Background: A retrospective analysis was performed to investigate the survival outcomes in pediatric acute lymphoblastic leukemia (ALL) based on time period. We hypothesized that improvement has been obtained with the time-dependent therapeutic era and rise in the gross domestic product (GDP) and Human Development Index (HDI). Materials and Methods: Data from 710 children who were treated for ALL between 1958 and 2018 at a single pediatric center were analyzed for probability of 5-year overall survival (pOS), event-free survival (pEFS) and relapse risk (pRR). Time periods were defined by the treatment protocols used in seven consecutive therapeutic eras. Results: Over the 60-year period analyzed, pOS increased from 1.2% to 90.7%, pEFS from 1.2% to 86.6%, and pRR decreased from 98.8% to 9.9% for patients treated in the past decade. Risk of mortality for patients who received chemotherapy and hematopoietic cell transplant was reduced to 9.9% in the recent era, however, no statistically significant survival difference was found between patients treated with stem cell transplant and those not. Conclusion: The therapeutic era, related to improved GDP and HDI, was a statistically significant predictor of increased OS from ALL.
Background: Activated PI3K delta syndrome (APDS) belongs to the heterogeneous group of primary immunodeficiency disorders (PIDs). Progress in next-generation sequencing (NGS) enabled identification of gain-offunction mutations in phosphoinositide 3-kinase (PI3K) genes. Depending on the type of causative mutation, APDS is classified into two types: APDS 1 and APDS 2. To date, less than 100 cases of APDS have been reported. Clinical symptoms of APDS result from impaired immune regulation and are clinically manifested by recurrent infections, allergies, lymphoproliferation and autoimmunity. They show similarity to other PIDs. Therefore, many patients were diagnosed incorrectly. The availability of genetic testing has allowed establishing the correct diagnosis in increasing number of patients suffering from APDS. Case presentations:The first male patient presented in infancy with recurrent infections. Subsequently he was found to suffer from hepatosplenomegaly, early portal hypertension, massive lymphoproliferation and hypogammaglobulinemia. The common E1021K mutation in the PI3KCD gene was identified. The patient underwent successful hematopoietic stem cell transplantation with resolution of most symptoms. The second patient suffered from persistent growth retardation since early life, facial dysmorphism and recurrent respiratory infections from early childhood. He was found to have systemic lympho-proliferation, panhypoglobulinemia and impaired antibody responses to vaccines. The introduction of NGS in Poland enabled rapid identification of a mutation in the PI3KR1 gene. Growth hormone administration seemed to have worsened the lymphoproliferation. Conclusions:Patients with suspected common variable immunodeficiency (CVID) and additional symptoms, such as allergy, facial dysmorphia, short stature, enhanced lymphoproliferation and lack of adequate response to human immunoglobulin replacement therapy, should be considered for NGS-based genetic testing. It may substantially shorten the time needed to establish the correct diagnosis, direct appropriate treatment and avoid potentially harmful therapies. To date, few cases of APDS have been described. It is important to report each of them to establish clinical indices and laboratory biomarkers of APDS 1 and APDS 2, to develop the standards of care in these conditions.
Background/Aim: Comparison of transplant outcomes in long-term follow-up of children after total body irradiation (TBI)-or chemotherapy-based conditioning allogeneic hematopoietic cell transplantation (allo-HCT).Patients and Methods: Patients undergoing allo-HCT for Acute lymphoblastic leukemia (ALL) conditioned either with TBI (n=55) or chemotherapy (n=84) were compared. The following transplant outcomes were analyzed: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graftversus-host-disease (GVHD)-free-relapse-free survival (GRFS). Results: All analyzed long-term transplant outcomes were significantly better for patients conditioned with TBI at 2 years after transplant. OS at 2 years was 84% after TBI and 60.5% after chemotherapy-conditioning (p=0.005). Risk factor analysis showed that two factors, TBI-based conditioning and transplant in first remission of ALL, significantly improved OS, EFS, GRFS, and decreased RI. Conclusion: TBI-based conditioning before allogeneic HCT in children with acute lymphoblastic leukemia provides significantly better transplant outcomes, when compared to chemotherapy-based conditioning.Acute lymphoblastic leukemia (ALL) is the most frequent type of malignancy in children. With international cooperation, outcomes have improved remarkably during the last decades and reached 90% of long-term survival (1, 2). ALL is also the most frequent indication for allogeneic hematopoietic cell transplantation (allo-HCT) in children, comprising both patients with high-risk disease in first complete remission (CR1) or in relapsed phase (rALL) (3). Two basic types of high-dose conditioning therapy before HCT for ALL are used both in children and adults, based on total body irradiation (TBI) or on chemotherapy (CHT), mainly with the use of busulfan or treosulfan (4, 5). Differences in the efficacy and short-and long-term safety between TBI and CHT-based transplantations is a matter of debate (4, 6, 7). A benefit in the outcome after the use of TBI has been observed in adults ( 6), but not univocally in children, as presented in a meta-analysis in 2011 (8). A recent large international prospective trial showed improved survival and lower relapse risk in patients following TBI+etoposide conditioning in comparison to CHT-based allo-HCT in children aged over 4 years (9). However, there are almost no real-world data on pediatric ALL-HCT (10).Herein, we present our experience with allo-HCT in pediatric ALL with respect to the type of conditioning. The objective of this analysis was comparison of transplant outcomes: overall survival (OS), event-free survival (EFS), relapse incidence (RI), and graft-versus-host-disease (GVHD)-3315 This article is freely accessible online.
Objective: Iron overload (IO) is a common and life-threatening complication resulting from the therapy of AL and HCT patients. This study aimed to evaluate the prognostic value of 12 serum biomarkers of iron metabolism in pediatric patients treated for AL or undergoing HCT. Patients: Overall, 50 patients with AL after intensive treatment and 32 patients after HCT were prospectively included in the study. AL patients at diagnosis and healthy controls served as reference groups. Methods: The impact of the following 12 serum iron metabolism parameters on the outcome of AL/HCT patients was analyzed: iron, transferrin (Tf), total iron-binding capacity (TIBC), ferritin, ferritin heavy chains (FTH1), ferritin light chains (FTL), hepcidin, soluble hemojuvelin (sHJV), soluble ferroportin-1 (sFPN1), erythroferrone (ERFE), erythropoietin (EPO), and soluble transferrin receptor (sTfR). Results: With a median follow-up of 2.2 years, high levels of ferritin and low levels of sHJV had an adverse prognostic impact on OS and EFS in children after HCT. If these patients were combined with those with AL after intensive chemotherapy, the results were confirmed for OS and EFS both for ferritin and sHJV. Conclusions: Among the 12 analyzed serum parameters of iron metabolism, increased levels of ferritin and decreased levels of sHJV had an adverse prognostic impact on survival in children after HCT. More data are needed to clarify the relationship between ferritin, sHJV, and mortality of AL children after intensive chemotherapy, and more extensive prospective studies are required to prove sHJV predictivity.
Objective: The aim of this study was to evaluate non-transferrin-bound iron (NTBI) and labile plasma iron (LPI) levels and other parameters of iron metabolism in children undergoing therapy for acute leukemia or after hematopoietic cell transplantation (HCT), in the context of iron overload. Patients: A total number of 85 children were prospectively included into four groups: controls, acute leukemia de novo, acute leukemia after intensive treatment, and after HCT. Methods: The following iron metabolism parameters were analyzed: (1) parameters measuring functional and storage iron pools: NTBI, LPI, iron, transferrin, total iron-binding capacity, ferritin, ferritin heavy and light chains; (2) proteins regulating iron absorption and its release from tissue stores: hepcidin, soluble hemojuvelin, soluble ferroportin-1; (3) proteins regulating the erythropoietic activity of bone marrow: erythroferrone, erythropoietin, soluble transferrin receptor. Results: Intensive treatment of leukemia in children was associated with the presence of serum NTBI and LPI, which was the highest in the HCT group followed by the acute leukemia after treatment and de novo groups. In patients after HCT, the most significant changes were found in NTBI, LPI, iron, ferritin, hepcidin, and ferroportin-1 levels. Conclusions: The occurrence of NTBI and LPI in the circulation and the intensification of disturbances in iron metabolism were associated with the intensity of the anti-leukemic treatment.
Objectives: The association between hepcidin and acute leukemia (AL) or hematopoietic cell transplantation (HCT) in children and adults remains obscure. We aimed to assess this potential relationship through a systematic review of observational studies. Methods: An electronic search of three databases, including PubMed, Scopus, and Web of Science Core Collection, was performed up to 31 March 2022. Two independent reviewers assessed the search results according to predetermined inclusion and exclusion criteria, following PRISMA guidelines. Results: Of the 3607 titles identified, 13 studies published between 2008 and 2021 met the inclusion criteria. Most studies included a moderate number of participants and controls and used enzyme-linked immunosorbent assay (ELISA) to determine serum hepcidin levels. The principal findings: (1) serum hepcidin levels in patients with AL or undergoing HCT are increased compared to controls, regardless of the patient’s age and the phase of disease treatment; (2) AL therapy and HCT significantly influence serum hepcidin levels; (3) serum hepcidin may predict a worse outcome in patients with AL and post-HCT. Conclusions: This systematic review provides an overview of observational studies that deal with the association of hepcidin with AL and HCT. Although disturbances in iron metabolism are common in AL and HCT, and hepcidin seems to play a cardinal role in their modulation, more extensive research is needed.
Background: Oral mucositis (OM) is considered to be one of the worst and most debilitating complications of conditioning for hematopoietic cell transplantation (HCT). Prevention and treatment of this complication is one of the utmost priorities of supportive therapy during transplant procedure. The objective of this study was the analysis of the influence of palifermin, keratinocyte growth factor (KGF), on transplant outcomes in patients undergoing allo-HCT. Patients and Methods: A total of 253 allo-HCTs performed between 2003-2018 in patients aged 0-19 years at a single center were analyzed. KGF was administered in 161 HCTs. Uni-and multivariate risk factor analyses were performed. Results: In spite of reducing the duration and grade of mucositis, no prognostic impact of KGF was shown for overall survival, event-free survival, relapse incidence, acute and chronic graftversus-host disease (GVHD), nor GVHD-free relapse-free survival. Conclusion: Palifermin had no impact on transplant outcomes in children and adolescents undergoing allo-HCT.Oral mucositis (OM) is one of the most common and distressful (debilitating) complications in cancer chemotherapy, radiotherapy, conditioning and transplantation (1-5). It is often accompanied by pain, dysgeusia, odynophagia and occurs more frequent in children and adolescents than that in adult patients (2). OM is reported in 75% to 100% patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) (6-10).Numerous methods for the prevention and treatment of OM have been developed including palifermin [recombinant human keratinocyte growth factor (KGF)], granulocytecolony stimulating factor, amifostine, aloe vera, honey and polymixin/tobramycin/amphotericin, antibiotic pastille/paste, intravenous glutamine, polaprezinc sodium alginate suspension and sucralfate, cryotherapy, and laser (2, 11). Current recommendations of Multinational Association of Supportive Care in Cancer and International Society of Oral Oncology for the prevention of OM include: KGF, benzydamine, morphine, cryotherapy and low-level laser light therapy (12,13).The use of palifermin in prophylaxis can significantly reduce the incidence and severity of mucositis in patients after total body irradiation (TBI)/high-dose chemotherapy. We previously showed that patients receiving KGF after autologous HCT had better overall survival (OS) (5). We have also shown that patients with allo-HCT who received palifermin prophylactically, had shorter duration of mucositis (median: 9 vs. 13 days), lower OM grade (median: III vs. IV), shorter total parenteral nutrition (median: 19 vs. 22 days) and lower incidence of episodes of febrile neutropenia (median: 39% vs. 83%) ( 14). Since data on the effect of palifermin on outcomes of allo-HCT in children are scarce, we analyzed the impact of prophylactic use of palifermin on transplant outcomes in a large cohort of children undergoing allo-HCT. Patients and MethodsStudy design. We carried out analysis of the impact of palifermin administered under compassionate use on...
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