190 results on '"Krzysztof Kałwak"'
Search Results
2. Incidence of bacterial and fungal infections in Polish pediatric patients with acute lymphoblastic leukemia during the pandemic
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Joanna Zawitkowska, Katarzyna Drabko, Monika Lejman, Adrian Kowalczyk, Krzysztof Czyżewski, Magdalena Dziedzic, Kamila Jaremek, Patrycja Zalas-Więcek, Anna Szmydki-Baran, Łukasz Hutnik, Wojciech Czogała, Walentyna Balwierz, Iwona Żak, Małgorzata Salamonowicz-Bodzioch, Bernarda Kazanowska, Grażyna Wróbel, Jowita Frączkiewicz, Krzysztof Kałwak, Renata Tomaszewska, Tomasz Szczepański, Olga Zając-Spychała, Jacek Wachowiak, Marcin Płonowski, Maryna Krawczuk-Rybak, Aleksandra Królak, Tomasz Ociepa, Tomasz Urasiński, Filip Pierlejewski, Wojciech Młynarski, Justyna Urbańska-Rakus, Katarzyna Machnik, Sonia Pająk, Wanda Badowska, Tomasz Brzeski, Katarzyna Mycko, Hanna Mańko-Glińska, Agnieszka Urbanek-Dądela, Grażyna Karolczyk, Agnieszka Mizia-Malarz, Weronika Stolpa, Katarzyna Skowron-Kandzia, Jakub Musiał, Radosław Chaber, Ninela Irga-Jaworska, Ewa Bień, and Jan Styczyński
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Medicine ,Science - Abstract
Abstract The most common complications related to the treatment of childhood acute lymphoblastic leukemia (ALL) are infections. The aim of the study was to analyze the incidence and mortality rates among pediatric patients with ALL who were treated in 17 Polish pediatric hematology centers in 2020–2021 during the pandemic. Additionally, we compared these results with those of our previous study, which we conducted in the years 2012–2017. The retrospective analysis included 460 patients aged 1–18 years with newly diagnosed ALL. In our study, 361/460 (78.5%) children were reported to have microbiologically documented bacterial infections during chemotherapy. Ten patients (2.8%) died due to sepsis. Fungal infections were reported in 99 children (21.5%), of whom five (5.1%) died due to the infection. We especially observed an increase in bacterial infections during the pandemic period compared to the previous study. The directions of our actions should be to consider antibiotic prophylaxis, shorten the duration of hospitalization, and educate parents and medical staff about complications (mainly infections) during anticancer therapy. It is necessary to continue clinical studies evaluating infection prophylaxis to improve outcomes in childhood ALL patients.
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- 2023
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3. Hematopoietic stem cell transplantation in a patient with activated phosphoinositide 3‑kinase δ syndrome: A case report and literature review
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Mateusz P. Łyżwa, Karolina Kędziora, Natalia Kałamarz, Jowita Frączkiewicz, Anna Panasiuk, Joanna Owoc-Lempach, Barbara Piątosa, Marcin Hennig, Ninela Irga-Jaworska, and Krzysztof Kałwak
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primary immunodeficiency ,hematopoietic stem cell transplantation ,activated phosphoinositide 3-kinase δ syndrome ,nonmalignant lymphoproliferation ,Medicine - Abstract
Activated phosphoinositide 3-kinase δ syndrome (APDS) is a recently described disease characterized by recurrent infections, lymphoproliferation with a high risk of malignancy, early-onset cytopenia, and a propensity for autoimmune diseases. Hematopoietic stem cell transplantation (HSCT) has proven to be an effective treatment method; however, the recovery process after HSCT is prolonged and accompanied by complications. In this study, we present the case of a patient with APDS type 1. Despite showing signs of immunodeficiency at the age of 6 months, it took almost 6 years to reach a definitive diagnosis. The patient experienced recurrent infections, often accompanied by anemia requiring transfusions, and multifocal nonmalignant lymphoproliferation. Only after receiving the appropriate diagnosis was it possible to implement proper and accurate treatment. HSCT was performed when the patient was 6 years old, leading to significant improvement in his condition. At the 17-month post-HSCT follow-up, the boy is asymptomatic and in good general health, although close monitoring continues due to mixed chimerism and delayed humoral immune recovery. Applying HSCT before the patient develops malignancy contributes to expanding the use of HSCT as a treatment option for APDS type 1.
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- 2023
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4. Acute Pancreatitis in Pediatric Acute Lymphoblastic Leukemia (AcuPA Study): A Nationwide Survey in Poland
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Anna Morawiak, Małgorzata Salamonowicz-Bodzioch, Aleksandra Królak, Krzysztof Kałwak, Joanna Owoc-Lempach, Jerzy Kowalczyk, Joanna Zawitkowska, Tomasz Szczepański, Ninela Irga-Jaworska, Elżbieta Adamkiewicz-Drożyńska, Katarzyna Albrecht, Anna Szmydki-Baran, Walentyna Balwierz, Małgorzata Czogała, Jacek Wachowiak, Katarzyna Derwich, Wojciech Młynarski, Beata Zalewska-Szewczyk, Maryna Krawczuk-Rybak, Małgorzata Sawicka-Żukowska, Jan Styczyński, Andrzej Kołtan, Krzysztof Safranow, Tomasz Urasiński, and Tomasz Ociepa
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acute lymphoblastic leukemia ,children ,acute pancreatitis ,risk factors ,intensive chemotherapy ,asparaginase ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Purpose: This study aimed to identify the risk factors for acute pancreatitis (AP) and its impact on outcomes in Polish children treated for ALL. Methods: The study group included 2303 children receiving intensive chemotherapy for ALL. The group was divided into patients with at least one episode of AP and those who did not develop AP after treatment for ALL. Results: The cumulative incidence of AP in the study group was 4.08%. Older age was an independent risk factor for the development of AP (OR = 1.05; 95%CI = 1.006–1.098; p = 0.03). The overall mortality associated with AP was 2.13%. The probabilities of disease-free survival (p-DFS) and event-free survival (p-EFS) in both subgroups were 0.84 vs. 0.86, log-rank p = 0.65 and 0.75 vs. 0.80, log-rank p = 0.12, respectively. A total of 22 out of 94 patients (23.4%) with AP were re-exposed to asparaginase (ASP) during the subsequent treatment phases. Only one patient re-exposed to ASP (4.5%) developed a second episode of AP. There were no significant differences in p-DFS and p-EFS between patients re-exposed and not re-exposed to asparaginase (0.78 vs. 0.86, log-rank p = 0.27 and 0.63 vs. 0.79, log-rank p = 0.09, respectively). Conclusions: The incidence of AP in children with ALL is low and related to patients’ age. The development of AP does not seem to influence p-DFS and p-EFS in children with ALL. Recurrence of AP after re-exposure to asparaginase in patients with ALL and a history of AP is low (4.5%). Re-exposure to asparaginase after the first episode of AP does not improve either p-DFS or p-EFS in children with ALL.
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- 2024
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5. The Kinetics of Inflammation-Related Proteins and Cytokines in Children Undergoing CAR-T Cell Therapy—Are They Biomarkers of Therapy-Related Toxicities?
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Paweł Marschollek, Karolina Liszka, Monika Mielcarek-Siedziuk, Iwona Dachowska-Kałwak, Natalia Haze, Anna Panasiuk, Igor Olejnik, Tomasz Jarmoliński, Jowita Frączkiewicz, Zuzanna Gamrot, Anna Radajewska, Iwona Bil-Lula, and Krzysztof Kałwak
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chimeric antigen receptors ,CAR-T cells ,CRS ,ICANS ,cytokines ,biomarkers ,Biology (General) ,QH301-705.5 - Abstract
CD19-targeted CAR-T cell therapy has revolutionized the treatment of relapsed/refractory (r/r) pre-B acute lymphoblastic leukemia (ALL). However, it can be associated with acute toxicities related to immune activation, particularly cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Cytokines released from activated immune cells play a key role in their pathophysiology. This study was a prospective analysis of proinflammatory proteins and cytokines in children treated with tisagenlecleucel. Serial measurements of C-reactive protein, fibrinogen, ferritin, IL-6, IL-8, IL-10, IFNγ, and TNFα were taken before treatment and on consecutive days after infusion. The incidence of CRS was 77.8%, and the incidence of ICANS was 11.1%. No CRS of grade ≥ 3 was observed. All complications occurred within 14 days following infusion. Higher biomarker concentrations were found in children with CRS grade ≥ 2. Their levels were correlated with disease burden and CAR-T cell dose. While cytokine release syndrome was common, most cases were mild, primarily due to low disease burden before lymphodepleting chemotherapy (LDC). ICANS occurred less frequently but exhibited various clinical courses. None of the toxicities were fatal. All of the analyzed biomarkers rose within 14 days after CAR-T infusion, with most reaching their maximum around the third day following the procedure.
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- 2024
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6. Infections with Klebsiella pneumoniae in Children Undergoing Anticancer Therapy or Hematopoietic Cell Transplantation: A Multicenter Nationwide Study
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Alicja Sękowska, Krzysztof Czyżewski, Kamila Jaremek, Patrycja Zalas-Więcek, Olga Zając-Spychała, Jacek Wachowiak, Anna Szmydki-Baran, Łukasz Hutnik, Agnieszka Gietka, Olga Gryniewicz-Kwiatkowska, Bożenna Dembowska-Bagińska, Katarzyna Semczuk, Katarzyna Dzierżanowska-Fangrat, Wojciech Czogała, Walentyna Balwierz, Iwona Żak, Renata Tomaszewska, Tomasz Szczepański, Ewa Bień, Ninela Irga-Jaworska, Katarzyna Machnik, Justyna Urbańska-Rakus, Sonia Pająk, Marcin Płonowski, Maryna Krawczuk-Rybak, Aleksandra Królak, Tomasz Ociepa, Tomasz Urasiński, Paweł Wawryków, Jarosław Peregud-Pogorzelski, Tomasz Brzeski, Katarzyna Mycko, Hanna Mańko-Glińska, Wanda Badowska, Agnieszka Urbanek-Dądela, Grażyna Karolczyk, Weronika Stolpa, Katarzyna Skowron-Kandzia, Agnieszka Mizia-Malarz, Filip Pierlejewski, Wojciech Młynarski, Jakub Musiał, Radosław Chaber, Joanna Zawitkowska, Agnieszka Zaucha-Prażmo, Katarzyna Drabko, Jolanta Goździk, Jowita Frączkiewicz, Małgorzata Salamonowicz-Bodzioch, Krzysztof Kałwak, and Jan Styczyński
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acute leukemia ,children ,hematopoietic cell transplantation ,infection ,Klebsiella pneumoniae ,Medicine - Abstract
Background: Klebsiella pneumoniae is a nosocomial pathogen that causes severe infections in immunocompromised patients. The aim of the study was to conduct a microbiological and clinical analysis of K. pneumoniae infections in children with malignancies or undergoing hematopoietic cell transplantation in Poland. Methods: We conducted a retrospective, multicenter study including children and adolescents under 19 years old treated between 2012 and 2021. We analyzed patients’ characteristics, microbiological data, and the outcomes of antibiotic therapy. Results: A total of 9121 newly diagnosed children were treated for malignancy and 1697 pediatric patients underwent hematopoietic cell transplantation. K. pneumoniae infections were diagnosed in 527 patients. Their overall incidence was 4.86% in pediatric hematology and oncology patients and 4.95% in patients who underwent hematopoietic cell transplantation. The incidence of infection was higher in patients with acute leukemia than with solid tumors (7.8% vs. 4.1%; OR = 2.0; 95% CI = 1.6–2.4; p < 0.0001). The most frequent source of infection was in the urinary tract at 55.2%. More than 57% of K. pneumoniae strains were extended-spectrum β-lactamase-positive and almost 34% were multidrug-resistant. Infections with K. pneumoniae contributed to death in 3.22% of patients. Conclusions: K. pneumoniae is one of the most critical pathogens in children suffering from malignancies or undergoing hematopoietic cell transplantation. The incidence of multidrug-resistant K. pneumoniae strains is increasing and contributing to poor clinical outcome.
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- 2024
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7. Severe complications of nivolumab monotherapy in an adolescent with malignant melanoma
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Aleksandra Grzegorczyk, Zuzanna Marczyńska, Rafał Matkowski, Marcin Ziętek, Wojciech Pietras, Elżbieta Latos-Grażyńska, Krzysztof Kałwak, and Iwona Dachowska-Kałwak
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melanoma ,hypothyroidism ,nivolumab ,capillary leak syndrome ,Medicine - Abstract
This study presents a case of a 17-year-old female patient who had previously undergone surgical resection of melanoma in the right periscapular area. She was administered adjuvant treatment with the PD-1 inhibitor nivolumab as monotherapy. The mechanism of action of this drug is based on increased stimulation of the immune system. The patient developed a series of complications including capillary leak syndrome and hypothyroidism after the fifth cycle of therapy, as a result of dysregulation of immunity. Nivolumab treatment had to be discontinued and glucocorticosteroids were administered as a salvage therapy. After several months, two relapses developed in the subcutaneous tissue – first in the left and then in the right iliac region, confirmed as distant metastases of malignant melanoma, treated with resections of the lesions and intensity-modulated radiation therapy. Follow-up imaging studies and clinical examinations showed no metastases or pathologically enlarged lymph nodes.
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- 2023
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8. Assessment of Risk Factors for Acute Kidney Injury with Machine Learning Tools in Children Undergoing Hematopoietic Stem Cell Transplantation
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Kinga Musiał, Jakub Stojanowski, Monika Augustynowicz, Izabella Miśkiewicz-Migoń, Krzysztof Kałwak, and Marek Ussowicz
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acute graft versus host disease ,acute kidney disease ,artificial intelligence ,random forest classifier ,tubular damage ,Medicine - Abstract
Background: Although acute kidney injury (AKI) is a common complication in patients undergoing hematopoietic stem cell transplantation (HSCT), its prophylaxis remains a clinical challenge. Attempts at prevention or early diagnosis focus on various methods for the identification of factors influencing the incidence of AKI. Our aim was to test the artificial intelligence (AI) potential in the construction of a model defining parameters predicting AKI development. Methods: The analysis covered the clinical data of children followed up for 6 months after HSCT. Kidney function was assessed before conditioning therapy, 24 h after HSCT, 1, 2, 3, 4, and 8 weeks after transplantation, and, finally, 3 and 6 months post-transplant. The type of donor, conditioning protocol, and complications were incorporated into the model. Results: A random forest classifier (RFC) labeled the 93 patients according to presence or absence of AKI. The RFC model revealed that the values of the estimated glomerular filtration rate (eGFR) before and just after HSCT, as well as methotrexate use, acute graft versus host disease (GvHD), and viral infection occurrence, were the major determinants of AKI incidence within the 6-month post-transplant observation period. Conclusions: Artificial intelligence seems a promising tool in predicting the potential risk of developing AKI, even before HSCT or just after the procedure.
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- 2024
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9. Pre-Exposure Prophylaxis and Treatment with Tixagevimab/Cilgavimab for COVID-19 among Immunocompromised Pediatric Patients
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Jowita Frączkiewicz, Katarzyna Pawińska-Wąsikowska, Katarzyna Szymbor, Walentyna Balwierz, Szymon Skoczeń, Krzysztof Czyżewski, Sylwia Kołtan, Jan Styczyński, Anna Małecka, Ninela Irga-Jaworska, Joanna Trelińska, Wojciech Młynarski, Olga Zając-Spychała, Agnieszka Sobkowiak-Sobierajska, Katarzyna Derwich, Wioletta Bal, Radosław Chaber, Agnieszka Książek, Tomasz Szczepański, Joanna Zawitkowska, Katarzyna Drabko, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Christopher Kobierzycki, and Krzysztof Kałwak
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COVID-19 ,immunocompromised patients ,monoclonal antibodies ,tixagevimab ,cilgavimab ,evusheld ,Medicine - Abstract
Background: Patients treated with hemato-oncological malignancies (HO) or undergoing cellular therapies such as hematopoietic stem cell transplantation (HSCT) or chimeric antigen receptor T cells (CAR-T) were significantly affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Despite the success of SARS-CoV-2 vaccination, immunocompromised patients remain at increased risk for severe coronavirus disease (COVID-19), rendering this group of population a high priority for additional prevention and treatment options. Tixagevimab and Cilgavimab (TIXA/CILGA, AZD7442, Evusheld®) is a combination of two fully human, long-acting monoclonal antibodies. TIXA/CILGA have been approved as pre-exposure prophylaxis and treatment in patients at risk of severe disease with impaired vaccine response. Our objective was to describe the efficacy and safety among immunocompromised pediatric patients. Methods: This was an observational multicenter cohort study of immunocompromised pediatric patients receiving TIXA/CILGA conducted at nine Polish centers of Pediatric Oncology, Hematology and Bone Marrow Transplantation. We analyzed patients in two groups; those treated with HO and those undergoing cellular therapies: HSCT or CAR-T cells. In addition, two other cohorts were identified: patients given TIXA/CILGA as pre-exposure prophylactic and therapeutic intervention. Results: A total of 78 patients were evaluated during the study period: 69 (88.5%) received TIXA/CILGA as pre-exposure prophylaxis and 9 (11.5%) as a treatment strategy. A total of 52 (66.6%) patients were treated with standard chemotherapy at HO departments; 21 (27%) underwent HSCT, and 5 (6.4%) received CAR-T cell therapy. All children with COVID-19 receiving TIXA/CILGA presented a mild degree of severity. The most common clinical manifestations were fever, cough and coryza. At least one adverse event (AE) was reported in two (3.8%) patients excluding standard injection site reactions. Reported AEs were mild or moderate in intensity. One child reported mild myalgia and one reported moderate bone pain and weakness. Conclusions: In our observational multicenter cohort study, we explored the use of TIXA/CILGA as pre-exposure prophylaxis and treatment for COVID-19 among immunocompromised pediatric patients. While our findings suggest a potential benefit in preventing and managing COVID-19 in this vulnerable population, it is important to note the study’s non-comparative design. Our results highlight the need for well-designed clinical trials to confirm these observations and further assess the efficacy and safety of TIXA/CILGA in immunocompromised children.
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- 2024
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10. Treatment Outcomes of Adolescents Compared to Younger Pediatric Patients with Acute Myeloid Leukemia: Do They Need a Special Approach?
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Katarzyna Pawińska-Wąsikowska, Małgorzata Czogała, Karolina Bukowska-Strakova, Marta Surman, Monika Rygielska, Teofila Książek, Beata Sadowska, Agnieszka Pac, Jolanta Skalska-Sadowska, Magdalena Samborska, Jacek Wachowiak, Małgorzata Ciebiera, Radosław Chaber, Renata Tomaszewska, Tomasz Szczepański, Karolina Zielezińska, Tomasz Urasiński, Małgorzata Moj-Hackemer, Krzysztof Kałwak, Marta Kozłowska, Ninela Irga-Jaworska, Barbara Sikorska-Fic, Paweł Łaguna, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Anna Fałkowska, Katarzyna Drabko, Katarzyna Bobeff, Wojciech Młynarski, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Natalia Bartoszewicz, Jan Styczyński, Katarzyna Machnik, Agnieszka Mizia-Malarz, Walentyna Balwierz, and Szymon Skoczeń
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acute myeloid leukemia ,adolescents ,young adults ,children ,treatment-related mortality ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The reports of studies that compare the survival of adolescents and young adults with younger children with acute myeloid leukemia (AML) are contradictory. Patients and Methods: We retrospectively analyzed 220 AML patients aged 0–18 years treated in pediatric oncologic centers in Poland from 2015 to 2022. The evaluated group included 31 infants (below 1 year), 91 younger children (1–9.9 years), 59 older children (10–14.9 years), and 39 adolescents (15–18 years). Results: A 5-year overall survival for adolescents was not significantly inferior compared to younger and older children (74.3 ± 7.6% vs. 80.5 ± 4.4% vs. 77.9 ± 5.1, p = 0.243). However, relapse-free survival was lower in adolescents compared to younger children (76.5 ± 7.8% vs. 65.7 ± 9.0%, p = 0.049), and treatment-related mortality tended to be higher (10.3% vs. 4.4%, p = 0.569). In the univariate analysis, high-risk genetics [HR, 2.0 (95% CI 1.1–3.6; p = 0.014)] and a leukocyte count at diagnosis above 100,000/μL [HR, 2.4 (95% CI 1.3–4.6; p = 0.004)] were found to be unfavorable prognostic factors for survival. Conclusions: Although we have not found that age over 15 years is an unfavorable factor for overall survival, the optimal approach to therapy in adolescents, as in other age groups, is to adjust the intensity of therapy to individual genetic risk and introduce targeted therapies when indicated.
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- 2024
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11. Anti-PD-1 Therapy in Advanced Pediatric Malignancies in Nationwide Study: Good Outcome in Skin Melanoma and Hodgkin Lymphoma
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Agata Marjańska, Katarzyna Pawińska-Wąsikowska, Aleksandra Wieczorek, Monika Drogosiewicz, Bożenna Dembowska-Bagińska, Katarzyna Bobeff, Wojciech Młynarski, Katarzyna Adamczewska-Wawrzynowicz, Jacek Wachowiak, Małgorzata A. Krawczyk, Ninela Irga-Jaworska, Jadwiga Węcławek-Tompol, Krzysztof Kałwak, Małgorzata Sawicka-Żukowska, Maryna Krawczuk-Rybak, Anna Raciborska, Agnieszka Mizia-Malarz, Agata Sobocińska-Mirska, Paweł Łaguna, Walentyna Balwierz, and Jan Styczyński
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nivolumab ,pembrolizumab ,ipilimumab ,anti-PD-1 ,immune checkpoint inhibitor ,pediatric cancer ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background/aim: The role of immune checkpoint inhibitors (ICIs; anti-PD1) in the treatment of childhood cancers is still evolving. The aim of this nationwide retrospective study was to assess the safety and effectiveness of ICIs used in a group of 42 patients, with a median age of 13.6 years, with various types of advanced malignancies treated in pediatric oncology centers in Poland between 2015 and 2023. Results: The indications for treatment with anti-PD1 were as follows: Hodgkin lymphoma (11); malignant skin melanoma (9); neuroblastoma (8); and other malignancies (14). At the end of follow-up, complete remission (CR) was observed in 37.7% (15/42) of children and disease stabilization in 9.5% (4/42), with a mean survival 3.6 (95% CI = 2.6–4.6) years. The best survival (OS = 1.0) was observed in the group of patients with Hodgkin lymphoma. For malignant melanoma of the skin, neuroblastoma, and other rare malignancies, the estimated 3-year OS values were, respectively, 0.78, 0.33, and 0.25 (p = 0.002). The best progression-free survival value (0.78) was observed in the group with malignant melanoma. Significantly better effects of immunotherapy were confirmed in patients ≥ 14 years of age and good overall performance ECOG status. Severe adverse events were observed in 30.9% (13/42) patients.
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- 2024
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12. S111: TREATMENT OF POST-TRANSPLANT RELAPSE IN CHILDREN, ADOLESCENTS AND YOUNG ADULTS WITH BCP ALL USING CD19-CAR-T: A EUROPEAN RETROSPECTIVE ANALYSIS OF REAL-WORLD DATA
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Peter Bader, Anna Alsonso, Andishe Attarbaschi, Nicole Bodmer, Halvard Bonig, Saskia Burridge, Jean-Pierre Bourquin, Veit Bücklein, Gunnar Cario, Macarena Oporto Espuelas, Tobias Feuhtinger, Anna Fuereder, Julia Hauer, Martin Hutter, Krzysztof Kałwak, Annette Künkele, Roland Meisel, Monika Mielcarek-Siedziuk, Ingo Müller, Sara Napolitano, Olaf Penack, Susana Rives, Claudia Rossig, Arend von Stackelberg, Andrea Jarisch, Sara Ghorashian, and Adriana Balduzzi
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Diseases of the blood and blood-forming organs ,RC633-647.5 - Published
- 2023
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13. The impact of NKG2A and NKG2D receptors and HLA-E and MICA ligands polymorphisms on post-transplant complications after paediatric allogeneic HSCT: a single-centre experience
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Jagoda Siemaszko, Marek Ussowicz, Blanka Rybka, Renata Ryczan-Krawczyk, Krzysztof Kałwak, and Katarzyna Bogunia-Kubik
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HSC ,NK cells ,NK cell receptors ,paediatric HSCT patients ,MICA ,HLA-E ,Genetics ,QH426-470 - Abstract
Introduction: Natural Killer cells are the first subpopulation of lymphocytes that reconstitute after allogeneic haematopoietic stem cell transplantation (HSCT). Their activity is regulated by various receptor-ligand interactions, including stimulation of the activating NKG2D receptor by the MICA molecule, and inhibitory NKG2A receptor interacting with the HLA-E. In this study the research effort focused on the effect of selected NKG2A and NKG2D receptors and their ligands (HLA-E and MICA molecules) polymorphisms that may affect the pathomechanisms of post-transplant complications after HSCT in children.Methods: One hundred donor-recipient pairs from a single paediatric transplantation centre were investigated. Altogether six single nucleotide substitutions (NKG2A rs7301582; NKG2D rs1049174, rs1154831; HLA-E rs1264457; MICA rs1051792, rs1063635) were genotyped, and the influence of polymorphisms was analysed on acute and chronic graft-versus-host disease (GvHD), cytomegalovirus (CMV) infection incidence, disease relapse and survival.Results: The distribution of the evaluated polymorphisms did not differ between patients and their donors. The results showed a significant influence of HLA-E rs1264457 polymorphism in patients’ HLA-E*01:01 allele, which was associated with increased risk of CMV infection (p = 0.050), especially in children positive for CMV IgG before transplantation (p = 0.001). Furthermore, the effect of HLA-E*01:01 allele on CMV infections was more evident in children above the age of 7 years (p = 0.031). Strong tendencies (0.05 < p < 0.10) towards association with the risk of acute GvHD were also observed for the NKG2A or MICA polymorphisms of the recipients. In addition, NKG2D rs1154831 AA and MICA rs1063635 GG might play a protective role as they were not present in any recipient who died after transplantation.Conclusion: In summary, there is emerging evidence that genotyping results of NKG2 receptors and their ligands, may have prognostic value for the outcome of paediatric allogeneic HSCT, but more extensive studies performed on larger groups of donors and transplant recipients are required to confirm these observations.
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- 2023
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14. KIM-1, IL-18, and NGAL, in the Machine Learning Prediction of Kidney Injury among Children Undergoing Hematopoietic Stem Cell Transplantation—A Pilot Study
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Kinga Musiał, Jakub Stojanowski, Justyna Miśkiewicz-Bujna, Krzysztof Kałwak, and Marek Ussowicz
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acute kidney disease ,acute kidney injury ,allogeneic hematopoietic stem cell transplantation ,augmented renal clearance ,hyperfiltration ,random forest classifier ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Children undergoing allogeneic hematopoietic stem cell transplantation (HSCT) are prone to developing acute kidney injury (AKI). Markers of kidney damage: kidney injury molecule (KIM)-1, interleukin (IL)-18, and neutrophil gelatinase-associated lipocalin (NGAL) may ease early diagnosis of AKI. The aim of this study was to assess serum concentrations of KIM-1, IL-18, and NGAL in children undergoing HSCT in relation to classical markers of kidney function (creatinine, cystatin C, estimated glomerular filtration rate (eGFR)) and to analyze their usefulness as predictors of kidney damage with the use of artificial intelligence tools. Serum concentrations of KIM-1, IL-18, NGAL, and cystatin C were assessed by ELISA in 27 children undergoing HSCT before transplantation and up to 4 weeks after the procedure. The data was used to build a Random Forest Classifier (RFC) model of renal injury prediction. The RFC model established on the basis of 3 input variables, KIM-1, IL-18, and NGAL concentrations in the serum of children before HSCT, was able to effectively assess the rate of patients with hyperfiltration, a surrogate marker of kidney injury 4 weeks after the procedure. With the use of the RFC model, serum KIM-1, IL-18, and NGAL may serve as markers of incipient renal dysfunction in children after HSCT.
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- 2023
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15. National experience with adenosine deaminase deficiency related SCID in Polish children
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Nel Dąbrowska-Leonik, Barbara Piątosa, Ewa Słomińska, Nadezda Bohynikova, Katarzyna Bernat-Sitarz, Ewa Bernatowska, Beata Wolska-Kuśnierz, Krzysztof Kałwak, Sylwia Kołtan, Anna Dąbrowska, Jolanta Goździk, Marek Ussowicz, and Małgorzata Pac
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adenosine deaminase (ADA) deficiency ,SCID - severe combined immunodeficiency ,ERT (enzyme replacement therapy) ,HSCT = hematopoietic stem cell transplant ,lymphopenia ,Immunologic diseases. Allergy ,RC581-607 - Abstract
IntroductionDeficiency of adenosine deaminase (ADA) manifests as severe combined immunodeficiency (SCID), caused by accumulation of toxic purine degradation by-products. Untreated patients develop immune and non-immune symptoms with fatal clinical course. According to ESID and EBMT recommendations enzyme replacement therapy (ERT) should be implemented as soon as possible to stabilize the patient’s general condition, normalize transaminases, treat pulmonary proteinosis, bone dysplasia, and protect from neurological damage. Hematopoietic stem cell transplantation (HSCT) from a matched related donor (MRD) is a treatment of choice. In absence of such donor, gene therapy (GT) should be considered. HSCT from a matched unrelated donor (MUD) and haploidentical hematopoietic stem cell transplantation (hHSCT) are associated with worse prognosis.Material and methodsWe retrospectively evaluated the clinical course and results of biochemical, immunological and genetic tests of 7 patients diagnosed in Poland with ADA deficiency since 2010 to 2022.ResultsAll patients demonstrated lymphopenia affecting of T, B and NK cells. Diagnosis was made on the basis of ADA activity in red blood cells and/or genetic testing. Patients manifested with various non-immunological symptoms including: lung proteinosis, skeletal dysplasia, liver dysfunction, atypical hemolytic-uremic syndrome, and psychomotor development disorders. Five patients underwent successful HSCT: 3 patients from matched unrelated donor, 2 from matched sibling donor, and 1 haploidentical from a parental donor. In 4 patients HSCT was preceded by enzyme therapy (lasting from 2 to 5 months). One patient with multiple organ failure died shortly after admission, before the diagnosis was confirmed. None of the patients had undergone gene therapy.ConclusionsIt is important to diagnose ADA SCID as early as possible, before irreversible multi-organ failure occurs. In Poland HSCT are performed according to international immunological societies recommendations, while ERT and GT are less accessible. Implementation of Newborn Screening (NBS) for SCID in Poland could enable recognition of SCID, including ADA-SCID.
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- 2023
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16. Physical Activity Level and Quality of Life of Children Treated for Malignancy, Depending on Their Place of Residence: Poland vs. the Czech Republic: An Observational Study
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Aleksandra Kowaluk, Katarzyna Siewierska, Marie Choniawkova, Petr Sedlacek, Krzysztof Kałwak, and Iwona Malicka
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oncology ,children ,paediatrics patients ,physical activity ,quality of life ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
This study aimed to assess the level of physical activity (PA) and quality of life of cancer-treated children, depending on their place of residence (Poland vs. the Czech Republic, where incidence and mortality rates of childhood malignancies are similar). A total of 68 school-age children (7–18 years) undergoing oncological treatment were included in this study. This study used the quality of life questionnaire (KIDSCREEN-10) and the HBSC questionnaire. This study showed statistically significant differences in the level of PA between Polish and Czech children. In Poland, 93.75% of children exhibited no weekly physical effort at the level of moderate to vigorous PA. In the Czech Republic, 69.44% of children engaged in PA lasting at least 60 min per day, or at least 1 day weekly. Physically active children engaging in more frequent effort, at least 60 min daily, reported higher physical performance (rho = 0.41), higher energy levels (rho = 0.41), and less mood disturbance (rho = −0.31). Children with good relationships with parents were more likely to engage in submaximal PA and spend less time on stationary games. Our study showed that an appropriate level of PA improves well-being and quality of life. It is crucial to promote attractive PA programs tailored for cancer-treated children.
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- 2023
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17. Characteristics and Outcome of FLT3-ITD-Positive Pediatric Acute Myeloid Leukemia—Experience of Polish Pediatric Leukemia and Lymphoma Study Group from 2005 to 2022
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Małgorzata Czogała, Wojciech Czogała, Katarzyna Pawińska-Wąsikowska, Teofila Książek, Karolina Bukowska-Strakova, Barbara Sikorska-Fic, Paweł Łaguna, Anna Fałkowska, Katarzyna Drabko, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Marta Kozłowska, Ninela Irga-Jaworska, Karolina Zielezińska, Tomasz Urasiński, Natalia Bartoszewicz, Jan Styczyński, Jolanta Skalska-Sadowska, Jacek Wachowiak, Anna Rodziewicz-Konarska, Krzysztof Kałwak, Małgorzata Ciebiera, Radosław Chaber, Agnieszka Mizia-Malarz, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Bobeff, Wojciech Młynarski, Katarzyna Mycko, Wanda Badowska, Renata Tomaszewska, Tomasz Szczepański, Katarzyna Machnik, Natalia Zamorska, Walentyna Balwierz, and Szymon Skoczeń
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FLT3 ,acute myeloid leukemia ,children ,kinase inhibitor ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: The FMS-like tyrosine kinase 3 (FLT3) gene mutated in 10–15% of pediatric acute myeloid leukemia (AML) is associated with an inferior outcome. The aim of the study was to analyze the outcome and characteristics of FLT3-ITD-positive pediatric AML. Methods: We retrospectively analyzed the nationwide pediatric AML database from between 2005 and 2022. FLT3-ITD was found in 54/497 (10.7%) patients with available analysis. Three consecutive treatment protocols were used (AML-BFM 2004 Interim, AML-BFM 2012 Registry, AML-BFM 2019 recommendations). Results: Probabilities of 5-year overall (OS), event-free (EFS) and relapse-free survival were significantly lower in the FLT3-ITD-positive patients compared to FLT3-ITD-negative (0.54 vs. 0.71, p = 0.041; 0.36 vs. 0.59, p = 0.0004; 0.47 vs. 0.70, p = 0.0029, accordingly). An improvement in the outcome was found in the analyzed period of time, with a trend of better survival in patients treated under the AML-BFM 2012 and AML-BFM 2019 protocols compared to the AML-BFM 2004 protocol (5-year EFS 0.52 vs. 0.27, p = 0.069). There was a trend of improved outcomes in patients treated with FLT3 inhibitors (n = 9, 2-year EFS 0.67 vs. 0.33, p = 0.053) and those who received stem cell transplantation (SCT) (n = 26; 5-year EFS 0.70 vs. 0.27, p = 0.059). The co-occurrence of the WT1 mutation had a dismal impact on the prognosis (5-year EFS 0.23 vs. 0.69, p = 0.002), while the NPM1 mutation improved survival (5-year OS 1.0 vs. 0.44, p = 0.036). Conclusions: It seems that SCT and FLT3 inhibitors have a beneficial impact on the prognosis. Additional genetic alterations, like the WT1 and NPM1 mutations, significantly influence the outcome.
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- 2023
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18. Antifungal Drug-Drug Interactions with Commonly Used Pharmaceutics in European Pediatric Patients with Acute Lymphoblastic Leukemia
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Beata Sienkiewicz-Oleszkiewicz, Małgorzata Salamonowicz-Bodzioch, Justyna Słonka, and Krzysztof Kałwak
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acute lymphoblastic leukemia ,antifungal agents ,children ,drug interactions ,liposomal amphotericin B ,Medicine - Abstract
Leukemia is one of the leading childhood malignancies, with acute lymphoblastic leukemia (ALL) being the most common type. Invasive fungal disease is a concerning problem also at pediatric hemato-oncology units. Available guidelines underline the need for antifungal prophylaxis and give recommendations for proper treatment in various clinical scenarios. Nonetheless, antifungal agents are often involved in drug-drug interaction (DDI) occurrence. The prediction of those interactions in the pediatric population is complicated because of the physiological differences in adults, and the lack of pharmacological data. In this review, we discuss the potential DDIs between antifungal agents and commonly used pharmaceutics in pediatric hemato-oncology settings, with special emphasis on the use of liposomal amphotericin B and ALL treatment. We obtained information from Micromedex® and Drugs.com® interaction checking databases and checked the EudraVigilance® database to source the frequency of severe adverse drug reactions that resulted from antifungal drug interactions. Several major DDIs were identified, showing a favorable safety profile of echinocandins and liposomal amphotericin B. Interestingly, although there are numerous available drug interaction checking tools facilitating the identification of potential serious DDIs, it is important to use more than one tool, as the presented searching results may differ between particular checking programs.
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- 2023
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19. Short- and long-term outcome of allogeneic stem cell transplantation in infants: A single-center experience over 20 years
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Justyna Miśkiewicz-Bujna, Izabella Miśkiewicz-Migoń, Zofia Szmit, Dawid Przystupski, Monika Rosa, Anna Król, Krzysztof Kałwak, Marek Ussowicz, and Ewa Gorczyńska
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allogeneic ,hematopoietic (stem) cell transplantation (HCT) ,infant-age ,neurological complications ,sequelae ,Pediatrics ,RJ1-570 - Abstract
IntroductionAllogeneic hematopoietic stem cell transplantation (allo-HSCT) is a treatment method for a wide range of malignant and non-malignant diseases. Infants constitute a distinct patient group, especially due to their organ immaturity and differences in drug metabolism. The present paper aims to analyse the short- and long-term outcomes after allo-HSCT in infants.Material and methodsIn the study period, 67 patients under 12 months of age underwent allo-HSCT. This study is a retrospective analysis of patient medical records, in the form of paper and electronic documentation.ResultsThe probability of 5-year OS was 69% and 72% in patients with malignant and non-malignant diseases, respectively. The allo-HSCT from a matched donor was associated with improved OS in comparison to haploidentical donor (0.8 vs. 0.58%, p = 0.0425). The overall incidence of acute graft-vs.-host disease (aGVHD) was 59.3%, and grade III–IV aGVHD was diagnosed in 23% of patients. The 100-day non-relapse mortality (NRM) in the study cohort was 17.9%, while the 5-year NRM was 26.9%. Among the causes of NRM, infections occurred in 83.3% of patients, and aGVHD in 16.3% of individuals. Twenty-two children (32.8%) required hospitalization in the pediatric intensive care unit (PICU). The median length of PICU hospitalization was 6 days (range 1 to 12 days). Late sequelae diagnosed during post-transplant surveillance included ocular disorders in 26.8% of patients, cardiac complications in 4.4%, as well as endocrinopathy with short stature (
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- 2022
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20. Pediatric Acute Myeloid Leukemia Post Cytotoxic Therapy—Retrospective Analysis of the Patients Treated in Poland from 2005 to 2022
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Małgorzata Czogała, Wojciech Czogała, Katarzyna Pawińska-Wąsikowska, Teofila Książek, Karolina Bukowska-Strakova, Barbara Sikorska-Fic, Paweł Łaguna, Jolanta Skalska-Sadowska, Jacek Wachowiak, Anna Rodziewicz-Konarska, Małgorzata Moj-Hackemer, Krzysztof Kałwak, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Anna Fałkowska, Katarzyna Drabko, Marta Kozłowska, Ninela Irga-Jaworska, Katarzyna Bobeff, Wojciech Młynarski, Renata Tomaszewska, Tomasz Szczepański, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Katarzyna Mycko, Wanda Badowska, Karolina Zielezińska, Tomasz Urasiński, Natalia Bartoszewicz, Jan Styczyński, Walentyna Balwierz, and Szymon Skoczeń
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acute myeloid leukemia post cytotoxic therapy ,children ,secondary malignancy ,therapy-related ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Acute P./myeloid leukemia post cytotoxic therapy (AML-pCT) is rare complication of cancer treatment in childhood. The objective of the study was to identify clinical characteristics and provide an analysis of the outcomes in pediatric AML-pCT. We retrospectively analyzed the data of 40 children with AML-pCT, treated from 2005 to 2020 within the Polish Pediatric Leukemia and Lymphoma Study Group. The most common primary malignancies were acute lymphoblastic leukemia (32.5%) and brain tumors (20%). The median latency period was 2.9 years (range: 0.7–12.9). Probabilities of overall (OS), event-free (EFS), and relapse-free survival (RFS) in the whole cohort were 0.49 ± 0.08, 0.43 ± 0.08, and 0.64 ± 0.10, respectively. Significant improvements in outcomes were observed in patients treated from 2015–2022 (two induction cycles followed by stem cell transplantation—SCT in 69% of patients) compared to 2005–2014 (four induction cycles followed by SCT in 49% of patients). The probability of EFS increased from 0.30 ± 0.10 to 0.67 ± 0.12 (p = 0.07) and RFS increased from 0.46 ± 0.11 to 1.0 (p = 0.01). The poorest outcome (OS and EFS 0.25 ± 0.20) was in AML post brain tumor, mainly due to deaths from toxicities. To conclude, treatment results achieved in patients with AML-pCT treated from 2015–2022, with two induction cycles followed by immediate SCT, were better than those reported by other authors, and comparable to the results in de novo AML.
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- 2023
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21. COVID-19 mRNA Vaccine Tolerance and Immunogenicity in Hematopoietic Stem Cell Transplantation Recipients Aged 5–11 Years Old–Non-Randomized Clinical Trial
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Agnieszka Matkowska-Kocjan, Joanna Owoc-Lempach, Kamila Ludwikowska, Filip Szenborn, Natalia Moskwa, Katarzyna Kurek, Krzysztof Kałwak, Leszek Szenborn, and Marek Ussowicz
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COVID-19 ,vaccinations ,HSCT ,children ,Medicine - Abstract
The SARS-CoV-2 pandemic had a devastating impact on the world’s population in the years 2020–2022. The rapid development of vaccines enabled a reduction in the mortality and morbidity of COVID-19, but there are limited data about their effects on immunocompromised children. The aim of this prospective study was to evaluate the safety and efficacy of the mRNA BNT162b2 (Pfizer/Biontech) vaccine in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients. Material and methods: Two cohorts of 34 children after allo-HSCT and 35 healthy children aged 5–11 years were vaccinated with two doses of the mRNA BNT162b2 (10 µg) vaccine. All children were evaluated for adverse effects with electronic surveys and the immunogenicity of the vaccine was assessed with anti-SARS-CoV-2 IgG titer measurements. Results: All reported adverse events (AEs) were classified as mild. The most common AE was pain at the injection site. All the other AEs (both local and systemic) were rarely reported (2 years of age after HSCT who did not receive immunosuppressive treatment presented excellent antibody production after two doses of the vaccine, but children on immunosuppression may require a more intense vaccination schedule.
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- 2023
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22. Case Report: Liver as a Source of Hematopoietic Stem Cells After Liver Transplantation Following Hematopoietic Stem Cell Transplantation
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Tomasz Jarmoliński, Monika Rosa, Blanka Rybka, Renata Ryczan-Krawczyk, Kornelia Gajek, Katarzyna Bogunia-Kubik, Maja Klaudel-Dreszler, Piotr Czubkowski, Piotr Kaliciński, Joanna Teisseyre, Marek Stefanowicz, Ewa Gorczyńska, Krzysztof Kałwak, and Marek Ussowicz
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Fanconi anemia ,liver transplantation ,pediatric ,hematopoiesis ,graft-versus-host disease (GVHD) ,Pediatrics ,RJ1-570 - Abstract
We report a child with Fanconi anemia who, after hematopoietic stem cell transplantation (HSCT) complicated by acute graft-versus-host disease (GVHD), underwent orthotopic liver transplantation (OLT). Approximately 1 month after OLT, the presence of third-party genetic material from the liver donor was noted and in the next few weeks, the chimerism assessment revealed 100% liver donor leukocytes in the peripheral blood. The rapidly progressing GVHD with gut involvement resulted in patient’s death 6 months after OLT. The liver can act as a clinically significant source of hematopoietic stem cells, and the liver donor’s young age must be emphasized as potentially predisposing to this phenomenon. Transfer of OLT hematopoietic stem cells may not have clinical significance unless the patient is not immunocompetent or develops liver-transplantation associated GVHD, that can result in lymphocyte mediated elimination of original hematopoiesis. Patients with preexisting immunity disorder (such as primary or secondary immunodeficiency) might require intensified immunosuppressive therapy in peritransplant period as a prevention of liver-transplantation associated GVHD. Close monitoring of hematopoietic chimerism after OLT is warranted in patients at risk, because cytopenia or OLT hematopoiesis can reflect subclinical GVHD and further studies are necessary to elucidate this phenomenon.
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- 2022
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23. Blinatumomab Prior to CAR-T Cell Therapy—A Treatment Option Worth Consideration for High Disease Burden
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Paweł Marschollek, Karolina Liszka, Monika Mielcarek-Siedziuk, Blanka Rybka, Renata Ryczan-Krawczyk, Anna Panasiuk, Igor Olejnik, Jowita Frączkiewicz, Iwona Dachowska-Kałwak, Agnieszka Mizia-Malarz, Tomasz Szczepański, Wojciech Młynarski, Jan Styczyński, Katarzyna Drabko, Grażyna Karolczyk, Ewa Gorczyńska, Jan Maciej Zaucha, and Krzysztof Kałwak
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blinatumomab ,children ,BCP-ALL ,CAR-T cell therapy ,bridging therapy ,hematopoietic stem cell transplantation ,Biology (General) ,QH301-705.5 - Abstract
The optimal bridging therapy before CAR-T cell infusion in pediatric relapsed or refractory B-cell precursor acute lymphoblastic leukemia (r/r BCP-ALL) still remains an open question. The administration of blinatumomab prior to CAR-T therapy is controversial since a potential loss of CD19+ target cells may negatively impact the activation, persistence, and, as a consequence, the efficacy of subsequently used CAR-T cells. Here, we report a single-center experience in seven children with chemorefractory BCP-ALL treated with blinatumomab before CAR-T cell therapy either to reduce disease burden before apheresis (six patients) or as a bridging therapy (two patients). All patients responded to blinatumomab except one. At the time of CAR-T cell infusion, all patients were in cytological complete remission (CR). Four patients had low positive PCR-MRD, and the remaining three were MRD-negative. All patients remained in CR at day +28 after CAR-T infusion, and six out of seven patients were MRD-negative. With a median follow-up of 497 days, four patients remain in CR and MRD-negative. Three children relapsed with CD19 negative disease: two of them died, and one, who previously did not respond to blinatumomab, was successfully rescued by stem cell transplant. To conclude, blinatumomab can effectively lower disease burden with fewer side effects than standard chemotherapeutics. Therefore, it may be a valid option for patients with high-disease burden prior to CAR-T cell therapy without clear evidence of compromising efficacy; however, further investigations are necessary.
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- 2022
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24. First hematopoietic stem cell transplantation in a child with late infantile Krabbe disease in Poland
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Izabella Miśkiewicz-Migoń, Justyna Miśkiewicz-Bujna, Monika Mielcarek-Siedziuk, Jowita Frączkiewicz, Ewa Gorczyńska, and Krzysztof Kałwak
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hematopoietic stem cell transplantation ,globoid cell leukodystrophy ,krabbe disease ,lysosomal storage disorders. ,Pediatrics ,RJ1-570 - Abstract
Krabbe disease (KD) is a lysosomal storage disorder, caused by a deficiency of galactocerebrosidase (GALC) or a mutation in the prosaposin gene, which leads to psychosine accumulation. Consequently, demyelination and degradation of the nervous system occur. Newborns with early infantile Krabbe disease usually present with poor feeding, irritability, hypertonicity, deafness and visual impairment. They usually die, unless transplanted with hematopoietic stem cells (HSC) during the 1st month of life. Patients with late form KD have heterogeneous symptoms, like ataxia or spastic paresis followed by slow progression. Therapeutic options are limited and hematopoietic stem cell transplantation (HSCT) remains the only life-saving method. In this report, we describe the first HSCT in late-infantile Krabbe disease in Poland. The post-transplant period was complicated by graft versus host disease (GvHD), veno-occlusive disease (VOD), mucositis and impairment of renal function. The 5-year follow-up was uneventful, confirming clinical efficacy of the HSCT.
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- 2021
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25. Viral Infection Profile in Children Treated for Acute Lymphoblastic Leukemia—Results of Nationwide Study
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Joanna Zawitkowska, Katarzyna Drabko, Krzysztof Czyżewski, Magdalena Dziedzic, Kamila Jaremek, Patrycja Zalas-Więcek, Anna Szmydki-Baran, Łukasz Hutnik, Michał Matysiak, Wojciech Czogała, Walentyna Balwierz, Iwona Żak, Małgorzata Salamonowicz-Bodzioch, Bernarda Kazanowska, Grażyna Wróbel, Krzysztof Kałwak, Renata Tomaszewska, Tomasz Szczepański, Olga Zając-Spychała, Jacek Wachowiak, Marcin Płonowski, Maryna Krawczuk-Rybak, Aleksandra Królak, Tomasz Ociepa, Tomasz Urasiński, Filip Pierlejewski, Wojciech Młynarski, Justyna Urbańska-Rakus, Katarzyna Machnik, Sonia Pająk, Wanda Badowska, Tomasz Brzeski, Katarzyna Mycko, Hanna Mańko-Glińska, Agnieszka Urbanek-Dądela, Grażyna Karolczyk, Agnieszka Mizia-Malarz, Weronika Stolpa, Katarzyna Skowron-Kandzia, Jakub Musiał, Radosław Chaber, Ninela Irga-Jaworska, Ewa Bień, and Jan Styczyński
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viral infection ,acute lymphoblastic leukemia ,chemotherapy ,children ,Medicine - Abstract
Viral infections can be a serious complication of therapy in children with acute lymphoblastic leukemia (ALL). In this study, we focused on the incidence and the profile of viral infection in children with ALL treated in 17 pediatric oncology centers in Poland in the two-year periods of 2018–2019 and 2020–2021. We also compared the frequency of viral infections in 2018–2019 to that in 2020–2021. In 2020–2021, a total of 192 children with ALL had a viral infection during intensive chemotherapy. A total number of 312 episodes of viral infections were diagnosed. The most common infections detected in the samples were: COVID-19 (23%), rhinovirus (18%), and respiratory syncytial virus (14%). COVID-19 and BK virus infections were the reason for the death 1% of all patients. In 2018–2019, a total of 53 ALL patients who had a viral infection were reported and 72 viral events were observed, mainly adenovirus (48.6%), rotavirus (31.9%), and herpes zoster (8.3%). No deaths were reported during this period. The cumulative incidence of viral infections in 2018–2019 was 10.4%, while for 2020–2021, it was 36.7%. In conclusion, a high incidence of COVID-19 infection was observed among pediatric patients with ALL in Poland. The mortality rate in our material was low. The viral profile in ALL children undergoing chemotherapy can be useful for clinicians to improve prophylactic and therapeutic strategies.
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- 2022
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26. The Impact of High CMV Viral Load and Refractory CMV Infection on Pediatric HSCT Recipients with Underlying Non-Malignant Disorder
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Zofia Szmit, Jowita Frączkiewicz, Małgorzata Salamonowicz-Bodzioch, Anna Król, Marek Ussowicz, Monika Mielcarek-Siedziuk, Karolina Liszka, Paweł Marschollek, Ewa Gorczyńska, and Krzysztof Kałwak
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hematopoietic stem cell transplantation ,infectious complications ,cytomegalovirus ,pediatric ,Medicine - Abstract
Hematopoietic stem cell transplantation (HSCT) is a curative therapy for an increasing number of nonmalignant indications. Its use is restricted by severe transplant-related complications, including CMV infection; despite various prophylactic and therapeutic strategies, CMV reactivation has remarkable morbidity and mortality. The analysis included 94 children with nonmalignant disorder who underwent allogeneic HSCT in the Department of Pediatric Hematology, Oncology, and Bone Marrow Transplantation in Wrocław during years 2016–2020. Twenty-seven (29%) children presented with CMV infection, including ten (10/27; 37%) with high level CMV viremia (10,000 copies/mL). Six patients experienced subsequent CMV reactivation. The first-line ganciclovir-based (GCV) treatment was insufficient in 40% (11/27) of children. Overall survival (OS) was significantly lower in children with high CMV viremia compared to those with low levels/no CMV [1yrOS High CMV = 0.80 (95% CI 0.41–0.95) vs. 1yrOS others = 0.96 (95% CI 0.89–0.99)]. Similarly, patients with resistant and recurrent infections had greater risk of death. CMV reactivation at any level relevantly prolonged the hospital stay. CMV reactivation with high viremia load and resistant/recurrent CMV infections lead to a significant decrease in OS in children with nonmalignant disorders treated with HSCT. Our data proves there is an urgent need to introduce an effective anti-CMV prophylaxis in this cohort of patients.
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- 2022
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27. Comprehensive Investigation of miRNome Identifies Novel Candidate miRNA-mRNA Interactions Implicated in T-Cell Acute Lymphoblastic Leukemia
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Małgorzata Dawidowska, Roman Jaksik, Monika Drobna, Bronisława Szarzyńska-Zawadzka, Maria Kosmalska, Łukasz Sędek, Ludomiła Machowska, Anna Lalik, Monika Lejman, Marek Ussowicz, Krzysztof Kałwak, Jerzy R. Kowalczyk, Tomasz Szczepański, and Michał Witt
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive malignancy originating from T-cell precursors. The genetic landscape of T-ALL has been largely characterized by next-generation sequencing. Yet, the transcriptome of miRNAs (miRNome) of T-ALL has been less extensively studied. Using small RNA sequencing, we characterized the miRNome of 34 pediatric T-ALL samples, including the expression of isomiRs and the identification of candidate novel miRNAs (not previously annotated in miRBase). For the first time, we show that immunophenotypic subtypes of T-ALL present different miRNA expression profiles. To extend miRNome characteristics in T-ALL (to 82 T-ALL cases), we combined our small RNA-seq results with data available in Gene Expression Omnibus. We report on miRNAs most abundantly expressed in pediatric T-ALL and miRNAs differentially expressed in T-ALL versus normal mature T-lymphocytes and thymocytes, representing candidate oncogenic and tumor suppressor miRNAs. Using eight target prediction algorithms and pathway enrichment analysis, we identified differentially expressed miRNAs and their predicted targets implicated in processes (defined in Gene Ontology and Kyoto Encyclopedia of Genes and Genomes) of potential importance in pathogenesis of T-ALL, including interleukin-6–mediated signaling, mTOR signaling, and regulation of apoptosis. We finally focused on hsa-mir-106a-363 cluster and functionally validated direct interactions of hsa-miR-20b-5p and hsa-miR-363-3p with 3′ untranslated regions of their predicted targets (PTEN, SOS1, LATS2), overrepresented in regulation of apoptosis. hsa-mir-106a-363 is a paralogue of prototypic oncogenic hsa-mir-17-92 cluster with yet unestablished role in the pathogenesis of T-ALL. Our study provides a firm basis and data resource for functional analyses on the role of miRNA-mRNA interactions in T-ALL.
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- 2019
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28. Advances in the First Line Treatment of Pediatric Acute Myeloid Leukemia in the Polish Pediatric Leukemia and Lymphoma Study Group from 1983 to 2019
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Małgorzata Czogała, Walentyna Balwierz, Katarzyna Pawińska-Wąsikowska, Teofila Książek, Karolina Bukowska-Strakova, Wojciech Czogała, Barbara Sikorska-Fic, Michał Matysiak, Jolanta Skalska-Sadowska, Jacek Wachowiak, Małgorzata Moj-Hackemer, Krzysztof Kałwak, Katarzyna Muszyńska-Rosłan, Maryna Krawczuk-Rybak, Dominik Grabowski, Jerzy Kowalczyk, Lucyna Maciejka-Kembłowska, Ninela Irga-Jaworska, Katarzyna Bobeff, Wojciech Młynarski, Renata Tomaszewska, Tomasz Szczepański, Agnieszka Chodała-Grzywacz, Grażyna Karolczyk, Agnieszka Mizia-Malarz, Katarzyna Mycko, Wanda Badowska, Karolina Zielezińska, Tomasz Urasiński, Justyna Urbańska-Rakus, Małgorzata Ciebiera, Radosław Chaber, Natalia Bartoszewicz, Mariusz Wysocki, and Szymon Skoczeń
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pediatric acute myeloid leukemia ,survival ,management ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Background: From 1983, standardized therapeutic protocols for pediatric acute myeloid leukemia (AML) based on the BFM group experience were introduced in Poland. We retrospectively analyzed the results of pediatric AML treatment in Poland from 1983 to 2019 (excluding promyelocytic, therapy-related, biphenotypic, and Down syndrome AML). Methods: The study included 899 children suffering from AML treated with the following: AML-PPPLBC 83 (1983–1993, n = 187), AML-PPGLBC 94 (1994–1997, n = 74), AML-PPGLBC 98 (1998–2004, n = 151), AML-BFM 2004 Interim (2004–2015, n = 356), and AML-BFM 2012 (2015–2019, n = 131). Results: The probability of three-year overall survival was 0.34 ± 0.03, 0.37 ± 0.05, 0.54 ± 0.04, 0.67 ± 0.03, and 0.75 ± 0.05; event-free survival was 0.31 ± 0.03, 0.34 ± 0.05, 0.44 ± 0.04, 0.53 ± 0.03, and 0.67 ± 0.05; and relapse-free survival was 0.52 ± 0.03, 0.65 ± 0.05, 0.58 ± 0.04, 0.66 ± 0.03, and 0.78 ± 0.05, respectively, in the subsequent periods. A systematic reduction of early deaths and deaths in remission was achieved, while the percentage of relapses decreased only in the last therapeutic period. Surprisingly good results were obtained in the group of patients treated with AML-BFM 2012 with unfavorable genetic abnormalities like KMT2A-MLLT10/t(10;11)(p12;q23) and DEK-NUP214/t(6;9)(p23;q24), while unsatisfactory outcomes were found in the patients with FLT3-ITD. Conclusions: The use of standardized, systematically modified therapeutic protocols, with the successive consideration of genetic prognostic factors, and advances in supportive care led to a significant improvement in AML treatment outcomes over the last 40 years.
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- 2021
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29. Fludarabine–Cyclophosphamide-Based Conditioning with Antithymocyte Globulin Serotherapy Is Associated with Durable Engraftment and Manageable Infections in Children with Severe Aplastic Anemia
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Małgorzata Salamonowicz-Bodzioch, Monika Rosa, Jowita Frączkiewicz, Ewa Gorczyńska, Katarzyna Gul, Małgorzata Janeczko-Czarnecka, Tomasz Jarmoliński, Krzysztof Kałwak, Monika Mielcarek-Siedziuk, Igor Olejnik, Joanna Owoc-Lempach, Anna Panasiuk, Kornelia Gajek, Blanka Rybka, Renata Ryczan-Krawczyk, and Marek Ussowicz
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aplastic anemia ,fludarabine–cyclophosphamide-based conditioning ,ATG serotherapy ,hematopoietic cell transplantation ,children ,viral infections ,Medicine - Abstract
Severe aplastic anemia (SAA) is a bone marrow failure syndrome that can be treated with hematopoietic cell transplantation (HCT) or immunosuppressive (IS) therapy. A retrospective cohort of 56 children with SAA undergoing transplantation with fludarabine–cyclophosphamide–ATG-based conditioning (FluCyATG) was analyzed. The endpoints were overall survival (OS), event-free survival (EFS), cumulative incidence (CI) of graft versus host disease (GVHD) and CI of viral replication. Engraftment was achieved in 53/56 patients, and four patients died (two due to fungal infection, and two of neuroinfection). The median time to neutrophil engraftment was 14 days and to platelet engraftment was 16 days, and median donor chimerism was above 98%. The overall incidence of acute GVHD was 41.5%, and that of grade III-IV acute GVHD was 14.3%. Chronic GVHD was diagnosed in 14.2% of children. The probability of 2-year GVHD-free survival was 76.1%. In the univariate analysis, a higher dose of cyclophosphamide and previous IS therapy were significant risk factors for worse overall survival. Episodes of viral replication occurred in 33/56 (58.9%) patients, but did not influence OS. The main advantages of FluCyATG include early engraftment with a very high level of donor chimerism, high overall survival and a low risk of viral replication after HCT.
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- 2021
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30. The Impact of Allogeneic Hematopoietic Stem Cell Transplantation on Kidney Function in Children—A Single Center Experience
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Kinga Musiał, Krzysztof Kałwak, and Danuta Zwolińska
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acute kidney injury ,estimated glomerular filtration rate ,hyperfiltration ,pRIFLE criteria ,Medicine - Abstract
Background: Knowledge about the impact of allogeneic hematopoietic stem cell transplantation (alloHSCT) on renal function in children is still limited. Objectives: The aim of the study was to evaluate kidney function in children undergoing alloHSCT, with special focus on differences between patients transplanted due to oncological and non-oncological indications. Materials and Methods: The data of 135 children undergoing alloHSCT were analyzed retrospectively. The serum creatinine and estimated glomerular filtration rate (eGFR) values were estimated before transplantation at 24 h; 1, 2, 3, 4 and 8 weeks; and 3 and 6 months after alloHSCT. Then, acute kidney injury (AKI) incidence was assessed. Results: Oncological children presented with higher eGFR values and more frequent hyperfiltration rates than non-oncological children before alloHSCT and until the 4th week after transplantation. The eGFR levels rose significantly after alloHSCT, returned to pre-transplant records after 2–3 weeks, and decreased gradually until the 6th month. AKI incidence was comparable in oncological and non-oncological patients. Conclusions: Children undergoing alloHSCT due to oncological and non-oncological reasons demonstrate the same risk of AKI, but oncological patients may be more prone to sustained renal injury. Serum creatinine and eGFR seem to be insufficient tools to assess kidney function in the early post-alloHSCT period, when hyperfiltration prevails, yet they reveal significant differences in long-term observation.
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- 2021
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31. Clusterin as a New Marker of Kidney Injury in Children Undergoing Allogeneic Hematopoietic Stem Cell Transplantation—A Pilot Study
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Kinga Musiał, Monika Augustynowicz, Izabella Miśkiewicz-Migoń, Krzysztof Kałwak, Marek Ussowicz, and Danuta Zwolińska
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acute kidney injury ,cystatin C ,hyperfiltration ,kidney injury molecule (KIM)-1 ,tubular damage ,Medicine - Abstract
Background and aims: The markers of renal damage defining subclinical AKI are not widely used in children undergoing allogeneic hematopoietic stem cell transplantation (alloHSCT). The aim of the study was to evaluate serum and urinary clusterin as indices of kidney injury after alloHSCT in relation to damage (kidney injury molecule (KIM)-1) and functional (cystatin C) markers. Material and methods: Serum and urinary clusterin, KIM-1 and cystatin C concentrations were assessed by ELISA in 27 children before alloHSCT, 24 h, 1, 2, 3 and 4 weeks after alloHSCT and in controls. Results: All parameters were significantly higher in HSCT patients compared to controls even before the transplantation. The serum concentrations increased after HSCT and this rising trend was kept until the third (clusterin) or 4th (KIM-1, cystatin C) week. Urinary clusterin and KIM-1 were elevated until the third week and then decreased yet remained higher than before HSCT. Urinary cystatin C has risen from the second week after HSCT and decreased after the third week but was still higher than before alloHSCT. Conclusions: The features of kidney injury are present even before alloHSCT. Clusterin seems useful in the assessment of subclinical AKI and may become a new early marker of sublethal kidney injury in children.
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- 2020
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32. The presence of the gadolinium-based contrast agent depositions in the brain and symptoms of gadolinium neurotoxicity - A systematic review.
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Cyprian Olchowy, Kamil Cebulski, Mateusz Łasecki, Radosław Chaber, Anna Olchowy, Krzysztof Kałwak, and Urszula Zaleska-Dorobisz
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Medicine ,Science - Abstract
BACKGROUND AND PURPOSE:Gadolinium based contrast agents (GBCAs) are widely used in magnetic resonance imaging, but recently, high signal intensity in the cerebellum structures was reported after repeated administrations of contrast- enhanced magnetic resonance images. The aim of this systematic review was to investigate the association between increased signal intensity in the dentate nucleus and globus pallidus in the brain and repeated administrations of GBCAs. Additionally, we focused on possible short- and long-term consequences of gadolinium use in those patients. METHODS:Systematic review of retrospective investigations in PubMed and Medline was performed in July 2016. Primary outcomes included the presence of increased signal intensity within the dentate nucleus and globus pallidus on unenhanced T1-weighted MR images in patients following administrations of GBCAs. Two independent reviewers were responsible for search and data extraction. RESULTS:25 publications satisfied inclusion criteria (19 magnetic resonance images analyses, 3 case reports; 3 autopsy studies). Magnetic resonance images of 1247 patients with increased signal intensity on unenhanced T1-weighted MR images were analyzed as well as tissue specimens from 27 patients. Signal intensity correlated positively with the exposure to GBCAs and was greater after serial administrations of linear nonionic than cyclic contrast agents. Gadolinium was detected in all tissue examinations. CONCLUSIONS:High signal intensity in the dentate nucleus and globus pallidus on unenhanced T1-weighted magnetic resonance images were associated with previous administration of GBCAs. Signal intensity correlated negatively with stability of contrast agents. Clinical significance of gadolinium deposition in the brain remains unclear. There is a strong need for further research to identify type of gadolinium deposited in the brain as well as to gather knowledge about long-term consequences.
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- 2017
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33. Supplementary figure 2 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
- Abstract
Overall survival of patients with Nijmegen breakage syndrome depending on the time when they were treated due to malignancies: before and after 2000 year.
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- 2023
34. Supplementary figure 1 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
- Abstract
The dynamics of primary cancer incidence among patients with NBS described using the three-stage joint-point model.
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- 2023
35. Supplementary Figure 3 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
- Abstract
Overall survival of patients with Nijmegen breakage syndrome after cancer diagnosis. Patients who underwent HSCT were marked with an asterix.
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- 2023
36. Supplementary Data legend from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
- Abstract
Supplementary Data legend
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- 2023
37. Supplementary Table 1 from Hematopoietic Stem Cell Transplantation Positively Affects the Natural History of Cancer in Nijmegen Breakage Syndrome
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Wojciech Mlynarski, Krystyna Chrzanowska, Hanna Gregorek, Bendik Lund, Jochen Buechner, Johann Greil, Alexandra Kreins, Ewa Wiesik-Szewczyk, Agnieszka Tomaszewska, Sara S. Kilic, Markus G. Seidel, Peter Svec, Mary Eapen, Dmitry Balashov, Michael H. Albert, Sujal Ghosh, Karl-Walter Sykora, Andrew R. Gennery, Eva Hlavackova, Zdenka Krenova, Larysa Kostyuchenko, Elena Deripapa, Natalia Miakova, Alina Fedorova, Jan Styczynski, Jolanta Gozdzik, Sylwia Koltan, Monika Lejman, Katarzyna Drabko, Anna Pieczonka, Marek Ussowicz, Krzysztof Kałwak, Barbara Pietrucha, Barbara Piątosa, Edyta Heropolitanska-Pliszka, Bozena Dembowska-Baginska, Anna Wakulinska, Wojciech Fendler, Agata Pastorczak, and Beata Wolska-Kusnierz
- Abstract
Supplementary Table 1
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- 2023
38. Antimicrobial prophylaxis in adults and children undergoing hematopoietic cell transplantation: 2021 Polish recommendations
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Iwona Hus, Bogusław Machaliński, Mariola Sedzimirska, Jan Maciej Zaucha, Krzysztof Czyżewski, Grzegorz Helbig, Katarzyna Drabko, Adam Fronczak, Olga Zając-Spychała, Ewa Lech-Marańda, Agnieszka Wierzbowska, Krzysztof Kałwak, Agnieszka Druzd-Sitek, Bartłomiej Baumert, Malgorzata Sobczyk-Kruszelnicka, Ewa Lutwin, Dorota Hawrylecka, Katarzyna Smalisz, Tomasz Wróbel, Beata Piątkowska-Jakubas, Kazimierz Hałaburda, Piotr Rzepecki, Marek Hus, Sebastian Giebel, Agnieszka Sobkowiak-Sobierajska, Grzegorz W. Basak, Edyta Cichocka, Aleksandra Krasowska-Kwiecień, Jacek Wachowiak, Anna Czyż, Jan Styczyński, Adam Walter-Croneck, Piotr Boguradzki, Jarosław Dybko, Anna Łojko, Marek Ussowicz, Lidia Gil, Maria Bieniaszewska, Tomasz Szczepański, Jolanta Goździk, Agnieszka Piekarska, and Agnieszka Zaucha-Prażmo
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medicine.medical_specialty ,Hematopoietic cell ,business.industry ,Incidence (epidemiology) ,Hematology ,Guideline ,Antimicrobial ,medicine.disease ,Toxoplasmosis ,Vaccination ,Transplantation ,Leukemia ,Oncology ,Medicine ,business ,Intensive care medicine - Abstract
Infections are still a major reason of morbidity and one of the most common causes of death after hematopoietic cell transplantation (HCT). Antimicrobial prophylaxis plays a crucial role in decreasing non-relapse mortality after HCT. The objective of this guideline paper is presentation of current recommendations of antimicrobial prophylaxis for children and adults after hematopoietic cell transplantation, prepared in cooperation of Polish scientific hematological societies. Recommendations were prepared by the working group and finally approved by all 23 Polish transplant centers for children and adults. Existing ECIL (European Conference on Infections in Leukemia) and EBMT (European Society of Blood and Marrow Transplantation) guidelines, as well as results of survey performed among all Polish transplant centers, were the background material for working group. Recommendations are presented in sections dedicated to antibacterial prophylaxis, antifungal prophylaxis, antiviral prophylaxis, as well as prophylaxis of toxoplasmosis and infections with Pneumocystis jiroveci. Recommendations on principles of vaccination against COVID-19 are provided based on the state of knowledge in September 2021. A section on guidelines of environmental prophylaxis is also presented.
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- 2021
39. Therapeutic drug monitoring of posaconazole for effective prophylaxis of invasive fungal infections in pediatric patients: a pilot study
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Karolina Liszka, Matylda Resztak, Paulina Zalewska, and Krzysztof Kałwak
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Oncology ,Hematology - Published
- 2021
40. Analysis of incidence and risk factors of the multidrug resistant gastrointestinal tract infection in children and adolescents undergoing allogeneic and autologous hematopoietic cell transplantation: a nationwide study
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Mariusz Wysocki, Krzysztof Czyżewski, Dorota Sęga-Pondel, Bernarda Kazanowska, Jolanta Goździk, Małgorzata Salamonowicz-Bodzioch, Jacek Wachowiak, Ewa Gorczyńska, Jadwiga Węcławek-Tompol, Jerzy Kowalczyk, Magdalena Dziedzic, Krzysztof Kałwak, Jowita Frączkiewicz, Jan Styczyński, Grażyna Wróbel, Marek Ussowicz, Agnieszka Zaucha-Prażmo, and Olga Zając-Spychała
- Subjects
Male ,Autologous transplantation ,medicine.medical_specialty ,Adolescent ,Gastrointestinal Diseases ,medicine.medical_treatment ,Gastrointestinal tract infection ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,Transplantation, Autologous ,Risk Factors ,Drug Resistance, Multiple, Bacterial ,Internal medicine ,medicine ,Humans ,Transplantation, Homologous ,Child ,Malignant diseases ,Hematology ,Clostridioides difficile ,business.industry ,Incidence ,Incidence (epidemiology) ,Infant ,Clostridium difficile ,Bacterial Infections ,General Medicine ,HLA Mismatch ,Pediatric hematology and oncology ,Transplantation ,Multiple drug resistance ,Gram-negative multidrug-resistant bacteria ,Child, Preschool ,Clostridium Infections ,Original Article ,Female ,business - Abstract
The aim of this multi-center study was to evaluate the incidence, clinical course, and risk factors for bacterial multidrug-resistant (MDR) gastrointestinal tract infections (GTI) among children undergoing allogeneic and autologous hematopoietic cell transplantation. A total number of 175 pediatric patients (aged 1–18 years), transplanted between January 2018 and December 2019, who were tested for bacterial colonization/infection were enrolled into this multi-center analysis. Episodes of MDR GTI occurred in 77/175 (44%) patients. In multivariate analysis for higher GTI incidence, the following factors were significant: matched-unrelated donor (MUD) transplantation, HLA mismatch, presence of graft-versus-host disease (GVHD), and gut GVHD. The most common GTI were Clostridium difficile (CDI), multidrug-resistant Enterobacteriaceae (Klebsiella pneumoniae, Escherichia coli extended-spectrum β-lactamase), and Enterococcus HLAR (high-level aminoglycoside-resistant). No MDR GTI–attributed deaths were reported. MDR GTI is a frequent complication after HCT among children, causes prolonged hospitalization, but rarely contributes to death. We identified risk factors of MDR GTI development in children, with focus on GVHD and unrelated donor and HLA mismatch. We conclude that the presence of Clostridiales plays an important anti-inflammatory homeostatic role and decreases incidence of GVHD or alleviate its course.
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- 2021
41. Successful Salvage Haploidentical Bone Marrow Transplantation in a Child With Hemophagocytic Lymphohistiocytosis, When the Previously Matched Unrelated Donor Tested Positive for SARS-CoV-2 on the Day of Stem Cells Collection
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Jakub Musiał, Justyna Miskiewicz-Bujna, Krzysztof Kałwak, Paweł Marschollek, Radosław Chaber, Katarzyna Gul, Wojciech Młynarski, and Karolina Liszka
- Subjects
Male ,Epstein-Barr Virus Infections ,Herpesvirus 4, Human ,Pediatrics ,medicine.medical_specialty ,Transplantation Conditioning ,Coronavirus disease 2019 (COVID-19) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,medicine.medical_treatment ,Graft vs Host Disease ,Hematopoietic stem cell transplantation ,030230 surgery ,Lymphohistiocytosis, Hemophagocytic ,03 medical and health sciences ,0302 clinical medicine ,Full Length Article ,medicine ,Humans ,Bone Marrow Transplantation ,Salvage Therapy ,Transplantation ,Hemophagocytic lymphohistiocytosis ,business.industry ,Stem Cells ,Hematopoietic Stem Cell Transplantation ,COVID-19 ,Matched Unrelated Donor ,medicine.disease ,Apheresis ,Child, Preschool ,Concomitant ,030211 gastroenterology & hepatology ,Surgery ,Stem cell ,Unrelated Donors ,business - Abstract
The coronavirus disease 2019 pandemic has made us adjust our standards and cope with unpredictable circumstances affecting the whole world, including the medical field. A 2-year-old boy diagnosed with X-linked lymphoproliferative disease type 2 with concomitant positive polymerase chain reaction test for Epstein-Barr virus-DNA was admitted to our transplant ward. His treatment scheme had to be modified at the last moment because of a donor disqualification due to a positive polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 just before the apheresis. We decided to perform salvage haploidentical bone marrow transplant from the patient's mother because it was the only possible option. Now, in a 5-month observation period after the hematopoietic stem cell transplantation, our patient is in good general condition. His case convinced us to redirect our approach to transplant procedure preparation. Following the European Group of Blood and Marrow Transplantation recommendations, we use cryopreserved apheresis materials to ensure the availability of stem cell products before the start of a conditioning regimen.
- Published
- 2021
42. Program Racjonalnej Terapii Przeciwgrzybiczej 'WYLECZ!'
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Jan Styczyński, Tomasz Szczepański, Krzysztof Kałwak, Katarzyna Dzierżanowska-Fangrat, Michał Matysiak, and Ninena Irga-Jaworska
- Abstract
Epidemiologia inwazyjnej choroby grzybiczej (IFD) dowodzi rosnącego udziału szczepów opornych, dotyczącego wszystkich klas leków. Odpowiedź na leczenie zależy od wielu czynników, z których część jest modyfikowalna. Takim czynnikiem jest stosowanie zasad racjonalnej terapii przeciwgrzybiczej (zasady zarządzania środkami przeciwgrzybiczymi, AFS). Jest to strategia wprowadzona analogicznie do procesu stosowania zasad racjonalnej terapii przeciwdrobnoustrojowej (zarządzania środkami przeciwdrobnoustrojowymi, AMS). AFS w kontekście ogólnych AMS wyrażone jest w praktyce stosowaniem czynników, określonych jako 6D: diagnosis, debridement/drainage, drug, dose, deescalation, duration. Koncepcja zwracania uwagi na racjonalność działań i unikanie błędów występujących w codziennej praktyce klinicznej ma już swoją historię w medycynie, z początkiem w Stanach Zjednoczonych w 2012 roku w postaci kampanii „Choosing Wisely” („Wybierz mądrze”). Pomimo rozwoju możliwości profilaktyki, diagnostyki i terapii, problem inwazyjnych zakażeń grzybiczych utrzymuje się od wielu lat. W maju 2021 roku, podczas X Zjazdu Polskiego Towarzystwa Onkologii i Hematologii Dziecięcej (PTOHD), pod patronatem PTOHD został ogłoszony Program Racjonalnej Terapii Przeciwgrzybiczej. Cztery główne cele programu to: racjonalne stosowanie leków przeciwgrzybiczych, ograniczenie rosnącej oporności grzybów na leki przeciwgrzybicze, unikanie błędów występujących w praktyce klinicznej oraz edukacja personelu medycznego, pacjentów i rodzin. Koncepcja Programu Racjonalnej Terapii Przeciwgrzybiczej jest oparta na 6 zasadach określonych akronimem WYLECZ!: właściwe rozpoznanie, wyczyszczenie chorego miejsca, lek, efektywna dawka, czas trwania leczenia, zakończenie i podsumowanie terapii.
- Published
- 2021
43. Epidemiology and prevention strategies of SARS-CoV-2 infection in pediatric hematology and oncology centers in Poland
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Wanda Badowska, Krzysztof Kałwak, Wojciech Młynarski, M. Matysiak, Mariusz Wysocki, Jacek Wachowiak, Jolanta Goździk, Agnieszka Mizia-Malarz, Tomasz Szczepański, Anna Raciborska, Bernarda Kazanowska, Elżbieta Adamkiewicz-Drożyńska, Grażyna Karolczyk, Bożenna Dembowska-Bagińska, Jerzy Kowalczyk, Jan Styczyński, Jarosław Peregud-Pogorzelski, Walentyna Balwierz, Maryna Krawczuk-Rybak, Katarzyna Machnik, Tomasz Urasiński, and Radosław Chaber
- Subjects
Oncology ,medicine.medical_specialty ,business.industry ,Incidence (epidemiology) ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Hematology ,Intensive care unit ,Asymptomatic ,law.invention ,law ,Internal medicine ,Human biology ,Epidemiology ,Health care ,Pandemic ,medicine ,medicine.symptom ,business - Abstract
IntroductionEpidemiological analysis of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections in pediatric hematology and oncology (PHO) and hematopoietic cell transplant (HCT) centers in a Polish nationwide study, as well as analysis of the preventive strategies in these centers.MethodsAll of the 18 PHO/HCT centers participated in eight surveys and questionnaires conducted over the first 5 months of the SARS-CoV-2/coronavirus disease 2019 (COVID-19) pandemic in Poland. Epidemiological data were collected at eight regular time points, and the strategy of preventive management was done once after 4 months of the pandemic.ResultsDuring this analyzed period, eight patients were positive for SARS-CoV-2. The estimated incidence of SARS-CoV-2 positivity in Polish PHO/HCT centers was 0.5%. After exclusion of HCT patients (with one patient being infected), the estimated incidence of SARSCoV-2 positivity was between 0.5 and 0.6%. In all but one case, the course of COVID-19 was asymptomatic or mild, and it was moderate in one case. None of them developed SARS or respiratory insufficiency, none of them required treatment in the intensive care unit (ICU), and no patient died due to SARS-CoV-2 infection. As of July 1, parents staying in the hospital together with their children were regularly tested for the virus in 13 centers. Asymptomatic healthcare personnel were regularly tested for the virus in seven centers.ConclusionsThe estimated incidence of SARS-CoV-2 infection among PHO/HCT patients is lower than in Western Europe; however, these patients cannot be regarded as a low-risk group. The low COVID-19 incidence should be interpreted as a result of strictly and continuously implemented detailed preventive measures in the PHO/HCT wards and in hospitals.
- Published
- 2020
44. Severe congenital neutropenia‐associated JAGN1 mutations unleash a calpain‐dependent cell death programme in myeloid cells
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Miriam Entesarian, Magnus Nordenskjöld, Avinash Khandagale, Daniel Nilsson, Krzysztof Kałwak, Teresa Holmlund, Bengt Fadeel, Maja Klaudel-Dreszler, Jan-Inge Henter, and Göran Carlsson
- Subjects
Programmed cell death ,Neutropenia ,Necroptosis ,necroptosis ,HL-60 Cells ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Humans ,Point Mutation ,Congenital Bone Marrow Failure Syndromes ,Myeloid Cells ,Congenital Neutropenia ,Caspase ,calcium ,biology ,Cell Death ,business.industry ,Calpain ,apoptosis ,Membrane Proteins ,Hematology ,medicine.disease ,Haematopoiesis ,Cell culture ,Apoptosis ,030220 oncology & carcinogenesis ,Mutation ,biology.protein ,Cancer research ,business ,030215 immunology ,Research Paper - Abstract
Summary Severe congenital neutropenia (SCN) of autosomal recessive inheritance, also known as Kostmann disease, is characterised by a lack of neutrophils and a propensity for life‐threatening infections. Using whole‐exome sequencing, we identified homozygous JAGN1 mutations (p.Gly14Ser and p.Glu21Asp) in three patients with Kostmann‐like SCN, thus confirming the recent attribution of JAGN1 mutations to SCN. Using the human promyelocytic cell line HL‐60 as a model, we found that overexpression of patient‐derived JAGN1 mutants, but not silencing of JAGN1, augmented cell death in response to the pro‐apoptotic stimuli, etoposide, staurosporine, and thapsigargin. Furthermore, cells expressing mutant JAGN1 were remarkably susceptible to agonists that normally trigger degranulation and succumbed to a calcium‐dependent cell death programme. This mode of cell death was completely prevented by pharmacological inhibition of calpain but unaffected by caspase inhibition. In conclusion, our results confirmed the association between JAGN1 mutations and SCN and showed that SCN‐associated JAGN1 mutations unleash a calcium‐ and calpain‐dependent cell death in myeloid cells.
- Published
- 2020
45. Real-life experiences of letermovir prophylaxis for cytomegalovirus infection in patients after hematopoietic stem cell transplantation : Polish Acute Leukemia Group (PALG) analysis
- Author
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Anna Łojko, Jan Styczyński, Barbara Nasiłowska-Adamska, Joanna Mańko, Krzysztof Kałwak, Patrycja Mensah-Glanowska, Jarosław Dybko, Maciej Majcherek, Anna Czyż, Agnieszka Pluta, and Lidia Gil
- Subjects
Oncology ,Hematology - Published
- 2022
46. A dream that came true: Poland’s first successful CAR-T cell therapy in child with refractory B-cell acute lymphoblastic leukemia (ALL)
- Author
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Monika Mielcarek-Siedziuk, Ewa Gorczyńska, Karolina Liszka, Paweł Marschollek, Krzysztof Kałwak, Joanna Taha, and Blanka Rybka
- Subjects
Oncology ,medicine.medical_specialty ,Observation time ,business.industry ,Lymphoblastic Leukemia ,Treatment method ,Hematology ,B-cell acute lymphoblastic leukemia ,Cell therapy ,Refractory ,hemic and lymphatic diseases ,Internal medicine ,medicine ,CAR T-cell therapy ,business - Abstract
When all of the usually applied treatment methods fail, we have to try something innovative. In this vignette, we present the history of the first in Poland CAR-T cell therapy in a child with refractory B-cell acute lymphoblastic leukemia (ALL). In more than 10 months observation time post infusion the patient remains MRD-free with a chance for long awaited clinical cure.
- Published
- 2021
47. Lymphoblastic predominance of blastic phase in children with chronic myeloid leukaemia treated with imatinib: A report from the I-CML-Ped Study
- Author
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Petr Sedlacek, Krzysztof Kałwak, Arnaud Petit, Chi Kong Li, Joelle Guilhot, Frédéric Millot, Eveline S. J. M. de Bont, Barbara De Moerloose, Meinolf Suttorp, Andrea Biondi, Deborah Meyran, Srdjana Culic, Birgitte Lausen, Université de Paris (UP), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service d'hématologie-immunologie-oncologie pédiatrique [CHU Trousseau], CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CIC - Poitiers, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers)-Direction Générale de l'Organisation des Soins (DGOS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Meyran, D, Petit, A, Guilhot, J, Suttorp, M, Sedlacek, P, De Bont, E, Li, C, Kalwak, K, Lausen, B, Culic, S, de Moerloose, B, Biondi, A, and Millot, F
- Subjects
Male ,0301 basic medicine ,Cancer Research ,[SDV]Life Sciences [q-bio] ,RECOMMENDATIONS ,Tyrosine-kinase inhibitor ,Chronic myeloid leukaemia ,Children ,Accelerated phase ,Blastic phase ,Tyrosine kinase inhibitors ,Haematopoietic stem cell transplantation ,0302 clinical medicine ,hemic and lymphatic diseases ,Cumulative incidence ,Lymphocytes ,Child ,Incidence (epidemiology) ,CHRONIC MYELOGENOUS LEUKEMIA ,3. Good health ,Oncology ,Child, Preschool ,030220 oncology & carcinogenesis ,Imatinib Mesylate ,Female ,PROGNOSTIC DISCRIMINATION ,medicine.drug ,medicine.medical_specialty ,Adolescent ,medicine.drug_class ,Accelerated phase, Blastic phase, Children, Chronic myeloid leukaemia, Haematopoietic stem cell transplantation, Tyrosine kinase inhibitors ,Blastic Phase ,DIAGNOSIS ,03 medical and health sciences ,ADHERENCE ,Leukemia, Myelogenous, Chronic, BCR-ABL Positive ,Internal medicine ,MANAGEMENT ,medicine ,Humans ,neoplasms ,business.industry ,Infant ,Imatinib ,KINASE INHIBITOR ERA ,YOUNGER PATIENTS ,medicine.disease ,RANDOMIZED CML ,Transplantation ,030104 developmental biology ,Blast Crisis ,FOLLOW-UP ,business ,Chronic myelogenous leukemia ,Rare disease - Abstract
Background: Chronic myeloid leukaemia (CML) is a rare disease in children. The frequency and outcome of children evolving to accelerated phase (AP) or blastic phase (BP) under treatment with imatinib is unknown. The aim of the current study is to assess the inci-dence of progression from CML in chronic phase with imatinib frontline in a paediatric setting and describe the management and outcome of these patients.Patients and methods: In the I-CML-Ped Study database (www.clinicaltrials.gov, #NCT01281735), 19 of 339 paediatric patients in chronic phase treated with imatinib in the frontline evolved to CML-AP or CML-BP.Results: With a median follow-up of 38 months (range: 2-190 months), the cumulative inci-dence of progression at 1 and 3 years was 3% (confidence interval [CI] 95%: 1-5%) and 7% (CI 95%: 4-11%), respectively. We observed a large predominance of lymphoid-BP (70%) over myeloid-BP (30%) with imatinib in frontline therapy. Sixteen patients underwent haemato-poietic stem cell transplantation, and eight were treated with a tyrosine kinase inhibitor after transplant. Only the transplanted patients are alive. The 5-year overall survival rate of children with CML-AP/BP is 44%, with no statistical difference between the lymphoid-BP and myeloid-BP outcome.Conclusion: Children evolving to AP or BP under treatment with imatinib have a very poor prognosis with an overall survival under 50%, much worse than children with advanced phase at diagnosis. (c) 2020 Elsevier Ltd. All rights reserved.
- Published
- 2020
48. Antifungal management in adults and children with hematological malignancies or undergoing hematopoietic cell transplantation: recommendations of Polish Society of Hematology and Blood Transfusion, Polish Society of Pediatric Oncology and Hematology, and Polish Adult Leukemia Study Group, 2020
- Author
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Agnieszka Wierzbowska, Jan Styczyński, Lidia Gil, Iwona Hus, Joanna Góra-Tybor, Maria Bieniaszewska, Tomasz Szczepański, Agnieszka Piekarska, Sebastian Giebel, Krzysztof Kałwak, and Ewa Lech-Marańda
- Subjects
medicine.medical_specialty ,Hematology ,Acute myeloblastic leukemia ,business.industry ,Itraconazole ,Micafungin ,Aspergillosis ,medicine.disease ,Transplantation ,Leukemia ,chemistry.chemical_compound ,Oncology ,chemistry ,Internal medicine ,medicine ,Caspofungin ,business ,medicine.drug - Abstract
Invasive fungal disease (IFD) is one of the most serious complications of therapy in patients with immune suppression. It particularly concerns patients treated for malignant hematological diseases, immune deficiencies, or undergoing hematopoietic cell transplantation (HCT). Development of IFD can abrogate the effect of previous therapy and contributes to dismal outcome of the underlying disease. The Working Group consisting of members of the Polish Society of Hematology and Blood Transfusion, the Polish Society of Pediatric Oncology and Hematology, and the Polish Adult Leukemia Study Group has prepared recommendations for the diagnostic and therapeutic management of IFD in adults and children. This paper presents the current recommendations for patients in immune suppression treated in Polish pediatric and adult hematology and HCT centers, based on the guidelines of the European Conference on Infections in Leukaemia (ECIL) 2015–2019. Levels of diagnosis of IFD (possible, probable, and proven) and antifungal management (prophylaxis, as well as empirical and targeted therapies) are declared according to updated international criteria of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group (EORTC/MSG) 2019. Patients with primary diagnosis of acute lymphoblastic leukemia, acute myeloblastic leukemia, severe aplastic anemia, chronic granulomatous disease, and severe combined immunodeficiency, as well as patients after allogeneic HCT, are included in the high-risk groups for development of IFD. For these patients, antifungal prophylaxis based on azoles or micafungin is recommended. In empirical therapy, caspofungin or liposomal/lipid formulas of amphotericin B are recommended. The Working Group has discouraged the use of itraconazole in capsules and amphotericin deoxycholate. Detailed guidelines for first- and second-line targeted therapies for invasive candidiasis, aspergillosis, mucormycosis, fusariosis, and scedosporiosis, as well as the principles of the recommended dosing of antifungals, are presented in this paper.
- Published
- 2020
49. Introduction of new pediatric EBMT criteria for VOD diagnosis: is it time-saving or money-wasting?
- Author
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Marek Ussowicz, Ewa Gorczyńska, Igor Olejnik, Anna Panasiuk, Zofia Szmit, Anna Król, Monika Mielcarek-Siedziuk, and Krzysztof Kałwak
- Subjects
Pediatrics ,medicine.medical_specialty ,Hepatic veno-occlusive disease ,Cost effectiveness ,medicine.medical_treatment ,Hepatic Veno-Occlusive Disease ,Hematopoietic stem cell transplantation ,Defibrotide ,Polydeoxyribonucleotides ,medicine ,Humans ,Prospective Studies ,Child ,Prospective cohort study ,Wasting ,Transplantation ,business.industry ,Incidence ,Incidence (epidemiology) ,Hematopoietic Stem Cell Transplantation ,Hematology ,medicine.disease ,Child, Preschool ,medicine.symptom ,Complication ,business ,medicine.drug - Abstract
Hepatic veno-occlusive disease (VOD) is a potentially fatal complication following hematopoietic stem cell transplantation (HSCT). We evaluated in prospective analysis the usefulness of the pediatric EBMT criteria for VOD diagnosis and their presumable impact on cost effectiveness and patients' outcome. Study included all 282 HSCT procedures performed in Department of Pediatric Hematology/Oncology and BMT in Wrocław between January 2016 and March 2019. Data were compared with previous VOD research conducted in our center before year 2016. Twenty-five (8.9%) patients (median age 3.5 years) were diagnosed with VOD. Duration of defibrotide (DF) administration varied from 4 to 34 days (median: 16.5), with 96% response rate. Overall survival was 88%. If applying Baltimore and modified Seattle criteria, VOD incidence was 2.13% and 5.7%, respectively. Median diagnosis delay based on modified Seattle criteria was 3 days. Before 2016, VOD incidence was 4.9%, with 74% DF response rate (p = 0.033) and 56.2% OS (p = 0.008). After implementing new criteria length of hospitalization for VOD patients decreased by median of 12 days (p = 0.009). Earlier VOD diagnosis, facilitated by EBMT criteria, resulting in implementing immediate treatment significantly improved patients' outcome. Furthermore, it allows shortening of DF administration and minimizes length of hospital stay.
- Published
- 2020
50. Supportive care during pediatric hematopoietic stem cell transplantation: beyond infectious diseases. A report from workshops on supportive care of the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT)
- Author
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Krzysztof Kałwak, Peter Bader, Alice Bertaina, Riitta Niinimäki, Tayfun Güngör, Brenda Gibson, Marianne Ifversen, Marc Ansari, Christina Diaz de Heredia, Akif Yesilipek, Tiago Nava, Jerry Stein, Jochen Buechner, E. Trigoso, Jacek Wachowiak, Marco Deiana, Koray Yalcin, Christina Peters, Halvard Boenig, Simone Cesaro, Isaac Yaniv, Gergely Kriván, Kim Vettenranta, Toni Matic, Dominik Turkiewicz, Roland Meisel, Michaela Kuhlen, Giovanna Lucchini, Shahrzad Bakhtiar, Andre Willasch, Luisa Sisinni, Petr Sedlacek, Daphna Hutt, Thomas Lehrnbecher, Anita Lawitschka, Adriana Balduzzi, Jean Hugues Dalle, Tamara Diesch, Arnaud Dalissier, Selim Corbacioglu, Andrea Jarisch, Ulrike Falkenberg, Nava, T, Ansari, M, Dalle, J, de Heredia, C, Güngör, T, Trigoso, E, Falkenberg, U, Bertaina, A, Gibson, B, Jarisch, A, Balduzzi, A, Boenig, H, Krivan, G, Vettenranta, K, Matic, T, Büchner, J, Kalwak, K, Lawitschka, A, Yesilipek, A, Lucchini, G, Peters, C, Turkiewicz, D, Niinimäki, R, Diesch, T, Lehrnbecher, T, Sedlacek, P, Hutt, D, Dalissier, A, Wachowiak, J, Yaniv, I, Stein, J, Yalçin, K, Sisinni, L, Deiana, M, Ifversen, M, Kuhlen, M, Miesel, R, Bakhtiar, S, Cesaro, S, Willasch, A, Corbacioglu, S, and Bader, P
- Subjects
HEPATIC VENOOCCLUSIVE DISEASE ,medicine.medical_specialty ,bone marrow transplantation ,medicine.medical_treatment ,MEDLINE ,ENTERAL NUTRITION ,Hematopoietic stem cell transplantation ,ORAL MUCOSITIS ,Communicable Diseases ,03 medical and health sciences ,bone marrow transplantation, pediatric, supportive care ,0302 clinical medicine ,Bone Marrow ,Internal medicine ,IRON OVERLOAD ,Mucositis ,Humans ,Medicine ,Child ,Intensive care medicine ,SYNDROME/VENO-OCCLUSIVE DISEASE ,ANTICIPATORY NAUSEA ,Transplantation ,Hematology ,business.industry ,Marrow transplantation ,Research ,Hematopoietic Stem Cell Transplantation ,SEVERITY CRITERIA ,medicine.disease ,supportive care, hematopoietic stem cell transplantation, pediatric ,URSODEOXYCHOLIC ACID ,Europe ,supportive care ,Leukemia ,pediatric ,ANTINEOPLASTIC MEDICATION ,surgical procedures, operative ,Parenteral nutrition ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Bone marrow ,business ,CHEMOTHERAPY-INDUCED NAUSEA ,030215 immunology - Abstract
Hematopoietic stem cell transplantation (HSCT) is currently the standard of care for many malignant and nonmalignant blood diseases. As several treatment-emerging acute toxicities are expected, optimal supportive measurements critically affect HSCT outcomes. The paucity of good clinical studies in supportive practices gives rise to the establishment of heterogeneous guidelines across the different centers, which hampers direct clinical comparison in multicentric studies. Aiming to harmonize the supportive care provided during the pediatric HSCT in Europe, the Pediatric Diseases Working Party (PDWP) of the European Society for Blood and Marrow Transplantation (EBMT) promoted dedicated workshops during the years 2017 and 2018. The present paper describes the resulting consensus on the management of sinusoidal obstructive syndrome, mucositis, enteral and parenteral nutrition, iron overload, and emesis during HSCT.
- Published
- 2020
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