Lack of known hepatitis virus in hepatitis-associated aplastic anemia and outcome after bone marrow transplantation

Viral infection has been shown to induce aplastic anemia, unidentified type s of hepatitis being the most common cause for aplastic anemia-associated v iral hepatitis. The survival rate for this group of patients after bone mar row transplantation with stem cells from an HLA-matched sibling is not well known. The aim of this study was to determine the prevalence of hepatitis G virus (HGV) and transfusion transmitted virus (TTV) infection in non-A, n on-B, non-C hepatitis associated-aplastic anemia (HAAA) patients, and to de fine the role of bone marrow transplantation (BMT) as a therapeutic modalit y for this disease. Sixty-eight patients (43 males and 25 females) with apl astic anemia, underwent allogeneic BMT at the Hadassah University Hospital between 1981 and 1997. Onset of hepatitis was defined as jaundice and eleva ted alanine aminotransaminase (ALT) levels. Onset of aplastic anemia was de fined as the first date on which varying degrees of pancytopenia occurred: hemoglobin level below 10 g/dl, WBC below 2 x 10(9)/l and low platelet coun t 10 x 10(10)/l. Serial serum samples from HAAA patients were assayed for v irological and/or serological markers of hepatitis A, B, C, D, E, G viruses , TTV and parvovirus B19. Seventeen of the 68 patients with aplastic anemia (25%) suffered from hepatitis, 12 males and five females, ages 5 to 36 yea rs. The mean interval between onset of hepatitis and first indication of ap lastic anemia was 62 days (range 14-225 days). The development of aplastic anemia was unrelated to age, sex or severity of hepatitis. Ten of the 17 pa tients (59%) achieved complete ALT recovery prior to the diagnosis of aplas tic anemia. Serum samples were available for 15 patients; none had evidence of acute or active hepatitis A, B, C, D, E, G and TTV virus infection at t he time of diagnosis. Parvovirus B19 DNA sequences were not detectable in 1 0 of 12 tested cases; two positive results were detected in serum samples o btained after blood transfusion, making the analysis of these positive resu lts difficult. All 17 patients underwent BMT. The mean post-BMT follow-up p eriod was 38 months (range 1 day-123 months), five patients (30%) died 1 to 160 days post BMT, and 12 (70%) are alive 31 to 123 months after BMT. Rela psing hepatitis was not observed in any of the patients. In conclusion, HAA A is a disease of the young and the etiologic agent associated with HAAA re mains unknown. HGV, TTV and parvovirus B19 sequences were not detected in a ny of the HAAA cases. The survival rate after BMT with stem cells from an H LA-matched sibling is similar to that for patients with non-hepatitis-assoc iated aplastic anemia.