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1.
Ann Hematol ; 100(4): 865-878, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33547921

RESUMO

Post-transplantation lymphoproliferative disorder (PTLD) is a severe complication of haematopoietic stem cell transplantation (HSCT), occurring in a setting of immune suppression and dysregulation. The disease is in most cases driven by the reactivation of the Epstein-Barr virus (EBV), which induces B cell proliferation through different pathomechanisms. Beyond EBV, many factors, variably dependent on HSCT-related immunosuppression, contribute to the disease development. PTLDs share several features with primary lymphomas, though clinical manifestations may be different, frequently depending on extranodal involvement. According to the WHO classification, histologic examination is required for diagnosis, allowing also to distinguish among PTLD subtypes. However, in cases of severe and abrupt presentation, a diagnosis based on a combination of imaging studies and EBV-load determination is accepted. Therapies include prophylactic and pre-emptive interventions, aimed at eradicating EBV proliferation before symptoms onset, and targeted treatments. Among them, rituximab has emerged as first-line option, possibly combined with a reduction of immunosuppression, while EBV-specific cytotoxic T lymphocytes are effective and safe alternatives. Though prognosis remains poor, survival has markedly improved following the adoption of the aforementioned treatments. The validation of innovative, combined approaches is the future challenge.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transtornos Linfoproliferativos/etiologia , Adulto , Idoso , Linfócitos B/patologia , Linfócitos B/virologia , Criança , Diagnóstico Diferencial , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/imunologia , Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/prevenção & controle , Herpesvirus Humano 4/patogenicidade , Herpesvirus Humano 4/fisiologia , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , MicroRNAs/genética , Pessoa de Meia-Idade , Mutação , Prognóstico , Fatores de Risco , Rituximab/uso terapêutico , Linfócitos T Citotóxicos/transplante , Condicionamento Pré-Transplante/efeitos adversos , Transplante Homólogo/efeitos adversos , Ativação Viral
2.
Ann Hematol ; 100(4): 969-978, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33594448

RESUMO

A head-to-head comparison of outcomes of unrelated donor allogeneic peripheral blood stem cell transplantation for AML between reduced intensity conditioning (RIC) and myeloablative conditioning (MAC) regimens using thymoglobulin for GVHD prophylaxis is limited. We evaluated outcomes of 122 AML patients who received either busulfan (Bu)/fludarabine (Flu)/low-dose total body irradiation (TBI) as RIC (n = 64, 52%) or Bu/Flu as MAC (n = 58, 48%), and thymoglobulin 4.5 mg/kg total dose between day - 3 to - 1 for GVHD prophylaxis. Grades III-IV acute GVHD (aGVHD) was lower with Bu/Flu/TBI compared with Bu/Flu (6.2% vs 26.1%, p = 0.009). At 1 year, Bu/Flu/TBI was associated with similar chronic GVHD (41.2% vs 44.8%, p = 0.75), OS (61.9% vs 56.9%, p = 0.69), relapse rate (29.9% vs 20.7%, p = 0.24), relapse-free survival (52.8% vs 50%, p = 0.80), non-relapse mortality (17.4% vs 29.3%, p = 0.41), and GVHD-free relapse-free survival (24.2% vs 27.5%, p = 0.80) compared with Bu/Flu. Multivariable analysis did not reveal any difference in outcomes between both regimens. In summary, thymoglobulin at 4.5 mg/kg did not have any adverse impact on survival when used with RIC regimen. Both Bu/Flu/TBI and Bu/Flu conditioning regimens yielded similar survival.


Assuntos
Soro Antilinfocitário/uso terapêutico , Bussulfano/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/terapia , Agonistas Mieloablativos/uso terapêutico , Transplante de Células-Tronco de Sangue Periférico , Condicionamento Pré-Transplante/métodos , Vidarabina/análogos & derivados , Idoso , Aloenxertos , Bussulfano/efeitos adversos , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Infecções/epidemiologia , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Ácido Micofenólico/uso terapêutico , Agonistas Mieloablativos/efeitos adversos , Intervalo Livre de Progressão , Estudos Retrospectivos , Linfócitos T , Tacrolimo/uso terapêutico , Resultado do Tratamento , Doadores não Relacionados , Vidarabina/efeitos adversos , Vidarabina/uso terapêutico , Irradiação Corporal Total
3.
Int Dent J ; 71(1): 9-20, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33616057

RESUMO

INTRODUCTION: Graft-versus-host disease (GVHD) is a complication of haematopoietic stem cell transplantation (HSCT). GVHD may also develop following solid transplants or blood transfusions if white blood cells are transferred. GVHD affects multiple organs, including the oral tissues. OBJECTIVE: This pictorial review provides a background of GVHD to dental practitioners, describes the most common oral manifestations of GVHD and highlights the main treatment modifications needed to deliver dental care to patients with GVHD. METHODS: A narrative review enhanced with clinical photographs. RESULTS: Acute GVHD may manifest in the oral mucosa; however, it often develops immediately following HSCT when routine dental treatment is postponed. Chronic GVHD may manifest in the oral mucosa, the salivary glands and the musculoskeletal compartment. It may indirectly affect the teeth and the oral flora, putting the patient at risk for infections. Importantly, GVHD poses an increased risk for oral cancer. CONCLUSION: GVHD has a wide range of oral manifestations, some of which may affect dental treatment.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Crônica , Odontólogos , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Mucosa Bucal , Papel Profissional
4.
Lancet Haematol ; 8(3): e229-e239, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33636143

RESUMO

Immune-mediated cytopenia after allogeneic haematopoietic stem-cell transplantation is rare. The pathophysiology of immune-mediated anaemia, thrombocytopenia, and neutropenia, which occur alone or in combination with other cytopenias, is unclear and most probably a consequence of immune dysregulation. Risk factors for this complication have been identified in retrospective studies but these should be interpreted with caution and should not be generalised to this heterogeneous patient population. Diagnosis is challenging, requires awareness of such complications, and has to be differentiated from a multitude of other, and sometimes overlapping, possible complications. The clinical course of immune-mediated cytopenia is highly variable. Treatment requires an interdisciplinary approach and ranges from observation to symptomatic measures and directed therapies. Intensive immunosuppression is associated with an increased risk of infections and relapse, and current treatments are based on approaches in patients who have not undergone transplantation. Plasma cell-directed therapies, immunomodulation, and receptor-stimulating agents can be used to treat immune-mediated cytopenia.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neutropenia/etiologia , Trombocitopenia/etiologia , Transplante Homólogo/efeitos adversos , Antineoplásicos Imunológicos/uso terapêutico , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Neutropenia/tratamento farmacológico , Fatores de Risco , Trombocitopenia/tratamento farmacológico
5.
Br J Haematol ; 193(1): 43-51, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538335
6.
Blood Adv ; 5(3): 861-871, 2021 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-33560397

RESUMO

The novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), identified in late 2019 as the causative agent of COVID-19, was declared a pandemic by the World Health Organization on 11 March 2020. Widespread community transmission in the United States triggered a nationwide shutdown, raising major challenges for administration of hematopoietic stem cell transplant (HSCT) and chimeric antigen receptor (CAR)-T cell therapies, leading many centers to delay or cancel operations. We sought to assess the impact of the COVID-19 pandemic on operations and clinical outcomes for HSCT and CAR-T cellular therapies at the Dana-Farber Cancer Institute by reviewing administration and outcomes in 127 cell therapy patients treated during the initial COVID-19 surge: 62 adult allogeneic HSCT (allo-HSCT), 38 autologous HSCT (auto-HSCT), and 27 CAR-T patients. Outcomes were compared with 66 allo-HSCT, 43 auto-HSCT, and 33 CAR-T patients treated prior to the pandemic. A second control cohort was evaluated for HSCT groups to reflect seasonal variation in infections. Although there were changes in donor selection and screening as well as cryopreservation patterns of donor products, no differences were observed across groups in 100-day overall survival, progression-free survival, rates of non-COVID-19 infections, including hospital length of stay, neutrophil engraftment, graft failure, acute graft-versus-host disease in allo-HSCT patients, or cytokine release syndrome and neurotoxicity in CAR-T patients. No HSCT patients contracted COVID-19 between days 0 and 100. One CAR-T patient contracted COVID-19 at day +51 and died of the disease. Altogether, our data indicate that cellular therapies can be safely administered throughout the ongoing COVID-19 pandemic with appropriate safeguards.


Assuntos
/terapia , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , /patologia , Feminino , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Imunoterapia Adotiva , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Intervalo Livre de Progressão , Transplante Autólogo , Transplante Homólogo , Estados Unidos , Adulto Jovem
7.
Drug Discov Ther ; 14(6): 304-312, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33390570

RESUMO

Acute graft-versus-host disease (aGvHD) remains lethal as a life-threatening complication after allogeneic hematopoietic stem cell transplantation (HSCT). Inflammatory responses play an important role in aGvHD. 5-Aminolevulinic acid combined with sodium ferrous citrate (5-ALA/SFC) has been widely reported to have a major effect on the anti-inflammatory response; however, these effects in aGvHD models have never been reported. In this study, a murine aGvHD model was developed by transferring spleen cells from donor B6/N (H-2kb) mice into recipient B6D2F1 (H-2kb/d) mice. In addition to evaluating manifestations in aGvHD mice, we analyzed the serum ALT/AST levels, liver pathological changes, infiltrating cells and mRNA expression of inflammation-related cytokines and chemokines. 5-ALA/SFC treatment significantly ameliorated liver injury due to aGvHD and decreased the population of liver-infiltrating T cells, resulting in a reduced expression of pro-inflammatory cytokines and chemokines. Furthermore, the mRNA expression proliferator-activated receptor-γcoactivator (PGC-1α) was enhanced, which might explain why 5-ALA/SFC treatment downregulates inflammatory signaling pathways. Our results indicated that 5-ALA/SFC can ameliorate liver injury induced by aGvHD through the activation of PGC-1α and modulation of the liver mRNA expression of inflammatory-related cytokines and chemokines. This may be a novel strategy for treating this disease.


Assuntos
Citocinas/genética , Compostos Ferrosos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Ácidos Levulínicos/administração & dosagem , Fígado/efeitos dos fármacos , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Regulação para Cima , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Modelos Animais de Doenças , Quimioterapia Combinada , Compostos Ferrosos/química , Compostos Ferrosos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Ácidos Levulínicos/farmacologia , Fígado/imunologia , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Citrato de Sódio/química , Linfócitos T/metabolismo , Resultado do Tratamento
8.
Ann Hematol ; 100(3): 799-808, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33416901

RESUMO

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) has been regarded as a potential strategy for myeloid sarcoma (MS). The previous reports focused mainly on matched sibling donor (MSD) or matched unrelated donor (MUD) transplantation. There are no reports on haploidentical HSCT (haplo-HSCT) in MS. We retrospectively reviewed 14 MS patients who underwent haplo-HSCT. All patients achieved complete donor engraftment. The median time for neutrophil engraftment and platelet engraftment were 10 (12-21) days and 18 (8-31) days. The 100-day cumulative incidence of grade II-IV acute graft-versus-host disease (GVHD) and 3-year cumulative incidence of chronic GVHD were 37.7% (95%CI, 23.2-52.1%) and 35.7% (95%CI, 22.2-49.2%). Cytomegalovirus (CMV) reactivation was documented in 86% patients, and only one patient developed CMV pneumonia. Treatment-related mortality occurred in one (7%) patient. The 1- and 3-year cumulative incidence of relapse was 21.4% (95%CI, 11.8-31.1%) and 35.7% (95%CI, 22.4-49.0%). The probability of overall survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 64.3% (95%CI, 43.5-95.0%), respectively. The probability of disease-free survival at 1 and 3 years was 71.4% (95%CI, 51.3-99.5%) and 57.1% (95%CI, 36.3-89.9%), respectively. In conclusion, haplo-HSCT is a feasible method for patients with MS who have no MSD or MUD.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Sarcoma Mieloide/terapia , Transplante Haploidêntico , Adolescente , Adulto , Quimioprevenção , Criança , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Humanos , Masculino , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Sarcoma Mieloide/diagnóstico , Sarcoma Mieloide/epidemiologia , Sarcoma Mieloide/mortalidade , Irmãos , Análise de Sobrevida , Condicionamento Pré-Transplante/métodos , Transplante Haploidêntico/efeitos adversos , Transplante Haploidêntico/estatística & dados numéricos , Resultado do Tratamento , Adulto Jovem
9.
Ann Hematol ; 100(3): 743-752, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33427909

RESUMO

To overcome the delayed or failed engraftment after unrelated cord blood transplantation (CBT), we conducted a multicenter phase II study of intrabone single-unit CBT without antithymocyte globulin (ATG) for adult patients with hematological malignancies (UMIN-CTR, UMIN000020997). Sixty-four patients received an intrabone injection of unwashed (n = 61) or washed (n = 3) cord blood after local anesthesia. All injection-related adverse events were mild and resolved spontaneously. Sixty-two patients were evaluable for the efficacy of intrabone CBT of serological HLA-A, -B, and -DR ≥ 4/6 matched cord blood with a median number of 2.57 × 107/kg cryopreserved total nucleated cells. The probability of survival with neutrophil engraftment on day 28 was 77.4% (95% confidence interval, 67.0-85.8%), which exceeded the threshold value. The cumulative incidences of neutrophils ≥ 0.5 × 109/L on day 60 was 80.6% (68.2-88.6%), with a median time to recovery of 21 days after transplantation. The cumulative incidences of platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L on day 100 were 75.8% (62.6-84.9%) and 72.6% (59.4-82.1%), respectively, with median time to platelets ≥ 20 × 109/L and platelets ≥ 50 × 109/L of 38 and 45 days after transplantation, respectively. The cumulative incidences of grade II-IV and III-IV acute graft-versus-host disease were 29.0% and 6.5%, respectively. All responded to steroid therapy, and secondary treatments were not required. The present study suggests the efficacy of intrabone single-unit CBT without ATG in terms of early engraftment and controllable acute graft-versus-host disease.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical/métodos , Neoplasias Hematológicas/terapia , Infusões Intraósseas/métodos , Adolescente , Adulto , Idoso , Soro Antilinfocitário , Osso e Ossos , Transplante de Células-Tronco de Sangue do Cordão Umbilical/efeitos adversos , Feminino , Sangue Fetal/fisiologia , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/epidemiologia , Humanos , Incidência , Infusões Intraósseas/efeitos adversos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Ann Hematol ; 100(3): 763-777, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33491135

RESUMO

Allogeneic hematopoietic cell transplant (allo-HCT) is a potentially curative therapeutic strategy that showed encouraging long-term outcomes in hematological diseases. A number of factors can influence post-transplant clinical outcomes. While Epstein-Barr virus (EBV) constitutes a trigger for development of various adverse conditions, no clinical study yet has been powered to assess the effect of EBV serostatus on the clinical outcomes in allo-HCT population. To systematically summarize and analyze the impact of donor and recipient EBV serostatus on transplant outcomes in allo-HCT recipients, meta-analyses were conducted. Selected endpoints were overall survival (OS), relapse-free survival (RFS), relapse incidence (RI), non-relapse mortality (NRM), acute graft-versus-host disease (aGVHD), chronic graft-versus-host disease (cGVHD), and de novo cGVHD. Three studies with 26,650 patients, transplanted for acute leukemias, lymphomas, chronic hematological malignancies, or non-malignant hematological diseases were included in the meta-analysis. In the whole population, with a total of 53,300 donors and recipients, the rate of EBV seropositivity was 85.1%, including 86.6% and 83.6% among transplant recipients and healthy donors, respectively. Donor EBV seropositivity increased the risk of cGVHD by 17%, de novo cGVHD by 14%, and aGHVD by 5%. Recipient EBV seropositivity increased the risk of cGVHD by 12%, de novo cGVHD by 17%; increased NRM by 11%, increased RI by 11%, decreased OS by 14%, and decreased RFS by 11%. In performed meta-analyses, donor and recipient EBV seropositivity was found to have a significant impact on transplant outcomes in patients after allo-HCT.


Assuntos
Infecções por Vírus Epstein-Barr/epidemiologia , Neoplasias Hematológicas/epidemiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas , Doadores de Tecidos/estatística & dados numéricos , Transplantados/estatística & dados numéricos , Adolescente , Adulto , Idoso , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/mortalidade , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/diagnóstico , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante de Células-Tronco Hematopoéticas/mortalidade , Transplante de Células-Tronco Hematopoéticas/estatística & dados numéricos , Herpesvirus Humano 4/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Recidiva , Estudos Soroepidemiológicos , Análise de Sobrevida , Transplante Homólogo/efeitos adversos , Transplante Homólogo/mortalidade , Resultado do Tratamento , Adulto Jovem
11.
JAMA Netw Open ; 4(1): e2034750, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33502484

RESUMO

Importance: Ruxolitinib, a selective inhibitor of the Janus kinases 1/2 signaling pathway, has shown a significant response in steroid-refractory chronic graft-vs-host disease (SR-cGVHD), a major cause of morbidity and mortality in individuals who have undergone allogeneic hematopoietic stem cell transplantation (HSCT). Objectives: To investigate the clinical response to ruxolitinib in patients with SR-cGVHD after allogeneic HSCT and to evaluate its safety profile during the treatment course. Design, Setting, and Participants: This single-center case series included 41 consecutive patients who were treated with ruxolitinib for SR-cGVHD after allogeneic HSCT between August 2017 and December 2019. Data were collected from each patient's medical record at the First Affiliated Hospital of Zhejiang University School of Medicine. Data analysis was conducted from March to May 2020. Exposure: Ruxolitinib. Main Outcomes and Measures: Treatment responses, factors associated with response, and adverse effects during ruxolitinib administration. Findings: Overall, 41 patients (median [range] age, 31 [17-56] years; 14 [34.1%] women) were treated with ruxolitinib and included in this study. A total of 15 patients (36.6%) had a complete remission, and 14 (34.1%) had a partial remission, with an overall response rate of 70.7% (29 patients; 95% CI, 56.2%-85.3%). Lung involvement (odds ratio, 0.112; 95% CI, 0.020-0.639; P = .01) and matched related donors (odds ratio, 0.149; 95% CI, 0.022-0.981; P = .048) were associated with less favorable treatment response. Major adverse events associated with ruxolitinib were cytopenias and infectious complications. The median (range) follow-up for this cohort was 14.9 (1.4-32.5) months. Prolonged survival was observed in patients with a male donor (P = .006), complete remission before transplantation (P = .02), baseline moderate cGVHD (P = .02), and skin cGVHD (P = .001). Conclusions and Relevance: In this small, single-site case series, ruxolitinib demonstrated a significant response in heavily pretreated patients with SR-cGVHD and a reasonably well-tolerated safety profile. The results add to the body of literature suggesting ruxolitinib as a promising treatment option in SR-cGVHD.


Assuntos
Doença Enxerto-Hospedeiro/tratamento farmacológico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas , Pirazóis/uso terapêutico , Adolescente , Adulto , Doença Crônica , Feminino , Doença Enxerto-Hospedeiro/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Esteroides/uso terapêutico
14.
Ter Arkh ; 92(7): 23-30, 2020 Sep 01.
Artigo em Russo | MEDLINE | ID: mdl-33346442

RESUMO

AIM: Analysis of the effectiveness of the MSCs aministration as the second- or third-line therapy of acute GVHD (aGVHD) resistant to glucocorticosteroid treatment. MATERIALS AND METHODS: The study included 35 patients who received MSCs obtained from the bone marrow of healthy donors as a treatment of steroid-resistant aGVHD. The clinical parameters of patients, MSCs cultural characteristics, the MSC expression profile for various genes including those involved in immunomodulation, expression of cells surface markers, the source of MSCs, as well as the frequency and number of MSC administrations were analyzed. RESULTS: Response to therapy was achieved in 74% of cases, a complete response was reached in 13 (37%) patients, partial response/clinical improvement was demonstrated in 13 (37%). This treatment was ineffective in 9 patients. The prediction of a group of patients with good response to MSC therapy turned to be impossible. The differences between the effective and ineffective for the GVHD treatment MSCs samples were found. The effective ones were characterized with a decreased total MSCs production and an increase in the main histocompatibility complex and PDL-1 antigens expression. CONCLUSION: These data allow to select optimal samples for aGVHD treatment that can improve clinical results. aGVHD treatment with MSCs has shown efficacy comparable to other treatment approaches. Given the low percentage of complications and the absence of significant adverse effects, MSC therapy seems to be one of the optimal approaches to the treatment of resistant forms of GVHD.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Doença Aguda , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/terapia , Humanos , Transplante Homólogo
15.
Int J Mol Sci ; 21(24)2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33371421

RESUMO

(1) Background: survivors of allogeneic hematopoietic cell transplantation (alloHCT) suffer from morbidity and mortality due to cardiovascular events. We hypothesized that vascular injury and pro-coagulant activity are evident in alloHCT survivors without existing alloHCT complications or relapse. (2) Methods: we enrolled consecutive adult alloHCT survivors without established cardiovascular disease and control individuals matched for traditional cardiovascular risk factors (January-December 2019). Circulating microvesicles (MVs) of different cellular origins (platelet, erythrocyte, and endothelial) were measured by a standardized flow cytometry protocol as novel markers of vascular injury and pro-coagulant activity. (3) Results: we recruited 45 survivors after a median of 2.3 (range 1.1-13.2) years from alloHCT, and 45 controls. The majority of patients suffered from acute (44%) and/or chronic (66%) graft-versus-host disease (GVHD). Although the two groups were matched for traditional cardiovascular risk factors, alloHCT survivors showed significantly increased platelet and erythrocyte MVs compared to controls. Within alloHCT survivors, erythrocyte MVs were significantly increased in patients with a previous history of thrombotic microangiopathy. Interestingly, endothelial MVs were significantly increased only in alloHCT recipients of a myeloablative conditioning. Furthermore, MVs of different origins showed a positive association with each other. (4) Conclusions: endothelial dysfunction and increased thrombotic risk are evident in alloHCT recipients long after alloHCT, independently of traditional cardiovascular risk factors. An apparent synergism of these pathophysiological processes may be strongly involved in the subsequent establishment of cardiovascular disease.


Assuntos
Fatores de Coagulação Sanguínea , Doenças Cardiovasculares/diagnóstico , Micropartículas Derivadas de Células/patologia , Endotélio Vascular/lesões , Doença Enxerto-Hospedeiro/etiologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Adolescente , Adulto , Sobreviventes de Câncer/estatística & dados numéricos , Doenças Cardiovasculares/etiologia , Estudos de Casos e Controles , Feminino , Doença Enxerto-Hospedeiro/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo , Adulto Jovem
16.
Adv Clin Exp Med ; 29(10): 1221-1230, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33064381

RESUMO

The increasing number of hematopoietic stem cell transplantation (HSCT) procedures and lower transplant-related mortality has led to a growing population of survivors facing long-term increased risk of secondary malignancy, including cutaneous neoplasms. In this review, we aim to discuss the incidence, risk factors and preventive strategies for secondary skin neoplasms after autologous and allogeneic HSCT. Cutaneous neoplasms, such as basal cell carcinoma, squamous cell carcinoma and melanoma, are among the most common solid cancers arising in patients after HSCT. Besides risk factors established in the general population, primary disease, chronic graft-versus-host disease (CGvHD), prolonged immunosuppression, especially with the use of cyclosporine and azathioprine, radiation exposure, light skin color, male sex, and young age at transplantation play a role in the development of cutaneous neoplasms in HSCT recipients. Skin cancer development after HSCT may be explained by cumulative effects of chemotherapy and radiotherapy-induced DNA damage, prolonged immunosuppressive conditions and chronic mucosal inflammation, particularly after allogeneic HSCT. Delayed immune recovery and persistent immunodeficiency in patients with graft-versus-host disease (GvHD) may also contribute to carcinogenesis. Regular dermatological surveillance and prompt recognition of precancerous and cancerous lesions is crucial for patient's prognosis and management.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neoplasias Cutâneas , Ciclosporina , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/etiologia , Transplante Homólogo
17.
Medicine (Baltimore) ; 99(43): e22781, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120791

RESUMO

RATIONALE: Hematopoietic stem cell transplantation (HSCT) is the most effective treatment for the majority of patients who have malignant haemolytic disease. Although the success rate of HSCT has increased, the increasing number of cases suffering from secondary solid malignancies after HSCT has attracted more interest recently. PATIENT CONCERNS: A 16-year-old female patient from China presented with a crusty and painful lesion on the left buccal mucosa with a history of chronic graft-versus-host disease following allogeneic HSCT for acute myeloid leukaemia. DIAGNOSIS: An incisional biopsy of the lesion showed stratified squamous epithelium mucosa with severe dysplasia (carcinoma in situ). Subsequently, a wide local excision was performed and histological examination revealed early infiltrating squamous epithelial mucosa (carcinoma in situ). INTERVENTIONS: She was being treated in the oral and maxillofacial surgery clinic with an incisional biopsy of the left buccal mucosa. She also received a wide local excision. OUTCOMES: Follow-up for 4 years showed no recurrence. LESSONS: This case helps raise awareness of the diagnosis of oral symptoms in young patients after HSCT. Due to the increasing application of HSCT, raising awareness in oral and dental physicians may be required to improve long-term clinical outcome of patients who underwent HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Neoplasias Bucais/etiologia , Adolescente , Feminino , Doença Enxerto-Hospedeiro/etiologia , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Neoplasias Bucais/patologia , Neoplasias Bucais/cirurgia
18.
J Am Dent Assoc ; 151(11): 846-856, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33121606

RESUMO

BACKGROUND: Long-term survivors of allogeneic hematopoietic cell transplantation will increasingly seek care from dental providers. METHODS: The authors highlight the importance of minimizing oral symptoms and complications associated with oral chronic graft-versus-host-disease (cGVHD). RESULTS: Chronic GVHD is the result of an immune response of donor-derived cells against recipient tissues. Oral cGVHD can affect the mucosa and damage salivary glands and cause sclerotic changes. Symptoms include sensitivity and pain, dry mouth, taste changes, and limited mouth opening. Risk of developing caries and oral cancer is increased. Food intake, oral hygiene, and dental interventions can represent challenges. Oral cGVHD manifestations and dental interventions should be managed in close consultation with the medical team, as systemic treatment for cGVHD can have implications for dental management. CONCLUSIONS: General dental practitioners can contribute substantially to alleviating oral cGVHD involvement and preventing additional oral health deterioration. PRACTICAL IMPLICATIONS: Frequent examinations, patient education, oral hygiene reinforcement, dry mouth management, caries prevention, and management of dental needs are indicated. In addition, oral physical therapy might be needed. Invasive dental interventions should be coordinated with the transplantation team. Screening for oral malignancies is important even years after resolution of GVHD symptoms. Management of the oral manifestations of cGVHD might require referral to an oral medicine professional.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Doença Crônica , Odontólogos , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Papel Profissional
19.
Anticancer Res ; 40(11): 6531-6537, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33109594

RESUMO

BACKGROUND: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. PATIENTS AND METHODS: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni- and multivariate risk factor analyses were performed. RESULTS: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graft-versus-host disease (GVHD), nor GVHD-free relapse-free survival. CONCLUSION: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.


Assuntos
Fator 7 de Crescimento de Fibroblastos/administração & dosagem , Doença Enxerto-Hospedeiro/tratamento farmacológico , Células-Tronco Hematopoéticas/efeitos dos fármacos , Estomatite/terapia , Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/patologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Intervalo Livre de Progressão , Estomatite/complicações , Estomatite/patologia , Transplante Homólogo/efeitos adversos , Resultado do Tratamento , Adulto Jovem
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