A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience

IntroductionMixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the “know-how” of MPAL is based only on retrospective analyses performed on small groups of patients.Materials and methodsIn this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed.ResultsSixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16–24) and 17 days (range, 12–24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes.ConclusionsCLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control

Plerixafor for patients who fail cytokine-or chemotherapy-based stem cell mobilization: Results of a prospective study by the Polish Lymphoma Research Group (PLRG)

Autologous hematopoietic stem cell transplantation (autoHSCT) requires collection of sufficient number of hematopoietic stem cells. The goal of this study was to evaluate efficacy of plerixafor used in patients with lymphoid malignancies failing conventional stem cell mobilization.This was a prospective, non-interventional study. All consecutive patients (n = 109) treated with plerixafor in 11 centers were reported. The drug was used either in case of previous mobilization failure (n = 67) or interventionally, in case of insufficient CD34 cell output during current mobilization (n = 42). Successful mobilization was defined as resulting in collection of ≥ 2 × 10 CD34 cells/kg for single autoHSCT or ≥ 4 × 10 CD34 cells/kg for double procedure.The overall rate of successful mobilization was 55% (55% for single and 56% for double autoHSCT). The median total number of collected CD34 cells/kg was 2.4 (range, 0-11.5) for patients intended for a single transplantation while 4.0 (0.6-16.9) for double procedure. The number of circulating CD34 cells increased after the use of plerixafor regardless of baseline values. The median fold increase was 3.3 (0.3-155). Data from this observational study confirm high efficacy of plerixafor used in routine clinical practice as salvage for patients with lymphoid malignancies failing conventional stem cell mobilization

Neuroimaging of Basal Ganglia in Neurometabolic Diseases in Children

Diseases primarily affecting the basal ganglia in children result in characteristic disturbances of movement and muscle tone. Both experimental and clinical evidence indicates that the basal ganglia also play a role in higher mental states. The basal ganglia can be affected by neurometabolic, degenerative diseases or other conditions from which they must be differentiated. Neuroradiological findings in basal ganglia diseases are also known. However, they may be similar in different diseases. Their assessment in children may require repeated MRI examinations depending on the stage of brain development (mainly the level of myelination). A large spectrum of pathological changes in the basal ganglia in many diseases is caused by their vulnerability to metabolic abnormalities and chemical or ischemic trauma. The diagnosis is usually established by correlation of clinical and radiological findings. Neuroimaging of basal ganglia in neurometabolic diseases is helpful in early diagnosis and monitoring of changes for optimal therapy. This review focuses on neuroimaging of basal ganglia and its role in the differential diagnosis of inborn errors of metabolism

From the Difficult Airway Management to Diagnosis of Retropharyngeal Synovial Cell Carcinoma

Respiratory complications are among the most common problems addressed in neonatology in the first hours after birth, whereas the risk of any cancer in the neonatal period is 28 per million. Sarcomas, malignant mesenchymal neoplasms, account for about 8% of all neoplasms in the neonatal period. We report on a male neonate born at 36 + 4/7 weeks of gestation, diagnosed with retropharyngeal synovial carcinoma. Ineffective respiratory movements and generalized cyanosis were the first symptoms to be noted. On the ultrasound examination of the neck, a tumor of the retropharyngeal space was exposed, then visualized by an MRI of the head and neck. The biopsy analysis revealed the diagnosis of an extremely rare tumor in a neonate. The location of its growth was atypical, contributing to a diagnostic challenge. The neoplasm was treated solely with chemotherapy concordantly with the CWS protocol, individually customized for our patient. Preterm birth, as in our case, 36 + 4/7 weeks of gestation, may imply a possible need for resuscitation or support in the transition period. Aggressive high-grade tumors of the head and neck region are locally invasive and prone to metastasize. However, prognosis in infants is hard to estimate, therefore both individualized treatment and multidisciplinary care should be tailored to the needs of the patient

Mucopolysaccharidosis Type 1 among Children—Neuroradiological Perspective Based on Single Centre Experience and Literature Review

Mucopolysaccharidosis 1 (MPS 1) is a group of rare lysosomal genetic disorders resulting from the accumulation of undegraded glycosaminoglycans (GAGs) leading to multiorgan damage. Neurological symptoms vary from mild to severe. Neuroimaging—mainly magnetic resonance (MRI)—plays a crucial role in disease diagnosis and monitoring. Early diagnosis is of the utmost importance due to the necessity of an early therapy implementation. New imaging tools like MR spectroscopy (MRS), semiquantitative MRI analysis and applying scoring systems help substantially in MPS 1 surveillance. The presented analysis of neuroimaging manifestations is based on 5 children with MPS 1 and a literature review. The vigilance of the radiologist based on knowledge of neuroradiological patterns is highlighted

Anaphylactic reaction in patient allergic to shrimp

Introduction. The prevalence of shellfish allergy depends on the climate zone and the population. It is assumed that about 0.5-2.5% of the general population is allergic to shrimps. The best-characterized allergens are tropomyosin, arginine kinase, sarcoplasmic calcium-binding protein and hemocyanin. Case report. The patient, 28 year old male, was admitted in July 2017 to the Department of Allergology to diagnose the cause of anaphylactic reaction which occurred 3 months prior to the hospitalization after consumption of king prawns. Immediately after the meal the patient developed pruritus and generalized urticaria as well as swelling of the hands and face. Next the patient developed vast urticaria on limbs and trunk, followed by tachycardia and hypotension. During the diagnosis, the patient underwentskin prick tests with extracts of food and inhalant allergens, including standardized shrimp allergen extract - with a positive result for D. pteronyssinus and D. farinae, grass, weeds, cat dander, hazel, birch and alder, but negative for all food allergens tested, including shrimp. The prick by prick tests performed with fresh royal shrimp (both raw and cooked) yielded strongly positive results. The concentration of IgE specific to shrimp allergen was elevated - 5.25 kU/l, while the concentration of IgE of shrimp tropomiosin was negative (ImmunoCap). In addition, elevated concentrations of IgE specific for D. pteronyssinus were found 9.86 kU/l, D. farinae 7.90 kU/l, grass 19.09 kU/l, cat's dander 2.94 kU/l. We also established the level of IgE specific to allergen components using the ImmunoCap ISAC method. Allergen-specific IgE was not elevated to any shrimp allergens available in ImmunoCap ISAC: n Pen m1 (tropomyosin), n Pen m2 (arginine kinase) and n Pen m4 (calcium binding sarcoplasmic protein). Conclusions. On the basis of conducted examinations the patient was diagnosed with a shrimp allergy. The applied molecular diagnostics did not explain which allergen component the patient is allergic to. It is possible that the patient is allergic to hemocyanin, which can also cross-react with house dust mite allergens, but confirmation of this diagnosis requires further investigation.Wprowadzenie. Rozpowszechnienie alergii na skorupiaki zależy od strefy klimatycznej i populacji. Przyjmuje się, że około 0,5-2,5% populacji ogólnej jest uczulona na krewetki. Najlepiej scharakteryzowane alergeny to tropomiozyna, kinaza argininowa, białko sarkoplazmatyczne wiążące wapń oraz hemocyjanina. Opis przypadku. Chory, lat 28, został przyjęty w lipcu 2017 roku do Kliniki Alergologii celem diagnostyki ostrej reakcji anafilaktycznej, która wystąpiła po raz pierwszy w życiu, po spożyciu krewetek królewskich. Po spożyciu krewetek u chorego wystąpił świąd i zaczerwienienie skóry całego ciała, a także obrzęk dłoni i twarzy. Następnie na kończynach i tułowiu wystąpiły rozległe zmiany skórne o charakterze pokrzywki, po czym spadek ciśnienia tętniczego i tachykardia. W trakcie diagnostyki u chorego wykonano testy skórne punktowe z wyciągami alergenów wziewnych i pokarmowych w tym ze standaryzowanym wyciągiem alergenowym krewetki - wynik dodatni w przypadku D. pteronyssinus i D. farinae, traw, chwastów, sierści kota, leszczyny, brzozy i olchy natomiast ujemny w przypadku wszystkich badanych alergenów pokarmowych, w tym krewetki. Wykonano testy natywne punktowo-punktowe ze świeżą krewetką królewską - surową oraz gotowaną uzyskując wyniki wybitnie dodatnie. Stężenie IgE swoistego z wyciągiem alergenowym krewetki było podwyższone - 5,25 kU/l natomiast stężenie IgE swoistego dla tropomiozyny krewetki (ImmunoCap) było ujemne. Ponadto stwierdzono podwyż- szone stężenie IgE swoistych dla D. pteronyssinus 9,86 kU/l, D. farinae 7,90 kU/l, mieszanki traw 19,09 kU/l, naskórka kota 2,94 kU/l. Diagnostykę poszerzono o badanie poziomów IgE swoistych dla komponent alergenowych metodą ImmunoCap ISAC - w którym nie wykazano obecności alergenowo swoistych przeciwciał IgE (asIgE) dla obecnych w nim gatunkowo swoistych alergenów krewetki: n Pen m1 (tropomiozyna), n Pen m2 (kinaza argininowa) oraz n Pen m4 (białko sarkoplazmatyczne wiążące wapń). Wnioski. Na podstawie przeprowadzonych badań u chorego rozpoznano alergię na krewetkę. Zastosowana diagnostyka molekularna nie wyja- śniła na którą komponentę alergenową pacjent jest uczulony. Nie można wykluczyć, że chory jest uczulony na hemocyjaninę lub ubwikwitynę, któ- re również reaguje krzyżowo z alergenami roztoczy kurzu domowego, jednak potwierdzenie takiego rozpoznania wymaga dalszych badań

Anaphylactic reaction in patient allergic to mango

Abstract Background An allergy to mango is extremely rare. The antigenic composition of the fruit is not fully known. Profilin from mango has a structure similar to birch tree profiling: it is responsible for cross-reactions between mango and pear, apple, and peach. A panallergen with a structure similar to mugwort defensin (Art v 1) which cross-reacts with celery, carrot, peanuts, pepper, aniseed, and caraway has been previously described. Case study A female patient, 30 years old, was admitted in February 2017 because of recurrent allergic reactions following consumption of various foods. The most severe allergic reaction in the patient’s life occurred after eating a mango fruit. Within several minutes the patient developed a generalised urticaria, followed by facial oedema, strong stomach pain and watery diarrhoea. The diagnostics involved skin tests with a set of inhalatory and food allergens, including native skin tests. The patient also experienced symptoms of recurrent, generalized urticaria in connection with consumption of various types of food, especially complex dishes containing many different ingredients. Additionally, an interview revealed that the patient was experiencing symptoms of the oral allergy syndrome after ingesting various fruit and vegetables, especially during late summer and fall. Diagnostics was extended by determining the levels of IgE specific for allergen components, using the ImmunoCap ISAC method. In order to confirm the occurence of a cross-reaction between mugwort and mango allergens, we performed the inhibition test of IgE specific for mugwort using a mango allergen extract and ImmunoCap matrix. Results Skin prick tests (SPT) were positive for allergens of grass 7 mm; weeds 8 mm; cat’s fur 5 mm; mugwort 6 mm. SPT were also positive for mango. The level of specific IgE was increased for allergens of mugwort, grass, celery, pepper, carrot, mango, banana, peach, and apple. The ImmunoCap ISAC test demonstrated a high level of specific IgE rPhl p 1 (timothy grass) and Art v 1 (mugwort). We also performed the IgE inhibition test using both mango extract and ImmunoCap matrix and confirmed a cross-reaction with Art v 1 in the pathogenesis of symptoms observed in the patient. Conclusions An anaphylactic reaction to consumed mango, resulting from cross-allergy with mugwort Art v 1 was diagnosed in the patient. Acute urticarial in this case is a manifestation of IgE-mediated food allergy. During in vitro diagnostic procedures we found an elevated concentration of IgE specific to several food allergens (including celery, peppers, carrot, banana, peach, apple, shrimp). The elimination diet removing allergens the patient was allergic to was recommended. Considering the anaphylactic reaction the patient was instructed to carry a rescue set composed of an adrenaline autosyringe, steroids, and antihistamines

PPARγ—A Factor Linking Metabolically Unhealthy Obesity with Placental Pathologies

Obesity is a known factor in the development of preeclampsia. This paper links adipose tissue pathologies with aberrant placental development and the resulting preeclampsia. PPARγ, a transcription factor from the ligand-activated nuclear hormone receptor family, appears to be one common aspect of both pathologies. It is the master regulator of adipogenesis in humans. At the same time, its aberrantly low activity has been observed in placental pathologies. Overweight and obesity are very serious health problems worldwide. They have negative effects on the overall mortality rate. Very importantly, they are also conducive to diseases linked to impaired placental development, including preeclampsia. More and more people in Europe are suffering from overweight (35.2%) and obesity (16%) (EUROSTAT 2021 data), some of them young women planning pregnancy. As a result, we will be increasingly encountering obese pregnant women with a considerable risk of placental development disorders, including preeclampsia. An appreciation of the mechanisms shared by these two conditions may assist in their prevention and treatment. Clearly, it should not be forgotten that health education concerning the need for a proper diet and physical activity is of utmost importance here