TABLE 1.
Clinical and Molecular Characteristics at Time of Diagnosis for Eligible Patients
| Total Enrolled | 27 |
|---|---|
| Male Sex | 17 (63%) |
| Median Age at Diagnosis (range) | 13.3 months (0.7–148 months) |
| Splenomegaly at Diagnosis | 24 (89%) |
| Median WBC Count, × 109/L (range) | 26.9 (7–122) |
| Median Absolute Monocyte Count, × 106/L(range) | 4430 (1120–96,000) |
| Median Platelet Count, × 109/L (range) | 46 (10–227) |
| Median Peripheral Blood Blasts (range) | 2% (0–13%) |
| Median Bone Marrow Blasts (range) | 3% (0–16%) |
| Median Hemoglobin F (range) | 8% (1–66%) |
| RAS-Pathway Mutation Identified | |
| PTPN11 | 11 (41%) p.E76K (N=8); p.E76G (N=1); p.D61Y (N=1); p.E69K (N=1); |
| KRAS | 6 (22%) p.G13D (N=3); p.G13Y (N=1); p.G12D (N=1); p.G12V (N=1) |
| NRAS | 3 (11%) p.G12D (N=2); p.G13D (N=1) |
| RRAS | 1 (4%) p.Q87L (N=1) |
| RRAS2 | 1 (4%) p.Q72L (N=1) |
| CBL | 4 (15%) p.C404R (N=1); p.Y371H (N=1); pY371splice_site (N=1); |
| None | 1 (4%) |
| Median Mutant Allele Burden (range)* | 43.5% (8.1–50.2%) |
| Cytogenetic Abnormality | |
| Monosomy 7 | 3 (11%) |
| Other [t(3;5)] | 1 (4%) |
| None | 23 (85%) |
| Secondary Mutations | 5 (19%) |
| DNA Hypermethylation (Transplanted Patients Only) | |
| Low | 7 (47%) |
| Intermediate | 4 (27%) |
| High | 3 (20%) |
| Not Available | 1 (6%) |
| Median IgG, mg/dL (range) | 1045 (15–2990) |
| Direct Antibody Test (Coomb’s) Positive | 5/23 (22%) |
| Elevated IgG for Age or DAT Positive | 5/11 (46%) with RAS mutation; 7/16 (44%) without RAS mutation |
*
For patients with mutations in PTPN11, KRAS, NRAS, or RRAS