Improvement of the Outcome of Relapsed or Refractory Acute Lymphoblastic Leukemia in Children Using a Risk-Based Treatment Strategy

Abstract

Relapsed/refractory acute lymphoblastic leukemia (ALL) is a leading cause of death by cancer in children. Our institution has switched relapse treatment strategy to improve survival. We reviewed records of first relapse/refractory childhood ALL between 1996 and 2012. Based on length of first remission, relapse site and immunophenotype, patients were classified into two groups: standard-risk relapse (SRR) and high-risk relapse and refractory (HRRR). Before 2007, all patients were uniformly treated with the same induction as at presentation, followed by hematopoietic stem cell transplantation (HSCT). Since 2007, treatment was given according to risk of failure: SRR were mostly treated with chemotherapy; HRRR patients underwent HSCT after intensive chemotherapy, aiming reduction of pre-transplant disease burden. Sixty-four patients were included. Thirty (47%) were SRR and 34 (53%) HRRR, including 11 with refractory ALL. Five-years overall survival (OS) and event-free survival (EFS) were similar for SRR, but were significantly higher with new risk-based strategy for HRRR: 56% versus 17% (P = 0.03) for OS, and 56% vs 11% for EFS (P = 0.008), respectively. In multivariate analysis, treatment strategy was significantly associated with survival. In conclusion, change for a risk-based strategy in our institution increased survival of high-risk patients to levels similar of those of standard-risk patients.

Mechanisms of extramedullary relapse in acute lymphoblastic leukemia: Reconciling biological concepts and clinical issues

“…However, extramedullary relapses are still a problem and have been reported in many other organs. Several studies have reported that extramedullary relapses occur in approximately 40% of cases (approximately 20% combined and 20% presumably isolated) [3,8,37]. Here, we summarize the evidence that shows the role of the microenvironment in extramedullary relapses.…”

“…BM is the most frequent site of ALL relapse and is involved as an isolated or combined site of relapse in 75-90% of cases [3,8,[38][39][40][41]. BM relapses are most often the unique site involved (approximately 65% of cases) [3,8,[34][35][36][37]. There is no clear evidence for a privileged BM site in which lymphoblasts primarily reside.…”

<p>Cost-Effectiveness Analysis of Tisagenlecleucel in the Treatment of Relapsed or Refractory B-Cell Acute Lymphoblastic Leukaemia in Children and Young Adults in Spain</p>

“…Between 15% and 20% of children and young adults with ALL are estimated to have refractory disease or relapses (r/r ALL). [5][6][7][8] These patients have a very poor prognosis and the survival rate may be <10% after two or more relapses. 6 Children and young adults with r/r ALL generally receive salvage chemotherapy to achieve complete remission (CR) and become candidates for allogeneic hematopoietic stem cell transplantation (HSCT), a potentially curative procedure.…”

Cell death-based treatment of childhood cancer

“…1 ). There are, nevertheless, subgroups of paediatric malignancies that we cannot control as well, for example, 2–3% of childhood acute lymphoblastic leukaemia (ALL) are refractory at presentation, while 15% relapse reducing long-term survival to 40–50%, thus, making recurrent ALL one of the leading causes of cancer-related death in children and highlighting the need for novel therapeutic approaches 11 . Similarly, Ewing’s Sarcoma has a long-term survival rate of ~75%, which is reduced to <30% when the disease has metastasised, which is the case in 20–30% of all children at clinical presentation 12 , while other paediatric cancers generally present with a dismal diagnosis such as diffuse intrinsic pontine glioma, which is associated with an overall survival of just 8–10 months 13 .…”