Post-transplant lymphoproliferative disorders (PTLDs) are life-threatening complications of iatrogenic immune impairment after allogeneic hematopoietic stem cell transplantation (HSCT). In the pediatric setting, the majority of PTLDs are related to the Epstein-Barr virus (EBV) infection, and present as B-cell lymphoproliferations. Although considered rare events, PTLDs have been increasingly observed with the widening application of HSCT from alternative sources, including cord blood and HLA-haploidentical stem cell grafts, and the use of novel agents for the prevention and treatment of rejection and graft-vs.-host disease. The higher frequency initially paralleled a poor outcome, due to limited therapeutic options, and scarcity of controlled trials in a rare disease context. In the last 2 decades, insight into the relationship between EBV and the immune system, and advances in early diagnosis, monitoring and treatment have changed the approach to the management of PTLDs after HSCT, and significantly ameliorated the prognosis. In this review, we summarize literature on the impact of combined viro-immunologic assessment on PTLD management, describe the various strategies for PTLD prevention and preemptive/curative treatment, and discuss the potential of novel immune-based therapies in the containment of this malignant complication.
In recent years, the influence of nutrition on the health and growth of children has become increasingly important. The relevance of nutrition is even greater for children who are facing cancer. Malnutrition, within the context of undernutrition and overnutrition, may impact not only the effectiveness of treatments and outcomes, but also the quality of life for patients and their families. In this article, we review nutritional assessment methods for children with cancer, focusing on the specific characteristics of this population and analyze the efficacy of nutritional interventions, which include enteral, parenteral, and nutritional education. From our analysis, two important conclusions emerged: i) there is a need to focus our attention on the nutritional status and the body composition of oncologic children, since these factors have a relevant impact on clinical outcomes during treatment as well as after their conclusion; ii) the support of skilled clinical nutrition personnel would be extremely helpful for the global management of these patients.
Background: Pediatric myelodysplastic syndromes (MDSs) are a heterogeneous group of clonal disorders, accounting for less than 5% of childhood hematologic malignancies. Usual indications to HSCT are: MDSs with excess of blasts, MDSs secondary to previously administered chemoradiotherapy and RCC associated with monosomy 7, complex karyotype, severe neutropenia, or erythrocyte/platelet transfusion dependence [Locatelli & Strahm, Blood 2018]. We previously demonstrated that TBdepl-haploHSCT is a suitable option for children with acute leukemia, with outcomes comparable to those reported in studies using either an HLA-identical sibling or an unrelated volunteer as donor. Here we present the results of this approach in children with MDSs. Patients and methods: Between February 2013 and February 2021, 23 children with MDSs other than juvenile myelomonocytic leukemia received TBdepl-haploHSCT from an HLA-partially matched relative at Ospedale Pediatrico Bambino Gesù, Rome, Italy or at IRCCS Fondazione Policlinico San Matteo, Pavia, Italy as part of a prospective study (#NCT01810120). All patients were prepared to the allograft using a fully-myeloablative conditioning regimen including a combination of cytotoxic drugs and/or total body irradiation (TBI). Anti-T-lymphocyte globulin (ATLG) was used before transplantation (12 mg/kg total dose, from days -5 to day -3) to modulate bi-directional donor/recipient alloreactivity. Rituximab (200 mg/sqm) was administered on day -1 to prevent post-transplantation EBV-induced lymphoproliferative disorders (PTLD). No patient received any post-transplant pharmacological GvHD prophylaxis. Results: Characteristics of patients enrolled in the study are shown in Table 1 (which reports also donor and graft characteristics). Median follow-up of surviving patients is 4.2 years (range: 0.5 - 8.5 years). Seventeen children were affected by refractory cytopenia of childhood (RCC) (2 cases occurring in the context of inherited bone marrow failure syndromes: one had GATA2 deficiency and the other SAMD9L mutation), while 1 and 5 were affected by MDS with excess of blasts 1 (EB1) and EB2 (one had GATA2 deficiency), respectively. Median time to neutrophil and platelet recovery was 14 (range 10-19) and 11 (range 9-14) days, respectively, with four patients (3 with RCC and 1 with EB2) experiencing primary graft failure, the cumulative incidence of this complication being 17.3% (95% CI 0.3-31.5). All these 4 patients were rescued with a second TBdepl-haploHSCT from the same or the other parent. Cumulative incidence of grade II-III acute GvHD was 11.4% (95% CI 0-25.2). One patient developed skin and gut GvHD after the second TBdepl-haploHSCT, while for all other patients skin was the sole organ involved; no case of grade IV GvHD was observed. One patient developed moderate chronic GvHD [cumulative incidence 5.2% (95% CI 0-14.8)], which completely resolved with low-dose steroids and ruxolitinib. Notably, no patient died for transplant-related complications. Six patients experienced CMV, 2 HHV-6 and 1 adenoviral infection/reactivation; one patient developed lung aspergillosis, which resolved with specific treatment. One patient affected by EB2, not in remission at time of transplant, relapsed 27 months after HSCT, the 5-year cumulative incidence of relapse being 7.1% (95% CI, 0-19.7); she eventually died after failing a second HSCT. The 5-year probability of overall and event-free survival were 92.3% (95% CI 56.6 -98.9) and 76.3% (95% CI 51.3-89.6) (Figure 1A and B), respectively. Five-year disease-free-survival was 90% (95% CI 47.3-98.5). Because of the low number of events, no prognostic factor related to OS and EFS was found. In particular, the MDS variant did not influence the patient's outcome. The median CD3+ cell count on day +30, +90, +180 and +360 were 113, 171, 558 and 1307/mcl, respectively. Conclusions: These data indicate that TBdepl-haploHSCT is a safe and effective transplant option also in children with MDS. Indeed, the low risk of both non-relapse mortality and acute/chronic GvHD makes this approach particularly attractive in the pediatric setting. Moreover, this haplo strategy compares favorably with T-cell replete approaches [Suo et al., 2020]. Figure 1 Figure 1. Disclosures Merli: JAZZ: Consultancy; SOBI: Consultancy. Locatelli: Miltenyl: Honoraria; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Bellicum: Consultancy, Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Consultancy; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees.
Despite the substantial transfusion requirements, there are few studies on the optimal transfusion strategy in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Our study aimed to retrospectively analyze red blood cell (RBC) and platelet (PLT) transfusion practices during the first 100 days after HSCT at the pediatric hematology/oncology unit of our hospital between 2016 and 2019, due to a more restrictive approach adopted after 2016. We also evaluated the impact on patient outcomes. A total of 146 consecutive HSCT patients were analyzed. In patients without hemorrhagic complications, the Hb threshold for RBC transfusions decreased significantly from 2016 to 2017 (from 7.8 g/dL to 7.3 g/dL; p = 0.010), whereas it remained the same in 2017, 2018, and 2019 (7.3, 7.2, and 7.2 g/dL, respectively). Similarly, the PLT threshold decreased significantly from 2016 to 2017 (from 18,000 to 16,000/μL; p = 0.026) and further decreased in 2019 (15,000/μL). In patients without severe hemorrhagic complications, the number of RBC and PLT transfusions remained very low over time. No increase in 100-day and 180-day non-relapse mortality or adverse events was observed during the study period. No patient died due to hemorrhagic complications. Our preliminary observations support robust studies enrolling HSCT patients in patient blood management programs.
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