Patients with MDS/AML and germline GATA2 mutation who underwent HSCT from a healthy mutation-positive related donor
| Family/Patient . | 1 . | 2 . | 3A . | 3B . |
|---|---|---|---|---|
| Age | 21 | 13 | 15 | 18 |
| Gender | M | M | F | F |
| Recipient | ||||
| Family history | ||||
| At presentation | Negative | Negative | Positive | |
| Other family members | Mother, healthy | Two older siblings, healthy; twin brother, healthy at donation, subsequently developed MDS-EB | Father, died with dx of AA at 41 y; 1 female sibling died at 2 mo of age due to sepsis; 3 male siblings were dxed with MDS/AML at ages 27, 29, and 51 | |
| GATA2 mutation | ||||
| Genomic | c.1061C>T | c.1082G>A | c.1018-50_1143+247del | |
| Protein | p.T354M | p.R361H | p.340_381del | |
| Pre-HSCT | ||||
| Clinical features | Pancytopenia | Weakness, epistaxis | Weakness | Weakness, pancytopenia |
| Infection | None | Warts | Multiple | None |
| Bone marrow | AML-MRC | MDS-EB | MDS | MDS |
| Cytogenetics | 45,XY, −7[5]/47,XY,+13 [5]/46,XY[8] | 45,XY,−7[18]/46, idem,+mar [1]/45,XY,−14[1] | Unknown | 46, XX, −18, +22 [3]/48, XX, +22, +mar[13] |
| Molecular | NRAS mutation (c.182A>G, p.Q61R) | Unknown | Unknown | Unknown |
| Post-HSCT | ||||
| Donor | Mother | Monozygotic twin | Brother | |
| Time post-HSCT | 3 y | 140 d | 30 d | 121 d |
| Bone marrow | MDS | Recurrent MDS/AML | Not done | Hypocellular |
| Chimerism | 100% donor | Not done | Unknown | 100% donor |
| Cytogenetics | 45,XX,−7[20] | 45,XY, −7[6] ;45,idem, t(6;20)(q15;p13)[2] | Unknown | Unknown |
| Molecular | SETBP1 mutation (c.2608G>A, p.G870S) | Unknown | Unknown | Unknown |
| Cause of death | Not applicable | Recurrent MDS/AML | Candida sepsis | CMV & fungal pneumonia |
| Donor | ||||
| After donating HSC | ||||
| Age at donation | 64 | 13 | 9 | 11 |
| Age of MDS/AML presentation | Healthy to date | 31 | 29 | |
| Clinical features | Healthy to date | Pancytopenia & lung infiltrates | Cytopenias and pneumonia | |
| Infection | None | Disseminated warts | Disseminated MAC | |
| Bone marrow | Not done | MDS-EB | MDS with transformation to AML | |
| Cytogenetics | Not done | 46,XY | 47,XY,del(7)(q22q32),+8[5]/47,XY,+8,der(11)t(1;11)(q21;q21)[2] | |
| Molecular | Unknown | STAG2 mutation (c.993T>A, p.Y331termination) | Unknown | Unknown |
| Outcome | Healthy | Died of sepsis prior to MUD HSCT | Died post-MUD HSCT due to MAC infection, GVHD, sepsis | |
| Family/Patient . | 1 . | 2 . | 3A . | 3B . |
|---|---|---|---|---|
| Age | 21 | 13 | 15 | 18 |
| Gender | M | M | F | F |
| Recipient | ||||
| Family history | ||||
| At presentation | Negative | Negative | Positive | |
| Other family members | Mother, healthy | Two older siblings, healthy; twin brother, healthy at donation, subsequently developed MDS-EB | Father, died with dx of AA at 41 y; 1 female sibling died at 2 mo of age due to sepsis; 3 male siblings were dxed with MDS/AML at ages 27, 29, and 51 | |
| GATA2 mutation | ||||
| Genomic | c.1061C>T | c.1082G>A | c.1018-50_1143+247del | |
| Protein | p.T354M | p.R361H | p.340_381del | |
| Pre-HSCT | ||||
| Clinical features | Pancytopenia | Weakness, epistaxis | Weakness | Weakness, pancytopenia |
| Infection | None | Warts | Multiple | None |
| Bone marrow | AML-MRC | MDS-EB | MDS | MDS |
| Cytogenetics | 45,XY, −7[5]/47,XY,+13 [5]/46,XY[8] | 45,XY,−7[18]/46, idem,+mar [1]/45,XY,−14[1] | Unknown | 46, XX, −18, +22 [3]/48, XX, +22, +mar[13] |
| Molecular | NRAS mutation (c.182A>G, p.Q61R) | Unknown | Unknown | Unknown |
| Post-HSCT | ||||
| Donor | Mother | Monozygotic twin | Brother | |
| Time post-HSCT | 3 y | 140 d | 30 d | 121 d |
| Bone marrow | MDS | Recurrent MDS/AML | Not done | Hypocellular |
| Chimerism | 100% donor | Not done | Unknown | 100% donor |
| Cytogenetics | 45,XX,−7[20] | 45,XY, −7[6] ;45,idem, t(6;20)(q15;p13)[2] | Unknown | Unknown |
| Molecular | SETBP1 mutation (c.2608G>A, p.G870S) | Unknown | Unknown | Unknown |
| Cause of death | Not applicable | Recurrent MDS/AML | Candida sepsis | CMV & fungal pneumonia |
| Donor | ||||
| After donating HSC | ||||
| Age at donation | 64 | 13 | 9 | 11 |
| Age of MDS/AML presentation | Healthy to date | 31 | 29 | |
| Clinical features | Healthy to date | Pancytopenia & lung infiltrates | Cytopenias and pneumonia | |
| Infection | None | Disseminated warts | Disseminated MAC | |
| Bone marrow | Not done | MDS-EB | MDS with transformation to AML | |
| Cytogenetics | Not done | 46,XY | 47,XY,del(7)(q22q32),+8[5]/47,XY,+8,der(11)t(1;11)(q21;q21)[2] | |
| Molecular | Unknown | STAG2 mutation (c.993T>A, p.Y331termination) | Unknown | Unknown |
| Outcome | Healthy | Died of sepsis prior to MUD HSCT | Died post-MUD HSCT due to MAC infection, GVHD, sepsis | |
CMV, cytomegalovirus; Dx, diagnosis; Dxed, diagnosed; F, female; GVHD, graft-versus-host-disease; M, male; MAC, Mycobacterium avium complex; MDS-EB, MDS with excess blasts; MUD, matched unrelated.