Table 1.
Clinical characteristics
| Patient | Group | Age at diagnosis | Sex | Pathological diagnosis | Flow cytometry positive markers (of selected seta) | Clinical indication for genetic testing | Clinical presentation | Treatment | Follow-up status | Time to event |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | Non-DS AMKL | 32 mo | M | AML, not otherwise specified | All negative | Leukemia | Unexplained bruising, leg discomfort, and some night-time sweating; marked anemia and thrombocytopenia with concern for malignancy | Matched unrelated BMT per AAML0531 arm B | Relapsed | 9 mo |
| 2 | Non-DS AMKL | 23 mo | F | Acute myeloid (megakaryoblastic) leukemia | CD41+, CD56+, CD61+ | AML | 6 wk of fevers, viral illness, ear infections | Matched unrelated BMT per AAML0531 arm B; MRD positive (0.8%) at the time of BMT | Deceased | 8.5 mo |
| 3 | Non-DS AMKL | 17 mo | M | Myeloid sarcoma (cranial mass), AML (bone marrow) | CD41+, CD56+, CD61+ | Cranial mass | Soft tissue/bony mass of the left temporal area with intracranial extension and mass effect later diagnosed as a myeloid sarcoma | Matched-unrelated BMT per AAML0531 arm B; proton radiation to sarcoma | Remission | 9 mo |
| 4 | Non-DS AMKL | 18 mo | M | AMKL | CD41+, CD56+, CD61+ | AML/ megakaryo-blastic leukemia, abnormal CBC | Extensive petechial rash on hands spread to legs/feet, easy bruising, low platelets, and pancytopenia | NA—treated at outside hospital | NA | NA |
| 5 | Non-DS AMKL | 23 mo | F | Relapsed/recurrent AMKL | CD41+, CD56+, CD61+ | Relapsed/recurrent AML | Early medullar relapse of AML, day 15 post reinduction | Matched unrelated BMT; conditioned with busulfan, fludarabine, and anti-thymocyte globulin | Remission | 2 mo |
| 6 | Non-DS AMKL | 11 yr | M | AMKL | CD41+, CD42b dim, CD61+ | History of low-risk ALL, now with concern for relapsed leukemia | Progressive thrombocytopenia concerning for relapsed B-ALL (70 mo from treatment of low-risk B-ALL) | Planned BMT; AAML0531 arm B-like | Undergoing treatment | NA |
| 7 | TAM | 2 wk | M | NA | CD41+, CD56+, CD61+, CD7+ | TAM plus presumed trisomy 21; 47, XY, +21. | Concern for germline GATA1 | NA—treated at outside hospital | NA | NA |
| 8 | TAM | 6 wk | M | NA | CD41subset, CD42b subset, CD61subset, CD7 subset | 6 wk old with trisomy 21, TAM | Preterm with congenital heart defect, ascites, hepatic dysfunction, disseminated intravascular coagulation, and leukocytosis | Low-dose cytarabine | Deceased from cardiac and ascites complications | 2 mo |
| 9 | TAM | 2 d | M | NA | CD41subset, CD7+, CD56 subset, CD61subset | Concern for acute leukemia, TAM | Cardiorespiratory failure, leukocytosis with >70% circulating blasts, with Hgb ∼ 10 and platelets ∼ 200 | Low-dose cytarabine | Remission | 20 mo |
| 10 | TAM | 20 d | M | NA | CD41subset, CD42b subset, CD56+, CD61subset, CD7+ | TAM and presumed trisomy 21 | Concern for TAM and respiratory distress; WBC 57,600 | None | Remission | 12 mo |
| 11 | DS-AMKL | 2 yr | M | NA | CD41+, CD61+, CD7+ | Myeloid leukemia of DS | Persistent thrombocytopenia | COG AAML1531 | Remission | 9 mo |
| 12 | DS-AMKL | 14 mo | M | Myeloid leukemia associated with DS | CD41variable, CD56 subset, CD61variable, CD7+ | New diagnosis AMKL with history of TAM | Patient with trisomy 21 who previously had TAM (not requiring chemoreduction) | COG AAML1531 | Remission | 8.5 mo |
| 13 | DS-AMKL | 25 mo | M | Myeloid leukemia associated with DS | CD38+, CD41+, CD56 subset, CD61+, CD7+, MPO+ | 25 mo old with trisomy 21 and new AMKL | Trisomy 21 with hyperleukocytosis, profound anemia, thrombocytopenia, and splenomegaly | COG AAML1531 | Remission | 26.5 mo |
| 14 | DS-AMKL | 18 mo | M | Myeloid leukemia associated with DS | CD41subset, CD56+, CD61subset, CD7+ | New diagnosis leukemia | Irritability, significant jaundice, splenomegaly, and petechial rash; WBC 21.2, hgb 4.0, platelets 32, and 52% circulating blasts | COG AAML1531 | Remission | 26 mo |
| 15 | DS-AMKL | 15 mo | F | Myeloid leukemia associated with DS | CD41+, CD42b+, CD61+, CD7+ | Myeloid leukemia associated with DS | Irritability, poor feeding, and recurring fevers | COG AAML1531 intensification II (MRD 2.4% at the end of induction I; switched to Arm B) | Remission | 20.5 mo |
Blast counts, when present, refer to total blasts seen.
(AMKL) Acute megakaryoblastic leukemia, (AML) acute myeloid leukemia, (B-ALL) B-cell acute lymphoblastic leukemia, (BMT) bone marrow transplant, (COG) Children's Oncology Group, (d) days old, (DS) Down syndrome, (mo) months old, (MRD) minimal residual disease, (TAM) transient abnormal myelopoiesis, (y) years old.
aSelected markers include CD2, CD38, CD41, CD42b, CD56, CD61, CD7, MPO, and TDT. Only positive markers are listed; the remaining are negative, except in patient 8 for whom markers TdT, CD2, CD56, and CD38 were not evaluated.