Table 1.
Clinical characteristics, therapy, and outcome
| Characteristic | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 |
|---|---|---|---|---|---|---|---|
| Sex | Male | Male | Male | Male | Female | Male | Female |
| Previous diagnosis at age | Localized osteosarcoma, 10 y 9 mo |
Localized osteosarcoma, 13 y 11 mo |
Localized stage V Ewing sarcoma, 18 y 8 mo |
Stage IV, high-risk neuroblastoma, 1 y 9 mo |
T-ALL, 14 y 1 mo |
MDS-EB with underlying CDL syndrome, 17 y 2 mo |
None |
| Myeloid malignancy | AML | AML | AML | AML | AML | MDS/AML | AML with MDS-related changes |
| Blast count in BM, % | 60 | 47 | 56 | 71 | 57 | 24 | 32 |
| Age at diagnosis | 13 y 6 mo | 19 y 1 mo | 23 y 10 mo | 16 y 9 mo | 18 y 8 mo | 17 y 4 mo | 13 y 3 mo |
| Cytogenetics | Del5q, del7q, add3q, t(2;3)(p21;q26.2) | Del11p, t(5;5)(p12;p15.33), inv3(p24.3;q26.2) |
Multiple gains and losses | Complex | Monosomy 7 | Normal | Complex with monosomy 7 |
| Somatic mutations | KRAS, IKZF1, NF1, CSNK1A1 deletion | WT1 |
TP53, NF1, PDGFRA; deletions: ETV6, CSNK1A1; amplifications: KMT2A, ATM |
RUNX1, NF1 | NPM1, CEBPA, NRAS, FLT3-ITD | Deletions: TP53, RUNX1, ZBTB7A | |
| Treatment | |||||||
| CPX-351 | 2 cycles | 3 cycles | 2 cycles | 1 cycle | 2 cycles | 1 cycle | 1 cycle |
| Venetoclax | — | — | — | — | — | — | 1 cycle |
| Venetoclax and cytarabine | 1 cycle | — | — | — | — | — | — |
| Venetoclax and decitabine | — | — | — | — | — | — | 1 cycle |
| Decitabine | 1 cycle | 1 cycle (pre-CPX351) | 1 cycle | — | — | — | — |
| Azacytidine | — | — | — | — | Once per month after HCT | — | — |
| FLAG | — | — | 1 cycle | — | — | — | — |
| Gilteritinib | — | — | — | — | — | Before and after HCT | — |
| Allogeneic HCT | Haplo-father (first), haplo-mother (second) |
Haplo-brother | — | Haplo-sister | Haplo-uncle | MUD | Haplo-grandmother |
| No. of surgeries | — | 2 | — | — | — | — | — |
| Status at last follow-up | Alive, 18.5 mo after HCT | Alive, 39.1 mo after HCT | Deceased 4 mo after diagnosis (disease progress and infection) | Alive, 6.2 mo after HCT | Alive, 34.1 mo after HCT | Alive, 6.3 mo after HCT | Alive, 7.5 mo after HCT |
Details on cytogenetics and molecular findings are provided in supplemental Table 2. Details on marrow response are depicted in Figure 2.
FLAG, fludarabine, cytarabine, and granulocyte colony-stimulating factor regimen; haplo, haploidentical; MDS-EB, MDS with excess blasts; MUD, matched unrelated donor; T-ALL, T-cell acute lymphoblastic leukemia.