Systemic mastocytosis with chronic myelomonocytic leukemia followed by transformation into acute myeloid leukemia

IntroductionSystemic mastocytosis (SM) with an associated hematological neoplasm (SM-AHN) constitutes about 40% of all patients with SM. AHN commonly includes myeloid neoplasms and chronic myelomonocytic leukemia (CMML) is seen in about 30% of these patients. Case reportA 67-year-old male presented to hematologist with fatigue and significant weight loss. Abdominal ultrasound and computed tomography (CT) detected hepatosplenomegaly, abdominal lymphadenopathy, and ascites. He was anemic with leukocytosis and eosinophilia. Trephine biopsy showed > 30% of spindle-shaped mast cells. The mutation was present. Serum tryptase level was elevated to 62 ng/mL. The patient was diagnosed with aggressive SM and received six cycles of cladribine with partial response. Three years later, he developed severe anemia. Eosinophilia and monocytosis (5.6 × 10/L) were demonstrated in blood film. Hepatosplenomegaly and abdominal lymphadenopathy were also present. Trephine biopsy did not demonstrate the presence of spindle-shaped mast cells, but dysplasia in erythroid and myeloid lineages was evident. The histological result of lymph node biopsy as well as blood and bone marrow findings were in line with CMML. He received hydroxyurea, but he transformed soon into fatal acute monocytic leukemia. ConclusionsThe prognosis of SM-AHN depends on AHN component. Leukemic transformation of AHN component may occur in a proportion of patients

Olfactory Neuromodulation of Motion Vision Circuitry in Drosophila

It is well established that perception is largely multisensory; often served by modalities such as touch, vision, and hearing that detect stimuli emanating from a common point in space; and processed by brain tissue maps that are spatially aligned. However, the neural interactions among modalities that share no spatial stimulus domain yet are essential for robust perception within noisy environments remain uncharacterized. Drosophila melanogaster makes its living navigating food odor plumes. Odor acts to increase the strength of gaze-stabilizing optomotor reflexes to keep the animal aligned within an invisible plume, facilitating odor localization in free flight. Here, we investigate the cellular mechanism for cross-modal behavioral interactions. We characterize a wide-field motion-selective interneuron of the lobula plate that shares anatomical and physiological similarities with the "Hx" neuron identified in larger flies. Drosophila Hx exhibits cross-modal enhancement of visual responses by paired odor, and presynaptic inputs to the lobula plate are required for behavioral odor tracking but are not themselves the target of odor modulation, nor is the neighboring wide-field "HSE" neuron. Octopaminergic neurons mediating increased visual responses upon flight initiation also show odor-evoked calcium modulations and form connections with Hx dendrites. Finally, restoring synaptic vesicle trafficking within the octopaminergic neurons of animals carrying a null mutation for all aminergic signaling is sufficient to restore odor-tracking behavior. These results are the first to demonstrate cellular mechanisms underlying visual-olfactory integration required for odor localization in fruit flies, which may be representative of adaptive multisensory interactions across taxa

Multiparameter flow cytometry for assessment of minimal residual disease in patients with myelodysplastic syndromes treated with allogeneic stem cell transplantation

BackgroundMyelodysplastic syndromes (MDSs) are a heterogeneous group of clonal myeloid neoplasms. Allogeneic stem cell transplantation (allo-SCT) remains the curative method for MDS treatment. Little is known about the monitoring of minimal residual disease (MRD) in patients with MDS after allo-SCT. AimWe aimed to evaluate the significance of leukemia-associated immunophenotypes (LAIPs) identified in acute myeloid leukemia (AML) for MRD monitoring in patients with MDS after allo-SCT. Material and methodsSeven males and 4 females with a median age of 55 years were included. The diagnosis of MDS was established according to 2016 World Health Organization (WHO) criteria. The significance of eight LAIPs in bone marrow samples using multiparameter flow cytometry (MFC) was evaluated for MRD. ResultsEight patients were positive for several LAIPs before allo-SCT. The identified LAIPs included the presence of aberrant lymphoid antigens on myeloblasts and lack of CD33 expression on myeloblasts. All studied MDS patients were negative for LAIPs at Day +30 after the procedure. This was followed by full-donor chimerism in all cases. The Ogata score after allo-SCT decreased in all patients in whom it was indicative for MDS before allo-SCT. ConclusionsMFC could be useful in monitoring MRD in MDS patients after allo-SCT. Further studies in this field are needed

A Glial Variant of the Vesicular Monoamine Transporter Is Required To Store Histamine in the Drosophila Visual System

Unlike other monoamine neurotransmitters, the mechanism by which the brain's histamine content is regulated remains unclear. In mammals, vesicular monoamine transporters (VMATs) are expressed exclusively in neurons and mediate the storage of histamine and other monoamines. We have studied the visual system of Drosophila melanogaster in which histamine is the primary neurotransmitter released from photoreceptor cells. We report here that a novel mRNA splice variant of Drosophila VMAT (DVMAT-B) is expressed not in neurons but rather in a small subset of glia in the lamina of the fly's optic lobe. Histamine contents are reduced by mutation of dVMAT, but can be partially restored by specifically expressing DVMAT-B in glia. Our results suggest a novel role for a monoamine transporter in glia that may be relevant to histamine homeostasis in other systems

Efficacy and Safety of Conditioning Treatment Using Bendamustine in Autologous Hematopoietic Cell Transplantation in Heavily Pretreated Patient with Lymphoma

Abstract Abstract 4537 Most of lymphoma patients are chemo- and radiosensitive. Using a conventional therapy we can cure about 50% of patients (pts). Unfortunately the rests achieved only partial remission or have a rapid relapse after treatment. These pts are a real challenge for nowadays hematology. Till now there is not a recommended scheme of therapy. Using high dose chemotherapy with autologous hematopoietic cell transplantation (AHCT) is the most popular one. During the last year in our Department we have been started using BeEAM as the conditioning treatment, and the results of a single centre observation are presented now. Material and Methods Actually: between April, 2011 and February, 2012 we conducted AHCT using BeEAM as conditioning treatment in 23 pts with lymphoma (18 pts with Hodgkin Lymphoma (HLy), 2pts with diffuse large B cell lymphoma (DLBCL), 2 pts with T cell lymphoma (TCL), 1 with follicular lymphoma (FL). There were 14 male and 9 female, with a median age of 37,6 (range 21–62 yrs). Ann Arbor staging at diagnosis was as follows: II-33%, III-50%, IV-17%; 83% of patients manifested B-symptoms. Clinical manifestation at diagnosis included: enlargement of the lymph nodes (n=18), bone marrow infiltration (n=2), lung infiltrates (n=3). Initially, all patients received at least 2 cycles of chemotherapy; in HLy all pts received ABVD, in non HLy- RCHOP. None of them achieved complete remission (CR). Partial response (PR), defined as the reduction of measurable disease by ≥50% without the appearance of any new lesions, achieved 11pts. The rests underwent high dose chemotherapy (HDT) followed by AHCT without remission (NR). Stem cells were collected from peripheral blood after IVE chemotherapy (Ifosfamide 3g/m2 iv in 1–3d, Etoposide200mg/m2 iv in 1–3d, Epirubicine 50mg iv in1d) and subsequent administration of G-CSF at a dose of 10ug/kg/d, starting from +5 day after chemotherapy till the last day of collection. Collections were performed using Optia Spectra. All pts collected the sufficient number of CD34+ cells for AHCT procedure. Conditioning regimens before AHCT consisted of BeEAM (Bendamustine 200mg/m2 in -8-7d, Etoposide 200mg/m2 in -6-3d, Ara-C 400mg/m2 in -6-3d, Melphalan 140mg/m2 in -2d). A median number of transplanted CD34+ cells was 5,58 (2,05–17,8×10∧6/kg). All except one pt successfully engrafted. 1 pt with Hly died within 8 day after transplantation due to infection. Hematopoietic recovery was as following: WBC count &gt; 1,0×10∧9/L after median of 12 days (range 9–15 days),ANC&gt; 0,5×10∧9/L after median of 13 days (range 9–16 days) and platelet count &gt;20×10∧9/L after median of 13days (range 7–20 days). Results 3 pts died after AHCT. Two of them due to progression of the disease within 5 and 16 months after AHCT. Both were without remission before AHSCT. 1 pt died due to heart insufficient after 3 months after AHCT. The complications after transplantation procedure were rare and included mainly: bacterial infection in the upper respiratory tract (n=3), viral skin infection (n=1), oral mucositis (n=2). At the last contact, 19 pts are alive and 9 of them achieved CR, and 3 – stable disease. One pt underwent sibling alloHCT and 2 others will undergo alloHCT within 2 months. 4 pts with Hly were treated with anty CD 30+. Conclusion Autologous hematopoietic cell transplantation using IVE for mobilization and BeEAM as conditioning is effective treatment for lymphoma patients with refractory disease. Disclosures: No relevant conflicts of interest to declare. </jats:sec

Pre-transplant FLT3/ITD status predicts outcome in FLT3-mutated acute myeloid leukemia following allogeneic stem cell transplantation

AbstractAcute myeloid leukemia (AML) with fetal liver tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) is associated with poor prognosis, and allogeneic stem cell transplantation (Allo-SCT) seems to be the preferred therapeutic approach. However, the predictors of post-transplant outcomes were not well-defined. The aim of the study was to evaluate the significance of FLT3/ITD mutation by polymerase chain reaction as minimal residual disease (MRD) marker of outcomes after transplantation. We identified 43 patients (28 females and 15 males) with FLT3-mutated AML at the median age of 45 years who were allografted between 2009 and 2019. Hematological status at transplant was as follows: the first complete remission (CR1) in 29 patients, CR2 in 5, and 9 patients were transplanted in marrow aplasia (MA). Twenty-seven patients were FLT3 MRD negative at transplant. Median time from diagnosis to transplant was 16.7 months. Post-allograft CR rate was 88%. The relapse incidence (RI) was lower for patients who were FLT3 MRD negative at transplant when compared with those with FLT3 MRD positivity (41% vs 59%; p = 0.01). The patients who eradicated FLT3/ITD at day + 30 after transplant had lower RI than those with detectable FLT3/ITD (23% vs 76%; p = &lt;0.001). The 2-year LFS and OS were 53% and 54%, with the median OS and LFS of 28 months and 27 months, respectively. Patients with CR1/2 and FLT3 MRD(−) had a 2-year OS of 80%. The FLT3 MRD negativity at transplant prolonged LFS in multivariate analysis (HR 5.3 95%CI 1.97–14.2); p &lt; 0.001), whereas FLT3 MRD negativity and unrelated donor predicted favorable OS.</jats:p

The measurement site of the greenhouse gases turbulent fluxes in Kopytkowo (Biebrza National Park)

The aim of the study is characteristic of the measurement site of the greenhouse gases fluxes. The site is located in the Central Basin of Biebrza Valley in Biebrza National Park. The natural environmental conditions of the Central Basin are presented with the focus on nearest neighborhood of the site. The configuration of the open-path eddy-covariance measurement system is described in detail as well as the low-respond sensors. Issues of the choice of eddy-covariance site in terms of the theoretical foundations of the method and practical limitations were discussed.Celem opracowania jest charakterystyka stanowiska pomiarowego turbulencyjnych strumieni gazów cieplarnianych zlokalizowanego w Środkowym Basenie Kotliny Biebrzańskiej w Biebrzańskim Parku Narodowym. Krótko scharakteryzowano warunki naturalne Środkowego Basenu ze szczególnym uwzględnieniem bezpośredniego otoczenia punktu pomiarowego. Szczegółowo opisano konfigurację systemu pomiarowego metodą kowariancji wirów z otwartą ścieżką pomiarową oraz charakterystyką pomiarów wolnozmiennych. Przedyskutowano problemy wyboru lokalizacji stanowiska pomiarowego strumieni turbulencyjnych w aspekcie założeń teoretycznych i możliwości praktycznych.Praca wykonana w ramach projektu “Bilans absorpcji i emisji gazów cieplarnianych (metanu, dwutlenku węgla i pary wodnej) na obszarach bagiennych (studium Biebrzańskiego Parku Narodowego)”sfinansowanego ze środków Narodowego Centrum Nauki przyznanych na podstawie decyzji numer DECR2011/01/B/ST10/07550