Table 1:

Clinical characteristics and tissue description of children with pulmonary TA-TMA

Pt	Age	Transplant Characteristics	Infections	GVHD	TA-TMA Features	Pulmonary Features	Pulm HTN*	Tissue diagnosis	Tx (Day post HCT treated)	Status
1	7 yr	8/8 URD BMT for T-ALL	Culture negative sepsis	Stage 4, grade 4 lower gut acute GVHD	Clinical Dx D+ 197 sC5b9 308 UPC 4.22 mg/dl LDH 1,805 (ULN 237) Other organ involvement: pro-BNP 13,833 pg/mL (nl <1100), haptoglobin undetectable, bloody stools	RD, Hypoxia D+ 194, RF D +206 DAH	No, 5 ECHOs Pulm HTN protocol	Biopsy Day +216 interstitial eosinophilic bundles of protein occlusion in the vessels with thrombi endothelium with reactive changes media thickened asymmetrical diffuse alveolar hemorrhage	Eculizumab (D+200) Sildenafil	Alive D+ 1273
2	3 yr	Autologous #2 for NB	CMV reactivation RSV	--	Clinical Dx D+ 24 Recurrence D+ 108 sC5b9 522 ng/dL UPC 4.25 mg/mg LDH 627 U/L (ULN 321)	RD, Hypoxia, D +31, RF D +36	Yes, 16 ECHOs, Pulm HTN protocol	Biopsy Day +35 Interstitial plasmocytic pneumonitis diffuse alveolar hemorrhage	Eculizumab (D+24) Sildenafil Steroids	Dead D +136
3	19 yr	7/8 URD BMT for B-ALL	EBV viremia	Severe, extensive chronic GVHD	Clinical Dx D+ 716 sc5b-9 422 ng/dL UPC 0.7mg/mg	RD, hypoxia, D+ 580, RF D+733	No, 5 ECHOs Pulm HTN protocol	Biopsy Day 592 lymphoplasmocytic infiltrative vessel intimal hyperplasia and endothelialitis Eber positive	Rituximab Eculizumab (D 718)	Dead D + 947
4	2 yr	7/8 PBSC for MDS	Adenovirus pneumonitis	Stage 2, grade 3 lower gut acute GVHD	Clinical Dx D + 57 sC5b-9 298 ng/dL UPC 23.3 mg/mg LDH 680 U/L (ULN 321 U/L) Renal failure Refractory HTN	RD, Hypoxia D+ 31, RF D+ 57	Yes, 6 ECHOs, Pulm HTN protocol	Autopsy (lung only) small arterioles have endothelial cells damage with extravasation of fragmented red blood cells, thickened vascular wall diffuse alveolar hemorrhage adenovirus positive **Pleural vessels with TA-TMA	Eculizumab (D+68) Sildenafil	Dead D+ 83
5	14 yr	10/10 URD BMT for MDS	Candida Pneumonia	stage 2, grade 3 lower gut acute GVHD	Post Mortem Diagnosis LDH 1233 U/L (ULN 272 U/L) Renal failure	RD, Hypoxia, D+16, RF D+ 25 DAH	No, 3 ECHOs, Pulm HTN protocol	Autopsy capillary microthrombi, arteriole thrombi, expanded, thickened muscle wall diffuse alveolar hemorrhage **Kidney demonstrated TA-TMA	Steroids	Dead D+ 43
6	19 yr	7/8 URD PBSC for HLH	CMV reactivation, Staphylococc us Epidermidis Bacteremia and Klebsiella Pneumoniae UTI	Stage 2 lower GI, Stage 1 upper GI, overall grade 3 acute GVHD	Clinical Dx D+ 14 sC5b-9 509 ng/dL UPC 2.94 mg/mg LDH 1680 u/L (ULN 246 u/L) Renal failure Refractory HTN	RD, hypoxia D+ 113 RF D+ 119	No, 6 ECHOs, Pulm HTN protocol	Autopsy: diffuse alveolar hemorrhage multiple different stages of organizing thrombi identified in veins, arteries, and arterioles; fragmented RBCs in the artery wall **Kidney and intestines demonstrated TA-TMA	Eculizimab (D+ 15)	Dead D+ 134
7	13 yr	10/10 MSD for AML	Rhinovirus, culture negative sepsis	None	Post mortem diagnosis LDH 516 Proteinuria Renal Failure	RD, hypoxia D+8 RF D+8	No, 3 ECHOs Pulm HTN protocol	Autopsy: diffuse alveolar hemorrhage -Endothelial proliferation, fibrin accumulation, focal intravascular thrombi, red cell fragmentation, and fibrinoid changes **Cardiac vessel TA-TMA	None	Dead D+13
8	1 yr	7/8 MUD for MDS/SAMD9L	Culture negative sepsis	None	Post mortem diagnosis LDH 345 U/L Proteinuria Renal failure	RD D+19 DAH	No, 1 ECHO, Pulm HTN protocol	Autopsy: hyaline membranes deposit along the walls of the alveol thrombi identified in veins; thickened vascular wall	None	Dead D+23
9	18 yr	7/8 MUD for mycosis fungoides	CMV viremia with pneumonitis	None	Post mortem diagnosis LDH 595 U/L Cytopenias, low hapto Renal failure Pericardial effusion	D +56 pericardial/pleur al effusions requiring drainage RD D +70 RF D+114	No, 19 ECHOs, Pulm HTN protocol	Autopsy (lung only): diffuse alveolar hemorrhage multiple different stages of thrombi identified in veins, arteries, and arterioles thickened vascular wall	None	Dead D + 126
10	5 yr	7/10 haplo related for AML	Aspergillus, stenotrophom onas, adenovirus, PJP, pseudomonas	Severe chronic lung (BO) and liver	Dx D+90 Schistocytes, proteinuria, sC5b-9 448 ng/dL, GI biopsy TMA and GvHD	RD and hypoxia D + 101 D+ 480 relapse	No. 5 ECHOs, Pulm HTN protocol	Autopsy: diffuse alveolar hemorrhage multiple different stages of thrombi identified in veins, arteries, and arterioles Fungi infection and necrosis	Eculizumab (D+ 101) Steroids	Dead D+ 541

Transplant associated thrombotic microangiopathy (TA-TMA), , Pulmonary HTN detected on ECHO,

^*DAH not clinically diagnosed, but noted on tissue,

^#not clinically diagnosed, but retrospectively met criteria and autopsy of multiple organs demonstrate TMA. sC5b9 upper limit of normal is 244 ng/dL. Nephrotic range proteinuria is ≥2 mg/mg. Abbreviations: unrelated donor (URD), bone marrow transplant (BMT), peripheral blood stem cell (PBSC), hemophagocytic lymphohistiocytosis (HLH), myelodysplastic syndrome (MDS), acute b- lymphoblastic leukemia (B-ALL), neuroblastoma (NB), respiratory distress (RD), respiratory failure (RF), diffuse alveolar hemorrahage (DAH), urine protein to creatinine (UPC), lactate dehydrogenase (LDH), upper limit of normal (ULN), hypertension (HTN), sc5b-9 upper limit of normal 244 ng/dL.