Kumar, Riten

Abstract We conducted this systematic review to evaluate outcomes of thrombolysis followed by anticoagulation vs anticoagulation alone in pediatric patients with venous thromboembolism (VTE). This systematic review addresses mortality, VTE resolution, recurrence, bleeding, and organ-specific outcomes in 5 PICO (population, intervention, comparison, outcomes) questions on thrombolysis across pulmonary embolism (PE), extremity deep vein thrombosis (DVT), right atrial thrombosis (RAT), cerebral sinus venous thrombosis (CSVT), and renal vein thrombosis (RVT). Meta-analysis reported risk ratios or differences (95% confidence intervals [CIs]), and absolute effects per 1000 patients. Certainty of evidence was assessed using GRADE (Grading of recommendation, assessment, Development, and Evaluation) guidelines. Thirteen nonrandomized studies were included and no randomized clinical trials addressed these questions. Thrombolysis might be associated with a higher risk of major bleeding, clinically relevant nonmajor bleeding, or unspecified bleeding with risk differences of 0.09 (95% CI, −0.06 to 0.23), 0.06 (95% CI, −0.11 to 0.22), and 0.09 (95% CI, −0.04 to 0.23), respectively. In PE with hemodynamic compromise, thrombolysis might be associated with a lower risk of mortality but conclusions on PE progression were uncertain in submassive PE. In DVT, thrombolysis may have little to no effect on mortality or thrombus resolution but might be associated with lower risk of postthrombotic syndrome. In RAT, thrombolysis might have little to no effect on thrombus resolution but a higher risk of major bleeding and mortality. For CSVT and RVT, the evidence was very limited. These findings were based on very-low-certainty evidence because of confounding and imprecision from small sample sizes. This systematic review highlights key challenges in developing recommendations for thrombolysis in children with VTE.

AbstractTo evaluate the correlation between an uncapped, actual body weight‐based unfractionated heparin dosing strategy, we performed a body mass index‐based subanalysis of a previously reported pediatric cohort. Nearly half (45%) of obese patients were supra‐therapeutic on initial anti‐FXa assessment. Obese patients achieved therapeutic anti‐FXa significantly faster than nonobese patients (median 4 vs 12 hours, P = .0192) and were more likely to have any supra‐therapeutic anti‐FXa levels (77% vs 35%; P = .0021). There was no statistically significant difference in major or clinically relevant nonmajor bleeding rates between weight categories (P = .69). Prospective pediatric studies are warranted to confirm our findings.

Abstract Background: Acute chest syndrome is defined as the presence of acute pulmonary findings in an individual with sickle cell disease. A brief course of dexamethasone was shown to significantly attenuate the course of mild to moderate ACS, but treated patients appeared to have an increased risk of readmission, generally for pain episodes, as compared to controls (31.5% vs. 4.7%; p=0.09). In a more recent retrospective review of patients with ACS, the readmission rate was even more alarming, with 59% of patients who received steroids alone (without transfusion) readmitted, again primarily for vaso-occlusive pain episodes. Over the past several years low dose steroid therapy [1–2mg/kg (maximum 80mg) of prednisone for 3 – 7 days] has been embraced as routine care for ambulatory and hospitalized patients with status asthmaticus. Potentially deleterious effects of steroid therapy, namely immunosuppression, especially in patients with concurrent pneumonia, and rebound wheezing after discontinuation of therapy have not been problematic. We reasoned that such a regimen to treat ACS might be beneficial without a “rebound effect” potentially leading to pain episodes, and over the past several years have increasingly used an asthma regimen of steroid therapy in our ACS patients who showed worsening clinical severity. Methods: Admissions recorded in a Pediatric Hematology – Oncology inpatient register were reviewed from July 1, 2005 to June 30, 2007 to identify patients hospitalized at the University Hospital of Brooklyn and King’s County Hospital Center with ACS; the register included children with ACS on admission and those who developed ACS during hospitalization for other complications. The clinical course of patients who received prednisone was compared to those who did not, particularly to assess the frequency of early (within two weeks) readmission after discharge. Results: Between July 2005 and June 2007, 63 patients were admitted for 78 episodes of ACS. Fifty-three patients received prednisone and 25 did not. Prednisone was used more frequently in patients with moderate or severe ACS (p<0.001). Eight patients (15.1%) who received prednisone were re-admitted within 2 weeks versus two (8.3%) who did not receive steroids (p=0.41). Overall the duration of hospital stay was similar in both groups, 3.1 days in patients who did not receive steroids and 3.8 days in patients who did (p=0.13). Seventeen patients (21.8%) received a simple blood transfusion, fifteen in the prednisone group and two in the non prednisone group. None had exchange transfusion. No patient required mechanical ventilation. Conclusion: In our retrospective chart analysis, we did see re-admissions after short course prednisone therapy; however, the re-admission rate was not significantly greater than that seen in children not receiving steroids and lower than that previously reported. Duration of stay and transfusion frequency were no different between steroidtreated and untreated patients, though the former had more severe disease at diagnosis; this may suggest clinical benefit. In summary, it may be possible to achieve the previously documented beneficial effects of steroid therapy for ACS without an unacceptable readmission rate by adjusting the treatment regimen. An asthma regimen similar to that used here would be reasonable to assess in a large prospective trial.

Abstract Abstract 4651 Introduction Graft versus host disease remains a major cause of mortality and morbidity following matched unrelated hematopoietic stem cell transplantation. Campath-1H (Alemtuzumab) is a humanized monoclonal antibody to CD52, an antigen expressed on T and B lymphocytes, monocytes and natural killer cells and is thought to reduce GVHD incidence through in vivo T cell depletion. Through the same mechanism it can potentially increase the risk of relapse by reducing the graft vs. leukemia effect and also possibly increase the risk of infection due to delayed immune recovery. This study looks at our experience with Campath-1H substituted in place of the conventional anti-thymocyte globulin (ATG) in our transplant conditioning regimen. Patients and Methods This retrospective case study included 17 pediatric (9 male; 8 female) matched unrelated bone marrow transplants done in our institution between January 2003 and June 2009 with Campath-1H as part of the pretransplant conditioning regimen. The primary transplant indication was leukemia/lymphoma (n=9), MDS/ MDS evolving into AML (n= 3), severe aplastic anemia (n=4) and Fanconi anemia (n=1). The conditioning regimen included Campath-1H given with cytoxan/ total body irradiation (TBI) in 14 patients, fludarabine/ TBI in 2 patients, and melphalan/ fludarabine in 1 patient. Campath-1H dosing was body weight based: 3mg (if between 5-15kg), 5 mg (if between 16-30kg) and 10 mg (if >30 kg) and 3 doses were administered when underlying condition was a malignancy and 4 doses when it was a bone marrow failure state. The last dose was given at least 24 hours prior to the bone marrow/ peripheral stem cell infusion. GVHD prophylaxis was with tacrolimus/methotrexate (n=12), tacrolimus (n=4) and cyclosporine/methotrexate (n=1). Standard institutional infectious prophylaxis was followed. Results The median age at transplant was 12.2 years (range; 0.7-19.7 years). All but one patient engrafted with a median of 21 days (range; 14-25 days). 5 out of 17 developed Grade I-II acute GVHD which resolved with steroids. No patient developed chronic GVHD. One patient had a CMV reactivation but no patient developed active CMV disease. 4 patients had varicella one of whom died of disseminated infection (day +376). The same patient also had adeno viral infection and BK viremia. 1 patient developed PCP pneumonia and retinal toxoplasmosis. 5 patients (6 transplants) relapsed (range; 40-641 days) with 3 relapsing within +100 days. 1 patient developed PTLD which was successfully treated with rituximab. Of the 4 patient deaths 3 were due to relapse and one due to disseminated varicella infection. The median follow-up time was 719 days (range; 147-2175 days). Overall survival as calculated using the Kaplan-Meir analysis was 100 % at 100 days and 94% at 1 year. Event free survival censoring for death, relapse and rejection was 76% at 100 days and 64% at 1 year. Conclusions Based on our experience, Campath-1H used as part of pretransplant conditioning regimen in pediatric matched unrelated transplants seems to reduce the risk of serious GVHD. This is in concordance with other published literature. T cell depletion is considered to increase the risk of life threatening infections. Our study had one infection related death. There were no patients with active CMV disease. This may in part be attributed to strict prophylactic measures and increased surveillance. Longer duration of follow-up is required to adequately analyze the relapse rates. Also, given our small patient numbers the effect of primary disease state and stage on relapse could not be assessed. Larger studies in the pediatric population with longer duration of follow-up comparing Campath-1H with conventional regimens are required to further assess its role with regards to graft vs. leukemia effect and also to establish if the decreased incidence of GVHD is sustained in larger cohorts. Disclosures: No relevant conflicts of interest to declare.