Clinical Profile and Outcomes of Patients with â Thalassemia Major and Hepatitis C Virus Infection Undergoing an Allogeneic Stem Cell Transplant

There is limited data on the prevalence, clinical profile and outcome of patients with β thalassemia major (TM) who was HCV sero-positive (HCV+) prior to an allogeneic stem cell transplant (SCT). From October, 1991 to June, 2012, 370 SCT were done for TM at our center. The median age was 7.5 years (range: 2-24) and there were 232 (62.87%) males. 209 (56.5%) belonged to Lucarelli Class III. There were 44 (11.9%) cases who were HCV+, 6 (1.6%) who were HBsAg positive and 350 (94.6%) who were CMV sero-positive at the time of pre-transplant screening.

HCV+ cases were significantly older (P=0.000) and had a significantly larger liver size (P=0.001). There were significantly more number of HCV+ cases who were Lucarelli Class III (84% Vs. 52.8%; P=0.000). The number of graft rejections was significantly higher in the HCV+ group (22.7% Vs. 10.4%; P=0.025) while the treatment related mortality was comparable between the two groups. It is well recognized that patients with TM are at a high risk of developing sinusoidal obstruction syndrome (SOS) post SCT. In this series, 165 (44.6%) patients developed SOS. HCV+ cases did not have a significantly higher incidence of SOS compared to those that were HCV negative (47.7% Vs. 44.3%; P=0.747). Among the 15 (34%) of HCV+ cases that died, the major contributory cause of death was infection (40%), graft failure (20%) and SOS (20%). The overall and event free survival among those that were HCV+ve Vs. those that were negative was 63.7±8.1% Vs. 75±2.5% and 47.4±8.1% Vs. 70±2.7%; P-Value=0.158 and 0.019 respectively. On a univariate cox regression analysis, HCV+ had an adverse impact on EFS (RR=1.710; 95%CI 1.066-1.744; P=0.026). However, on a forward stepwise multivariate analysis after adjusting for conventional risk factors HCV+ status did not confer an independent adverse risk factor. Of the 29 HCV+ patients who are surviving, at a median follow up of 25 months, none have had progression to chronic liver disease. 20 (69%) had a normal liver function test at last follow up while only 3 have had HCV directed therapy post transplant.        

From August, 2009 at our center we have been using a treosulfan based conditioning regimen for our Class III patients. Among the 44 HCV+ patients 10 were conditioned with this regimen. This regimen was well tolerated with 100% engraftment. Two patients died, one due to sepsis and the other to GVHD. This compared favorably with the historical control of HCV+ cases conditioned with a conventional busulfan based regimen.

In conclusion HCV+ status is a surrogate risk factor for other adverse risk factors such as older age, increased liver size and inadequate medical therapy prior to SCT. After adjusting for such risk factors HCV+ cases with TM undergoing an allogeneic SCT transplant have comparable outcomes to HCV negative cases. Use of a treosulfan based regimen is well tolerated in the HCV+ group and could potentially improve the outcome in this high risk group.