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1.
Rinsho Ketsueki ; 62(8): 1308-1318, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34497221

RESUMO

Leukemias diagnosed in <1-year-old infants generally have an aggressive clinical nature and unique biological characteristics. Acute lymphoblastic leukemia (ALL) in infants is still intractable and difficult to treat as compared with other pediatric ALLs, for which considerable progress in treatment outcomes has been recently achieved. Infant leukemia cells frequently carry chromosome translocations involving the 11q23 locus, resulting in the rearrangement and fusion of the KMT2A (MLL) gene. Among several KMT2A fusion genes, KMT2A-AFF1 (MLL-AF4) fusion is characteristically observed in neonatal and infant ALL, representing a hallmark of poor prognosis. The cytogenetic/molecular abnormalities t (1;22)(p13.3;q13.1)/RBM15-MKL1 and t (8;16)(p11.2;p13.3)/KAT6A-CREBBP (MOZ-CBP) are also well-known in acute myeloblastic leukemia in this population. Although many neonatal leukemias occurring within the first 28 days of birth are refractory, spontaneous remissions are occasionally observed, especially in the case of t (8;16). Therefore, international collaborative studies are necessary to improve understanding and facilitate the development of better treatment for this rare disease. Thus, this study summarizes the recently reported clinical, cytogenetic, and molecular biology aspects of neonatal and infant leukemias.


Assuntos
Leucemia Mieloide Aguda , Leucemia-Linfoma Linfoblástico de Células Precursoras , Doença Aguda , Aberrações Cromossômicas , Humanos , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Proteínas de Fusão Oncogênica/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras/terapia , Translocação Genética
2.
Stem Cell Res Ther ; 12(1): 465, 2021 08 20.
Artigo em Inglês | MEDLINE | ID: mdl-34412685

RESUMO

Acute myeloid leukemia (AML) is a serious, life-threatening, and hardly curable hematological malignancy that affects the myeloid cell progenies and challenges patients of all ages but mostly occurs in adults. Although several therapies are available including chemotherapy, allogeneic hematopoietic stem cell transplantation (alloHSCT), and receptor-antagonist drugs, the 5-year survival of patients is quietly disappointing, less than 30%. alloHSCT is the major curative approach for AML with promising results but the treatment has severe adverse effects such as graft-versus-host disease (GVHD). Therefore, as an alternative, more efficient and less harmful immunotherapy-based approaches such as the adoptive transferring T cell therapy are in development for the treatment of AML. As such, chimeric antigen receptor (CAR) T cells are engineered T cells which have been developed in recent years as a breakthrough in cancer therapy. Interestingly, CAR T cells are effective against both solid tumors and hematological cancers such as AML. Gradually, CAR T cell therapy found its way into cancer therapy and was widely used for the treatment of hematologic malignancies with successful results particularly with somewhat better results in hematological cancer in comparison to solid tumors. The AML is generally fatal, therapy-resistant, and sometimes refractory disease with a disappointing low survival rate and weak prognosis. The 5-year survival rate for AML is only about 30%. However, the survival rate seems to be age-dependent. Novel CAR T cell therapy is a light at the end of the tunnel. The CD19 is an important target antigen in AML and lymphoma and the CAR T cells are engineered to target the CD19. In addition, a lot of research goes on the discovery of novel target antigens with therapeutic efficacy and utilizable for generating CAR T cells against various types of cancers. In recent years, many pieces of research on screening and identification of novel AML antigen targets with the goal of generation of effective anti-cancer CAR T cells have led to new therapies with strong cytotoxicity against cancerous cells and impressive clinical outcomes. Also, more recently, an improved version of CAR T cells which were called modified or smartly reprogrammed CAR T cells has been designed with less unwelcome effects, less toxicity against normal cells, more safety, more specificity, longer persistence, and proliferation capability. The purpose of this review is to discuss and explain the most recent advances in CAR T cell-based therapies targeting AML antigens and review the results of preclinical and clinical trials. Moreover, we will criticize the clinical challenges, side effects, and the different strategies for CAR T cell therapy.


Assuntos
Leucemia Mieloide Aguda , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia , Imunoterapia Adotiva , Leucemia Mieloide Aguda/terapia , Receptores de Antígenos Quiméricos/genética , Linfócitos T
4.
Zhonghua Xue Ye Xue Za Zhi ; 42(7): 549-554, 2021 Jul 14.
Artigo em Chinês | MEDLINE | ID: mdl-34455741

RESUMO

Objective: To retrospectively analyze the clinical outcomes of single unrelated cord blood transplantation (UCBT) in children with high risk and refractory acute myeloid leukemia (AML) . Methods: Between June 2008 and December 2018, a total of 160 consecutive pediatric patients with AML received single UCBT (excluding acute promyelocytic leukemia) . Myeloablative conditioning (MAC) regimen were applied. All patients received a combination of cyclosporine A (CsA) and mycophenolate mofetil (MMF) for the prophylaxis of graft -versus- host disease (GVHD) . Results: The cumulative incidence of neutrophil cells engraftment at day +42 and platelet recovery at day +120 was 95.0% (95% CI 90.0%-97.5%) at a median of 16 days after transplantation (range, 11-38 days) and 85.5% (95%CI 83.3%-93.4%) with a median time to recovery of 35 days (range, 13-158) , respectively. Incidence of grades Ⅱ-Ⅳ and Ⅲ-Ⅳ acute GVHD and chronic GVHD were 37.3% (95%CI 29.3%-45.2%) , 27.3% (95%CI 20.0%-35.0%) and 22.4% (95%CI 15.5%-28.7%) , respectively. The transplant-related mortality (TRM) at 360 day was 13.1% (95%CI 8.4%-18.9%) . The 5-year cumulative incidence of relapse was 13.8% (95%CI 8.5%-20.3%) . The 5-year disease-free survival (DFS) and overall survival (OS) were 71.7% (95%CI 62.7%-77.8%) and 72.2% (95%CI 64.1%-78.7%) , respectively. The 5-year GVHD and relapse free survival (GRFS) was 56.1% (95%CI 46.1%-64.9%) . The 5-year cumulative recurrence rates of CR1, CR2, and NR groups were 5.3%, 19.9%, and 30.9% (P=0.001) , and the 5-year OS rates were 79.9% (95%CI 70.3%-86.7%) , 71.1% (95%CI 50.4%-84.4%) and 52.9% (95%CI 33.0%-69.3%) (χ(2)=7.552, P=0.020) , respectively. Conclusions: For pediatric patients with high risk and refractory AML, UCBT is a safe and effective treatment option, and it is favorable to improve the survival rate in CR1 stage.


Assuntos
Transplante de Células-Tronco de Sangue do Cordão Umbilical , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Criança , Humanos , Leucemia Mieloide Aguda/terapia , Estudos Retrospectivos
5.
JCO Glob Oncol ; 7: 1220-1232, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34343012

RESUMO

PURPOSE: Acute myeloid leukemia (AML) is the most prevalent acute leukemia in adults and is responsible for the majority of cancer-related mortality. In Saudi Arabia, leukemia is ranked the fifth most prevalent type of malignancy in adults. Our aim is to review existing epidemiologic data in Saudi Arabia and develop consensus guidelines for management of AML. METHODS: We review literature related to AML epidemiology, treatment patterns, and outcomes in Saudi Arabia, as well as literature related to the current advances in AML treatment. A panel of 10 experts from eight institutions in Saudi Arabia reviewed the literature and developed a consensus statement. RESULT: We provide an update of the available AML epidemiologic data in Saudi Arabia and describe recent developments in the diagnostic workup, risk stratification, and treatment algorithm. The consensus recommendations for the management of AML in Saudi Arabia were developed. CONCLUSION: The recommendations are in parallel with the recent international guidelines for the diagnosis and management of AML.


Assuntos
Leucemia Mieloide Aguda , Medicina , Medula Óssea , Consenso , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Arábia Saudita/epidemiologia
6.
Blood ; 138(3): 273-282, 2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34292325

RESUMO

Posttransplant cyclophosphamide (PTCy) graft-versus-host disease (GVHD) prophylaxis has enabled haploidentical (Haplo) transplantation to be performed with results similar to those after matched unrelated donor (MUD) transplantation with traditional prophylaxis. The relative value of transplantation with MUD vs Haplo donors when both groups receive PTCy/calcineurin inhibitor/mycophenolate GVHD prophylaxis is not known. We compared outcomes after 2036 Haplo and 284 MUD transplantations with PTCy GVHD prophylaxis for acute leukemia or myelodysplastic syndrome in adults from 2011 through 2018. Cox regression models were built to compare outcomes between donor types. Recipients of myeloablative and reduced-intensity regimens were analyzed separately. Among recipients of reduced-intensity regimens, 2-year graft failure (3% vs 11%), acute grades 2 to 4 GVHD (hazards ratio [HR], 0.70; P = .022), acute grades 3 and 4 GVHD (HR, 0.41; P = .016), and nonrelapse mortality (HR, 0.43; P = .0008) were lower after MUD than with Haplo donor transplantation. Consequently, disease-free (HR, 0.74; P = .008; 55% vs 41%) and overall (HR, 0.65; P = .001; 67% vs 54%) survival were higher with MUD than with Haplo transplants. Among recipients of myeloablative regimens, day-100 platelet recovery (95% vs 88%) was higher and grades 3 and 4 acute (HR, 0.39; P = .07) and chronic GVHD (HR, 0.66; P = .05) were lower after MUD than with Haplo donor transplantation. There were no differences in graft failure, relapse, nonrelapse mortality, and disease-free and overall survival between donor types with myeloablative conditioning regimens. These data extend and confirm the importance of donor-recipient HLA matching for allogeneic transplantation. A MUD is the preferred donor, especially for transplantations with reduced-intensity conditioning regimens.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Transplante de Células-Tronco Hematopoéticas/métodos , Imunossupressores/uso terapêutico , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/terapia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante , Transplante Haploidêntico/métodos , Transplante Homólogo/métodos , Resultado do Tratamento , Doadores não Relacionados
7.
Ann Hematol ; 100(9): 2387-2398, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34232360

RESUMO

Relapse of acute leukemia is a frequent complication with uncertain outcome and poorly defined risk factors. From 1621 patients entered into two prospective clinical trials (AML02; n = 740 and AML04; n = 881), 74.2% reached complete remission (CR) 1 after induction(s) and 59 patients after additional induction ± hematopoietic cell transplantation (HCT). Of the non-refractory patients, 48.4% with a median age of 63 (range 17-85) years relapsed. Relapses occurred within 6 months after CR in 46.5%, between 7 and 18 months in 38.7%, and after 18 months in 14.8% of patients. Relapse treatment resulted in CR2 in 39% of patients depending upon age (54.5% of ≤ 60 and 28.6% of > 60 years), duration of CR1, and treatment of relapse. Overall survival (OS) was 10.9 (7.4-16.2) %, but OS after HCT ± intensive chemotherapy (ICT) was 39.3% (31.8-48.6) at 5 years and not different in younger and older patients. Donor lymphocyte infusion ± chemotherapy and ICT alone resulted only in OS of 15.4% and of 5%, respectively. Independent favorable factors for OS were long CR1 duration, and HCT, while non-monosomal disease was beneficial for OS in elderly patients. Leukemia-free survival [LFS; 24.9 (19.5-31.7) % at 10 years] was affected by similar risk factors. In a competing risk model, the relapse incidence at 5 years was 53.5 ± 3.5% and the non-relapse mortality rate 21.7 ± 2.9%. Lower relapse incidence was observed in patents with HCT, long CR1 duration, and female gender. Risk factors for non-relapse mortality were HCT in younger and type of AML in elderly patients. In conclusion, allogeneic HCT ± IC improved the results in relapsed AML in younger and elderly patients. Increasing CR2 rates and HCT frequency will be the challenge for the next years. Relapse of the disease remains the major problem.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda/terapia , Recidiva Local de Neoplasia/terapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Alemanha/epidemiologia , Humanos , Leucemia Mieloide Aguda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Transplante Homólogo , Resultado do Tratamento , Adulto Jovem
8.
Rinsho Ketsueki ; 62(5): 486-495, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34248126

RESUMO

Relapse is an issue of concern for patients with acute myeloid leukemia and myelodysplastic syndromes (AML/MDS) who underwent allogeneic hematopoietic stem cell transplantation (allo HSCT). The conventional minimal residual disease (MRD) test of the bone marrow has serious limitations regarding invasiveness and applicability. To address this problem, we investigated the utility of a novel MRD test using tumor-derived fragmentary DNA, or circulating tumor DNA (ctDNA) for the identification of patients with high risk of AML/MDS relapse after undergoing myeloablative allo HSCT. We retrospectively collected tumor specimens and available matched serum samples at diagnosis and at 1 and 3 months post-allo HSCT from 53 patients with AML/MDS. After identifying driver mutations in 51 patients using next-generation sequencing, we designed at least one personalized digital polymerase chain reaction assay per case. Diagnostic ctDNA and matched tumor DNA exhibited excellent correlations with variant allele frequencies. Sixteen patients relapsed after a median of 7 months post allo HSCT. Both the mutation persistence in the bone marrow at 1 and 3 months post allo HSCT and the corresponding ctDNA persistence in the matched serum were comparably associated with higher 3-year cumulative incidence of relapse rates. These results demonstrate, for the first time, the utility of ctDNA as a noninvasive prognostic biomarker in patients with AML/MDS who underwent allo HSCT.


Assuntos
DNA Tumoral Circulante , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicas , Humanos , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Síndromes Mielodisplásicas/diagnóstico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/terapia , Prognóstico , Estudos Retrospectivos , Transplante Homólogo
9.
Rinsho Ketsueki ; 62(5): 496-504, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-34248127

RESUMO

The most significant prognostic factor in allogeneic hematopoietic cell transplantation (HCT) for acute myeloid leukemia (AML) is the remission status at HCT. Although HCT is recommended to be performed after complete remission, there are cases in which HCT is performed in non-remission status. Although the outcomes of HCT for non-remission AML have been very poor, the subjects in these studies had heterogeneous backgrounds in terms of relapsed, refractory, and untreated AML. In this review article, non-remission AML is classified into the following two categories: refractory/relapsed AML and untreated AML. Recent advances in HCT for non-remission AML, such as prognostic factors and pre and postHCT interventions, have been summarized. In the preHCT setting, preHCT tumor burden was confirmed to be the primary prognostic factor. Preconditioning intervention that successfully eliminated blasts in the peripheral blood was associated with better outcomes after HCT. PostHCT maintenance therapy may be one of the treatment options after HCT. Even in untreated AML, lower tumor burden at HCT was associated with superior outcomes after HCT. With the primary significance of tumor control before and after HCT, it is crucial to establish a comprehensive strategy for HCT in the non-remission stage, including preHCT and postHCT interventions.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Humanos , Leucemia Mieloide Aguda/terapia , Indução de Remissão , Estudos Retrospectivos , Transplante Homólogo
11.
Int J Mol Sci ; 22(13)2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34202238

RESUMO

Acute myeloid leukemia (AML) is a hematologic malignancy caused by a wide range of alterations responsible for a high grade of heterogeneity among patients. Several studies have demonstrated that the hypoxic bone marrow microenvironment (BMM) plays a crucial role in AML pathogenesis and therapy response. This review article summarizes the current literature regarding the effects of the dynamic crosstalk between leukemic stem cells (LSCs) and hypoxic BMM. The interaction between LSCs and hypoxic BMM regulates fundamental cell fate decisions, including survival, self-renewal, and proliferation capacity as a consequence of genetic, transcriptional, and metabolic adaptation of LSCs mediated by hypoxia-inducible factors (HIFs). HIF-1α and some of their targets have been associated with poor prognosis in AML. It has been demonstrated that the hypoxic BMM creates a protective niche that mediates resistance to therapy. Therefore, we also highlight how hypoxia hallmarks might be targeted in the future to hit the leukemic population to improve AML patient outcomes.


Assuntos
Medula Óssea/metabolismo , Medula Óssea/patologia , Hipóxia/metabolismo , Leucemia Mieloide Aguda/etiologia , Leucemia Mieloide Aguda/metabolismo , Microambiente Tumoral , Animais , Linhagem Celular Tumoral , Reprogramação Celular , Gerenciamento Clínico , Suscetibilidade a Doenças , Metabolismo Energético , Epigênese Genética , Regulação Leucêmica da Expressão Gênica , Humanos , Fator 1 Induzível por Hipóxia/metabolismo , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/terapia , Terapia de Alvo Molecular , Células-Tronco Neoplásicas/metabolismo , Transdução de Sinais
12.
Med Oral Patol Oral Cir Bucal ; 26(5): e642-e650, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34162819

RESUMO

BACKGROUND: Acute myeloid leukemia belongs to proliferative diseases of the hematopoietic system. It is currently the leading indication for allogeneic hematopoietic stem cell transplantation. This study was designed to determine the most common subjective oral mucosa complaints in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. MATERIAL AND METHODS: Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups depending on the intensity of the conditioning regimen before transplantation: myeloablative and reduced-intensity chemotherapy. The oral symptoms were evaluated based on an authorial questionnaire designed for this analysis. The following oral mucosa subjective complaints were included: pain, paraesthesia, burning mouth sensation, taste disorders, excessive salivation, halitosis, and dryness of the oral mucosa. RESULTS: The most commonly reported subjective oral complaint in the examined patients was xerostomia, which was found in 92% of patients during the second visit, followed by spontaneous pain in the mouth (55%), burning (36%), and dysgeusia (20%). It occurred significantly more frequently in patients who underwent myeloablative conditioning. Moreover, it was observed that the frequency of complaints increased considerably after the transplantation, reaching a peak intensity during the second week following the procedure. CONCLUSIONS: Oral complaints significantly decrease the patients' quality of life during the transplantation and may lead to premature termination of the treatment. As the number of transplantations in patients with acute myeloid leukemia increases, further investigations of oral complaints and symptoms induced by the disease itself and by the therapeutic approaches are required.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Leucemia Mieloide Aguda , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Qualidade de Vida , Estudos Retrospectivos , Condicionamento Pré-Transplante/efeitos adversos
13.
Blood Adv ; 5(11): 2539-2549, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34100902

RESUMO

The clinicopathologic features of DNA methyltransferase 3A (DNMT3A)-mutated de novo acute myeloid leukemia (AML), and the significance of variant type, variant allele frequency (VAF), and multiple concomitant DNMT3A mutations, remain poorly defined. We examined 104 DNMT3A-mutated de novo AML patients from 2 major centers. Most (82%) had normal karyotype (NK); R882H variants were frequent(38%). The most commonly comutated genes included nucleophosmin (NPM1; 53%), Fms-related tyrosine kinase 3 (FLT3)-internal tandem duplication (25%), IDH1 (23%), IDH2 (23%), and TET2 (21%). Patients with high DNMT3A VAF at diagnosis (≥44%; DNMT3AHIGH) had more significant leukocytosis and higher blast counts in peripheral blood and bone marrow. DNMT3AHIGH cases were associated with much shorter event-free survival (EFS; 14.1 vs 56.8 months) and overall survival (OS; 18.3 months vs not reached) compared with cases of patients with low DNMT3A (DNMT3ALOW). Thirteen patients had 2 DNMT3A variants and similar VAFs at diagnosis that tracked together at multiple time points after chemotherapy and/or stem cell transplantation (SCT). In multivariable analyses performed in NK patients who received standard induction chemotherapy, presence of 2 DNMT3A mutations (hazard ratio [HR] = 3.192; P = .038) and SCT in first complete remission (HR = 0.295; P = .001) independently affected EFS; increasing marrow blast percentage (HR = 1.026; P = .025), high DNMT3A VAF (HR = 3.003; P = .010), and 2 DNMT3A mutations (HR = 4.816; P = .020) had independent effects on OS. These data support the adverse prognostic significance of DNMT3AHIGH reveal a novel association between 2 concomitant DNMT3A mutations and inferior outcome in DNMT3A-mutated de novo AML with a NK.


Assuntos
DNA (Citosina-5-)-Metiltransferases , Leucemia Mieloide Aguda , DNA (Citosina-5-)-Metiltransferases/genética , Frequência do Gene , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação
14.
Cancer Sci ; 112(8): 3233-3242, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34107135

RESUMO

Vγ9Vδ2 T cells are attractive effector cells for immunotherapy with potent cytotoxic activity against a variety of malignant cells. However, the effect of Vγ9Vδ2 T cells on chemotherapy-resistant acute myeloid leukemia (AML) blasts, especially highly refractory leukemia stem cells (LSCs) is still unknown. In this study, we investigated the effect of cytotoxicity of allogeneic Vγ9Vδ2 T cells on chemotherapy-resistant AML cell lines, as well as on primary AML blasts and LSCs obtained from refractory AML patients. The results indicated that Vγ9Vδ2 T cells can efficiently kill drug-resistant AML cell lines in vitro and in vivo, and the sensitivity of AML cells to Vγ9Vδ2 T cell-mediated cytotoxicity is not influenced by the sensitivity of AML cells to chemotherapy. We further found that Vγ9Vδ2 T cells exhibited a comparable effect of cytotoxicity against LSCs to primary AML blasts. More importantly, we revealed that the CD226-extracellular signal-regulatory kinase1/2 (ERK1/2)-lysosome-associated membrane protein 1 (LAMP1) pathway is an important mechanism for Vγ9Vδ2 T cell-induced cytotoxicity against AML cells. First, Vγ9Vδ2 T cells recognized AML cells by receptor-ligand interaction of CD226-Nectin-2, which then induced ERK1/2 phosphorylation in Vγ9Vδ2 T cells. Finally, triggering the movement of lytic granules toward AML cells induced cytolysis of AML cells. The expression level of Nectin-2 may be used as a novel marker to predict the susceptibility/resistance of AML cells to Vγ9Vδ2 T cell treatment.


Assuntos
Antígenos de Diferenciação de Linfócitos T/metabolismo , Resistencia a Medicamentos Antineoplásicos , Leucemia Mieloide Aguda/terapia , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Linfócitos T Citotóxicos/transplante , Animais , Citotoxicidade Imunológica , Feminino , Células HL-60 , Humanos , Imunoterapia Adotiva , Células K562 , Leucemia Mieloide Aguda/imunologia , Sistema de Sinalização das MAP Quinases , Camundongos , Linfócitos T Citotóxicos/imunologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
15.
Leuk Lymphoma ; 62(8): 1940-1948, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34180767

RESUMO

Patients with hematological malignancies are at risk for poor outcomes when diagnosed with coronavirus disease 2019 (COVID-19). It remains unclear whether cytopenias and specific leukemia subtypes play a role in the clinical course of COVID-19 infection. Here, we report outcomes and their clinical/laboratory predictors for 65 patients with acute and chronic leukemias diagnosed with COVID-19 between 8 March 2020 and 19 May 2020 at Memorial Sloan Kettering Cancer Center in New York City. Most patients had CLL (38%) or AML (26%). A total of 14 (22%) patients required high flow nasal cannula or were intubated for mechanical ventilation and 11 patients (17%) died. A diagnosis of AML (OR 4.7, p=.028), active treatment within the last 3 months (OR 5.22, p=.047), neutropenia within seven days prior and up to 28 days after SARS-CoV-2 diagnosis (11.75, p=.001) and ≥3 comorbidities (OR 6.55, p=.019) were associated with increased odds of death.


Assuntos
COVID-19 , Leucemia Mieloide Aguda , Neutropenia , Adulto , Teste para COVID-19 , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/epidemiologia , Leucemia Mieloide Aguda/terapia , Neutropenia/epidemiologia , Neutropenia/etiologia , Fatores de Risco , SARS-CoV-2
16.
J Clin Neurosci ; 89: 158-160, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34119261

RESUMO

Intracranial myeloid sarcoma (IMS) is a rare central nervous system manifestation of hematopoietic neoplasms of myeloid origin. We report the first case of IMS treatment with an isocitrate dehydrogenase-2 (IDH-2) inhibitor, Enasidenib, following surgical resection, whole-brain radiation, and consolidation Etoposide/Cytarabine therapy. A 42-year-old female was diagnosed with IMS after a 10-year remission of her acute myeloid leukemia (AML). She underwent surgical debulking and had postoperative resolution of her visual symptoms. She received adjuvant radiation and medical management, and continues to show no evidence of recurrence or progression at 17 months postoperatively. This case is notable for an isolated IMS presentation in a patient with a very distant history of AML remission, and without evidence of concurrent bone marrow relapse. The goals of neurosurgical intervention should be symptomatic relief of mass effect and pathological diagnosis, due to the sensitivity of IMS to adjuvant radiation and medical management such as IDH-2 inhibitors.


Assuntos
Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Leucemia Mieloide Aguda/diagnóstico por imagem , Leucemia Mieloide Aguda/terapia , Sarcoma Mieloide/diagnóstico por imagem , Sarcoma Mieloide/terapia , Adulto , Aminopiridinas/administração & dosagem , Citarabina/administração & dosagem , Feminino , Humanos , Quimioterapia de Indução/métodos , Indução de Remissão/métodos , Triazinas/administração & dosagem
17.
Ann Hematol ; 100(8): 2079-2086, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34117519

RESUMO

This study was designed to investigate the frequency and severity of oral mucositis in patients with acute myeloid leukemia after allogeneic hematopoietic cell transplantation, in relation to the type of conditioning used. Eighty patients diagnosed with acute myeloid leukemia were assigned to two groups based on the conditioning regimen used before transplantation. The intensity of oral inflammatory lesions induced by chemotherapy (oral mucositis) was evaluated according to a 5-point scale recommended by World Health Organization. Oral mucosa was investigated in all patients before the transplantation and during two subsequent stages of the post-transplantation procedure in relation to the conditioning regimen used. Mucositis in the oral cavity was observed in the majority of patients (66%) in the first week after transplantation, whereas the largest percentage of patients suffering oral lesions (74%) occurred in the second week after transplantation. A significantly higher percentage of patients with mucositis was observed in the group which underwent myeloablation therapy (74% of MAC and 50% of RIC patients in the first week; 83% of MAC and 53% of RIC patients in the second examination).The severity of mucositis after transplantation was higher in the MAC patients compared to the RIC patients. The highest mean value of the mucositis index was recorded in the second week in the MAC group (1.59). In AML sufferers receiving allo-HSCT, oral mucositis is a significant complication of the transplantation. This condition is more frequent and more severe in patients after treatment with myeloablation therapy.


Assuntos
Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Leucemia Mieloide Aguda/terapia , Estomatite/etiologia , Condicionamento Pré-Transplante/efeitos adversos , Adulto , Idoso , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Transplante Homólogo/efeitos adversos , Adulto Jovem
18.
Medicine (Baltimore) ; 100(26): e26316, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190149

RESUMO

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


Assuntos
Tecido Adiposo/citologia , Cistite/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemorragia/terapia , Transplante de Células-Tronco Mesenquimais , Condicionamento Pré-Transplante/efeitos adversos , Terapia Combinada , Cistite/etiologia , Feminino , Hematúria/etiologia , Hemorragia/etiologia , Humanos , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/terapia , Pessoa de Meia-Idade , Fatores de Risco , Transtornos Urinários/etiologia
19.
Crit Rev Oncol Hematol ; 163: 103379, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34087345

RESUMO

Acute myeloid leukemia with bi-allelic CEBPA mutation was categorized as an independent disease entity with favorable prognosis, however, recent researches have revealed huge heterogeneity within this disease group, and for some patients, relapse remained a major cause of treatment failure. Further risk stratification is essentially needed. Here by reviewing the latest literature, we summarized the characteristics of CEBPA mutation profiles and clinical features, with a special intention of dissecting the heterogeneity within the seemingly homogeneous AML with bi-allelic CEBPA mutations. Specifically, non-classical CEBPA mutation, miscellaneous companion genetic aberrations and the presence of germline CEBPA mutation are three major sources of heterogeneity. Identifying these factors can help us predict patients at a higher risk of relapse, for whom aggressive treatment may be recommended. Novel therapeutic approaches regarding manipulating potentially druggable targets as well as the debate over post remission consolidation regimens has also been discussed.


Assuntos
Proteínas Estimuladoras de Ligação a CCAAT , Leucemia Mieloide Aguda , Proteínas Estimuladoras de Ligação a CCAAT/genética , Dissecação , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/terapia , Mutação , Prognóstico
20.
Rev Med Liege ; 76(5-6): 470-475, 2021 May.
Artigo em Francês | MEDLINE | ID: mdl-34080382

RESUMO

Acute leukemias are a heterogeneous group of malignant hemopathies which are subdivided according to the cytological orientation of the pathological blast cell into lymphoblastic (ALL) and myeloblastic (AML) acute leukemias. Recent advances in the biological and genetic understanding of these diseases have led to improved treatments. Specific chemotherapy treatment or so-called «targeted¼ treatments, advances in bone marrow transplantation and better supportive care have gradually improved the prognosis. This review, focused on the adult patient, aims to describe recent progress in terms of diagnosis, prognostic markers and therapy.


Assuntos
Leucemia Mieloide Aguda , Doença Aguda , Adulto , Transplante de Medula Óssea , Humanos , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Prognóstico
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