RESUMO
Ewing sarcoma is the second most common bone cancer in children, accounting for 2% of pediatric cancer diagnoses. Patients who present with metastatic disease at the time of diagnosis have a dismal prognosis, compared to the >70% 5-year survival of those with localized disease. Here, we utilized single cell RNA-sequencing to characterize the transcriptional landscape of primary Ewing sarcoma tumors and surrounding tumor microenvironment (TME). Copy-number analysis identified subclonal evolution within patients prior to treatment. Primary tumor samples demonstrate a heterogenous transcriptional landscape with several conserved gene expression programs, including those composed of genes related to proliferation and EWS targets. Single cell RNA-sequencing and immunofluorescence of circulating tumor cells at the time of diagnosis identified TSPAN8 as a novel therapeutic target.
RESUMO
BACKGROUND: Optimal therapy for high risk and relapsed acute lymphoblastic leukemia (ALL) remains uncertain. Wider availability of cord blood from related and unrelated donors has prompted studies of its use for hematopoietic stem cell transplant (HSCT). PROCEDURE: We evaluated 26 consecutive cord blood transplants (CBT) for ALL performed at our center from 1996 to 2002 on studies using consistent conditioning therapy and graft-versus-host disease (GVHD) prophylaxis. Median patient age was 8.5 years (range, 0.5-24 year). Cord blood (CB) was from unrelated donors in 25/26 cases. Median CB nucleated cell dose was 3.26e7/kg (range, 0.8-12.9). RESULTS: With median follow-up of 548 days, 16/26 patients (62%) are event-free survivors. Acute GVHD developed in 14/24 evaluable patients, reaching grade III-IV in 7 patients. Chronic GVHD occurred in 10/22 evaluable patients. Multivariate analysis showed higher total nucleated cell dose per kilogram to be the strongest predictor of event-free survival. CONCLUSIONS: We conclude that CBT can effectively treat ALL in children with high risk features and following relapse.
