Table 1.
Patient, disease and stem cell transplant characteristics of the cases with pediatric MDS/BMF due to germline GATA2 mutation, control A (pMDS/BMF without GATA2 mutations) and control B (ALL/AML without GATA2 mutations)
| GATA2 cohort n=15 | Control A n=25 | Control B n=40 | p-value for GATA2 vs Control A | p-value for GATA2 vs Control B | ||
|---|---|---|---|---|---|---|
| Follow-up, years | Median (range) | 5 (1-8.5) (n=9) | 5.8 (1.1-12.1) (n=14) | 6.5 (1.4-10.9) (n=19) | - | - |
| Patient age*, years | Median (range) | 15.7 (5.7-20) | 12 (0.9-22.2) | 13.2 (2.8-20.3) | 0.03 | 0.3 |
| Patient age at diagnosis, years | Median (range) | 15.2 (5.4-19.8) | 9 (0.3-22) | 12.3 (0.6-20.2) | 0.07 | 0.14 |
| Sex, n (%) | Male | 10 (67) | 15 (60) | 24 (60) | 0.7 | 0.8 |
| Female | 5 (33) | 10 (40) | 16 (40) | |||
| Diagnosis, n(%) | RCC | 8 (53) | 9 (36) | 0 (0) | – | – |
| RAEB/RAEB-T/AML-MRC | 4 (27) | 11 (44) | 0 (0) | |||
| SAA | 0 (0) | 4 (16) | 0 (0) | |||
| BMF, NOS# | 0 (0) | 1 (4) | 0 (0) | |||
| ALL | 1 (7) | 0 (0) | 20 (50) | |||
| AML | 2 (13) | 0 (0) | 20 (50) | |||
| Karyotype, n (%) | 5q- | 0 (0) | 0 (0) | 1 (3) | – | – |
| +8 (trisomy 8) | 5 (33) | 2 (8) | 2 (5) | 0.08 | 0.01 | |
| Other | 2 (13) | 10 (4) | 22 (55) | - | - | |
| Monosomy 7# | 9 (60) | 9 (36) | 9 (25) | 0.19 | 0.0001 | |
| -7 | 7 (47) | 9 (36) | 3 (8) | - | - | |
| 7q | 2 (13) | 0 (0) | 0 (0) | - | - | |
| CBC, median (ranges) | WBC | 2.2 (0.7-39) | 3.5 (1.4-12.8) | 3.2 (0.8-62.4) | 0.07 | 0.16 |
| Hgb | 0.8 | 0.7 | ||||
| Platelets | 10.2 (3.5-13.9) | 9.9 (2.7-17.4) | 10.5 (7.9-13.8) | 0.015 | 0.11 | |
| ANC | 0.2 | 0.0008 | ||||
| AMC | 98 (12-443) | 41.5 (9-269) | 151 (16-759) | 0.3 | 0.04 | |
| 0.6 (0.1-17) | 1 (0-7.2) | 2.2 (0.3-8.7) | ||||
| 0.1 (0-72) | 0.2 (0-1.6) | 0.4 (0-441) | ||||
| Associated pathologies/Pre-SCT morbidities, n (%) | Lymphedema | 4 (27%) | 0 (0%) | 0 (0%) | 0.015 | 0.004 |
| Warts | 4 (27%) | 1 (4%) | 0 (0%) | 0.056 | 0.004 | |
| PAP | 1 (7%) | 0 (0%) | 0 (0%) | 0.4 | 0.3 | |
| Polyneuropathy | 1 (7%) | 0 (0%) | 1 (3%) | 0.4 | 0.5 | |
| Hearing loss | 1 (7%) | 0 (0%) | 0 (0%) | 0.4 | 0.3 | |
| Infection | 3 (2%) | 5 (2%) | 5 (13%) | 1 | 0.7 | |
| Other | 5 (33%) | 9 (36%) | 23 (58%) | 1 | 0.14 | |
| Pre-SCT chemo, n (%) | 4 (27) | 9 (36) | 40 (100) | 0.7 | <0.0001 | |
| Conditioning, n (%) | CY/TBI +/− ATG | 11 (73) | 17 (68) | 31 (78) | 0.9 | 0.9 |
| BU/CY +/− ATG | 2 (13) | 5 (20) | 4 (10) | |||
| Flu/Cy/TBI | 2 (13) | 3 (12) | 5 (13) | |||
| Cell source, n (%) | BM-MRD (10/10) | 3 (20) 5 (33) |
4 (16) 11 (44) |
10 (25) 11 (28) |
0.7 | 1 |
| BM-MUD (10/10) | 3 (20) | 7 (28) | 8 (20) | |||
| BM-mmURD (8 or 9/10) | 4 (27) | 3 (12) | 11 (28) | |||
| UCB | ||||||
| GVHD prophylaxis§, n (%) | Steroids | 10 (67) | 20 (80) | 24 (60) | - | - |
| CSA | 15 (100) | 22 (88) | 38 (95) | |||
| Tacrolimus | 0 (0) | 3 (12) | 2 (5) | |||
| MTX | 9 (60) | 20 (80) | 28 (70) | |||
| MMF | 3 (20) | 2 (8) | 5 (13) | |||
p-values were generated using Wilcoxon rank sum or Fisher exact test (two-sided).
“–” indicates not performed
Patient age at the time of transplantation.
Monosomy 7 is defined as having -7 or -7q.
GVHD prophylaxis agents are not mutually exclusive.
ALL – acute lymphoblastic leukemia; AML – acute myeloid leukemia excluding inherited bone marrow failure syndromes; AM-MRC – acute myeloid leukemia with myelodysplastic related changes; AMC – absolute monocyte count; ANC – absolute neutrophil count; ATG – antithymoglobulin; BM – bone marrow; BMF – bone marrow failure; BMF, NOS – bone marrow failure, not otherwise specified (excluding inherited bone marrow failure syndromes); BU – busulfan; CBC – complete blood count (baseline, prior to SCT); CSA – cyclosporine A; CY – cyclophosphamide; Hgb – hemoglobin; Flu – fludarabine; MMF – mycophenolate mofetil; mmURD – mismatched unrelated donor; MRD – matched related donor; MTX – methotrexate; MUD – matched unrelated donor; PAP – pulmonary alveolar proteinosis; RAEB – refractory anemia with excess blasts; RAEB-T – refractory anemia with excess blasts in transformation; RCC – refractory cytopenia of childhood; SAA – severe aplastic anemia; SCT – stem cell transplant; TBI – total body irradiation; UCB – umbilical cord blood.
Other GATA2 associated pathologies prior to transplant (n=5) included hypoplastic kidney (n=1), ventricular septal defect and benign mass at elbow (n=1), elliptocytosis (n=1), undescended testis and developmental delay (n=1), Klinefelter syndrome (n=1).