The state of the art in the treatment of severe aplastic anemia: immunotherapy and hematopoietic cell transplantation in children and adults.

Acquired aplastic anemia (AA) is an immune-mediated bone marrow (BM) failure where marrow disruption is driven by a cytotoxic T-cell-mediated autoimmune attack against hematopoietic stem cells. The key diagnostic challenge in children, but also in adults, is to exclude the possible underlying congenital condition and myelodysplasia. The choice of treatment options, either allogeneic hematopoietic cell transplantation (alloHCT) or immunosuppressive therapy (IST), depends on the patient's age, comorbidities, and access to a suitable donor and effective therapeutic agents. Since 2022, horse antithymocyte globulin (hATG) has been available again in Europe and is recommended for IST as a more effective option than rabbit ATG. Therefore, an update on immunosuppressive strategies is warranted. Despite an improved response to the new immunosuppression protocols with hATG and eltrombopag, some patients are not cured or remain at risk of aplasia relapse or clonal evolution and require postponed alloHCT. The transplantation field has evolved, becoming safer and more accessible. Upfront alloHCT from unrelated donors is becoming a tempting option. With the use of posttransplant cyclophosphamide, haploidentical HCT offers promising outcomes also in AA. In this paper, we present the state of the art in the management of severe AA for pediatric and adult patients based on the available guidelines and recently published studies.

Associated Risk Factors with Low Back Pain in White-Collar Workers-A Cross-Sectional Study.

Objective: The purpose of the study was to compare the pressure pain threshold (PPT) of soft tissue and the curvatures of the spine in a sitting position and to estimate associated physical risk factors with low back pain (LBP) in young adults. Subjects: White-collar workers (n= 139), both women (n = 51) and men (n = 88) were separated into a control group (n = 82) and a low-intensity LBP (NRS < 3) (n = 57). Methods: The PPTs were tested utilizing the Wagner algometer. The curvatures of the spine were measured employing the photogrammetric method. In the logistic regression model, the odds ratio (OR) was estimated with ±95% confidence interval (CI) indicating the probability of the reported LBP. Results: The PPTs of soft tissue (OR = 1.1; CI = 1.02−1.19; p < 0.05) and the angle of the thoracolumbar spine in the everyday, habitual sitting position (OR = 1.19; CI = 1.05−1.34; p < 0.05) were associated with low-intensity LBP in female subjects. Additionally, the low intensity LBP were associated with the angles of the torso (OR = 1.14; CI = 1.01−1.29; p < 0.05) and the lumbosacral spine in the corrected sitting position (OR = 1.06; CI = 0.98−1.15; p > 0.05) and BMI (OR = 1.56; CI = 0.84−2.90; p > 0.05) in male subjects. Conclusion: Individual risk factors were associated with the low-intensity LBP only in females utilizing the PPT and the thoracolumbar angle in the habitual sitting position study factors. Men from the LBP group did not effectively correct the lumbosacral angle. Therefore, re-educated, self-corrected posture with specific postural training would be expected to improve proprioception in postural control capacity and result in decreasing pain.

Habitual and ready positions in female table tennis players and their relation to the prevalence of back pain.

BACKGROUND: The current body of knowledge shows that there is very little research into the occurrence and scale of asymmetry or postural defects in table tennis. It is interesting which regions of the spine are exposed to the greatest changes in the shape of its curvatures and whether the asymmetrical position of the shoulder and pelvic girdles in table tennis players changes when adopting the ready position. Consequently, can overload occur in certain parts of the spine and can the asymmetry deepen as a response of adopting this position? The reply to these questions may be an indication of the need for appropriate compensatory or corrective measures. Therefore, the aim of the study was to evaluate the effect of body position during play on the change in the shape of anterior-posterior spinal curvatures and trunk asymmetry in table tennis players. METHODS: To evaluate body posture the photogrammetric method based on the Moiré phenomenon with equipment by CQ electronic was applied. The study involved 22 female players practicing competitive table tennis (the age of 17 ± 4.5, with the average training experience of 7 ± 4.3 years, body mass of 47.8 ± 15.8, and body height of 161.2 ± 10.4). Each participant completed an author's own questionnaire on spinal pain. The shape of curvatures in the sagittal and frontal plane was evaluated in the participant in the habitual standing position and in the table tennis ready position. Descriptive statistical analysis was performed and the significance of differences was tested using the Mann-Whitney U test. RESULTS AND CONCLUSIONS: This study demonstrated the dominance of kyphotic body posture in table tennis players, which can be caused by many hours of using the ready position during playing. After adopting this position, there are significant differences in the angles of anterior and posterior spinal curvatures compared to the habitual posture. This may be the cause of overloads and pain complaints reported by the study participants. Adopting the ready position is also associated with an increase in asymmetry in the position (rotation) of the pelvis and spinous processes (frontal plane). Therefore, training programs should be extended with exercises that relieve the spine in the vertical line and exercises that improve symmetry of the work of the upper limbs, body trunk muscles and the pelvis.

Efficacy and Safety of Imatinib in Paediatric CML - A Single Centre Study.

BACKGROUND/AIM: Chronic myeloid leukaemia (CML) rarely affects the paediatric population and has an incidence of 0.06-0.12/100,000 children per year. The dire clinical course of paediatric CML is further exacerbated by the adverse effects of long-term imatinib therapy. PATIENTS AND METHODS: Our cohort comprised 14 CML patients who were treated with imatinib between July 2010 and September 2018. The European Leukaemia Net (ELN) standard milestones of response criteria were used to evaluate its therapeutic effectiveness. RESULTS: Complete haematological remission and partial cytogenetic response were achieved in all patients. Complete cytogenetic response was achieved in seven patients. Major molecular response was achieved in six patients. Two patients underwent haematopoietic stem cell transplantation due to unsatisfactory response to imatinib. CONCLUSION: Imatinib is effective in treating paediatric CML and limits the progression to advanced stages, however, the quality of life still needs to be optimised.

Static and dynamic plantar pressure distribution in amateur marathon runners.

BACKGROUND: The aim of the study was to compare the static and dynamic plantar pressure profiles of amateur marathon runners with sedentary cohorts. RESEARCH QUESTIONS: Are there differences in the plantar pressures of these two populations? Is there a correlation between body mass and BMI with plantar loading? METHODS: The study involved 43 runners involved in marathon training and 30 age-matched untrained individuals. Plantar pressure was measured using a baropodometric system. RESULTS: The marathon runners showed greater forefoot plantar pressure of the dominant extremity in the static condition and reduced medial plantar pressure of both extremities in the dynamic condition. A correlation was observed between body mass and BMI with mean plantar pressure only in the marathon group and only for the dominant extremity in the dynamic condition. CONCLUSIONS: Marathon training may modify the forefoot plantar loading characteristics of the dominant extremity during static conditions and increase lateral plantar pressure of both extremities in a dynamic (gait) condition.

Imatinib in the treatment of chronic myeloid leukemia in children and adolescents is effective and well tolerated: Report of the Polish Pediatric Study Group for the Treatment of Leukemias and Lymphomas.

BACKGROUND: Chronic myeloid leukemia (CML) constitutes only 2-3% of all leukemias in pediatric patients. Philapelphia chromosome and BCR-ABL fusion are genetic hallmarks of CML, and their presence is crucial for targeted molecular therapy with tyrosine kinase inhibitors (TKIs), which replaced hematopoietic stem cell transplantation (HSCT) as a standard first-line therapy. The disease in pediatric population is rare, and despite molecular and clinical similarities to CML in adults, different approach is needed, due to the long lifetime expectancy and distinct developmental characteristics of affected children. OBJECTIVES: The objective of this study is to evaluate treatment with imatinib in Polish pediatric patients with CML. MATERIAL AND METHODS: We analyzed the results of treatment with imatinib in 57 pediatric patients (June 2006 - January 2016) from 14 Polish pediatric hematology and oncology centers. RESULTS: In the study group, 40 patients continued imatinib (median follow-up: 23.4 months), while in 17 the treatment was terminated (median follow-up: 15.1 months) due to therapy failure. In the latter group, 13 patients underwent HSCT, while 4 switched to second-generation TKIs. The 5-year overall survival rate (OS) in the study group was 96%, and the 5-year event-free survival (EFS) was 81%. CONCLUSIONS: Our results confirm that the introduction of TKI therapy has revolutionized the treatment of CML in the pediatric population by replacing the previous method of treatment with HSCT and allowing a high percentage of OS and EFS.

Infectious mononucleosis-like syndrome with high lymphocytosis and positive IgM EBV and CMV antibodies in a three-year-old girl.

Primary Epstein-Barr virus (EBV) and cytomegalovirus (CMV) infection usually affects preadolescent children or young adults, causing similar clinical presentation. Signs and symptoms are typically mild, and the majority of clinical and laboratory findings resolve spontaneously within one month after onset. In adulthood, the risk of fulminant EBV infection and severe complications is much higher, which may be related to increasing memory CD8+ T-cell population with age. It is still not clear what exactly triggers T-cell clonal proliferation. Animals model studies on heterologous immunity between viruses revealed that pre-existing memory T-cells may contribute to excessive immune response during subsequent infection with a new, unrelated pathogen. A 3.5-year-old girl was admitted to hospital with a suspicion of lymphoproliferative disorder. Peripheral blood smear revealed a massive lymphocytosis (61,600 cells/µl) with 62% share of atypical lymphocytes. The clinical presentation and positive EBV and CMV IgM test strongly suggested infectious mononucleosis syndrome as a result of EBV and CMV coinfection.

Spinal range of motion and plantar pressure in sport climbers.

PURPOSE: The aim of the study was to investigate the range of motion (ROM) of lumbar and thoracic articulations and static and dynamic plantar pressure in sport climbing athletes. METHODS: The sample included 30 sport climbers with a minimum of 2 years training experience and 30 physical education students who served as an active untrained control. ROM was assessed by a Saunders digital inclinometer and plantar pressure by a baropodometric platform. RESULTS: Mean spinal ROMs were greater in the sport climbers with an exception of extension, rotation, and lateral thoracic flexion, with a high degree of statistical significance obtained in the majority of the analyzed ROMs. The climbers exhibited increased mean forefoot pressure (smaller rearfoot pressure) in both the dominant and nondominant extremities, with significant intergroup differences found in dominant forefoot/rearfoot pressure distribution. CONCLUSIONS: Sport climbers present increased lumbar and thoracic ROM. The characteristics of climbing may also affect transverse arch structure and plantar pressure distribution.

Correlations between somatic features, anteroposterior spinal curvatures and trunk muscle strength in schoolchildren.

BACKGROUND: Evaluation of body posture and strength of spinal muscles in children during their progressive ontogenesis is significant for the evaluation of their physical health condition and physical fitness. It is also a reference point in a process of control and medical care. PURPOSE: The aim if this study was to evaluate correlation between the selected features of somatic body structure, shape of anteroposterior spinal curves and force-velocity (FV) parameters of trunk muscles in school children. PARTICIPANTS AND METHODS: The sample involved 104 children aged 10-11 years, 60 females (10.74 ±0.7) and 44 males (10.50 ±0.9). Body posture was assessed using the Moiré photogrammetry while trunk muscles (flexors and extensors) strength was measured isokinetically. RESULTS: The results of the research revealed the existence of many average and strong correlations observed between the analysed somatic characteristics and forcevelocity (FV) parameters of trunk muscles. Correlation between the volume of the spinal curvatures in the sagittal plane and forcevelocity parameters of trunk extensors and flexors were average or weak for both groups of children. CONCLUSION: Somatic features indicated stronger correlation with trunk muscles' strength than with the size of the anteroposterior spinal curves.

Active self-correction of spinal posture in pain-free women in response to the command "straighten your back".

Evidence is limited regarding the regional changes in spinal posture after self-correction. The aim of the present study was to evaluate whether active self-correction improved standing and sitting spinal posture. Photogrammetry was used to assess regional spinal curvatures and vertical global spine orientation (GSO) in 42 asymptotic women aged 20-24 years. Upper thoracic spine angle and GSO increased in response to self-correction, while the thoracolumbar and lumbosacral angles decreased. Self-correction in the standing position resulted in decreased inclination of the upper thoracic and thoracolumbar spinal angles. Correction of sitting posture reduced the angle of the upper thoracic spine and GSO. The effects of active self-correction on spinal curvature and GSO were different for the standing versus sitting position; the greatest effects of active correction were noted in the thoracic spine. Balanced and lordotic postures were most prevalent in the habitual and actively self-corrected standing positions, whereas the kyphotic posture was most prevalent in the habitual sitting position, indicative that self-correction back posture in the standing position could be an important health-related daily activity, especially during prolonged sitting.

Association of germline genetic variants in RFC, IL15 and VDR genes with minimal residual disease in pediatric B-cell precursor ALL.

Minimal residual disease (MRD) enables reliable assessment of risk in acute lymphoblastic leukemia (ALL). However, little is known on association between MRD status and germline genetic variation. We examined 159 Caucasian (Slavic) patients with pediatric ALL, treated according to ALL-IC-BFM 2002/2009 protocols, in search for association between 23 germline polymorphisms and MRD status at day 15, day 33 and week 12, with adjustment for MRD-associated clinical covariates. Three variants were significantly associated with MRD: rs1544410 in VDR (MRD-day15); rs1051266 in RFC (MRD-day33, MRD-week12), independently and in an additive effect with rs10519613 in IL15 (MRD-day33). The risk alleles for MRD-positivity were: A allele of VDR (OR = 2.37, 95%CI = 1.07-5.21, P = 0.03, MRD-day15); A of RFC (OR = 1.93, 95%CI = 1.05-3.52, P = 0.03, MRD-day33 and MRD-week12, P < 0.01); A of IL15 (OR = 2.30, 95%CI = 1.02-5.18, P = 0.04, MRD-day33). The risk for MRD-day33-positive status was higher in patients with risk alleles in both RFC and IL15 loci than in patients with risk alleles in one locus or no risk alleles: 2 vs. 1 (OR = 3.94, 95% CI = 1.28-12.11, P = 0.024), 2 vs. 0 (OR = 6.75, 95% CI = 1.61-28.39, P = 0.012). Germline variation in genes related to pharmacokinetics/pharmacodynamics of anti-leukemic drugs and to anti-tumor immunity of the host is associated with MRD status and might help improve risk assessment in ALL.

The Effect of Chronic Pain Intensity on Sit-to-Stand Strategy in Patients With Herniated Lumbar Disks.

OBJECTIVE: Recurrent symptoms of low back pain and its transition to a chronic state are associated with specific motor strategies used by people to avoid pain. The aim of the study was to determine the impact of chronic pain intensity on sit-to-stand (STS) strategy in chronic low back pain (CLBP) patients with herniated disks. METHOD: Vertical ground reaction forces (counter, peak, and postpeak rebound) and their respective times of occurrence were measured on 2 Kistler force plates. Thirty-two healthy persons served as a control group. People with CLBP (n = 40) were divided into 2 subgroups according to the reported pain intensity at rest as measured by the numeric pain rating scale (NRS): low pain (NRS ≤ 3) and high pain (HP; NRS > 3). RESULTS: Both CLBP subgroups achieved shorter time to counter force but longer time to postpeak rebound force (P < .01). The time to peak force was extended in HP on the right side (P < .01). HP presented lower peak force on the right and lower postpeak rebound force on the left side (P < .001) compared with controls. CONCLUSION: Patients with CLBP were characterized by an individual, compensatory STS movement strategy with shorter preparation and longer stabilization times. Avoidance behavior in STS execution was presented in HP individuals only, indicating that intensity of chronic pain was a significant factor in decreasing ground reaction peak force and increasing time to peak force.

Analysis of the Structure of the Torso in the Frontal Plane in Girls with Rett Syndrome Taking into Account Their Functional Status.

BACKGROUND: Rett syndrome is a rare developmental disorder with a genetic background, and scoliosis is one of its many complications. The aim of the present study was to assess the structure of the torso in the frontal plane in RTT. It was assumed that asymmetry of the structure of the torso in the frontal plane would be smaller in girls who are able to maintain a vertical body position. MATERIAL AND METHODS: The study included 14 girls previously diagnosed with RTT aged between 3 and 15 years, who were divided into 2 groups. Group 1 comprised 5 girls who were not able to maintain a vertical position. Group 2 comprised 9 girls who were able to maintain a vertical position. Body mass and weight were measured with an electronic scales and a height measuring device. The Body Mass Index was calculated. Photogrammetry was used to assess the structure of the torso in the frontal plane. The study results were subjected to a statistical analysis involving the calculation of the arithmetic mean (x), standard deviation (sd), coefficient of variation (v%) and significance of differences (p). RESULTS: Left-sided asymmetries were most common in both groups. All angles and linear values were higher in Group 1. 80% of the subjects in Group 1 demonstrated significant asymmetry of the pelvic tilt angle (PTA). There were no statistically significant differences between Group 1 and 2 regarding all study indices. CONCLUSIONS: 1. The study demonstrated that asymmetry of the torso in the frontal plane was common in the girls with RTT. 2. Torso asymmetry was more pronounced in girls with a poorer functional status. 3. Analysis of BMI values demonstrated a poor nutritional status of the girls.

The Influence of Primary Cytomegalovirus or Epstein-Barr Virus Infection on the Course of Idiopathic Thrombocytopenic Purpura.

Idiopathic thrombocytopenic purpura (ITP) in children is usually triggered by a viral infections such as cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection. The aim of this study was to assess the frequency of CMV and EBV infections in children with first relapse of ITP, and the influence of these infections on the course and response to treatment of ITP. Sixty patients (30 boys and 30 girls) with ITP were enrolled into the study. We found that the age at the onset of ITP was from 1 month to 17 years (mean 7.0 ± 5.7 years), the platelet number was from 1 to 79 x 10(9)/L (mean 18.1 ± 19.0 x 10(9)/L) at the time of diagnosis and it increased from 17 to 395 x 10(9)/L (mean 134.4 ± 81.2 x 10(9)/L)(p < 0.05) after the first course of therapy. Forty seven patients required pharmacological treatment, the duration of the treatment was from 2 to 25 days (mean 6.1 ± 4.1 days). Relapses were observed in 27 (45%) of the patients. Active CMV infection was found in 19 patients (31.7%), EBV infection in 5 patients (8.3%), and both infections concomitantly in 1 patient (1.7%). The group of patients with CMV or EBV infection(n = 25) did not differ from the patients free of infection (n = 35) in regard to the age, number of platelets at onset, duration of treatment, number of platelets after treatment, number of relapses, and the interval between the onset and first relapse. In conclusion, active CMV or EBV infection is common in children with ITP. These infections do not seem to have an appreciable bearing on the clinical course and the response to treatment on children with ITP.

Evaluation of isokinetic trunk muscle strength in adolescents with normal and abnormal postures.

OBJECTIVE: The aim of this study was to assess existing differences in the isokinetic trunk muscle strength in males and females aged between 10 and 11 years depending on body posture. METHODS: The study included 145 children (67 males and 78 females) divided into 2 age groups: 10-year-old males (x¯ = 9.98 ± 2.34 years) and females (x¯ = 9.85 ± 2.94 years) and 11-year-old males (x¯ = 11.14 ± 2.22 years) and females (x¯ = 11.15 ± 2.32 years). Posture in the sagittal plane was assessed by photogrammetry using the moiré projection technique. Based on a classification system, the participants were divided into subgroups of males and females with normal and abnormal postures. Trunk muscle strength was measured using isokinetic dynamometry. RESULTS: A high prevalence of abnormal posture in children aged between 10 and 11 years was observed, primarily represented by an excessive curvature of the spine in the sagittal plane. The males and females with poor posture recorded lower values in isokinetic trunk muscle strength. CONCLUSION: The results of the study point to the need for the application of suitable physiotherapy treatment (corrective measures/exercises) to treat musculoskeletal disorders to compensate for the loss of trunk flexor muscle strength in children with improper posture.

Influence of Iron Overload on Immunosuppressive Therapy in Children with Severe Aplastic Anemia.

Children with severe aplastic anemia (AA) require multiple transfusions of the red blood cells during the immunosuppressive therapy. This leads to iron overload and manifests as elevated levels of ferritin in blood. The aim of this study was a retrospective analysis of the influence of the elevated serum ferritin on the overall survival, event-free survival, the risk of relapse, and response to treatment in children with AA during immunosuppressive therapy. We analyzed 38 children with AA (19 girls, 19 boys, aged 2-17 years) treated according to the obligatory protocol for AA in Poland. The response rate was assessed on days 84, 112, and 360. Patients were divided into three groups: group I consisted of children with ferritin below 285 ng/mL (6 children), group II with ferritin between 286 and 1,000 ng/mL (13 children), and group III ferritin>1,000 ng/mL (19 children). Kaplan-Meier plot was used to estimate the overall survival and event-free survival. We found the overall survival did not differ between the three groups. Event-free survival was significantly shorter (p=0.03) in patients with ferritin levels>1,000 ng/mL compared with the groups with ferritin bellow 1,000 ng/mL. The time to relapse was significantly shorter in group III than in the other two groups (p=0.02). We also found the differences in the treatment response at day 84 (p=0.03) and day 112 (p<0.0001) of immunosuppressive therapy. These findings confirm a negative influence of iron overload in children with AA on the effect of treatment and the risk of relapse.

Effects of selected forms of physical activity on body posture in the sagittal plane in women post breast cancer treatment.

BACKGROUND: Breast cancer treatment may be a cause of postural disorders. OBJECTIVE: Assessment of the effects of various forms of physical activity on body posture in the sagittal plane in women post breast cancer treatment. STUDY GROUP: Sixty women who had received breast cancer treatment. The study group was intentionally divided into three groups of 20 women who followed different exercise regimens: NordicWalking (NW), water resistance exercise (WE) or general fitness exercise (GE). METHODS: Photogrammetric examination of body posture using a Computer-Based Body Posture Diagnostics apparatus performed at baseline and after an 8-week regimen of appropriately selected physical exercise. RESULTS: A favourable tendency for the shallowing of thoracic kyphosis and the reduction of lumbar cu rvature of the spine was noted in the NW group. Reduced kyphosis was also noted in the WE group, however it was accompanied by more pronounced lumbar lordosis and a tendency for excessive forward bending of the trunk. In the GE group, on the other hand, no significant differences were observed in terms of the shape of anteroposterior spinal curvatures. CONCLUSIONS: The diversity observed in the shape of anteroposterior spinal curvatures following physical training regimens of different type and nature demonstrates the need of appropriate exercise selection to attain the desired therapeutic outcome. Balanced postural changes were only identified among the women in the NW group. In the GE group, however, training only sustained the status existing prior to the initiation of the exercise regimen.

Central nervous system haemorrhage causing early death in acute promyelocytic leukaemia.

Acute promyelocytic leukaemia (APL) is a rare type of paediatric leukaemia characterised by a specific genetic mutation and life-threatening coagulopathy. The discovery of all-trans retinoic acid (ATRA), which acts directly on promyelocytic locus-retinoic acid receptor α (PML-RARα) gene product, brought a revolution to the therapy of this disorder. Unfortunately, despite an improvement in the complete remission rate, the early death (ED) rate has not changed significantly, and the haemorrhages remain a major problem. The most common bleeding site, which accounts for about 65-80% of haemorrhages, is the central nervous system. Second in line are pulmonary haemorrhages (32%), while gastrointestinal bleedings are relatively rare. Haemorrhages result from thrombocytopaenia, disseminated intravascular coagulopathy (DIC), and systemic fibrinolysis. Herein we present a boy aged one year and nine months with APL. The patient was not eligible for ATRA administration due to poor clinical condition. He developed bleeding diathesis that presented as disseminated intravascular coagulation (DIC) and led to intracranial haemorrhage, which resulted in the patient's death.

Respiratory and systemic infections in children with severe aplastic anemia on immunosuppressive therapy.

In the present study we investigated the occurrence of systemic and respiratory infections in a cohort of 123 children with severe acquired aplastic anemia (SAA) on immunosuppressive therapy (IST). We recorded 101 episodes of infection in 77 patients (62.6 %). Pneumonia was among the most frequently observed clinical forms of infection (17 cases - 16.8 %). In the entire group, 23 children died, mostly in the course of fatal sepsis (15/23) and in 3 cases because of pneumonia complications. All patients were treated with horse (h-ATG) or rabbit antithymocyte globulin (r-ATG) supplemented with cyclosporine and corticosteroids. The crude incidence rate for serious infections in h-ATG group and r-ATG group was comparable. The relative risk of infectious complications was lower in patients treated with granulocyte colony stimulating factors (G-CSF) by 36 % (RR 0.64; p < 0.0001). The analysis confirmed that respiratory tract and disseminated infections comprise a very serious clinical problem and are the leading cause of death of SAA children. Active surveillance and the analysis of associated risk factors are required to detect opportunistic infections in this group of patients.