Response to azacitidine in children with JMML
| Disease status . | Patient identifier . | Age (y) and gender . | Cytogenetics . | Mutational group* . | Azacitidine cycles . | Concomitant treatment . | Response to azacitidine† . | HSCT (total number) . | Status . | Follow-up (mo)‡ . |
|---|---|---|---|---|---|---|---|---|---|---|
| Prior to first HSCT | A062 | 1.1, male | Del(5)(q13q33) | NRAS | 1 | None | PR | Yes (2) | Alive with leukemia | 38 |
| 2-3 | None | PD | ||||||||
| Prior to first HSCT | CH058 | 2.8, male | Normal | PTPN11 | 1-3 | None | SD | Yes (2) | Alive with leukemia | 16 |
| 4-7 | None | PR | ||||||||
| Prior to first HSCT | D644§ | 1.4, male | −7 | KRAS | 1 | None | PD | Yes (1) | Alive in remission | 62 |
| 2-4 | None | SD | ||||||||
| 5-8 | None | CR|| | ||||||||
| Prior to first HSCT | D706 | 5.9, male | −7 | PTPN11 | 1 | None | PD | Yes (3) | Alive in remission | 66 |
| Prior to first HSCT | D712 | 6.3, female | Normal | NRAS | 1 | None | PD | Yes (1) | Dead, TRM | 1 |
| Prior to first HSCT | D827 | 0.4, male | Normal | PTPN11 | 1-2 | 6MP | Not evaluable | Yes (1) | Alive in remission | 38 |
| 3-7 | None | CR¶ | ||||||||
| Prior to first HSCT | I255 | 9.1, male | Inv(2)(p23q13), −7 | No mutation | 1-4 | AraC, 6MP | Not evaluable | Yes (1) | Alive in remission | 49 |
| Prior to first HSCT | NS001 | 5.4, male | −7 | NRAS | 1-3 | None | PR | No | Dead, progressive disease | No data |
| Prior to first HSCT | NS002 | 0.8, male | −7 | PTPN11 | 1 | None | SD | Yes (1) | Dead, TRM | 13 |
| 2-3 | None | PR | ||||||||
| 4-11 | None | CR# | ||||||||
| Relapse after HSCT** | NL121 | 4.6, male | Not done | PTPN11 | 2-4 | None | SD | Yes (3) | Dead, third relapse | 6 |
| 1, 5-8 | None | PD | ||||||||
| Relapse after HSCT** | SC108 | 5.0, male | Normal†† | NF1 | 1-2 | None | SD | Yes (2) | Dead, progressive disease | 1 |
| 3-4 | None | PR | ||||||||
| 5 | None | PD | ||||||||
| Relapse after HSCT** | SC156 | 5.3, male | Normal†† | PTPN11 | 2-4 | None | PR | Yes (3) | Dead, third relapse | 5 |
| 1, 5-6 | None | PD |
| Disease status . | Patient identifier . | Age (y) and gender . | Cytogenetics . | Mutational group* . | Azacitidine cycles . | Concomitant treatment . | Response to azacitidine† . | HSCT (total number) . | Status . | Follow-up (mo)‡ . |
|---|---|---|---|---|---|---|---|---|---|---|
| Prior to first HSCT | A062 | 1.1, male | Del(5)(q13q33) | NRAS | 1 | None | PR | Yes (2) | Alive with leukemia | 38 |
| 2-3 | None | PD | ||||||||
| Prior to first HSCT | CH058 | 2.8, male | Normal | PTPN11 | 1-3 | None | SD | Yes (2) | Alive with leukemia | 16 |
| 4-7 | None | PR | ||||||||
| Prior to first HSCT | D644§ | 1.4, male | −7 | KRAS | 1 | None | PD | Yes (1) | Alive in remission | 62 |
| 2-4 | None | SD | ||||||||
| 5-8 | None | CR|| | ||||||||
| Prior to first HSCT | D706 | 5.9, male | −7 | PTPN11 | 1 | None | PD | Yes (3) | Alive in remission | 66 |
| Prior to first HSCT | D712 | 6.3, female | Normal | NRAS | 1 | None | PD | Yes (1) | Dead, TRM | 1 |
| Prior to first HSCT | D827 | 0.4, male | Normal | PTPN11 | 1-2 | 6MP | Not evaluable | Yes (1) | Alive in remission | 38 |
| 3-7 | None | CR¶ | ||||||||
| Prior to first HSCT | I255 | 9.1, male | Inv(2)(p23q13), −7 | No mutation | 1-4 | AraC, 6MP | Not evaluable | Yes (1) | Alive in remission | 49 |
| Prior to first HSCT | NS001 | 5.4, male | −7 | NRAS | 1-3 | None | PR | No | Dead, progressive disease | No data |
| Prior to first HSCT | NS002 | 0.8, male | −7 | PTPN11 | 1 | None | SD | Yes (1) | Dead, TRM | 13 |
| 2-3 | None | PR | ||||||||
| 4-11 | None | CR# | ||||||||
| Relapse after HSCT** | NL121 | 4.6, male | Not done | PTPN11 | 2-4 | None | SD | Yes (3) | Dead, third relapse | 6 |
| 1, 5-8 | None | PD | ||||||||
| Relapse after HSCT** | SC108 | 5.0, male | Normal†† | NF1 | 1-2 | None | SD | Yes (2) | Dead, progressive disease | 1 |
| 3-4 | None | PR | ||||||||
| 5 | None | PD | ||||||||
| Relapse after HSCT** | SC156 | 5.3, male | Normal†† | PTPN11 | 2-4 | None | PR | Yes (3) | Dead, third relapse | 5 |
| 1, 5-6 | None | PD |
AraC, cytarabine; CR, complete response; PD, progressive disease; PR, partial response; SD, stable disease; 6MP, 6-mercaptopurine; TRM, transplantation-related mortality.
All mutations were confirmed to be somatic. Neurofibromatosis type 1 was diagnosed clinically.
Cycles of azacitidine with concomitant antineoplastic medication were considered not evaluable.
From the end of azacitidine treatment to death or last follow-up.
This case was published previously by Furlan et al.5
The patient reached genetic CR with disappearance of monosomy 7 and KRAS mutation after 5 and 7 cycles, respectively. Monosomy 7 was tested by fluorescence in situ hybridization, and KRAS mutation was assessed by Sanger sequencing.
Material for mutational studies was not available at the time of clinical CR.
The patient reached genetic CR with disappearance of monosomy 7 and PTPN11 mutation after 6 cycles. Monosomy 7 was tested by fluorescence in situ hybridization, and PTPN11 mutation was assessed by Sanger sequencing.
Relapse after second HSCT.
Last cytogenetic analysis: SC108, at start of azacitidine treatment; SC156, prior to second HSCT.