Veno-occlusive disease of the liver after busulfan, melphalan, and thiotepa conditioning therapy: Incidence, risk factors, and outcome

Abstract

The purpose of this study was to determine the incidence of veno-occlusive disease (VOD) after a high-dose regimen of busulfan, melphalan, and thiotepa and the risk factors for a more severe outcome. We followed 253 consecutive patients with malignant disorders who received autologous transplants after stem cell harvest followed by 12 mg/kg busulfan, 100 mg/m2 melphalan, and 500 mg/m2 thiotepa. Diagnosis of VOD was based on weight gain, hepatomegaly, and jaundice. Risk factors for moderate or severe VOD were identified using logistic regression models. VOD occurred in 70 of 253 patients (28%), of whom 31 (12%) had moderate and 11 (4%) severe VOD. The median day of onset of hyperbilirubinemia was day 9, significantly later than the onset of jaundice after our cyclophosphamide-based regimens (p < 0.001). Resolution of weight gain and jaundice, followed by their reappearance several weeks later, occurred in 23 of 70 patients with VOD and was an adverse prognostic sign. Risk factors for moderate or severe VOD were a diagnosis of lymphoma or myeloma (odds ratio [OR] 2.65 compared with breast cancer), tumor involvement in the liver (OR 3.95), fever in the month before transplant (OR 3.32), and prior radiation therapy (OR 2.70). We conclude that VOD after busulfan, melphalan, and thiotepa was less frequent and less severe and developed later than VOD after our historical cyclophosphamide-based regimens. Significant risk factors included a diagnosis other than breast cancer, hepatic metastases, persistent fever, and prior radiation therapy. This study suggests that alkylating agents of comparable overall toxicity differ in their liver toxicity.

Target dose adjustment of busulfan in pediatric patients undergoing bone marrow transplantation

“…12,13 Therefore, patients receiving melphalan or thiotepa in combination with low-dose cyclophosphamide were excluded from statistical analysis. VP-16 was added to the conditioning regimen of the three patients with familial hemophagocytic lymphohistiocytosis (FEL) in an attempt to eliminate residual disease rather than to increase myelosuppression or effect circulating lymphocytes.…”

Recent decrease in non-relapse mortality due to GVHD and infection after allogeneic hematopoietic cell transplantation in non-remission acute leukemia

“…Although intensified antitumor treatment may be required in allo-HCT in non-remission, continuous effort is needed for monitoring, prevention and intervention with regard to regimen-related toxicity, including late effects. [38][39][40] As this analysis is based on a retrospectively collected multicenter database, our results may be susceptible to the disadvantages of any retrospective study using a multicenter registry database. In patients who died without a confirmed hematological remission, we assumed the disease status from the survival time.…”

Portal vein thrombosis after hematopoietic cell transplantation: frequency, treatment and outcome

“…As VOD develops in 30-50% of patients who undergo myeloablative hematopoietic cell transplantation at our center, 19,20,22 we estimate the frequency of PVT among patients with VOD at 1%. An Australian group has previously reported three patients with PVT after autologous hematopoietic cell transplantation, with a denominator of 47 patients undergoing autologous hematopoietic cell transplantation.…”