Table 1.
Patient Demographics and Disease Characteristics
| Responders | Non-responders | |||||
|---|---|---|---|---|---|---|
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| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | |
| Gender | F | F | M | F | M | M |
| Age at HSCT, y | 4.9y | 5.1y | 2.4y | 4.3y | 7.2y | 10.9y |
| Weight, kg | 4.9 | 5.1 | 2.4 | 4.3 | 7.2 | 10.9 |
| Diagnosis | NBL | NBL | WAS | CID | WAS | CID |
| Stem cell source | Autologous | Autologous | Allogeneic | Allogeneic | Allogeneic | Allogeneic |
| HSCT conditioning regimen | MA | MA | MA | RIC | MA | RIC |
| Day post-HSCT when TMA was diagnosed | 13 | 68 | 390 | 6 | 41 | 57 |
| Cystatin C-eGFR (mL/min) at TMA diagnosis | 48 | 20 | 16 | 30 | 15 | 17 |
| Renal replacement therapy at TMA diagnosis | No | No | Yes | No | No | Yes |
| Urine protein-to-creatinine ratio (normal <.2 mg/ mg, nephrotic >2 mg/mg) | 81.6 | 11.3 | 4.5 | 10.6 | 14.1 | 6.4 |
| HSCT-TMA–related complications | HTN, PH, pericardial effusion | HTN, pericardial effusion | HTN, pericardial tamponade | HTN, PRES, seizures, pericardial effusion | HTN, pulmonary bleeding | HTN, pericardial effusion |
| Complement profile* | ↑C2, ↑C6, ↑CFB | ↓C4 | ↓C4 | ↑C5, ↑C7, ↑C4BP | ↑ C8, ↑C1Inhib, ↓ CFH | ↑ C1Q, ↑C4, ↑C8 |
| sC5b-9 (normal, 119 to 17 5 ng/mL) | 283 | 307 | 139(on TPE) | 328 | 432 | 375 |
| CFH antibody | Absent | Absent | Absent | Absent | Absent | Absent |
| CFHR3-CFHR1 (by MLPA) | Not tested | Normal | Heterozygous deletion | Normal | Not tested | Not tested |
| CFHR1 protein | Present | Present | Present | Present | Present | Present |
| Renal biopsy/autopsy | Not done | TMA, C4d deposits in arterioles | Not done | Not done | Not done | TMA |
| Infections | None | None | None | None | None | Adenovirus, BK, and HSV viremia |
| Acute GVHD | n/a | n/a | Yes (skin) | No | Yes (skin, gut) | Yes (skin, gut) |
| Eculizumab start from HSCT-TMA diagnosis, days | 3 | 40 | 122 | 26 | 24 | 97 |
| Number of eculizumab doses given | 9 | 13 | 6 | 4 | 7 | 2 |
| Number of TPE sessions done before starting eculizumab | None | 32 | 79 | 15 | 24† | 17† |
NBL indicates neuroblastoma; WAS, Wiskott-Aldridge syndrome; CID, combined immunodeficiency; MA, myeloablative regimen; RIC, reduced intensity regimen; HTN, systemic hypertension; PH, pulmonary hypertension; PRES, posterior reversible encephalopathy syndrome; HSV, herpes simplex 1 virus; MLPA, multiplex ligation-dependent probe amplification; Del (CFHR3-CFHR1), heterozygous deletion of CFH gene 3 and 1; n/a, not applicable.
*
Complement profile includes C1inhib, complement component 1 inhibitor; C1Q, complement component 1q complex; C2–C9, complement components 2–9; C4BP, C4d binding protein; complement factors (CF) F, B, H, and I.
†
Died while on eculizumab therapy.