Content of nonessential elements and chemical composition of main community of grassland in ecological zones

Result of studying a nutrition value of main communities in grasslands is depending on ecological zones and growth stage. Contamination of non essential elements, macro-micro element is non-significant difference between forest steppe and steppe while a significant difference came out in semi desert area.Journal of agricultural sciences №15 (02): 113-117, 201

Translocation (8;21) Presenting As Severe Aplastic Anemia

Abstract Translocation of 8;21 (q22;q22), generating a fusion of RUNX1 and AML1 genes is considered leukemia-defining and typically presents as an unequivocal acute myeloid leukemia (AML) with peripheral blood blasts and a hypercellular marrow, although it has been reported in patients with Fanconi anemia and myelodysplastic syndrome (MDS) (Quentin S et al. Blood 2011 Apr 14;117(15)). Aplastic anemia is a rare disease characterized by severe pancytopenia and a hypocellular marrow. A few cytogenetic abnormalities, namely trisomy 8 and monosomy 7, are associated with particularly refractory aplastic anemia, and monosomy 7 is associated with clonal evolution to MDS and rapid progression to AML. We describe a case of newly-acquired severe aplastic anemia in a 23 year old woman. Laboratory studies at presentation showed white blood cells 1.38 k/uL, absolute neutrophil count 0 k/uL, hemoglobin 7.4 g/dL, absolute reticulocyte count 5 k/uL, and platelets 38 k/uL. Bone marrow biopsy was 5% cellular with trilineage hematopoiesis and absolutely no dysplasia, even on repeated review. Initial cytogenetic analysis performed outside the NIH at presentation was normal. The patient was transferred to our institution and promptly received standard immunosuppressive therapy given the severity of neutropenia. However, a repeat bone marrow analysis performed immediately prior to immunosuppression showed t(8:21) (q22;q22) by standard cytogenetics in 3 out of 20 metaphases, with confirmation by fluorescence in situ hybridization (FISH). Blasts were not identified despite multiple repeat bone marrow aspirations utilizing immunohistochemistry and flow cytometry. Testing for Fanconi anemia was negative and leukocyte telomere length was normal for age. She remained severely pancytopenic and transfusion dependent for many months. Chemotherapy for AML was withheld given the severe pancytopenia and absence of blasts, and a search for a bone marrow transplant donor was initiated. Progression to frank leukemia with circulating blasts occurred 8 months following initial presentation, just prior to unrelated donor allogeneic stem cell transplantation. To our knowledge, this is the first reported case of acquired severe aplastic anemia, profound marrow hypocellularity, hypocellular MDS or hypocellular AML occurring in association with the t(8;21)(q22;q22). This unusual case prompted us to perform comparative genomic hybridization (CGH) using the single nucleotide polymorphism (SNP) based CytoScan high density microarrays on DNA from the patient’s bone marrow mononuclear cells. We detected multiple, large regions of copy neutral loss of heterozygosity (also referred to as uniparental disomy) in the patient’s marrow, ranging in size from 3 to 29 Mbp on multiple chromosomes. We hypothesized that the copy-neutral loss of heterozygosity observed in this case would not be present in other patients with acquired aplastic anemia at diagnosis or in normal controls. CGH did not demonstrate any large regions of copy neutral loss of heterozygosity in 10 patients with acquired severe aplastic anemia and normal cytogenetics at diagnosis, nor in 35 healthy controls. Emerging data show that SNP arrays can detect abundant copy neutral loss of heterozygosity amongst select hematologic malignancies and are associated with the duplication of oncogenic mutations. In our patient, copy neutral loss of heterozygosity possibly provided a second lesion, in addition to the RUNX1/AML1 abnormality, that facilitated initiation or progression to leukemia. These results suggest SNP based CGH arrays may be useful in distinguishing hypocellular AML from aplastic anemia and further studies utilizing this technology are warranted. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Translocation (8;21) acute myeloid leukemia presenting as severe aplastic anemia

AbstractWe report a case of t(8;21) acute myeloid leukemia presenting as severe aplastic anemia. While initial bone marrow biopsy lacked any cytogenetic abnormalities in 20 analyzed metaphases, repeat bone marrow biopsy eight days later demonstrated this translocation. Initial cytogenetic analysis of 20 metaphases was therefore insufficient to make the diagnosis of hypocellular acute myeloid leukemia. We discuss that further complementary molecular tests, such as CGH, would likely provide a more robust diagnosis of hematopoietic diseases

Excellent Engraftment and Reduced Acute and Chronic Graft Versus Host Disease (GVHD) in ATG-Refractory Severe Aplastic Anemia (SAA) Following Transplantation of a PBSC Allograft Containing CD34+ Selected Cells Combined with Non-Mobilized Donor T-Cells

Abstract Introduction: The risk of graft-rejection after allogeneic hematopoietic cell transplantation using bone marrow and conventional cyclophosphamide-based conditioning is increased in HLA allo-immunized and heavily transfused patients with bone marrow failure syndromes. Recently, we showed that fludarabine-based peripheral blood stem cells transplantation (PBSCT) overcomes the risk of graft-failure in patients with SAA who have failed immunosuppressive therapy (IST). However, this approach was complicated by a high incidence of acute and chronic GVHD. Multivariate analysis showed rapid donor T-cell engraftment (defined as &gt;= 95% donor T-cell chimerism by post-transplant day 30) significantly increased the risk of cGVHD. Based on these data, we developed a novel transplant approach in which a G-CSF mobilized PBSC allograft that was T-cell depleted and CD34+ selected was co-infused with a bone marrow transplant (BMT)-equivalent dose of non-mobilized donor T-cells to facilitate donor engraftment and reduce GVHD by delaying the speed of donor T-cell engraftment. Method: Patients with transfusion-dependent SAA, refractory to conventional IST, underwent allogeneic PBSCT following cyclophosphamide (60 mg/kg/d IV x 2 days), equine antithymocyte globulin (hATG; 40 mg/kg/d IV x 4 days), and fludarabine (25 mg/m2/d IV x 5 days) conditioning. On day 0, patients received a G-CSF mobilized PBSC allograft from an HLA identical sibling, containing CD34+ selected cells (MiltenyiCliniMACS system: target CD34+ cell dose 8 x 106 cells/kg and target T-cell dose &lt; 3 x 105 cells/kg) combined with 2 x 107CD3+ T-cells/kg that had been collected by apheresis and cryopreserved from the same donor prior to G-CSF mobilization. CSA and mini-dose MTX (5 mg/m2 IV on days 1, 3, 6) were used as GVHD prophylaxis. Transplant outcomes were compared to our historical cohort of patients (n=56) with SAA and other bone marrow failure syndromes who received a T-cell replete PBSC from an HLA matched donor following the identical conditioning and GVHD prophylaxis regimens. Results: 11 patients with SAA were transplanted. Patients were heavily transfused and highly allo-immunized; the pre-transplant serum ferritin level was markedly elevated at a median 3003 µg/L (range 286 to 13928 µg/L) and 7 patients (64%) were HLA allo-immunized with a median 21% (HLA class I) and 31% (HLA class II) panel-reactive antibodies. All 11 patients (100%) engrafted. The median time to neutrophil and platelet recovery was 14 (range 12 to 23) and 18 (range 14 to 321) days respectively. All patients achieved full and sustained donor T-cell chimerism and myeloid chimerism, which occurred at a median 45 and 15 days post-transplant, respectively. Among those at risk, 6/7 (86%) developed CMV reactivation. EBV reactivation occurred in all cases, including 5 who received preemptive treatment with rituximab. At a median follow-up of 2 years, only 1 patient (9%) has developed acute and another (9%) developed cGVHD (limited, skin). Neither corticosteroid-refractory aGVHD nor extensive cGVHD occurred. Long-term survival was excellent; 10 of 11 patients (91%) survived to day 200; at a median follow-up of 2.7 years, 9/11 (80%) survive. One patient died on day 46 from Klebsiella Pneumoniae carbapenemase bacteremia, which predated the transplant, and another died 18 months post-transplant from bacterial pneumonia. Compared to our historical cohort of marrow failure patients who received a T-cell replete PBSC allograft, patients receiving CD34+ selected cells combined with non-mobilized T-cells (partially T cell depleted PBSC) had similar survival (80% vs 87%;p=0.5), a delay in the time to achieving full donor T-cell chimerism (45 days vs 30 days; p=0.046) and dramatic reductions in both acute grade II-IV GVHD (9% vs 52%; p=0.017) and cGVHD (1 year incidence 9% vs 63%; p=0.002). Conclusion: In SAA, transplantation of a PBSC allograft containing high numbers of CD34+ selected cells co-infused with a BMT-equivalent dose of non-mobilized T-cells results in excellent engraftment and reduces acute and chronic GVHD by delaying the speed of donor T-cell engraftment. Figure: Figure:. Disclosures Townsley: GSK: Research Funding. </jats:sec

Mosunetuzumab in combination with CHOP in previously untreated DLBCL: safety and efficacy results from a phase 2 study

Please note that the abstract has been provided separately as it is now over the word count due to the incorporation of reviewer suggestions

Mosunetuzumab plus Pola-CHP compared with Pola-R-CHP in previously untreated DLBCL: final results from a phase 2 study

Abstract: This phase 2 study evaluated mosunetuzumab plus cyclophosphamide, doxorubicin, prednisone, and polatuzumab vedotin (Pola-M-CHP) vs Pola-rituximab (R)-CHP for first-line treatment of diffuse large B-cell lymphoma. Patients were randomized 2:1 to receive 6 cycles of Pola-M-CHP or Pola-R-CHP on day 1 of each 21-day cycle. Mosunetuzumab was administered intravenously via step-up dosing during cycle 1 and at 30 mg on day 1 of subsequent cycles. The primary end point was independent review committee–assessed complete response (CR) rate by positron emission tomography–computed tomography. Overall, 62 patients were enrolled and received Pola-M-CHP (n = 40) or Pola-R-CHP (n = 22). CR rates were similar in both arms (72.5% with Pola-M-CHP vs 77.3% with Pola-R-CHP); the 24-month investigator-assessed progression-free survival rate was 70.8% (95% confidence interval [CI], 55.6-86.1) with Pola-M-CHP vs 81.8% (95% CI, 65.7-97.9) with Pola-R-CHP. The most common adverse event (AE) was cytokine release syndrome (68.4%; mostly grade 1 [52.6%], and primarily confined to cycle 1) with Pola-M-CHP and neutropenia/neutrophil count decreased (54.5%) with Pola-R-CHP. Neutropenia/neutrophil count decreased was the most frequently observed grade ≥3 AE in both arms (Pola-M-CHP, 36.8%; Pola-R-CHP, 22.7%). Rates of grade ≥3 AEs (86.8% vs 59.1%), serious AEs (63.2% vs 13.6%), and AEs leading to treatment discontinuation (13.2% vs 0%) were higher with Pola-M-CHP than Pola-R-CHP, respectively. Pharmacodynamic changes were supportive of mosunetuzumab’s mechanism of action and its addition to the Pola-CHP combination. Pola-M-CHP, although an active combination, did not demonstrate a clinical benefit over Pola-R-CHP in this small study. This trial was registered at www.clinicaltrials.gov as #NCT03677141