Abstract
Abstract 3597
Poster Board III-534
An increased risk for malignant transformation (MDS or leukemia) is well documented in patients with congenital neutropenia (CN). In this study we assessed the incidence of leukemic transformation and potential risk factors for leukemic transformation in CN patients with known gene mutations, e.g. ELA2, HAX1, G6PC3, p14, WAS or no identified mutation, respectively, by combining all available data from the European and US Branches of the Severe Chronic Neutropenia Registry (SCNIR) and the French Neutropenia Registry (FR).
Data from mutational analysis were available for 407 patients. Mutations were identified in 259 CN patients, of whom 209 patients revealed ELA2 mutations, 20 HAX1 mutations, 18 WAS, 8 G6PC3 and 4 p14 mutations. In addition, in 57 patients neither ELA2 nor HAX 1 mutation were detectable and in another 91 patients ELA2 mutations could be excluded, but further genetic evaluation is not yet completed.
Secondary malignancies occurred in 50 of the 407 CN patients. The distribution by genetic subtype is shown in the table below:
| CN subtype by gene mutation . | Total patient number (n) . | MDS/Leukemia (n/%) . |
|---|---|---|
| ELA2-CN | 209 | 31 (14. 8%) |
| HAX1-CN | 20 | 4 (20%) |
| ELA2 neg + HAX1 neg | 57 | 6 (10.5%) |
| ELA2 neg/ HAX1 not tested | 91 | 5 (5.5%) |
| WAS | 18 | 4 (22.2%) |
| G6PC3 | 8 | 0 |
| p14 | 4 | 0 |
| Total | 407 | 50 (12.3%) |
| CN subtype by gene mutation . | Total patient number (n) . | MDS/Leukemia (n/%) . |
|---|---|---|
| ELA2-CN | 209 | 31 (14. 8%) |
| HAX1-CN | 20 | 4 (20%) |
| ELA2 neg + HAX1 neg | 57 | 6 (10.5%) |
| ELA2 neg/ HAX1 not tested | 91 | 5 (5.5%) |
| WAS | 18 | 4 (22.2%) |
| G6PC3 | 8 | 0 |
| p14 | 4 | 0 |
| Total | 407 | 50 (12.3%) |
All subgroups benefit from G-CSF treatment. Median G-CSF maintenance doses required during the years prior to leukemic transformation compared by genetic subtype is shown in the following table 2:
| CN subtype by gene mutation . | Without leukemia (n) . | Median G-CSF dose (μg/kg/d) . | With leukemia (n) . | Median G-CSF dose (μg/kg/d) . |
|---|---|---|---|---|
| ELA2-CN | 75 | 5.0 | 15 | 15 |
| HAX1-CN | 15 | 5.0 | 4 | 13.4 |
| ELA2-/HAX1- | 36 | 7.2 | 4 | 10.5 |
| WAS | 15 | 2.6 | 4 | 3.0 |
| G6PC3 | 8 | 3.9 | 0 | na |
| p14 | 4 | 5.1 | 0 | na |
| CN subtype by gene mutation . | Without leukemia (n) . | Median G-CSF dose (μg/kg/d) . | With leukemia (n) . | Median G-CSF dose (μg/kg/d) . |
|---|---|---|---|---|
| ELA2-CN | 75 | 5.0 | 15 | 15 |
| HAX1-CN | 15 | 5.0 | 4 | 13.4 |
| ELA2-/HAX1- | 36 | 7.2 | 4 | 10.5 |
| WAS | 15 | 2.6 | 4 | 3.0 |
| G6PC3 | 8 | 3.9 | 0 | na |
| p14 | 4 | 5.1 | 0 | na |
Patients with severe congenital neutropenia who have mutations in ELA2, HAX1, or WAS and also those with no recognized mutation are at risk of secondary leukemia. So far, progression to MDS leukemia has not yet been described in the small number G6PC3 or p14 CN cases in our database. ELA2-CN or HAX1-CN patients requiring higher doses of G-CSF are at greater risk. Mutational analysis is helpful to identify the genetic cause of severe congenital neutropenia but does not serve to identify patients at risk of leukemic transformation.
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
