IMPORTANCE Blinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule with efficacy in children with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL).OBJECTIVE To evaluate event-free survival in children with high-risk first-relapse B-ALL after a third consolidation course with blinatumomab vs consolidation chemotherapy before allogeneic hematopoietic stem cell transplant. DESIGN, SETTING, AND PARTICIPANTSIn this randomized phase 3 clinical trial, patients were enrolled November 2015 to July 2019 (data cutoff, July 17, 2019). Investigators at 47 centers in 13 countries enrolled children older than 28 days and younger than 18 years with high-risk first-relapse B-ALL in morphologic complete remission (M1 marrow, <5% blasts) or with M2 marrow (blasts Ն5% and <25%) at randomization. INTERVENTION Patients were randomized to receive 1 cycle of blinatumomab (n = 54; 15 μg/m 2 /d for 4 weeks, continuous intravenous infusion) or chemotherapy (n = 54) for the third consolidation. MAIN OUTCOMES AND MEASURESThe primary end point was event-free survival (events: relapse, death, second malignancy, or failure to achieve complete remission). The key secondary efficacy end point was overall survival. Other secondary end points included minimal residual disease remission and incidence of adverse events.RESULTS A total of 108 patients were randomized (median age, 5.0 years [interquartile range {IQR}, 4.0-10.5]; 51.9% girls; 97.2% M1 marrow) and all patients were included in the analysis. Enrollment was terminated early for benefit of blinatumomab in accordance with a prespecified stopping rule. After a median of 22.4 months of follow-up (IQR, 8.1-34.2), the incidence of events in the blinatumomab vs consolidation chemotherapy groups was 31% vs 57% (log-rank P < .001; hazard ratio [HR], 0.33 [95% CI, 0.18-0.61]). Deaths occurred in 8 patients (14.8%) in the blinatumomab group and 16 (29.6%) in the consolidation chemotherapy group. The overall survival HR was 0.43 (95% CI, 0.18-1.01). Minimal residual disease remission was observed in more patients in the blinatumomab vs consolidation chemotherapy group (90% [44/49] vs 54% [26/48]; difference, 35.6% [95% CI, 15.6%-52.5%]). No fatal adverse events were reported. In the blinatumomab vs consolidation chemotherapy group, the incidence of serious adverse events was 24.1% vs 43.1%, respectively, and the incidence of adverse events greater than or equal to grade 3 was 57.4% vs 82.4%. Adverse events leading to treatment discontinuation were reported in 2 patients in the blinatumomab group.CONCLUSIONS AND RELEVANCE Among children with high-risk first-relapse B-ALL, treatment with 1 cycle of blinatumomab compared with standard intensive multidrug chemotherapy before allogeneic hematopoietic stem cell transplant resulted in an improved event-free survival at a median of 22.4 months of follow-up.

Dual-energy x-ray bone densitometry was used to study the lumbar vertebral bone mass in 218 healthy children (134 girls and 84 boys) aged 1-19 years. Vertebral bone mass increased with weight, age, and pubertal Tanner stage. Results of multiple regression analyses showed that Tanner stage and weight were the best predictive indicators of bone mass and bone mineral density. The influences of age, sex, race, physical activity, and diet were not significant when Tanner stage and weight were controlled. Two tables of predictive intervals for lumbar vertebral bone mineral density in healthy children (one based on Tanner stage and weight; the other, on age and weight) are presented. With normative data now available for use with this precise technique, clinicians can better detect abnormal bone mineral density in children and evaluate changes in mineralization over time.

Summary:with lethal organ dysfunction in the renal, pulmonary and cardiac systems. 5-8A hypercoaguable state has been demonstrated to occur A hypercoaguable state has been shown to follow highdose chemotherapy for bone marrow transplantation in many patients following bone marrow transplantation (BMT). 6,7,[9][10][11][12][13][14][15][16] Specifically, the natural anticoagulants (BMT). Deficiency of the natural anticoagulants, antithrombin III (AT-III), protein C and protein S cor-(antithrombin-III (AT-III), protein C and protein S) have been reported to be decreased in BMT patients, while prorelate with organ dysfunction following BMT. We treated 10 patients with severe post-BMT organ dyscoagulants (fibrinogen and factor VIII) were increased. The resulting imbalance between procoagulants and the natfunction with AT-III concentrate. Indications for treatment included AT-III anticoagulant level less than 88% urally occurring anticoagulants has been implicated in the development of VOD. and life-threatening single or multiorgan dysfunction. All patients were loaded with 50 units/kg AT-III every Fibrinolytics (tissue plasminogen activator, tPA) and anticoagulants (heparin) in addition to fluid restriction, 8 h for three doses followed by 50 units/kg/day each day for 3-12 days. Clinical improvement was seen within 1-diuretics, and supportive care have been used to treat VOD. 1,4,[17][18][19][20][21][22] The use of tPA and heparin in this patient 5 days of start of therapy in all patients. Patients with veno-occlusive disease (VOD) showed a decrease in platpopulation has been reported to have a high risk of bleeding and low response rate. 21elet consumption in nine of nine patients, resolution of hepatic tenderness in six of eight patients, and reduction Low levels of AT-III have correlated with the development of organ dysfunction during BMT in previously pubof severe ascites and weight gain in four of five patients. The probability of death due to VOD and life-threatenlished reports. 6,7,9,16 In addition, VOD or other single organ dysfunction has been associated with progression to fatal ing organ dysfunction was significantly less in the AT-III-treated group when compared to a historical control multiorgan failure. 5-8 Based on these reports, we hypothesized that correction of the AT-III deficit with AT-III congroup receiving the same preparative regimen (P ‫؍‬ 0.047 and P ‫؍‬ 0.034, respectively). Significant centrate might prevent progression to lethal organ dysfunction. Patients who developed organ dysfunction following improvements in organ dysfunction following AT-III treatment in this small study supports a causal relationhigh-dose chemotherapy for BMT and who also had low AT-III activity levels were treated with AT-III concentrate. ship between AT-III deficiency and post-BMT chemotherapy-induced organ dysfunction.This paper reports the outcome of our AT-III-treated patients compared to historical control patients treated at Keywords: bone marrow transplantation; antithrombin III; veno-occlusive disease; orga...

To evaluate long-term durability of blinatumomab, a BiTE â (bispecific T-cell engager) molecule, in adults with relapsed/refractory (R/R) Philadelphia chromosomeepositive (Phþ) B-cell precursor acute lymphoblastic leukaemia (ALL). M e t h o d s : I n t h i s fi n a l a n a l y s i s o f a n o p e n -l a b e l , s i n g l e -a r m , p h a s e 2 , multicentre ALCANTARA study (NCT02000427), adults (age !18 years) with Phþ ALL who had relapsed or were refractory to at least one TKI were included. The primary endpoint was the proportion of patients who achieved complete remission (CR)/CR with partial haematologic recovery (CRh) during the first two cycles of blinatumomab treatment.

We report a 3-month-old infant in whom Sweet's syndrome was a presenting manifestation of pediatric human immunodeficiency virus infection. Although rare in children, Sweet's syndrome may be associated with certain infections and malignancies. The diagnosis of Sweet's syndrome in a child should always prompt a thorough evaluation to assess for an associated systemic disease.