Prognosis and prognostic factors

Length of first remission. Length of first remission is an important factor affecting the ability to attain a second remission. Children with a first remission of less than 1 year have substantially lower rates of second remission (50%–60%) than children whose first remission is greater than 1 year (70%–90%).[2-4] Survival rates for children with shorter first remissions are also substantially lower (approximately 10%) than those for children with first remissions exceeding 1 year (approximately 40%).[2-5] The Therapeutic Advances in Childhood Leukemia and Lymphoma (TACL) Consortium also identified duration of previous remission as a powerful prognostic factor. The 5-year overall survival (OS) rates were 54% (± 10%) for patients with greater than 12 months first remission duration and 19% (± 6%) for patients with shorter periods of first remission.[6]

Molecular alterations. In addition, specific molecular alterations at the time of relapse have been reported to impact subsequent survival. For instance, the presence of either WT1 or FLT3 internal tandem duplication (ITD) variants at first relapse were associated, as independent risk factors, with worse OS in patients achieving a second remission.[7]

Achieving a second remission.[8]

Early response to salvage therapy. The international Relapsed AML 2001/01 (NCT00186966) trial also found that early response to salvage therapy was a highly favorable prognostic factor.[9][Level of evidence C2]

No hematopoietic stem cell transplant (HSCT) in first remission.[8,10]

Favorable cytogenetics.[8,10]

In a report of 379 children with AML whose disease relapsed after initial treatment on the German Berlin-Frankfurt-Muenster (BFM) group protocols, the second complete remission (CR) rate was 63% and the OS rate was 23%.[8][Level of evidence C1] The most significant prognostic factors associated with a favorable outcome after relapse included achieving a second CR, a relapse greater than 12 months from initial diagnosis, no allogeneic bone marrow transplant in first remission, and favorable cytogenetics (t(8;21), t(15;17), and inv(16)).

A retrospective study of 71 patients with relapsed AML from Japan reported a 5-year OS rate of 37%. Patients who had an early relapse had a 27% second remission rate, compared with 88% for patients who had a late relapse. The 5-year OS rate was higher in patients who underwent HSCT after achieving a second CR (66%) than in patients not in remission (17%).[5]

Patients who relapsed on two consecutive Nordic Society of Pediatric Hematology and Oncology (NOPHO) AML trials between 1993 to 2012 were analyzed for survival (208 patients with relapse of 543 children initially treated). Second remissions were achieved in 146 children (70%) with a variety of reinduction regimens. The 5-year OS rate was 39%. Favorable prognostic factors included late relapse (≥1 year from diagnosis), no HSCT in first remission, and a core-binding factor AML subtype. For the children in second remission who underwent HSCT, the 5-year OS rate was 61%, as opposed to a 5-year OS rate of 18% for those who did not include HSCT in their therapy (P < .001).[10]