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Incidence of subsequent malignancies after total body irradiation-based allogeneic HSCT in children with ALL - long-term follow-up from the prospective ALL-SCT 2003 trial
Eichinger, A., Poetschger, U., Glogova, E., Bader, P., Basu, O., Beier, R., Burkhardt, B., Classen, C. F., Claviez, A., Corbacioglu, S., et al
Leukemia. 2022
Abstract
Total body irradiation (TBI)-based conditioning is associated with superior leukemia-free survival in children with ALL undergoing HSCT. However, the risk for subsequent malignant neoplasms (SMN) remains a significant concern. We analyzed 705 pediatric patients enrolled in the prospective ALL-SCT-BFM-2003 trial and its subsequent registry. Patients >2 years received conditioning with TBI 12 Gy/etoposide (n = 558) and children ≤2 years of age or with contraindications for TBI received busulfan/cyclophosphamide/etoposide (n = 110). The 5- and 10-year cumulative incidence of SMN was 0.02 ± 0.01 and 0.13 ± 0.03, respectively. In total, 39 SMN (34 solid tumors, 5 MDS/AML) were diagnosed in 33 patients at a median of 5.8 years (1.7-13.4), exclusively in the TBI group. Of 33 affected patients, 21 (64%) are alive at a median follow-up of 5.1 years (0-9.9) after diagnosis of their first SMN. In univariate analysis, neither age at HSCT, donor type, acute GVHD, chronic GVHD, nor CMV constituted a significant risk factor for SMN. The only significant risk factor was TBI versus non-TBI based conditioning. This analysis confirms and quantifies the increased risk of SMN in children with ALL after conditioning with TBI. Future strategies to avoid TBI will need careful tailoring within prospective, controlled studies to prevent unfavorable outcomes.
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Psychometric properties of the Activities Ccale for Kids-performance after allogeneic hematopoietic stem cell transplantation in adolescents and children : Results of a prospective study on behalf of the German-Austrian-Swiss GVHD Consortium
Lawitschka, A., Brunmair, M., Bauer, D., Zubarovskaya, N., Felder-Puig, R., Strahm, B., Bader, P., Strauss, G., Albert, M., von Luettichau, I., et al
Wiener klinische Wochenschrift. 2020
Abstract
BACKGROUND The psychometric properties of an instrument, the Activity Scale for Kids-performance (ASKp), were assessed which was proposed to capture physical functioning after allogeneic hematopoietic stem cell transplantation (HSCT). Additionally, this multicenter observational prospective study investigated the influence of clinical correlates focusing on chronic graft-versus-host disease (cGVHD). METHODS Patient-reported ASKp, clinician-reported Karnofsky/Lansky status (KPS/PSS), patient characteristics and cGVHD details were assessed of 55 patients with a median age of 12 years at baseline after day +100 post-HSCT and every 3 months during the next 18 months. The psychometric properties were evaluated and ASKp and KPS/PSS status was compared using ANOVAS and multiple regression models. RESULTS The German version of the ASKp showed good psychometric properties except for ceiling effects. Discrimination ability of the ASKp was good regarding the need for devices but failed to predict cGVHD patients. Both the ASKp and the KPS/PSS were associated with patients after adoptive cell therapy being in need for devices, suffering from overlap cGVHD and from steroid side effects but not with patients' age and gender. In contrast to the KPS/PSS the ASKp only showed significant differences after merging moderate and severe cGHVD patients when comparing them to No-cGVHD (F= 4.050; p= 0.049), being outperformed by the KPS/PSS (F= 20.082; p < 0.001). CONCLUSION The ASKp showed no clear advantages compared to KPS/PSS even though economical and patients' effort was higher. Further application range may be limited through ceiling effects. Both should be taken into consideration. Therefore, the results may not support the usage of ASKp after HSCT and rather suggest KPS/PSS, both patient and clinician reported.
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Guidance to bone morbidity in children and adolescents undergoing allogeneic hematopoietic stem cell transplantation
Kuhlen, M., Kunstreich, M., Niinimaki, R., Dunstheimer, D., Lawitschka, A., Bardit, E., Willasch, A., Bader, P., Hogler, W., Peters, C., et al
Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2019
Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) is widely performed in children and adolescents with hematologic diseases including very high-risk leukemia. With increasing success and survival rates, the long-term sequelae of HSCT have become important. Here, we provide guidance to the prevention and treatment of the most common bone morbidities - osteoporosis and osteonecrosis - emerging in the context of HSCT in children and adolescents. We give an overview on definitions, symptoms and diagnostics and propose an algorithm for clinical practice based on discussions within the International BFM SCT Committee and the Pediatric Disease Working Party of the European Society for Blood and Marrow Transplantation, our expert knowledge and a literature review.
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Management of growth failure and growth hormone deficiency after pediatric allogeneic HSCT: Endocrinologists are of importance for further guidelines and studies
Lawitschka, A., Schwarze, P., Rovelli, A., Badoglio, M., Socie, G., Tichelli, A., Bauer, D., Rovo, A., Basak, G., Schoemans, H., et al
Pediatric hematology and oncology. 2019;:1-10
Abstract
Growth failure (GF) is a frequent problem after pediatric allogeneic hematopoietic stem cell transplantation (HSCT). Growth hormone deficiency (GHD) occurs in 20 to 85%, but published data on the efficacy of growth hormone treatment (GHT) are conflicting. Currently, there are no recommendations on screening for and treatment of GHD after HSCT. We aimed to describe the management of endocrine follow-up (FU)and details of GHT within European Society for Blood and Marrow Transplantation (EBMT) centers. In a retrospective questionnaire study, all EBMT centers performing pediatric HSCT were invited. Results were evaluated in correlation with the structure of endocrine aftercare (HSCT-clinicians and endocrinologists). The majority of centers (80%) reported endocrine FU by an endocrinologist - either within the HSCT-center or in a separate endocrine clinic. Fifty-four percent reported FU outside of the HSCT-center. As diagnostic tests the insulin-like growth factor IGF-I and insulin-like growth factor binding protein IGFBP3, insulin tolerance test and arginine stimulation test were most frequently used. Sixty-four percent of centers performed GHT and endocrinologists were more likely to prescribe GH (74%) compared to HSCT-clinicians (33%). The most frequent indication for GHT was GHD in 60%, with a distinct different approach of endocrinologists in comparison with HSCT-clinicians. Our study reveals substantial variation in practice and emphasizes the need for endocrine aftercare performed by dedicated endocrinologists in close collaboration with the HSCT-center. Our results indicate that the management of GHT depends on the structure of endocrine aftercare, which is important for the future development and distribution of studies and guidelines.
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Low incidence of symptomatic osteonecrosis after allogeneic HSCT in children with high-risk or relapsed ALL - results of the ALL-SCT 2003 trial
Kuhlen, M., Bader, P., Sauer, M., Albert, M. H., Gruhn, B., Gungor, T., Kropshofer, G., Lang, P., Lawitschka, A., Metzler, M., et al
British journal of haematology. 2018
Abstract
Osteonecrosis (ON) was prospectively assessed in 557 children and adolescents in the Berlin-Frankfurt-Munster Stem Cell Transplantation in children with acute lymphoblastic leukaemia 2003 trial. Median age at haematopoietic stem cell transplantation (HSCT) was 10.3 years (range 0.5-26). Cumulative incidence of symptomatic ON (sON) was 9% at 5 years (standard deviation 1%), median time from HSCT to diagnosis of sON was 12.4 months (range 1-126). Multivariate analysis identified age at HSCT [10-15 years vs. <10 years: hazard ratio (HR) 3.73, P = 0.009; >15 years vs. <10 years: HR 5.46, P = 0.001], diagnosis of sON prior to HSCT and chronic graft-versus-host disease (yes versus no: HR 2.696, P = 0.015) as significant independent risk factors for the development of sON.
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Incidence and severity of crucial late effects after allogeneic HSCT for malignancy under the age of 3 years: TBI is what really matters
Bresters, D., Lawitschka, A., Cugno, C., Potschger, U., Dalissier, A., Michel, G., Vettenranta, K., Sundin, M., Al-Seraihy, A., Faraci, M., et al
Bone Marrow Transplantation. 2016;51(11):1482-1489
Abstract
Younger children are considered to be more vulnerable to late effects (LE), which prompted us to study LE in patients after haematopoietic stem cell transplantation (HSCT) for a haematological malignancy before the age of 3. In this multicentre EBMT study, cumulative incidence (CI) and severity of endocrine LE, central nervous system complications and secondary malignancies at 5, 10, 15 and 20 years of follow-up were assessed. Risk factors (RF) like gender, diagnosis, age at and year of HSCT, TBI- or chemo-conditioning and GVHD were analysed. CI of any LE was 0.30, 0.52, 0.66 and 0.72 at 5, 10, 15 and 20 years after HSCT, respectively. In 25% of the patients, LE were severe at a median follow-up of 10.4 years. In multivariate analysis, only TBI was a RF for having any LE and for thyroid dysfunction and growth disturbance. Female gender was a RF for delayed pubertal development. Some more insight could be gained by descriptive analysis regarding the role of TBI and GVHD on the severity of LE. Although only five selected LE have been studied and median follow-up is relatively short, the incidence and severity of these LE are considerable but not different from what has been found in older children and TBI is the main RF.