ; 9(2)2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33637601

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) are being used after allogeneic hematopoietic stem cell transplantation (alloHCT) to reverse immune dysfunction. However, a major concern for the use of ICIs after alloHCT is the increased risk of graft-versus-host disease (GVHD). We analyzed the association between GVHD prophylaxis and frequency of GVHD in patients who had received ICI therapy after alloHCT. METHODS: A retrospective study was performed in 21 patients with acute myeloid leukemia (n=16) or myelodysplastic syndromes (n=5) who were treated with antiprogrammed cell death protein 1 (16 patients) or anticytotoxic T lymphocyte-associated antigen 4 (5 patients) therapy for disease relapse after alloHCT. Associations between the type of GVHD prophylaxis and incidence of GVHD were analyzed. RESULTS: Four patients (19%) developed acute GVHD. The incidence of acute GVHD was associated only with the type of post-transplantation GVHD prophylaxis; none of the other variables included (stem cell source, donor type, age at alloHCT, conditioning regimen and prior history of GVHD) were associated with the frequency of acute GVHD. Twelve patients received post-transplantation cyclophosphamide (PTCy) for GVHD prophylaxis. Patients who received PTCy had a significantly shorter median time to initiation of ICI therapy after alloHCT compared with patients who did not receive PTCy (median 5.1 months compared with 26.6 months). Despite early ICI therapy initiation, patients who received PTCy had a lower observed cumulative incidence of grades 2-4 acute GVHD compared with patients who did not receive PTCy (16% compared with 22%; p=0.7). After controlling for comorbidities and time from alloHCT to ICI therapy initiation, the analysis showed that PTCy was associated with a 90% reduced risk of acute GVHD (HR 0.1, 95% CI 0.02 to 0.6, p=0.01). CONCLUSIONS: ICI therapy for relapsed acute myeloid leukemia/myelodysplastic syndromes after alloHCT may be a safe and feasible option. PTCy appears to decrease the incidence of acute GVHD in this cohort of patients.

3.
Br J Haematol ; 193(2): 216-230, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33216984

RESUMO

Chimeric antigen receptor (CAR) T cells are a rapidly emerging form of cancer treatment, and have resulted in remarkable responses in refractory lymphoid malignancies. However, their widespread clinical use is limited by toxicity related to cytokine release syndrome and neurotoxicity, the logistic complexity of their manufacturing, cost and time-to-treatment for autologous CAR-T cells, and the risk of graft-versus-host disease (GvHD) associated with allogeneic CAR-T cells. Natural killer (NK) cells have emerged as a promising source of cells for CAR-based therapies due to their ready availability and safety profile. NK cells are part of the innate immune system, providing the first line of defence against pathogens and cancer cells. They produce cytokines and mediate cytotoxicity without the need for prior sensitisation and have the ability to interact with, and activate other immune cells. NK cells for immunotherapy can be generated from multiple sources, such as expanded autologous or allogeneic peripheral blood, umbilical cord blood, haematopoietic stem cells, induced pluripotent stem cells, as well as cell lines. Genetic engineering of NK cells to express a CAR has shown impressive preclinical results and is currently being explored in multiple clinical trials. In the present review, we discuss both the preclinical and clinical trial progress made in the field of CAR NK-cell therapy, and the strategies to overcome the challenges encountered.


Assuntos
Imunidade Inata/efeitos dos fármacos , Imunoterapia Adotiva/efeitos adversos , Células Matadoras Naturais/imunologia , Neoplasias/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Aloenxertos , Ensaios Clínicos como Assunto , Síndrome da Liberação de Citocina/induzido quimicamente , Engenharia Genética/métodos , Doença Enxerto-Hospedeiro/induzido quimicamente , Humanos , Imunoterapia/métodos , Imunoterapia Adotiva/economia , Imunoterapia Adotiva/métodos , Células-Tronco Pluripotentes Induzidas/imunologia , Células-Tronco Pluripotentes Induzidas/transplante , Síndromes Neurotóxicas/etiologia , Receptores de Antígenos Quiméricos/administração & dosagem , Segurança , Tempo para o Tratamento/estatística & dados numéricos
4.
Adv Exp Med Biol ; 1342: 143-192, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34972965

RESUMO

The past decade has witnessed a revolution in the development of immune checkpoint inhibitors for the treatment of multiple tumor types, including genitourinary cancers. Immune checkpoint inhibitors have notably improved the treatment outcomes of patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma. In prostate cancer, the role of immunotherapy with checkpoint inhibitors is not yet established except for microsatellite instability high (MSI-H) tumors. Other immunotherapeutic approaches that have been explored in these malignancies include cytokines, vaccines, and cellular therapy. Ongoing studies are exploring the use of immunotherapy combinations as well as combination with chemotherapy and targeted therapy in these types of tumors. The use of immunotherapy beyond the metastatic setting is an active area of research. Moreover, there is great interest in biomarker development to predict response to immunotherapy and risk of toxicity. This book chapter is a comprehensive review of immunotherapeutic approaches, both approved and investigational, for the treatment of renal cell carcinoma, urothelial carcinoma, and prostate cancer.


Assuntos
Carcinoma de Células Renais , Carcinoma de Células de Transição , Neoplasias Renais , Neoplasias da Bexiga Urinária , Carcinoma de Células Renais/terapia , Humanos , Imunoterapia , Neoplasias Renais/terapia , Masculino
5.
Blood Adv ; 4(24): 6117-6126, 2020 12 22.
Artigo em Inglês | MEDLINE | ID: mdl-33351107

RESUMO

In relapsed/refractory acute myeloid leukemia (AML), the prognostic impact of complete remission (CR) and measurable residual disease (MRD) negativity is not well established. We retrospectively analyzed 141 patients with relapsed/refractory AML who received first salvage therapy and had MRD assessed by multiparameter flow cytometry at the time of response. Patients who achieved CR with full hematologic recovery as best response vs those with incomplete hematology recovery had lower cumulative incidence of relapse (P = .01) and better relapse-free survival (P = .004) but not overall survival (P = .15); a similar trend was observed in patients who achieved MRD negativity vs those who were MRD positive (P = .01, P = .05, and P = .21, respectively). By multivariate analysis, CR and MRD negativity were each independently associated with lower cumulative incidence of relapse (P = .001 and P = .003, respectively) and better relapse-free survival (P < .001 and P = .02) but not overall survival. Patients who achieved CR with MRD negativity had the lowest rates of relapse and best survival (2-year overall survival rate, 37%), which was driven largely by lower rates of early relapse and an increased ability in this group to undergo hematopoietic stem cell transplantation (HSCT); however, post-HSCT outcomes were similar regardless of response to salvage chemotherapy. Overall, in patients with relapsed/refractory AML, CR with MRD negativity was associated with the best outcomes, supporting it as the optimal response in this setting.


Assuntos
Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasia Residual , Prognóstico , Indução de Remissão , Estudos Retrospectivos
6.
Blood ; 136(4): 401-409, 2020 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-32526029

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-SCT) offers cure for a variety of conditions, in particular, but not limited to, hematologic malignancies. However, it can be associated with life-threatening complications, including graft-versus-host disease (GVHD) and infections, which are factors limiting its widespread use. Technical advances in the field of microbiome research have allowed for a better understanding of the microbial flora of the human intestine, as well as dissection of their interactions with the host immune system in allo-SCT and posttransplant complications. There is growing evidence that the commensal microbiome is frequently dysregulated following allo-SCT and that this dysbiosis can predispose to adverse clinical outcomes, especially including acute intestinal GVHD and reduced overall survival. In this review, we discuss the interactions between the microbiome and the components of the immune system that play a major role in the pathways leading to the inflammatory state of acute intestinal GVHD. We also discuss the microbiome-centered strategies that have been devised or are actively being investigated to improve the outcomes of allo-SCT patients in regard to acute intestinal GVHD.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro/microbiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Doença Aguda , Disbiose , Doença Enxerto-Hospedeiro/etiologia , Humanos , Transplante Homólogo
7.
Adv Exp Med Biol ; 1244: 107-147, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32301013

RESUMO

The past decade has witnessed a revolution of immune checkpoint inhibitors in the treatment of multiple tumor types, including genitourinary cancers. Immune checkpoint inhibitors improved the treatment outcomes of patients with metastatic renal cell carcinoma and metastatic urothelial carcinoma. In prostate cancer, the role of immunotherapy with checkpoint inhibitors is not yet established, but clinical trials investigating their use are ongoing. Other immunotherapeutic approaches that have been explored in these malignancies include cytokines, vaccines, and cellular therapy. Ongoing studies are exploring the use of immunotherapy combinations as well as combination with chemotherapy and targeted therapy in these types of tumors. The use of immunotherapy beyond the metastatic setting is an active area of research. Moreover, there is a great interest in biomarker development to predict response to immunotherapy and risk of toxicity. This chapter is a comprehensive review of the immunotherapeutic approaches, both approved and investigational, for the treatment of renal cell carcinoma, urothelial carcinoma, and prostate cancer.


Assuntos
Imunoterapia , Neoplasias Urogenitais/terapia , Antígeno B7-H1/antagonistas & inibidores , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Humanos , Neoplasias Renais/imunologia , Neoplasias Renais/terapia , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Neoplasias Urogenitais/imunologia
8.
Br J Haematol ; 188(2): 207-223, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31566728

RESUMO

The past decade has witnessed tremendous progress in the treatment of acute lymphoblastic leukaemia (ALL), primarily due to the development of targeted therapies, including tyrosine kinase inhibitors targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20 and CD22), bispecific antibodies and chimeric antigen receptor T- cell therapy. A number of new therapies have been approved by the US Food and Drug Administration in the past 5 years, including blinatumomab in 2014, inotuzumab ozagamicin in 2017 and tisagenlecleucel in 2017 for relapsed/refractory ALL. This has led to tremendous improvement in long-term survival, of more than 50% in patients with precursor B-ALL [50-70% in patients with Philadelphia chromosome (Ph)-positive ALL)], 50-60% in T-ALL and 80% in mature B-ALL. Research is ongoing to optimize the benefit of targeted therapeutics with the goal of decreasing the use of cytotoxic therapies.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Antineoplásicos Imunológicos/farmacologia , Humanos , Pessoa de Meia-Idade , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia
10.
Best Pract Res Clin Haematol ; 32(2): 163-176, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31203998

RESUMO

Myelodysplastic syndromes and acute myeloid leukemia are sporadic for the majority of cases affecting the elderly population. Inherited cases, however, do occur. Genetic predispositions to myeloid malignancies can be classified into three categories: familial cancer syndromes associated with increased risk of various malignancies including myelodysplasia and acute myeloid leukemia such as Li-Fraumeni syndrome and constitutional mismatch repair deficiency (CMMRD); germline mutations conferring a specific increased risk of myelodysplastic syndrome and acute myeloid leukemia such as mutations in ANKRD26, CEBPA, DDX41, ETV6, GATA2, RUNX1, SRP72 genes; and finally primarily pediatric inherited bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, severe congenital neutropenia, Shwachman-Diamond syndrome and Diamond Blackfan anemia. The recognition of these germline syndromes is essential in the management and follow-up of patients. Herein, we review the conditions associated with hereditary myeloid leukemia with a special clinical focus on management and monitoring.


Assuntos
Mutação em Linhagem Germinativa , Neoplasias Hematológicas , Transtornos Mieloproliferativos , Proteínas de Neoplasias , Síndromes Neoplásicas Hereditárias , Neoplasias Hematológicas/diagnóstico , Neoplasias Hematológicas/genética , Neoplasias Hematológicas/metabolismo , Neoplasias Hematológicas/terapia , Humanos , Transtornos Mieloproliferativos/diagnóstico , Transtornos Mieloproliferativos/genética , Transtornos Mieloproliferativos/metabolismo , Transtornos Mieloproliferativos/terapia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Síndromes Neoplásicas Hereditárias/diagnóstico , Síndromes Neoplásicas Hereditárias/genética , Síndromes Neoplásicas Hereditárias/metabolismo , Síndromes Neoplásicas Hereditárias/terapia
12.
Leuk Lymphoma ; 60(11): 2606-2621, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31092071

RESUMO

Acute lymphoblastic leukemia (ALL) is a heterogeneous disease with a bimodal distribution. The progresses made in understanding its biology led to the development of targeted therapies. In this review, we summarize the current and future approaches in management of adult ALL. Tyrosine kinase inhibitors (TKI) targeting BCR-ABL1 tyrosine kinase, monoclonal antibodies targeting cell surface antigens (CD19, CD20, and CD22), bispecific antibodies, and chimeric antigen receptor (CAR)-T therapy are breakthrough treatments. They resulted in FDA approvals of blinatumomab in 2014, inotuzumab ozagamicin in 2017, and tisagenlecleucel in 2017 for relapsed/refractory ALL. Currently, long-term survival is achieved in more than 50% of patients with precursor B-ALL (50-70% in patients with Philadelphia chromosome (Ph)-positive ALL), 50-60% T-ALL, and 80% mature B-ALL. Ongoing efforts exist to optimize therapeutic options in both the relapsed/refractory as well as the frontline settings. In the era of precision medicine, the future lies in using less cytotoxic and more targeted agents.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Antineoplásicos/uso terapêutico , Imunoterapia Adotiva/métodos , Imunoterapia/métodos , Terapia de Alvo Molecular/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Animais , Terapia Combinada , Humanos , Leucemia-Linfoma Linfoblástico de Células Precursoras/imunologia , Leucemia-Linfoma Linfoblástico de Células Precursoras/patologia , Prognóstico
13.
Curr Opin Oncol ; 31(3): 207-215, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30844889

RESUMO

PURPOSE OF REVIEW: Advanced urothelial carcinoma is a heterogeneous disease with high burden of morbidity, mortality, and cost. Significant progress has been made in understanding the biology of the disease and the development of immunotherapies and targeted therapies. In this review, we summarize the current and future therapeutic approaches in the management of urothelial carcinoma. RECENT FINDINGS: Advances in immune checkpoint inhibitors resulted in the Food and Drug Administration (FDA) approvals of atezolizumab in 2016, and pembrolizumab, avelumab, durvalumab, and nivolumab in 2017 for the treatment of advanced urothelial carcinoma. More recently, development of inhibitors targeting the fibroblast growth factor receptor genetic alterations and antibody-drug conjugates targeting specific cell surface antigens (trop2, nectin4, and SLITRK6) resulted in several FDA breakthrough designations for urothelial carcinoma. CONCLUSION: The development of novel therapies targeting the immune and molecular pathways of advanced urothelial carcinoma is promising for the improvement of outcomes in this lethal disease. Ongoing efforts are poised to optimize therapeutic options in the post-chemotherapy arena. In the era of precision medicine, the future of urothelial carcinoma lies in using less cytotoxic chemotherapy, more targeted therapy and immunotherapy, and possibly a combination of these therapeutic approaches.


Assuntos
Neoplasias Urológicas/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/imunologia , Carcinoma/metabolismo , Humanos , Terapia de Alvo Molecular , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptores de Fatores de Crescimento/antagonistas & inibidores , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias Urológicas/imunologia , Neoplasias Urológicas/metabolismo
14.
Am J Clin Oncol ; 42(3): 317-329, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30557165

RESUMO

Multiple myeloma (MM) is a B-cell malignancy characterized by the abnormal proliferation of clonal plasma cells in the bone marrow leading to end-organ manifestations. Despite the advancement in the therapy and care of patients with MM, relapse and resistance to standard therapy remain significant. The development of immunotherapy as a treatment modality for many types of cancers has led investigators to explore its use in MM in order to elicit myeloma-targeted immune responses, especially given that immune dysregulation is an underlying feature in the pathogenesis and progression of MM. In this concise review, we discuss the different advances in the immune-based therapy of MM, from immunomodulation, vaccines, to monoclonal antibodies, checkpoint inhibitors, adoptive T-cell therapies, and future promising therapies under investigation.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Imunoterapia/métodos , Mieloma Múltiplo/imunologia , Mieloma Múltiplo/prevenção & controle , Humanos , Prognóstico
15.
Head Neck ; 41(5): 1220-1226, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30537085

RESUMO

BACKGROUND: Our objective was to determine the effect of post-diagnosis aspirin use on survival in veterans with head and neck squamous cell carcinoma. METHODS: Retrospective cohort study of 584 veterans with head and neck squamous cell carcinoma treated at the Washington DC VA Medical Center between 1995 and 2015. Charts were queried for clinical-pathologic data, aspirin prescriptions, and outcome. The Kaplan-Meier method was used to determine overall survival (OS) and disease-specific survival (DSS) among aspirin users and nonusers. RESULTS: A total of 329 patients met inclusion criteria. Primary subsites included oropharynx (n = 143), larynx (n = 105), oral cavity (n = 62), and hypopharynx (n = 19). Eighty-four patients were aspirin users (25.5%). Aspirin users demonstrated significantly better 3-year OS and DSS (78.6% and 88.1%) compared to nonaspirin users (OS: 55.9% and DSS: 70.2%; P = .0003 and P = .0019, respectively). On multivariate analysis, aspirin use remained independently associated with improved survival. CONCLUSION: Aspirin use following diagnosis and curative treatment of head and neck squamous cell carcinoma is associated with improved OS and DSS.


Assuntos
Aspirina/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Veteranos , Idoso , Carcinoma de Células Escamosas/mortalidade , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Análise de Sobrevida , Estados Unidos
16.
Biol Blood Marrow Transplant ; 24(6): 1250-1259, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29412158

RESUMO

Allogeneic hematopoietic stem cell transplantation (HSCT) reverses the bone marrow failure syndrome due to GATA2 deficiency. The intensity of conditioning required to achieve reliable engraftment and prevent relapse remains unclear. Here, we describe the results of a prospective study of HSCT in 22 patients with GATA2 deficiency using a busulfan-based conditioning regimen. The study included 2 matched related donor (MRD) recipients, 13 matched unrelated donor (URD) recipients, and 7 haploidentical related donor (HRD) recipients. MRD and URD recipients received 4 days of busulfan and 4 days of fludarabine. HRD recipients received low-dose cyclophosphamide for 2 days, fludarabine for 5 days, 2 to 3 days of busulfan depending on cytogenetics, and 200 cGy total body irradiation. MRD and URD recipients received tacrolimus and short-course methotrexate for graft-versus-host disease (GVHD) prophylaxis. HRD recipients received high-dose post-transplant cyclophosphamide (PTCy) followed by tacrolimus and mycophenolate mofetil. At a median follow-up of 24 months (range, 9 to 50), 19 of 22 patients were alive with reversal of the disease phenotype and correction of the myelodysplastic syndrome, including eradication of cytogenetic abnormalities. Three patients died: 1 from refractory acute myelogenous leukemia, 1 from GVHD, and 1 from sepsis. There was a 26% incidence of grades III to IV acute GVHD in the MRD and URD groups and no grades III to IV acute GVHD in the HRD cohort. Similarly, there was a 46% incidence of chronic GVHD in the MRD and URD cohorts, whereas only 28% of HRD recipients developed chronic GVHD. Despite excellent overall disease-free survival (86%), GVHD remains a limitation using standard prophylaxis for GVHD. We are currently extending the use of PTCy to the MRD and URD cohorts to reduce GVHD.


Assuntos
Bussulfano/uso terapêutico , Deficiência de GATA2/terapia , Transplante de Células-Tronco Hematopoéticas/métodos , Condicionamento Pré-Transplante/métodos , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Deficiência de GATA2/mortalidade , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Doadores de Tecidos , Transplante Homólogo , Adulto Jovem
17.
Hematol Oncol Stem Cell Ther ; 11(1): 1-12, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28549767

RESUMO

More effective therapies are emerging, with better toxicity profiles, and are being incorporated into modern treatment algorithms of chronic lymphocytic leukemia at various stages of the disease, including for patients harboring Del17p and/or aberrant TP53. Ibrutinib, an inhibitor of Bruton's tyrosine kinase, has demonstrated impressive response rates in the relapsed/refractory setting, including in the setting of Del17p and/or TP53 mutations. Venetoclax, an inhibitor of BCL-2 known to play an important role in regulating cell death, has been approved recently for treatment of patients with chronic lymphocytic leukemia with Del17p who have received at least one prior therapy. Unfortunately, a cure remains unattainable unless eligible patients are offered an allogeneic hematopoietic cell transplant. However, hematopoietic cell allografting is limited by the availability of suitable donors and significant morbidity and mortality. Recent clinical practice recommendations by the American Society for Blood and Marrow Transplantation have relegated the role of transplantation to later stages of the disease. In patients with evidence of Richter syndrome, frontline consolidation allogeneic hematopoietic cell transplantation remains the most desirable approach owing to the limited activity of ibrutinib or other novel therapies. Further therapeutic advances would require enrolling these patients in large clinical trials that evaluate novel therapies alone or in combination with traditional chemotherapies or even in the setting of posttransplant consolidation/maintenance.


Assuntos
Compostos Bicíclicos Heterocíclicos com Pontes/uso terapêutico , Deleção Cromossômica , Transplante de Células-Tronco Hematopoéticas , Leucemia Linfocítica Crônica de Células B , Pirazóis/uso terapêutico , Pirimidinas/uso terapêutico , Síndrome de Smith-Magenis , Sulfonamidas/uso terapêutico , Proteína Supressora de Tumor p53/genética , Adenina/análogos & derivados , Aloenxertos , Cromossomos Humanos Par 17 , Humanos , Leucemia Linfocítica Crônica de Células B/genética , Leucemia Linfocítica Crônica de Células B/terapia , Piperidinas
18.
Case Rep Hematol ; 2017: 9561013, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29090101

RESUMO

Clinical Practice Points. Plasmablastic lymphoma (PBL) is a rare and highly aggressive variant of diffuse large B cell lymphoma with median survival of advanced stage patients varying between 6 and 15 months in previous reports. We report here a human immunodeficiency virus-infected patient surviving over 12 years following treatment for advanced PBL with EPOCH chemotherapy and intrathecal therapy. This case highlights the potential for improved survival in PBL with intensive chemotherapy. Further, literature review suggests promising prospects utilizing novel targeted therapies to increase the rate of prolonged responses.

19.
Biomedicines ; 5(4)2017 10 11.
Artigo em Inglês | MEDLINE | ID: mdl-29019937

RESUMO

Although significant advances have been made in the biologic understanding of graft-versus-host disease (GVHD) and its treatment options, GVHD remains the single most challenging obstacle to the success of allogeneic hematopoietic cell transplantation (HCT) due to high risk of disabling morbidity and mortality. Extracorporeal photopheresis (ECP) has promising effects in controlling steroid-refractory GVHD, both acute and chronic, and it has been studied extensively. Its putative immunomodulatory mechanisms, while not immunosuppressive, position ECP as an attractive treatment strategy for GVHD patients who are already receiving global immunosuppression. However, ECP is relatively underutilized due in part to limited access and time commitment. Here, we review the recent findings on the ECP efficacy in both acute and chronic GVHD, primarily for steroid-refractory status, and we critically appraise its benefits. We also explore salient considerations on the optimal use of ECP in the treatment of refractory GVHD.

20.
Cureus ; 9(5): e1207, 2017 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-28580204

RESUMO

Post-transfusion purpura is a rare transfusion-related complication that often goes undiagnosed. It is due to alloimmunization against platelet antigens which leads to acute profound thrombocytopenia following the transfusion of any platelet-containing product (red blood cells or platelets). It is commonly seen in multiparous women. Here, we report a case of post-transfusion purpura in a 56-year-old multiparous woman who developed acute thrombocytopenia seven days following a packed red blood cell transfusion. We will discuss the clinical presentation, diagnosis, workup and treatment of this rare disease. It is important to recognize this entity separately and to include it in the differential diagnosis of acute thrombocytopenia after a recent blood transfusion. Treatment for this condition consists of intravenous immunoglobulins, corticosteroids or plasmapheresis.

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