ABSTRACT
INTRODUCTION: Few studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: We retrospectively analysed the clinical features, treatment response, and long-term outcomes of 42 AYA patients, in comparison to older patients. The initial therapies of AYA patients between 2001 and 2016 included imatinib (n = 24), dasatinib (n = 13) and nilotinib (n = 5). RESULTS: In AYA patients, the peripheral blood (PB) white blood cell count and percentage of blasts at the diagnosis were significantly higher, haemoglobin levels were lower and the spleen size was larger. The major molecular response (MMR), event-free survival (EFS) and overall survival (OS) rates were comparable. A sub-analysis comparing imatinib to second-generation TKIs as the initial therapy also showed that their prognosis was comparable. DISCUSSION: In conclusion, the tumour burden at the diagnosis of CML-CP is higher in AYA patients; however, their prognosis was not worse in comparison to older patients treated with TKIs. KEY MESSAGESFew studies have reported the outcomes of adolescents and young adults (AYAs) with chronic-phase chronic myeloid leukaemia (CML-CP) on tyrosine kinase inhibitors (TKIs). This study showed the tumour burden at the diagnosis of CML-CP is higher in AYA pa tients; however, their prognosis was not worse in comparison to older patients treated with TKIs. Understanding the biological and non-biological features of AYA patients with CML-CP on TKI therapy is essential for better management and to improve the outcomes.
Subject(s)
Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Leukemia, Myeloid, Chronic-Phase , Adolescent , Humans , Imatinib Mesylate/adverse effects , Imatinib Mesylate/therapeutic use , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myeloid, Chronic-Phase/diagnosis , Leukemia, Myeloid, Chronic-Phase/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Retrospective Studies , Young AdultABSTRACT
Inflammation is a major hallmark of several cancers. The present study evaluated the prognostic value of the Fibrinogen-Albumin Ratio Index (FARI) at the diagnosis in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) treated with azacitidine (AZA). A retrospective study was conducted in a single cohort of 99 patients with de novo MDS and AML-MRC who were treated with AZA between May 2011 and June 2019 in our hospital. Plasma fibrinogen and serum albumin levels were measured before the start of AZA treatment. A total of 99 patients were included in the analysis. The optimal cut-off value of FARI for predicting the 1-year overall survival (OS) was determined by a receiver operating characteristic (ROC) analysis to be 0.079. A total of 59 (60%) and 40 (40%) patients had an FARI ≥0.079 (high-FARI group) and < 0.079 (low-FARI group), respectively. The high-FARI patients had a significantly shorter OS than low-FARI patients (1-year OS, 35.6% vs. 77.5%, p < 0.001). In a multivariate analysis, parameters with independent adverse significance for the OS were a high FARI (≥0.079) (hazard ratio (HR) 2.41, 95% confidence interval (CI), 1.36-4.29; p = 0.006), and Revised-International Prognostic Scoring System (IPSS-R) very high (HR 1.483, 95% CI, 1.12-1.963, p = 0.006). A high FARI was found to be associated with a poor outcome in MDS and AML-MRC patients treated with AZA, and FARI was an independent prognostic factor for the OS in these patients. Further internal and external validations are needed to clarify the prognostic role of the FARI for MDS and AML-MRC patients.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Azacitidine/therapeutic use , Fibrinogen/analysis , Leukemia, Myeloid, Acute/blood , Myelodysplastic Syndromes/blood , Serum Albumin, Human/analysis , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Inflammation , Kaplan-Meier Estimate , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Prognosis , Proportional Hazards Models , ROC Curve , Retrospective StudiesSubject(s)
Azacitidine/administration & dosage , Leukemia, Myeloid, Acute , Myelodysplastic Syndromes , Nutritional Status , Adult , Age Factors , Aged , Aged, 80 and over , Disease-Free Survival , Female , Humans , Leukemia, Myeloid, Acute/drug therapy , Leukemia, Myeloid, Acute/mortality , Male , Middle Aged , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/mortality , Survival RateABSTRACT
BACKGROUND: The ABO blood group is reported to be associated with survival for several types of malignancy. We conducted a retrospective study to evaluate the prognostic significance of the ABO blood group in patients with malignant lymphoma. PATIENTS AND METHODS: A total of 523 patients with malignant lymphoma were included in this study. The primary outcome measured was the association between the ABO blood group and survival. RESULTS: Patients with blood group B had shorter 5-year overall survival (OS) than patients with non-B blood groups (40.9% vs. 57.3%; P < .01). Among 240 patients with diffuse large B-cell lymphoma (DLBCL), patients with blood group B had shorter 5-year OS in comparison with patients with non-B blood groups (36.3% vs. 56.9%; P < .01). Among male patients with DLBCL, those with blood group B had significantly shorter 5-year OS than those with non-B blood groups (27.5% vs. 55.8%; P = .003). On the other hand, there was no significant difference in the survival between female patients with blood group B and those with non-B blood groups (5-year OS: 49.2% vs. 58.2%; P = .67). A multivariate analysis demonstrated that blood group B (hazard ratio, 1.83; 95% confidence interval, 1.21-2.78; P = .04) was an independent predictor of shorter OS in male patients with DLBCL. CONCLUSION: The ABO blood group is associated with survival in patients with lymphoma. Interestingly, only male patients with DLBCL with blood group B had significantly shorter OS than those male patients with DLBCL with non-B blood groups.
Subject(s)
ABO Blood-Group System/metabolism , Lymphoma/blood , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Lymphoma/mortality , Male , Middle Aged , Prognosis , Survival Analysis , Young AdultSubject(s)
Antineoplastic Agents/administration & dosage , Brain/drug effects , Imidazoles/administration & dosage , Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy , Pyridazines/administration & dosage , Aged, 80 and over , Brain/diagnostic imaging , Central Nervous System/physiopathology , Female , Humans , Philadelphia Chromosome , Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics , Recurrence , Tomography, X-Ray ComputedSubject(s)
Antineoplastic Agents/therapeutic use , Eye Neoplasms/diagnostic imaging , Eye Neoplasms/drug therapy , Lymphoma, Mantle-Cell/complications , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use , Adenine/analogs & derivatives , Aged , Humans , Magnetic Resonance Imaging , Male , Piperidines , Treatment Outcome , Visual AcuityABSTRACT
BACKGROUND: Restoration of virus-specific immunity by virus specific T cells (VSTs) offers an attractive alternative to conventional drugs, and can be highly effective in immunocompromised patients, including hematopoietic stem cell transplant (HSCT) recipients. However, conventional VSTs manufacture requires preparation of specialized antigen-presenting cells (APCs), prolonged ex vivo culture in serum-containing medium and antigen re-stimulation with viruses or viral vectors to provide viral antigens for presentation on APCs. METHODS: To simplify this complex process, we developed a method to generate multiple VSTs by direct stimulation of peripheral blood mononuclear cells (PBMCs) with overlapping peptide libraries in serum-free medium. RESULTS: We generated VSTs that targeted seven viruses (cytomegalovirus [CMV], Epstein-Barr virus [EBV], adenovirus [AdV], human herpesvirus 6 [HHV-6], BK virus [BKV], JC virus [JCV] and Varicella Zoster virus [VZV]) in a single line. The phenotype, growth and specificity of multiple VSTs produced in serum-free medium were equivalent to those generated in conventional serum-containing medium. DISCUSSION: The use of serum-free medium allows this approach to be readily introduced to clinical practice with lower cost, greater reproducibility due to the absence of batch-to-batch variability in serum and without concerns for infectious agents in the serum used. This simplified approach will now be tested in recipients of Human Leukocyte Antigen (HLA)-matched sibling HSCT.
Subject(s)
Antigens, Viral/immunology , Leukocytes, Mononuclear/immunology , Peptides/pharmacology , T-Lymphocytes/immunology , T-Lymphocytes/virology , Adenoviridae/immunology , Antigen-Presenting Cells/immunology , Cell Proliferation , Cells, Cultured , Culture Media, Serum-Free/pharmacology , Cytomegalovirus/immunology , Herpesvirus 3, Human/immunology , Herpesvirus 4, Human/immunology , Humans , Immunophenotyping , Leukocytes, Mononuclear/drug effects , Peptide Library , Peptides/immunology , Reproducibility of ResultsABSTRACT
T-cell protein tyrosine phosphatase (TC-PTP, also known as PTPN2) is a negative regulator of the JAK/STAT pathway. STAT5 is activated by BCR-ABL kinase and STAT1 is an important transcription factor for interferon (IFN)-α-induced signaling in chronic myeloid leukemia (CML). We used siRNA to delete TC-PTP in the CML cell line, KT-1, and examined changes in the sensitivity to imatinib and IFN-α. Suppression of TC-PTP induced activation of STAT5, leading to imatinib resistance, while prolonged phosphorylation of STAT1 was induced by IFN-α, triggering cell death in KT-1 cells. These findings suggest that TC-PTP modulates sensitivity to imatinib and IFN-α in CML.