Outcome of Children With Hypodiploid Acute Lymphoblastic Leukemia: A Retrospective Multinational Study

Abstract

PURPOSE We determined the prognostic factors and utility of allogeneic hematopoietic cell transplantation among children with newly diagnosed hypodiploid acute lymphoblastic leukemia (ALL) treated in contemporary clinical trials. PATIENTS AND METHODS This retrospective study collected data on 306 patients with hypodiploid ALL who were enrolled in the protocols of 16 cooperative study groups or institutions between 1997 and 2013. The clinical and biologic characteristics, early therapeutic responses as determined by minimal residual disease (MRD) assessment, treatment with or without MRD-stratified protocols, and allogeneic transplantation were analyzed for their impact on outcome. RESULTS With a median follow-up of 6.6 years, the 5-year event-free survival rate was 55.1% (95% CI, 49.3% to 61.5%), and the 5-year overall survival rate was 61.2% (95% CI, 55.5% to 67.4%) for the 272 evaluable patients. Negative MRD at the end of remission induction, high hypodiploidy with 44 chromosomes, and treatment in MRD-stratified protocols were associated with a favorable prognosis, with a 5-year event-free survival rate of 75% (95% CI, 66.0% to 85.0%), 74% (95% CI, 61.0% to 89.0%), and 62% (95% CI, 55.0% to 69.0%), respectively. After exclusion of patients with high hypodiploidy with 44 chromosomes and adjustment for waiting time to transplantation and for covariables in a Poisson model, disease-free survival did not differ significantly ( P = .16) between the 42 patients who underwent transplantation and the 186 patients who received chemotherapy only, with an estimated 5-year survival rate of 59% (95% CI, 46.5% to 75.0%) versus 51.5% (95% CI, 44.7% to 59.4%), respectively. Transplantation produced no significant impact on outcome compared with chemotherapy alone, especially among the subgroup of patients who achieved a negative MRD status upon completion of remission induction. CONCLUSION MRD-stratified treatments improved the outcome for children with hypodiploid ALL. Allogeneic transplantation did not significantly improve outcome overall and, in particular, for patients who achieved MRD-negative status after induction.

Nationwide survey of pediatric hypodiploid acute lymphoblastic leukemia in Japan

“…Nevertheless, these data suggest that treatment intensification including allogeneic HSCT is not sufficient for these patients. In addition, both the Children's Oncology Group and the Ponte di Legno Childhood ALL working Group reported that HSCT did not improve outcome for patients with hypodiploid ALL . Therefore, we should consider other strategies for these patients, including new drugs such as blinatumomab, or even chimeric antigen receptor T‐cell therapy.…”

“…reported that MRD is an important prognostic indicator for childhood hypodiploid ALL . Recently, the Ponte di Legno Childhood ALL Working Group reported an international retrospective study in which the outcomes were significantly better in MRD‐stratified protocols than in MRD‐non‐stratified protocols . EFS of hypodiploid patients who were MRD negative at the end of induction was >70%.…”

“…Recently, the Ponte di Legno Childhood ALL Working Group reported an international retrospective study in which the outcomes were significantly better in MRD‐stratified protocols than in MRD‐non‐stratified protocols . EFS of hypodiploid patients who were MRD negative at the end of induction was >70%. A prospective study by the Children's Oncology Group also found that patients with MRD less than 0.01% at end‐of‐induction had favorable outcomes.…”

Adult hypodiploid B‐acute lymphoblastic leukaemia and stem cell transplantation

“…Although the study group is small because of the rarity of the entity studied, it is one of the largest such groups in the literature to date. Their results suggest that young adults (<30 years of age) with lowhypodiploid B-ALL achieving MRD levels of <0Á1% at the end of induction therapy have an acceptable outcome with intensive chemotherapy alone, as others have reported for children Mullighan et al, 2015;Pui et al, 2019). However, patients older than 35 years of age had a very poor prognosis for relapse and survival despite achieving an acceptable MRD response to induction therapy.…”

Pediatric Acute Lymphoblastic Leukemia, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology

“…141 In the latter group, it should be noted that some studies have examined the role of HSCT in pediatric patients with hypodiploid B-ALL, and it is unclear whether HSCT improves outcomes when given in CR1 in patients who are MRD-positive at the EOI. [152][153][154][155] However, HSCT for hypodiploid ALL may be considered in the context of a clinical trial.…”