Adverse Drug Reactions in Pediatric Oncohematology: A Systematic Review

Adverse drug reactions; Neoplasms; PediatricsReacciones adversas a medicamentos; Neoplasias; PediatríaReaccions adverses als medicaments; Neoplàsies; PediatriaIntroduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6–68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement

Off-label use of rituximab in patients with systemic lupus erythematosus with extrarenal disease activity: a retrospective study and literature review

Effectiveness; Rituximab; Systemic erythematosus lupusEficacia; Rituximab; Lupus eritematoso sistémicoEficàcia; Rituximab; Lupus eritematós sistèmicIntroduction: Off-label rituximab is commonly used for patients with systemic lupus erythematosus (SLE) with extrarenal disease activity. Methods: The outcomes and tolerability of rituximab in adult patients with non-renal SLE treated at our hospital from 2013 to 2020 were described. Patients were followed-up until December 2021. Data were retrieved from electronic medical records. Response was classified into complete, partial or no response according to the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI 2 K)-based definitions. Results: A total of 44 cycles were administered to 33 patients. Median age was 45 years and 97% were female. Median follow-up was 5.9 years (IQR 3.7–7.2). The most frequent symptoms that motivated rituximab use were thrombocytopenia (30.3%), arthritis (30.3%), neurological manifestations (24.2%) and cutaneous lupus (15.2%). After most treatment cycles a partial remission was achieved. The median SLEDAI-2 K score declined from 9 (IQR 5–13) to 1.5 (IQR 0–4) (p < 0.00001). The median number of flares significantly declined after receiving rituximab. Platelet counts significantly improved in patients with thrombocytopenia and patients with skin disorders or neurological manifestations also had a partial or complete response. Only 50% of patients with a predominant joint involvement had either a complete or a partial response. The median time to relapse after the first cycle was 1.6 years (95% CI, 0.6–3.1). Anti-dsDNA levels decreased significantly after rituximab from a median of 64.3 (IQR 12–373.9) to 32.7 (IQR 10–173), p = 0.00338. The most frequent adverse events were infusion-related reactions (18.2%) and infections (57.6%). All patients needed further treatment to maintain remission or to treat new flares. Conclusion: A partial or complete response was documented after most rituximab cycles in patients with non-renal SLE. Patients with thrombocytopenia, neurolupus, and cutaneous lupus had better response than those with a predominant joint involvement

Anàlisi de la utilització de medicaments en població pediàtrica i adulta : utilització de medicaments en condicions no aprovades /

Els estudis d'utilització de medicaments permeten identificar els patrons d'ús dels medicaments en diferents poblacions, ja siguin adults o nens. Un aspecte és l'anàlisi de l'ús de medicaments en condicions diferents a les autoritzades a la fitxa tècnica. Aquesta tesi és una anàlisi de diferents aspectes de l'ús de medicaments en condicions no aprovades després que es publiqués el Reial Decret 1015/2009 del 19 de juny pel qual es regula la disponibilitat de medicaments en diferents situacions especials (entre les quals hi ha l'ús en condicions no aprovades), i s'establís una normativa de l'Institut Català de la Salut (ICS), amb uns procediments estandarditzats de treball per revisar, avaluar i registrar l'ús de medicaments en les situacions especials. En la publicació Medicina Clínica 2014;143:327-9, es descriuen els medicaments utilitzats en condicions no aprovades i les indicacions en les que s'utilitzen a dos hospitals de tercer nivell durant els tres anys posteriors a la publicació del Reial Decret. Es van rebre 671 sol·licituds de 117 medicaments o combinacions per a ser emprats en aquestes condicions. Els subgrups més sol·licitats van ser antineoplàstics, immunosupressors i relaxants musculars, i els fàrmacs més freqüents van ser rituximab (170 sol·licituds), toxina botulínica (81), omalizumab (39) i anakinra (21). Les principals malalties van ser neoplàstiques, del sistema nerviós i òrgans dels sentits i de l'aparell digestiu. En la publicació European Journal of Clinical Pharmacology 2014;70:1385-93 s'analitzen les indicacions d'ús, els resultats clínics (resposta clínica i tolerabilitat de la medicació) i els resultats econòmics (cost total i per pacient) de l'ús dels medicaments en condicions no aprovades en cinc hospitals de l'ICS durant un any. S'hi van incloure de manera prospectiva 226 pacients, amb una edat mediana (RIQ) de 46 (33-62) anys; el 59% eren dones. Els pacients havien rebut una mediana de tres tractaments previs, i la principal raó per demanar l'ús no aprovat era la manca de resposta o resposta subòptima (72,1%). Es van donar 232 fàrmacs per a 102 indicacions diferents. Els fàrmacs més freqüents van ser rituximab (49; 21,1%), toxina botulínica (25; 10,7%) i omalizumab (14; 6,0%). En 117 casos (51,8%) el nivell d'evidència disponible per al seu ús era baix. Es va observar resposta parcial en 82 pacients (36,3%), completa en 71 (31,4%) i estabilització en 11 (4,9%). Va presentar efectes indesitjats 58 pacients (26,5%). El cost medià (RIQ) per pacient va ser de 2.943,07 € (541,9 - 5.872,54). En la publicació European Journal of Clinical Pharmacology 2013;69:1689-99 s'analitzen i es descriuen les indicacions d'ús, les evidències científiques disponibles i els resultats clínics a curt i llarg termini i econòmics, del fàrmac més utilitzat en condicions no aprovades que ha estat el rituximab. Es van analitzar 101 casos d'ús de rituximab en condicions no aprovades, amb una mediana d'edat (RIQ) dels pacients de 53 anys (37,5-68,0]; el 55,4% eren dones. Les indicacions principals eren malalties hematològiques (46%), malalties sistèmiques del teixit connectiu (27%) i malalties renals (20%). Les evidències eren principalment estudis de cohort individuals (53,5% dels casos) i sèries de casos (25,7%). La resposta observada a curt termini (mediana de 3 mesos [IQR 2-4]) va ser completa en el 38% dels casos i parcial en el 32,6%. Les més altes es van observar en el lupus eritematós sistèmic i la glomerulonefritis membranoproliferativa, i les respostes més baixes, en la neuromielitis òptica, i la púrpura trombocitopènica idiopàtica. En el 69,2% dels casos amb resposta a curt termini es va mantenir una certa resposta a llarg termini (mediana de 23 mesos [RIQ 12-30]). El cos per pacient (mediana va ser de 5.187,5€ (RIQ 5.187,5-7.781,3)Drug utilization studies can be useful to identify patterns of drug use in different populations, whether adult or children. One aspect is the analysis of drug use in conditions other than those authorized in the technical specifications or labelling. This thesis is an analysis of various aspects of off-label drug use after the publication of a Royal Decree 1015/2009 of 19 June regulating the availability of medicines in various special situations (including off-label drug use) and after the establishment of a rule of the Catalan Institute of Health (ICS) with standardized work procedures to review, evaluate and register the use of drugs in special situations. The publication Medicina Clínica 2014;143:327-9 describes the drugs used in conditions not approved in two tertiary hospitals during the three years following the publication of Royal Decree. There were 671 applications for 117 single drugs or combinations to use in these conditions. The main groups were antineoplastic, immunosuppressive and muscle relaxants, and the most involved drugs were rituximab (170 applications), botulinum toxin (81), omalizumab (39) and anakinra (21). The main diseases were neoplastic diseases, those affecting nervous system and sense organs and digestive disorders. The publication European Journal of Clinical Pharmacology 2014;70:1385-93 describes the analysis of indications for use, clinical outcomes (clinical response and tolerability of the medication) and cost of off-label drug use in five hospitals of the ICS during one year. A total of 226 patients were included. The median [IQR] age of patients was 46 (33-62) years; 59% were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1%). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1%), botulinum toxin (25; 10.7%) and omalizumab (14; 6.0%). In 117 (51.8%) cases the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3%), complete response in 71 (31.4%) and stabilization in 11 (4.9%). A total of 58 (26.5%) patients had adverse effects, which in 11 (4.9%) were severe. The median (IQR) cost per patient was € 2,943.07 (541.9 - 5,872.54). The publication European Journal of Clinical Pharmacology 2013;69:1689-99 describes the indications for use, the available scientific evidence and clinical results in the short and long term, and the cost of off-label use of rituximab. A total of 101 cases of off-label rituximab use were analyzed (median [IQR] age 53 years [37.5-68.0]; 55.4% women). The requested indications were mainly haematological diseases (46%), systemic connective tissue disorders (27%) and kidney diseases (20%). Available evidence in these indications were mainly individual cohort studies (53.5% of cases), and case series (25.7%). Short-term outcome (median 3 months [IQR 2-4]) was a complete response in 38% of cases and partial response in 32.6%. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest for neuromyelitis optica and idiopathic thrombocytopenic purpura. Some response was maintained in long-term follow-up (median 23 months [IQR 12-30]) in 69.2% of patients with short-term response. Median cost per patient was € 5,187.5 (IQR 5,187.5-7,781.3)

Outcomes of off-label drug uses in hospitals: a multicentric prospective study

Purpose: The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. Methods: A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. Results: A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (3362) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was 2,943.07 (541.95,872.54). Conclusions: There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed

La consulta terapèutica : una eina complementària d'informació per a la individualització de la terapèutica

En aquest article es presenten els resultats d'un treball de recerca que analitza les característiques de la demanda d'informació sobre terapéutica atesa durant els darrers quinze anys a la Fundació Institut Catalá de Farmacologia. En una época en qué, per una banda, el volum creixent de nova informació médica disponible fa que al metge sovint sigui difícil mantenir-se al dia i, per una altra banda, davant la progressiva acceptació de la medicina basada en proves, la prestació d'un servei de consulta terapéutica representa una activitat complementária d'informació en la qual s'utilitzen les millors evidencies disponibles per a la individualització de la terapéutica

Safety of Drugs Used during the First Wave of COVID-19: A Hospital-Registry-Based Study

COVID-19; Adverse drug reactions; HydroxychloroquineCOVID-19; Reaccions adverses als medicaments; HidroxicloroquinaCOVID-19; Reacciones adversas a los medicamentos; HidroxicloroquinaThe emergency of the coronavirus disease 2019 (COVID-19) pandemic led to the off-label use of drugs without data on their toxicity profiles in patients with COVID-19, or on their concomitant use. Patients included in the COVID-19 Patient Registry of a tertiary hospital during the first wave were analyzed to evaluate the adverse drug reactions (ADRs) with the selected treatments. Twenty-one percent of patients (197 out of 933) had at least one ADR, with a total of 240 ADRs. Patients with ADRs were more commonly treated with multiple drugs for COVID-19 infection than patients without ADRs (p &lt; 0.001). They were younger (median 62 years vs. 70.1 years; p &lt; 0.001) and took less medication regularly (69.5% vs. 75.7%; p = 0.031). The most frequent ADRs were gastrointestinal (67.1%), hepatobiliary (10.8%), and cardiac disorders (3.3%). Drugs more frequently involved included lopinavir/ritonavir (82.2%), hydroxychloroquine (72.1%), and azithromycin (66.5%). Although most ADRs recovered without sequelae, fatal cases were described, even though the role of the disease could not be completely ruled out. In similar situations, efforts should be made to use the drugs in the context of clinical trials, and to limit off-label use to those drugs with a better benefit/risk profile in specific situations and for patients at high risk of poor disease prognosis

Outcomes of off-label drug uses in hospitals : a multicentric prospective study

Altres ajuts: We would to thank the Spanish Ministry of Health, Social Affairs and Equality for their financial support given though a grant from the scholarship EC-206 in the public call for the promotion of independent clinical research (SAS/2370/2010 order of September 27)The study aims to assess the clinical evidence, outcome and cost of off-label use of medicines in the hospital setting. A multicentric prospective cohort study of patients treated with off-label medicines was carried out in five tertiary hospitals from May 2011 to May 2012. Information on clinical characteristics of patients, drugs, outcomes and costs was collected. Patients were followed up to 6 months, and information was assessed by reviewing clinical records and interviewing physicians. A total of 226 patients were included. The median (interquartile range (IQR)) age of patients was 46 (33-62) years; 59 % were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1 %). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1 %), botulinum toxin (25; 10.7 %) and omalizumab (14; 6.0 %). In 117 (51.8 %) cases, the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3 %), complete response in 71 (31.4 %) and stabilization in 11 (4.9 %). A total of 58 (26.5 %) patients had adverse effects, which in 11 (4.9 %) were severe. The median (IQR) cost per patient was €2,943.07 (541.9-5,872.54). There was a high variability of off-label medicines and indications. Although the clinical evidence of off-label medicines was often low, clinical response was observed in many patients with previous multiple treatment failure, but at the expense of some adverse effects and a high cost. Registers of patients would be helpful for clinical decisions, although clinical trials are needed. The online version of this article (doi:10.1007/s00228-014-1746-2) contains supplementary material, which is available to authorized users

Educational sessions in pharmacovigilance: What do the doctors think?

Background: The aim of this study was to determine physicians"opinion regarding pharmacovigilance feedback sessions. A survey was conducted in a teaching hospital, and the physicians who attended the sessions were invited to participate by filling out a structured questionnaire. All sessions included a review of adverse drug reactions identified at the hospital and information on pharmacovigilance issues (news on warnings released by regulatory agencies or drug toxicity problems identified by recently published studies in medical journals). The survey questions were related to the interest, satisfaction, and belief in the utility of the sessions. A Likert scale (0-10 points) was used to assess physicians" opinions. Findings: A total of 159 physicians attended the sessions and 115 (72.3%) participated in the survey. The mean (SD) age was 38.9 (12.1) years, and 72 (62.6%) were men. The mean (SD) scores of interest, satisfaction with the information provided, and belief in the utility of these sessions were 7.52 (1.61), 7.58 (1.46), and 8.05 (1.38) respectively. Significant differences were observed among physicians according to medical category and speciality in terms of interest, satisfaction, and belief in the utility of those sessions. Conclusions: Educational activities for physicians, such as feedback sessions, can be integrated into the pharmacovigilance activities. Doctors who attend the sessions are interested in and satisfied with the information provided and consider the sessions to be useful. Additional studies on the development and effectiveness of educational activities in pharmacovigilance are necessary

Anàlisi de la utilització de medicaments en població pediàtrica i adulta. utilització de medicaments en condicions no aprovades

Els estudis d'utilització de medicaments permeten identificar els patrons d'ús dels medicaments en diferents poblacions, ja siguin adults o nens. Un aspecte és l’anàlisi de l’ús de medicaments en condicions diferents a les autoritzades a la fitxa tècnica. Aquesta tesi és una anàlisi de diferents aspectes de l’ús de medicaments en condicions no aprovades després que es publiqués el Reial Decret 1015/2009 del 19 de juny pel qual es regula la disponibilitat de medicaments en diferents situacions especials (entre les quals hi ha l’ús en condicions no aprovades), i s’establís una normativa de l'Institut Català de la Salut (ICS), amb uns procediments estandarditzats de treball per revisar, avaluar i registrar l'ús de medicaments en les situacions especials. En la publicació Medicina Clínica 2014;143:327-9, es descriuen els medicaments utilitzats en condicions no aprovades i les indicacions en les que s'utilitzen a dos hospitals de tercer nivell durant els tres anys posteriors a la publicació del Reial Decret. Es van rebre 671 sol·licituds de 117 medicaments o combinacions per a ser emprats en aquestes condicions. Els subgrups més sol·licitats van ser antineoplàstics, immunosupressors i relaxants musculars, i els fàrmacs més freqüents van ser rituximab (170 sol·licituds), toxina botulínica (81), omalizumab (39) i anakinra (21). Les principals malalties van ser neoplàstiques, del sistema nerviós i òrgans dels sentits i de l’aparell digestiu. En la publicació European Journal of Clinical Pharmacology 2014;70:1385-93 s’analitzen les indicacions d'ús, els resultats clínics (resposta clínica i tolerabilitat de la medicació) i els resultats econòmics (cost total i per pacient) de l'ús dels medicaments en condicions no aprovades en cinc hospitals de l'ICS durant un any. S’hi van incloure de manera prospectiva 226 pacients, amb una edat mediana (RIQ) de 46 (33-62) anys; el 59% eren dones. Els pacients havien rebut una mediana de tres tractaments previs, i la principal raó per demanar l’ús no aprovat era la manca de resposta o resposta subòptima (72,1%). Es van donar 232 fàrmacs per a 102 indicacions diferents. Els fàrmacs més freqüents van ser rituximab (49; 21,1%), toxina botulínica (25; 10,7%) i omalizumab (14; 6,0%). En 117 casos (51,8%) el nivell d’evidència disponible per al seu ús era baix. Es va observar resposta parcial en 82 pacients (36,3%), completa en 71 (31,4%) i estabilització en 11 (4,9%). Va presentar efectes indesitjats 58 pacients (26,5%). El cost medià (RIQ) per pacient va ser de 2.943,07 € (541,9 – 5.872,54). En la publicació European Journal of Clinical Pharmacology 2013;69:1689-99 s’analitzen i es descriuen les indicacions d'ús, les evidències científiques disponibles i els resultats clínics a curt i llarg termini i econòmics, del fàrmac més utilitzat en condicions no aprovades que ha estat el rituximab. Es van analitzar 101 casos d’ús de rituximab en condicions no aprovades, amb una mediana d’edat (RIQ) dels pacients de 53 anys (37,5-68,0]; el 55,4% eren dones. Les indicacions principals eren malalties hematològiques (46%), malalties sistèmiques del teixit connectiu (27%) i malalties renals (20%). Les evidències eren principalment estudis de cohort individuals (53,5% dels casos) i sèries de casos (25,7%). La resposta observada a curt termini (mediana de 3 mesos [IQR 2-4]) va ser completa en el 38% dels casos i parcial en el 32,6%. Les més altes es van observar en el lupus eritematós sistèmic i la glomerulonefritis membranoproliferativa, i les respostes més baixes, en la neuromielitis òptica, i la púrpura trombocitopènica idiopàtica. En el 69,2% dels casos amb resposta a curt termini es va mantenir una certa resposta a llarg termini (mediana de 23 mesos [RIQ 12-30]). El cos per pacient (mediana va ser de 5.187,5€ (RIQ 5.187,5-7.781,3).Drug utilization studies can be useful to identify patterns of drug use in different populations, whether adult or children. One aspect is the analysis of drug use in conditions other than those authorized in the technical specifications or labelling. This thesis is an analysis of various aspects of off-label drug use after the publication of a Royal Decree 1015/2009 of 19 June regulating the availability of medicines in various special situations (including off-label drug use) and after the establishment of a rule of the Catalan Institute of Health (ICS) with standardized work procedures to review, evaluate and register the use of drugs in special situations. The publication Medicina Clínica 2014;143:327-9 describes the drugs used in conditions not approved in two tertiary hospitals during the three years following the publication of Royal Decree. There were 671 applications for 117 single drugs or combinations to use in these conditions. The main groups were antineoplastic, immunosuppressive and muscle relaxants, and the most involved drugs were rituximab (170 applications), botulinum toxin (81), omalizumab (39) and anakinra (21). The main diseases were neoplastic diseases, those affecting nervous system and sense organs and digestive disorders. The publication European Journal of Clinical Pharmacology 2014;70:1385-93 describes the analysis of indications for use, clinical outcomes (clinical response and tolerability of the medication) and cost of off-label drug use in five hospitals of the ICS during one year. A total of 226 patients were included. The median [IQR] age of patients was 46 (33-62) years; 59% were women. Patients had received a median of three previous treatments, and a lack of response (or suboptimal) was the main reason for off-label use (72.1%). A total of 232 off-label medicines were administered for 102 different indications. The most frequent medicines were rituximab (49; 21.1%), botulinum toxin (25; 10.7%) and omalizumab (14; 6.0%). In 117 (51.8%) cases the level of clinical evidence for their use was low. A partial clinical response was observed in 82 patients (36.3%), complete response in 71 (31.4%) and stabilization in 11 (4.9%). A total of 58 (26.5%) patients had adverse effects, which in 11 (4.9%) were severe. The median (IQR) cost per patient was € 2,943.07 (541.9 – 5,872.54). The publication European Journal of Clinical Pharmacology 2013;69:1689-99 describes the indications for use, the available scientific evidence and clinical results in the short and long term, and the cost of off-label use of rituximab. A total of 101 cases of off-label rituximab use were analyzed (median [IQR] age 53 years [37.5-68.0]; 55.4% women). The requested indications were mainly haematological diseases (46%), systemic connective tissue disorders (27%) and kidney diseases (20%). Available evidence in these indications were mainly individual cohort studies (53.5% of cases), and case series (25.7%). Short-term outcome (median 3 months [IQR 2-4]) was a complete response in 38% of cases and partial response in 32.6%. The highest short-term responses were observed for systemic lupus erythematosus and membranous glomerulonephritis, and the lowest for neuromyelitis optica and idiopathic thrombocytopenic purpura. Some response was maintained in long-term follow-up (median 23 months [IQR 12-30]) in 69.2% of patients with short-term response. Median cost per patient was € 5,187.5 (IQR 5,187.5-7,781.3)

Adverse Drug Reactions in Pediatric Oncohematology : A Systematic Review

Introduction: Adverse drug reactions (ADR) are an important cause of morbidity and mortality in pediatric patients. Due to the disease severity and chemotherapy safety profile, oncologic patients are at higher risk of ADR. However, there is little evidence on pharmacovigilance studies evaluating drug safety in this specific population. Methods: In order to assess the incidence and characteristics of ADR in pediatric patients with oncohematogical diseases and the methodology used in the studies, a systematic review was carried out using both free search and a combination of MeSH terms. Data extraction and critical appraisal were performed independently using a predefined form. Results: Fourteen studies were included, of which eight were prospective and half focused in inpatients. Sample size and study duration varied widely. Different methods of ADR identification were detected, used alone or combined. Causality and severity were assessed frequently, whereas preventability was lacking in most studies. ADR incidence varied between 14.4 and 67% in inpatients, and 19.6-68.1% in admissions, mainly in the form of hematological, gastrointestinal and skin toxicity. Between 11 and 16.4% ADR were considered severe, and preventability ranged from 0 to 74.5%. Conclusion: ADR in oncohematology pediatric patients are frequent. A high variability in study design and results has been found. The use of methodological standards and preventability assessment should be reinforced in order to allow results comparison between studies and centers, and to detected areas of improvement. Systematic Review Registration: , identifier CRD42018096513