MRD by FCM is a strong independent predictor of outcome in terms of DFS and OS and is a powerful informative parameter in guiding individual treatment in ALL patients.
Protein Phosphatase 2A (PP2A) is a crucial regulator of the cellular signalling pathways, proliferation, cell cycle checkpoints and apoptosis. The PPP2R5C gene encodes PP2A regulatory B56c subunit. Malignant transformation may occur, if mRNA of PPP2R5C is functionally deregulated, structurally altered, decreased or overexpressed. Therefore, the purpose of the study was to examine PPP2R5C mRNA expression, evaluate its association with the different clinical and haematological parameters and determine its prognostic impact in Egyptian adult acute myeloid leukaemia patients with normal cytogenetics (CN-AML). Peripheral blood samples of 50 de novo CN-AML patients and 20 age-and gender-matched healthy controls were examined for PPP2R5C expression by Quantitative Real Time-Polymerase Chain Reaction. The expression levels of PPP2R5C mRNA were significantly higher in the CN-AML samples than in the control samples (P B 0.001). There was a statistical significant difference between the low and high expression levels of PPP2R5C with regard to age (P = 0.005, r = -0.447, P = 0.001). The patients with an unfavourable response to induction chemotherapy had significant higher PPP2R5C expression levels than those with a favourable response (P = 0.002). There was a significant influence of high PPP2R5C expression levels on the overall survival and progression free survival (P = 0.03, 0.026), respectively. PPP2R5C overexpression is an adverse prognostic factor which affects leukaemogenesis in the CN-AML, it may predict the disease progression and overall survival during the follow-up of the patients.
Introduction: The vast majority ofmyeloproliferative neoplasms (MPNs) patients are characterized by a molecular genetic background and by variable symptoms reflecting disease burden that may correlate with prognosis. Aim: To study the impact of triple negative status of driver gene mutations: Janus kinase 2 (JAK2), calreticulin (CALR) and myeloproliferative leukemia virus oncogene (MPL) on disease burden and its correlation with symptom severity (MPN10 score) and degree of bone marrow (BM) fibrosis in MPNs patients. Patients and Methods: MPN Symptom Assessment Form Total Symptom Score (MPN-SAF TSS) was assessed as median of 10 items: fatigue, concentration, early satiety, inactivity, night sweats, itching, bone pains, abdominal discomfort, weight loss and fever. JAK2V617F and MPL W515exon 10 mutations were performed by allele-specific oligonucleotide polymerase chain reaction (ASO-PCR) while CALR exon 9 insertion/deletion was detected by high-resolution melting (HRM) curve analysis. Results: 100 MPNs patients (54 males and 46 females): 18 polycythemia vera (PV), 41 essential thrombocythemia (ET), 24 primary myelofibrosis (PMF), 10 Post-ET/PV-myelofibrosis (post-ET/PV-MF) and 7 myelodysplastic/myeloproliferative neoplasms (MDS/MPN) were included. Median age at diagnosis was 55 years (17-75) and was lower in ET than PV and PMF patients; 44 (19-75) years vs. 56 (34-70) years and 56 (20-75) years, respectively (p=0.06). JAK2 mutation was positive in 15 (85%) PV patients, 14 (34%) ET patients, 15 (62%) PMF patients, 8(80%) post-ET/PV-MF patients and zero (0%) MDS/MPN patients (p<0.001). CALR mutation was positive in zero (0%) PV patients, 10 (24%) ET patients, 4 (17%) PMF patients, zero (0%) Post-ET/PV-MF patients and zero (0%) MDS/MPN patients (p<0.05). MPL mutation was positive in zero (0%) PV patients, 2 (5%) ET patients, 1(4%) PMF patients, zero (0%) Post ET/PV-MF patients and zero (0%) MDS/MPN patients. Twenty four/93 (26%) patients were triple negative; 15 ET (16%), 3 PV (3%), 6 PMF (6%). Median MPN10 score was 21 (4-45) in ET versus 37.5 (25-56) in PV, 54 (15-80) in PMF and 59 (45-75) in Post-ET/PV-MF (p<0.001). Median MPN10 score was 25 (10-50) in triple negative patients vs. 40 (4-80) in MPNs patients showing at least one driver mutation positivity (p<0.001). BM fibrosis was present in 6 (15%) patients with triple negative vs. 33 (85%) patients showing at least one molecular marker positivity (p=0.007). Out of 52 patients having splenomegaly; seven (13.5%) patients were triple negative vs. 45 (87%) patients with at least one gene mutation (p<0.001). Out of the 24 triple negative patients, 19 (80%), 4 (16%), 1 (3%) and 0(0%) had BM fibrosis grades 0, 1, 2 and 3 vs. 36 (52%), 7 (10%), 12 (17%), 14 (20%) out of 69 patients with at least one gene mutation, respectively (p=0.002). After a median follow-up period of 16 months (3-151), overall survival (OS) was 95%. OS in PV and ET patients was 100 % versus 83 % in PMF patients (p=0.08). OS in triple negative group was 100% versus 94% in the gene mutations group (p=0.387). Conclusion: Driver gene mutations show an impact on disease symptoms and burden. Triple negative MPNs patients in our cohort have significantly low MPN10 score and less BM fibrosis which may indicate a more indolent disease course. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.
Introduction: Numerous factors affect the outcome of Allogeneic Peripheral blood stem cells transplantation (PBSCs). In Egypt, roughly 15 million patients are currently suffering from Hepatitis C (HCV) viremia with 40,000 deaths each year. Aim: To study the impact of HCV viremia on the tempo of engraftment and on incidence of acute and chronic graft versus host disease (GVHD) as well as sinusoidal obstruction syndrome (SOS). Patients and methods: Between March 1997 and June 2014, 332 HCV seropositive patients with various hematological disorders were enrolled; 54 acute lymphoblastic leukemia (ALL), 131 acute myeloid leukemia (AML), 46 severe aplastic anemia (SAA), 29 B thalassemia major (B-TM), 22 chronic myeloid leukemia (CML) and 25 myelodysplastic syndrome (MDS) patients; all received allogeneic peripheral blood stem cells transplantation (PBSCT) at the BMT unit of Nasser Institute hospital for Research and Treatment, Cairo, Egypt . Conditioning regimens using Fludarabine (FLU), Busalphan (BU), cyclophosphamide (CY), antithymocyte globulin (ATG), melphalane (MELPH) and total body irradiation (TBI) differed according to disease entity including (BU/CY, FLU/BU for AML and CML, , BU/CY/ATG for B-TM, TBI/CY for ALL, FLU/CY for SAA and FLU/MELPH). GVHD prophylaxis consisted of methotrexate (MTX) at days 1, 3, 6 & 11 plus Cyclosporin A (CSA) starting from day -1. Mycophenolate mofetil (MMF) was added to cases transplanted using reduced intensity conditioning (RIC). Results: Neutrophil engraftment was reached at a median of 15, 14, 12, 16, 17, and 17 days for ALL, AML, SAA, B-TM, CML and MDS patients, respectively. Platelet engraftment was reached at a median of 11, 12, 13, 15, 22 and 11 days for ALL, AML, SAA, B-TM, CML and MDS patients, respectively. The incidence of SOS was 2.7%, 2.2%, 2.1%, 3.4%, zero%, and zero % in ALL, AML, SAA, B-TM, CML and MDS patients, respectively. Acute GVHD grade 2-4 was reported in 6 ALL, 18 AML, 2 SAA, 3 BTM, 10 CML and 2 MDS patients while chronic GVHD was reported in 7 ALL, 16 AML, 2 SAA, 2 BTM, 3 CML, and 2 MDS patients. Event free survival (EFS) in all disease entities was 44.7% at 3 years & 44.3% at 5 years while overall survival (OS) was 55.9% at 3 years & 54.2 % at 5 years for all patients, respectively. Conclusion: Analysis of 332 HCV positive patients subjected to PBSCT show that HCV does not affect platelet or neutrophil engraftment or the incidence of SOS. HCV viremia does not show a significant impact on the incidence of aGVHD and cGVHD or OS. However, a comparative study with a negative HCV patient's cohort is still ongoing. Figure 1 Figure 1. Figure 2 Figure 2. Figure 3 Figure 3. Disclosures No relevant conflicts of interest to declare.
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