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Purpose: Invasive Pulmonary Fungal Infections (IPFIs) represent a diagnostic and therapeutic challenge. The exact role of surgery is not well defined. This study analyzes our experience with surgical treatment of IPFI in immunocompromised pediatric patients and, secondarily, compares IPFI caused by Aspergillus spp. with other fungal infections., Methods: This is a retrospective review (2000-2019) of patients with IPFI surgically treated at our pediatric institution. Statistical analysis was used to compare data between Aspergillus spp. and non-Aspergillus IPFI., Results: Twenty-five patients (64% female) underwent 29 lung resections. Median age at surgery was 7.19 years (1.63-19.14). The most frequent underlying condition (64%) was acute leukemia. Surgical indications included persistence or worsening of symptoms and pathological image findings (52%) or asymptomatic suspicious lesions in patients scheduled for intensive cytotoxic treatments or hematopoietic stem cell transplantation (48%). All patients underwent atypical lung resections, except one lobectomy. Aspergillus spp. was the most frequently isolated pathogen (68%). Follow-up was 4.07 years (0.07-18.07). Surgery-related mortality was 0%, but 4 patients died in the 100 days following surgery (2 due to disseminated fungal infection); the remaining 21 did not show signs of IPFI recurrence. Non-specific consolidations on CT scan were more frequent in non-Aspergillus IPFI (p < 0.05)., Conclusion: Surgical treatment of IPFI should be considered as a part of the treatment in selected pediatric immunocompromised patients, and it may have both diagnostic and therapeutic advantages over non-surgical management. When there is clinical suspicion of IPFI but CT scan shows unspecific alterations, the possibility of a non-Aspergillus IPFI should be considered., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Transplantation-associated thrombotic microangiopathy (TA-TMA) is associated with high morbidity and mortality. Although survival has improved significantly with the introduction of eculizumab, the need for improvement remains, especially in high-risk patients. This study aimed to describe the results obtained with eculizumab in a pediatric cohort with the attempt to define which risk factors could determine the response to treatment. We designed a national multicenter retrospective study of children treated with eculizumab for high-risk TA-TMA. The study cohort comprised 29 patients who had undergone a first (n = 28) or second (n = 1) allogeneic hematopoietic stem cell transplantation (HSCT) for malignant (n = 17) or nonmalignant (n = 12) disease. The median time from HSCT to TA-TMA diagnosis was 154 days (interquartile range [IQR], 103 to 263 days). Eleven patients (38%) who were initially diagnosed with low- to intermediate-risk TA-TMA progressed to high-risk TA-TMA (hrTA-TMA), within a median time of 4 days (IQR, 1 to 33 days). SC5b-9 was increased in 90% of 20 patients in whom it was measured. Renal (n = 12), pulmonary (n = 1), and intestinal (n = 1) biopsy confirmed the diagnosis in 12 of 14 patients (85%). Seventeen patients (58%) had extrarenal involvement with serositis (n = 13; 44,8%), pulmonary (n = 12; 41,4%), gastrointestinal (n = 8; 27.6%), cardiovascular (n = 7; 24.1%), or central nervous system (CNS) (n = 2; 6.9%) involvement. The median time from hrTA-TMA diagnosis to the initiation of eculizumab was 7 days (IQR, 1 to 8 days). Overall, 19 patients (65.5%) responded to eculizumab, of whom 17 (58.6%) achieved a complete response and 2 (6.9%) achieved a partial response. The remaining 10 patients (34.5%) did not show any of response. The overall response rate to eculizumab for TA-TMA was 27.59% (95% confidence interval [CI], 14.87% to 47.66%) at 1 month, 55.17% (95% CI, 38.43% to 73.48%) at 3 months, and 62.07% (95% CI, 45.10% to 79.13%) at 6 months after eculizumab initiation. In multivariate analysis, the pulmonary involvement decreased the probability of response (hazard ratio [HR], .18; P = .0298). The 1-year overall survival (OS) was 55.2% (95% CI, 35.6% to 71.0%) for the whole cohort and 83.3% (95% CI, 56.7% to 94.3%) for patients who responded to eculizumab. Pulmonary involvement (HR, 14.93; P = .0043) and CNS involvement (HR, 8.63; P = .0497) were associated with a statistically significant decrease in survival. We found that patients diagnosed with hrTA-TMA with pulmonary involvement had a poor response to eculizumab, and that patients with pulmonary and CNS involvement had significantly decreased survival. Given these results, we hypothesize that providing eculizumab therapy at an early stage of the disease before organ damage is established might significantly improve the response and, consequently, survival., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Objectives: To describe mesenchymal stromal cells (MSCs) in the treatment of hematopoietic stem cell transplantation (HSCT) complications and to assess its safety and efficacy., Methods: Single-center retrospective study (2016-2023). Patients under 20 years who received MSCs for the treatment of HSCT-related complications were included., Results: Thirty patients (53.7% boys), median age at transplant 11 years (range 2-19) were included. MSCs indications were: graft-vs.-host disease (GVHD) in 18 patients (60%), of them 13 had acute GVHD (43.3%) and 5 chronic GVHD (16.7%); Grade 3-4 hemorrhagic cystitis (HC) in 4 (13.3%); poor graft function (PGF) in 6 (20%), 5 of them receiving MSCs with a CD34 stem cell-boost coinfusion; graft failure (GF) in 2 (6.7%), to enhance engraftment after a subsequent HSCT. Infusion-related-adverse-events were not reported. Overall response (OR) was 83% (25/30); 44% of responders (11/25) showed complete response (CR). OR for GVHD, HC, PGF and GF was 83.3%, 100%, 66.7% and 100% respectively. Response rate was 40% (95% CI: 20-55) and 79% (95% CI: 57-89) at 15 and 30 days. With a median follow-up of 21 months (IQR11-52.5), overall survival (OS) was 86% (95% CI: 74-100) and 79% (95% CI: 65-95) at 6 and 12 months post-MSCs infusion., Conclusion: In our study, the most frequent indication of MSCs was refractory aGVHD (43.3%). Response rates were high (OR 83%) and safety profile was good., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Pérez-Torres Lobato, Benitez-Carabante, Alonso, Torrents, Castillo Flores, Uria Oficialdegui, Panesso, Alonso-Martínez, Oliveras, Renedo-Miró, Vives and Diaz-de-Heredia.)

Introduction: Hematopoietic stem cell transplantation (HCT) can cure chronic granulomatous disease (CGD). However, transplant-associated morbidity or mortality may occur, and it is still controversial which patients benefit from this procedure. The aim of this retrospective study was to evaluate the outcome of pediatric patients who received HCT in one of the Spanish pediatric transplant units., Results: Thirty children with a median age of 6.9 years (range 0.6-12.7) were evaluated: 8 patients received a transplant from a sibling donor (MSD), 21 received a transplant from an unrelated donor (UD), and 1 received a haploidentical transplant. The majority of the patients received reduced-intensity conditioning regimens based on either busulfan plus fludarabine or treosulfan. Relevant post-HCT complications were as follows: i) graft failure (GF), with a global incidence of 28.26% (CI: 15.15-48.88), 11.1% in patients with MSD (1.64-56.70) and 37.08% in unrelated donors (19.33-63.17); and ii) chronic graft-versus-host disease (GVHD), with an incidence of 20.5% (8.9-43.2), 11.1% in patients with MSD (1.64-56.70) and 26.7% in unrelated donors (10.42-58.44). Post-HCT infections were usually manageable, but two episodes of pulmonary aspergillosis were diagnosed in the context of graft rejection. The 2-year OS was 77.3% (55.92-89.23). There were no statistically significant differences among donor types., Discussion: HCT in patients with CGD is a complex procedure with significant morbidity and mortality, especially in patients who receive grafts from unrelated donors. These factors need to be considered in the decision-making process and when discussing conditioning and GVHD prophylaxis., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Alonso García, Bueno Sánchez, Fernández Navarro, Regueiro Garcia, Blanquer Blanquer, Benitez Carabante, Mozo del Castillo, Fuster Soler, Uria Oficialdegui, Sisinni, Perez Martinez and Diaz de Heredia Rubio.)

Background: Dyskeratosis congenita (DC) is a multisystem and ultra-rare hereditary disease characterized by somatic involvement, bone marrow failure, and predisposition to cancer. The main objective of this study is to describe the natural history of DC through a cohort of patients diagnosed in childhood and followed up for a long period of time., Material and Methods: Multicenter, retrospective, longitudinal study conducted in patients followed up to 24 years since being diagnosed in childhood (between 1998 and 2020)., Results: Fourteen patients were diagnosed with DC between the ages of 3 and 17 years (median, 8.5 years). They all had hematologic manifestations at diagnosis, and nine developed mucocutaneous manifestations during the first decade of life. Seven presented severe DC variants. All developed non-hematologic manifestations during follow-up. Mutations were identified in 12 patients. Thirteen progressed to bone marrow failure at a median age of 8 years [range, 3-18 years], and eight received a hematopoietic stem cell transplant. Median follow-up time was 9 years [range, 2-24 years]. Six patients died, the median age was 13 years [range, 6-24 years]. As of November 2022, eight patients were still alive, with a median age of 18 years [range, 6-32 years]. None of them have developed myeloblastic syndrome or cancer., Conclusions: DC was associated with high morbidity and mortality in our series. Hematologic manifestations appeared early and consistently. Non-hematologic manifestations developed progressively. No patient developed cancer possibly due to their young age. Due to the complexity of the disease multidisciplinary follow-up and adequate transition to adult care are essential., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Uria-Oficialdegui, Navarro, Murillo-Sanjuan, Rodriguez-Vigil, Benitez-Carbante, Blazquez-Goñi, Salinas and Diaz-de-Heredia.)

Introduction: Hematopoietic stem cell transplantation (HSCT) is a curative option for patients with Fanconi anemia (FA) and hematological manifestations but it does not prevent solid tumors, especially squamous cell carcinomas (SCC)., Methods: Retrospective study in 22 FA patients who had received HSCT and had been followed up beyond 2 years after HSCT., Results: The median follow-up was 15 years. Six patients developed head-and-neck SCC after transplantation. The cumulative incidence of SCC at 15 and 30 years from the HSCT was 14.2% and 71.2%, respectively. One patient was diagnosed in stage IV and the rest, who were being followed up in cancer screening programs, in stage I. Treatment of SCC consisted of surgery in all patients; radiotherapy and chemotherapy were used in two patients and were poorly tolerated., Conclusion: FA patients have high risk of head-and-neck SCC. Multi-disciplinary programs for early cancer detection are of special relevance in these patients., (© 2021. Federación de Sociedades Españolas de Oncología (FESEO).)

The main objective of this study was to determine whether Eltrombopag, a synthetic thrombopoietin receptor agonist, could improve peripheral blood counts in the three hematopoietic lineages and achieve transfusion independence in children with poor graft function (PGF) after allogenic hematopoietic stem cell transplantation (HSCT). Retrospective study of patients under 18 years who developed PGF post-HSCT in a large tertiary institution between January 2013 and March 2019. Out of 198 allogeneic HSCT, five patients met PGF criteria and were treated with eltrombopag. Median time from HSCT to eltrombopag initiation was 120 days. The median starting dose was 50 mg/day and the maximum dose reached was 75 mg/day. Median treatment duration was 9 months. Three patients achieved complete response and one partial response. The median dose among responders was 75 mg/day and the median time to response 8 weeks. Responses were sustained in three patients and two required a booster dose of CD34 + -selected cells from the original donor. None of the patients had to stop treatment due to adverse effects. The use of eltrombopag in children with PGF achieved responses in 80% of cases and demonstrated to be an effective and safe therapeutic option in pediatric patients with PGF., (© 2021 Wiley Periodicals LLC.)

Hematopoietic stem cell transplantation (HSCT) is currently the only curative option for hematological manifestations in patients with Fanconi anemia (FA). We report the outcome of 34 patients with FA inside a collaborative multicenter national study based on recommendations of Spanish Working Group for Bone Marrow Transplantation in Children (GETMON) between 2009 and 2016. Fludarabine-based conditioning regimen was carried out in all patients, with low dose total body irradiation in unrelated transplants. Disease status before HSCT was bone marrow failure (BMF) in 30 patients and myelodysplastic syndrome (MDS) in four. Donors were matched siblings donors (MSD) in 18, matched unrelated donors (MUD) in 15, and one haploidentical donor. All except one patient engrafted. Cumulative incidence of grades II-IV acute graft-versus-host disease (GVHD) was 29% and 11% for chronic GVHD. Median follow-up after HSCT was 6.5 years. Seven patients (21%) died due to transplant-related causes, two (6%) because of MDS relapse, and one (3%) after a squamous cell carcinoma. Overall survival (OS) was 73% at 5 years post-transplant, with no differences between MSD and MUD transplants. OS for patients with BMF was 80% while for MDS was 25%. Our data suggest HSCT can cure hematologic manifestations of most FA patients with BMF.