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Objective Mevalonic aciduria represents the most severe form of mevalonate kinase deficiency (MKD). Patients with mevalonic aciduria have an incomplete response even to high doses of anti-cytokine drugs such as anakinra or canakinumab and stem cell transplantation (SCT) represents a possible therapy for this severe disease. Methods We report the first two children affected by severe MKD who received haploidentical α/β T-cell and B-cell depleted SCT. Both patients received a treosulfan-based conditioning regimen and one received a second haploidentical-SCT for secondary rejection of the first. Results Both patients obtained a stable full donor engraftment with a complete regression of clinical and biochemical inflammatory signs, without acute organ toxicity or acute and chronic GvHD. In both, the urinary excretion of mevalonic acid remained high post-transplant in the absence of any inflammatory signs. Conclusion Haploidentical α/β T-cell and B-cell depleted SCT represents a potential curative strategy in patients affected by MKD. The persistence of urinary excretion of mevalonic acid after SCT, probably related to the ubiquitous expression of MVK enzyme, suggests that these patients should be carefully monitored after SCT to exclude MKD clinical recurrence. Prophylaxis with anakinra in the acute phase after transplant could represent a safe and effective approach. Further biological studies are required to clarify the pathophysiology of inflammatory attacks in MKD in order to better define the therapeutic role of SCT. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the association of neuroimaging, clinical, and laboratory findings in children with different underlying diseases who developed posterior reversible encephalopathy syndrome (PRES). All consecutive pediatric patients referred to our institute between 2000 and 2017 were retrospectively evaluated for newly diagnosed PRES. Clinical data, medical history, and therapies administered at the time of PRES and laboratory findings were reviewed as the magnetic resonance imaging (MRI) obtained at PRES presentation and during follow-up. Statistics included Mann–Whitney U, Chi-square, and Fisher's exact tests. A total of 39 pediatric patients (25 males, median age = 8.8 years) with a confirmed diagnosis of PRES were included. The patients were divided into four groups based on the underlying disease: (1) patients with hemato-oncological diseases not transplanted ( n  = 15, 38.5%), (2) who underwent hematopoietic stem cell transplantation (HSCT; n  = 12, 30.8%), (3) affected by renal ( n  = 8, 20.5%), and (4) by autoimmune diseases ( n  = 4, 10.2%). Hemato-oncological patients and those undergoing HSCT presented a higher incidence of involvement of deep gray matter structures and hemorrhagic lesions when compared with patients with renal and autoimmune disorders ( p  = 0.036 and p  = 0.036, respectively). No differences emerged among different groups of patients regarding presenting PRES symptoms, arterial blood pressure, laboratory findings, and extent of MRI abnormalities and these parameters did not show association with outcome. In conclusion, in pediatric patients with different diseases who develop PRES, involvement of deep gray matter structures and hemorrhagic lesions are more common in hemato-oncological patients and those undergoing HSCT. Clinical and radiologic outcome is favorable independently of clinical data and extent of MRI abnormalities. [ABSTRACT FROM AUTHOR]

• This study compared gonadal function after Bu or Treo in pre- and postpubertal children. • Spontaneous puberty was reached more frequently after Treo (P =.02). • Spontaneous menarche was reached more frequently after Treo (P <.001). • Luteinizing hormone (LH) levels were lower in patients treated with Treo. Gonadal impairment is an important late effect with a significant impact on quality of life of transplanted patients. The aim of this study was to compare gonadal function after busulfan (Bu) or treosulfan (Treo) conditioning regimens in pre- and postpubertal children. This retrospective, multicenter study included children transplanted in pediatric European Society for Blood and Marrow Transplantation (EBMT) centers between 1992 and 2012 who did not receive gonadotoxic chemoradiotherapy before the transplant. We evaluated 137 patients transplanted in 25 pediatric EBMT centers. Median age at transplant was 11.04 years (range, 5 to 18); 89 patients were boys and 48 girls. Eighty-nine patients were prepubertal at transplant and 48 postpubertal. One hundred eighteen children received Bu and 19 Treo. A higher proportion of girls treated with Treo in the prepubertal stage reached spontaneous puberty compared with those treated with Bu (P =.02). Spontaneous menarche was more frequent after Treo than after Bu (P <.001). Postpubertal boys and girls treated with Treo had significantly lower luteinizing hormone levels (P =.03 and P =.04, respectively) compared with the Bu group. Frequency of gonadal damage associated with Treo was significantly lower than that observed after Bu. These results need to be confirmed in a larger population. [ABSTRACT FROM AUTHOR]

Highlights • The overall response rate to etanercept (ET) in children with steroid-refractory acute graft-versus-host disease (SR aGVHD) was 68%. • The better response was obtained in cutaneous and gastrointestinal SR aGVHD. • Overall survival in responders was 76.5% (P =.004). • ET represents an effective treatment of SR aGVHD with a high response rate. Graphical Abstract Image, graphical abstract ABSTRACT Corticosteroids are the standard of care for first-line treatment of patients who develop grade II-IV of acute graft-versus-host disease (aGVHD), but the optimal second-line treatment has not yet been determined. We prospectively evaluated the use of the anti-TNFα monoclonal antibody etanercept (ET) as second-line treatment in children with steroid-refractory (SR) aGVHD. Twenty-five children with either malignant or nonmalignant diseases experiencing grade II-IV SR aGVHD received ET as second-line treatment. ET was administered after a median of 14days (range, 5 to 135 days) from the onset of aGVHD. Seventeen out of 25 patients (68%) developed a complete response (CR) or partial response (PR) to ET. The overall response rate (CR plus PR) was 78% in patients with cutaneous SR aGVHD, 78% in those with gastrointestinal aGVHD, and 57% in those with hepatic aGVHD. On day +100 after the start of ET, 52% of the children were in CR, 16% were in PR, and the remaining 32% failed to respond. Overall survival was 76.5% in responders and 16.7% in nonresponders (P =.004). Transplantation-related mortality at 5years was 34.1% (95% confidence interval, 18.6% to 57.1%). In our experience, ET has proven to be effective as second-line treatment in children with SR aGVHD. [ABSTRACT FROM AUTHOR]

Highlights • In our cohort the incidence of SOS/VOD was 2%, and by applying the new pediatric EBMT criteria, all SOS/VOD were severe. • Age at HSCT < 2 years, Bu, female gender, and HLH increased the risk of SOS/VOD. • The OS at 1 year was lower in patients with SOS/VOD. • The NRM at 1 and 5 years was higher in patients with SOS/VOD. Abstract Sinusoidal obstruction syndrome (SOS), also known as veno-occlusive disease (VOD), is a potentially life-threatening complication that may develop after hematopoietic stem cell transplantation (HSCT). The aims of this retrospective multicenter study were to evaluate the incidence of SOS/VOD in a large cohort of children transplanted in centers across Italy by applying the new European Society for Blood and Marrow Transplantation (EBMT) criteria and to analyze the risk factors underlying this complication. We retrospectively reviewed data of pediatric HSCTs performed in 13 AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica)-affiliated centers between January 2000 and April 2016. The new pediatric EBMT criteria were retrospectively applied for diagnoses of SOS/VOD and severity grading. Among 5072 transplants considered at risk for SOS/VOD during the study period, 103 children (2%) developed SOS/VOD, and the grade was severe or very severe in all patients. The median time of SOS/VOD occurrence was 17 days after HSCT (range, 1 to 104). Sixty-nine patients (67%) were treated with defibrotide for a median time of 16 days (range, 4 to 104). In multivariable analysis age < 2 years, use of busulfan during the conditioning regimen, female gender, and hemophagocytic lymphohistiocytosis were risk factors statistically associated with the development of SOS/VOD. The overall mortality directly related to SOS/VOD was 15.5%. Overall survival at 1 year was worse in patients with SOS/VOD (P =.0033), and this difference disappeared 5 years after HSCT. Nonrelapse mortality was significantly higher 1 and 5 years after transplantation in patients who developed SOS/VOD (P <.001). Based on the application of new EBMT criteria, the overall incidence of SOS/VOD recorded in this large Italian pediatric retrospective study was 2%. Nonrelapse mortality was significantly higher in patients who developed SOS/VOD. Identifying the risk factors associated with SOS/VOD can lead to more effective early treatment strategies of this potentially fatal HSCT complication in childhood. [ABSTRACT FROM AUTHOR]

Once‐a‐week cotrimoxazole is an effective prophylaxis for pneumocystosis during antineoplastic chemotherapy or autologous stem cell transplant. Following allogeneic stem cell transplant, this schedule is at risk of pneumocystosis or neurotoxoplasmosis, as demonstrated by these case reports. Therefore, a 3‐times‐a‐week schedule must be adopted in these patients. [ABSTRACT FROM AUTHOR]

The objective of the study was to determine the incidence of invasive fungal disease ( IFD) in children undergoing autologous haematopoietic stem cell transplantation (au HSCT) for solid tumours ( ST). Retrospective study on au HSCT was performed in children with ST (January 2006-December 2015). Data on the number of patient-days at risk (pdr) during the first 30 and 90 days after au HSCT and cases of proven/probable IFDs were collected. Infection rate ( IR, episodes/1000 pdr) and proportions and cumulative risk ( CR) of IFD were evaluated. In 186 patients, 270 au HSCT were performed, for a total of 8327 pdr during the first 30 days and 24 366 up to day 90. Median age was 5 years (interquartile range 2;8), 63% were male. At day 30, seven procedures were complicated by IFD, with an IR of 0.84 (95% CI 0.66-1.02) and aCR of 2.6% (95% CI 1.4-5.4) at 18 days after HSCT. Within day 90, two further IFDs were detected with an IR of 0.37 (95% CI −0.49 to 1.23) and a CR of 3.3% (95% CI 1.7-6.3) at day 69. Children undergoing au HSCT for ST have a low incidence of IFDs in the first 90 days after the procedure. [ABSTRACT FROM AUTHOR]

Abstract: Autoimmune hematological diseases (AHDs) may occur after allogeneic hematopoietic stem cell transplantation (HSCT), but reports on these complications in large cohorts of pediatric patients are lacking. Between 1998 and 2011, 1574 consecutive children underwent allogeneic HSCT in 9 Italian centers. Thirty-three children (2.1%) developed AHDs: 15 autoimmune hemolytic anemia (45%), 10 immune thrombocytopenia (30%), 5 Evans' syndrome (15%), 2 pure red cell aplasia (6%), and 1 immune neutropenia (3%). The 10-year cumulative incidence of AHDs was 2.5% (95% confidence interval, 1.7 to 3.6). In a multivariate analysis, the use of alternative donor and nonmalignant disease was statistically associated with AHDs. Most patients with AHDs (64%) did not respond to steroids. Sustained complete remission was achieved in 87% of cases with the anti-CD20 monoclonal antibody (rituximab). Four patients (9%) (1 autoimmune hemolytic anemia, 1 Evans' syndrome, 2 immune thrombocytopenia) died at a median of 87 days after AHD diagnosis as a direct or indirect consequence of their disorder. Our data suggest that AHDs are a relatively rare complication occurring after HSCT that usually respond to treatment with rituximab. [Copyright &y& Elsevier]

a- Gv HD may complicate allogeneic HSCT. In this retrospective single-center study, we evaluated incidence and risk factors of a- Gv HD in 197 consecutive allogeneic pediatric HSCTs applying Glucksberg and NIH a-Gv HD classifications. Among 179 eligible transplants, the cumulative incidence of grade 0-I a- Gv HD was 48% and grade II- IV was 52%. None of the considered variables significantly influenced the incidence of grade II- IV a- Gv HD. Malignancy and myeloablation were associated with an increased risk of classic a- Gv HD (p < 0.01). Seventy-two percentage of children are alive, with a significant difference in OS and TRM between grade 0 and I vs. grade II and IV a- Gv HD; this observation was reproduced in the non-malignant setting, while only a disparity in TRM was evidenced in children with malignancy. In our experience, the incidence of a- Gv HD was similar, regardless of donor type. Myeloablation and malignant disease represented the only risk factors for classic a- Gv HD. Our results highlight the need for a better prevention of this complication in the non-malignant setting. [ABSTRACT FROM AUTHOR]

Sala I, Faraci M, Magnano GM, Sementa A, di Marco E, Garaventa A, Micalizzi C, Lanino E, Morreale G, Moroni C, Castagnola E. HHV-8-related visceral Kaposi's sarcoma following allogeneic HSCT: Report of a pediatric case and literature review. Pediatr Transplantation 2011: 15:E8-E11. © 2010 John Wiley & Sons A/S. An HHV-8-related visceral KS was diagnosed in a 10-yr-old boy after partially matched allogeneic HSCT. This complication occurred 463 days after HSCT and involved tonsils, lymph nodes, hard palate, lung, skin, and paranasal sinuses. Treatment with pegylated liposomal doxorubicin induced long-term remission (33 months) of this disease. HHV-8 infection is quite frequent after HSCT, but KS, and especially its visceral form, is a very rare complication, and its association with HHV-8 has been documented even less frequently. However, our observation suggests that HHV-8-related KS should be taken into consideration in the differential diagnosis of late post-HSCT complications. [ABSTRACT FROM AUTHOR]

Abstract: Data on epidemiology of severe infectious complications, ie, bacteremia or invasive fungal disease (IFD), in children with acute graft-versus-host disease (aGVHD) after allogeneic hemopoietic stem cell transplantation (HSCT) are scarce. In a retrospective, single-center study, we analyzed the risk (hazard ratio [HR]) and the rate (episodes/1000 patients days at risk) of bacteremias and IFD in children receiving allogeneic HSCT, according to the type of donor (matched related [MRD] or alternative [AD]) and presence and grade of aGVHD. From 2000 to 2009, 198 children receiving 217 allogeneic HSCT developed 134 severe infectious episodes (103 bacteremias and 31 IFD). The type of donor (AD versus MRD) was the most important risk factor for the severe infections (P = .0052). In separate multivariable analysis for bacteremia and IFD, children receiving an AD HSCT had increased HR and rate of bacteremia compared with those receiving a MRD transplantation (P = .0171 and P = .0001, respectively), whereas the HR and the rate of IFD were significantly influenced by the grade of aGVHD (P = .0002 and P < .0001, respectively). Finally, infectious episodes occurred late after HSCT, especially in presence of severe aGVHD, and bacteremias were 3 to 6 times more frequent than IFD. These data may be important to design management strategies of infections in pediatric allogeneic HSCT. [Copyright &y& Elsevier]