Discussion
This study aimed to examine the outcomes of pediatric AML with KMT2A rearrangements at our institution that were treated both by chemotherapy alone as well as HSCT. Our numbers were limited in this retrospective analysis for identifying significant prognostic factors when looking at outcomes. In our qualitative analysis the outcome for patients with KMT2A rearrangements undergoing chemotherapy versus HSCT was equal (50%).
Studies have identified that residual disease is an important prognostic factor when discussing outcomes of transplant in patients.[10-12] Aiming for negative measurable residual disease (MRD) is essential given its impact on outcomes of relapse and survival seen in adults patients with AML undergoing HSCT.[13] We had no data on deeper remission with MRD in our patient cohort and we might have missed patients with lower levels of MRD going to HSCT. Despite this possibility of having taken some of our patients with MRD to HSCT, they did manage to have relatively better outcomes when taking into account their myeloablative conditioning and its treatment related mortality (TRM). There are reports underscoring the significance of cytogenetics in AML patients undergoing HSCT. All of the KMT2A rearrangements seen in our study fall in the intermediate group classification except for the KMT2A/MLLT4 or t(6;11).[14,15] We had only patient with t(6;11) who expired despite being in morphological remission prior to HSCT. Among the rest KMT2A/MLLT3 or t(9;11) translocations were associated with better prognosis.[4] In our patients, KMT2A/MLLT3 translocations were frequently encountered and had a good prognosis (alive=4; 50%) when compared to other KMT2A rearrangements.
During the 1980-90’s HSCT was widely endorsed for patients with newly diagnosed AML having a matched-sibling donor. Over the decades not only were the intensive chemotherapy regimens optimized along with better supportive care but also reports of low-risk favorable genetics such as t(8;21), inversion (16), myeloid-leukemia of Down syndrome (ML-DS) emerged.[16-18] Hence treating groups moved away from HSCT for low-risk patients. For the other cytogenetic risk-stratifications in myeloid neoplasms the study groups varied in their approach.[19-21] In general there is support for HSCT in patients falling into the high-relapse and unfavorable cytogenetic subsets as well as those with positive MRD after induction cycles.[22]
Apart from the small numbers in this retrospective analysis the other limitations of our study include the lack of MRD data and the analysis of newer mutations such as WT1, NRAS, KRAS, KIT, FLT3-ITD etc. with respect to known KMT2A rearrangements.
In conclusion, we have shared our experience from a major tertiary care hospital in Saudi Arabia with pediatric KMT2A/MLLT3 and MLLT11 rearranged AML patients doing relatively well with chemotherapy alone. We believe HSCT is a curative option for patients with KMT2A rearrangements and we need to study this prospectively to better delineate those partner-gene subsets that will benefit from HSCT given the high treatment related mortality associated with this approach.