Radiation recall reaction induced by gemcitabine/docetaxel in children: A retrospective study on risk factors and outcomes.

INTRODUCTION: Radiation recall reaction (RRR) is a rare inflammatory reaction developing in a previously irradiated field after a triggering agent. In pediatric patients, it is poorly understood and deficiently studied. Gemcitabine-docetaxel (G/D) in childhood cancer is mainly used as a salvage regimen for sarcomas. We aim to describe RRR triggered by G/D in children. PATIENTS AND METHODS: Retrospective review of 21 patients receiving G/D along with radiotherapy at two hospitals from 2010 until 2022. RRR was considered as any toxicity occurring after G/D administration in a previously irradiated field. RRR features were described. Fisher's and Mann-Whitney tests were utilized to analyze the risk factors involved. RESULTS: Sixteen episodes of RRR developed in 16 (76.2%) patients. RRR mainly involved deep layers of the skin (58%) and occurred predominantly after two G/D cycles. The mean time between radiotherapy and chemotherapy was 28.5 days (0-1359 days), and the mean radiation volume 391 mL (157-1810 mL) for RRR. RRR treatment was mainly systemic steroids, with partial responses in six of 11 (58%) patients. Re-exposure to G/D was associated with a high rate of recurrence in nine of 15 (56.2%), prompting drug discontinuation. The major risk factors for RRR after G/D include, without statistical significance, a larger volume of the irradiated field and a shorter interval between chemotherapy and radiotherapy. CONCLUSIONS: The incidence of RRR after G/D in the pediatric population is higher than previously reported. Drug re-exposure is usually followed by recurrence. Higher irradiated volumes and a shorter time to the start of chemotherapy could be related with an increased risk of RRR.

Naxitamab combined with granulocyte-macrophage colony-stimulating factor as consolidation for high-risk neuroblastoma patients in complete remission.

BACKGROUND: Naxitamab is a humanized anti-disialoganglioside (GD2) monoclonal antibody approved for treatment of bone/bone marrow refractory high-risk neuroblastoma (HR-NB). Compassionate use (CU) expanded access program at Hospital Sant Joan de Deu permitted treatment of patients in complete remission (CR). We here report the survival, toxicity, and relapse pattern of patients in first or second CR treated with naxitamab and sargramostim (GM-CSF). PROCEDURE: Seventy-three consecutive patients with HR-NB (stage M at age >18 months or MYCN-amplified stages L1/L2 at any age) were treated in first or second CR. Treatment comprised five cycles of subcutaneous (SC) GM-CSF for 5 days at 250 µg/m2 /day (days -4 to 0), followed by naxitamab + SC GM-CSF for 5 days at 500 µg/m2 /day (days 1-5). Naxitamab was infused over 30 minutes at 3 mg/kg/day, days 1, 3, and 5, outpatient. RESULTS: Fifty-five patients were in first CR and 18 in second CR. Seventeen patients had MYCN-amplified NB and 11 detectable minimal residual disease in the bone marrow. Fifty-eight (79.5%) patients completed therapy. Four (5%) experienced grade 4 toxicities and 10 (14%) early relapse. Three-year event-free survival (EFS) 58.4%, 95% CI = (43.5%, 78.4%) and overall survival (OS) 82.4%, 95% CI = (66.8%, 100%). First CR patients 3-year EFS 74.3%, 95% CI = (62.7%, 88.1%), and OS 91.6%, 95% CI = (82.4%, 100%). EFS is significantly different between first and second CR (p = .0029). The pattern of relapse is predominantly (75%) of an isolated organ, mainly bone (54%). Univariate Cox models show prior history of relapse as the only statistically significant predictor of EFS but not OS. CONCLUSIONS: Consolidation with naxitamab and GM-CSF resulted in excellent survival rates for HR-NB patients in CR.

Transverse myelitis as an unexpected complication following treatment with dinutuximab in pediatric patients with high-risk neuroblastoma: A case series.

Immunotherapy with the anti-GD2 monoclonal antibody ch14.18, or dinutuximab, represents an important therapeutic advance in the treatment of pediatric high-risk neuroblastoma and is now considered part of standard of care in this patient population. To date, transverse myelitis as a result of dinutuximab therapy has not been reported in clinical trials or in the published literature. We describe three patients with clinical symptoms of transverse myelitis, confirmed via magnetic resonance imaging, shortly following initiation of dinutuximab. All patients were discontinued from dinutuximab treatment and received urgent treatment, with rapid improvement in symptoms and resultant functional recovery.

Management of High-Risk Neuroblastoma with Soft-Tissue-Only Disease in the Era of Anti-GD2 Immunotherapy.

Neuroblastoma presents with two patterns of disease: locoregional or systemic. The poor prognostic risk factors of locoregional neuroblastoma (LR-NB) include age, MYCN or MDM2-CDK4 amplification, 11q, histology, diploidy with ALK or TERT mutations, and ATRX aberrations. Anti-GD2 immunotherapy has significantly improved the outcome of high-risk (HR) NB and is mostly effective against osteomedullary minimal residual disease (MRD), but less so against soft tissue disease. The question is whether adding anti-GD2 monoclonal antibodies (mAbs) benefits patients with HR-NB compounded by only soft tissue. We reviewed 31 patients treated at SJD for HR-NB with no osteomedullary involvement at diagnosis. All tumors had molecular genetic features of HR-NB. The outcome after first-line treatment showed 25 (80.6%) patients achieving CR. Thirteen patients remain in continued CR, median follow-up 3.9 years. We analyzed whether adding anti-GD2 immunotherapy to first-line treatment had any prognostic significance. The EFS analysis using Cox models showed a HR of 0.20, p = 0.0054, and an 80% decrease in the risk of relapse in patients treated with anti-GD2 immunotherapy in the first line. Neither EFS nor OS were significantly different by CR status after first-line treatment. In conclusion, adding treatment with anti-GD2 mAbs at the stage of MRD helps prevent relapse that unequivocally portends poor survival.

Desensitizing the autonomic nervous system to mitigate anti-GD2 monoclonal antibody side effects.

Background: Anti-GD2 monoclonal antibodies (mAbs) have shown to improve the overall survival of patients with high-risk neuroblastoma (HR-NB). Serious adverse events (AEs), including pain, within hours of antibody infusion, have limited the development of these therapies. In this study, we provide evidence of Autonomic Nervous System (ANS) activation as the mechanism to explain the main side effects of anti-GD2 mAbs. Methods: Through confocal microscopy and computational super-resolution microscopy experiments we explored GD2 expression in postnatal nerves of infants. In patients we assessed the ANS using the Sympathetic Skin Response (SSR) test. To exploit tachyphylaxis, a novel infusion protocol (the Step-Up) was mathematically modelled and tested. Results: Through confocal microscopy, GD2 expression is clearly visible in the perineurium surrounding the nuclei of nerve cells. By computational super-resolution microscopy experiments we showed the selective expression of GD2 on the cell membranes of human Schwann cells in peripheral nerves (PNs) significantly lower than on NB. In patients, changes in the SSR were observed 4 minutes into the anti-GD2 mAb naxitamab infusion. SSR latency quickly shortened followed by gradual decrease in the amplitude before disappearance. SSR response did not recover for 24 hours consistent with tachyphylaxis and absence of side effects in the clinic. The Step-Up protocol dissociated on-target off-tumor side effects while maintaining serum drug exposure. Conclusion: We provide first evidence of the ANS as the principal non-tumor target of anti-GD2 mAbs in humans. We describe the development and modeling of the Step-Up protocol exploiting the tachyphylaxis phenomenon we demonstrate in patients using the SSR test.

Novel infusion strategy reduces severe adverse events caused by the anti-GD2 monoclonal antibody naxitamab.

Introduction: Anti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) are associated with Grade ≥3 (≥G3) adverse events (AEs) such as severe pain, hypotension, and bronchospasm. We developed a novel method of administering the GD2-binding mAb naxitamab, termed "Step-Up" infusion (STU), to reduce the risk of AEs of severe pain, hypotension, and bronchospasm. Methods: Forty-two patients with GD2-positive tumors received naxitamab under "compassionate use" protocols and administered via either the standard infusion regimen (SIR) or the STU regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and delivered in 90 min according to the same gradual-increase strategy. AEs were graded according to Common Terminology Criteria for Adverse Events version 4.0. Results: The frequency of infusions with an associated G3 AE was reduced from 8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR. Discussion: The comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.

Early Salvage Chemo-Immunotherapy with Irinotecan, Temozolomide and Naxitamab Plus GM-CSF (HITS) for Patients with Primary Refractory High-Risk Neuroblastoma Provide the Best Chance for Long-Term Outcomes.

Patients with high-risk neuroblastoma (HR-NB) who are unable to achieve a complete response (CR) to induction therapy have worse outcomes. We investigated the combination of humanized anti-GD2 mAb naxitamab (Hu3F8), irinotecan (I), temozolomide (T), and sargramostim (GM-CSF)-HITS-against primary resistant HR-NB. Eligibility criteria included having a measurable chemo-resistant disease at the end of induction (EOI) treatment. Patients were excluded if they had progressive disease (PD) during induction. Prior anti-GD2 mAb and/or I/T therapy was permitted. Each cycle, administered four weeks apart, comprised Irinotecan 50 mg/m2/day intravenously (IV) plus Temozolomide 150 mg/m2/day orally (days 1-5); naxitamab 2.25 mg/kg/day IV on days 2, 4, 8 and 10, (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously was used (days 6-10). Toxicity was measured using CTCAE v4.0 and responses through the modified International Neuroblastoma Response Criteria (INRC). Thirty-four patients (median age at treatment initiation, 4.9 years) received 164 (median 4; 1-12) HITS cycles. Toxicities included myelosuppression and diarrhea, which was expected with I/T, and pain and hypertension, expected with naxitamab. Grade ≥3-related toxicities occurred in 29 (85%) of the 34 patients; treatment was outpatient. The best responses were CR = 29% (n = 10); PR = 3% (n = 1); SD = 53% (n = 18); PD = 5% (n = 5). For cohort 1 (early treatment), the best responses were CR = 47% (n = 8) and SD = 53% (n = 9). In cohort 2 (late treatment), the best responses were CR = 12% (n = 2); PR = 6% (n = 1); SD = 53% (n = 9); and PD = 29% (n = 5). Cohort 1 had a 3-year OS of 84.8% and EFS 54.4%, which are statistically significant improvements (EFS p = 0.0041 and OS p = 0.0037) compared to cohort 2. In conclusion, naxitamab-based chemo-immunotherapy is effective against primary chemo-resistant HR-NB, increasing long-term outcomes when administered early during the course of treatment.

Naxitamab Combined with Granulocyte-Macrophage Colony-Stimulating Factor as Consolidation for High-Risk Neuroblastoma Patients in First Complete Remission under Compassionate Use-Updated Outcome Report.

Naxitamab is an anti-GD2 antibody approved for the treatment of relapsed/refractory HR-NB. We report the survival, safety, and relapse pattern of a unique set of HR-NB patients consolidated with naxitamab after having achieved first CR. Eighty-two patients were treated with 5 cycles of GM-CSF for 5 days at 250 µg/m2/day (-4 to 0), followed by GM-CSF for 5 days at 500 µg/m2/day (1-5) and naxitamab at 3 mg/kg/day (1, 3, 5), on an outpatient basis. All patients but one were older than 18 months at diagnosis and had stage M; 21 (25.6%) pts had MYCN-amplified (A) NB; and 12 (14.6%) detectable MRD in the BM. Eleven (13.4%) pts had received high-dose chemotherapy and ASCT and 26 (31.7%) radiotherapy before immunotherapy. With a median follow-up of 37.4 months, 31 (37.8%) pts have relapsed. The pattern of relapse was predominantly (77.4%) an isolated organ. Five-year EFS and OS were 57.9% (71.4% for MYCN A) 95% CI = (47.2, 70.9%); and 78.6% (81% for MYCN A) 95% CI = (68.7%, 89.8%), respectively. EFS showed significant differences for patients having received ASCT (p = 0.037) and pre-immunotherapy MRD (p = 0.0011). Cox models showed only MRD as a predictor of EFS. In conclusion, consolidation with naxitamab resulted in reassuring survival rates for HR-NB patients after end-induction CR.

EpiGe: A machine-learning strategy for rapid classification of medulloblastoma using PCR-based methyl-genotyping.

Molecular classification of medulloblastoma is critical for the treatment of this brain tumor. Array-based DNA methylation profiling has emerged as a powerful approach for brain tumor classification. However, this technology is currently not widely available. We present a machine-learning decision support system (DSS) that enables the classification of the principal molecular groups-WNT, SHH, and non-WNT/non-SHH-directly from quantitative PCR (qPCR) data. We propose a framework where the developed DSS appears as a user-friendly web-application-EpiGe-App-that enables automated interpretation of qPCR methylation data and subsequent molecular group prediction. The basis of our classification strategy is a previously validated six-cytosine signature with subgroup-specific methylation profiles. This reduced set of markers enabled us to develop a methyl-genotyping assay capable of determining the methylation status of cytosines using qPCR instruments. This study provides a comprehensive approach for rapid classification of clinically relevant medulloblastoma groups, using readily accessible equipment and an easy-to-use web-application.t.

Clinical and Pathological Evidence of Anti-GD2 Immunotherapy Induced Differentiation in Relapsed/Refractory High-Risk Neuroblastoma.

BACKGROUND: Neuroblastic tumors (NBTs) originate from a block in the process of differentiation. Histologically, NBTs are classified in neuroblastoma (NB), ganglioneuroblastoma (GNB), and ganglioneuroma (GN). Current therapy for high-risk (HR) NB includes chemotherapy, surgery, radiotherapy, and anti-GD2 monoclonal antibodies (mAbs). Anti-GD2 mAbs induce immunological cytoxicity but also direct cell death. METHODS: We report on patients treated with naxitamab for chemorefractory NB showing lesions with long periods of stable disease. Target lesions with persisting 123I-Metaiodobenzylguanidine (MIBG) uptake after 4 cycles of immunotherapy were further evaluated by functional Magnetic Resonance Imaging (MRI) and/or Fluorodeoxyglucose (FDG)-positron emission tomography (PET). MIBG avid lesions that became non-restrictive on MRI (apparent diffusion coefficient (ADC) > 1) and/or FDG-PET negative (SUV < 2) were biopsied. RESULTS: Twenty-seven relapse/refractory (R/R) HR-NB patients were enrolled on protocol Ymabs 201. Two (7.5%) of the 27 showed persistent bone lesions on MIBG, ADC high, and/or FDG-PET negative. Forty-four R/R HR-NB patients received chemo-immunotherapy. Twelve (27%) of the 44 developed persistent MIBG+ but FDG-PET- and/or high ADC lesions. Twelve (86%) of the 14 cases identified were successfully biopsied producing 16 evaluable samples. Histology showed ganglioneuroma maturing subtype in 6 (37.5%); ganglioneuroma mature subtype with no neuroblastic component in 4 (25%); differentiating NB with no Schwannian stroma in 5 (31%); and undifferentiated NB without Schwannian stroma in one (6%). Overall, 10 (62.5%) of the 16 specimens were histopathologically fully mature NBTs. CONCLUSIONS: Our results disclose an undescribed mechanism of action for naxitamab and highlight the limitations of conventional imaging in the evaluation of anti-GD2 immunotherapy clinical efficacy for HR-NB.

Prognostic value of patient-derived xenograft engraftment in pediatric sarcomas.

The goals of this work were to identify factors favoring patient-derived xenograft (PDX) engraftment and study the association between PDX engraftment and prognosis in pediatric patients with Ewing sarcoma, osteosarcoma, and rhabdomyosarcoma. We used immunodeficient mice to establish 30 subcutaneous PDX from patient tumor biopsies, with a successful engraftment rate of 44%. Age greater than 12 years and relapsed disease were patient factors associated with higher engraftment rate. Tumor type and biopsy location did not associate with engraftment. PDX models retained histology markers and most chromosomal aberrations of patient samples during successive passages in mice. Model treatment with irinotecan resulted in significant activity in 20 of the PDXs and replicated the response of rhabdomyosarcoma patients. Successive generations of PDXs responded similarly to irinotecan, demonstrating functional stability of these models. Importantly, out of 68 tumor samples from 51 patients with a median follow-up of 21.2 months, PDX engraftment from newly diagnosed patients was a prognostic factor significantly associated with poor outcome (p = 0.040). This association was not significant for relapsed patients. In the subgroup of patients with newly diagnosed Ewing sarcoma classified as standard risk, we found higher risk of relapse or refractory disease associated with those samples that produced stable PDX models (p = 0.0357). Overall, our study shows that PDX engraftment predicts worse outcome in newly diagnosed pediatric sarcoma patients.

The Role of Autologous Stem-Cell Transplantation in High-Risk Neuroblastoma Consolidated by anti-GD2 Immunotherapy. Results of Two Consecutive Studies.

Background: Treatment of HR-NB comprise induction, consolidation with autologous stem cell transplant (ASCT) followed by anti-GD2 immunotherapy and isotretinoin. Childrens Oncology Group and SIOPEN studies used dinutuximab and cytokines to treat patients in complete remission or refractory Bone/Bone marrow (B/BM) disease after ASCT. Methods: HR-NB patients referred to Hospital Sant Joan de Déu for anti-GD2 immunotherapy were eligible for two consecutive studies (dinutuximab for EudraCT 2013-004864-69 and naxitamab for 017-001829-40) and naxitamab/Sargramostim CU with or without prior ASCT. Patients enrolled in first complete remission or with primary refractory B/BM disease. We accrued a study population of two groups whose therapy, aside from ASCT, was similar. This is a retrospective analysis of their outcome calculated from study entry. Results: From December 2014-2019, 67 patients were treated with dinutuximab and cytokines (n = 21) in the Hospital Sant Joan de Déu-HRNB-Ch14.18 study or with naxitamab and Sargramostim either in the Ymabs study 201 (n = 12) or CU (n = 34). 23 patients were treated with primary refractory disease in the B/BM (11 with dinutuximab and 12 with naxitamab), and 44 in first CR (10 with dinutuximab and 34 with naxitamab). Study patients included 13 (19.4%) treated following single ASCT and 54 following conventional chemotherapy. Median follow-up for all patients is 16.2 months. Two-year rates for ASCT and non-ASCT patients were, respectively, EFS 64.1% vs. 54.2% (p = 0.28), and OS 66.7% vs. 84.1% (p = 0.81). For the 44 pts in first CR, 2-years rates for ASCT and non-ASCT patients were, respectively, EFS 65.5% vs. 58.7% (p = 0.48), and OS 71.4% vs. 85.4% (p = 0.63). Conclusions: In this retrospective, single center study, ASCT did not provide survival benefit when anti-GD2 immunotherapy was used after induction chemotherapy.

Impact of COVID-19 in paediatric early-phase cancer clinical trials in Europe: A report from the Innovative Therapies for Children with Cancer (ITCC) consortium.

INTRODUCTION: Data regarding real-world impact on cancer clinical research during COVID-19 are scarce. We analysed the impact of the COVID-19 pandemic on the conduct of paediatric cancer phase I-II trials in Europe through the experience of the Innovative Therapies for Children with Cancer (ITCC). METHODS: A survey was sent to all ITCC-accredited early-phase clinical trial hospitals including questions about impact on staff activities, recruitment, patient care, supply of investigational products and legal aspects, between 1st March and 30th April 2020. RESULTS: Thirty-one of 53 hospitals from 12 countries participated. Challenges reported included staff constraints (30% drop), reduction in planned monitoring activity (67% drop of site initiation visits and 64% of monitoring visits) and patient recruitment (61% drop compared with that in 2019). The percentage of phase I, phase II trials and molecular platforms closing to recruitment in at least one site was 48.5%, 61.3% and 64.3%, respectively. In addition, 26% of sites had restrictions on performing trial assessments because of local contingency plans. Almost half of the units suffered impact upon pending contracts. Most hospitals (65%) are planning on improving organisational and structural changes. CONCLUSION: The study reveals a profound disruption of paediatric cancer early-phase clinical research due to the COVID-19 pandemic across Europe. Reported difficulties affected both patient care and monitoring activity. Efforts should be made to reallocate resources to avoid lost opportunities for patients and to allow the continued advancement of oncology research. Identified adaptations to clinical trial procedures may be integrated to increase preparedness of clinical research to futures crises.

Treatment-driven selection of chemoresistant Ewing sarcoma tumors with limited drug distribution.

Ewing sarcoma is a bone and soft tissue tumor predominantly affecting adolescents and young adults. To characterize changes in anticancer drug activity and intratumor drug distribution during the evolution of Ewing sarcomas, we used immunodeficient mice to establish pairs of patient-derived xenografts (PDX) at early (initial diagnosis) and late (relapse or refractory progression) stages of the disease from three patients. Analysis of copy number alterations (CNA) in early passage PDX tissues showed that two tumor pairs established from patients which responded initially to therapy and relapsed more than one year later displayed similar CNAs at early and late stages. For these two patients, PDX established from late tumors were more resistant to chemotherapy (irinotecan) than early counterparts. In contrast, the tumor pair established at refractory progression showed highly dissimilar CNA profiles, and the pattern of response to chemotherapy was discordant with those of relapsed cases. In mice receiving irinotecan infusions, the level of SN-38 (active metabolite of irinotecan) in the intracellular tumor compartment was reduced in tumors at later stages compared to earlier tumors for those pairs bearing similar CNAs, suggesting that distribution of anticancer drug shifted toward the extracellular compartment during clonal tumor evolution. Overexpression of the drug transporter P-glycoprotein in late tumor was likely responsible for this shift in drug distribution in one of the cases.

Feocromocitoma: Enfoque Multidisciplinario, Consideraciones Perioperatorias / Pheochromocytoma: Multidisciplinary Approach Perioperative Considerations

Paciente programada para una suprarrenalectomía con la técnica laparoscópica, debido a un tumor de la glándula suprarrenal izquierda, su diagnóstico Hipertensión arterial crónica, se volvió difícil de controlar, por tal motivo se le solicita batería para descartar Feocromocitoma, resultando portadora de un tumor de la glándula suprarrenal izquierdo. El trabajo en equipo de las especialidades involucradas en el cuidado de la paciente, la comunicación efectiva, la preparación pre quirúrgica y el manejo periopertorio; dió como resultado que la paciente presentara mínimas complicaciones perioperatorias, permaneció en unidad de cuidados intensivos un día y se disminuyó la estancia hospitalaria.

Patient scheduled for an adrenalectomy with laparoscopic technique, due to a tumor of the left adrenal gland. The diagnosis of chronic arterial hypertension was difficult to control, so a test was requested to rule out pheochromocytoma, resulting in a tumor of the left adrenal gland. The teamwork of the specialties involved in the care of the patient, effective communication, pre-surgical preparation and perioperative management, resulted in minimal perioperative complications in the patient, remaining in the intensive care unit for one day and reducing the hospital stay.

Estudio Exploratorio sobre Estrategias y Errores de un Estudiante con Trastorno del Espectro Autista al Resolver Problemas de División Partitiva / An Exploratory Study on Strategies and Errors of a Student with Autism Spectrum Disorder when Solving Partitive Division Problems

RESUMEN: En los últimos años ha aumentado notablemente el interés por analizar el rendimiento académico de los estudiantes con trastorno del espectro autista (TEA). Entre las materias escolares, las matemáticas son uno de los grandes obstáculos que encuentran estos estudiantes. Por consiguiente, es fundamental mejorar nuestro conocimiento sobre el modo en que los estudiantes con TEA aprenden diferentes conceptos matemáticos para luego proporcionarles métodos de enseñanza adaptados a sus necesidades. Este documento explora las estrategias y los errores que un estudiante de 11 años diagnosticado con TEA muestra al resolver problemas aritméticos verbales de división. Se diseñó una secuencia de enseñanza compuesta por problemas en dos formatos diferentes: con y sin material manipulativo. Se recogieron datos durante 15 sesiones de una hora en las cuales el estudiante resolvió un total de 49 problemas. Los resultados muestran una clara preferencia por la estrategia de reparto por múltiplos para los problemas en los que dispone de material manipulativo, mientras que recurre principalmente a la estrategia de reparto uno a uno cuando no dispone de material. Se identifica un conjunto de errores relacionados con los significados de las nociones de partición, equidad y representatividad, necesarios para resolver con éxito problemas aritméticos verbales de división partitiva.

ABSTRACT: In recent years there has been an increasing interest in studying the academic performance of students with Autism Spectrum Disorder (ASD). Among school subjects, mathematics is one of the great obstacles that face students with ASD. It is therefore crucial to go in depth into the understanding that they develop on mathematical concepts, to later provide learning instructions adapted to their needs. This paper explores the strategies and errors that an 11-year old student diagnosed with ASD shows when solving partitive division word problems. A teaching sequence has been designed that includes problems in two different formats: with and without support material. The data was collected during 15 one-hour sessions in which the student solved a total of 49 problems. Results show a clear preference for the one-to-many correspondence strategy in the problems with support material whereas the student mainly resorted to the sharing one-by-one strategy when he did not have the material. A list of errors has been identified related to the meaning of the notions of partition, equity and representativeness, required in partitive division word problems.