Clofarabine in Pediatric Acute Relapsed or Refractory Leukemia: Where Do We Stand on the Bridge to Hematopoietic Stem Cell Transplantation?

Background: Despite pronounced improvement in overall survival (OS) in pediatric leukemia, a proportion of patients continue to suffer from lack of response or relapse, and the management of such patients is exceedingly difficult. Immunotherapy and engineered chimeric antigen receptor (CAR) T-cell therapy have shown promising results in the course of relapsed or refractory acute lymphoblastic leukemia (ALL). However, conventional chemotherapy continues to be utilized for re-induction purposes whether independently or in combination with immunotherapy. Methods: Forty-three pediatric leukemia patients (age < 14 years at diagnosis) consecutively diagnosed at our institution and got treated with clofarabine based regimen at a single tertiary care hospital between January 2005 and December 2019 were enrolled in this study. ALL comprised of 30 (69.8%) patients of the cohort while the remaining 13 (30.2%) were with acute myeloid leukemia (AML). Results: Post-clofarabine bone marrow (BM) was negative in 18 (45.0%) cases. Overall clofarabine failure rate was 58.1% (n = 25) with 60.0% (n = 18) in ALL and 53.8% (n = 7) in AML (P = 0.747). Eighteen (41.9%) patients eventually underwent hematopoietic stem cell transplantation (HSCT); 11 (61.1%) were from ALL group and remaining seven (38.9%) were AML (P = 0.332). Three- and 5-year OS of our patients was 37.7±7.6% and 32.7±7.3%. There was a trend of better OS for ALL patients compared to AML (40.9±9.3% vs. 15.4±10.0%, P = 0.492). Cumulative probability of 5-year OS was significantly better in transplanted patients (48.1±12.1% vs. 21.4±8.4%, P = 0.024). Conclusions: Though almost 90% of our patients proceeded to HSCT with complete response post-clofarabine treatment, yet clofarabine-based regimens are associated with the significant burden of infectious complications and sepsis-related deaths.

Recurrent vincristine-associated fever in a child with Wilms tumor.

BACKGROUND: Fever is a common complaint among children with an underlying oncologic diagnosis, especially during chemotherapy courses and periods of neutropenia. Chemotherapy-induced fever is well described in relation to specific chemotherapy agents. However, fever induced by vincristine (VCR) has only been rarely reported. CASE: We describe a case of a 5-year-old female with stage III Wilms tumor who had recurrent VCR-associated fever that was controlled with prophylactic dexamethasone and acetaminophen. CONCLUSION: In patients developing recurrent fever following chemotherapy with VCR, febrile allergic reaction and prophylactic treatment should be considered after exhaustion of appropriate investigations.

Clinical utility of viscoelastic testing (TEG and ROTEM analyzers) in the management of old and new therapies for hemophilia.

Hemophilia A and B are rare inherited bleeding disorders resulting from deficiency of coagulation factors VIII and IX respectively. In the past few decades, the field of hemophilia has witnessed pivotal management challenges and therapeutic advances. Routine coagulation and factor assays, while useful in the classification of severity and treatment monitoring in hemophilia patients, have been shown to be of limited use in managing clinical presentations and outcomes. This prompted the investigation of viscoelastic studies in hemophilia care, which have established their utility in various bleeding and thrombotic states. In this review, we will discuss and critically assess the current literature highlighting the use of viscoelastic studies in various aspects of hemophilia including the determination of clinical phenotype, management of patients with inhibitors, perioperative management, and monitoring of novel agents.

Pulmonary Embolism in Children.

Pulmonary embolism (PE) in children is a rare condition with potential for high mortality. PE incidence is increasing owing to increased survival of children with predisposing conditions, increased use of central venous catheters, and improved awareness and recognition. Although pediatric PE is distinct from adult PE, management guidelines in children are extrapolated from the adult data. Treatment includes thrombolysis or thrombectomy, and pharmacologic anticoagulation. Ongoing clinical trials are evaluating the use of direct oral anticoagulants in children. Further research is required to develop pediatric-specific evidence-based guidelines for diagnosis and management of PE.