Results
Twenty-one (10.4%) AML patients (n=201) were identified to have the
KMT2A rearrangement. Three of these died within a few weeks of diagnosis
and were thus excluded from the analysis. The characteristics of the
remaining 18 patients are described in Table 1. The age ranged from
0-13.5 years (median 4.12 years; average 4.6 years). There was no
difference seen in gender predisposition. Morphologically, FAB
classification M5 was most frequently seen. Common translocation
partners seen in our patients are shown in Figures 1B. The most common
translocation seen was KMT2A/MLLT3.
Patient outcomes in relation to the KMT2A translocation are provided in
Table 2. In the eight children with the KMT2A/MLLT3 translocation 3
(37.5%) were treated with HSCT and 5 (62.5%) patients with
chemotherapy alone. In general, three patients with KMT2A/MLLT3 needed
2nd line chemotherapy for remission induction, amongst which two
(66.7%) went into disease remission while one failed to get into
remission.
We had four (22.2%) patients with KMT2A/MLLT1 who presented with high
white blood counts (WBCs) and despite achieving induction early did
poorly because of disease relapse. They were all treated with
chemotherapy except for one with HSCT. The only surviving patient in
this set had chemotherapy. Another equally common (n=4, 22.2%)
translocation seen was KMT2A/MLLT11 with most of the patients being
infants with age range of 0.54-1 year and having a balanced sex ratio
(2-boys and 2-girls). Both the girls were in the HSCT group and survived
while the boys were in the chemotherapy alone set and succumbed to their
disease.
Among the total of 18 patients 10 were treated with chemotherapy alone
while eight got HSCT. For those who continued with chemotherapy alone 7
(70%) were in remission after 2-cycles of induction and 9 (90%) were
in remission after completing 4-cycles of chemotherapy. In the HSCT
cohort three (37.5%) patients were in remission after 2-induction
cycles and of the remaining five patients four had to be switched to 2nd
line chemotherapy in order to achieve remission. All of the eight
patients were in morphological remission prior to transplant.
The donor source for our HSCT patients was mostly (87.5%) matched
related donor except for one patient who got an umbilical cord blood
transplant. All the patients got myeloablative conditioning with
Busulfan and Cyclophosphamide. Patients got a median of 4-courses before
proceeding to transplant. Except for one patient where engraftment
testing was not available all the rest of the seven patients had more
than 96% myeloid chimerism at Day+100. Four patients relapsed
post-transplant and three of these included those who had been moved to
2nd line chemotherapy regimens. All of the four relapsed patients died.
Cumulative probability of overall survival (OS) at 5-year of KMT2A
rearranged AML was 50.0±11.8%; 50.0%±15.8% in chemotherapy alone
compared to 50.0%±17.7% in HSCT group (P-Value: 0.639, Fig. 2). Five
(50%) out of the 10 patients treated with chemotherapy alone died where
four were due to progressive disease while one (1) death was secondary
to treatment-related-toxicity (TRT). All of the mortality (n=4, 50%) in
the HSCT group was also due to progressive disease. None of our patients
in the transplant group had problems with acute graft-versus-host
disease (GvHD), chronic GvHD, hemorrhagic cystitis or viral infections
such as cytomegalovirus (CMV).