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2.
Medicine (Baltimore) ; 100(25): e26446, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34160438

RESUMO

RATIONALE: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1 year after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment. PATIENT CONCERNS: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units. DIAGNOSES: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed. INTERVENTIONS: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin. OUTCOMES: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative. LESSONS: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus Humano NL63/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia de Células B/terapia , Pneumonia Viral/diagnóstico , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Coronavirus Humano NL63/genética , Coronavirus Humano NL63/imunologia , Quimioterapia Combinada/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hospedeiro Imunocomprometido , Leucemia de Células B/imunologia , Pulmão/diagnóstico por imagem , Masculino , Metagenômica , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X , Transplante Homólogo/efeitos adversos , Adulto Jovem , gama-Globulinas/administração & dosagem
3.
Medicine (Baltimore) ; 100(26): e26316, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190149

RESUMO

INTRODUCTION: Severe hemorrhagic cystitis (HC) is still a common complication after allogeneic hematopoietic stem cell transplantation, which affects the quality of life of patients, and may even cause kidney failure. This study reports the clinical effect of adjuvant treatment of adipose-derived mesenchymal stem cells (ADSCs) on severe refractory HC after of reduced intensity conditioning haplotype high-dose peripheral blood hematopoietic stem cell transplantation (RIC-PBSCT) in one case. PATIENT CONCERNS: A 53-year-old female patient with acute myeloid leukemia (FLT3-ITD) at high risk received RIC-PBSCT. The patient was relieved with complete donor chimerism of 99.01%, and normal hemogram. However, the patient developed frequent urination, urgency, and dysuria with gross hematuria with blood clots and difficult urinating, especially at night and early in the morning. There were obvious hyperemia and bleeding points in the mucosa of the posterior wall of the bladder. DIAGNOSIS: The patient was diagnosed as delayed HC of degree IV. INTERVENTIONS AND OUTCOMES: The patient was treated with antiviral drugs, urine alkalization, and diuretic drugs for more than 1 month, but no significant effect was obtained. Thus, the patient was then given ADSCs (1 × 106 kg per kg of body weight, infused once a week for a total of 3 infusions). Symptoms of frequent urination, urgency, and dysuria that happened during the first infusion were improved, and blood clots in the urine were also reduced. After the third infusion, HC symptoms disappeared, the red blood cells were normal, and there was no fever, chills, low infusion blood pressure, or rash. The patient's HC was cured. During follow-up, HC recurrence was not observed. CONCLUSION: ADSCs adjuvant treatment of relapsed and refractory severe HC is safe and reliable with good clinical efficacy. It shows certain clinical application value, which however requires more clinical cases to further verify this.


Assuntos
Tecido Adiposo/citologia , Cistite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/terapia , Transplante de Células-Tronco Mesenquimais , Condicionamento Pré-Transplante/efeitos adversos , Terapia Combinada , Cistite/etiologia , Feminino , Hematúria/etiologia , Hemorragia/etiologia , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Fatores de Risco , Transtornos Urinários/etiologia
4.
Medicine (Baltimore) ; 100(25): e26446, 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: covidwho-1279283

RESUMO

RATIONALE: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1 year after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment. PATIENT CONCERNS: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units. DIAGNOSES: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed. INTERVENTIONS: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin. OUTCOMES: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative. LESSONS: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner.


Assuntos
Infecções por Coronavirus/diagnóstico , Coronavirus Humano NL63/isolamento & purificação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia de Células B/terapia , Pneumonia Viral/diagnóstico , Antivirais/administração & dosagem , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/virologia , Coronavirus Humano NL63/genética , Coronavirus Humano NL63/imunologia , Quimioterapia Combinada/métodos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Hospedeiro Imunocomprometido , Leucemia de Células B/imunologia , Pulmão/diagnóstico por imagem , Masculino , Metagenômica , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Pneumonia Viral/virologia , Tomografia Computadorizada por Raios X , Transplante Homólogo/efeitos adversos , Adulto Jovem , gama-Globulinas/administração & dosagem
5.
Medicina (B Aires) ; 81(3): 438-451, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34137706

RESUMO

Invasive fungal infections (IFI) are among the main infectious complications in patients with hematological malignancies and with hematopoietic stem cell transplant (HSCT), causing high morbidity and mortality and significantly increasing the healthcare cost and hospital stay. The epidemiology of IFIs has changed in recent decades, with filamentous fungi, particularly Aspergillus spp., being the main etiological agents. There are multiple risk factors for having an IFI; however, the most important are profound and prolonged neutropenia and severe cellular immunodeficiency. For this reason, the population at greatest risk is made up of patients with acute leukemias, myelodysplasias and allogeneic HSCT with graft-versus-host disease (GVHD) treated with corticosteroids. Numerous randomized clinical trials and meta-analyses have shown that primary antifungal prophylaxis (AFP) significantly reduces the incidence of IFI, particularly those caused by Candida spp. and Aspergillus spp., IFI-related mortality, and overall mortality in some group of patients. Likewise, in high-risk patients, where a high incidence of IFI is expected, it is a cost-effective strategy. Several antifungals have demonstrated clinical benefit. They can be used as a AFP strategy in different settings, presenting advantages and disadvantages that must be taken into account in each case. For this, national and international scientific societies have issued recommendations for the indication of AFP. Aspects related to the different antifungals' clinical efficacy are analyzed considering the population at risk, the potential disadvantages, timing, and form of administration.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas , Neutropenia , Antifúngicos/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neutropenia/tratamento farmacológico
6.
Microbiome ; 9(1): 148, 2021 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-34183060

RESUMO

BACKGROUND: Patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) exhibit changes in their gut microbiota and are experiencing a range of complications, including acute graft-versus-host disease (aGvHD). It is unknown if, when, and under which conditions a re-establishment of microbial and immunological homeostasis occurs. It is also unclear whether microbiota long-term dynamics occur at other body sites than the gut such as the mouth or nose. Moreover, it is not known whether the patients' microbiota prior to HSCT holds clues to whether the patient would suffer from severe complications subsequent to HSCT. Here, we take a holobiont perspective and performed an integrated host-microbiota analysis of the gut, oral, and nasal microbiota in 29 children undergoing allo-HSCT. RESULTS: The bacterial diversity decreased in the gut, nose, and mouth during the first month and reconstituted again 1-3 months after allo-HSCT. The microbial community composition traversed three phases over 1 year. Distinct taxa discriminated the microbiota temporally at all three body sides, including Enterococcus spp., Lactobacillus spp., and Blautia spp. in the gut. Of note, certain microbial taxa appeared already changed in the patients prior to allo-HSCT as compared with healthy children. Acute GvHD occurring after allo-HSCT could be predicted from the microbiota composition at all three body sites prior to HSCT. The reconstitution of CD4+ T cells, TH17, and B cells was associated with distinct taxa of the gut, oral, and nasal microbiota. CONCLUSIONS: This study reveals for the first time bacteria in the mouth and nose that may predict aGvHD. Monitoring of the microbiota at different body sites in HSCT patients and particularly through involvement of samples prior to transplantation may be of prognostic value and could assist in guiding personalized treatment strategies. The identification of distinct bacteria that have a potential to predict post-transplant aGvHD might provide opportunities for an improved preventive clinical management, including a modulation of microbiomes. The host-microbiota associations shared between several body sites might also support an implementation of more feasible oral and nasal swab sampling-based analyses. Altogether, the findings suggest that the microbiota and host factors together could provide actionable information to guiding precision medicine. Video Abstract.


Assuntos
Microbioma Gastrointestinal , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Microbiota , Bactérias/genética , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos
7.
Zhonghua Nei Ke Za Zhi ; 60(6): 556-560, 2021 Jun 01.
Artigo em Chinês | MEDLINE | ID: mdl-34058813

RESUMO

To compare the clinical features and prognosis in patients with cytomegalovirus pneumonia from other pneumonia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). A total of 118 patients with pulmonary complications after allo-HSCT from March 2016 to June 2019 were analyzed retrospectively, who were divided into cytomegalovirus (CMV) pneumonia group (n=34) and the non-CMV pneumonia group (n=84). Compared with non-CMV pneumonia group, CMV pneumonia group presented earlier median onset time (1.8 vs.6.0 months, P=0.015) after allo-HSCT, more dyspnea (41.2% vs. 19.0%, P=0.012), hypoxemia (38.2% vs. 13.1%, P=0.006), and interstitial pneumonia (82.4% vs. 23.8%,P<0.01).The incidence of CMV-viremia and serum viral load in CMV pneumonia group were significantly higher than those in non-CMV pneumonia group. Consistently, and the development of mixed infection in CMV pneumonia group was higher than that of non-CMV pneumonia group (41.2% vs. 16.7%, P=0.013). The median follow-up time was 12.8 (0.4-46.5) months. The 1-year attributable mortality in CMV pneumonia group was significantly higher than that in non-CMV pneumonia group (26.5% vs. 10.7%, P=0.004), while the 1-year overall survival rate was significantly lower than that in non-CMV pneumonia group (61.8% vs. 85.7%, P=0.001). Reduced-intensity conditioning (RIC)(P=0.036), high flow ventilation (P=0.033) and negative CMV-viremia (P=0.009) were unfavorable prognostic factors of patients with CMV pneumonia. Compared with those with non-CMV pneumonia, patients with CMV pneumonia had more characteristic clinical manifestations and imaging features. However, due to the higher incidence of mixed infections, the causes of pneumonia need to be identified by bronchoscopic alveolar lavage. In conclusion, patients with CMV pneumonia have worse clinical outcome. RIC, high flow ventilation and negative CMV-viremia are adverse prognostic factors for CMV pneumonia.


Assuntos
Infecções por Citomegalovirus , Transplante de Células-Tronco Hematopoéticas , Pneumonia , Citomegalovirus , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pneumonia/epidemiologia , Pneumonia/etiologia , Estudos Retrospectivos
8.
Chin Med J (Engl) ; 134(12): 1431-1440, 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34091525

RESUMO

BACKGROUND: The impacts of previous cardio-cerebrovascular disease (pre-CCVD) on the outcomes of hematopoietic cell transplantation (HCT) are not well described. Patients with pre-CCVD may often be poor candidates for HCT. This study aimed to investigate the impact of pre-CCVD on transplant outcomes. METHODS: A retrospective study was conducted between patients with and without pre-CCVD who consecutively received allogeneic or autologous HCT between November 2013 and January 2020 with a matching of age and disease status. The cardiovascular complications and HCT outcomes of the two groups were evaluated and compared. The primary endpoints were post-transplant cardio-cerebrovascular disease (post-CCVD) and non-relapse mortality (NRM). We used a multivariable Cox proportional hazard model and the Fine-Gray competing risk regressions for analyses to estimate the hazard ratios (HRs). RESULTS: The outcomes of 23 HCT recipients with pre-CCVD were compared with those of 107 patients in the control group. No significant differences were noted in terms of engraftment, overall survival (OS) (67.00% vs. 67.90%, P = 0.983), or relapse (29.78% vs. 28.26%, P = 0.561) between the pre-CCVD group and the control group. The cumulative incidences of 2-year NRM were similar between patients with pre-CCVD and the controls (14.68% vs. 17.08%, P = 0.670). However, pre-CCVD was associated with an increased incidence of post-CCVD (HR: 12.50, 95% confidence interval [CI]: 3.88-40.30, P < 0.001), which was an independent risk factor for increased NRM (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001) and inferior OS (HR: 10.29, 95% CI: 3.84-27.62, P < 0.001). CONCLUSIONS: These findings suggest that the existence of pre-CCVD before transplantation might not result in increased mortality directly but superpose the toxicity of the transplantation procedure, leading to a risk of post-CCVD. Post-CCVD was a powerful predictor for high NRM and inferior OS. Further risk stratification of pre-CCVD is needed to reduce NRM in various transplantation settings.


Assuntos
Transtornos Cerebrovasculares , Transplante de Células-Tronco Hematopoéticas , Transtornos Cerebrovasculares/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Condicionamento Pré-Transplante , Transplante Autólogo
9.
Hematology ; 26(1): 435-443, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34130602

RESUMO

A retrospective study on 287 patients with SAA who underwent allo-HSCT between October 2012 and January 2020 was conducted to explore the outcomes, risk factors and treatment options for MC. Among 287 AA patients who excluded Fanconi anemia (FA), Congenital dyskeratosis (DKC), Paroxysmal nocturnal hemoglobinuria (PNH), etc.112 underwent matched sibling donor (MSD)-HSCT, 91 matched unrelated donor-HSCT and 84 haploidentical-HSCT. Patients were divided into the following 4 groups: group 1: Donor chimerism (DC); group 2: MC without cytopenia; group 3: MC with cytopenia; group 4: secondary graft failure (SGF).Compared with the other three groups, SGF predicted a poor prognosis of SAA (P< 0.001). In addition, SGF was associated with the early (within 3 months after transplantation) presence of MC and the high levels of MC. Uni- and multivariate logistic regression analysis showed that donor/recipient sex-mismatching and CTX + ATG regimen were high-risk factors for MC. Of note, in MC patients with cytopenia (group 3), the effective response rate reached 55% (6/11) following enhanced immunosuppression combined with cellular therapy, while only one of the four was effective who received enhanced immunosuppression alone.SGF was associated with poor prognosis, early presence of MC and increased levels of recipient chimerism. The donor/recipient sex-mismatching and CTX + ATG regimen based MSD-HSCT were risk factors for MC. Cellular therapy could improve the effective response rate of patients with progressive MC.


Assuntos
Anemia Aplástica/terapia , Quimerismo , Transplante de Células-Tronco Hematopoéticas , Adulto , Anemia Aplástica/diagnóstico , Anemia Aplástica/genética , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Transplante Homólogo/efeitos adversos
10.
Rev Bras Enferm ; 74Suppl 1(Suppl 1): e20201088, 2021.
Artigo em Inglês, Português | MEDLINE | ID: mdl-34161518

RESUMO

OBJECTIVE: to describe the experience of building the technology "Care for the prevention of COVID-19 in post-hematopoietic stem cell transplant patients". METHODS: experience report conducted in a hematopoietic stem cell transplant outpatient clinic that supported the construction of an educational technology in the form of a booklet for the prevention of COVID-19. In May 2020, a literature review in scientific databases and guidelines of health organizations were used for its development. RESULTS: printed booklet with information on the definition of coronavirus, hand hygiene, use of the mask by the patient and caregiver, isolation and social distancing and general hygiene care. FINAL CONSIDERATIONS: the use of technologies is characterized as a tool for educational actions therefore, nurses, patients and caregivers benefit from guidance processes for health care. The developed technology has the potential to minimize the impact and spread of SARS-CoV-2 among high-risk populations.


Assuntos
COVID-19 , Transplante de Células-Tronco Hematopoéticas , Tecnologia Educacional , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pandemias , SARS-CoV-2
11.
Am J Case Rep ; 22: e931731, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-34129542

RESUMO

BACKGROUND Nocardia infections have rarely been reported in hematopoietic stem cell transplantation (HSCT) patients, who usually receive the prophylactic use of sulfamethoxazole/trimethoprim (ST) against Pneumocystis jiroveci. However, the ST prophylaxis, sensitive to Nocardia species, sometimes induces renal toxicities. Therefore, alternative prophylactic or therapeutic drugs are required for nocardiosis in HSCT patients. CASE REPORT A 34-year-old Japanese man with acute mixed phenotypic leukemia with t(9; 22) received allogenic peripheral blood HSCT from a haplo-identical sibling donor. He developed graft versus host disease (GVHD) with grade II, and was treated with prednisolone and cyclosporine A with concurrent ciprofloxacin, fluconazole, valacyclovir, and ST. However, the prophylactic ST was ceased because of its renal toxicity. He developed a pulmonary nodular lesion with elevated ß-D-glucan and Aspergillus galactomannan antigen. Repeated blood and sputum culture isolated no pathogens. Voriconazole treatment administered once improved these lesions and laboratory findings. One month later, he presented with right pleuritic chest pain and multiple ring-enhancing cavitation lesions along the ribs. A needle biopsy demonstrated Nocardia elegans, which is an extremely rare infection induced by Nocardia species, in the cavitation lesions, shown by 16S rRNA gene sequencing. He was started on doripenem and liposomal amphotericin B, and a subsequent treatment kept him free from Nocardia elegans infection, without any adverse effects, while continuing the cyclosporine A and prednisolone treatment for chronic GVHD. CONCLUSIONS Clarithromycin has fewer adverse effects than ST. This case suggests that clarithromycin is an appropriate alternative and prophylactic therapy for patients with nocardiosis and ST toxicities.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Nocardiose , Nocardia , Adulto , Claritromicina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Nocardia/genética , RNA Ribossômico 16S
12.
Transplant Cell Ther ; 27(6): 504.e1-504.e6, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34158154

RESUMO

Chronic graft-versus-host disease (cGVHD) is a complication of hematopoietic cell transplantation (HCT). Although the clinical outcomes of cGVHD are well documented, few studies have assessed treatment practices outside of clinical trials. The present study aimed to quantify the prevalence of cGVHD, examine provider prescribing patterns, and evaluate the healthcare cost and resource utilization (HCRU) in a US cGVHD population. We analyzed anonymized claims from the Medicare Fee-for-Service (FFS) 5% sample for beneficiaries enrolled between 2013 and 2016 and PharMetrics commercial 2013 to 2018 databases to identify cGVHD in allogeneic HCT recipients. cGVHD was identified based on International Classification of Diseases Ninth/Tenth Revision diagnosis codes for cGVHD or unspecified GVHD with a first diagnosis >180 days post-HCT or a maintained unspecified GVHD diagnosis for >12 months postindex of unspecified GVHD diagnosis. Longitudinal and line of therapy (LOT) analyses were based on the PharMetrics dataset for 2013 to 2018. Healthcare costs were calculated by adding the inpatient, outpatient, and pharmacy insurer and beneficiary paid amounts for the commercially insured population. Total HCRU was assessed using the number of inpatient and outpatient visits following the initial cGVHD diagnosis. In 2016, the projected prevalence of cGVHD in the United States based on the Medicare FFS and PharMetrics commercial databases was 14,017 individual patients. Within 3 years after undergoing allogeneic HCT, 42% of patients developed cGVHD; 66% of the cGVHD patients had a prior diagnosis of acute GVHD. The majority of cGVHD patients received at least one systemic therapy; 71% and 47% of cGVHD patients progressed to a second and third LOT, respectively. A total of 24 unique therapeutic agents and more than 150 combinations were used in the second and third LOTs. Corticosteroids and corticosteroid combination therapy were the most common forms of treatment across all examined LOTs. Furthermore, the most commonly used agents in the first LOT, second LOT, and third LOT were corticosteroids only, calcineurin inhibitors only, and corticosteroids only, respectively. In the 12 months postdiagnosis, cGVHD patients had an average of 21.0 cGVHD-related inpatient and outpatient visits (2.8 inpatient and 18.2 outpatient visits). A significant proportion of allogeneic HCT recipients continue to develop cGVHD, and despite advances in the understanding of cGVHD, corticosteroids remain the mainstay of therapy. Patients often progress beyond the first LOT, at which time the utilization of systemic therapies is highly variable, demonstrating the need for evidence-based treatment approaches.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Idoso , Inibidores de Calcineurina , Doença Enxerto-Hospedeiro/epidemiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Revisão da Utilização de Seguros , Medicare , Estados Unidos/epidemiologia
13.
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
14.
Front Immunol ; 12: 605766, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34025637

RESUMO

Patients often undergo consolidation allogeneic hematopoietic stem cell transplantation (allo-HSCT) to maintain long-term remission following chimeric antigen receptor (CAR) T-cell therapy. Comparisons of safety and efficacy of allo-HSCT following complete remission (CR) achieved by CAR-T therapy versus by chemotherapy for B-cell acute lymphoblastic leukemia (B-ALL) has not been reported. We performed a parallel comparison of transplant outcomes in 105 consecutive B-ALL patients who received allo-HSCT after achieving CR with CAR-T therapy (n=27) or with chemotherapy (n=78). The CAR-T-allo-HSCT group had more patients in second CR compared to the chemotherapy-allo-HSCT group (78% vs. 37%; p<0.01) and more with complex cytogenetics (44% vs. 6%; p<0.001) but the proportion of patients with pre-transplant minimal residual disease (MRD) was similar. The median follow-up time was 49 months (range: 25-54 months). The CAR-T cohort had a higher incidence of Grade II-IV acute graft-versus-host disease (aGVHD 48.1% [95% CI: 46.1-50.1%] vs. 25.6% [95%CI: 25.2-26.0%]; p=0.016). The incidence of Grade III-IV aGVHD was similar in both groups (11.1% vs.11.5%, p=0.945). The overall incidence of chronic GVHD in the CAR-T group was higher compared to the chemotherapy group (73.3% [95%CI: 71.3-75.3%] vs. 55.0% [95%CI: 54.2-55.8%], p=0.107), but the rate of extensive chronic GVHD was similar (11.1% vs.11.9%, p=0.964). Efficacy measures 4 years following transplant were all similar in the CAR-T vs. the chemotherapy groups: cumulative incidences of relapse (CIR; 11.1% vs.12.8%; p=0.84), cumulative incidences of non-relapse mortality (NRM; 18.7% vs. 23.1%; p=0.641) leukemia-free survival (LFS; 70.2% vs. 64.1%; p=0.63) and overall survival (OS; 70.2% vs. 65.4%; p=0.681). We found that pre-transplant MRD-negative CR predicted a lower CIR and a higher LFS compared with MRD-positive CR. In conclusion, our data indicate that, in B-ALL patients, similar clinical safety outcomes could be achieved with either CD19 CAR T-cell therapy followed by allo-HSCT or chemotherapy followed by allo-HSCT. Despite the inclusion of more patients with advanced diseases in the CAR-T group, the 4-year LFS and OS achieved with CAR T-cells followed by allo-HSCT were as remarkable as those achieved with chemotherapy followed by allo-HSCT. Further confirmation of these results requires larger, randomized clinical trials.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Imunoterapia Adotiva , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Adolescente , Antígenos CD19 , Antígenos de Neoplasias , Criança , Terapia Combinada , Resistencia a Medicamentos Antineoplásicos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/métodos , Humanos , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Prognóstico , Receptores de Antígenos de Linfócitos T , Receptores de Antígenos Quiméricos , Recidiva , Retratamento , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
15.
Vaccine ; 39(25): 3338-3345, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-33992440

RESUMO

BACKGROUND AND OBJECTIVE: Vaccination with the live attenuated measles vaccine is currently recommended two years after hematopoietic stem cell transplantation (HSCT) and generally contraindicated after solid organ transplantation (SOT) due to safety concerns. However, in the last few years new data on the administration of the measles vaccine to HSCT recipients less two years post-transplantation and to SOT recipients have become available. This new data may change current guidelines and practices. The objective of this review is to provide an overview of the current data on the safety and efficacy of early measles vaccination for HSCT- and SOT recipients. METHOD: PubMed and EMBASE were searched from the earliest date available through October 2019 to identify all research that reported on the safety and efficacy of measles vaccination after SOT or less than two years after HSCT. RESULTS: A total of ten studies was included in this review. In the six studies that evaluated the efficacy of measles vaccination after SOT, seroconversion rates ranged from 41 to 100% after one dose and 73 to 100% after two doses. In the four studies that evaluated the efficacy of measles vaccination less than two years after HSCT, seroconversion rates ranged from 33 to 100% after one dose and 100% after two doses. In all studies, the administration of the measles vaccine after transplantation was considered to be safe. There were no cases of infection with the attenuated vaccine strain, and there were no adverse events related to the vaccination. CONCLUSION: Data on the administration of the measles vaccine after SOT and less than two years after HSCT is scarce. However, the current data available suggest that it is efficacious and well tolerable. Therefore, early measles vaccination could be considered in selected groups of SOT- and HSCT recipients during increased measles transmission or an outbreak setting.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Transplante de Órgãos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Vacina contra Sarampo , Transplantados , Vacinação , Vacinas Atenuadas/efeitos adversos
16.
Echocardiography ; 38(6): 1084-1088, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34018636

RESUMO

We report isolated extramedullary relapse in a 14-year-old boy, sequentially presenting with intestinal and cardiac myeloid sarcoma (MS). Acute myeloblastic leukemia M5 was diagnosed 41 months ago. On the 14th month of the second HSCT, he presented with ileus and underwent surgical treatment. After 2 weeks, arrhythmia, bradycardia, complete heart block, and atrial flutter developed and echocardiography revealed multiple cardiac masses. There was no bone marrow relapse but pathology of the intestinal biopsy showed leukemic infiltration. Patient was successfully treated with a permanent pacemaker and salvage chemotherapy. To the best of our knowledge, this is the first pediatric cardiac MS developed after HSCT.


Assuntos
Flutter Atrial , Bloqueio Atrioventricular , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Sarcoma Mieloide , Adolescente , Arritmias Cardíacas , Flutter Atrial/etiologia , Criança , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Masculino , Recidiva , Sarcoma Mieloide/diagnóstico por imagem , Transplante Homólogo
17.
Transplant Cell Ther ; 27(5): 428.e1-428.e9, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965185

RESUMO

Haploidentical hematopoietic cell transplantation (HaploHCT) is an alternative treatment option for patients without a suitable 10/10 HLA matched donor. We share an updated experience at our center of using in vivo dual T-cell depletion with anti-thymocyte globulin (ATG) and post-transplantation cyclophosphamide (PTCy) in peripheral blood haploHCT and report the impact of reducing the dose of ATG from 4.5 mg/kg to 2 mg/kg on post-transplantation complications and outcomes. Ninety-five consecutive adults underwent haploHCT at our center between August 2016 and February 2020, all of whom were included in the study. Nine (9.5%) patients received myeloablative conditioning, and 86 (90.5%) patients underwent reduced-intensity haploHCT. All patients received thymoglobulin, PTCy and cyclosporine (CsA) for graft-versus-host disease (GVHD) prophylaxis: Sixty (63.2%) patients received 4.5 mg/kg, and 35 (36.8%) patients received 2 mg/kg of ATG. Clinical information was collected retrospectively and updated in June 2020. The median age was 57 (18-73), and acute myeloid leukemia was the most prevalent diagnosis (58.9%). The day 100 cumulative incidence of grade II-IV and grade III-IV aGVHD, and 1-year moderate/severe cGVHD were 22.3%, 11.1%, and 20.2%, respectively. Those patients who received 2 mg/kg of ATG had higher incidence of grade III-IV aGVHD (23.9% vs 3.5%, P = .006) and comparable moderate/severe cGVHD (1-year 20.6% vs 19.8%, P = .824) than those patients who received 4.5 mg/kg. Overall, the 18-month overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) were 43.8%, 38.4%, and 40.2%, respectively. The reduction of the ATG dose did not have a significant impact in OS (hazard ratio [HR] 1.06, P = .847), RFS (HR 0.984, P = .955), and in NRM (HR 1.38; P = .348). The reduction of the ATG resulted in a negative impact on aGVHD without conferring any benefit in OS, RFS, and NRM. Consequently, the ATG dose used at our institution in combination with PTCy and CsA for haploHCT continues to be 4.5 mg/kg.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Adulto , Soro Antilinfocitário/uso terapêutico , Ciclofosfamida/efeitos adversos , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
18.
Transplant Cell Ther ; 27(5): 437.e1-437.e9, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33965190

RESUMO

Post-transplantation acute limbic encephalitis (PALE) is a rare, severe inflammatory disorder in the bilateral limbic system, including the hippocampus. To date, only a few studies have reported details, including risk factors for PALE; however, further clinical evidence of PALE, especially in cerebrospinal fluid human herpesvirus 6-negative cases, is warranted. In addition, data are sparse regarding the risk factors for calcineurin inhibitor (CNI)-induced encephalopathy (CNIE) following allogeneic hematopoietic cell transplantation (allo-HCT) in adults. Therefore, we examined the risk factors for and clinical details of PALE and CNIE. We retrospectively analyzed consecutive patients who underwent allo-HCT between January 2005 and November 2017. A total of 485 patients age 46 years (median) were eligible. In total, 14 PALE cases and 11 CNIE cases were identified. Multivariable analyses identified older age, use of an HLA-mismatched unrelated donor (URD), graft-versus-host disease (GVHD) prophylaxis with CNI and mycophenolate mofetil, and grade II-IV acute GVHD as significantly associated with an increased risk of PALE. In 13 patients who received high-dose methylprednisolone (mPSL) therapy, 6 (46%) responded to mPSL therapy, and 3 (23%) achieved complete remission at day 90 after mPSL administration. Furthermore, myelodysplastic syndrome (MDS), HLA-mismatched URD, and grade II-IV acute GVHD were significantly associated with an increased risk of CNIE. The 5-year nonrelapse mortality rate was 50% in PALE and 63% in CNIE, suggesting a very poor prognosis. In conclusion, this study provides evidence that HLA-mismatched URD and acute GVHD may independently contribute to the development of PALE, possibly in part through HLA-mismatch-derived alloimmune responses. Other than acute GVHD, we have identified MDS and HLA-mismatched URD as novel predictors of CNIE after allo-HCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Encefalite Límbica , Adulto , Idoso , Inibidores de Calcineurina/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
19.
Transplant Cell Ther ; 27(5): 371-379, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33969823

RESUMO

Many patients with hematologic malignancies receive RBC transfusion support, which often causes systemic and tissue iron toxicity. Because of their compromised bone marrow function, hematopoietic stem cell transplant (HSCT) recipients are especially vulnerable to excess iron levels. Iron toxicity may compromise transplant engraftment and eventually promote relapse by mediating oxidative and genotoxic stress in hematopoietic stem cells (HSCs) and further impairing the already dysfunctional bone marrow microenvironment in HSCT recipients. Iron toxicity is thought to be primarily mediated by its ability to induce reactive oxygen species and trigger inflammation. Elevated iron levels in the bone marrow can decrease the number of HSCs and progenitor cells, as well as their clonogenic potential, alter mesenchymal stem cell differentiation, and inhibit the expression of chemokines and adhesion molecules involved in hematopoiesis. In vivo, in vitro, and clinical studies support the concept that iron chelation therapy may limit iron toxicity in the bone marrow and promote hematologic improvement and engraftment in HSCT recipients. This review will provide an overview of the current knowledge of the detrimental impact of iron toxicity in the setting of HSCT in patients with hematologic malignancies and the use of iron restriction approaches to improve transplant outcome.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Sobrecarga de Ferro , Terapia por Quelação , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Ferro/toxicidade , Sobrecarga de Ferro/etiologia , Recidiva Local de Neoplasia , Microambiente Tumoral
20.
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
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