- Incidence and survival of T-cell acute lymphoblastic leukemia in the United States. [Journal Article]
- LLLeuk Lymphoma 2018 Nov 08; :1-8
- T-cell acute lymphoblastic leukemia (T-ALL) is a curable malignancy in the pediatric population. However, population-level data on its incidence and outcomes among adults is sparse. Using SEER databa...
T-cell acute lymphoblastic leukemia (T-ALL) is a curable malignancy in the pediatric population. However, population-level data on its incidence and outcomes among adults is sparse. Using SEER database, we identified 1141 patients aged ≥20 years with pathologically confirmed T-ALL diagnosed between the years 2001 and 2014 and actively followed. Incidence of T-ALL was 0.13 cases/100,000 population with significant variations by age, gender, race, and period. The 5-year overall survival (OS) declined significantly with increasing age (age <40, 51.9%; age 40-59, 37.3%; age 60-79, 19.2%; age ≥80, 0%; p < .001) and varied by race (whites - 45.7%, blacks - 25.1%, others - 40.3%; p < .001). Over time, OS has improved significantly in patients <60 years (2001-2007, 42.8% vs 2008-2014, 53.1%; p = .005), but not in patients older than 60 years (2001-2007, 18% vs 2008-2014, 22.8%; p = .71), highlighting the need for effective and safe treatments in this population.
- [Clinical and prognostic significance of ABO promotor methylation level in adult leukemia and myelodydysplastic syndrome]. [Journal Article]
- ZNZhonghua Nei Ke Za Zhi 2018 Nov 01; 57(11):816-823
- Objective: To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods: ABO promoter methy...
Objective: To investigate the clinical and prognostic significance of ABO promotor methylation level in adult patients with leukemia and myelodydysplastic syndrome(MDS). Methods: ABO promoter methylation level of 182 malignant hematological disease patients and 68 normal controls were detected by bisulfite sequencing PCR.Then clinical features and outcome were compared between hypermethylation group and hypomethylation group. Results: The median methylation rate of ABO promoter in newly diagnosed acute myeloid leukemia (AML) and acute lymphocytic leukemia (ALL) were 46.98% and 11.01% respectively, which were both higher than that in controls (2.30%, P<0.05). The methylation rates in remission AML and ALL were 1.58% and 2.30% respectively, which were comparable with that in normal group (P>0.05). As to relapse AML and ALL, methylation rates were 41.26% and 17.50% respectively, also significantly higher than that in controls (P<0.05).In patients with chronic myeloid leukemia (CML) chronic phase, the median methylation rate was 1.00%, which was similar to normal group. But a CML patient who transformed to ALL hadextremely high methylation rate 92.56%. The median methylation rate in patients with MDS significantly elevated as 5.81% compared with that in controls (P<0.05). The median overall survival (OS) of ALL and AML (non-M3) patients with hypermethylation were 12.5 months and 15.3 months, which were significantly shorter than those with hypomethylation (24.0 months and 20.0 months)(P<0.05).The median disease-free survival (DFS) of ALL and AML (non-M3) patients with hypermethylation were 9.9 months and 12.0 months, which were significantly shorter than those with hypomethylation (22.3 months and 18.5 months), (P<0.05). Multivariable analysis suggested that ABO promoter methylation level was an independent predictive factor of OS and DFS in ALL and AML (non-M(3)) patients. Conclusion: ABO promoter hypermethylation is closely related to genesis, development and prognosis of leukemia and MDS. Hypermethylationis related to a clinical poor prognosis compare with hypomethylation.
- Esophageal Varices in Adolescent and Young Adult Males with Acute Lymphocytic Leukemia. [Journal Article]
- JAJ Adolesc Young Adult Oncol 2018 Oct 18
- Hepatic late effects are not commonly reported in survivors of childhood leukemia. Four young male patients with acute lymphoblastic leukemia (ALL) were diagnosed with bleeding esophageal varices (EV...
Hepatic late effects are not commonly reported in survivors of childhood leukemia. Four young male patients with acute lymphoblastic leukemia (ALL) were diagnosed with bleeding esophageal varices (EVs) during or shortly after completion of maintenance chemotherapy. EVs were identified from 0 to 60 months after completion of leukemia therapy. All four patients were men between 20 to 24 years old. Hematemesis was the most common presenting symptom. Associated features included splenomegaly, cytopenias, azole therapy, alcohol use, and hepatic iron overload. EVs may be an under-recognized complication of ALL therapy, with adolescent and young adult males at highest risk.
- The distinguishable DNA whole genome methylation profile of 2 cases of pediatric precursor B acute lymphoblastic leukaemia (BCP ALL) with prodromal, preleukemic phase: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(42):e12763
- CONCLUSIONS: The biological implication of this observation remains unclear, with many differentially methylated loci involved in many processes like neurogenesis, cell projection organization and adhesion along with leucocyte activation and apoptosis. The prevalence and clinical significance of these methylation changes is unknown but this data indicates that the epigenetic basis of BCP ALL with a prolonged, prodromal phase requires a more detailed assessment.
- Isolation, purification, characterisation and application of L-ASNase (L-ASNase): A review. [Journal Article]
- RPRecent Pat Biotechnol 2018 Oct 12
- CONCLUSIONS: L-ASNase is used as a potential anti-tumour medicine. It plays a very much essential role for the growth of tumour cells. Tumour cells require a lot of asparagine for their growth. But ASNase converts to aspartate and ammonia from asparagine. So the tumour cell does not proliferate and fails to survive. The L-ASNase is used as the medicine for the major type of cancer like acute lymphocytic leukaemia (ALL), brain. It also used as a medicine for central nervous system (CNS) tumours, and also for neuroblastoma. Two types of L-ASNase have been found.L-ASNase becomes a powerful anti-tumour medicine and researchers should develop a potent strain of asparaginase which can produce asparaginase in the industrial level. It also used in pharmaceutical industry and food industry as a broad scale.
- Diagnostic challenges in T-lymphoblastic lymphoma, early T-cell precursor acute lymphoblastic leukemia or mixed phenotype acute leukemia: A case report. [Case Reports]
- MMedicine (Baltimore) 2018; 97(41):e12743
- CONCLUSIONS: For the diagnosis of T-LBL, the molecular markers of the myeloid and lymphoid tissues need to be included, such as CD117, CD33, Lys and MPO. The bone marrow puncture also needs to be conducted to distinguish T-LBL and T-ALL. Secondly, to identify ETP-ALL and MPAL, bone marrow cell morphology, cytochemical staining as well as flow cytometric analysis were needed to make a clear diagnosis. It is recommended that at least CD8, CD1a, Lys and MPO should be included in the panel to identify ETP-ALL.
- Increasing G9a automethylation sensitizes B acute lymphoblastic leukemia cells to glucocorticoid-induced death. [Journal Article]
- CDCell Death Dis 2018 Oct 10; 9(10):1038
- Synthetic glucocorticoids (GCs) are used to treat lymphoid cancers, but many patients develop resistance to treatment, especially to GC. By identifying genes that influence sensitivity to GC-induced ...
Synthetic glucocorticoids (GCs) are used to treat lymphoid cancers, but many patients develop resistance to treatment, especially to GC. By identifying genes that influence sensitivity to GC-induced cell death, we found that histone methyltransferases G9a and G9a-like protein (GLP), two glucocorticoid receptor (GR) coactivators, are required for GC-induced cell death in acute lymphoblastic leukemia (B-ALL) cell line Nalm6. We previously established in a few selected genes that automethylated G9a and GLP recruit heterochromatin protein 1γ (HP1γ) as another required coactivator. Here, we used a genome-wide analysis to show that HP1γ is selectively required for GC-regulated expression of the great majority of GR target genes that require G9a and GLP. To further address the importance of G9a and GLP methylation in this process and in cell physiology, we found that JIB-04, a selective JmjC family lysine demethylase inhibitor, increased G9a methylation and thereby increased G9a binding to HP1γ. This led to increased expression of GR target genes regulated by G9a, GLP and HP1γ and enhanced Nalm6 cell death. Finally, the KDM4 lysine demethylase subfamily demethylates G9a in vitro, in contrast to other KDM enzymes tested. Thus, inhibiting G9a/GLP demethylation potentially represents a novel method to restore sensitivity of treatment-resistant B-ALL tumors to GC-induced cell death.
- Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. [Journal Article]
- EOExpert Opin Biol Ther 2018; 18(11):1095-1106
- Cellular immunotherapy with autologous or allogeneic T cells, genetically engineered to express chimeric antigen receptors (CARs) or T-cell receptors, in order to redirect their cytotoxic specificity...
Cellular immunotherapy with autologous or allogeneic T cells, genetically engineered to express chimeric antigen receptors (CARs) or T-cell receptors, in order to redirect their cytotoxic specificity toward malignant cells, is emerging as a promising new treatment modality. The most advanced approach in clinical development is the use of anti-CD19 CAR T-cells for the treatment of CD19+ B-cell malignancies, including acute lymphocytic leukemia (ALL). Areas covered: Recently, the Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell product, tisagenlecleucel, for the treatment of pediatric and young adult patients with relapsed/refractory ALL. In this overview, we described the advances in the field, including a summary of clinical trials with tisagenlecleucel in ALL published to date. Expert opinion: CAR T-cell therapy has been developed in the context of small clinical studies and very few centers have had to deal with the challenges of managing CAR T-cells administration. However, this approach is likely to become a standard option for patients with relapsed/refractory B-cell lineage ALL.
- Hematopoietic Stem Cell Transplantation in the Era of Engineered Cell Therapy. [Review]
- CHCurr Hematol Malig Rep 2018 Oct 02
- Cellular therapy using T cells modified to express chimeric antigen receptors (CAR-T cells) has had striking success in patients that have failed previous treatment for CD19+ B cell non-Hodgkin lymph...
Cellular therapy using T cells modified to express chimeric antigen receptors (CAR-T cells) has had striking success in patients that have failed previous treatment for CD19+ B cell non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), or acute lymphoblastic leukemia (ALL). Curative therapy for this group of diseases has previously been limited to allogeneic hematopoietic cell transplantation HCT (alloHCT). The recent results of CAR-T cell therapy raise the question of how best to integrate CAR-T cell therapy and alloHCT in the care of these patients.
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- Allogeneic CAR-T Cells: More than Ease of Access? [Review]
- CCells 2018 Oct 01; 7(10)
- Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaem...
Patient derived anti-CD19 chimeric antigen receptor-T (CAR-T) cells are a powerful tool in achieving a complete remission in a range of B-cell malignancies, most notably B-acute lymphoblastic leukaemia (B-ALL) and diffuse large B-cell lymphoma (DLBCL). However, there are limitations, including inability to manufacture CAR-T cells from the patient's own T cells, disease progression and death prior to return of engineered cells. T cell dysfunction is known to occur in cancer patients, and several groups have recently described differences in CAR-T cells generated from chronic lymphocytic leukaemia (CLL) patients compared with those from a healthy donor. This is thought to contribute to the low response rate in this disease group. Healthy donor, gene-edited CAR-T cells which do not require human leucocyte antigen (HLA) matching have the potential to provide an 'off the shelf' product, overcoming the manufacturing difficulties of producing CAR-T cells for each individual patient. They may also provide a more functional, potent product for malignancies such as CLL, where T cell dysfunction is common and frequently cannot be fully reversed during the manufacturing process. Here we review the potential benefits and obstacles for healthy donor, allogeneic CAR-T cells.