Hepatitis C (HC) Virus Infection Is Associated with Worse Survival after Allogeneic Hematopoietic Stem Cell Transplantation (alloSCT) for Hematological Malignancies.
Authors: Ramos Carlos A. , Saliba Rima M. , Khorshid Ola , de Padua Leandro , Giralt Sergio , Andersson Borje S. , Ueno Naoto T. , Shpall Elizabeth J. , Khouri Issa F. , Hosing Chitra , Alousi Amin , Nieto Yago , Qureshi Suhail R. , Champlin Richard E. , de Lima Marcos 
Published: November 2019

The influence of chronic HC on the outcome of patients undergoing alloSCT is not clearly defined. We hypothesized that HC is associated with increased risk of non-relapse mortality (NRM) after alloSCT. We performed a retrospective matched-control study of the outcomes of 31 patients (table 1) with serological evidence of HC at the time of alloSCT performed between 1998 and 2007. Control patients (N=31) had negative serology for HC and were matched on age, diagnosis, disease stage, type of conditioning regimen and donor type (referred to as matched controls). To confirm the validity of the matching procedure we extended the comparison to the 1800 seronegative patients (all controls) transplanted for the same diagnoses during the same period of time in our institution. Multivariate analysis took into account all variables used in our matching algorithm.

All HC patients had ALT levels less than 3 times the upper limit of normal and normal bilirubin levels at alloSCT. There were no significant differences in these parameters compared to control patients. Median follow-up was 34 (range 3–53), 27 (4–74) and 29 months (1–108), respectively for HC, matched and all controls. Overall survival post-alloSCT was significantly inferior in the HC group, with a median OS of 3 versus 18 and 20 months in the control groups. The cumulative rate of disease progression and acute or chronic GVHD was comparable, but NRM was significantly increased in the HC group (table 2). Results were similar regardless of the control group used, which validated our matching procedure.

In conclusion, serological evidence of HC virus infection at the time of alloSCT, even with normal or minimally abnormal liver tests, is associated with worse survival in the context of alloSCT, due to an increased rate of non-relapse deaths.

Table 1: Patient characteristics Characteristic HC (N=31) All controls (N=1800) P Matched controls (N=31) patient characteristics are identical to the HC group Median age (range) 49 (26–72) 47 (3–75) 0.2 Status at transplant: 0.2 - High risk (%) 19 (61) 905 (50) - Low risk (%) 12 (39) 895 (50) Donor type: 0.2 - Sibling (%) 21 (68) 1026 (57) - Unrelated (%) 10 (32) 760 (42) Preparative regimen: 0.02 - Reduced intensity (%) 21 (68) 754 (42) - Myeloablative (%) 10 (32) 1046 (58) Diagnosis: 0.7 - AML/MDS (%) 15 (48) 740 (41) - CML/MPD (%) 6 (19) 274 (15) - Lymphoma (%) 7 (22) 514 (29) - Myeloma (%) 2 (6) 87 (5) - ALL (%) 1 (3) 185 (10) Table 2: Patients with HC have worse OS and NRM than controls Matched analysis Multivariate analysis Outcome HC (N=31) vs. matched controls (N=31), % HR (95% CI) P HC (N=31) vs. all controls (N=1800), % HR (95% CI) P HC: hepatitis C, OS: Overall survival, NRM: Non-relapse mortality OS: 3 mo 58 vs. 87 3.6 (1.2–11.0) 0.03 58 vs. 87 3.9 (2.2–6.8) <0.001 1 yr 29 vs. 56 2.4 (1.2–4.9) 0.01 29 vs. 56 3.1 (1.9–5.6) <0.001 NRM: 3 mo 29 vs. 13 2.5 (0.8–8.1) 0.1 29 vs. 10 3.6 (1.8–7.1) <0.001 1 yr 43 vs. 24 2.9 (1.1–7.7) 0.03 43 vs. 23 3.3 (1.9–5.6) <0.01