Blanca Herrero’s research while affiliated with Hospital Infantil Universitario Niño Jesús and other places

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Publications (38)


Current situation of central nervous system tumour survivors in a spanish hospital
  • Article

January 2025

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5 Reads

Anales de Pediatría (English Edition)

Ivonne Marcela Rincón-Mantilla

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Blanca Herrero

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Elena Herranz Valero

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[...]

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Recruitment of patients in clinical trials from 2014 to 2022. The recruitment is shown per year and by trial type (non-specific trial, tumor-specific trial, and target-specific trial).
Patient flow through the trial.
(A) Kaplan–Meier curves for event-free survival of patients enrolled in phase I clinical trials (green) and phase II clinical trials (orange). (B) Kaplan–Meier curves for Overall Survival of patients enrolled in phase I clinical trials (green) and phase II clinical trials (orange).
(A) Kaplan–Meier curves for event-free survival of patients enrolled in non-specific trials (green), tumor-specific trials (orange) and trials using target-specific therapies (blue). (B) Kaplan–Meier curves for Overall Survival of patients enrolled in non-specific trials (green), tumor-specific trials (orange) and trials using target-specific therapies (blue).
Kaplan–Meier curves overall survival of patients with hematological malignancies (green) vs. solid tumors (orange).
Safety and outcome of children, adolescents and young adults participating in phase I/II clinical oncology trials: a 9-year center experience
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  • Full-text available

September 2024

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60 Reads

Introduction Enrolling children with cancer in early phase trials is crucial to access innovative treatments, contributing to advancing pediatric oncology research and providing tailored therapeutic options. Our objective is to analyze the impact of these trials on patient outcomes and safety, and to examine the evolution and feasibility of trials in pediatric cancer over the past decade. Methods All patients recruited in pediatric anticancer phase I/II clinical trials from January 2014 to December 2022 were included. Clinical records and trial protocols were analyzed. Results A total of 215 patients (median age 11.2 years, range 1–29.5) were included in 52 trials (258 inclusions). Patients with extracranial solid tumors (67%), central nervous system (CNS) tumors (24%), and leukemia (9%) were included. The most common investigational drugs were small molecules (28.3%) and antibodies (20.5%). Serious adverse events were experienced by 41% of patients, 4.4% discontinued treatment because of toxicity and two had toxic deaths. Median event-free survival was 3.7 months (95%CI: 2.8–4.5), longer in phase II trials than in phase I (2 vs. 6.3 months; p ≤ 0.001). Median overall survival was 12 months (95%CI: 9–15), higher in target-specific vs. non-target-specific trials (14 vs. 6 months; p ≤ 0.001). Discussion A significant and increasing number of patients have been included in early clinical trials, suggesting that both oncologists and families consider it valuable to be referred to specialized Units to access new therapies. Moreover, our data suggests that participation in early clinical trials, although not without potential toxicities, might have a positive impact on individual outcomes.

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Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients

August 2024

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45 Reads

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1 Citation

Background/Objectives: Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥ 3 thrombocytopenia occurs in around one-third of patients, and many of them become platelet transfusion-dependent. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP). Its role in managing thrombocytopenia and other cytopenias in CAR-T cell-treated patients has been scarcely addressed. Our aim was to report the safety and efficacy of this approach in patients included in the Spanish Group for Hematopoietic Transplantation and Cellular Therapy (GETH-TC) registry. Methods: This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion dependence subsequently to CAR-T cells and received eltrombopag to improve platelet counts were recruited in 10 Spanish hospitals. Results: Thirty-eight patients were enrolled and followed up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At the moment eltrombopag was indicated, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units transfused correlated with the time needed to restore platelet counts higher than 20 × 10⁹/L (Rho = 0.639, p < 0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of twenty-three (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of thirty-five (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only two transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions: Eltrombopag could be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.


Use of Eltrombopag to Improve Thrombocytopenia and Transfusion Requirement in Anti-CD19 Car-T Cell-Treated Patients

July 2024

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36 Reads

Background/Objectives Immune effector cell-associated hematotoxicity (ICAHT) is a frequent adverse event after chimeric antigen receptor (CAR)-T cell therapy. Grade ≥3 thrombocytopenia occurs in around one third of patients, many of whom become platelet transfusion-dependent. Without pharmacological support, platelet recovery may last for months. Eltrombopag is a thrombopoietin receptor agonist (TPO-RA) able to accelerate megakaryopoiesis, which has been used successfully in patients with bone marrow failure and immune thrombocytopenia (ITP.) Its role to manage thrombocytopenia, and other cytopenias, in CAR-T cell-treated patients has been scarcely addressed in the real-world setting. Our aim was to report the Feasibility of this approach and the outcome of patients included in the GETH-TC registry. Methods This is a retrospective, multicenter, observational study. Patients who developed platelet transfusion-dependence subsequently to CAR-T cell treatment were recruited in 10 Spanish hospitals and followed-up for at least 30 days after the first dose of eltrombopag was administered. Results Thirty-eight patients were enroled and followed-up for a median (interquartile range [IQR]) of 175 (99, 489) days since CAR-T cell infusion. At eltrombopag start, 18 patients had thrombocytopenia and another severe cytopenia, while 8 patients had severe pancytopenia. After 32 (14, 38) days on eltrombopag, 29 (76.3%) patients recovered platelet transfusion independence. The number of platelet units used correlated with the time needed to restore platelet counts to levels &sup3;20x109/L (Rho = 0.639, p <0.001). Non-responders to eltrombopag required more platelet units (58 [29, 69] vs. 12 [6, 26] in responders, p = 0.002). Nineteen out of 23 (82.6%) patients recovered from severe neutropenia after 22 (11, 31) days on eltrombopag. Twenty-nine out of 35 (82.9%) patients recovered red blood cell (RBC) transfusion independence after 29 (17, 44) days. Seven patients recovered all cell lineages while on treatment. No thromboembolic events were reported. Only 2 transient toxicities (cholestasis, hyperbilirubinemia) were reported during eltrombopag treatment, none of which compelled permanent drug withdrawal. Conclusions Eltrombopag can be safely used to manage thrombocytopenia and accelerate transfusion independence in CAR-T cell-treated patients.


Fig. 1 ECLIM-SEHOP structured organigram 2023
Fig. 2 Distribution of ECLIM-SEHOP studies according to cancer type
ECLIM-SEHOP: how to develop a platform to conduct academic trials for childhood cancer

April 2024

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94 Reads

Clinical and Translational Oncology

Introduction ECLIM-SEHOP platform was created in 2017. Its main objective is to establish the infrastructure to allow Spanish participation into international academic collaborative clinical trials, observational studies, and registries in pediatric oncology. The aim of this manuscript is to describe the activity conducted by ECLIM-SEHOP since its creation. Methods The platform’s database was queried to provide an overview of the studies integrally and partially supported by the organization. Data on trial recruitment and set-up/conduct metrics since its creation until November 2023 were extracted. Results ECLIM-SEHOP has supported 47 studies: 29 clinical trials and 18 observational studies/registries that have recruited a total of 5250 patients. Integral support has been given to 25 studies: 16 trials recruiting 584 patients and nine observational studies/registries recruiting 278 patients. The trials include front-line studies for leukemia, lymphoma, brain and solid extracranial tumors, and other key transversal topics such as off-label use of targeted therapies and survivorship. The mean time from regulatory authority submission to first patient recruited was 12.2 months and from first international site open to first Spanish site open was 31.3 months. Discussion ECLIM-SEHOP platform has remarkably improved the availability and accessibility of international academic clinical trials and has facilitated the centralization of resources in childhood cancer treatment. Despite the progressive improvement on clinical trial set-up metrics, timings should still be improved. The program has contributed to leveling survival rates in Spain with those of other European countries that presented major differences in the past.


Cancer is not a risk factor for severe COVID-19 in children, except in patients with recent allogeneic hematopoietic stem cell transplantion recipients or comorbidities.

March 2024

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35 Reads

The EPICO-SEHOP platform gathers data from children with SARS-CoV-2 in Spain, allowing comparison between children with cancer or allogeneic hematopoietic stem cell transplantation (alloHSCT) and those without. The infection is milder in the cancer/alloHSCT group than in children without comorbidities (7.1% vs. 15%), except in children with recent alloHSCT (less than 300 days), of which 35.7% experienced severe COVID-19. These data have been shared with the SEHOP members to support treatment and isolation policies akin to those for children without cancer, except for those with recent alloHSCT or additional comorbidities. This highlights the collaborative registries potential in managing pandemic emergencies.



Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring

January 2024

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43 Reads

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7 Citations

Introduction Loss of B-cell aplasia (BCA) is a well-known marker of functional loss of CD19 CAR-T. Most relapses and loss of BCA occur in the first months after CD19 CAR-T infusion. In addition, high tumor burden (HTB) has shown to have a strong impact on relapse, especially in CD19-negative. However, little is known about the impact of late loss of BCA or the relationship between BCA and pre-infusion tumor burden in patients infused with tisagenlecleucel for relapsed/refractory B-cell acute lymphoblastic leukemia. Therefore, the optimal management of patients with loss of BCA is yet to be defined. Methods We conducted a Spanish, multicentre, retrospective study in patients infused with tisagenlecleucel after marketing authorization. A total of 73 consecutively treated patients were evaluated. Results Prior to infusion, 39 patients had HTB (≥ 5% bone marrow blasts) whereas 34 had a low tumor burden (LTB) (<5% blasts). Complete remission was achieved in 90.4% of patients, of whom 59% relapsed. HTB was associated with inferior outcomes, with a 12-month EFS of 19.3% compared to 67.2% in patients with LTB (p<0.001) with a median follow-up of 13.5 months (95% CI 12.4 – 16.2). In the HTB subgroup relapses were mainly CD19-negative (72%) whereas in the LTB subgroup they were mainly CD19-positive (71%) (p=0.017). In the LTB group, all CD19-positive relapses were preceded by loss of BCA whereas only 57% (4/7) of HTB patients experienced CD19-positive relapse. We found a positive correlation between loss of BCA and CD19-positive relapse (R-squared: 74) which persisted beyond six months post-infusion. We also explored B-cell recovery over time using two different definitions of loss of BCA and found a few discrepancies. Interestingly, transient immature B-cell recovery followed by BCA was observed in two pediatric patients. In conclusion, HTB has an unfavorable impact on EFS and allo-SCT might be considered in all patients with HTB, regardless of BCA. In patients with LTB, loss of BCA preceded all CD19-positive relapses. CD19-positive relapse was also frequent in patients who lost BCA beyond six months post-infusion. Therefore, these patients are still at significant risk for relapse and close MRD monitoring and/or therapeutic interventions should be considered.


Role of urine culture in paediatric patients with cancer with fever and neutropenia: a prospective observational study

August 2023

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21 Reads

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1 Citation

Archives of Disease in Childhood

Objective To evaluate the need for routine urine studies in children with febrile neutropenia with cancer. Design A prospective, observational study was conducted in two hospitals between November 2019 and October 2021. Patients We recruited 205 patients in total. Main outcome measures The primary outcome was presence of positive urine culture (UC). Urinary tract infection (UTI) was defined as urinary signs/symptoms and positive UC with or without pyuria. A descriptive analysis of data is provided. We conducted a prospective study of paediatric patients with cancer with urinary continence. Data were analysed using descriptive statistics. The diagnostic performance of urinalysis was calculated using positive UC as the gold standard. Results Positive UC was found in 7 of the 205 patients (3.4%; 95% CI 1.4% to 6.9%), 2 presenting urinary symptoms. UTI prevalence was 1.0% (95% CI 0.1% to 3.5%). A 23.8% prevalence of positive UC was found in patients with urinary symptoms and/or history of urinary tract disease (95% CI 8.2% to 47.2%) as compared with 1.1% of those without symptoms or history (95% CI 0.1% to 3.9%) (p<0.001). The sensitivity, specificity, negative predictive value, and area under the curve for urinalysis were 16.7% (95% CI 3.0% to 56.4%), 98.4% (95% CI 95.3% to 99.4%), 97.3% (95% CI 93.9% to 98.9%), and 0.65 (95% CI 0.51 to 0.79), respectively. Conclusions UTI is an infrequent cause of infection in these patients. Urinalysis is indicated only in children with febrile neutropenia with urinary signs/symptoms and in asymptomatic patients with a history of urinary tract disease or unknown history. When urine is collected, UC should be requested regardless of the result of the urinalysis.


Citations (17)


... 48 In r/r B-ALL, it has been suggested that loss of BCA is associated with relapse, especially for patients with low tumor burden compared to patients with high tumor burden. 51 Despite the same target antigen (CD19), our results question this general principle in B-NHL since long-term treatment responses were noted even in the absence of persistent immune deficits. Indeed, this could indicate a "sweet spot" wherein a subset of lymphoma patients receiving CD19 CAR-T are able to reconstitute endogenous immunity in a disease-free state. ...

Reference:

Prognostic significance of immune reconstitution following CD19 CAR T‐cell therapy for relapsed/refractory B‐cell lymphoma
Impact of disease burden and late loss of B cell aplasia on the risk of relapse after CD19 chimeric antigen receptor T Cell (Tisagenlecleucel) infusion in pediatric and young adult patients with relapse/refractory acute lymphoblastic leukemia: role of B-cell monitoring

... Unlike acute respiratory or gastrointestinal infections, UTIs may present with nonspecific symptoms and no obvious clinical signs other than fever. Therefore, it may be missed unless urine cultures are routinely performed [10,11]. ...

Role of urine culture in paediatric patients with cancer with fever and neutropenia: a prospective observational study
  • Citing Article
  • August 2023

Archives of Disease in Childhood

... However, a few case reports have shown the feasibility of CAR-T in infants, and it is hoped more infants could be enrolled in future trials [193,194]. Consortia studies have equally validated the use of CAR-T in KMT2A-rearranged infant leukaemia [195,196]. ...

Tisagenlecleucel therapy for relapsed or refractory B-cell acute lymphoblastic leukaemia in infants and children younger than 3 years of age at screening: an international, multicentre, retrospective cohort study

The Lancet Haematology

... Hoste et al.'s international study of 273 children post-PIMS-TS also showed no concerning post-vaccination symptoms, with a single case of Bell's paralysis resolving without complications [20]. A Spanish study involving 32 post-PIMS-TS patients vaccinated without severe adverse reactions or PIMS-TS recurrence further supports the safety of vaccination [21]. Enthralling data from MAS/sJIA and Vaccination Working Parties of the Pediatric Rheumatology European Society described the results of a survey involving respondents from over 60 countries who provide vaccinations to children with a history of PIMS-TS. ...

Safety and Acceptance of COVID-19 Vaccination After Multisystem Inflammatory Syndrome in Children (MIS-C) in Spain
  • Citing Article
  • July 2022

Journal of the Pediatric Infectious Diseases Society

... In our cohort, the need for PICU admission was double, perhaps overestimated due to the limited sample size and also due to the selection of the sample including only patients with pneumonia (in other series published in our center, the actual PICU admission rate relative to all admitted COVID patients was lower [23][24][25][26]). Fortunately, in the current study the prognosis was found to be favorable, with a low rate of complications and mortality (<5% reported in previous articles; 4.5% in our study); the latter is directly associated with the presence of underlying conditions and not with SARS-CoV-2 as such [27,28]. ...

Comparison of pneumonia features in children caused by SARS-CoV-2 and other viral respiratory pathogens
  • Citing Article
  • June 2022

Pediatric Pulmonology

... Un meta-análisis que incluyó más de 21.000 NNA, concluyó que la presencia de 3 o más comorbilidades duplicaba la probabilidad de ingreso a cuidados críticos y cuadriplicaba la probabilidad de morir, confirmando el grupo que desde un comienzo sabíamos que era de riesgo 56 . Es importante recalcar que en segundo y tercer año de pandemia se logró establecer la baja frecuencia de bronquiolitis y de infección respiratoria baja por COVID-19, sin una distribución marcadamente estacional 58,59 . ...

SARS-CoV-2 acute bronchiolitis in hospitalized children: Neither frequent nor more severe

... Dehydration is associated with disease severity through organic osmolyte production, resulting in protein breakdown [41]. Fortunately, the high incidence of fever in this study was not correlated with disease severity (91% [31] of mild cases had fever), which was similar to Tagarro et al. [42]. On the other hand, a meta-analysis by Zhou et al. considered fever as a symptom for severe COVID-19 in children [43]. ...

Clinical spectrum of COVID-19 and risk factors associated with severity in Spanish children · EPICO-AEP Working Group

European Journal of Pediatrics

... However, the delayed and unstable immune reconstitution and the incidence of GVHD increase the rate of non-relapse mortality (NRM) in haplo-HSCT (10,11). Umbilical cord blood (UCB) transplantation (UCBT) is another option for HSCT due to its rapid graft acquisition and low incidence of GVHD and relapse (12,13), while UCB stem cells are less prone to delay and failure of engraftment (14,15). Recent studies reported that haplo-HSCT combined with third-party cord blood accelerated engraftment reduced the incidence of GVHD and the recurrence of hematologic malignancies, which was superior to either haploidentical or UCB transplantation alone (16)(17)(18). ...

Comparison of clinical outcomes between unrelated single umbilical cord blood and “ex-vivo” T-cell depleted haploidentical transplantation in children with hematological malignancies. World Journal of Pediatrics. 2021;1–10.
  • Citing Article
  • September 2021

World Journal of Pediatrics

... En segundo lugar, la manipulación genética de esos linfocitos T y, en tercer lugar, la infusión de nuevo al paciente de las células T modificadas. 18 En la actualidad y con el objetivo de tratar las formas resistentes del linfoma no Hodgkin de células grandes, el antígeno utilizado de forma mayoritaria es el CD19, que solo se encuentra en las células B. 19,20 ...

Anti-CD19 CAR-T cell theraphy in pediatric patients with relapsed/refractory acute lymphoblastic leukemia. Experience at Hospital Infantil Universitario Niño Jesús
  • Citing Article
  • August 2021

ANALES RANM

... Another important difference is that the available literature is limited to the adult population. The dynamics of the antibody response has been well described in adults [26], while there are few data in the pediatric population. A difference in the distribution, maturation and functioning of viral receptors has been mentioned as a possible reason for the age-related peculiarities [27]. ...

Dynamics of RT-PCR and Serologic Test Results in Children with SARS-CoV-2 Infection
  • Citing Article
  • September 2021

The Journal of Pediatrics