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1.
Artigo em Inglês | MEDLINE | ID: mdl-38871963

RESUMO

Disparities in access to hematopoietic cell transplant (HCT) are well established. Prior studies have identified barriers, such as referral and travel to an HCT center, that occur before consultation. Whether differences in access persist after evaluation at an HCT center remains unknown. The psychosocial assessment for transplant eligibility may impede access to transplant after evaluation. We performed a single-center retrospective review of 1102 patients who underwent HCT consultation. We examined the association between race/ethnicity (defined as Hispanic, non-Hispanic Black, non-Hispanic White, and Other) and socioeconomic status (defined by zip code median household income quartiles and insurance type) with receipt of HCT and Psychosocial Assessment of Candidates for Transplantation (PACT) scores. Race/ethnicity was associated with receipt of HCT (p = 0.02) with non-Hispanic Whites comprising a higher percentage of HCT recipients than non-recipients. Those living in higher income quartiles and non-publicly insured were more likely to receive HCT (p = 0.02 and p < 0.001, respectively). PACT scores were strongly associated with income quartiles (p < 0.001) but not race/ethnicity or insurance type. Race/ethnicity and socioeconomic status impact receipt of HCT among patients evaluated at an HCT center. Further investigation as to whether the psychosocial eligibility evaluation limits access to HCT in vulnerable populations is warranted.

2.
World J Gastroenterol ; 29(43): 5865-5871, 2023 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-38074918

RESUMO

BACKGROUND: Patients with autoimmune conditions receiving immunosuppressants are at risk of non-Hodgkin lymphomas (NHL). Vedolizumab (anti-α4ß7-integrin antibody), a treatment-of-choice for Crohn's disease (CD), reduces inflammatory lymphocyte trafficking into the intestinal mucosa. This effect is believed to be confined to the colon. CASE SUMMARY: We report the case of a CD patient on vedolizumab for five years who developed pediatric-type follicular lymphoma. Work-up prior to therapy revealed a reduction in circulating T-lymphocytes and their suppressed response to mitogens. Rituximab, cyclophosphamide, vincristine, and prednisone chemo-immunotherapy resulted in durable lymphoma remission, and vedolizumab treatment was continued. While the patient's T-lymphocyte population and immunoglobulin production recovered, the T-lymphocyte mitogen response remained suppressed. CONCLUSION: This patient's NHL may be linked to receiving anti-α4ß7 therapy. Further research could be beneficial to determine if proactive surveillance for NHL and other systemic diseases is indicated in patients on vedolizumab.


Assuntos
Doença de Crohn , Linfoma Folicular , Criança , Humanos , Doença de Crohn/diagnóstico , Doença de Crohn/tratamento farmacológico , Linfoma Folicular/tratamento farmacológico , Rituximab/uso terapêutico , Imunossupressores/uso terapêutico , Integrinas , Fármacos Gastrointestinais/efeitos adversos
4.
Blood Adv ; 7(13): 3225-3231, 2023 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-36897253

RESUMO

Outcomes for children and adolescents with relapsed and refractory Hodgkin lymphoma (HL) are poor, with ∼50% of patients experiencing a subsequent relapse. The anti-CD30 antibody-drug conjugate brentuximab vedotin improved progression-free survival (PFS) when used as consolidation after autologous stem cell transplantation (ASCT) in adults with high-risk relapsed/refractory HL. Data on brentuximab vedotin as consolidative therapy after ASCT in pediatric patients with HL are extremely limited, with data of only 11 patients reported in the literature. We performed a retrospective analysis of 67 pediatric patients who received brentuximab vedotin as consolidation therapy after ASCT for the treatment of relapsed/refractory HL to describe the experience of this regimen in the pediatric population. This is the largest cohort reported to date. We found that brentuximab vedotin was well tolerated with a safety profile similar to that of adult patients. With a median follow-up of 37 months, the 3-year PFS was 85%. These data suggest a potential role for the use of brentuximab vedotin as consolidation therapy after ASCT for children with relapsed/refractory HL.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Adulto , Adolescente , Humanos , Criança , Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Transplante Autólogo , Estudos Retrospectivos
5.
J Bone Oncol ; 36: 100454, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36204417

RESUMO

Background: Langerhans cell histiocytosis (LCH) is a rare monoclonal histiocytic neoplasm. Little is known about clinical factors associated with LCH single- vs multi-system involvement at the time of diagnosis. Methods: Data on 1549 LCH patients diagnosed between years 2010 and 2018 were extracted from the Surveillance, Epidemiology and End Results Program. Patterns of single- vs multisystem involvement were examined using multivariable logistic regression analysis. Odd ratio (OR) and 95% confidence interval (CI) were reported. Results: 968 children and adolescents (0-19 years; median: 4 years) and 581 adults (≥20 years; median: 49 years) were included in the analysis. Multi-system LCH was reported for 30.9 % patients. Bone marrow (BM) (OR = 3.776; 95 %CI = 1.939-7.351; P < 0.001) and lymph node (LN) (OR = 3.274; 95 %CI = 1.443-7.427; P = 0.005) involvement were most commonly associated with multi-system LCH at the time of diagnosis; similar pattern was also observed in adult patients (OR = 17.780; 95 %CI = 6.469-48.867; P < 0.001 for BM LCH; and OR = 5.156; 95 %CI = 2.131-12.471; P < 0.001 for LN LCH). Among pediatric patients, craniofacial osseous LCH was more likely to be treated with surgery (OR = 2.822; 95 %CI = 1.199-6.639; P = 0.018) compared to skeletal lesions in other sites, whereas vertebral body LCH was less likely to be treated with surgery (OR = 0.175; 95 %CI = 0.058-0.527; P = 0.002). In pediatric patients with bone LCH, the non-white patients were less likely to be treated surgically compared to the white patients (OR = 0.470; 95 %CI = 0.272-0.812; P = 0.007). Conclusions: BM and LN LCH are associated with the highest risks of multi-system disease, which may require active surveillance. Furthermore, active attempts are needed to mitigate the racial disparity in surgery utilization in pediatric patients with skeletal LCH.

7.
Pediatr Blood Cancer ; 69(6): e29649, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35338689

RESUMO

Patients with therapy-refractory or high-risk relapsed classical Hodgkin lymphoma are typically treated with the high-dose chemotherapy and autologous stem cell transplantation (HDC/ASCT) to consolidate the response to salvage therapy. The combination of brentuximab vedotin with gemcitabine has recently been shown to be an effective and safe salvage regimen. While the majority of patients with complete responses to this regimen ultimately underwent HDC/ASCT consolidation, four subjects, reported herein, achieved durable complete remissions lasting more than 4 years after the study treatment but without ASCT consolidation. Further investigation of treatment strategies incorporating targeted agents may allow omission of HDC/ASCT for select patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin , Imunoconjugados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Brentuximab Vedotin , Criança , Desoxicitidina/análogos & derivados , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/patologia , Humanos , Imunoconjugados/uso terapêutico , Recidiva Local de Neoplasia/tratamento farmacológico , Terapia de Salvação , Transplante de Células-Tronco , Transplante Autólogo , Gencitabina
8.
J Pediatr Hematol Oncol ; 44(7): e1006-e1015, 2022 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-35082244

RESUMO

Langerhans cell histiocytosis (LCH) is a disorder with highly diverse clinical manifestations. We explored if age, sex, race, organ system involved, and therapy approaches determine patient survival in the era of modern treatments. LCH patient data reported to the Surveillance, Epidemiology, and End Results (SEER) program in 2010-2016 (n=1282; age: 0 to 100 y) was analyzed. Age-specific LCH incidence flattening to a low level suggests an age cutoff for pediatric patients of 20 years. The overall survival probability is lower for patients 21 to 100 years old ( P <0.0001), irrespective of sex and race. The commonest sites involved in the 0- to 20-year age group were bone, skin, and bone marrow; this shifted to lung, bone, and skin as the commonest disease sites in patients 21 to 100 years of age. The treatments applied differed between age groups, as younger versus older patients were more likely to receive chemotherapy-based treatment (48.4% vs. 17%; P <0.0001). There also was a trend toward nonwhite versus white patients being less likely to receive chemotherapy-based treatment (31.7% vs. 38.2%; P =0.067). Whereas there are treatment disparities related to LCH patient age and perhaps race, patient age is the strongest predictor of survival, with patients 21 to 100 years of age with lung, lymph node, skin, and bone marrow disease having the worst outcomes ( P <0.0001).


Assuntos
Doenças da Medula Óssea , Histiocitose de Células de Langerhans , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Osso e Ossos/patologia , Criança , Pré-Escolar , Histiocitose de Células de Langerhans/epidemiologia , Histiocitose de Células de Langerhans/patologia , Histiocitose de Células de Langerhans/terapia , Humanos , Incidência , Lactente , Recém-Nascido , Linfonodos/patologia , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
10.
J Natl Compr Canc Netw ; 19(11): 1277-1303, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34781268

RESUMO

Histiocytic neoplasms are rare hematologic disorders accounting for less than 1% of cancers of the soft tissue and lymph nodes. Clinical presentation and prognosis of these disorders can be highly variable, leading to challenges for diagnosis and optimal management of these patients. Treatment often consists of systemic therapy, and recent studies support use of targeted therapies for patients with these disorders. Observation ("watch and wait") may be sufficient for select patients with mild disease. These NCCN Guidelines for Histiocytic Neoplasms include recommendations for diagnosis and treatment of adults with the most common histiocytic disorders: Langerhans cell histiocytosis, Erdheim-Chester disease, and Rosai-Dorfman disease.


Assuntos
Doença de Erdheim-Chester , Neoplasias Hematológicas , Histiocitose de Células de Langerhans , Histiocitose Sinusal , Adulto , Doença de Erdheim-Chester/tratamento farmacológico , Histiocitose de Células de Langerhans/diagnóstico , Histiocitose de Células de Langerhans/tratamento farmacológico , Histiocitose de Células de Langerhans/patologia , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/tratamento farmacológico , Histiocitose Sinusal/patologia , Humanos , Prognóstico
12.
Cureus ; 13(5): e14922, 2021 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-34123621

RESUMO

Acute promyelocytic leukemia (APML), characterized by the reciprocal translocation between chromosomes 15 and 17 [t(15;17)], is a result of proliferation of myeloid cells maturation which is interrupted at the promyelocytic stage. The central, and the most important, distinguishing feature of APML is a predisposition to disseminated intravascular coagulation (DIC). The overall prognosis of APML is very good, with 90% of patients achieving complete remission. We find it important to remind pediatric practitioners, both in the ambulatory and urgent care room settings, of presenting signs and symptoms of leukemia, as well as, up-to-date on management of such fulminant scenarios as DIC. Intracranial hemorrhage (ICH) is one of the commonest, and frequently fulminant complication of APML seen after initiation of induction chemotherapy. We report on a young female presenting with non-specific upper respiratory illness symptoms and recurrent headache, who was found to already have ICH and to be in DIC in the setting of APML at the time of initial evaluation. This case illustrates importance of thorough assessment and prompt consideration of wide differential diagnosis, which became somewhat limited and biased towards web-based telemedicine in the COVID-19 pandemics era.

14.
Oncoimmunology ; 10(1): 1893500, 2021 03 11.
Artigo em Inglês | MEDLINE | ID: mdl-33763293

RESUMO

The role of T cells in controlling human cancers is well known. Their success requires continued persistence in vivo and efficient trafficking to tumor sites, requirements shared by other effectors such as Natural Killer (NK) cells. To date, cytokine IL2 remains the only clinically approved cytokine therapy available to expand, maintain, and activate these effector lymphoid cells, but toxicities can be severe. Cytokine IL15 offers similar T cell proliferation and activation properties, but without the unwanted side-effects seen with IL2. Several IL15-cytokine fusion proteins have been developed to improve their in vivo function, typically exploiting the IL15Rα to complex with IL15, to extend serum half-life and increase affinity for IL15ß receptor on immune cells. Here we describe a novel IL15 complex incorporating the full-length IL15Rα to complex with wild type IL15 to form spontaneous trimers of dimers (6 IL15 + 6 IL15Rα) during co-expression, resulting in a substantial increase in serum half-life and enhancement of in vivo cytokine effect on IgG or T cell engaging antibody-dependent cell-mediated cytotoxicities, when compared to alternative strategies.


Assuntos
Subunidade alfa de Receptor de Interleucina-15 , Neoplasias , Linhagem Celular Tumoral , Humanos , Imunoterapia , Interleucina-15/genética , Células Matadoras Naturais , Neoplasias/tratamento farmacológico
18.
Pediatr Hematol Oncol ; 37(2): 176-183, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31971458

RESUMO

Cytotoxic T-lymphocyte-associated protein 4 (CTLA4) haploinsufficiency (HI) is an immune dysregulation disorder characterized by T lymphocyte hyperactivation, and generalized lymphoproliferative and autoimmune disorders. Patients with CTLA4 haploinsufficiency are also prone to developing various malignancies. Due to the rare nature of this condition, the longitudinal evolution of CTLA4 haploinsufficiency clinical manifestations remains to be described. We report on over a decade-long course of a young adult men patient with known CTLA4 haploinsufficiency, who sequentially developed multiple autoimmune conditions along with two distinct episodes of classical Hodgkin Lymphoma (cHL) of unique histologies. Notably, the patient had serological and molecular evidence of Epstein Barr virus (EBV) infection at the time of diagnosis of both cHL. The allogeneic stem cell transplantation consolidated durable remission of cHL and CTLA-4 haploinsufficiency-related clinical manifestations, but failed to enable the patient to permanently suppress EBV viremia, which raises concerns for the development of other EBV infection-related conditions in the future. This case report adds on the current understanding of the natural clinical history of patients with CTLA4 haploinsufficiency, and their unique susceptibility to developing cHL.


Assuntos
Antígeno CTLA-4/genética , Doença de Hodgkin/genética , Adulto , Criança , Predisposição Genética para Doença , Haploinsuficiência , Doença de Hodgkin/patologia , Humanos , Masculino
20.
Cancer Immunol Immunother ; 60(12): 1789-800, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21792658

RESUMO

The huKS-IL2 immunocytokine (IC) consists of IL2 fused to a mAb against EpCAM, while the hu14.18-IL2 IC recognizes the GD2 disialoganglioside. They are under evaluation for treatment of EpCAM(+) (ovarian) and GD2(+) (neuroblastoma and melanoma) malignancies because of their proven ability to enhance tumor cell killing by antibody-dependent cell-mediated cytotoxicity (ADCC) and by antitumor cytotoxic T cells. Here, we demonstrate that huKS-IL2 and hu14.18-IL2 bind to tumor cells via their antibody components and increase adhesion and activating immune synapse (AIS) formation with NK cells by engaging the immune cells' IL-2 receptors (IL2R). The NK leukemia cell line, NKL (which expresses high affinity IL2Rs), shows fivefold increase in binding to tumor targets when treated with IC compared to matching controls. This increase in binding is effectively inhibited by blocking antibodies against CD25, the α-chain of the IL2R. NK cells isolated from the peritoneal environment of ovarian cancer patients, known to be impaired in mediating ADCC, bind to huKS-IL2 via CD25. The increased binding between tumor and effector cells via ICs is due to the formation of AIS that are characterized by the simultaneous polarization of LFA-1, CD2 and F-actin at the cellular interface. AIS formation of peritoneal NK and NKL cells is inhibited by anti-CD25 blocking antibody and is 50-200% higher with IC versus the parent antibody. These findings demonstrate that the IL-2 component of the IC allows IL2Rs to function not only as receptors for this cytokine but also as facilitators of peritoneal NK cell binding to IC-coated tumor cells.


Assuntos
Sinapses Imunológicas/imunologia , Imunoterapia/métodos , Subunidade alfa de Receptor de Interleucina-2/imunologia , Interleucina-2/análogos & derivados , Células Matadoras Naturais/imunologia , Anticorpos Monoclonais , Linhagem Celular Tumoral , Separação Celular , Feminino , Citometria de Fluxo , Gangliosídeos/imunologia , Humanos , Interleucina-2/imunologia , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Ativação Linfocitária/imunologia , Microscopia Confocal , Neoplasias Ovarianas/imunologia , Transporte Proteico/imunologia , Proteínas Recombinantes de Fusão
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