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1.
Prospective analysis of BKV hemorrhagic cystitis in children and adolescents undergoing hematopoietic cell transplantation
Salamonowicz-Bodzioch, M., Fraczkiewicz, J., Czyzewski, K., Zajac-Spychala, O., Gorczynska, E., Panasiuk, A., Ussowicz, M., Kalwak, K., Szmit, Z., Wróbel, G., et al
Annals of hematology. 2021
Abstract
BK virus is one of the most common causes of hemorrhagic cystitis (HC) in children undergoing hematopoietic cell transplantation (HCT). Viruses can be found in urine and serum samples of immunocompromised patients. Malignant diseases, age, cell source, day of granulocyte reconstitution, conditioning regimen, or use of total body irradiation may play an important role in BKV epidemiology, development of hemorrhagic cystitis course, and outcome. The aim of this study was to evaluate the incidence, clinical course, and risk factors for BKV-HC in children undergoing HCT. A total number of 133 patients who were prospectively tested for BKV colonization/infection were enrolled into this multicenter analysis. Episodes of BKV-HC occurred in 36/133 (27%) enrolled subjects. In a univariate analysis for BKV-HC incidence, the following factors were significant: age >5 years, peripheral blood transplantation, matched unrelated donor (MUD) transplantation, busulfan-cyclophosphamide-melphalan conditioning regimen, and acute myeloblastic leukemia (AML) diagnosis. Presence of acute graft-versus-host disease (aGVHD) in liver and gut GVHD was a significant risk factor of BKV-HC. No BKV-attributed deaths were reported. In multivariate analysis, the incidence of HC was significantly higher in patients with AML, age >5 years, MUD transplants, and children with GVHD. HC is a frequent complication after HCT among children causes prolonged hospitalization but rarely contributes to death. We identified risk factors of BKV-HC development in children, with focus on aGVHD: we concluded that excessive immune reaction connected with GVHD and immunosuppression drugs might play a pivotal role in the development of BKV-HC.
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2.
Myeloablative conditioning for allo-HSCT in pediatric ALL: FTBI or chemotherapy?-A multicenter EBMT-PDWP study
Willasch, A. M., Peters, C., Sedlacek, P., Dalle, J. H., Kitra-Roussou, V., Yesilipek, A., Wachowiak, J., Lankester, A., Prete, A., Hamidieh, A. A., et al
Bone marrow transplantation. 2020
Abstract
Although most children with acute lymphoblastic leukemia (ALL) receive fractionated total body irradiation (FTBI) as myeloablative conditioning (MAC) for allogeneic hematopoietic stem cell transplantation (allo-HSCT), it is an important matter of debate if chemotherapy can effectively replace FTBI. To compare outcomes after FTBI versus chemotherapy-based conditioning (CC), we performed a retrospective EBMT registry study. Children aged 2-18 years after MAC for first allo-HSCT of bone marrow (BM) or peripheral blood stem cells (PBSC) from matched-related (MRD) or unrelated donors (UD) in first (CR1) or second remission (CR2) between 2000 and 2012 were included. Propensity score weighting was used to control pretreatment imbalances of the observed variables. 3.054 patients were analyzed. CR1 (1.498): median follow-up (FU) after FTBI (1.285) and CC (213) was 6.8 and 6.1 years. Survivals were not significantly different. CR2 (1.556): median FU after FTBI (1.345) and CC (211) was 6.2 years. Outcomes after FTBI were superior as compared with CC with regard to overall survival (OS), leukemia-free survival (LFS), relapse incidence (RI), and nonrelapse mortality (NRM). However, we must emphasize the preliminary character of the results of this retrospective "real-world-practice" study. These findings will be prospectively assessed in the ALL SCTped 2012 FORUM trial.
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3.
Adenovirus infection among pediatric patients with cancer and in pediatric recipients of hematopoietic stem cell: a multicenter nationwide study
Zajac-Spychala, O., Pieczonka, A., Wachowiak, J., Fraczkiewicz, J., Salamonowicz, M., Kalwak, K., Gorczynska, E., Kazanowska, B., Wrobel, G., Chybicka, A., et al
Journal of medical virology. 2020
Abstract
The aim was to evaluate the incidence, clinical course and outcome of adenoviral infection (AdVI) in pediatric patients diagnosed and treated due to cancer and in pediatric recipients of hematopoietic stem cell. Over a 72-month period, all-in 5,599 children with cancer: 2,441 patients with hematological malignancy (HM) and 3,158 with solid tumors (ST) and 971 patients after transplantation: 741 after allogeneic (allo-HSCT) and 230 after autologous (auto-HSCT) were enrolled into the study. Among cancer patients, 67 episodes of AdVI appeared in 63 (1.1%) children, including 45 (1.8%) with HM and 18 (0.6%; p<0.001) with ST. Within transplanted patients, AdVIs were responsible for 88 episodes in 81 (8.3%) children (p<0.001), including 78 (10.5%) patients after allo-HSCT and 3 (1.3%) after auto-HSCT. Time to develop AdVI was short, especially after allo-HSCT. The most common clinical manifestation in cancer patients was enteritis diagnosed in 63 (94.0%) cases, while among HSCT recipient asymptomatic adenoviremia was found in 36 (40.9%) cases and the most common clinical manifestation was urinary tract infection. Cancer patients with disseminated disease, as well as HSCT recipients with either asymptomatic viremia or disseminated disease, received antiviral treatment. The most commonly used first-line therapy was cidofovir. None of the cancer patients died due to adenoviral infection, while within HSCT recipients three patients developed disseminated adenoviral disease and died despite antiviral treatment. In cancer patients AdVIs are rare and associated with very good prognosis, even without specific treatment. However, in allo-HSCT recipients disseminated disease with fatal outcome is more likely to occur This article is protected by copyright. All rights reserved.
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4.
Hematopoietic stem cell transplantation does not increase the risk of infection-related complications for pediatric patients with Hodgkin and non-Hodgkin lymphomas: a multicenter nationwide study
Zajac-Spychala, O., Wachowiak, J., Czyzewski, K., Dziedzic, M., Wysocki, M., Zalas-Wiecek, P., Szmydki-Baran, A., Hutnik, L., Matysiak, M., Malas, Z., et al
Transplant infectious disease : an official journal of the Transplantation Society. 2020;:e13292
Abstract
BACKGROUND Hodgkin (HL) and non-Hodgkin lymphoma (NHL) represent a spectrum of lymphoid malignancies that are often curable with currently applied treatment regimens, however 15-30% of lymphoma patients still suffer from relapsed or refractory (rel/ref) disease. Although hematopoietic stem cell transplantation (HSCT) improves outcomes of second-line therapy for lymphoma in childhood, the complication rates in this group of patients, especially infectious complications, remain unclear. OBJECTIVE The aim of this population-based cohort study was a retrospective analysis of incidence, epidemiology and profile of bacterial infections (BI), invasive fungal disease (IFD) and viral infections (VI) in primary or rel/ref lymphoma patients, both HL and NHL. PATIENTS AND METHODS We subdivided lymphoma patients into three groups: patients with primary conventional chemotherapy/radiotherapy regimens (group A); patients with rel/ref lymphoma treated with second-line chemotherapy (group B) and rel/ref lymphoma patients who underwent HSCT (group C). The medical records of the patients were biannually reported by each pediatric oncology center and the data were analyzed centrally. RESULTS Within 637 patients with primary lymphoma, at least one infectious complication (IC) was diagnosed in 255 (40.0%), among 52 patients with rel/ref lymphoma 24 (46.2%) ICs were observed and in transplanted group 28 (57.1%) out of 49 children were diagnosed with IC (p=0.151). The distribution of etiology of IC differed between the patient groups (A, B, C), with a predominance of BI in group A (85.6% vs 72.0% and 47.9%, respectively), VI in group C (9% and 16.0% vs 46.6%, respectively), and IFD in group B (5.4% vs 12.0% vs. 5.5%, respectively). Overall, 500 (68.0%) episodes of bacterial IC was diagnosed in the entire group. Apart from HL patients treated with chemotherapy, in all the other subgroups of patients Gram-positives were predominant. The rate of multi-drug resistant bacteria was high, especially for Gram-negatives (41.1% in group A, 62.5% in group B and 84.6% in group C). The infection-related mortality was comparable for each group. CONCLUSIONS The incidence of infectious complications was comparable during first- and second-line chemotherapy and after HSCT, but their profile was different for primary or re/ref lymphoma and depended on the type of therapy.
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5.
Infectious complications after hematopoietic stem cell transplantation for primary immunodeficiency in children: a multicenter nationwide study
Zajac-Spychala, O., Zaucha-Prazmo, A., Zawitkowska, J., Wachowiak, J., Kowalczyk, J. R., Fraczkiewicz, J., Salamonowicz, M., Kalwak, K., Gorczynska, E., Chybicka, A., et al
Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology. 2020
Abstract
PURPOSE The aim of this nation-wide study was to evaluate the characteristics of bacterial (BI), invasive fungal disease (IFD) and viral infections (VI) in pediatric patients with PID after allogeneic hematopoietic stem cell transplantation (allo-HSCT). PATIENTS AND METHODS All-in 114 HSCT recipients were enrolled into the study. At least one infectious complication (IC) was diagnosed in 60 (52.6%) patients aged 0.1-17.7 years, i.e. 59.5% with SCID and 49.4% with non-SCID. RESULTS Among 60 HSCT recipients diagnosed with at least one IC, 188 episodes of infectious complications (EIC) were recorded, i.e. 46.8% of BI, 41.5% of VI and 11.7% of proven/probable IFD. According to PID and HSCT donor type the incidence of EIC was comparable (p=0.679). The localization of infections differed significantly due to PID type (p=0.002). After each HSCT donor type the most common site of infection was GI. Overall, BI caused by Gram-positive strains (59.1%) were prevalent, especially Staphylococcaceae. The multidrug-resistant (MDR) pathogens was diagnosed in 52.3%, especially ESBL+ Enterobacteriaceae. The profile of VI was comparable for SCID and non-SCID patients (p=0.839). The incidence of IFD was comparable for each PID and HSCT donor type. Survival after infection was 91.5% and was comparable for PID and HSCT donor type. CONCLUSIONS The rate of patients diagnosed with IC among pediatric PID HSCT recipients did not depend on PID type, but rather on HSCT donor type. The localization of IC depended on PID and HSCT donor type. Within bacterial infections predominated Gram-positive strains and the MDR pathogens were responsible for more than half of EIC.
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6.
Incidence, course, and outcome of Clostridium difficile infection in children with hematological malignancies or undergoing hematopoietic stem cell transplantation
Salamonowicz, M., Ociepa, T., Fraczkiewicz, J., Szmydki-Baran, A., Matysiak, M., Czyzewski, K., Wysocki, M., Galazka, P., Zalas-Wiecek, P., Irga-Jaworska, N., et al
European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology. 2018
Abstract
Clostridium difficile infection (CDI) is one of the most common causes of nosocomial infectious diarrhea in children during anticancer therapy or undergoing hematopoietic stem cell transplantation (HSCT) in Europe. Immunosuppression in these patients is a risk factor for CDI. Malignant diseases, age, acute graft-versus-host disease (aGVHD), HLA mismatch, or use of total body irradiation may play an important role in CDI course. The aim of this study was to evaluate the incidence, course, and outcome of CDI in children treated for malignancy or undergoing HSCT. Between 2012 and 2015, a total number of 1846 patients were treated for malignancy in Polish pediatric oncological centers (PHO group) and 342 underwent transplantation (HSCT group). In PHO group, episodes of CDI occurred in 210 patients (14%). The incidence of CDI was higher in patients with hematological malignancies in comparison to that with solid tumors. Patients with acute myeloblastic leukemia had shorter time to episode of CDI than those with acute lymphoblastic leukemia. Patients over 5 years and treated for acute leukemia had more severe clinical course of disease in PHO group. In HSCT group, CDI occurred in 29 (8%) patients. The incidence of CDI was higher in patients transplanted for acute leukemia. The recurrence rate was 14.7% in PHO and 20.7% in HSCT patients. CDI incidence was highest in patients with hematological malignancies. Most of patients experienced mild CDI. Age < 5 years and diagnosis other than acute leukemia were the positive prognostic factors influencing clinical CDI course.
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7.
A risk factor analysis of outcomes after unrelated cord blood transplantation for children with Wiskott-Aldrich syndrome
Shekhovtsova, Z., Bonfim, C., Ruggeri, A., Nichele, S., Page, K., AlSeraihy, A., Barriga, F., de Toledo Codina, J. S., Veys, P., Boelens, J. J., et al
Haematologica. 2017;102(6):1112-1119
Abstract
Wiskott-Aldrich syndrome is a severe X-linked recessive immune deficiency disorder. A scoring system of Wiskott-Aldrich syndrome severity (0.5-5) distinguishes two phenotypes: X-linked thrombocytopenia and classic Wiskott-Aldrich syndrome. Hematopoietic cell transplantation is curative for Wiskott-Aldrich syndrome; however, the use of unrelated umbilical cord blood transplantation has seldom been described. We analyzed umbilical cord blood transplantation outcomes for 90 patients. The median age at umbilical cord blood transplantation was 1.5 years. Patients were classified according to clinical scores [2 (23%), 3 (30%), 4 (23%) and 5 (19%)]. Most patients underwent HLA-mismatched umbilical cord blood transplantation and myeloablative conditioning with anti-thymocyte globulin. The cumulative incidence of neutrophil recovery at day 60 was 89% and that of grade II-IV acute graft-versus-host disease at day 100 was 38%. The use of methotrexate for graft-versus-host disease prophylaxis delayed engraftment (P=0.02), but decreased acute graft-versus-host disease (P=0.03). At 5 years, overall survival and event-free survival rates were 75% and 70%, respectively. The estimated 5-year event-free survival rates were 83%, 73% and 55% for patients with a clinical score of 2, 4-5 and 3, respectively. In multivariate analysis, age <2 years at the time of the umbilical cord blood transplant and a clinical phenotype of X-linked thrombocytopenia were associated with improved event-free survival. Overall survival tended to be better in patients transplanted after 2007 (P=0.09). In conclusion, umbilical cord blood transplantation is a good alternative option for young children with Wiskott-Aldrich syndrome lacking an HLA identical stem cell donor. Copyright© Ferrata Storti Foundation.
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8.
More chronic GvHD and non-relapse mortality after peripheral blood stem cell compared with bone marrow in hematopoietic transplantation for paediatric acute lymphoblastic leukemia: a retrospective study on behalf of the EBMT Paediatric Diseases Working Party
Simonin, M., Dalissier, A., Labopin, M., Willasch, A., Zecca, M., Mouhab, A., Chybicka, A., Balduzzi, A., Volin, L., Peters, C., et al
Bone Marrow Transplantation. 2017;52(7):1071-1073
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9.
Increased risk of infections and infection-related mortality in children undergoing haematopoietic stem cell transplantation compared to conventional anticancer therapy: a multicentre nationwide study
Styczynski, J., Czyzewski, K., Wysocki, M., Gryniewicz-Kwiatkowska, O., Kolodziejczyk-Gietka, A., Salamonowicz, M., Hutnik, L., Zajac-Spychala, O., Zaucha-Prazmo, A., Chelmecka-Wiktorczyk, L., et al
Clinical Microbiology & Infection. 2016;22(2):179.e1-179.e10
Abstract
This nationwide multicentre study analysed the epidemiology of bacterial, viral and fungal infections in paediatric haematopoietic stem cell transplantation (HSCT) and paediatric haematology and oncology (PHO) patients over a period of 24 consecutive months, including incidence, hazard risk and outcome of infections as well as occurrence of multidrug-resistant bacteria. During this period, 308 HSCTs were performed and 1768 children were newly diagnosed for malignancy. Compared to PHO, the risk in HSCT patients was significantly higher for all infections (hazard ratio (HR) 2.7), bacterial (HR 1.4), fungal (HR 3.5) and viral (HR 15.7) infections. The risk was higher in allo- than auto-HSCT for bacterial (HR 1.4), fungal (HR 3.2) and viral (HR 17.7) infections. The incidence of resistant bacteria was higher in HSCT than in PHO patients for both G-negative (72.5% vs. 59.2%) and G-positive (41.4% vs. 20.5%) strains. Cumulative incidence of bacterial, fungal and viral infections in HSCT patients was 33.9, 22.8 and 38.3%, respectively. Cumulative incidence of viral infections in allo-HSCT was 28.0% for cytomegalovirus, 18.5% for BK virus, 15.5% for Epstein-Barr virus, 9.5% for adenovirus, 2.6% for varicella zoster virus, 0.9% for influenza, 0.9% for human herpesvirus 6 and 0.3% for hepatitis B virus. Survival rates from infections were lower in HSCT than in PHO patients in bacterial (96.0 vs. 98.2%), fungal (75.5 vs. 94.6%) and most viral infections. In conclusion, the risk of any infections and the occurrence of resistant bacterial strains in allo-HSCT patients were higher than in auto-HSCT and PHO patients, while the outcome of infections was better in the PHO setting. Copyright © 2015 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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10.
Bacterial infections in pediatric hematopoietic stem cell transplantation recipients: incidence, epidemiology, and spectrum of pathogens: report of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation
Zajac-Spychala, O., Wachowiak, J., Pieczonka, A., Siewiera, K., Fraczkiewicz, J., Kalwak, K., Gorczynska, E., Chybicka, A., Czyzewski, K., Jachna-Sawicka, K., et al
Transplant Infectious Disease. 2016;18(5):690-698
Abstract
BACKGROUND Infectious complications are a significant cause of hematopoietic stem cell transplantation (HSCT) failure, especially allogeneic HSCT (allo-HSCT) because of delayed immune reconstitution and graft-versus-host disease (GVHD) occurrence. Identifying the factors responsible for bacterial infections (BI) in patients undergoing HSCT will provide much more effective empirical antimicrobial treatment in this group of patients. OBJECTIVE The aim of this study was to evaluate the epidemiology and profile of BI in patients after HSCT in 5 centers of the Polish Pediatric Group for Hematopoietic Stem Cell Transplantation in 2012-2013. PATIENTS AND METHODS In 308 HSCT recipients, we retrospectively analyzed 273 episodes of BI in 113 (36.7%) children aged 0.02-22 years (median age: 7 years), 92 after allo-HSCT and 22 after autologous HSCT (auto-HSCT). We assessed incidence of BI in different HSCT types by calculating the Index of Bacterial Infection (IBI) as a ratio of patients with at least 1 BI to all patients who underwent this type of HSCT in the analyzed period. We assessed the profile of BI with particular emphasis on multidrug-resistant organisms, and impact of underlying disease and of graft-versus-host disease on BI episodes. RESULTS In the studied group, 273 episodes of BI were diagnosed, including 237 episodes after allo-HSCT and 36 after auto-HSCT. Among allo-HSCT recipients diagnosed with at least 1 BI, the IBI was 0.4 (matched sibling donor-HSCT 0.3; matched donor-HSCT 0.4; mismatched unrelated donor [MMUD]-HSCT 0.8; P = 0.027) and after auto-HSCT 0.3 per 1 transplanted patient. In patient after allo-HSCT because of myelo- or lymphoproliferative diseases and bone marrow failures, the major cause of infections was Enterobacteriaceae, while gram-positive bacteria predominated in the group with primary immunodeficiencies. In all patients after auto-HSCT, the dominant pathogen of BI were Enterobacteriaceae (P = 0.011). Time from each type of HSCT to infection caused by different pathogens did not differ significantly. CONCLUSIONS The risk of BI does not depend on the underlying disease, but only on HSCT donor type and is the highest after MMUD-HSCT procedure. The profile of BI depends on the underlying disease and HSCT donor type, but does not depend on the occurrence of acute GVHD. Gram-negative bacteria predominated in patients with myelo- and lymphoproliferative diseases, while in patients with primary immunodeficiencies gram-positive strains were predominant. Copyright © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.