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.