Preemptive immunotherapy in childhood acute myeloid leukemia for patients showing evidence of mixed chimerism after allogeneic stem cell transplantation

Abstract

Previous studies have shown that children with acute myeloid leukemia (AML) who developed mixed chimerism (MC) were at high risk for relapse after allogeneic stem-cell transplantation (allo-SCT). We investigated the feasibility of intensified preemptive immunotherapy in children receiving allo-SCT for AML. Eightyfour children were registered in our trial from May 2005 to April 2009; of these, 71 fulfilled the inclusion criteria and were treated according to the study protocol. Serial and semiquantitative analyses of posttransplantation chimerism were performed. Defined immunotherapy approaches were considered in MC patients. Continuous complete chimerism (CC) was observed in 51 of 71 patients. MC was detected in 20 patients and was followed by immunotherapy in 13. Six of 13 MC patients returned to CC without toxicity and remained in long-term remission. Overall, the probability of event-free survival (pEFS) was 66% (95% confidence interval [95% CI] ‫؍‬ 53%-76%) for all patients and 46% (95% CI ‫؍‬ 19%-70%) in MC patients with intervention; however, this number increased to 71% (95% CI ‫؍‬ 26%-92%) in 7 of 13 MC patients on immunotherapy who were in remission at the time of transplantation. All MC patients without intervention relapsed. These results suggest that MC is a prognostic factor for impending relapse in childhood AML, and that preemptive immunotherapy may improve the outcome in defined high-risk patients after transplantation. (Blood. 2011;118(20):5681-5688)

Adoptive therapy with donor lymphocyte infusion after allogenic hematopoietic SCT in pediatric patients

“…In serial multicenter investigations, German authors proved, that in hematologic malignancies in children undergoing HSCT, promising results could be achieved with immunotherapy based on immunosupression cessation followed by DLI applied as pre-emptive therapy of impending relapse when compared with frank post transplant disease recurrence treatment. [28][29][30] Similar results were presented also by Rujkijyanont et al 31 In our cohort, in over 1/3 of patients, DLI complications of different severity were observed. The most frequent was GVHD, a further was BM aplasia.…”

CD34+ lineage specific donor cell chimerism for the diagnosis and treatment of impending relapse of AML or myelodysplastic syndrome after allo-SCT

“…With a 64% success rate, defined by reconversion in complete DCC, our results are comparable to recently published results from a prospective study in children with AML. 28 In a retrospective analysis, Sairafi et al 29 were also able to demonstrate that early immune intervention in case of impending relapse was more effective compared with late intervention after overt relapse. Nevertheless, even with immune intervention the survival of the group with incomplete CD34 þ lineage-specific DCC was inferior to the survival of the control group with stable DCC.…”

Long-term results of adjuvant donor lymphocyte transfusion in AML after allogeneic stem cell transplantation

“…Hence, our limited experience with high-risk AML patients differs from studies showing better success in chimerism-guided preemptive DLT therapy. 10,15,21,22 Interventions based on minimal residual disease detection are promising. Yan et al 23 recently published a study on a large cohort of standard-risk AML patients showing improved outcome of minimal residual disease-positive patients after treatment with modified donor lymphocytes.…”