Allogeneic stem cell transplantation for refractory acute myeloid leukemia in pediatric patients: the UK experience

Abstract

We report outcomes for 44 children who underwent stem cell transplantation (SCT) for refractory AML in the UK between 2000 and 2012. Median age at SCT was 11.5 years. Twenty-three patients had primary refractory and 21 relapsed refractory AML. Refractory disease was confirmed by cytogenetics/molecular genetics in 24 cases. Median follow-up of the whole cohort is 6.8 years (2.1-14.9 years). Thirty patients (68%) achieved a CR following SCT. Transplant-related mortality at 1 year was 18%. Acute GVHD incidence was 52% (grade ⩾III 19%), chronic 7%. Relapse was the major cause of treatment failure and occurred in 32% of patients at a median of 61 days post SCT. Five-year overall survival and leukemia-free survival (LFS) were 43% (95% CI 31-61%). All patients with favorable cytogenetics (n=6) are alive in CR. Outcomes in patients with primary refractory disease were equivalent to those with relapsed refractory AML. Blast percentage ⩽30% in the BM pre-SCT, myeloablative conditioning and acute GVHD proved to be favorable prognostic features. We could stratify patients according to age ⩾10 years and >30% blasts in BM pre-SCT. Patients with none/one of these risk factors were highly salvageable (5 years LFS 53%) whereas those with both factors had a very poor prognosis (5 years LFS 10%). This may facilitate decision making on whether it is appropriate to consider transplant in such patients.

Therapy‐related acute myeloid leukemia following treatment for cancer in childhood: A population‐based registry study

“…For example, if the reason patients were not offered HSCT was because they were too unwell or that they died before it was possible to perform the procedure, then our finding may simply represent their pre‐existing poor condition rather than the effectiveness of HSCT as a therapy for t‐AML. Furthermore, it has been shown that outcomes following HSCT in AML are inferior when performed in the setting of refractory disease, particularly for children aged over 10 years with >30% blasts in the bone marrow, so it is likely that patients failing to achieve remission after initial chemotherapy were either not offered or declined HSCT. Our results should also be interpreted with the understanding that HSCT is continually being refined, with studies demonstrating a clear trend towards a reduction in transplant‐related mortality over time .…”

Hematopoietic stem cell transplantation for children with acute myeloid leukemia in second remission: A report from the Australasian Bone Marrow Transplant Recipient Registry and the Australian and New Zealand Children's Haematology Oncology Group

“…Despite the poorer outcomes for many children with relapsed AML, in the absence of novel therapies, HSCT remains the only treatment modality that is capable of curing a substantial proportion of these high‐risk patients . Recently published data from the United Kingdom showed that children with primary refractory or relapsed/refractory AML undergoing HSCT with overt disease had a 5‐year leukemia‐free survival of 43% . Similarly, AML patients not in remission (≥5% blasts) in the cohort reported by Leung et al.…”

“…However, in a pediatric setting, it has also been suggested that the dose effect of MRD pretransplant may not be as strong an influence on outcomes in AML as it is in acute lymphoblastic leukemia (ALL) and hence that attempts to reduce the level of MRD might be less beneficial in AML . Furthermore, while outcomes for patients with ALL and morphological evidence of disease at the time of HSCT are dismal, a significant number of refractory AML patients can be salvaged by HSCT . Moreover, once a patient has relapsed, the optimum number of cycles of chemotherapy prior to HSCT is unclear, particularly once second complete remission (CR2) has been achieved.…”

Salvaged allogeneic hematopoietic stem cell transplantation for pediatric chemotherapy refractory acute leukemia

“…Thus, relapsed ALL is considered as the fourth most common pediatric malignancy in the world. Meanwhile, a prevalence of 5% to 10% de novo and 23% of relapsed pediatric AML exhibit the characteristic of multi-drug resistance and refractory disease [ 12 ]. The overall survival (OS) rates of this extreme subgroup of patients were only 22% in the P/Ref and 14% in the R/Ref settings [ 12 ].…”

“…Meanwhile, a prevalence of 5% to 10% de novo and 23% of relapsed pediatric AML exhibit the characteristic of multi-drug resistance and refractory disease [ 12 ]. The overall survival (OS) rates of this extreme subgroup of patients were only 22% in the P/Ref and 14% in the R/Ref settings [ 12 ]. With limited studies, widely varying survival rates of 0% to 35% and a non-relapse-related mortality (NRM) rate as high as 40% have been reported from four studies involving less than 200 subjects [ 8 – 11 ].…”