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).