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1.
N Engl J Med ; 384(1): 11-19, 2021 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33406328

RESUMO

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4; also known as CD26), a transmembrane receptor expressed on T cells, has a costimulatory function in activating T cells. In a mouse model, down-regulation of CD26 prevented graft-versus-host disease (GVHD) but preserved graft-versus-tumor effects. Whether inhibition of DPP-4 with sitagliptin may prevent acute GVHD after allogeneic stem-cell transplantation is not known. METHODS: We conducted a two-stage, phase 2 clinical trial to test whether sitagliptin plus tacrolimus and sirolimus would reduce the incidence of grade II to IV acute GVHD from 30% to no more than 15% by day 100. Patients received myeloablative conditioning followed by mobilized peripheral-blood stem-cell transplants. Sitagliptin was given orally at a dose of 600 mg every 12 hours starting the day before transplantation until day 14 after transplantation. RESULTS: A total of 36 patients who could be evaluated, with a median age of 46 years (range, 20 to 59), received transplants from matched related or unrelated donors. Acute GVHD occurred in 2 of 36 patients by day 100; the incidence of grade II to IV GVHD was 5% (95% confidence interval [CI], 1 to 16), and the incidence of grade III or IV GVHD was 3% (95% CI, 0 to 12). Nonrelapse mortality was zero at 1 year. The 1-year cumulative incidences of relapse and chronic GVHD were 26% (95% CI, 13 to 41) and 37% (95% CI, 22 to 53), respectively. GVHD-free, relapse-free survival was 46% (95% CI, 29 to 62) at 1 year. Toxic effects were similar to those seen in patients undergoing allogeneic stem-cell transplantation. CONCLUSIONS: In this nonrandomized trial, sitagliptin in combination with tacrolimus and sirolimus resulted in a low incidence of grade II to IV acute GVHD by day 100 after myeloablative allogeneic hematopoietic stem-cell transplantation. (Funded by the National Heart, Lung, and Blood Institute; ClinicalTrials.gov number, NCT02683525.).


Assuntos
Inibidores da Dipeptidil Peptidase IV/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Fosfato de Sitagliptina/uso terapêutico , Adulto , Inibidores da Dipeptidil Peptidase IV/administração & dosagem , Inibidores da Dipeptidil Peptidase IV/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/uso terapêutico , Leucemia Mieloide/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/terapia , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Recidiva , Sirolimo/uso terapêutico , Fosfato de Sitagliptina/administração & dosagem , Fosfato de Sitagliptina/efeitos adversos , Análise de Sobrevida , Tacrolimo/uso terapêutico , Transplante Homólogo , Adulto Jovem
2.
Artigo em Inglês | MEDLINE | ID: mdl-33371225

RESUMO

The impact on health care of patients with myelodysplastic syndromes (MDS) is continuously rising. To investigate the perception of hemato-oncologists concerning the recommended MDS patient care in Switzerland, we conducted a web-based survey on diagnosis, risk-stratification and treatment. 43/309 physicians (13.9%) replied to 135 questions that were based on current guidelines between 3/2017 and 2/2018. Only questions with feedback-rates >50% were further analysed and ratios >90% defined "high agreement", 70-90% "agreement", 30-70% "insufficient agreement" and <30% "disagreement". For diagnosis, we found insufficient agreement on using flow-cytometry, classifying MDS precursor conditions, performing treatment response assessment after hypomethylating agents (HMA) and evaluating patients with suspected germ-line predisposition. For risk-stratification, we identified agreement on using IPSS-R but insufficient agreement for IPSS and patient-based assessments. For treatment, we observed disagreement on performing primary infectious prophylaxis in neutropenia but agreement on using only darbepoetin alfa in anaemic, lower-risk MDS patients. For thrombopoietin receptor agonists, insufficient agreement was found for the indication, preferred agent and triggering platelet count. Insufficient agreement was also found for immunosuppressive treatment in hypoplastic MDS and HMA dose adjustments. In conclusion, we identified areas for improvement in MDS patient care, in need of further clinical trials, information, and guiding documents.


Assuntos
Assistência à Saúde , Síndromes Mielodisplásicas/terapia , Adulto , Humanos , Imunossupressores , Síndromes Mielodisplásicas/tratamento farmacológico , Contagem de Plaquetas , Suíça
3.
Hematology ; 25(1): 494-501, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33317419

RESUMO

OBJECTIVES: RUNX1 mutations have been widely found in patients with myelodysplastic syndrome (MDS). Majority of reports revealed that RUNX1 mutations are associated with a poor prognosis. However, discrepancies still remain. The results of univariate analysis were not confirmed in multivariate analysis in some cases. Therefore, we performed a meta-analysis to assess the prognostic effect of RUNX1 mutations in MDS. METHODS: We extracted data from qualified studies that were searched from PubMed, Embase and the Cochrane Library. Hazard ratios (HRs) and their 95% confidence intervals (CIs) for the overall survival (OS) and leukemia free survival (LFS) were pooled from the multivariate Cox proportional hazard models. RESULTS: Sixteen studies containing 5422 patients were included in this meta-analysis. There were 617 patients with mutated RUNX1 and 4805 patients with wide type RUNX1. The total HR for OS was 1.43 (95% CI = 1.21-1.70, P < 0.0001) and the counterpart of LFS was 1.88 (95% CI = 1.42-2.51, P < 0.0001). DISCUSSION AND CONCLUSION: These results suggest that the RUNX1 mutations are associated with unfavorable outcomes and shorter survival in patients with MDS. Furthermore, poor prognosis of patients might be alleviated by stem cell transplantation. Patients bearing these mutations should be prioritized for aggressive therapy.


Assuntos
Subunidade alfa 2 de Fator de Ligação ao Core/genética , Predisposição Genética para Doença , Mutação , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/mortalidade , Alelos , Terapia Combinada , Gerenciamento Clínico , Estudos de Associação Genética , Humanos , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/terapia , Prognóstico , Modelos de Riscos Proporcionais
4.
Isr Med Assoc J ; 22(10): 645-647, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33070490

RESUMO

BACKGROUND: Histiocytic sarcoma (HS) is a rare hematopoietic malignancy originating from the monocyte/macrophage bone marrow lineage. HS can occur in isolation or in association with other hematological neoplasms such as non-Hodgkin lymphoma (NHL), myelodysplasia, or acute leukemia. Clinically, HS can affect lymph nodes, gastrointestinal tract, skin, bone marrow, and spleen as well as the central nervous system. Most cases of HS follow an aggressive clinical course, with most patients dying of progressive disease within one year of diagnosis.


Assuntos
Medula Óssea/patologia , Sarcoma Histiocítico/patologia , Linfonodos/patologia , Biópsia por Agulha , Diagnóstico Diferencial , Feminino , Sarcoma Histiocítico/diagnóstico , Sarcoma Histiocítico/terapia , Humanos , Imuno-Histoquímica , Linfoma não Hodgkin/patologia , Linfoma não Hodgkin/terapia , Masculino , Síndromes Mielodisplásicas/patologia , Síndromes Mielodisplásicas/terapia , Prognóstico , Doenças Raras , Medição de Risco , Tomografia Computadorizada por Raios X/métodos
5.
Chest ; 158(4): e139-e142, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33036110

RESUMO

Infection with the severe acute respiratory syndrome coronavirus 2 causes severe acute lung injury in approximately 5% of infected adults, but few reports have been made of severe pediatric disease. We present an adolescent patient who contracted severe acute respiratory syndrome coronavirus 2 one week after a paternal haplo-identical hematopoietic stem cell transplant, with development of severe hyperferritinemic acute lung injury and macrophage activation-like syndrome. We present her case and a comparison of her laboratory data with those of a cohort of pediatric patients with coronavirus disease 2019 without severe disease.


Assuntos
Betacoronavirus , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Síndromes Mielodisplásicas/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adolescente , Infecções por Coronavirus/etiologia , Feminino , Humanos , Síndromes Mielodisplásicas/complicações , Pandemias , Pneumonia Viral/etiologia
6.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(5): 1648-1653, 2020 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-33067968

RESUMO

OBJECTIVE: To investigate the transfusion effectiveness of suspended leucocyte depleted red blood cells (sld RBC) and fresh and irradiated apheresis platelets (fia Plt) in patients with myelodysplastic syndromes (MDS), and to explore the causes and mechanisms of ineffective platelet transfusion in patients with MDS. METHODS: Clinical data of 37 patients with confirmed MDS (WHO standard) such as the sex, age, Hb levels, Plt count, hemorrhage and coagulation functions, TEG and so on, were retrospectively analyzed. RESULTS: Among the 37 patients, 15 patients (40.5%) received only sld RBC transfusion, 9 patients (24.3%) received only fia Plt transfusion, and 13 patients (35.1%) received both transfusion. Among the 15 patients with only red blood cell transfusion, 3 patients were ineffective and the ineffectual transfusion rate was 20.0%. Among the 9 patients with only received platelet transfusion, 5 patients were ineffective and the ineffectual transfusion rate was 55.6%, there were significant statistical differences between the two groups (P﹤0.01). The red blood cell transfusion ineffective were 3 patients (23.1%) , the platelet transfusion ineffective were 8 patients (61.5%) and the both transfusion ineffective were 2 patients (15.4%) among the patients both transfusion . The positive rate of platelet antibody in MDS patients with ineffective platelet transfusion was 23.1%. Compared with the normal control group, Human P selectin (P-SelectinCD62P) (P<0.001) and human anti-thrombin 3 antibody (AT-III Ab) (P<0.001) significantly increased and human tissue factor pathway inhibitor (TFPI) significantly decreased (P<0.05) in MDS patients with ineffective platelet transfusion. CONCLUSION: In the process of component transfusion for MDS patients, compared with the transfusion of red blood cells, the inefficiencies of platelet transfusion significantly increased, mainly due to the disorder of blood coagulation and the generation of platelet antibodies in MDS patients with ineffective platelet transfusion. Compared with the normal control group, human P selectin and human anti-thrombin 3 antibody significantly increase and human tissue factor pathway inhibitor significantly decreases in MDS patients with ineffective platelet transfusion. Human P selectin, human anti-thrombin 3 antibody and human tissue factor pathway inhibitor in molecular markers and fibrinolytic markers can be used as indicators of platelet transfusion time and efficiency in patients with MDS.


Assuntos
Transfusão de Sangue , Síndromes Mielodisplásicas , Transfusão de Eritrócitos , Humanos , Síndromes Mielodisplásicas/terapia , Transfusão de Plaquetas , Estudos Retrospectivos
7.
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
10.
Int J Hematol ; 112(6): 825-834, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803698

RESUMO

The prognosis of patients with hypoplastic myelodysplastic syndrome (hMDS) after receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains unclear. This study aimed to evaluate the outcomes of patients with hMDS after allo-HSCT. Between September 2013 and October 2019, a total of 20 consecutive patients with hMDS and 1 patient with clonal cytopenia of undermined significance (CCUS) who underwent allo-HSCT, which included procedures with 9 matched sibling donors, 2 matched unrelated donors, 4 mismatched unrelated donors and 6 haploidentical donors, were enrolled in this study. The median time for myeloid engraftment was 11 days (range 9-17 days), and that for platelet engraftment was 10 days (range 7-17 days). The cumulative incidence (CI) of myeloid and platelet recovery was 95.2 ± 6.0% and 90.5 ± 7.3%, respectively. The CI rates were 40.0 ± 11.3% for grades II-III acute graft-versus-host disease (GVHD), 36.8 ± 11.5% for chronic GVHD and 23.8 ± 9.6% for nonrelapse mortality. No patients experienced relapse. Sixteen surviving patients were followed up for a median of 1113 days (range 110-2305 days), and the overall survival and relapse-free survival rates were both 72.7 ± 10.6%. This limited retrospective analysis suggests that patients with hMDS had a favorable survival after allo-HSCT.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Síndromes Mielodisplásicas/terapia , Adolescente , Adulto , Intervalo Livre de Doença , Feminino , Doença Enxerto-Hospedeiro/epidemiologia , Doença Enxerto-Hospedeiro/etiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/sangue , Síndromes Mielodisplásicas/mortalidade , Estudos Retrospectivos , Taxa de Sobrevida , Fatores de Tempo , Doadores de Tecidos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
11.
Int J Hematol ; 112(6): 871-877, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32803699

RESUMO

Hematological diseases after solid organ transplant (SOT) are an emerging issue as the number of long-term SOT survivors increases. Expertise in managing patients requiring allogeneic hematopoietic stem cell transplantation (HSCT) after SOT from independent donors is needed; however, clinical reports of HSCT after SOT are limited, and the feasibility and risk are not well understood. In particular, HSCT in prior lung transplant recipients is thought to be complicated as the lung is immunologically distinct and is constantly exposed to the surrounding environment. Herein, we describe a case of successful HSCT in a patient with myelodysplastic syndromes who had previously received a lung transplant from a deceased donor for bronchiolitis obliterans syndrome. Reports about cases of HSCT after lung transplant are quite rare; thus, we discuss the mechanisms of immune tolerance through the clinical course of our case. This case suggests that HSCT after SOT can be considered a therapeutic option in cases where the transplanted organ is functionally retained and the hematological disease is in remission.


Assuntos
Bronquiolite Obliterante/cirurgia , Transplante de Células-Tronco Hematopoéticas , Transplante de Pulmão , Síndromes Mielodisplásicas/terapia , Adulto , Bronquiolite Obliterante/complicações , Estudos de Viabilidade , Humanos , Tolerância Imunológica , Pulmão/imunologia , Masculino , Síndromes Mielodisplásicas/etiologia , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
12.
Int J Hematol ; 112(4): 510-523, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32656637

RESUMO

An optimal pretransplant conditioning regimen for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in older adults has not been established. Three prospective multicenter phase II studies were conducted, in which 142 patients older than 54 years (median age, 61 years; range 55-70 years) with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) received a myeloablative dose of intravenous busulfan (ivBu, 12.8 mg/kg) along with fludarabine (180 mg/m2) ± low dose total body irradiation for allo-HSCT between September 2009 and February 2013. A total of 103 AML and 39 MDS patients including 21 related bone marrow (BM) or peripheral blood (PB), 50 unrelated BM, and 71 unrelated cord blood (UCB) transplantation were enrolled. Grade 3 or greater toxicities were observed in 105 patients. Neutrophil engraftment was achieved in 70 out of the 71 related PB/BM or unrelated BM recipients, and 61 out of the 71 UCB recipients. The cumulative incidence rates of relapse and non-relapse mortality after 2 years were 24.0 and 24.1%, respectively. The overall and event-free survival rates at 2 years were 53.3 and 47.4%, respectively. The myeloablative dose of ivBu was well tolerated without increased toxicity-related mortality in older adults who underwent allo-HSCT with any donor source.


Assuntos
Bussulfano/administração & dosagem , Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Condicionamento Pré-Transplante/métodos , Fatores Etários , Idoso , Bussulfano/efeitos adversos , Ensaios Clínicos Fase II como Assunto , Intervalo Livre de Doença , Feminino , Humanos , Infusões Intravenosas , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Estudos Prospectivos , Doses de Radiação , Transplante Homólogo , Resultado do Tratamento , Vidarabina/administração & dosagem , Vidarabina/análogos & derivados , Irradiação Corporal Total/métodos
13.
Leukemia ; 34(10): 2552-2560, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32661295

RESUMO

Indications of allogeneic hematopoietic stem cell transplantation (HSCT) remain controversial in patients with lower risk myelodysplastic syndrome. We review prognostic factors in lower risk MDS, delineating patients with relatively poor risk who may potentially benefit from HSCT during the disease course. Results of HSCT in those patients, and main efforts to decrease non-relapse mortality (NRM) are detailed. Prospective studies are needed to determine more precisely which lower risk MDS patients may benefit from transplantation.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Síndromes Mielodisplásicas/terapia , Humanos , Prognóstico , Risco , Condicionamento Pré-Transplante , Transplante Homólogo
14.
Ann Hematol ; 99(8): 1855-1862, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32564196

RESUMO

Allogeneic stem cell transplantation (allo-SCT) represents the most beneficial treatment for patients with active relapsed/refractory (R/R) hematologic malignancies. Recently, sequential regimens combining debulking chemotherapy followed by reduced-intensity conditioning (RIC) have shown encouraging results for these patients. In this retrospective study, we report the extended results of a sequential regimen of clofarabine, cytosine arabinoside, and RIC in 131 adults with active R/R myeloid disease at transplant. Conditioning consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a rest of 3 days, by an RIC combining cyclophosphamide (60 mg/kg) for 1 day, iv busulfan (3.2 mg/kg/day) for 2 days, and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Between 2007 and 2016, 131 patients (males n = 75, median age: 52.6 years) were identified from the SFGM-TC registry. There were 111 acute myeloid leukemia (AML) patients and 20 cases with myelodysplastic or myeloproliferative syndrome. Status at transplant was known for all but 4 patients and was primary refractory (n = 81) and 1st or 2nd relapse (n = 46). All patients received allo-SCT from a matched donor (sibling n = 64, unrelated n = 67). Engraftment was observed in 105/122 (86%) evaluable cases and 63% of the patients achieved complete remission (CR) after transplant. The 1-year overall survival, disease-free survival, relapse incidence, non-relapse mortality, and graft-versus-host disease-free/relapse-free survival were 39.2%, 28.1%, 41.0%, 30.8%, and 22.2%, respectively. This study confirms that this sequential clofarabine-based regimen provides a high CR rate in this critical population, although relapse remains a matter of concern.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Condicionamento Pré-Transplante , Adolescente , Adulto , Idoso , Aloenxertos , Clofarabina/administração & dosagem , Citarabina/administração & dosagem , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Estudos Retrospectivos , Taxa de Sobrevida
15.
Leuk Res ; 95: 106402, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32590108

RESUMO

INTRODUCTION: Chromosome 17 abnormalities, especially disorders of the 17p region and including TP53 gene mutations, result in very low rates of cure for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) treated with conventional chemotherapy or allogeneic hematopoietic cell transplant (allo-HCT). Our retrospective study analyzed outcomes in patients with chromosome 17 (ch17) abnormalities who received conventional chemotherapy followed by allo-HCT versus those who did not receive a transplant. We analyzed whether poor outcomes extend to patients with all types of ch17 abnormalities and the impact of concomitant TP53 gene mutations assessed by next-generation sequencing (NGS) on prognosis. METHODS: We retrospectively analyzed diagnostic and outcome data on 98 patients treated at our institution from 2012 to 2018 with AML or MDS who possessed ch17 abnormalities by cytogenetic analysis. The presence of TP53 mutations was analyzed by NGS. Primary endpoint of our study was overall survival (OS). RESULTS: 61 patients with AML and 37 with MDS were included. Complete remission (CR) with first line treatment was similar between induction chemotherapy or hypomethylating agents (HMA), 22.9 % versus 21.6 % (p = 0.33). Median OS for all patients (with or without transplant) was 10 months. Patients with abnormal ch17 in conjunction with any TP53 mutation(s) exhibited worse OS compared to patients without a TP53 mutation (10 versus 23 months, p = 0.02). 30 patients (19 AML, 11 MDS) underwent HCT, with a median OS of 11 months. For AML patients who underwent allo-HCT, 18 were in CR (13 with cytogenetic remission) and 1 had persistent disease at transplant. In the MDS cohort, 3 patients were in CR (2 with cytogenetic remission) and 8 had stable disease. Post allo-HCT survival of AML and MDS cohorts did not differ (p = 0.6), although cytogenetic CR at time of HCT trended towards improved OS (17 versus 8 months; p = 0.6). CONCLUSIONS: AML/MDS patients with ch17 abnormalities have poor outcomes with or without HCT. Our results show that patients with ch17 abnormalities and TP53 mutations have a significantly poorer survival compared to patients who have ch17 abnormalities but no TP53 mutations. Drugs targeting abnormalities of the p53 pathway, improvement in depth of response prior to HCT, and novel maintenance strategies are needed for improved outcomes in these patients.


Assuntos
Transplante de Células-Tronco Hematopoéticas/métodos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Aberrações Cromossômicas , Cromossomos Humanos Par 17 , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/mortalidade , Prognóstico , Estudos Retrospectivos , Proteína Supressora de Tumor p53/genética
17.
Int J Hematol ; 112(1): 46-56, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32451786

RESUMO

We analyzed clinical cutoffs for defining computed tomography (CT) methods for sarcopenia and examined the prognostic value of CT for allogeneic hematopoietic stem cell transplantation (allo-HCST) outcomes of patients with myeloid malignancy. One hundred twenty-five adult patients with acute myeloid leukemia and myelodysplastic syndrome who underwent first allo-HSCT between 2000 and 2017 were included. Sarcopenia was assessed using CT-based skeletal muscle index (SMI) and mean muscle attenuation at L3. A statistical difference in SMI was confirmed between sarcopenia (n = 52) and nonsarcopenia (n = 73) patients. There were no significant correlations of muscularity with age, performance status, or other characteristics of HSCT. After 2 years, overall survival (OS) was 43.5% and 70.1%, disease-free survival was 52.9% and 68.6%, nonrelapse mortality (NRM) was 20.8% and 8.4%, incidence of acute GVHD (≥ grade 2) was 38.8% and 39.1%, that of chronic GVHD was 53.2% and 37.3%, and median duration of hospitalization was 88 days and 74 days (P = 0.026), respectively, in the sarcopenia and nonsarcopenia groups. Multivariate analysis showed that presence of sarcopenia is a novel adverse factor for high NRM and poor OS. Pretransplant CT-defined sarcopenia is correlated with decreased OS, increased NRM, and prolonged hospitalization.


Assuntos
Transplante de Células-Tronco Hematopoéticas/mortalidade , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/mortalidade , Síndromes Mielodisplásicas/terapia , Sarcopenia/diagnóstico por imagem , Sarcopenia/etiologia , Tomografia Computadorizada por Raios X , Adolescente , Adulto , Idoso , Feminino , Humanos , Leucemia Mieloide Aguda/complicações , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/complicações , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Transplante Homólogo , Adulto Jovem
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