Impact of Hepatitis B Core Antibody Seropositivity on the Outcome of Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

Abstract

Background Hepatitis B core antibody (HBcAb) seropositivity has been associated with a higher rate of hepatitis B virus (HBV) reactivation after chemotherapy, even in patients who are hepatitis B surface antigen (HBsAg) negative. We evaluated the incidence of hepatitis B reactivation and liver toxicity in patients with multiple myeloma (MM) who received high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (auto-HCT) at our institution. Methods We identified 107 MM patients with resolved HBV infection (HBcAb positive, HBsAg negative) and 125 patients with negative HBV serology (control) who were matched for age, time of auto-HCT, disease status and preparative regimen. Both groups received HDC and auto-HCT between 1991 and 2013. Primary endpoints were: 1) HBV reactivation defined as HBsAg positivity or ≥10-fold increase in HBV DNA; 2) hepatotoxicity, as defined in NCI CTCv3.0. Results Approximately 70% in each group received melphalan alone as preparative regimen. In the resolved HBV infection group, 52 patients (49%) were Hepatitis B surface antibody (HBsAb) positive, and 24 (22%) had detectable HBV DNA prior to auto-HCT. Serum HBV DNA level was <100 IU/m in 22 patients, and <300 IU/ml in 2 patients. Hepatitis B e antigen (HBeAg) was non-reactive in all 4 patients evaluated prior to auto-HCT. Only 1 patient with resolved HBV infection received pre-emptive antiviral therapy with Lamivudine, while 4 patients received Lamivudine (3) or Tenofovir (1) at reactivation for a median duration of 1 year. HBV reactivation was seen in 7 of 107 (6.5%) patients in the resolved HBV group. There was a ≥10-fold increase in HBV DNA in 5 of 7 patients with HBV reactivation, and 2 of 7 also became positive for HBeAg. Median time to HBV reactivation from auto-HCT was 16 months. The cumulative incidence of grade 2 or more hepatotoxicity in resolved HBV infection and the control groups was 30% and 22%, respectively (hazard ratio [HR] 1.3; 95% confidence interval [CI], 0.7–2.3; P = 0.4). There was a trend for higher NRM in the control group at 1 year 7% vs 1%, with a HR of 0.15 (95% CI 0.02–1.2, P = 0.08) and at 2 years 8% vs 1% with a HR of 0.13 (95% CI 0.02–1.1, P= 0.06) after auto-HCT. With a median follow up of 18 and 35 months in resolved HBV infection vs. control groups, the median progression free survival was 21 and 18 months (p=0.5), respectively. Median overall survival in resolved HBV infection and control groups was 53 vs. 67 months (p=0.2), respectively. Conclusion Resolved HBV infection is associated with a significant risk of HBV reactivation and hepatotoxicity in patients undergoing auto-HCT for MM. These complications were reversible and were not associated with a decrease in PFS or OS.

Overlooked prophylaxis of Hepatitis B in patients undergoing hematopoietic stem cell transplantation

“…Hepatitis B virus (HBV) infection is a global public health problem affecting approximately 240 million people all over the world (1). The prevalence of Hepatitis B surface (HBs) antigen positivity varies between 4 -6% in Turkey (2).…”

“…The prevalence of Hepatitis B surface (HBs) antigen positivity varies between 4 -6% in Turkey (2). Hepatitis B virus-related diseases can be seen as an acute infection, chronic infection, inactive carrier, reactivation, and hepatic flare (1).…”

Impact of Hepatitis B Core Antibody Seropositivity on the Liver Function Tests After Autologous Hematopoietic Stem Cell Transplantation for Multiple Myeloma

“…Sınırlı serilerde geçirilmiş HBV infeksiyonu sonrası %6'dan %86'ya kadar değişen reaktivasyon oranları bildirilmiştir (13,14). İtalya'dan yapılan retrospektif bir çalışmada hematolojik malignitesi olup allojeneik hematopoietik kök hücre nakli (HKHN) yapılan hastalar arasında HBV reaktivasyon oranı %10 olarak bildirilmiştir (15 (18). Bu çalışmada merkezlerinde 22 yıllık takipte nakil planlanan miyelom hastaları arasında %8 oranında geçirilmiş HBV infeksiyonu tespit edilmiştir.…”

“…Bu hastalarda HBV reaktivasyon oranı %6.5 olarak ve grade 2 hepatotoksisite açısından seronegatif miyelom hastaları ile benzer sonuçlar elde edildiği bildirilmiştir. Geçirilmiş HBV infeksiyonu olan 107 hastanın sadece 1 (%0.9)'inin pre-emptif antiviral tedavi kullandığı ve 4 (%3.7)'ünün de HBV reaktivasyonu sırasında antiviral tedavi kullandığı görülmüştür (18). Bizim kohortumuzda ise; nakile alınan 79 geçirilmiş HBV infeksiyonlu hastanın hepsinin antiviral kullanıyor olması nedeniyle hiç HBV reaktivasyon görülmemiştir.…”

Incidence and risk factors of hepatitis B virus reactivation in patients with multiple myeloma in an era with novel agents: a nationwide retrospective study in Japan

“…However, before the era of novel agents, such as proteasome inhibitors and immunomodulatory drugs (IMiDs), there were few reports of HBVr in patients with multiple myeloma (MM). Since the approval of these novel agents, the number of reports has increased 1 – 3 . In our previous study of 641 patients with MM, we reported that 9 of 99 (9.1%) patients with resolved HBV infection experienced HBVr 4 .…”