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1.
Medicine (Baltimore) ; 99(40): e22642, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019490

RESUMO

RATIONALE: Reactivation of hepatitis B virus (HBV) after treatment with bortezomib-based regimens in HBV-positive patients with multiple myeloma (MM) has been reported in the past few years. Nevertheless, there is evidence of inhibition of HBV replication by bortezomib in transgenic mice. However, there is still no clinical evidence that bortezomib inhibits HBV. PATIENT CONCERNS: A 55-year-old MM patient with a family history of MM, who was also a chronic HBV carrier, achieved HBV clearance after treatment with a bortezomib-based regimen in combination with anti-HBV drugs. DIAGNOSES: The diagnosis was MM with chronic carrier of HBV. INTERVENTIONS: He received bortezomib-based regimen for MM as well as entecavir as a prophylaxis to prevent HBV reactivation. OUTCOMES: This patient achieved HBsAg and HBV-DNA clearance after 2 months and the remission was maintained during the next 2 years. He also achieved complete remission of MM and underwent consolidation therapy with autologous hematopoietic stem cell transplantation. LESSONS: This is the first case of MM with HBV clearance after receiving a bortezomib-based regimen combined with anti-HBV drug. Research on related mechanisms might provide new suggestions and hope for better management of HBV positive patients with MM and for the treatment of HBV patients.


Assuntos
Antineoplásicos/uso terapêutico , Antivirais/uso terapêutico , Bortezomib/uso terapêutico , Guanina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Protocolos Clínicos , Quimioterapia Combinada , Guanina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Antígenos de Superfície da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/efeitos dos fármacos , Vírus da Hepatite B/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/prevenção & controle , Hepatite B Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Autólogo/métodos , Resultado do Tratamento
2.
F1000Res ; 92020.
Artigo em Inglês | MEDLINE | ID: mdl-32953089

RESUMO

Aplastic anemia (AA) in its severe form has historically been associated with high mortality. With limited supportive care and no effective strategy to reverse marrow failure, most patients diagnosed with severe AA (SAA) died of pancytopenia complications. Since the 1970s, hematopoietic stem cell transplantation (HSCT) and immunosuppressive therapy (IST) have changed SAA's natural history by improving marrow function and pancytopenia. Standard IST with horse anti-thymocyte globulin plus cyclosporine produces a hematologic response rate of 60 to 70%. In the long term, about one-third of patients relapse, and 10 to 15% can develop cytogenetic abnormalities. Outcomes with either HSCT or IST are similar, and choosing between these modalities relies on age, availability of a histocompatible donor, comorbidities, and patient preference. The introduction of eltrombopag, a thrombopoietin receptor agonist, improved SAA outcomes as both salvage (second-line) and upfront therapy combined with IST. As a single agent, eltrombopag in doses up to 150 mg daily improved cytopenias in 40 to 50% in those who failed initial IST, which associated with higher marrow cellularity, suggesting a pan-stimulatory marrow effect. When eltrombopag was combined with IST as upfront therapy, overall (about 90%) and complete responses (about 50%) were higher than observed extensively with IST alone of 65% and 10%, respectively. Not surprisingly, given the strong correlation between hematologic response rates and survival in SAA, most (>90%) were alive after a median follow-up of 18 months. Longer follow-up and real-word data continue to confirm the activity of this agent in AA. The use of eltrombopag in different combinations and doses are currently being explored. The activity of another thrombopoietin receptor agonist in AA, romiplostim, suggests a class effect. In the coming years, the mechanisms of their activity and the most optimal regimen are likely to be elucidated.


Assuntos
Anemia Aplástica/terapia , Soro Antilinfocitário/uso terapêutico , Ciclosporina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Imunossupressores/uso terapêutico , Animais , Cavalos , Humanos , Terapia de Salvação
3.
Bull Cancer ; 107(9): 925-933, 2020 Sep.
Artigo em Francês | MEDLINE | ID: mdl-32921398

RESUMO

Sickle cell disease is associated with severe complications and early mortality in adults. In children, hematopoietic stem cell transplant from HLA-identical sibling can stop the progression of the disease and leads to more than 95% long-term free survival without sickle cell disease. The aim of this workshop was to define indications and modalities of allogeneic hematopoietic stem cell transplant in children and adults with sickle cell disease. Patient and sibling HLA typing should be proposed, early in the course of the disease, when intensification therapies are required. Indications of transplant from HLA-identical sibling in children and adults are, cerebral vasculopathy, occurrence of vaso-occlusive events despite hydroxycarbamide, renal and hepatic diseases related to SCD, chronic anemia<7g/dL despite hydroxycarbamide, need to maintain transfusion programs longer than six months, and major transfusion difficulties related to red blood cell alloimmunization. In children with an HLA-identical sibling donor, we recommend a myeloablative conditioning regimen associating high dose busulfan, cyclophosphamide and ATG, considering the excellent results of this approach In patients over 15 years of age, we recommend the NIH approach consisting of a reduced intensity conditioning regimen by alemtuzumab, and 3Gy total body irradiation, followed by peripheral hematopoietic stem cells and post-transplant immunosuppression by sirolimus In the absence of HLA-identical sibling donor, there is no definitive data for preferring transplant from unrelated versus haplo-identical donors but we recommend to evaluate these approaches in prospective trials.


Assuntos
Anemia Falciforme/cirurgia , Transplante de Células-Tronco Hematopoéticas , Adulto , Criança , Humanos , Transplante Homólogo
4.
Medicine (Baltimore) ; 99(38): e22062, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957327

RESUMO

RATIONALE: Primary central nervous system lymphoma (PCNSL) involving the choroid plexus is exceedingly rare. The differential diagnosis for choroid plexus enhancing lesions in addition to lymphoma includes infections, sarcoidosis, tuberculosis, papilloma, meningioma, subependymoma, and metastatic lesions. PATIENT CONCERNS: A 71-year-old man presented with 3 days of episodic memory loss and gait disturbance. Brain magnetic resonance imaging showed homogenously enhancing lesions with mildly restricted diffusion and T2 hypointensity in the lateral ventricles, as well as T2 hyperintensity and enhancement in the right hippocampus. His episodic memory loss was thought to be secondary to subclinical focal seizures, supported by EEG revealing right temporal lobe epileptiform discharges. DIAGNOSES: Large B-cell lymphoma, nongerminal center type was revealed on pathological examination. INTERVENTIONS: Stereotactic biopsy of his right thalamic lesion was performed. OUTCOMES: The patient underwent induction therapy with high-dose methotrexate, temozolomide, and rituximab, which resulted in complete resolution of the enhancing lesions. He then underwent conditioning chemotherapy with carmustine and thiotepa, followed by autologous stem cell transplantation. His PCNSL remains in remission 42 weeks after the onset of symptoms. LESSONS: We report a patient with multifocal PCNSL involving the choroid plexus, who presented with abnormal gait and episodic confusion and memory loss. PCNSL should be considered in the differential diagnosis of acute encephalopathy among immunocompetent older individuals who have choroid plexus enhancing lesions.


Assuntos
Neoplasias do Sistema Nervoso Central/diagnóstico , Linfoma não Hodgkin/diagnóstico , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biópsia , Neoplasias do Sistema Nervoso Central/terapia , Diagnóstico Diferencial , Eletroencefalografia , Transplante de Células-Tronco Hematopoéticas , Humanos , Linfoma não Hodgkin/terapia , Imagem por Ressonância Magnética , Masculino
5.
Medicine (Baltimore) ; 99(38): e22129, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32957333

RESUMO

INTRODUCTION: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. Patient concerns: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation. DIAGNOSIS: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy. INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-α receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out. OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before. CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD. RATIONALE: Fecal microbiota transplantation (FMT), administering fecal suspensions via a nasoduodenal tube, has achieved a promising effect in the treatment of intestinal graft-versus-host disease (GvHD) in some pilot studies. In this study, oral FMT capsules from unrelated donor were used for the first time in the treatment of intestinal GvHD. PATIENT CONCERNS: A 31-year-old male who was diagnosed as "myelodysplastic syndromes with excess blasts II" (intermediate risk 2 of international prognostic scoring system) received human leukocyte antigen -matched sibling donor allogeneic hematopoietic stem cell transplantation. The patient developed diarrhea, vomiting, and bloody stool on 28 days after transplantation. DIAGNOSES: Intestinal acute GvHD was diagnosed clinically with histological confirmation by colonoscopy and pathological biopsy. INTERVENTIONS: This patient was treated with first cycle of oral FMT capsules after failure to initial treatment of methylprednisolone (2 mg/kg/d) combined with recombinant human tumor necrosis factor-a receptorII: IgG Fc fusion protein (25 mg, biw). The symptoms of intestinal GvHD were relieved but recurred 11 days later. Second cycle of oral FMT capsules was carried out. OUTCOMES: After 2 cycles of fecal bacteria transplantation, intestinal GvHD was gradually controlled and did not recur again during the 2-month follow-up. The diversity and structure of the intestinal flora after FMT was closer to that of healthy donors than that before. CONCLUSION: Our case showed oral FMT capsules could be used as a treatment option for corticosteroid refractory intestinal GvHD. Further studies are warranted to assess the clinical efficacy and safety of oral FMT capsules in the treatment of intestinal GvHD. LESSONS: There is still a possibility of recurrence after the treatment of GvHD with capsule fecal microbiota transplantation. How to optimize the dosage and treatment course of fecal microbiota capsule administration needs further exploration.


Assuntos
Transplante de Microbiota Fecal , Doença Enxerto-Hospedeiro/terapia , Enteropatias/terapia , Adulto , Cápsulas , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Síndromes Mielodisplásicas/terapia , Doadores não Relacionados
6.
Zhonghua Yi Xue Za Zhi ; 100(37): 2892-2896, 2020 Oct 13.
Artigo em Chinês | MEDLINE | ID: mdl-32993246

RESUMO

Objective: To Explore the current status and risk factors of perioperative allogenic red blood cell transfusion following enhanced recovery hip and knee joint arthroplasty. Methods: Patients who have taken their primary unilateral total hip and knee arthroplasty (THA, TKA) or simultaneous primary THA were retrospectively included from January, 2019 to December, 2019 in West China Hospital. The baseline characteristics were compared between patients with allogeneic transfusion and those without. And logistic regression were used to analyze the risk factors of perioperative allogeneic red blood cell transfusion. Results: A total of 2 034 patients (2072 arthroplasties) were included, 705 males and 1 329 females, aged (60±24) years. Of all, 1 137 patients received primary THA (38 simultaneous THA), 897 patients received primary unilateral TKA. Eleven (0.54%) patients received allogeneic red blood cell transfusion, and the mean volume was (2.6±1.2) U. Deep venous thrombosis occurred in 2 patients (0.09%) undergoing primary TKA. The transfusion rate in primary THA patients was 0.79% (9/1 137), and 0.22% (2/897) in TKA. Lower preoperative hemoglobin level (P=0.041) and more hematological comorbidities (P=0.005) were detected in transfused patients. And logistic analysis further revealed that preoperative substandard hemoglobin level was the most important risk factor for transfusion (OR=5.663, P=0.018). Conclusions: Under the intervention of enhanced recovery after surgery concept and modern blood management strategies, the transfusion requirement has been significantly reduced following primary joint arthroplasty. Pre-operative hemoglobin level should be an important threshold for perioperative blood management.


Assuntos
Artroplastia do Joelho , Transplante de Células-Tronco Hematopoéticas , Adulto , Idoso , Idoso de 80 Anos ou mais , Transfusão de Sangue , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
7.
Medicine (Baltimore) ; 99(35): e22064, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871966

RESUMO

RATIONALE: Patients with relapsed acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) have poor prognosis. Many patients are not eligible for 2nd HSCT due to organ dysfunction or other complications that prevent them from tolerating conditioning chemotherapy. In those ineligible patients for 2nd HSCT with myeloablative conditioning regimen, reduced intensity conditioning (RIC) are often used. RIC regimens are less toxic but has a less direct anti-tumor efficacy so that RIC regimens are not suitable for the patients with high tumor burden. To overcome this dilemma, Gemtuzumab Ozogamicin (GO) has been used as a part of RIC regimens to add anti-tumor efficacy. We report here a relapsed AML patient who was treated with GO monotherapy followed by stem cell infusion. PATIENT CONCERNS: A 25-year-old male with AML experienced relapse 9 months after allo-HSCT. DIAGNOSIS: Since he had mild renal and cardiac dysfunction and his AML did not progress rapidly, we decided not to give him an intensive chemotherapy. However, after azacitidine (AZA) and donor lymphocyte infusion therapy, his leukemic blasts did not decrease. INTERVENTIONS: Originally, we had planned to proceed with a 2nd allo-HSCT with RIC regimen that consisted of fludarabine, melphalan and fractionated GO (3 mg/m/dose) on day -21, -18, and -15. However, the patient developed appendicitis after the last dose of GO when his neutrophil was 0 cells/µl. Based on his medical acuity, we terminated the rest of the patients conditioning regimen and the patient did not receive any further chemotherapeutics. The patient was still infused with peripheral blood stem cells from the donor on day 0. OUTCOMES: His appendicitis was resolved by antibiotics without surgery. His AML has been in CR more than 18 months under AZA maintenance therapy. LESSONS: GO monotherapy could be a conditioning regimen of 2nd allo HSCT from the same donor as the first HSCT for relapsed AML patients.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Gemtuzumab/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Adulto , Humanos , Masculino , Recidiva , Transplante Homólogo
8.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 34(9): 1184-1189, 2020 Sep 15.
Artigo em Chinês | MEDLINE | ID: mdl-32929914

RESUMO

Objective: To study the effect of chemical extraction of allogeneic tendon and allogeneic chondrocytes for reconstruction of anterior labrum of shoulder joint in rabbits. Methods: The body weight of 45 adult New Zealand white rabbits ranged from 2.5 to 3.0 kg. The Achilles tendons of 15 rabbits were taken and the allogeneic tendons were prepared by chemical extraction with antigen inactivation. The extracted tendons were compared with untreated tendons by HE and Masson stainings. Chondrocytes were isolated and cultured by trypsin method and identified by immunohistochemical staining of collagen type Ⅱ. The remaining 30 rabbits were used to prepare the model of anterior labrum defect of shoulder joint. After the allogeneic tendon was transplanted to the damaged labrum, the rabbits was randomly divided into two groups (15 in each group). In group A, the allogeneic chondrocytes were injected into the joint immediately after transplantation, while in group B, no treatment was made. At 4, 6, and 8 weeks after operation, 5 transplanted tendons of each group were taken. After general observation, HE staining was used to observe the number of nuclei, Masson staining was used to observe the expression of collagen fibers in muscle fiber tissues, and AB staining was used to detect the glycosaminoglycan level after transplantation, to evaluate the cell growth in the tissues of the two groups of allogeneic tendon. Results: By HE and Masson stainings, the allogeneic tendon antigen prepared by chemical extraction method was inactivated and the fibrous tissue structure was intact; collagen type Ⅱ immunohisto-chemistry staining showed that the cultured cells were chondrocytes. After tendon transplantation, the content of glycosaminoglycan in group A was significantly higher than that in group B ( P<0.05). At 6 weeks after operation, HE staining showed that the nuclear in tendon tissue of group A was significantly more than that of group B ( t=20.043, P=0.000). Masson staining showed that the number of nuclei in tendon tissue of group A was significantly increased, the muscle fibers and collagen fibers were interlaced, the tissue structure was more compact, and the tendon tissue was mainly blue stained; while the number of nuclei in group B was less, mainly collagen fibers of the original graft. Conclusion: The allogeneic tendon inactivated by chemical extraction can be used to reconstruct the defect of anterior labrum of shoulder joint in rabbits, and the combination of allogeneic chondrocytes can promote the healing of tendon transplantation.


Assuntos
Tendão do Calcâneo , Transplante de Células-Tronco Hematopoéticas , Articulação do Ombro , Animais , Condrócitos , Coelhos , Cicatrização
9.
Rinsho Ketsueki ; 61(8): 890-900, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908053

RESUMO

Although Hodgkin lymphoma is now among the most curable of the lymphomas, the relapse rate after the first-line treatment remains at 20-30%. Brentuximab vedotin (BV) has been developed for the treatment of newly diagnosed classical Hodgkin lymphoma (cHL), relapsed/refractory cHL, or consolidation after autologous stem cell transplantation. Notably, BV treatment combined with doxorubicin, vinblastine, and dacarbazine treatment has been established as standard treatment for newly diagnosed advanced-stage cHL. Immune-checkpoint inhibitors represent another class of promising cancer immunotherapies that may be used to treat advanced cancers, including cHL. Anti-programmed death-1-blocking antibodies have been used to enhance immunity in cases of several malignancies and obtain durable responses, most notably in patients who have been administered heavy treatment for relapsed/refractory cHL. Several clinical trials, including single agents or combination therapies for cHL, have been developed or are currently under investigation. The results of the ongoing and future clinical trials may establish new paradigms for the treatment of cHL.


Assuntos
Brentuximab Vedotin/uso terapêutico , Doença de Hodgkin , Transplante de Células-Tronco Hematopoéticas , Doença de Hodgkin/tratamento farmacológico , Humanos , Imunoconjugados , Recidiva Local de Neoplasia , Transplante Autólogo
10.
Rinsho Ketsueki ; 61(8): 945-952, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908059

RESUMO

Human herpesvirus (HHV)-6B encephalitis has been increasingly recognized as an important central nervous system (CNS) complication after allogeneic hematopoietic stem cell transplantation. In this review, the best way to diagnose and treat this devastating complication is described. Diagnostic pitfalls: HHV-6B encephalitis should be diagnosed based on the presence of CNS symptoms, positive results for HHV-6 DNA in the cerebrospinal fluid (CSF), and exclusion of other causes of CNS symptoms. There are potential pitfalls when diagnosing HHV-6B encephalitis. Moreover, false-positive detection of HHV-6 DNA in the CSF can occur. Pleocytosis is observed in few patients, and CSF protein levels are often normal. Limbic encephalitis findings are not commonly detected through a brain MRI at the time of development. Prevention: Neither routine monitoring nor routine prophylactic antiviral therapy is recommended to prevent the development of HHV-6B encephalitis. Treatment: Empiric therapy should be started immediately after HHV-6B encephalitis is suspected. The Guideline Committee of the JSHCT recommends full-dose foscarnet (180 mg/kg/day) for the treatment of HHV-6B encephalitis. Therapeutic effect of anti-HHV6 therapy is assessed based on CNS symptoms and HHV-6 DNA in the CSF, which should be evaluated 1-2 weeks after initiating treatment. Even in patients exhibiting good therapeutic effects, antiviral treatment should be continued for at least 3 weeks.


Assuntos
Encefalite Viral , Transplante de Células-Tronco Hematopoéticas , Herpesvirus Humano 6 , Infecções por Roseolovirus , Foscarnet , Humanos , Transplante Homólogo
11.
Rinsho Ketsueki ; 61(8): 959-964, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908061

RESUMO

Graft-versus-host disease (GVHD) is a potentially life-threatening complication associated with allogeneic hematopoietic stem cell transplantation (allo-SCT). Although prophylaxis and GVHD treatment using immunosuppressants are essential for a successful allo-SCT, profound immunosuppression could lead to an infection and/or the recurrence of malignant diseases. Recently, the concept of tissue tolerance has emerged. This concept has been identified as a means to suppress GVHD by relying on tissue-intrinsic mechanisms that are independent from those underlying immune tolerance. Thus, GVHD prophylaxis and treatments targeting the mechanisms that promote tissue tolerance could help suppress GVHD and maintain leukocyte-mediated immune responses against tumors and infectious pathogens. Epithelial regeneration from LGR5-positive intestinal stem cells and epithelial maintenance mediated by metabolites from the intestinal microbiota are representative mechanisms that promote tissue tolerance in the gut. However, these protective mechanisms are weakened by GVHD and conditioning regimens. This review focuses on the pathophysiology of acute GVHD and tissue-intrinsic mechanisms that promote tissue tolerance.


Assuntos
Doença Enxerto-Hospedeiro , Microbioma Gastrointestinal , Transplante de Células-Tronco Hematopoéticas , Humanos , Condicionamento Pré-Transplante , Transplante Homólogo
12.
Rinsho Ketsueki ; 61(8): 971-978, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32908063

RESUMO

The event-free survival rate for childhood acute myeloid leukemia (AML) is approaching 60%, owing to the use of intensive chemotherapy, optimal indication of hematopoietic stem cell transplantation, and advances in supportive care. For further improvement, the development of more definitive risk stratification system and introduction of more effective treatment options are necessary. Recently, much attention has been drawn on minimal residual disease (MRD) that is considered a strong prognostic factor for children with AML. Recent studies from the United States and Europe have shown the prognostic impact of FCM-based MRD detection and it is already used for risk stratification in modern AML protocols. Myeloid leukemia in Down's syndrome (ML-DS) has unique characteristics, and ML-DS children are recently being treated separately from non-DS AML children with less intensive treatment. It has been shown that relapsed and refractory cases of ML-DS are difficult to treat; however, no universal prognostic factor has been found yet. In order to determine accurate methods for identifying a subgroup with poor prognosis, an attempt to analyze the role of MRD had been examined in the JPLSG AML-D11 study. In this study, the MRD by FCM and targeted deep sequencing for GATA1 after initial induction therapy were significant prognosis factors for predicting relapse.


Assuntos
Leucemia Mieloide Aguda , Criança , Europa (Continente) , Transplante de Células-Tronco Hematopoéticas , Humanos , Neoplasia Residual , Transplante Homólogo
14.
Anticancer Res ; 40(10): 5707-5713, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988896

RESUMO

BACKGROUND/AIM: Genetic variations of the non-coding RNA gene, ANRIL, have been associated with human diseases including cancer, type-2 diabetes, and atherosclerosis. In the present study, we investigated the potential associations of select ANRIL single nucleotide polymorphisms (SNPs) with overall survival and other clinical outcomes in adult patients with hematologic malignancies after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS: Genomic DNA was extracted from whole blood samples from 103 adult patients with hematologic malignancies who had received allo-HSCT followed by oral tacrolimus therapy. The genotypes of four select ANRIL SNPs, rs564398, rs1063192, rs2151280, and rs2157719 were determined using qRT-PCR-based genotyping assays. RESULTS: rs2151280 (C->T) in ANRIL was associated with worse overall survival in these patients (CT/CC vs. TT). Contrarily, rs2151280 and the other select ANRIL SNPs were not associated with death at Day-100 after transplantation, the incidence of graft-versus-host disease (GVHD), acute kidney injury (AKI), and neurotoxicity in the study cohort. CONCLUSION: rs2151280 represents a potential prognostic biomarker for overall survival in adult patients with hematologic malignancies after allo-HSCT.


Assuntos
Estudos de Associação Genética , Predisposição Genética para Doença , Neoplasias Hematológicas/genética , RNA Longo não Codificante/genética , Lesão Renal Aguda/etiologia , Lesão Renal Aguda/genética , Lesão Renal Aguda/patologia , Idoso , Feminino , Genótipo , Doença Enxerto-Hospedeiro/etiologia , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/patologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/patologia , Neoplasias Hematológicas/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Intervalo Livre de Progressão , Tacrolimo/farmacocinética , Transplante Homólogo/efeitos adversos
15.
Anticancer Res ; 40(10): 5909-5917, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32988922

RESUMO

BACKGROUND/AIM: Cytomegalovirus (CMV) replication may cause life-threatening complications after allogeneic haematopoietic stem cell transplantation (allo-HSCT). The aim of the study was to characterize CMV events, and the outcome of letermovir (LTV) CMV prophylaxis. PATIENTS AND METHODS: In this retrospective analysis of patients treated with an allo-HSCT between 2010 and 2020, we determined plasma CMV events, as well as associated risk factors. RESULTS: We identified 423 patients who had undergone allo-HSCT between 2010 and 2020. CMV DNAemia was found in 130/423 (30.7%) of patients. CMV reactivation rate was significantly higher in patients with acute graft-versus-host disease, HLA mismatch, and CMV IgG seropositivity of donors and recipients. Among 42 patients receiving LTV prophylaxis those, 5 (11.9%) showed CMV DNAemia under LTV versus 87/353 (24.6%) in a control group. CONCLUSION: Despite the development of better approaches with weekly monitoring and early treatment initiation, CMV reactivations play an important role after allo-HSCT.


Assuntos
Acetatos/administração & dosagem , Infecções por Citomegalovirus/tratamento farmacológico , Citomegalovirus/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Quinazolinas/administração & dosagem , Adulto , Idoso , Citomegalovirus/patogenicidade , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/etiologia , Infecções por Citomegalovirus/virologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Replicação Viral/efeitos dos fármacos
16.
Ann Hematol ; 99(11): 2619-2628, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32960314

RESUMO

In the era of tyrosine kinase inhibitors (TKIs), allogeneic hematopoietic stem cell transplantation (allo-HSCT) is recommended as a standard approach for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) achieving complete remission (CR). However, the role of autologous hematopoietic stem cell transplantation (auto-HSCT) in adult patients achieving complete molecular remission (CMR) is an alternative, less toxic treatment options, especially for the patients who lack suitable donors and are unfit for allo-HSCT. Thus, we conducted a systematic review and meta-analysis to compare the efficacy of allo-HSCT and auto-HSCT for the treatment of adult patients with Ph+ ALL. We searched the PubMed, Embase, Scopus, and Cochrane Library for studies published before June 2019 without language restriction. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for overall survival (OS) and relapse-free survival (RFS) and odds ratios (ORs) and 95% CIs for relapse rate (RR) and treatment-related mortality (TRM). Four prospective studies and one retrospective study were included with a total of 810 patients. We found auto-HSCT was superior to allo-HSCT in OS (HR = 1.42, 95% CI: 1.06-1.91, P = 0.02), and there was no difference between allo-HSCT and auto-HSCT for RFS (HR = 1.10, 95% CI: 0.86-1.40, P = 0.44) and RR (OR = 0.53, 95% CI: 0.22-1.26, P = 0.15). The risk of TRM for patients undergoing allo-HSCT was significantly higher than that of the patients who received auto-HSCT (OR = 5.06, 95% CI: 1.03-24.75, P = 0.05). Our meta-analysis shows that auto-HSCT may be an attractive and alternative treatment option for adult Ph+ ALL patients achieving CMR, with similar or better outcomes than allo-HSCT in the era of TKIs.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Taxa de Sobrevida
17.
Lancet Haematol ; 7(10): e715-e723, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32976751

RESUMO

BACKGROUND: The interferon lambda 4 gene (IFNL4) regulates immune responses by controlling the production of IFNλ4, a type III interferon. We hypothesised that IFNλ4 could play a role in infection clearance or alloreactivity in patients with acute leukaemia who received a myeloablative 10/10 HLA-matched haematopoietic stem-cell transplantation (HSCT). Therefore, we aimed to assess the association between recipient and donor IFNL4 genotype with post-HSCT survival outcomes in patients with acute leukaemia. METHODS: We did a two-stage retrospective cohort study using the Center for International Blood and Marrow Transplant Research (CIBMTR) repository and database, in which nearly all patients underwent the procedure in the USA. We included patients with acute myeloid leukaemia or acute lymphocytic leukaemia, who received a HSCT at any age from an unrelated 10/10 HLA-matched donor, with a myeloablative conditioning regimen, between Jan 1, 2000, and Dec 31, 2008, and had a pre-HSCT recipient or donor blood sample available. The discovery dataset included patients from an existing National Cancer Institute (NCI) cohort of the CIBMTR database, in which donor and recipient IFNL4 polymorphisms (rs368234815, rs12979860, and rs117648444) were genotyped with TaqMan assays. According to their genotype, donors and recipients were categorised into IFNL4-positive, if they had at least one copy of the allele that supports the production of IFNλ4, or IFNL4-null for the analyses. The findings were independently validated with patients from the DISCOVeRY-BMT cohort (validation dataset) with existing Illumina array genotype data. We also did a combined analysis using data from patients included in both the NCI and DISCOVeRY-BMT cohorts. FINDINGS: We assessed 404 patients (who had a HSCT from Jan 9, 2004, to Dec 26, 2008) in the discovery dataset and 1245 patients in the validation dataset (HSCT Jan 7, 2000, to Dec 26, 2008). The combined analysis included 1593 overlapping participants in both cohorts. Donor, but not recipient IFNL4-positive genotype was associated with increased risk of non-relapse mortality (HR 1·60, 95% CI 1·23-2·10; p=0·0005 in the discovery dataset; 1·22, 1·05-1·40; p=0·0072 in the validation dataset; and 1·27, 1·12-1·45; p=0·0001 in the combined dataset). Associations with post-HSCT overall survival were as follows: HR 1·24, 95% CI 1·02-1·51; p=0·034 in the discovery dataset; 1·10, 0·98-1·20; p=0·10 in the validation dataset; and 1·11, 1·02-1·22; p=0·018 in the combined dataset. INTERPRETATION: Prioritising HSCT donors with the IFNL4-null genotype might decrease non-relapse mortality and improve overall survival without substantially limiting the donor pool. If these findings are validated, IFNL4 genotype could be added to the donor selection algorithm. FUNDING: The National Cancer Institute Intramural Research Program. For full funding list see Acknowledgments.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Interleucinas/genética , Leucemia Mieloide Aguda/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Adulto , Feminino , Genótipo , Transplante de Células-Tronco Hematopoéticas/mortalidade , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/mortalidade , Estudos Retrospectivos , Resultado do Tratamento , Doadores não Relacionados , Adulto Jovem
19.
Medicine (Baltimore) ; 99(33): e21752, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32872067

RESUMO

RATIONALE: As the major complications post allogeneic hematopoietic stem cell transplantation (allo-HSCT), gastrointestinal disorders were most commonly ascribed to acute graft-versus-host disease (aGVHD) and opportunistic infections. Though Giardia lamblia (G lamblia) is the most common waterborne parasite of intestinal infection worldwide, seldom has it been reported in a patient with acute severe aplastic anemia after allo-HSCT. PATIENT CONCERNS: A 23-year-old male with severe aplastic anemia developed diarrhea, abdominal cramps, bloating, nausea, vomiting, fever, weight loss, and fatigue after allo-HSCT. DIAGNOSIS: Stool examinations for ova and parasites showed Giardia trophozoites and cysts. INTERVENTIONS: Methylprednisolone was stopped and the patient was intravenously treated with a 7-day course of metronidazole (500 mg, tid.). Simultaneously, cyclosporine (5 mg/kg) was continually utilized for suspicious gut GVHD. OUTCOMES: The Giardia lamblia in stool turned negative and his symptoms were resolved after the 7-day course. LESSONS: Incorporating non-invasive monitoring of stool examination for ova and parasites in the follow-up algorithm for post-HSCT patients can expedite clinical decision-making in the differential diagnoses for aGVHD even in the non-endemic area. Metronidazole therapy can be well-tolerated in HSCT patients with giardiasis.


Assuntos
Giardia lamblia/isolamento & purificação , Giardíase/diagnóstico , Doença Enxerto-Hospedeiro/diagnóstico , Transplante de Células-Tronco Hematopoéticas , Diagnóstico Diferencial , Humanos , Masculino , Transplante Homólogo , Adulto Jovem
20.
Blood Adv ; 4(17): 4147-4150, 2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32886750

RESUMO

Donor registries and transplantation societies recommend cryopreservation of unrelated donor hemopoietic progenitor cell (HPC) products before the recipient commences conditioning therapy to mitigate the donor and travel risks associated with the COVID-19 pandemic. However, little is known regarding the postthaw quality of such allogeneic products or the effect of precryopreservation storage and processing on these characteristics. We investigated the postthaw CD34+ cell recovery and viability of 305 allogeneic HPC products cryopreserved at 9 laboratories across Australia. Median postthaw CD34+ cell recovery was 76% and ranged from 6% to 122%. Longer transit time before cryopreservation, white cell count (WCC) during storage, and complex product manipulation before cryopreservation were independently associated with inferior postthaw CD34+ cell recovery. Longer precryopreservation transit time and WCC were also associated with inferior postthaw CD34+ cell viability. We conclude that although postthaw CD34+ cell recovery and viability of cryopreserved allogeneic HPC is generally acceptable, there is a significant risk of poor postthaw product quality, associated with prolonged storage time, higher WCC, and complex product manipulation precryopreservation. Awareness of expected postthaw recovery and practices that influence it will assist collection, processing, and transplant centers in optimizing outcomes for transplant recipients.


Assuntos
Antígenos CD34/análise , Criopreservação , Células-Tronco Hematopoéticas/citologia , Sobrevivência Celular , Infecções por Coronavirus/epidemiologia , Transplante de Células-Tronco Hematopoéticas , Humanos , Pandemias , Pneumonia Viral/epidemiologia , Transplante Homólogo
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