Demographics and brain tissue findings at autopsy in pediatric HCT recipients with TA-TMA
| Patient . | Diagnosis . | Age at HCT (y) . | Sex . | Transplant type . | TA-TMA diagnosis day . | TA-TMA risk . | Eculizumab therapy . | Max sC5b-9 (ng/mL) . | Grade 2-4 GVHD . | Day of death . | Cause of death . | Active TA-TMA at death . | Maximum urine protein/creatinine ratio in month before death (mg/mg) . | Maximum LDH in month before death (relative to upper limit of normal (ULN)) . | General tissue injury . | Vascular injury . | Neurologic symptom score . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | XLP | 18 | M | Allogeneic | 39 | Moderate | No | 628 | Yes | 193 | Necrotizing leukoencephalopathy | Yes | 10.5 | 1.5× ULN | 3 | 3 | 4 |
| 2 | HLH | 18 | F | Allogeneic | 3 | Moderate | No | 780 | No | 225 | Bacteremia, sepsis | Yes | 11.5 | 2.3× ULN | 3 | 3 | 3 |
| 3 | NBL | 4 | F | Autologous | 10 | High | No | 880 | No | 27 | Multiorgan failure | Yes | 61.5 | 7.6× ULN | 2 | 2 | 1 |
| 4 | HLH | 0.6 | M | Allogeneic | 160 | High | Yes | 299 | Yes | 247 | GVHD | Yes | 10 | 6× ULN | 2 | 2 | 0 |
| 5 | XLP | 1 | M | Allogeneic | 25 | High | No | 458 | No | 71 | Pneumonitis and ARDS | Yes | 3.5 | 4.5× ULN | 2 | 2 | 0 |
| 6 | XIAP deficiency | 14 | M | Allogeneic | 221 | High | Yes | 385 | Yes | 483 | GVHD | Yes | N/A | 1.9× ULN | 1 | 0 | 3 |
| 7 | WAS | 29 | M | Allogeneic | 20 | High | Yes | 769 | Yes | 164 | GVHD | Yes | 139 | 3.5× ULN | 1 | 0 | 4 |
| 8 | NBL | 3 | M | Autologous | 2 | High | Yes | 420 | No | 61 | Pulmonary fibrosis | Yes | 7.6 | 1.6× ULN | 1 | 1 | 0 |
| 9 | XMEN | 17 | M | Allogeneic | 10 | Moderate | No | >1990 | No | 92 | Multiorgan failure, CMV/EBV | Yes | N/A | 4.1× ULN | 1 | 1 | 2 |
| 10 | AML | 23 | M | Allogeneic | * | * | No | 302 | Yes | 828 | GVHD | Yes | N/A | N/A | 0 | 0 | 0 |
| 11 | Hyper IgE Syndrome | 10 | M | Allogeneic | 154 | High | Yes | 375 | Yes | 166 | GVHD | Yes | 7.4 | 4× ULN | 0 | 0 | 0 |
| 12 | GATA2 mutation | 18 | F | Allogeneic | 18 | Moderate | No | 577 | Yes | 384 | GVHD | Yes | 58.9 | 2.1× ULN | 0 | 0 | 2 |
| 13 | WAS | 0.6 | M | Allogeneic | 11 | High | Yes | 673 | Yes | 110 | GVHD | Yes | 41.1 | 2.8× ULN | 0 | 0 | 0 |
| Patient . | Diagnosis . | Age at HCT (y) . | Sex . | Transplant type . | TA-TMA diagnosis day . | TA-TMA risk . | Eculizumab therapy . | Max sC5b-9 (ng/mL) . | Grade 2-4 GVHD . | Day of death . | Cause of death . | Active TA-TMA at death . | Maximum urine protein/creatinine ratio in month before death (mg/mg) . | Maximum LDH in month before death (relative to upper limit of normal (ULN)) . | General tissue injury . | Vascular injury . | Neurologic symptom score . |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | XLP | 18 | M | Allogeneic | 39 | Moderate | No | 628 | Yes | 193 | Necrotizing leukoencephalopathy | Yes | 10.5 | 1.5× ULN | 3 | 3 | 4 |
| 2 | HLH | 18 | F | Allogeneic | 3 | Moderate | No | 780 | No | 225 | Bacteremia, sepsis | Yes | 11.5 | 2.3× ULN | 3 | 3 | 3 |
| 3 | NBL | 4 | F | Autologous | 10 | High | No | 880 | No | 27 | Multiorgan failure | Yes | 61.5 | 7.6× ULN | 2 | 2 | 1 |
| 4 | HLH | 0.6 | M | Allogeneic | 160 | High | Yes | 299 | Yes | 247 | GVHD | Yes | 10 | 6× ULN | 2 | 2 | 0 |
| 5 | XLP | 1 | M | Allogeneic | 25 | High | No | 458 | No | 71 | Pneumonitis and ARDS | Yes | 3.5 | 4.5× ULN | 2 | 2 | 0 |
| 6 | XIAP deficiency | 14 | M | Allogeneic | 221 | High | Yes | 385 | Yes | 483 | GVHD | Yes | N/A | 1.9× ULN | 1 | 0 | 3 |
| 7 | WAS | 29 | M | Allogeneic | 20 | High | Yes | 769 | Yes | 164 | GVHD | Yes | 139 | 3.5× ULN | 1 | 0 | 4 |
| 8 | NBL | 3 | M | Autologous | 2 | High | Yes | 420 | No | 61 | Pulmonary fibrosis | Yes | 7.6 | 1.6× ULN | 1 | 1 | 0 |
| 9 | XMEN | 17 | M | Allogeneic | 10 | Moderate | No | >1990 | No | 92 | Multiorgan failure, CMV/EBV | Yes | N/A | 4.1× ULN | 1 | 1 | 2 |
| 10 | AML | 23 | M | Allogeneic | * | * | No | 302 | Yes | 828 | GVHD | Yes | N/A | N/A | 0 | 0 | 0 |
| 11 | Hyper IgE Syndrome | 10 | M | Allogeneic | 154 | High | Yes | 375 | Yes | 166 | GVHD | Yes | 7.4 | 4× ULN | 0 | 0 | 0 |
| 12 | GATA2 mutation | 18 | F | Allogeneic | 18 | Moderate | No | 577 | Yes | 384 | GVHD | Yes | 58.9 | 2.1× ULN | 0 | 0 | 2 |
| 13 | WAS | 0.6 | M | Allogeneic | 11 | High | Yes | 673 | Yes | 110 | GVHD | Yes | 41.1 | 2.8× ULN | 0 | 0 | 0 |
TA-TMA was diagnosed according to Jodele criteria.1 Histologic grading in each category was performed by a pathologist at our institution. The histologic grading scale is as follows: 0, no or insignificant abnormal findings; 1, mildly abnormal; 2, moderately abnormal; and 3, severely abnormal. Descriptive details on “general” and “vascular” histologic findings are listed in Table 2. Neurologic symptom scores were also generated for these patients. These scores represent the total number of neurologic symptoms present from the following list of symptoms: seizure, AMS, vision change, motor deficit, sensory deficit, and generalized weakness. Active TA-TMA at was defined as laboratory evidence of TA-TMA at the time of death and/or autopsy findings of active TA-TMA.
Patient 10 was diagnosed with TA-TMA at autopsy, not based on laboratory criteria. Patients 6, 9, and 10 did not have a urine protein/creatinine checked within 1 month of death; however, at 2 months before death the ratios were 5.1, 28.4, and 1.8 mg/mg. Because LDH reference ranges vary with age, the LDH maximum is displayed relative to the upper limit of normal for each patient. Patient 10 did not have an LDH checked within 1 month of death; however, at 2 months before death, his LDH was 3× the upper limit of normal. AML, acute myeloid leukemia; ARDS, acute respiratory distress syndrome; CMV, cytomegalovirus; EBV, Epstein-Barr virus; F, female; HLH, hemophagocytic lymphohistiocytosis; LDH, lactate dehydrogenase; M, Male; N/A not available; NBL, neuroblastoma; WAS, Wiskott-Aldrich syndrome; XLP, X-linked lymphoproliferative syndrome; XMEN, X-linked immune deficiency with magnesium defect, Epstein-Barr virus infection, and neoplasia.