Patient baseline characteristics
| . | Defibrotide treatment group (n = 102) . | Historical-control cohort (n = 32) . |
|---|---|---|
| VOD/SOS eligibility | ||
| Elevated total bilirubin | 102 (100) | 32 (100) |
| Hepatomegaly | 84 (82.4) | 27 (84.4) |
| Ascites | 95 (93.1) | 27 (84.4) |
| Weight gain | 98 (96.1) | 29 (90.6) |
| Total bilirubin (mg/dL) | ||
| Mean (SD) | 7.3 (7.4) | 7.8 (10) |
| Median (min, max) | 4.9 (1, 41.4) | 4.9 (2.1, 57) |
| AST (U/L) | ||
| N | 101 | 30 |
| Mean (SD) | 458.3 (964.6) | 299.5 (742.3) |
| Median (min, max) | 90 (8, 5397) | 38 (11, 3790) |
| ALT (U/L) | ||
| N | — | 26 |
| Mean (SD) | 100 240 (403.3) | 304.8 (746.7) |
| Median (min, max) | 62 (5, 2130) | 33 (6, 3596) |
| Underlying disease, n (%) | ||
| Acute myelogenous leukemia | 29 (28.4) | 8 (25) |
| Acute lymphocytic leukemia | 17 (16.7) | 7 (21.9) |
| Myelodysplastic syndrome | 7 (6.9) | 3 (9.4) |
| Non-Hodgkin lymphoma | 5 (4.9) | 2 (6.3) |
| Neuroblastoma | 6 (5.9) | 0 |
| Chronic myelogenous leukemia | 4 (3.9) | 1 (3.1) |
| Multiple myeloma | 3 (2.9) | 1 (3.1) |
| Aplastic anemia | 1 (1) | 1 (3.1) |
| Hodgkin lymphoma | 1 (1) | 2 (6.3) |
| Immunodeficiency | 1 (1) | 0 |
| Chronic lymphocytic leukemia | 1 (1) | 0 |
| Other | 26 (25.4) | 6 (21.8) |
| Myelofibrosis | 4 (3.9) | 0 |
| Hemophagocytic lymphohistiocytosis | 3 (2.9) | 1 (3.1) |
| Medulloblastoma | 2 (2) | 1 (3.1) |
| Osteopetrosis | 2 (2) | 0 |
| Juvenile myelomonocytic leukemia | 2 (2) | 0 |
| β-thalassemia major | 1 (1) | 1 (3.1) |
| Chronic granulomatous disease | 1 (1) | 0 |
| Fanconi anemia | 1 (1) | 0 |
| Tay-Sachs disease | 1 (1) | 0 |
| Sickle cell disease | 1 (1) | 0 |
| Severe combined immunodeficiency | 1 (1) | 0 |
| Retinoblastoma | 1 (1) | 0 |
| Omenn syndrome | 1 (1) | 0 |
| Krabbe disease | 1 (1) | 1 (3.1) |
| Hurler syndrome | 2 (2) | 0 |
| Acute undifferentiated leukemia | 1 (1) | 0 |
| Myeloproliferative disease | 0 | 1 (3.1) |
| Congenital amegakaryocytic thrombocytopenia | 0 | 1 (3.1) |
| Thalassemia major | 1 (1) | 0 |
| Hepatosplenic T-cell lymphoma | 0 | 1 (3.1) |
| Waldenstrom macroglobulinemia | 1 (1) | 0 |
| HSCT graft type, n (%) | ||
| Allogeneic | 90 (88.2) | 27 (84.4) |
| Related matched donor | 33 (36.7) | 11 (40.7) |
| Related mismatched donor | 2 (2.2) | 1 (3.7) |
| Unrelated matched donor | 29 (32.2) | 10 (37) |
| Unrelated mismatched donor (including cord blood, donor bone marrow, peripheral blood stem cells) | 26 (28.9) | 5 (18.5) |
| Myeloablative conditioning regimen | 89 (87.3) | 30 (93.8) |
| Conditioning regimen, n (%)* | ||
| Cyclophosphamide | 75 (73.5) | 26 (81.3) |
| Busulfan | 45 (44.1) | 14 (43.8) |
| Fludarabine | 24 (23.5) | 3 (9.4) |
| Melphalan | 21 (20.6) | 5 (15.6) |
| Antithymocyte immunoglobulin | 20 (19.6) | 6 (18.8) |
| VP-16 (etoposide) | 15 (14.7) | 7 (21.9) |
| Thiotepa | 8 (7.8) | 2 (6.3) |
| Carboplatin | 8 (7.8) | 1 (3.1) |
| Alemtuzumab | 2 (2) | 0 |
| BCNU (carmustine) | 1 (1) | 1 (3.1) |
| Clofarabine | 1 (1) | 0 |
| Dexamethasone | 1 (1) | 0 |
| Gemtuzumab ozogamicin | 1 (1) | 0 |
| Rituximab | 1 (1) | 0 |
| Cytarabine | 0 | 2 (6.3) |
| Other therapeutic products | 41 (40.2) | 14 (43.8) |
| GVHD prophylaxis use at study entry (most common)* | ||
| None | 12 (11.8) | 5 (15.6) |
| Tacrolimus | 50 (49) | 5 (15.6) |
| Methotrexate | 42 (41.2) | 20 (62.5) |
| Cyclosporine | 39 (38.2) | 23 (71.9) |
| Mycophenolate mofetil | 29 (28.4) | 3 (9.4) |
| Sirolimus/tacrolimus | 15 (14.7) | 0 |
| Methylprednisolone | 4 (3.9) | 9 (28.1) |
| Methylprednisolone sodium succinate | 3 (2.9) | 1 (3.1) |
| MOF, n (%) | ||
| Renal dysfunction at study entry | 80 (78.4) | 24 (75) |
| Tripling of baseline creatinine at study entry | 75 (73.5) | 24 (75) |
| Dialysis dependence at study entry | 20 (19.6) | 2 (6.3) |
| Pulmonary dysfunction at study entry | 87 (85.3) | 31 (96.9) |
| Requirement for supplemental oxygen at study entry | 86 (84.3) | 30 (93.8) |
| Ventilator dependence at study entry | 26 (25.5) | 6 (18.8) |
| Hepatic VOD/SOS with MOF diagnosis according to: | ||
| Pulmonary dysfunction only | 22 (21.6) | 8 (25) |
| Renal dysfunction only | 15 (14.7) | 1 (3.1) |
| Both pulmonary and renal dysfunction | 65 (63.7) | 23 (71.9) |
| Hepatic VOD/SOS with MOF diagnosis by day +28 | ||
| Yes | 101 (99) | 32 (100) |
| No | 1 (1) | 0 |
| Time to hepatic VOD/SOS with MOF diagnosis (d)† | ||
| N | 102 | 32 |
| Mean (SD) | 13.8 (6.09) | 12.8 (4.92) |
| Median | 13 | 12.5 |
| Range (min, max) | (1, 29) | (4, 23) |
| . | Defibrotide treatment group (n = 102) . | Historical-control cohort (n = 32) . |
|---|---|---|
| VOD/SOS eligibility | ||
| Elevated total bilirubin | 102 (100) | 32 (100) |
| Hepatomegaly | 84 (82.4) | 27 (84.4) |
| Ascites | 95 (93.1) | 27 (84.4) |
| Weight gain | 98 (96.1) | 29 (90.6) |
| Total bilirubin (mg/dL) | ||
| Mean (SD) | 7.3 (7.4) | 7.8 (10) |
| Median (min, max) | 4.9 (1, 41.4) | 4.9 (2.1, 57) |
| AST (U/L) | ||
| N | 101 | 30 |
| Mean (SD) | 458.3 (964.6) | 299.5 (742.3) |
| Median (min, max) | 90 (8, 5397) | 38 (11, 3790) |
| ALT (U/L) | ||
| N | — | 26 |
| Mean (SD) | 100 240 (403.3) | 304.8 (746.7) |
| Median (min, max) | 62 (5, 2130) | 33 (6, 3596) |
| Underlying disease, n (%) | ||
| Acute myelogenous leukemia | 29 (28.4) | 8 (25) |
| Acute lymphocytic leukemia | 17 (16.7) | 7 (21.9) |
| Myelodysplastic syndrome | 7 (6.9) | 3 (9.4) |
| Non-Hodgkin lymphoma | 5 (4.9) | 2 (6.3) |
| Neuroblastoma | 6 (5.9) | 0 |
| Chronic myelogenous leukemia | 4 (3.9) | 1 (3.1) |
| Multiple myeloma | 3 (2.9) | 1 (3.1) |
| Aplastic anemia | 1 (1) | 1 (3.1) |
| Hodgkin lymphoma | 1 (1) | 2 (6.3) |
| Immunodeficiency | 1 (1) | 0 |
| Chronic lymphocytic leukemia | 1 (1) | 0 |
| Other | 26 (25.4) | 6 (21.8) |
| Myelofibrosis | 4 (3.9) | 0 |
| Hemophagocytic lymphohistiocytosis | 3 (2.9) | 1 (3.1) |
| Medulloblastoma | 2 (2) | 1 (3.1) |
| Osteopetrosis | 2 (2) | 0 |
| Juvenile myelomonocytic leukemia | 2 (2) | 0 |
| β-thalassemia major | 1 (1) | 1 (3.1) |
| Chronic granulomatous disease | 1 (1) | 0 |
| Fanconi anemia | 1 (1) | 0 |
| Tay-Sachs disease | 1 (1) | 0 |
| Sickle cell disease | 1 (1) | 0 |
| Severe combined immunodeficiency | 1 (1) | 0 |
| Retinoblastoma | 1 (1) | 0 |
| Omenn syndrome | 1 (1) | 0 |
| Krabbe disease | 1 (1) | 1 (3.1) |
| Hurler syndrome | 2 (2) | 0 |
| Acute undifferentiated leukemia | 1 (1) | 0 |
| Myeloproliferative disease | 0 | 1 (3.1) |
| Congenital amegakaryocytic thrombocytopenia | 0 | 1 (3.1) |
| Thalassemia major | 1 (1) | 0 |
| Hepatosplenic T-cell lymphoma | 0 | 1 (3.1) |
| Waldenstrom macroglobulinemia | 1 (1) | 0 |
| HSCT graft type, n (%) | ||
| Allogeneic | 90 (88.2) | 27 (84.4) |
| Related matched donor | 33 (36.7) | 11 (40.7) |
| Related mismatched donor | 2 (2.2) | 1 (3.7) |
| Unrelated matched donor | 29 (32.2) | 10 (37) |
| Unrelated mismatched donor (including cord blood, donor bone marrow, peripheral blood stem cells) | 26 (28.9) | 5 (18.5) |
| Myeloablative conditioning regimen | 89 (87.3) | 30 (93.8) |
| Conditioning regimen, n (%)* | ||
| Cyclophosphamide | 75 (73.5) | 26 (81.3) |
| Busulfan | 45 (44.1) | 14 (43.8) |
| Fludarabine | 24 (23.5) | 3 (9.4) |
| Melphalan | 21 (20.6) | 5 (15.6) |
| Antithymocyte immunoglobulin | 20 (19.6) | 6 (18.8) |
| VP-16 (etoposide) | 15 (14.7) | 7 (21.9) |
| Thiotepa | 8 (7.8) | 2 (6.3) |
| Carboplatin | 8 (7.8) | 1 (3.1) |
| Alemtuzumab | 2 (2) | 0 |
| BCNU (carmustine) | 1 (1) | 1 (3.1) |
| Clofarabine | 1 (1) | 0 |
| Dexamethasone | 1 (1) | 0 |
| Gemtuzumab ozogamicin | 1 (1) | 0 |
| Rituximab | 1 (1) | 0 |
| Cytarabine | 0 | 2 (6.3) |
| Other therapeutic products | 41 (40.2) | 14 (43.8) |
| GVHD prophylaxis use at study entry (most common)* | ||
| None | 12 (11.8) | 5 (15.6) |
| Tacrolimus | 50 (49) | 5 (15.6) |
| Methotrexate | 42 (41.2) | 20 (62.5) |
| Cyclosporine | 39 (38.2) | 23 (71.9) |
| Mycophenolate mofetil | 29 (28.4) | 3 (9.4) |
| Sirolimus/tacrolimus | 15 (14.7) | 0 |
| Methylprednisolone | 4 (3.9) | 9 (28.1) |
| Methylprednisolone sodium succinate | 3 (2.9) | 1 (3.1) |
| MOF, n (%) | ||
| Renal dysfunction at study entry | 80 (78.4) | 24 (75) |
| Tripling of baseline creatinine at study entry | 75 (73.5) | 24 (75) |
| Dialysis dependence at study entry | 20 (19.6) | 2 (6.3) |
| Pulmonary dysfunction at study entry | 87 (85.3) | 31 (96.9) |
| Requirement for supplemental oxygen at study entry | 86 (84.3) | 30 (93.8) |
| Ventilator dependence at study entry | 26 (25.5) | 6 (18.8) |
| Hepatic VOD/SOS with MOF diagnosis according to: | ||
| Pulmonary dysfunction only | 22 (21.6) | 8 (25) |
| Renal dysfunction only | 15 (14.7) | 1 (3.1) |
| Both pulmonary and renal dysfunction | 65 (63.7) | 23 (71.9) |
| Hepatic VOD/SOS with MOF diagnosis by day +28 | ||
| Yes | 101 (99) | 32 (100) |
| No | 1 (1) | 0 |
| Time to hepatic VOD/SOS with MOF diagnosis (d)† | ||
| N | 102 | 32 |
| Mean (SD) | 13.8 (6.09) | 12.8 (4.92) |
| Median | 13 | 12.5 |
| Range (min, max) | (1, 29) | (4, 23) |
AST, aspartate aminotransferase; ALT, alanine aminotransferase; BCNU, bis-chloroethylnitrosourea; SGOT, serum glutamic-oxaloacetic transaminase; SPGT, serum glutamic pyruvic transaminase.
Patients may have received >1 conditioning or prophylactic agent, so percentages add to >100%; P = .003 for difference between groups.
Time measured from date of HSCT.