A Retrospective Analysis Of The Association Between Common Myeloablative Conditioning Regimens and Hepatotoxicity

Abstract

High dose chemotherapy preceding stem cell transplant carries considerable risk of organ toxicity. Hepatic toxicity is one of the major causes of morbidity post transplant. The etiology is multi-factorial, with the common culprits being graft versus host disease as well as the agents used as part of the conditioning regimen. Evidence of pre-existing mild hepatic insufficiency demands an even more cautious approach while selecting a conditioning regimen prior to stem cell transplant. We analyzed the effect of various myeloablative conditioning regimens on post transplant liver function tests (LFT). CEP (cyclophosphamide, etoposide and cisplatin), BuCy (busulfan and cyclophosphamide), BEAM (carmustine, etoposide, cytarabine and melphalan) and Cy/TBI (cyclophosphamide with total body irradiation) were the four most commonly used regimens for autologous stem cell transplant (auto-SCT) at our center. A total of 404 patients were treated with CEP (210), BuCy (76), CyTBI (71) or BEAM (47) from 1988 to 2013. The majority of the patients underwent an auto-SCT for lymphoma (218 non-Hodgkin lymphoma, 98 Hodgkin's lymphoma), while 67 transplant patients had leukemia. Patient age ranged from 17 to 73 years at the time of transplant, and the sex distribution revealed a male:female ratio of 1.5:1. We looked at the incidence of total bilirubin greater than 2 mg/dl, alkaline phosphatase greater than upper limit of normal, ALT greater than 126 U/L and AST greater than 82 U/L. The outcome of univariate analysis using chi-square test demonstrated statistically significant inter-group variability for three of the LFTs. CyTBI had the lowest incidence of hepatic insufficiency. Further analysis comparing CyTBI to the other three regimens, confirmed a highly significant statistical difference (p<0.01 by two-sided Fisher's Exact test, see table below) in elevation of bilirubin, alkaline phosphatase as well as both the transaminases, favoring Cy/TBI as the safer regimen. This is an interesting finding given the common perception that TBI-based regimens are more toxic.CEP, BuCy and BEAMCy/TBIaffected/total (%)affected/total (%)p-valueTotal Bilirubin (≥ 2 mg/dl)27/263 (10.2 %)0/59 (0 %)0.007Alkaline Phosphatase (≥ upper limit of normal)97/262 (37 %)8/58 (13.7 %)0.0005ALT (≥ 126 U/L)39/263 (14.8 %)0/59 (0 %)0.0002AST (≥ 82 U/L)44/264 (16.7 %)2/59 (3.3 %)0.0065 Disclosures:No relevant conflicts of interest to declare.