Sirolimus is effective and safe in childhood relapsed-refractory autoimmune cytopenias: A multicentre study.

Autoimmune cytopenias are a heterogeneous group of disorders characterized by immune-mediated destruction of haematopoietic cell lines. Effective and well-tolerated treatment options for relapsed-refractory immune cytopenias are limited. In this study, the aim was to evaluate the efficacy and safety of sirolimus in this disease group within the paediatric age group. The study enrolled patients in the paediatric age group who used sirolimus with a diagnosis of immune cytopenia between December 2010 and December 2020, followed at six centres in Turkey. Of the 17 patients, five (29.4%) were treated for autoimmune haemolytic anaemia (AIHA), six (35.2%) for immune thrombocytopenic purpura (ITP) and six (35.2%) for Evans syndrome (ES). The mean response time was 2.7 months (range, 0-9 months). Complete response (CR) and partial response (PR) were obtained in 13 of 17 patients (76.4%) and nonresponse (NR) in four patients (23.5%). Among the 13 patients who achieved CR, three of them were NR in the follow-up and two of them had remission with low-dose steroid and sirolimus. Thus, overall response rate (ORR) was achieved in 12 of 17 patients (70.5%). In conclusion, sirolimus may be an effective and safe option in paediatric patients with relapsed-refractory immune cytopenia.

Concurrent Osteonecrosis of the Jaw and Hip in a Child With Severe Aplastic Anemia Undergoing Transplant.

We present the first case of concomitant hip and jaw osteonecrosis in a 10-year-old child with aplastic anemia undergoing a transplant. Biphosphonate treatment may be beneficial for hip osteonecrosis but harmful for jaw osteonecrosis. Our experience suggests that clinicians should be cautious when prescribing bisphosphonate to children with simultaneous hip and jaw osteonecrosis. They should be aware of the osteonecrosis locations and treatment choices.

The Prevalence, Risk Factors and Cardiometabolic Complications of Obesity in Childhood Survivors of Acute Lymphoblastic Leukemia.

Prevalence, risk factors and metabolic complications of overweight/obesity (OW/OB) are not well described in the childhood survivors of acute lymphoblastic leukemia (ALL). Longitudinal changes in body mass index-z score (BMIz) from diagnosis to the last follow-up visit after the end of treatment were evaluated in 73 children at first complete remission. Of them, 40 were tested for adipokine profiles at visit. The mean BMIz increased gradually from diagnosis (0.07 ± 1.68) to the end of dexamethasone containing reinduction therapy (0.70 ± 1.48, P:0.007), followed by a fall at the end of treatment (0.15 ± 1.24) and a rise again at visit (0.40 ± 1.23, P:0.007). OW/OB percentage of 15% at diagnosis, increased to 35% at visit (p < 0.05). Post-treatment OW/OB in survivors was related with being OW/OB at diagnosis (OR 5.4, 95% CI [0.94-31.7]; P = 0.02) and after dexamethasone containing reinduction therapy (OR 5.1, 95% CI [1.1-21.4]; P = 0.05), but not with age at diagnosis, gender, treatment intensity and cranial irradiation. Metabolic syndrome (MetS) was more prevalent in survivors (13%) than in Turkish children (2%). As compared with controls, survivors had higher leptin level (8.1 ± 8.6 vs 3.2 ± 2.2 ng/ml, P = 0.01) and leptin/adiponectin ratio (2.1 ± 3.5 vs 0.6 ± 0.5, P = 0.03). Leptin/adiponectin ratio was correlated with HOMA-IR (r: 0.57, P = 0.001). The prevalence of OW/OB and MetS are elevated in the childhood survivors of ALL. Post-treatment OW/OB in survivors is related with OW/OB at diagnosis and dexamethasone containing therapy. Elevated leptin level and leptin: adiponectin ratio may serve as an early sign of metabolic derangement increasing the risk for early cardiovascular disease.

Allogeneic Hematopoietic Stem Cell Transplantation-Induced Anaphylaxis in 2 Pediatric Cases.

Hematopoietic stem cell transplantation is a curative treatment for many malignant and nonmalignant diseases in children and adults. It is performed with peripheral blood stem cells, bone marrow, and umbilical cord blood. Anaphylaxis may occur during hematopoietic stem cell transplantation, similar to that shown with blood transfusions. In children, although a few cases of anaphylaxis have been reported with cord blood transplantation, no cases of anaphylaxis have been reported with other hematopoietic stem cell transplantations. In this case report, we present the cases of 2 children, one diagnosed with thalassemia major and the other with aplastic anemia, both of whom developed anaphylaxis associated with bone marrow transplantation products cryopreserved with dimethyl sulfoxide and hydroxyethyl starch. Hematopoietic stem cell transplantation-induced anaphylaxis could be associated with cryoprotective agents, especially dimethyl sulfoxide, and alloantigens. In both anaphy-lactic reactions, dimethyl sulfoxide was thought to be the trigger, but it could not be excluded that it was related to stem cell components, plasma, or hydroxyethyl starch.

Influence of invasive aspergillosis during acute leukaemia treatment on survival after allogeneic stem cell transplantation: a prospective study of the EBMT Infectious Diseases Working Party.

Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.