Bakgrund: Akut leukemi är en form av blodcancer med ett hastigt förlopp utan tydliga riskfaktorer. Syfte: Att beskriva personers upplevelser av att leva med akut leukemi. Metod: Litteraturstudien bestod av en induktiv kvalitativ innehållsanalys med manifest ansats. Litteratursökningen genomfördes i referensdatabaserna CINAHL, PsychInfo och PubMed där 14 vetenskapliga artiklar erhölls och analyserades. Resultat: Analysen resulterade i 5 slutkategorier som beskriver människors upplevelser av att leva med akut leukemi. Insjuknandet sker plötsligt och upplevs som chockerande av personer med akut leukemi. Det medför också en stor osäkerhet för personerna. Personer med akut leukemi upplever också att de måste kämpa för att få både information och kontroll i samband med deras behandling. Personerna får även biverkningar efter behandlingen som begränsar dem i deras vardagsliv. I samband med akut leukemi upplever personer att deras identitet är under förändring samt att de måste börja prioritera det som är viktigt för dem i deras liv. Slutsats: Personer med akut leukemi har varierande behov av stöd för att bland annat orka uthärda det chockerande sjukdomsförloppet samt att få den information just de är i behov av. Detta kräver att sjuksköterskan kan inta ett personcentrerat förhållningssätt för att möta personen och dennes behov.

Le myélome multiple (MM) est le second cancer hématologique le plus répandu après les lymphomes. Malgré une amélioration de sa prise en charge au cours des 20 dernières années, les traitements actuels ne permettent pas d’éviter les rechutes répétitives associées au développement de mécanismes de résistance. Les résistances aux traitements sont notamment expliquées par la forte hétérogénéité de la maladie qui rend nécessaire le développement de prises en charges adaptées aux profils moléculaires des patients. L’avènement des technologies de séquençage haut-débit permet d’accéder à des niveaux de plus en plus détaillés de l’hétérogénéité moléculaire tumorale, ce qui permettra de proposer des solutions plus performantes dans l’optique de développer une médecine personnalisée. Dans cet objectif, nous avons analysé l’exome, le transcriptome et l’épigénome de cellules primaires de patients et de lignées cellulaires de MM. Sur la base de ces analyses, nous avons non seulement mis en évidence de nouveaux mécanismes impliqués dans la physiopathologie du MM mais également de nouvelles cibles thérapeutiques potentielles, des biomarqueurs pronostiques ainsi que des signatures d’orientation thérapeutiques. Les données et résultats de nos études constituent une ressource d’intérêt pour la communauté scientifique et permettront d’améliorer la prise en charge thérapeutique des patients atteints de MM. / Multiple myeloma (MM) is the second most common hematological malignancy after lymphoma. Recent advances in treatment have led to an overall survival of intensively-treated patients of 6-7 years. However, patients invariably relapse after multiple lines of treatment, with shortened intervals between relapses, and finally become resistant to all treatments, resulting in loss of clinical control over the disease in association with drug resistance. Treatment improvements will come from a better comprehension of tumorigenesis and detailed molecular analyses to develop individualized therapies taking into account the molecular heterogeneity and subclonal evolution. In this purpose, we analyzed the exome, transcriptome and epigenome of primary MM cells from patients and human MM cell lines. Our results have highlighted new mechanisms involved in the pathophysiology of MM as well as potential new therapeutic targets, prognostic signatures and theranostic biomarkers. The data and results of our studies represent an important resource to understand the mechanisms of tumor progression and drug resistance and develop new ways to diagnose and treat patients.

La drépanocytose ou anémie falciforme est la maladie génétique la plus répandue dans le monde. Elle affecte plus particulièrement les populations des régions africaines sub-sahariennes, du sous-continent Indien et celles issues de ces populations. La Guadeloupe, archipel des Antilles françaises est une zone à forte prévalence drépanocytaire. La drépanocytose se caractérise par des anomalies de l’hémoglobine et du globule rouge qui mènent à des complications aigues et chroniques pouvant toucher tous les organes, dont les yeux. Récemment, plusieurs auteurs ont rapporté une prévalence importante de la maculopathie dans la drépanocytose mais la physiopathologie reste très mal comprise. Ainsi, nous avons réalisé deux études. La première, consistait à étudier la prévalence de la rétinopathie et de la maculopathie drépanocytaires et de tester l’association entre ces deux complications. De plus, nous avons recherché un éventuel lien avec différentes anomalies biologiques. Nous avons montré que la rétinopathie et la maculopathie étaient deux complications fréquentes mais indépendantes dans la drépanocytose. Les résultats de cette première étude ne supportent pas un lien éventuel entre les anomalies hématologiques, hémorhéocarlogiques ou le génotype et ces deux complications. Dans une deuxième étude nous avons essayé de mieux caractériser la maculopathie drépanocytaire en réalisant un électrorétinogramme multifocal (mfERG) et une tomographie en cohérence optique spectral domain (SD-OCT) chez des patients SS et SC sans signe clinique de maculopathie. Nous avons pu mettre en évidence des altérations maculaires électrophysiologiques chez les patients drépanocytaires paraissant exempt de toute maculopathie à l’examen clinique. Par ailleurs, nous avons retrouvé que la maculopathie drépanocytaire est aussi fréquente chez les SS que chez les SC.Notre travail confirme le caractère fréquent des complications rétiniennes drépanocytaires. Cependant, elles apparaissent comme complètement indépendantes l’une de l’autre et les mécanismes physiopathologiques sous-jacents restent mal compris / Sickle cell disease (SCD) also known as sickle cell anemia is the most common genetic affection in the world. Most of SCD cases occur in sub-Saharan Africa, india and among people of African and indian descent living in other parts of the world. SCD is common in Guadeloupe, French West indies. It results in an abnormal hemoglobin leading to rigid sickle like shape red blood cells responsible for a great number of acute and chronical systemic complications including ophthalmic affections. Recently, a wild prevalence of maculopathy has been reported by several authors but its pathophysiology remains unclear.We performed two studies. The aim of the first one was to investigate the prevalence of SCD retinopathy and maculopathy and to test the association between these two conditions. Moreover, we looked for a possible link with biological abnormalities. Our study confirmed that SCD maculopathy and retinopathy are common but they remain two independent affections. Nevertheless, we found no association with hematological parameters, blood rheology of genetic.In the second study, we described and compared spectral domain ocular coherence tomography (SD-OCT) and multifocal electroretinogram (mfERG) findings in patients with SCD without clinical sign of maculopathy, according to the hemoglobin genotype. We found electrophysiological macular dysfunction in SCD patients with no clinical maculopathy. Furthermore, maculopathy was as frequent in SCA than in SCC patients.Our work confirms that retinal affections are common in SCD. Nevertheless, retinopathy and maculopathy seem to be two independent complications and their pathophysiology remains misunderstood.

No description available.

Diamond-Blackfan anemia (DBA) is a rare congenital syndrome that presents with ane- mia and selective deficiency of erythroid precursors, while other blood lineages are usu- ally unaffected. Approximately half of the patients display additional somatic anoma- lies and growth retardation. The therapy is mostly symptomatic and is dominated by corticosteroids, other modalities include regular blood transfusions or hematopoietic stem cell transplantation. At the beginning of this work, only two DBA causal genes were known, RPS19 and RPS24, being mutated in approximately 1/4 of all DBA patients. The goals of this work were to study the consequences of the known DBA causal mutations on cellular level and to find novel DBA causal genes. To date, over a half of DBA patients have been reported to carry a mutation in one of nine known DBA causal genes, including RPS17, RPL11 and RPL5, that are reported in this dissertation. All confirmed DBA causal genes encode for ribosomal proteins (RPs) that were essential for ribosome assembly. We further hypothesized a non- ribosomal protein participating in this process might be involved in DBA pathogenesis, too. In one DBA patient, we identified a rare sequence variant in one such candidate, a protein arginine methyltransferase 3 (PRMT3). We reported that the patient PRMT3...

Congenital and infant acute leukemia remain one of the most puzzling clinical issues in pediatric hematology-oncology. There is a paucity of studies focused on these rare, aggressive, acute leukemias; specifically, there is little study on the differences in disease in the youngest of infants less than 1 year of age unlike the numerous studies of the disease in older children. The United States National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) cancer population registry program has been integral for a plethora of clinical population and pathology research studies for numerous diseases in the last 40 years and has an excellent resource for investigation of the infant population. Laboratory medicine and pathology professionals must use pathology results not only to diagnose individuals after the disease has been discovered, but the information must be applied retrospectively to develop new testing strategies. By classifying the intense heterogeneity within these cancers, the distinct changes of the diseases within individuals can be established, ultimately reshaping diagnostic methodologies. Through the application of Integrative Molecular Pathological Epidemiology to a 325-infant case series from the SEER program from 2008 to 2014, this dissertation study was used to evolve the classification of these pediatric cancers with the application of scientific nosology. This dissertation study has documented characteristics of this population for application in further precision medicine investigations to influence laboratory medicine algorithms for diagnosis and management of patients guiding health policy that are aimed at improving outcomes in the youngest of children.

Light Chain Deposition Disease (LCDD) is a type of monoclonal immunoglobulin deposition disease characterized by the non-amyloid deposition of monoclonal light chains in the tubular basement membranes and Bowman’s capsule. It was first described about 3 decades ago, but due to varied clinical presentations, many differential diagnoses and low incidence, it is both underrecognized and underreported. We present a case of 85-year-old female with past medical history significant for CKD and HTN, who presented with accelerated HTN, normocytic anemia and worsening renal function. Laboratory data showed Hgb <9.5 gm/dL, MCV 93 fL, Total protein 5.9, Albumin 3.2, Calcium 8.9, Serum Creatinine 2.37, BUN 45, Urine with hematuria (50–99 erythrocytes per high-power field) and nephrotic range proteinuria. Renal biopsy showed evidence of Membranoproliferative glomerulonephritis, with immunofluorescence features indicative of a monoclonal immunoglobulin deposition disease. Bone marrow biopsy showed mildly increased plasma cells (5-7%) confirmed to be clonal (lambda light chain) by flow cytometry, negative for Congo-Red stain. Although no underlying hematological abnormality like Multiple Myeloma or Amyloidosis was observed in this case, the renal pathological findings is consistent with proliferative glomerulonephritis with monoclonal IgG lambda deposits. There is no standard of care for the management of LCDD based on rarity of this condition. Many treatment modalities including chemotherapy and stem cell transplant have been tried. A combination of high dose melphalan or Cyclophosphamide with dexamethasone is preferred for Non-IgM type monoclonal protein kidney deposition, like in this case. Bortezomib and Thalidomide-based chemotherapy have been promising in recent research. For IgM type monoclonal protein deposition, Rituximab alone or in combination with cyclophosphamide and dexamethasone are used. This patient was not a good candidate for corticosteroid and chemotherapy or stem cell transplant due to old age (>77 years) and poor functional status, therefore, was started on hemodialysis. Following dialysis, improvement in renal function and general clinical condition was evident. The prognostic factors include age, degree of renal insufficiency at presentation affecting the renal prognosis, underlying hematologic disorder and extrarenal LC deposition. In this case, despite hemodialysis, long term survival and prognosis remain poor due to her inability to tolerate chemotherapy.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive, rare malignancy. Exact incidence is unknown due to lack of diagnostic criteria. Typically, it involves skin and bone marrow and less likely, lymph nodes and visceral organs. We present a 76 year old male who started having a lesion on the left side of his back that was progressively enlarging. He initially started on antibiotic and topical medications for more than a month which did not help. Punch biopsy of the lesion was consistent with blastic plasmacytoid dendritic cell neoplasm, positive for CD2, CD5, CD7, CD43, weak CD58,Tdt, bcl-6. Patient denies fever, chills, night sweats, weight loss, change in appetite. Physical exam revealed a purplish lesion raised in the left upper back with multiple satellite-like purple lesions throughout the back. Laboratory showed white cell count 3.2 K/uL, hemoglobin 13 g/dL, platelet 135 K/uL. Bone marrow biopsy shows immature blastic neoplasm involving 15% of the bone marrow. Cytogenetics showed normal karyotype. Flow cytometry shows an immature lymphoid population with expression of CD4, CD56, and CD 123, negative for FLT3, IDH1, IDH2, NPM1 mutations. Positron emission tomography (PET) scan showed skin thickening with minimal FDG uptake in left posterior skin soft tissue of the chest near the shoulder with no other abnormal focal uptake and splenomegaly. BPDCN is a rare aggressive malignancy that is more common in older populations. The origin is from type 2 dendritic cells. Typical presentations are skin lesions, cytopenia, lymphadenopathy, and splenomegaly. Some of the cytological features of BPDCN include cloudy sky (blue cytoplasm with clearer areas), pseudopods, and microvacuoles. Confirmation of diagnosis is with immunophenotyping. Workup after diagnosis include complete blood count, liver and renal function, hepatitis panel, peripheral blood smear, bone marrow evaluation, systemic imaging, cerebrospinal fluid cytology. Treatment of BPDCN is challenging in this era. Most patients respond to chemotherapy, although they relapse. Tegraxofusp is suggested for remission induction therapy following allogeneic hematopoietic cell transplantation. Median overall survival is about one year. Only patients who underwent hematopoietic stem cell transplant had prolonged survival. Myelemia, old age and altered general state have worse prognosis.

Sepsis, a life-threatening response to infection, represents a substantial global health concern. Each year, about 48,9 million people are affected by sepsis. While survival rates have improved, sepsis survivors often experience numerous challenges after discharge from the hospital. Therefore, the aim of this study was to describe patients’ experience of their life situation after surviving sepsis. A literature review was carried out using Friberg’s four step model for analyzing quantitative and qualitative research. The data were collected from seven quantitative and four qualitative studies. The analysis revealed two themes and eight subthemes: (1) Difficulties adjusting to new living conditions, (2) A challenging recovery process. The first theme had four subthemes: Changed quality of life after sepsis, Physical limitations in everyday life, The challenge of becoming dependent on others and The importance of social relationships. The second theme had four subthemes: A mental struggle to return to a normal life, Traumatization and fears of relapse, The importance of recovery, and Educational and informational gaps. Among sepsis survivors, various problems and challenges have been identified that impact their daily life. Numerous survivors suffered from persistent residual symptoms primarily related to physical, psychological, and cognitive domains. Survivors were widely dissatisfied with the information and education about sepsis and its aftermath provided by the healthcare system. Further research is needed to clarify the long-term consequences of sepsis survivorship, and to improve the healthcare guidelines and interventions aimed at improving the well-being of this patient group

Daratumumab är en antikropp som används vid behandling av multipelt myelom. Daratumumab är specifik för CD38, ytproteinet som uttrycks i stor mängd på myeloma plasmaceller. Vid antikroppsscreen orsakar daratumumab panreaktivitet då erytrocyter också uttrycker CD38. Dithiothreitol (DTT) behandling av testerytrocyter har visats kunna eliminera panreaktiviteten med daratumumab-antikropparna, detta genom att DTT klyver bort epitopet på CD38 som daratumumab reagerar mot utan att förstöra andra kliniskt relevanta antigen. På Södra Älvsborgs sjukhus skickas prover från daratumumab-behandlade patienter till Sahlgrenska sjukhuset för genotypning för att hitta kompatibelt blod. Förhoppningen är att den nya metoden ska möjliggöra antikroppsscreen på daratumumab-behandlade patienter vid Södra Älvsborgs sjukhus.Syftet med examensarbetet var att verifiera metoden för användning av DTT-behandlade testerytrocyter på plasma från daratumumab-behandlade patienter för att underlätta val av erytrocyter för blodtransfusion.Provmaterialet var venöst tagen patientplasma från 16 daratumumab-behandlade patienter testades mot 0,2 M DTT-behandlade- och obehandlade-testerytrocyter. DTT-behandlade testerytrocyter testades även mot kända antikroppar på plasmaprover från patienter som ej behandlats med daratumumab. Hållbarhetsstudie utfördes med behandlade BAS-testceller.Panreaktivitet sågs hos samtliga patientprover med obehandlade testerytrocyter. Vid test med DTT-behandlade testerytrocyter blev samtliga prover negativa. Behandlade testerytrocyter som testades mot kända antikroppar gav resultat som var oförändrat jämfört med originalscreen. Behandlade testceller var brukbara 25 dagar.DTT behandling av testerytrocyter är effektivt och billigt, resultatet var pålitligt då samtliga patientprover inte uppvisade panreaktivitet efter DTT-behandling av testerytrocyter. De DTT-behandlade erytrocyterna behöll kliniskt relevanta antigen efter behandling och var hållbara 25 dagar. Metoden anses som användbar för Södra Älvsborgs sjukhus. / Daratumumab is an antibody used for treatment of multiple myeloma. The antibody is specific for the surface protein CD38 which is being expressed in high quantity on myeloma plasma cells. Daratumumab is causing pan-reactivity during antibody screening due to regular erythrocytes also express CD38. Dithiothreitol (DTT) treatment of test erythrocytes has shown to eliminate the pan-reactivity caused by the daratumumab antibodies by cleaving the epitope on CD38 that daratumumab is specific to. Södra Älvsborgs hospital are currently sending patient samples from patients treated with daratumumab to Sahlgrenska hospital in Gothenburg for genotyping to find compatible blood.The purpose of the project was to verify the method for use of DTT-treated test erythrocytes on plasma from daratumumab treated patients to screen for antibodies and easier find compatible erythrocytes for blood transfusion at Södra Älvsborgs hospital.Plasma samples from 16 patients treated with daratumumab were tested with DTT-treated and untreated test erythrocytes. DTT-treated test erythrocytes were tested against samples with known antibodies from patients not treated with daratumumab. The cells durability was also tested.Pan-reactivity was shown with all daratumumab samples with non-treated test erythrocytes. Tests with DTT-treated test erythrocytes showed no pan-reactivity. Results from treated test erythrocytes tested against known antibodies were unchanged from original screening. The cells were durable for 25 days.DTT-treatment of test erythrocytes is effective and cheap, test results were reliable, all patient samples had their pan-reactivity eliminated. DTT-treated erythrocytes kept clinically significant antigens. The method is useful for clinical use at Södra Älvsborgs hospital.