RESUMO
It has been increasingly recognized that there is a subset of patients with refractory systemic JIA, who have failed all available medications and may benefit from HSCT. The increasing experience with HSCT in SJIA, suggests that despite the complicated post-HSCT course, short-term, the transplanted patients either achieved SJIA remission or reduced burden of disease. Longer follow-up, however, is needed to better define the long-term outcomes. The discussion at the NextGen 2022 conference was focused on the optimal timing for the procedure, the need for a good control of inflammatory SJIA activity prior to HSCT, and the role of the reduced intensity conditioning regimens as there was a remote concern that such regimens might increase the risk of SJIA relapse after the transplantation. There was unanimous agreement about the importance of long-term registries to address these questions.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Pneumopatias , Humanos , Europa (Continente) , América do Norte , Sistema de Registros , Pneumopatias/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversosRESUMO
PURPOSE: X-linked agammaglobulinemia (XLA) is an inborn error of immunity caused by variants in Bruton's tyrosine kinase (BTK). XLA patients require lifelong immunoglobulin replacement therapy (IgRT). Only few XLA patients are indicated for allogeneic hematopoietic cell transplantation (HCT) because of severe complications. Accordingly, the published transplantation experience in XLA is minimal. We aimed to collect clinical data of XLA patients who received HCT in an international framework and to establish appropriate transplantation criteria and methods for XLA patients. METHODS: XLA patients were recruited through a questionnaire and a literature review. The data are on patient characteristics and transplantation methods and outcomes. RESULTS: In this study, twenty-two XLA patients who underwent HCT were recruited. The indication for HCT was recurrent or life-threatening infection in sixteen patients, malignancy in three, and other factors in three. A myeloablative conditioning, reduced toxicity myeloablative conditioning (RT-MAC), and reduced intensity conditioning (RIC) were selected in four, ten, and eight patients, respectively. Engraftment was achieved in 21 patients (95%). In all patients, 2-year overall survival (OS) and event-free survival (EFS) were 86% and 77%, respectively. In patients who received RT-MAC or RIC using treosulfan, busulfan, or melphalan, 2-year OS and EFS were 82% and 71%, respectively. Finally, twenty-one patients (95%) obtained complete or stable high-level mixed chimerism (50-95%), and the 1-year discontinuation rate of IgRT was 89%. CONCLUSION: Based on the concept in which IgRT is the standard treatment for XLA, HCT may be an effective and safe alternative treatment option for XLA patients, and IgRT can be discontinued following transplantation. It is ideal to perform HCT in XLA patients for whom transplantation is indicated before they develop organ damage.
Assuntos
Agamaglobulinemia , Doenças Genéticas Ligadas ao Cromossomo X , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Transplante de Células-Tronco Hematopoéticas/métodos , Agamaglobulinemia/diagnóstico , Agamaglobulinemia/terapia , Agamaglobulinemia/etiologia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Doenças Genéticas Ligadas ao Cromossomo X/etiologia , Melfalan , Condicionamento Pré-Transplante/métodos , Doença Enxerto-Hospedeiro/etiologiaRESUMO
Systemic juvenile idiopathic arthritis (sJIA) is characterized by arthritis, fever, rash, lymphadenopathy, hepatosplenomegaly, and serositis. Macrophage activation syndrome is the most feared complication of sJIA with a high risk of mortality. We report a 16-year-old female diagnosed with refractory systemic juvenile idiopathic arthritis (sJIA) complicated by recurrent macrophage activation syndrome (MAS), severe joint disease, and lung involvement requiring prolonged immunosuppressive therapy. She received a matched unrelated allogeneic hematopoietic cell transplant (Allo-HCT) using a reduced-intensity conditioning regimen and is now, 3 years after the transplant, with complete resolution of sJIA symptoms, off immunosuppressants, and with significant improvement in the quality of life.
RESUMO
OBJECTIVES: To identify cytokeratins (CK) of significant correlations with clinical and histopathologic prognostic parameters in oral and oropharyngeal squamous cell carcinoma (SCC). DESIGN: The sample consisted of 100 cases retrieved from the archives of the Pathology Department/ King Hussein Cancer Center/Amman/ Jordan. Recorded data included: age, gender, location, grade, depth of invasion, the presence of epithelial dysplasia, tumor size, lymph node metastasis, number of positive lymph nodes, distant metastases, clinical stage, local recurrence, treatment modalities and 5-year survival rate. Immunohistochemical staining of 7 cytokeratins: 8, 10, 13, 14, 16, 18, and 19 was performed using standard protocols. Stained sections were digitized and analyzed using ImageJ-color deconvolution to identify the percentage of cytokeratin-positive area (score). Statistical tests used were: student t-test, analysis of variance, bivariate analysis and logistic regression. RESULTS: Lower CK8,18, 19 scores correlated with lower 5-year survival rate. Higher CK19 and lower CK 10, 14, 16 scores were associated with distant metastasis. Increased CK8, 18, 19 scores correlated with higher stage and with higher depth of invasion. Increased CK18 scores correlated with increased local recurrence. Higher CK10, 13, 16 scores correlated with well-differentiated grade. Higher CK19 and lower CK16 scores were associated with adjacent epithelial dysplasia. Regression analysis showed that better 5-year survival rate was significantly correlated with increased CK16, decreased CK18 and 19 scores. CONCLUSION: Expression scores of a panel of cytokeratin are potential prognostic indicators for 5-year survival and correlates with other prognostic parameters.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Queratinas/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Feminino , Gengiva/patologia , Humanos , Imuno-Histoquímica , Jordânia , Queratina-10 , Queratina-13 , Queratina-14 , Queratina-16 , Queratina-18 , Queratina-19 , Queratina-8 , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Orofaringe/patologia , Prognóstico , Análise de Regressão , Taxa de Sobrevida , Adulto JovemRESUMO
Blue rubber bleb nevus syndrome (BRBNS) is a rare disease with vascular malformations in several systems of the body, most commonly the skin and gastrointestinal tract. Bleeding from the gastrointestinal (GI) tract is a major complication, which may lead to chronic iron deficiency anemia and the need for frequent blood transfusions due to ongoing gastrointestinal blood loss. In this case report, we describe a now 19-year-old female with BRBNS who required six blood transfusions per year and after starting sirolimus is symptom- and transfusion-free.
RESUMO
AML with the RAM immunophenotype is associated with extremely poor prognosis. We report a rare case of monozygotic twins presenting simultaneously at the age of 2 years with RAM AML. Each twin underwent a myeloablative 7/10 unrelated umbilical cord blood transplant. Pretransplant Twin A's bone marrow was negative for MRD by flow cytometry (<0.01%) unlike Twin B's bone marrow (0.07%). Twin A is alive in remission 3 years from transplant. Twin B developed primary graft failure, but subsequently rescued with a haploidentical stem cell transplant. However, she relapsed and died 13 months from diagnosis. The twins' clinical courses demonstrate that upfront intensive chemotherapy to achieve negative MRD, followed by allogeneic hematopoietic stem cell transplant as postremission intensification strategy, should be considered in this high-risk AML.
Assuntos
Imunofenotipagem , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/imunologia , Medula Óssea/patologia , Pré-Escolar , Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doenças em Gêmeos , Evolução Fatal , Feminino , Sangue Fetal/metabolismo , Citometria de Fluxo , Humanos , Leucemia Mieloide Aguda/genética , Neoplasia Residual , Prognóstico , Indução de Remissão , Transplante Homólogo , Gêmeos MonozigóticosRESUMO
Maintaining fluid balance, pre- and post-MA-HCT is essential and usually requires frequent administration of diuretics. Hepatic sinusoidal obstructive syndrome is potentially life-threatening, especially when associated with AKI and MOF. This study describes six patients who developed AKI-associated SOS and diuretic-resistant FO who subsequently underwent CRRT using standardized management guidelines for fluid balance post-HCT. Retrospective chart review was done for HCT patients between September 2011 and October 2013 at a tertiary care children's hospital. Thirty-four patients underwent MA-HCT in the study period. Six patients had SOS complicated by diuretic-resistant FO and underwent CRRT. Defibrotide was used in three patients. Median time on CRRT was 10.5 days. Sixty-six percent (N = 4 of 6) of patients had full resolution of SOS symptoms with a mortality rate of 34% (N = 2 of 6). Among patients who had full recovery of SOS symptoms, one patient developed AKI, end-stage renal diseases and underwent kidney transplantation 34-months post-HCT. Thus, of six included patients, two died and one developed ESRD with only 50% (N = 3 of 6) good outcome. Use of a standardized, evidence-based fluid balance protocol and early initiation of CRRT for HCT-related AKI/SOS was associated with good outcomes.
Assuntos
Injúria Renal Aguda/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hepatopatia Veno-Oclusiva/terapia , Terapia de Substituição Renal/métodos , Injúria Renal Aguda/etiologia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Hepatopatia Veno-Oclusiva/etiologia , Humanos , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
X-linked agammaglobulinemia (XLA) is a primary immunodeficiency characterized by marked reduction in all classes of serum immunoglobulins and the near absence of mature CD19(+) B-cells. Although malignancy has been observed in patients with XLA, we present the first reported case of acute myeloid leukemia (AML) in a patient with XLA. We also demonstrate the complete correction of the XLA phenotype following allogeneic hematopoietic cell transplantation for treatment of the patient's leukemia.
Assuntos
Agamaglobulinemia/terapia , Doenças Genéticas Ligadas ao Cromossomo X/terapia , Leucemia Mieloide Aguda/terapia , Transplante de Células-Tronco de Sangue Periférico , Agamaglobulinemia/complicações , Aloenxertos , Anticorpos Antibacterianos/biossíntese , Antígenos CD19/análise , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Subpopulações de Linfócitos B/química , Pré-Escolar , Terapia Combinada , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/tratamento farmacológico , Contagem de Linfócitos , Masculino , Vacinas Pneumocócicas , Recidiva , Indução de Remissão , Streptococcus pneumoniae/imunologia , Condicionamento Pré-TransplanteRESUMO
Certain patients who receive granulocyte colony-stimulating factor (GCSF) for autologous hematopoietic stem cell (AHSC) collection fail to mobilize well enough to proceed with transplant. When plerixafor is used with GCSF, the likelihood of achieving the CD34⺠stem cell target in fewer collections is higher; plerixafor use in all patients is unlikely to be cost-effective. This study retrospectively evaluated the effectiveness of utilizing a peripheral blood CD34⺠stem cell count (PBCD34) ≤8/µL on day 4 of GCSF-based AHSC mobilization as a threshold for plerixafor administration, and compared the efficacy of collection and cost analysis using historical controls. All patients in the study cohort reached their CD34⺠targets in ≤3 collections. Significantly more patients who received plerixafor + GCSF versus GCSF alone reached their CD34⺠target in one collection (P = 0.045); however, there were no significant differences in the number of collections or in cumulative product yields. The historical cohort had 10.3% mobilization failures; the number of collections per patient needed to reach the target was significantly higher in the historical cohort versus study cohort (P = 0.001) as was the number of patients requiring more than one collection to reach their target (P = 0.023). However, the average cost per patient was also significantly higher in the study cohort (P = 0.025). Further refinement of the algorithm may reduce the difference in cost between the two mobilization strategies.
Assuntos
Algoritmos , Antígenos CD34/análise , Mobilização de Células-Tronco Hematopoéticas , Compostos Heterocíclicos/uso terapêutico , Receptores CXCR4/antagonistas & inibidores , Adolescente , Adulto , Idoso , Benzilaminas , Contagem de Células , Análise Custo-Benefício , Custos e Análise de Custo , Ciclamos , Feminino , Mobilização de Células-Tronco Hematopoéticas/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante AutólogoRESUMO
BACKGROUND: We evaluated the possibility of video-endoscopic dissection of both internal thoracic arteries (rTAs) through the left thoracic approach and right gastroepiploic artery (GEA) via a small laparoscopic access, for use in minimally invasive coronary artery bypass surgery. METHODS: The procedure was performed on twenty-two mongrel dogs. Three 10 mm ports were inserted in the left hemithorax to enable the introduction of a rigid 0-degree videoscope and forceps which allowed access to the left and right ITAs. For dissection of the GEA, one 10 mm and two 5 mm ports were inserted in the para-umbilical region. RESULTS: The left and right ITAs and the GEA were easily visualized and dissection and complete mobilization was achieved without injury, which was checked by the presence of good blood flow. The ITAs and GEA were divided distally, exteriorized through a small left anterior thoracotomy and the length of these three grafts were able to reach all of the left coronary artery branches. CONCLUSIONS: We have demonstrated, in dogs, the feasibility of video-assisted dissection of both the left and right ITAs through the left thoracic approach, without sternotomy, avoiding the risks of sternal complications and expanding its use for all patients. Furthermore, a third arterial conduit (the RGA) can be used without requiring laparotomy.