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KMT2A-rearranged (KMT2A-r) infant acute lymphoblastic leukemia (ALL) is a devastating malignancy with a dismal outcome, and younger age at diagnosis is associated with increased risk of relapse. To discover age-specific differences and critical drivers that mediate poor outcome in KMT2A-r ALL, we subjected KMT2A-r leukemias and normal hematopoietic cells from patients of different ages to single-cell multiomics analyses. We uncovered the following critical new insights: leukemia cells from patients

Thrombotic microangiopathies (TMA) are a rare group of life-threatening hematological conditions characterized by thrombocytopenia and microangiopathic hemolytic anemia. Although our understanding of the pathophysiology and the availability of diagnostic testing has improved for primary TMAs, such as thrombotic thrombocytopenic purpura, the pathophysiology underlying secondary TMAs, including drug-induced TMAs (DITMAs), remains less clear. In this case report, we present the unique case of a patient with a history of multiple myeloma that presented four months after the initiation of bortezomib therapy with a bortezomib-associated TMA that responded to therapeutic plasma exchange (TPE) with plasma replacement and eculizumab therapy. This case demonstrates the possible utility of TPE with plasma replacement and eculizumab therapy in DITMA patients that fail to respond following a trial of holding the suspected medication.

Folic acid was coupled to melphalan using glycyl-glycine (FA-Gly-Gly-Melphalan) to synthesise self-assembled nanomicelles for targeting ovarian cancer cells, SKOV3.FA-Gly-Gly-Melphalan self-assembled nanomicelles were prepared with critical micellar concentration (CMC) of 12-μg/ml. The mean particle size of FA-Gly-Gly-Melphalan self-assembled nanomicelles was measured to be 95.9 ± 3.4-nm significantly (FA-Gly-Gly-Melphalan self-assembled nanomicelles warrant in depth

The thalassemia is a group of disorders in which the normal ratio of alpha globin to beta globin production is disrupted due to a disease-causing variant in one or more of the globin genes. This abnormal alpha- to beta-chain ratio causes the unpaired chains to precipitate and causes destruction of red blood cell precursors in the bone marrow (ineffective erythropoiesis) and circulation (hemolysis). Affected individuals with thalassemia have variable degrees of anemia and extramedullary hematopoiesis, which in turn can cause bone changes, impaired growth, and iron overload. The aim and objectives are to describe the basic genetic differences between alpha-thalassemia and beta-thalassemia. Describe the hematologic findings and pathophysiological changes that are associated with beta-thalassemia major. Summarize the etiology of thalassemias and describe the basic genetic differences between alpha-thalassemia and beta-thalassemia. Describe the genetic, hematologic, and clinical differences between alpha-thalassemia trait, hemoglobin H disease, and hydrops fetalis. outline the challenges of thalassemia during Covid 19 crisis. Thalassemia is the most common, inherited, single-gene disorder in the world. Treatment of the inherited blood disorder thalassemia depends upon the level of severity.

Background: Thalassemia and hemoglobinopathies have significant complications on the children's health. Also, they have a higher cost for treatment. The prevalence of these diseases differs from one area to another in Saudi Arabia. Aims: To detect the different hemoglobin abnormality and their frequency in the premarital population in Makkah city. Methods: A cross-sectional study was conducted, which included 473 subjects who attended the premarital screening tests at the maternity and children Hospital laboratory and Heraa hospital. We were collected the data of the complete blood count, hemoglobin electrophoresis, and iron profile from the participants. The statistical analysis was performed by SPSS program version 20. Results: 74.8% of the participants were normal, 9.3% had iron deficiency anemia (IDA), 6.3% were suspected to be alpha thalassemia trait, 3.4% had sickle cell trait, 3% were polycythemia, 1.5% had hereditary persistence fetal hemoglobin (HPFH), 1.1% were IDA with thalassemia trait, 0.4% were beta thalassemia trait, 0.2% had hemoglobin E trait. Conclusion: thalassemia trait and hemoglobinopathies are present in the premarital population in Makkah city at a low prevalence. The highest frequency was for the alpha thalassemia trait, then sickle cell trait, then HPFH, then beta-thalassemia trait, and lastly, hemoglobin E trait. IDA is present at a high frequency. Education to the population is essential to decrease the prevalence of these disorders.

Root canal irrigation helps in eliminating the microorganisms present in the canal system. The present in vitro study was done to evaluate the efficacy root canal irrigants; sodium hypochlorite, neem, Tulsi, and Aloe vera against E. faecali. In present study 5 groups of root canal irrigants (sodium hypochlorite, neem, Tulsi, Aloe vera, and distilled water as controlled group) were tested for efficacy against E. faecali. There was highest inhibition zone observed with sodium hypochlorite group followed by Neem (Azadirachta indica), neem, Tulsi, Aloe vera and least was observed in control group with distilled water. The tested root canal irrigants sodium hypochlorite group followed by Neem (Azadirachta indica), Tulsi, and Aloe vera are effective against E. faecali.

We had two cases of trisomy 8-positive myelodysplastic syndrome (MDS) with incomplete Behçet’s disease (BD) in which the remissions of both diseases were maintained by allogeneic stem cell transplantation (allo-SCT). Among MDS with BD patients, sometimes it is difficult to control the symptoms of BD with standard therapies such as corticosteroids and tumor necrosis factor (TNF) inhibitors. Although there should be careful consideration regarding indications for transplantation, our two cases, in which refractory BD was completely controlled by allo-SCT, suggest that allo-SCT can be one of the treatment options for higher-risk MDS with BD patients.

Kawasaki disease is an acute, self-limited vasculitis of unknown etiology, which mainly occurs in infants and children. The target organs of Kawasaki disease are coronary arteries and other cardiovascular structures. The initial manifestations of Kawasaki disease are high fever, inflammation of skin and mucosa, and enlargement of cervical lymph nodes. About 25% of children who are not treated with intravenous immunoglobulin during the acute phase of the disease will develop coronary artery aneurysms. Nowadays, Kawasaki disease has replaced rheumatic fever as the main cause of acquired heart disease in children in developed countries. However, there is still no specific diagnostic test, echocardiography is still the main diagnostic method of coronary artery involvement in children with Kawasaki disease, and risk stratification assessment is carried out according to Z value to assist in the short-term and long-term diagnosis and treatment of Kawasaki disease. In the aspect of treatment, there are reports on the application of corticosteroids, infliximab, cyclosporine, methotrexate, interleukin receptor blockers and so on. This article makes a detailed elaboration on the epidemiology, pathology, diagnostic criteria, differential diagnosis, treatment and prognosis of Kawasaki disease, so as to improve clinicians' understanding of Kawasaki disease and reduce misdiagnosis possible.

Primary gastric lymphoma is a well-characterised disease in humans, but is poorly characterised in cats. This study retrospectively describes the presentation, diagnosis, treatment and outcome of cats with primary gastric lymphoma in a UK referral hospital. Medical records of cats diagnosed with primary gastric lymphoma, without ultrasonographic involvement of the intestinal tract, between 2009 and 2020 were reviewed. A total of 13 cats met the inclusion criteria. All cases were of large cell lymphoma. Cytology alone was diagnostic in nearly all cases (10/11). At diagnosis six cats were euthanised. The remaining seven cats were treated with a multiagent chemotherapy protocol (5/7) or a combination of prednisolone and chlorambucil (2/7). Median overall survival time was 300 days (ranging from 30–1980 days). The two cats treated with prednisolone and chlorambucil survived for 300 and 480 days respectively. This study raises awareness of feline primary gastric lymphoma for veterinary surgeons in clinical practice. Although an uncommon disease presentation, primary gastric lymphoma has unique characteristics that may differ from the high-grade intestinal form. Further studies are needed to evaluate the optimum therapeutic approach.

Lymphomas in the head and neck region (HNR) can be a diagnostic challenge owing to their indistinctive oral manifestations that frequently mimic other pathologies. This case report highlights a young male who experienced spontaneous paraesthesia of his lower lip with an accompanied localized dull ache. Initial clinical examination and investigations were inconclusive. A definitive diagnosis of extranodal low-grade B-cell non-Hodgkin lymphoma (NHL) was only confirmed after the second incisional biopsy, which was 15 months after onset of symptoms. This report offers insight of NHL in the HNR and its clinical presentation. It aims to improve awareness amongst dental practitioners to aid early diagnosis. CPD/Clinical Relevance: The reader should consider lymphomas as a differential diagnosis for unexplained symptoms, including paraesthesia, mucosal ulceration and soft tissue swelling.

Epstein syndrome is a rare disease characterized by macrothrombocytopenia, nephritis and progressive sensorineural hearing loss (SNHL). This syndrome is presently recognized as an autosomal dominant disease caused by mutations of non-muscle myosin heavy chain 9 (MYH9). Little information is available about the progress of SNHL, the efficacy of cochlear implants (CI) or the perioperative management of thrombocytopenia in patients with Epstein syndrome. We herein report a case of a patient with Epstein syndrome with the MYH9:c.2105G>A:p.R702H variant who underwent cochlear implantation after 27 years of follow-up for her progressive SNHL. The deterioration rates of hearing were 3.48 dB/year on the right ear and 2.46 dB/year on the left ear. The patient derived benefits from CI and had a speech recognition test result (for sentences) of 93% at 6-months postoperatively. Thrombocytopenia was successfully managed without any bleeding complications by using eltrombopag, an oral thrombopoietic agent, making transfusion of platelets unnecessary. The accurate diagnosis of Epstein syndrome was made only after long-term follow-up as the thrombocytopenia was initially diagnosed as idiopathic thrombocytopenic purpura. This case report highlights the perioperative management of thrombocytopenia, the progress of SNHL and the potential pitfalls of diagnosis.

Right neck swelling and pain occurred in a 49-year-old man. A Blood count showed a slight increase in platelet count without leukemoid reaction. After a biopsy of the cervical mass and bone marrow aspiration, a diagnosis of extramedullary blast crisis (EBC) of chronic myeloid leukemia (CML) was made. Fluorescence in situ hybridization (FISH) analysis showed a BCR-ABL1 fusion signal, but results of real-time polymerase chain reaction (RT-PCR) for major and minor BCR-ABL1 transcripts were negative. We identified a rare e1a 3 BCR-ABL1 fusion transcript. Administration of dasatinib resulted in disappearance of the extramedullary tumor. This is the first reported case of CML-EBC with e1a3 transcript. An aleukemic extramedullary tumor can be the initial presentation of CML.

Monica Bocchia,1 Angelo Michele Carella,2 Antonino Mulè,3 Lorenzo Rizzo,4 Mauro Turrini,5 Maria Chiara Abbenante,2 Roberto Cairoli,4 Valeria Calafiore,3 Marzia Defina,1 Angelo Gardellini,5 Giovanni Luzi,6 Caterina Patti,3 Maria Beatrice Pinazzi,6 Marta Riva,4 Giovanni Rossi,2 Vincenzo Sammartano,1 Luigi Rigacci6 1Hematology Unit, Azienda Ospedaliera Universitaria Senese, University of Siena, Siena, Italy; 2Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo Della Sofferenza, Foggia, Italy; 3UOC Hematology and Oncology, Ospedali Riuniti Villa Sofia-Cervello, Palermo, Italy; 4Department of Haematology, Niguarda Cancer Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy; 5Division of Hematology, Valduce Hospital, Como, Italy; 6UOC Hematology and Stem Cell Transplant Unit, Ospedale S, Camillo, Rome, ItalyCorrespondence: Angelo Michele Carella, Division of Hematology with Hematologic Intensive Care Unit and Cellular Therapies, Department of Medical Science, Fondazione IRCCS Casa Sollievo della Sofferenza, Viale Cappuccini, San Giovanni Rotondo, Foggia, 71013, Italy, Tel +390882410054, Fax +390882410322, Email am.carella@operapadrepio.itAbstract: Acute myeloid leukemia is a malignant disorder of the bone marrow, characterized by differentiation, clonal expansion, and uncontrolled proliferation of malignant myeloid progenitor cells and by several molecular and genetic abnormalities. A mutation of FMS-like tyrosine kinase 3 gene can be observed in about one-third of cases of acute myeloid leukemia. Two FLT3 inhibitors are actually approved for FLT3 mutated acute myeloid leukemia: midostaurin, a multikinase first generation inhibitor with lower affinity for FLT3 binding, and gilteritinib fumarate, a potent second-generation inhibitor of both FLT3-ITD and TKD. Gilteritinib is a new effective and well-tolerated drug for patients with relapsing or refractory FLT3-positive acute myeloid leukemia. Thanks to its efficacy, low toxicity, its good manageability (oral formulation), this drug is suitable for all the patients, including elderly frail patient with concomitant therapies or pre-existing or underlying diseases, and can be used also in the outpatient setting, reducing risks and costs related to the hospitalization. We report and discuss seven cases of different patients with FLT3 positive acute myeloid leukemia successfully managed with gilteritinib in the real clinical practice.Keywords: acute myeloid leukemia, FLT3, midostaurin, gilteritinib

Amr J Halawani,1 Abdullah A Mobarki,2 Ali H Arjan,3 Muhammad Saboor,2 Hassan A Hamali,2 Gasim Dobie,2 Khalaf F Alsharif4 1Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia; 2Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 3Department of Laboratory and Blood Bank, King Fahad Central Hospital, Ministry of Health, Jazan, Saudi Arabia; 4Department of Clinical Laboratory Science, College of Applied Medical Sciences, Taif University, Taif, Saudi ArabiaCorrespondence: Amr J Halawani, Department of Laboratory Medicine, Faculty of Applied Medical Sciences, Umm Al-Qura University, Makkah, Saudi Arabia, Email ajjhalawani@uqu.edu.saPurpose: Sickle cell disease (SCD) and thalassemia are common inherited blood disorders in Saudi Arabia, especially in Jazan Province. Patients with these disorders require multiple blood transfusions, which may lead to alloimmunization because of mismatched blood group antigens. In this study, we examined the alloimmunization and autoimmunization rates in patients with SCD and thalassemia together with the involved antibodies.Patients and Methods: A cross-sectional study was conducted to review the transfusion history records of patients with SCD and thalassemia at Prince Mohammed bin Nasser Hospital, Jazan Province, Saudi Arabia.Results: Four-hundred thirty-eight patients (385 with SCD, 52 with β-thalassemia, and 1 with α-thalassemia) were received leukoreduced red cell transfusions. The alloimmunization and autoimmunization rates in patients with SCD were 12.98% and 0.52%, respectively. In patients with thalassemia, the alloimmunization and autoimmunization rates were 13.21% and 3.77%, respectively. The most prevalent antibodies in the study population were anti-E (17.19%) and anti-K (14.06%).Conclusion: The alloimmunization and autoimmunization rates were determined in patients with SCD and thalassemia in Jazan Province, Saudi Arabia. The results highlight the need for extended phenotyping to include ABO, RH (D, C, c, E, e), K, Fya, Fyb, Jka and Jkb antigens in the screening panel. This will benefit patients to ensure better transfusion practices.Keywords: red cell alloimmunization, sickle cell disease, thalassemia, autoimmunization

Background aims The internal tandem duplication of FLT3 (FLT3ITD) and NPM1 mutations (NPM1mut) are well-established prognostic factors in cytogenetically intermediate-risk acute myeloid leukemia (AML) when treated with chemotherapy alone. However, their prognostic value in the setting of allogeneic hematopoietic cell transplantation (HCT) is controversial. Methods FLT3 and NPM1 mutational status was determined at diagnosis using single-gene polymerase chain reaction or next-generation sequencing in 247 adult patients with cytogenetically intermediate-risk AML who underwent myeloablative HCT. Multivariate Fine–Gray and Cox regression was used to analyze the cumulative incidence of relapse (CIR), relapse-free survival (RFS) and overall survival (OS). Results FLT3ITD and NPM1mut were present in 74 of 247 (30%) and 79 of 247 (32%) patients, respectively. There was no significant difference between patients without a FLT3ITD or NPM1mut (FLT3NONITD/NPM1WT) and patients with a FLT3ITD mutation alone (FLT3ITD/NPM1WT) with regard to CIR (P = 0.60), RFS (P = 0.91) or OS (P = 0.66). Similarly, there was no significant difference between FLT3NONITD/NPM1WT and FLT3NONITD/NPM1mut patients with regard to CIR (P = 0.70), RFS (P = 0.75) or OS (P = 0.95). The presence of a concurrent mutation in NPM1 did not appear to modify the impact of having a FLT3ITD mutation. Conclusions In contrast to chemotherapy-only treatment, FLT3 and NPM1 mutational status does not appear to predict outcomes in patients with cytogenetically intermediate-risk AML following HCT. These results suggest that HCT may ameliorate the poor prognostic effect of FLT3ITD mutation and that HCT should be considered over chemotherapy-only treatment in FLT3ITD-mutated AML.

Overexpression of the BCL2 protein has been reported as a poor prognostic factor for diffuse large B-cell lymphoma (DLBCL). However, there are currently no standardized criteria for evaluating BCL2 protein expression. We aimed to evaluate the prognostic value of BCL2 expression determined by immunohistochemistry (IHC), incorporating both the staining intensity and proportion, in patients with de novo DLBCL who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment. We defined tumors with BCL2 expression in nearly all tumor cells with a uniformly strong intensity by IHC as BCL2 super-expressor. The BCL2 super-expressors (n = 35) showed significantly worse event-free survival (EFS; HR, 1.903; 95% CI, 1.159-3.126, P = 0.011) and overall survival (OS; HR, 2.467; 95% CI, 1.474-4.127, P = 0.001) compared with the non-BCL2 super-expressors (n = 234) independent of the international prognostic index (IPI), cell of origin (COO), and double expressor status in the training set (n = 269). The adverse prognostic impact of BCL2 super-expression was confirmed in the validation set (n = 195). When the survival outcomes were evaluated in the entire cohort (n = 464), BCL2 super-expressor group was significantly associated with inferior EFS and OS regardless of IPI, COO, MYC expression, and stages. BCL2 super-expressors had genetic aberrations enriched in the NOTCH and TP53 signaling pathways. This study suggests that the BCL2 super-expressor characterizes a distinct subset of DLBCL with a poor prognosis and warrants further investigation as a target population for BCL-2 inhibitors.

Background: The fusion and rearrangement of the ALK gene of anaplastic lymphoma kinase is an important cause of a variety of cancers, including non-small cell lung cancer (NSCLC) and anaplastic large cell lymphoma (ALCL). Since crizotinib first came out, many ALK inhibitors have come out one after another, but the fatal flaw in each generation of ALK inhibitors is the body's resistance to drugs. Therefore, how to solve the problem of drug resistance has become an important bottleneck in the application and development of ALK inhibitors. This article briefly introduces the drug resistance of ALK inhibitors and the modified forms of ALK inhibitors, which provide a theoretical basis for solving the drug resistance of ALK inhibitors and the development of a new generation of ALK kinase inhibitors. Method: We use relevant databases to query relevant literature, and then screen and select based on the relevance and cutting edge of the content. We then summarize and analyze appropriate articles, integrate and classify relevant studies, and finally write articles based on topics. Result: This article starts with the problem of ALK resistance, first introduces the composition of ALK kinase, and then introduces the problem of resistance of ALK kinase inhibitors. Later, the structural modification to overcome ALK resistance was introduced, and finally, the method to overcome ALK resistance was introduced. Conclusion: This article summarizes the resistance pathways of ALK kinase inhibitors, and integrates the efforts made to overcome the structural modification of ALK resistance problems, and hopes to provide some inspiration for the development of the next generation of ALK kinase inhibitors.

Acute lymphoblastic leukemia (ALL) is a common malignancy in children. In this study, we aimed to explore putative mechanisms of microRNA-155-5p (miR-155-5p) involvement in childhood ALL (cALL) via interactions with casitas B-lineage lymphoma (CBL), interferon regulatory factor 4 (IRF4), and cyclin-dependent kinase 6 (CDK6). Bioinformatic analysis was performed initially to identify differentially expressed genes in cALL. The expression levels of miR-155-5p, CBL, IRF4, and CDK6 in peripheral blood lymphocytes from clinical ALL samples were determined using RT-qPCR and Western blot assays. A dual-luciferase reporter gene assay was used to ascertain a possible targeting relationship between miR-155-5p and CBL, CCK-8 assay and flow cytometry were used to measure cell activity and apoptosis of ALL cells. Co-IP was performed to investigate the interaction between CBL and IRF4 and the ubiquitination level of IRF4. Furthermore, in vivo validation was performed inducing xenograft tumor models with ALL cells in nude mice. As indicated by bioinformatic analysis, miR-155-5p and CDK6 were upregulated and CBL was downregulated in ALL. miR-155-5p was found to target CBL to inhibit CBL expression. miR-155-5p promoted the proliferation of ALL cells and inhibited their apoptosis by inhibiting the expression of CBL, which otherwise degraded IRF4 protein through ubiquitination, leading to inhibited CDK6 expression. Collectively, the results show that miR-155-5p can promote the development of cALL via the regulation on CBL-mediated IRF4/CDK6 axis. The authors explored the role of microRNA-155-5p (miR-155-5p) in childhood acute lymphoblastic leukemia (cALL). They found that miRNA-155-5p targets the E3 ubiquitin ligase CBL and inhibits its expression, reducing the ubiquitination and degradation of interferon regulatory factor 4, thus elevating expression of cyclin-dependent kinase 6. These findings suggest a basis for potential future therapeutic strategies for cALL.

The type II transmembrane glycoprotein CD38 has recently been implicated in regulating metabolism and the pathogenesis of multiple conditions, including aging, inflammation and cancer. CD38 is overexpressed in several tumor cells and microenvironment tumoral cells, associated to migration, angiogenesis, cell invasion and progression of the disease. Thus, CD38 has been used as a progression marker for different cancer types as well as in immunotherapy. This review focuses on describing the involvement of CD38 in various non-hematopoietic cancers.

Objective: This study aimed to validate the sensitivity analysis of all the available formulas for their ability to differentiate between IDA and thalassemia and propose a novel formula to improve the sensitivity of all thalassemia subtypes screening.Material and Methods: We conducted a 5-year, single-center, Cohort study on 227 microcytic anemia patients diagnosed between June 2015 and September 2020 at Chaophraya Yommarat Hospital, Suphanburi, Thailand to validate the sensitivity of all the available formulas and invent the novel predictive score.Results: Approximately three-quarters of our cases were all subtypes of thalassemia diseases while 26.9% were IDA. The sensitivity of almost all the previous formulas for thalassemia prediction ranged between 13.9%-44.0%, while the specificity varied between 0%–98.4%. Nevertheless, the sensitivity of the formulas that had favorable sensitivity was quite low. Here, a novel thalassemia–iron deficiency discrimination (TID) predictive score is proposed, which demonstrated a sensitivity of 90.4% the specificity of 78.7%, the positive predictive value of 92.0 %, the negative predictive value of 75.0%, and the accuracy of 87.2%.Conclusion: The proposed TID predictive score is a novel uncomplicated formulation which offers high sensitivity for all thalassemia subtypes prediction.

Background: Chronic Myeloid Leukemia (CML) is a myeloproliferative disease caused by BCR-ABL oncoprotein. Tyrosine kinase inhibitors have been developed to inhibit the activity of BCR-ABL; however, drug resistance and side effect occur in clinic application. Therefore, it is urgent to find novel drugs for CML treatment. Under the guidance of cytotoxic activity, crude extracts of 55 fungal strains from the medicinal mangrove Acanthus ilicifolius were evaluated, and one potent cytotoxic natural compound, brefeldin A (BFA), was discovered from Penicillium sp. (HS-N-29). Objective: This study was aimed to determine the cytotoxic activity of BFA and the effect on the activation and expression of BCR-ABL in K562 cells. Method: We evaluated cytotoxic activity by MTT assay and soft agar clone assay; apoptosis and cell cycle distribution by Muse cell analyzer. The protein level of BCR-ABL and signaling molecules was detected by western blotting, and the mRNA level of BCR-ABL was determined by RT-PCR. Results: BFA inhibited cell proliferation, induced G2/M cell cycle arrest, and stimulated cell apoptosis in K562 cells. Importantly, for the first time, we revealed that BFA inhibited the activation of BCR-ABL and consequently inhibited the activation of its downstream signaling molecules in K562 cells. Moreover, we found BFA degraded BCR-ABL without affecting its transcription in K562 cells, and BFA-induced BCR-ABL degradation was related to caspase activation, while not to autophagy or ubiquitinated proteasome degradation pathway. Conclusion: Our present results indicate that BFA acts as a dual functional inhibitor and degrader of BCR-ABL, and BFA is a potential compound for chemotherapeutics to overcome CML.

BACKGROUND: Treatment for adults with acute lymphoblastic leukaemia requires improvement. UKALL14 was a UK National Cancer Research Institute Adult ALL group study that aimed to determine the benefit of adding the anti-CD20 monoclonal antibody, rituximab, to the therapy of adults with de novo B-precursor acute lymphoblastic leukaemia.METHODS: This was an investigator-initiated, phase 3, randomised controlled trial done in all UK National Health Service Centres treating patients with acute lymphoblastic leukaemia (65 centres). Patients were aged 25-65 years with de-novo BCR-ABL1-negative acute lymphoblastic leukaemia. Patients with de-novo BCR-ABL1-positive acute lymphoblastic leukaemia were eligible if they were aged 19-65 years. Participants were randomly assigned (1:1) to standard-of-care induction therapy or standard-of-care induction therapy plus four doses of intravenous rituximab (375 mg/m2 on days 3, 10, 17, and 24). Randomisation used minimisation and was stratified by sex, age, and white blood cell count. No masking was used for patients, clinicians, or staff (including the trial statistician), although the central laboratory analysing minimal residual disease and CD20 was masked to treatment allocation. The primary endpoint was event-free survival in the intention-to-treat population. Safety was assessed in all participants who started trial treatment. This study is registered with ClincialTrials.gov, NCT01085617.FINDINGS: Between April 19, 2012, and July 10, 2017, 586 patients were randomly assigned to standard of care (n=292) or standard of care plus rituximab (n=294). Nine patients were excluded from the final analysis due to misdiagnosis (standard of care n=4, standard of care plus rituximab n=5). In the standard-of-care group, median age was 45 years (IQR 22-65), 159 (55%) of 292 participants were male, 128 (44%) were female, one (INTERPRETATION: Standard of care plus four doses of rituximab did not significantly improve event-free survival over standard of care. Rituximab is beneficial in acute lymphoblastic leukaemia but four doses during induction is likely to be insufficient.

T cells are established contributors to the pathogenesis of atopic dermatitis and psoriasis; yet, whether they are the key drivers or simply unwitting participants remains incompletely understood. Conversely, malignant T cells are the undisputed culprits of cutaneous T-cell lymphoma (CTCL), a group of diseases that share key clinical, histopathologic, and molecular features with inflammatory skin disease (ISD). Here, we compare the pathogenesis of ISD and CTCL and discuss the resulting insights. Recurrent, skin-limited disease implicates skin-resident memory T cells in both ISD and CTCL. In CTCL, malignant T cells recruit benign T cells into inflammatory skin lesions, a disease-amplifying function that has also been proposed for pathogenic T cells in ISD. Mechanistically, cytokines produced by malignant T cells in CTCL and by pathogenic T cells in ISD, respectively, are likely both necessary and sufficient to drive skin inflammation and pruritus, which in turn promotes skin barrier dysfunction and dysbiosis. Therapies for ISD target T-cell effector functions but do not address the chronicity of disease, whereas treatments for CTCL target malignant T cells but not primarily the symptoms of the disease. Integrating our understanding of ISD and CTCL can result in important insights into pathogenesis and therapy that may improve the lives of patients in both of these disease groups.

This is the first report describing primary pulmonary mucosa-associated lymphoid tissue (MALT) lymphoma with the high expression of IgG4. The histological findings were compatible with the diagnostic criteria for MALT lymphoma and IgG4-related respiratory disease (IgG4-RRD). An unfixed sample for Southern blotting was not obtained since computed tomography findings showed multiple lung cysts, which is rare in patients with MALT lymphoma. However, polymerase chain reaction using paraffin sections showed the clonality of the immunoglobulin heavy chain variable region gene rearrangement, confirming a diagnosis of MALT lymphoma. This is an instructive case in which primary pulmonary MALT lymphoma was histologically compatible with IgG4-RRD.

Rationale: von Willebrand factor (vWF) mediates platelet adhesion during thrombosis. While chronic thromboembolic pulmonary hypertension (CTEPH) is associated with increased plasma levels of vWF, the role of this protein in CTEPH has remained enigmatic. Objectives: To identify the role of vWF in CTEPH. Methods: CTEPH-specific patient plasma and pulmonary endarterectomy material from patients with CTEPH were used to study the relationship between inflammation, vWF expression, and pulmonary thrombosis. Cell culture findings were validated in human tissue, and proteomics and chromatin immunoprecipitation were used to investigate the underlying mechanism of CTEPH. Measurements and Main Results: vWF is increased in plasma and the pulmonary endothelium of CTEPH patients. In vitro, the increase in vWF gene expression and the higher release of vWF protein upon endothelial activation resulted in elevated platelet adhesion to CTEPH endothelium. Proteomic analysis revealed that nuclear factor (NF)-kB2 was significantly increased in CTEPH. We demonstrate reduced histone tri-methylation and increased histone acetylation of the vWF promoter in CTEPH endothelium, facilitating binding of NF-kB2 to the vWF promoter and driving vWF transcription. Genetic interference of NFkB2 normalized the high vWF RNA expression levels and reversed the prothrombotic phenotype observed in CTEPH-pulmonary artery endothelial cells. Conclusions: Epigenetic regulation of the vWF promoter contributes to the creation of a local environment that favors in situ thrombosis in the pulmonary arteries. It reveals a direct molecular link between inflammatory pathways and platelet adhesion in the pulmonary vascular wall, emphasizing a possible role of in situ thrombosis in the development or progression of CTEPH.

A diagnosis of lymphedema comes with a lifetime requirement for careful self-care and treatment to control skin deterioration and the consequences of excessive fluid and protein buildup leading to abnormal limb volume and an increased risk of infection. The burden of care and psychosocial aspects of physical disfiguration and loss of function are associated with compromised quality of life (QoL). The current standard therapeutic intervention is complex decongestive therapy with manual lymph drainage and frequent wearing of compression garments. With insurance limitations on therapy visits and the time and travel required, additional home treatment options are needed. Pneumatic compression pumps that mimic the manual massage pressure and pattern are sometimes prescribed, but these are bulky, difficult to apply, and require immobility during treatment. An open-label pilot study in 40 subjects was performed to evaluate the QoL and limb volume maintenance efficacy of a novel wearable compression system (Dayspring™) that is low profile, easy to use, and allows for mobility during treatment. After 28 days of use, subjects had a statistically significant 18% (

Background: Sexual functions in women with lymphedema secondary to breast cancer surgery have not been investigated sufficiently. This study aimed to compare patients with and without lymphedema af...

Purpose: Radiation dermatitis (RD) is a side effect experienced by many patients undergoing radiotherapy (RT) for breast cancer. In the present study, the Edmonton Symptom Assessment System (ESAS), a validated patient-reported symptom screening tool, was used to determine the impacts of RT-induced skin outcomes on ESAS items. Patient- and treatment-related factors and skin treatments to manage RD symptoms, were assessed for association with ESAS scores. Methods: Patient and treatment characteristics were collected retrospectively for breast cancer patients treated with adjuvant RT between December 2013 and November 2015. Prospective data was collected through clinician-reported surveys. Linear regression analyses were performed to detect the relationship between patient-reported ESAS scores and clinician-reported RD symptoms. Results: A total of 857 patients were included in the analysis. Moderate to severe scores were commonly reported for fatigue (n=412, 48%), wellbeing (n=386, 45%) and anxiety (n=266, 31%). Oral analgesic use was associated with ESAS fatigue, drowsiness, pain, nausea, lack of appetite, shortness of breath, and wellbeing (p Conclusions: The ESAS accurately reflects symptoms of fatigue, anxiety, and wellbeing for breast cancer patients undergoing RT. Our study, however, found no association between ESAS scores and RD severity, which may reflect the shortcomings of the ESAS in assessing symptom burden. Further research is necessary to warrant the development of a new site-specific symptom screening tool for use in RT for breast cancer. Micro Abstract: The Edmonton Symptom Assessment System (ESAS) is a routinely used patient-reported symptom scoring tool. In our patient population, ESAS fatigue, anxiety, and wellbeing were accurately captured. However, ESAS items showed no correlation with radiation dermatitis (RD) severity, despite the high prevalence of RD. As such, the development of a new patient-reported tool is warranted to adequately assess burden of RD.

Epigenetic dysregulation leads to aberrant DNA hypermethylation and is common in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). A large number of clinical trials in AML, MDS, and other hematologic malignancies have assessed hypomethylating agents (HMAs), used alone or in combination with other drugs, in the frontline, maintenance, relapsed/refractory, and peritransplant settings. Effective maintenance therapy has long been a goal for patients with AML in remission. Previous large, randomized clinical trials of maintenance with HMAs or other agents had not shown meaningful improvement in overall survival. Oral azacitidine (Oral-AZA [CC-486]) is approved in the United States, Canada, and European Union for treatment of adult patients with AML in first complete remission (CR) or CR with incomplete blood count recovery (CRi) following intensive induction chemotherapy who are ineligible for hematopoietic cell transplant. Regulatory approvals of Oral-AZA were based on outcomes from the randomized, phase III QUAZAR AML-001 trial, which showed a median overall survival advantage of 9.9 months with Oral-AZA versus placebo. Oral-AZA allows convenient extended AZA dosing for 14 days per 28-day treatment cycle, which is not feasible with injectable AZA. Focusing on AML and MDS, this report reviews the rationale for the use of orally bioavailable AZA and its potential use in all-oral combination therapy regimens; the unique pharmacokinetic and pharmacodynamic profile of Oral-AZA compared with injectable AZA; the clinical safety and efficacy of Oral-AZA maintenance therapy in patients with AML in first remission and for treatment of patients with active MDS; and ongoing Oral-AZA clinical trials.

Essential thrombocythemia is a condition caused by a high platelet count and a positive JAK2 (V617F) mutation. There is an increasing occurrence of malignancy, such as oral squamous cell carcinoma (OSCC), in patients with essential thrombocythemia. The objective of this case report is to document the novel instance of a patient with OSCC after being diagnosed with essential thrombocythemia and a positive JAK2 (V617F) mutation. The patient was a 42-year-old female who complained of an ulcer and pain in the dextral lateral tongue for three months. After two weeks, the pain diminished; however, there was swelling and tenderness on the ulcer. The patient was diagnosed with essential thrombocythemia and a positive JAK2 (V617F) mutation and began undergoing hydroxyurea therapy three months ago. The diagnosis of OSCC was based on exfoliative cytology and MRI. The patient was treated with an antiseptic mouthwash to prevent secondary infection and referred to an oncologist to manage the OSCC. It is possible to use the suspected markers of thrombocytosis and a positive JAK2 (V617F) mutation to define the OSCC diagnosis.

Back Ground: Myeloproliferative neoplasm (MPN) is a long-term blood disease that has an excess production of mature hematopoietic pluripotent stem cells in the bone marrow. In the early fifties, W. Dameshek structured the Myeloproliferative disorders that are at present the World Health Organization (WHO) changed it to Myeloproliferative Neoplasms (MPNs). According to the Iraqi cancer registry, Chronic Myeloproliferative disorders in the male is 0.62% and the incidence rate is 0.36, in female Chronic Myeloproliferative disorders (45 case) is 0.31% and the incidence rate is 0.24. The JAK2-V617F genetic mutation is approximately seventy percent of the Myeloproliferative Neoplasm cases. Interleukin-4 plasma and serum levels are significantly increased in MPNs different types. Objectives: The goal of this study is to estimate the IL-4 serum levels in the JAK2-V617F negative and positive mutation in the Iraqi MPNs patients. Materials and Methods: Total of (60) patients screened by cohort prospective study of having MPN who are patients presented to the National Center of Hematology / Al-Mustansiriyah University. Depending on the JAK2-V617F genetic mutation we classified our MPNs cases into 3 groups: JAK2-V617F negative (N: 20), JAK2-V617F positive (N: 40) and control group (10). Blood sample (5) ml was obtained from each individual in each group, by venipuncture using disposable syringes for IL-4 serum estimation by Enzyme Linked ImmunoSorbent Assay (ELISA) technique. Results: A clear indication of significant differences was observed between IL-4 serum level in JAK2-V617F negative samples and control samples (P < 0.05). Conclusion: The IL-4 serum level is high in MPNs patients, which is one of the immune evading mechanisms of the cancerous acting to imbalance the Th1/Th2 ratio and enhancing the anti-apoptotic activity inside those cells.

Aim: To compare the efficacy and safety of first-line chemotherapy (Chemo) plus immune checkpoint inhibitors (ICIs) or bevacizumab (Bev) in advanced non-squamous non-small-cell lung cancer without EGFR mutations or ALK fusions. Methods: A network meta-analysis was conducted to synthesize relative treatment outcomes. Results: Chemo + ICIs is superior to Chemo + Bev in both overall survival (hazard ratio: 0.92; 95% CI: 0.88–0.96) and progression-free survival (hazard ratio: 0.93; 95% CI: 0.90–0.97), with comparable severe adverse events. However, for patients with liver metastasis, Chemo + Bev has a 59.8% probability of providing better overall survival benefit. For specific regimens, pembrolizumab + Chemo showed an absolute advantage over other regimens. Conclusion: First-line Chemo + ICIs is superior to Chemo + Bev in advanced non-squamous non-small-cell lung cancer except for patients with liver metastasis.

Background: Laparoscopic pancreaticoduodenectomy (LPD) is one of the most technically challenging operations of minimally invasive surgery. We aimed to analyze the learning curve of a single surgeo...

The translocation t(5;12)(q31;p13)/ETV6::ACSL6 is a rare cytogenetic abnormality, although it is reported in various myeloid malignancies. To date, only 16 cases of t(5;12) and ETV6::ACSL6 rearrangement, confirmed by either molecular or Fluorescence In Situ Hyridization (FISH) analysis, have been reported. Eosinophilia is a distinctive and common feature associated with this rearrangement. Although few cases have been described, the prognosis of patients with ETV6::ACSL6 is considered poor. We report two additional cases of t(5;12)(q31;p13)/ETV6::ACLS6 rearrangement and eosinophilia. Unusually, in our cases, the ETV6::ACSL6 rearrangement occurred at the relapse of Acute Myeloid Leukemia (AML) patients who had t(6;9)(p23;q34)/DEK::NUP214 rearrangement at disease onset. The concurrence of these two rare abnormalities has never been reported and may suggest a cooperative role of t(5;12) and t(6;9), leading to disease relapse. Moreover, at relapse, both cases presented with eosinophilia, further strengthening the association of t(5;12) with eosinophilia in myeloid malignancies. Given the poor prognosis and the non-responsiveness to tyrosine kinase inhibitors of cases of ETV6::ACSL6 rearrangement, in contrast to cases of ETV6::PDGFRB rearrangement, we recommend the introduction of testing for this abnormality in myeloid malignancies with eosinophilia.

Primary central nervous system anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is an extremely rare type of primary central nervous system lymphoma (PCNSL). There are only nine cases reported in the literature to date, most of which have an overall survival time of no more than 8 months. Herein, we report such a rare case who has a good outcome with the longest survival time and perform a review of the literature. A 19-year-old male patient was admitted to the hospital complaining of dizziness. CT and MRI imaging showed a heterogeneous enhanced lesion in the left parieto-occipital lobe and the leptomeninges of the occipital lobe and the cerebellum. The lesion was resected and confirmed to be ALK-negative ALCL by pathological examination. Then, the patient received 10 cycles of chemotherapy with high-dose methotrexate (HD-MTX) and whole-brain radiotherapy. The patient recovered well and was regularly followed up. He was free of symptoms without recurrence on imaging examination 3 years later. ALCL is a rare type of PCNSL. HD-MTX combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify the biological characteristics of this rare type of PCNSL.

Background: There is a need for an appropriate instrument to measure the satisfaction of patients about therapeutic textile devices used for breast cancer-related lymphedema (BCRL). Methods and Res...

Lymphedema is a chronic disease with a high incidence in our society. In this paper, we present a review with the latest advances in imaging techniques and surgical reconstructive treatment of lymphedema (lymphovenous anastomosis, vascularized lymph node transfer, and prophylactic lymphedema surgery). In addition, a protocol is established based on a multidisciplinary team (composed of physiatrists, plastic surgeons, radiologists and nuclear medicine radiologists) to optimize the treatment of these patients.

Introduction: Treatment for patients with comorbid lymphedema and varicose veins is controversial. Surgical options for these patients are limited. The study was aimed to investigate the validity o...

Kidney injury caused by transplant-associated thrombotic microangiopathy (TA-TMA) in patients who underwent allogeneic hematopoietic stem cell transplantation (allo HSCT) is relatively frequent. However, it is rarely reported in patients undergoing autologous HSCT (aHSCT). There are a few studies reported that TA-TMA could occur in pediatric patients undergoing aHSCT, but the condition in adult patients is rarely described. Furthermore, almost all the patients who suffered from TA-TMA developed typical and severe manifestations which should be treated with aggressive target therapy. Nevertheless, we presented two cases of kidney injury caused by TA-TMA after aHSCT with specific clinical features. Case 1, a 33-year-old Chinese male diagnosed with Hodgkin's lymphoma developed TA-TMA -associated kidney injury 4 months after transplantation. Case 2, a 49-year-old Chinese female with central nervous lymphoma developed TA-TMA-related kidney injury 3 months after transplantation. Both patients presented "mild" and atypical features of TA-TMA and their kidney function was managed effectively with low-dose prednisone therapy. TA-TMA related kidney injury can occur in patients who underwent aHSCT. Patients with TA-TMA could develop atypically "mild" features. Low-dose prednisone may be effective in place of routine eculizumab treatment regimen. We recommend that clinicians prompt an investigation for TA-TMA in patients presenting kidney injury in the background of aHSCT to facilitate early diagnosis.

Classification of myeloid neoplasms with isolated isochromosome i(17q) [17p deletion with inherent monoallelic TP53 loss plus 17q duplication] is controversial. Most cases fall within the WHO unclassifiable myelodysplastic/myeloproliferative neoplasms (MDS/MPN-U) category. The uniformly dismal outcomes warrant better understanding of this entity. We undertook a multi-institutional retrospective study of 92 adult MDS/MPN-U cases from eight institutions. Twenty-nine (32%) patients had isolated i(17q) [MDS/MPN-i(17q)]. Compared to MDS/MPN without i(17q), MDS/MPN-i(17q) patients were significantly younger, had lower platelet and absolute neutrophil counts, and higher frequency of splenomegaly and circulating blasts. MDS/MPN-i(17q) cases showed frequent bilobed neutrophils (75% vs. 23%; P = 0.03), hypolobated megakaryocytes (62% vs. 20%; P = 0.06), and a higher frequency of SETBP1 (69% vs. 5%; P = 0.002) and SRSF2 (63% vs. 5%; P = 0.006) mutations that were frequently co-existent (44% vs. 0%; P = 0.01). TP53 mutations were rare. The mutation profile of MDS/MPN-U-i(17q) was similar to other myeloid neoplasms with i(17q) including atypical chronic myeloid leukemia, chronic myelomonocytic leukemia, myelodysplastic/myeloproliferative neoplasm with ring sideroblasts and thrombocytosis, myelodysplastic syndrome and acute myeloid leukemia, with frequent concomitant SETBP1/SRSF2 mutations observed across all the diagnostic entities. Over a median follow-up of 52 months, patients with MDS/MPN-i(17q) showed a shorter median overall survival (11 vs. 28 months; P < 0.001). The presence of i(17q) retained independent poor prognostic value in multivariable Cox-regression analysis [HR 3.686 (1.17-11.6); P = 0.026] along with splenomegaly. We suggest that MDS/MPN-i(17q) warrants recognition as a distinct subtype within the MDS/MPN-U category based on its unique clinico-biologic features and uniformly poor prognosis.

Nipple discharge is a common complaint among adult women and is often evaluated by galactography. Contrast-enhanced mammography (CEM) is an emerging breast imaging modality that is useful in the evaluation of patients with nipple discharge who have a negative galactogram, especially if they are not good candidates for contrast-enhanced MRI. Here we present a case of a 37-year-old female who was 22 weeks pregnant and presented with suspicious nipple discharge. The patient initially underwent galactography, which was negative, and was subsequently referred for CEM for further evaluation. One week after the galactogram, the patient underwent CEM which revealed persistent intraductal iodinated contrast from the galactogram. The retained intraductal contrast obscured the area of concern on the CEM and limited evaluation for underlying areas of enhancement. Given the increasing popularity of CEM in breast imaging practice and its utility in the evaluation of patients with nipple discharge, recognition of retained intraductal contrast as a source of artifact on CEM is important so that steps can be taken to prevent acquiring a limited and/or non–diagnostic CEM. We suggest several practical steps the radiologist can take when planning the diagnostic workup of patients with nipple discharge to ensure the patient will be able to successfully undergo CEM, if needed. These steps will help reduce unnecessary patient exposure to radiation and intravenous contrast and avoid a delay in diagnosis and treatment.

Background: Acute myeloid leukemia (AML) is a hematological neoplasm that affects adults of all ages and accounts for 1-2% of malignancies worldwide. T- cell function is significantly impaired in AML patients. Increasing evidence states that a recently identified subtype of CD4 + T cells called T helper 17(Th17) is associated with the pathogenesis of AML. Aim: This study aims to estimate the concentration of Th 17 related cytokines IL-23 and IL-17 in the plasma samples diagnosed with AML and to assess their clinical value in the prognosis of AML. Methods: This study includes 31 patients who were newly diagnosed with AML. Similarly, 21 healthy subjects were selected for normal control group. After two courses of induction chemotherapy 22 patients achieved complete remission (CR), whereas 9 patients failed to achieve CR. IL-23 and IL-17 plasma levels were measured using ELISA kits. Results: The IL-23 and IL-17 plasma levels in the newly diagnosed group were significantly higher than the CR and control group. Similarly, after two courses of standard chemotherapy, the IL-23 and IL-17 expression levels in the non-remission (NR) group were also much higher than in the CR and control group. No significant differences in the expression of IL-23 and IL-17 between CR and control groups were found. In AML patients, a significant positive correlation was found between IL-23 and IL-17. Conclusion: The IL-23 and IL-17 plasma levels correlate with the progression of AML, which may express clinical significance in the prognosis and therapeutic evaluation of AML.

Non-Hodgkin’s lymphoma of breast is a rare condition. NHL breast constitute about 0.5% of all malignancies of breast. NHL breast constitute nearly 1% of all cases of NHL. Among all subtypes of NHL, DLBCL (Diffuse large B-cell Lymphoma) is the most common type to be known. Marginal zone lymphoma (10-30%), follicular lymphoma (10-20%) and Burkit Lymphoma (5%) are other common histologic variants. Burkitt lymphoma is mainly seen in pregnant females or lactating females. Breast implant associated anapaestic large cell lymphoma (BIA-ALCL) constitutes remaining case. Thus, primary NHL of Breast is rare condition. DLBCL is most common histologic variant. We report here a rare case of primary NHL Breast. A 30 years old lactating mother came with history of swelling and nipple discharge from bilateral breast. -Treatment approach for low grade NHL breast is Radiotherapy only and for high grade NHL breast there is a role for combined modality approach that is chemotherapy followed by Radiotherapy with or without surgical intervention.

Background: Leukaemias are neoplastic proliferations of haematopoietic stem cells and form a major proportion of haematopoietic neoplasms that are diagnosed worldwide. Objective: To differentiate between morphological and immunophenotypic analysis in the diagnosis of acute leukemia. Materials and method: This cross sectional study was conducted in the department of Haematology, Armed Forces Institute of Pathology (AFIP), Dhaka, Bangladesh from January 2008 to December 2008. Total 50 patients were included after fulfilling inclusion and exclusion criteria. Results: The total of 50 bone marrow samples from suspected cases of acute leukaemia were included in the study. Out of 50 samples, 48 cases were diagnosed as either acute myeloid leukaemia (19 or 38%) or acute lymphoblastic leukaemia (29 or 58%) and 02 (04%) cases were morphologically indistinguishable. All 50 cases were subjected to immunophenotypic study. Out of 50 cases immunophenotypically 14(28%) were acute myeloid leukaemia (AML), 32(64%) were acute lymphoblastic leukaemia (ALL), and bi-phenotypic leukaemia and acute undifferentiated leukaemia were 02(04%) each. In this study Male: Female ratio was 1.3:1. Out of 19(38%) cases of AML, 29(58%) cases of ALL and 02(04%) cases of indistinguishable diagnosed morphologically, 14(28%) were found to be AML, 32(64%) ALL, 02(04%) bi-phenotypic and 02(04%) were acute undifferentiated leukaemias on immunophenotyping respectively. Out of 29 cases identified as ALL on morphology 25(86.2%) were confirmed as ALL, 02(07%) turned out to be AML, 01(3.4%) was bi-phenotypic and 01(3.4%) was undifferentiated. Conclusion: In this study, acute lymphoblastic leukaemia was the commonest type of leukemia followed by acute myeloid leukaemia with male predominance seen in all types of leukaemia. Delta Med Col J. Jul 2020 8(1): 15-20

Lymphomas account for approximately 5% of nonurothelial tumors of the urinary tract and develop in the bladder in 90% of cases. The most common lymphomas histologic type of this location is extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma). MALT lymphoma of the upper urinary tract is casuistically rare. The current study describes a case of a 74-year-old female patient with MALT lymphoma of the renal pelvis with metastases to the retroperitoneal lymph nodes who underwent radical surgical treatment with subsequent follow-up.

Background: Morphological diagnosis of leukemias may sometimes not correlate with flow cytometry diagnosis. Classification of hematological neoplasm by the World Health Organization gives priority to cytogenetic, molecular biology, and even patient history, in an attempt to classify patients primarily regarding prognosis. Cytomorphology and immunophenotyping complement each other. Morphology is burdened by a high degree of subjectivity. That is why correlation of information provided by the two techniques is still absolutely necessary. The aim of our study was to correlate between cytomorphological findings and immunophenotyping results on a group of patients investigated for acute leukemia. Materials and Methods: Study was conducted in department of pathology in Chirayu Medical College and Hospital, Bhopal from December 2018 to September 2019. Cases were diagnosed as acute leukemia based on complete blood count and bone marrow aspirate/peripheral smear.These cases were sent to flowcytometry for immunophenotyping for further confirmation. Results: Total 74 cases of acute leukemias were diagnosed, out of which 30 were Acute myeloid leukemia and 44 were Acute lymphoblastic leukemia. There was 95.95% correlation between diagnosis on cytomorphology and flowcytometry. Two cases remain unclassified on cytomorphology which turn out to be Acute myeloid leukemia on flowcytometry. One case of Acute myeloid leukemia on cytomorphology was diagnosed as Acute lymphoblastic leukemia on flowcytometry. Conclusions: Inclusion of flowcytometry in routine diagnostic workup of acute leukemia ensures proper characterization as well as management. Major challenges for the near future are the standardization of technical procedures, data interpretation, and reporting.

Anti-CD20 antibodies such as rituximab are broadly used to treat B-cell malignancies. These antibodies can induce various effector functions, including immune cell-mediated antibody-dependent cellular cytotoxicity (ADCC). Neutrophils can induce ADCC toward solid cancer cells by trogoptosis, a cytotoxic mechanism known to be dependent on trogocytosis. However, neutrophils seem to be incapable of killing rituximab-opsonized B-cell lymphoma cells. Nevertheless, neutrophils do trogocytose rituximab-opsonized B-cell lymphoma cells, but this only reduces CD20 surface expression and is thought to render tumor cells therapeutically resistant to further rituximab-dependent destruction. Here, we demonstrate that resistance of B-cell lymphoma cells toward neutrophil killing can be overcome by a combination of CD47-SIRPα checkpoint blockade and sodium stibogluconate (SSG), an anti-leishmaniasis drug and documented inhibitor of the tyrosine phosphatase SHP-1. SSG enhanced neutrophil-mediated ADCC of solid tumor cells but enabled trogoptotic killing of B-cell lymphoma cells by turning trogocytosis from a mechanism that contributes to resistance into a cytotoxic anti-cancer mechanism. Tumor cell killing in the presence of SSG required both antibody opsonization of the target cells and disruption of CD47-SIRPα interactions. These results provide a more detailed understanding of the role of neutrophil trogocytosis in antibody-mediated destruction of B cells and clues on how to further optimize antibody therapy of B-cell malignancies.

The phase 3 Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation (ADMIRAL) trial demonstrated the superiority of the FLT3 inhibitor, gilteritinib, to salvage chemotherapy (SC) in patients with FLT3-mutated relapsed or refractory (R/R) AML. Baseline comutations, FLT3-internal tandem duplication (ITD) allelic ratio and length, and treatment-emergent mutations were analyzed in patients in the ADMIRAL trial. Baseline comutations were grouped according to gene subgroups (DNA methylation/hydroxymethylation, transcription, chromatin–spliceosome, receptor tyrosine kinase-Ras signaling, TP53-aneuploidy, NPM1, DNMT3A, DNMT3A/NPM1, WT-1, and IDH1/IDH2). Across all but 1 gene subgroup (TP53-aneuploidy), higher pretransplant response rates and a trend toward longer overall survival were observed with gilteritinib vs SC. Patients with DNMT3A/NPM1 comutations who received gilteritinib had the most favorable outcomes of any molecular subgroup analyzed. Survival outcomes with gilteritinib were not adversely affected by FLT3-ITD allelic ratio, FLT3-ITD length, or multiple FLT3-ITD mutations. Among patients who relapsed on gilteritinib, Ras/mitogen-activated protein kinase (MAPK) pathway and FLT3 F691L gene mutations were the most common mutational events associated with treatment resistance. However, the occurrence of Ras/MAPK pathway gene mutations at baseline did not preclude a clinical benefit from gilteritinib. Acquisition of multiple Ras/MAPK pathway gene mutations at relapse suggests a high level of pathway reactivation is needed to overcome the gilteritinib treatment effect. These findings provide insight into the R/R AML molecular profile and the impact of FLT3 inhibitors on mutational evolution associated with treatment resistance and benefit of gilteritinib across a wide spectrum of molecular and genetic subgroups in FLT3-mutated R/R AML. This trial was registered at www.clinicaltrials.gov as #NCT02421939.

Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of the contact pathway in response to pathogen-associated or host-derived, damage-associated molecular patterns. The process is further amplified through inflammatory and immunothrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients is associated with worsening morbidities and increased mortality, regardless of the underlying pathology; therefore, timely recognition of DIC is critical for reducing the pathologic burden. Due to the diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia, and fibrinogen conversion. Because current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of nonovert DIC and/or pre-DIC states. Therapeutic strategies for patients with DIC involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in patients with DIC remains high, and new strategies, tailored to the underlying pathologic mechanisms, are needed.

INTRODUCTION: Preeclampsia (PE) is a multisystem pathological condition occurring after 20 weeks of pregnancy. According to some scientists, the pathogenetic mechanisms of PE are based on the abnormal response of the mothers immune system to factors of placental origin. AIM: To assess the parameters characterizing the condition of B-cells in female patients with PE and to develop the prognostic criterion for the effective treatment of moderate PE. MATERIALS AND METHODS: A total of 121 women at 2436 weeks of gestation were examined. The main group included 69 pregnant women with PE in which 36 had moderate PE (group 1a, 18 women with positive effects of PE treatment; group 1b, 18 women with no effect of PE treatment) and 33 had severe PE. The control group included 52 patients with no hypertensive disorders. In the peripheral blood, the relative content of CD19+ and CD20+ В-lymphocytes and their subpopulations, namely, regulatory B-cells (CD20+IL-10+), memory B-cells (CD19+CD27+IgD), and plasmocytes (СD19+СD20-СD38+), were evaluated by flow cytofluorometry. Statistical analysis was performed using Statistica for Windows 6.0, Microsoft Excel 2010, and MedCalс programs. The diagnostic significance of the studied parameters was evaluated by ROC analysis. RESULTS: The comparison of all the studied parameters of the content of B-lymphocytes and its subpopulations did not reveal any significant differences in patients with PE of different severities (p 0.05 in all cases). In the comparative analysis of women with moderate PE exhibiting either positive or no treatment effects, a low level of CD20+В-lymphocytes and a high level of CD19+CD20-CD38+ plasmocytes were noted in the former. In addition, the presence of 2.8% of CD19+CD20-CD38+ cells in the peripheral blood predicts a positive treatment effect on moderate PE, while 2.8% predicts an ineffective treatment and aggravation of the PE. CONCLUSION: The reduction of plasmocytes and absence of treatment effect on moderate PE may be associated with the migration of plasmocytes to the target organs, which leads to the worsening of the immunopathological process during the course of PE. The content of CD19+CD20-CD38+ cells in the peripheral blood can be used to predict treatment efficacy on moderate PE.