Acute Megakaryoblastic Leukemia in Childhood: Comparison Between Patients with and without Down Syndrome

Introduction: Acute Megakaryoblastic Leukemia (AMKL) is an unusual AML subtype in childhood, being the most frequent AML in Down syndrome (DS) patients. AMKL corresponds to 19.3% of AML in our Hospital and some special characteristics have been observed.

Objective: To analyze characteristics of AMKL and to compare patients with or without DS.

Patients and Methods:From January-1990 to June-2014 AMKL was diagnosed in 77 cases: 57 in non-DS and 20 in DS children. Fivecases were secondary leukemias and 3 cases had been previouslytreated with chemotherapy due to wrong diagnosis. One patient was on induction at the time of analysis. These 9 cases were not evaluable for follow-up. Forty-eight non-DS and 20 DS caseswere evaluable. Megakayocyte lineage commitment was confirmed in all cases by fluorescence microscopy. MPO was analyzedboth by flow cytometry and cytochemistry. G-banding and RT-PCR were performed according to standard techniques. Four successive BFM-based protocols were administeredwith schedule modification for DS patients.

Results: Mean age was:2 (range: 2 mo-13 y) years of age and mean WBC count was: 27,500 (range: 1,600-250,000)/mm3. No differences were observed in age or hematological findings at diagnosis. Extramedullar compromise was detected in 10 (17.5%) of non-SD cases. Immunophenotype defined ambiguous lineage leukemia in 3 (5.0%) of the non-DS cases, with compromise of T-lineage. Interestingly, in 4 cases the megakaryoblasts also co-expressed MPO.Cytogenetic findings showed hyperdiploidy (n=7), t(1;22)(p13;q23) (n=3), t(16;21)/FUS-ERG (n=2), abnormalities in chromosome 7 (n=5) and complex karyotype (n=9). Complete remission (CR) was achieved in 51 (33 non-DS and 18 DS) (75.0%) of 68 evaluable cases;null-responses observed in7(only non-DS, 10.3%). Early deaths occurred in 10 (14.7%) during induction phase, 2 of them before treatment onset. From the 51 patients who achieved CR, 16 (14 non-DS and 2 DS) presented relapses(p: 0.04) and 9 (6 in non-DS and 3 in DS) died in CR. EFS-probability for the total population was 34 (6)%, for non-DS 21 (6)% and for DS 63 (11)%(p-value: 0.0026). LFS-probability was 45 (7)% for the total population, for non-DS 29 (8)% and for DS 70 (11)% (p-value: 0.0117). Median follow-up: 148 (range: 2-194) months.

Conclusions:

1- Extramedullar compromise and T/myeloid mixed lineage or co-expression of MPO were observed only in non-DS AMKL, in 17.5% and 12.0% respectively.

2- Null-response was observed only in non-SD patients.

3- The most frequent event of non-DS was relapse, and toxic deaths in DS.

4- The significantly better outcome of patients with DS was confirmed in our setting.