Rituximab use in hematology and oncology practice has significantly and positively improved the clinical outcomes in patients with a wide variety of B-cell lymphoproliferative disorders. However, hepatitis B virus reactivation related to rituximab use is associated with increased morbidity and mortality in oncology practice. This article focuses on the current evidence that supports these recently revised clinical recommendations along with a review of the risk factors for reactivation, suggested monitoring, and preventative interventions.
After completing this course, the reader will be able to:
Perform screening for prior hepatitis B viral exposure in all patients with hematologic malignancies who will receive rituximab as part of their therapy.Implement prophylactic antiviral therapy in patients who are positive for hepatitis B and who are being treated with rituximab.Monitor serum viral load and clinical signs of hepatic injury for at least six months following the completion of rituximab treatment in patients who are hepatitis B-sAg positive.
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Rituximab use in hematology and oncology practice has significantly and positively improved the clinical outcomes in patients with a wide variety of B-cell lymphoproliferative disorders. However, emerging data reveal that there is a risk of viral hepatitis B reactivation in some patients treated with rituximab. Many of these cases result in treatment delays, inferior oncologic outcomes, increased morbidity, and more rarely fulminant hepatic decompensation and death. Indeed, the rituximab package insert and many clinical practice guidelines have been modified to reflect these concerns. The true incidence and mechanism of reactivation are still being elucidated. This article focuses on the current evidence that supports these recently revised clinical recommendations along with a review of the risk factors for reactivation, suggested monitoring, and preventative interventions.
Hepatitis B; Rituximab; Reactivation; Lymphoma; Viral hepatitis
The widespread use of cytotoxic chemotherapy and immunosuppressants has resulted in reactivation of hepatitis B virus (HBV) recently becoming an issue. Although rituximab (an anti-CD20 monoclonal antibody) has revolutionized the treatment of lymphoma, recent reports have suggested that rituximab therapy increases the risk of viral-mediated complications, and particularly HBV reactivation. This study analyzed real clinical practice data for rituximab-related HBV reactivation.
Between January 2005 and December 2011, 169 patients received treatment with rituximab. Screening status of the HBV infection and frequency of preemptive therapy were determined in these patients, and the clinical features of HBV reactivation were analyzed.
Seventy-nine of the 169 patients with chronic or past HBV infection were selected for evaluation of HBV reactivation. Of the 90 patients who were excluded, 22 (13.0%) were not assessed for HBsAg and anti-HBc, and 14 (8.3%) were not assessed for anti-HBc due to seronegativity for HBsAg. The selected patients were divided into those with chronic HBV infection (n=12) and those with past HBV infection (n=67); six patients (7.6%) experienced HBV reactivation. Eight patients received preemptive therapy, but three patients (37.5%) underwent HBV reactivation. Although HBsAg seropositivity was an independent risk factor for HBV reactivation (P=0.038), of the six patients with HBV reactivation, two (33.3%) had past HBV infection and three (50%) died of liver failure.
The findings of this study demonstrate that adherence to guidelines for screening and preemptive therapy for HBV reactivation was negligent among the included cohort. Attention should be paid to HBV reactivation in patients with past as well as chronic HBV infection during and after rituximab therapy.
Hepatitis B virus; Immunosuppressant; Rituximab
Systemic B-cell depletion and clinical remission of the systemic effects of cryoglobulins have already been achieved using rituximab in hepatitis C virus-positive immunocompetent patients. Conversely, to the best of our knowledge there are no reports in the literature regarding the use of rituximab in hepatitis B virus-associated cryoglobulinemia.
We report here the case of a 60-year-old Caucasian man who presented with hepatitis B virus-associated type II cryoglobulinemia with severe multisystem disease, including membranoproliferative glomerulonephritis with acute renal failure. The vasculitis was refractory to conventional and antiviral therapy but rituximab use led to a fall in cryoglobulin levels and disease control. The B-cell depletion was safe and efficient to induce a complete remission of the disease.
Our case highlights the benefit and the efficacy of rituximab in association with antiviral therapy in small vessel vasculitis related to hepatitis B virus-associated mixed cryoglobulinemia.
Adherence to established clinical guidelines in regard to hepatitis B screening, the use of antiviral prophylaxis prior to rituximab treatment, and clinical outcomes in patients receiving rituximab since its introduction in 2001 in a large health care network were investigated. A critical need to identify at-risk patients and provide timely prophylactic antiviral therapy to prevent serious morbidity and mortality was exposed.
Reactivation of hepatitis B virus (HBV) replication in patients receiving rituximab is well described. Current international guidelines recommend HBV screening prior to the commencement of immunosuppressive therapy. However, adherence to such protocols has not previously been studied. We therefore audited screening practices and clinical outcomes in patients prescribed rituximab since its introduction in a large metropolitan health service. All patients receiving rituximab over an 88-month period were identified via pharmacy records. Medical records and laboratory results were reviewed to determine the timing and type of hepatitis screening. HBV flares were identified and correlated with clinical outcomes and any screening or prophylaxis given. Rituximab was given to 355 patients over 88 months (average age, 61 years; 51% male, 48% born overseas); 83% received rituximab for treatment of a hematological malignancy. HBV screening occurred in 31% of patients and, of these, 66% had pre-emptive screening. Five patients given cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab experienced HBV flares. Four died from viral reactivation. None received antiviral prophylaxis. Hepatitis screening rates in patients receiving rituximab in this study were lower than recommended in clinical guidelines. The identification of five patients with clinically important flares and four deaths in this group highlight the critical need to identify at-risk patients and provide timely prophylactic antiviral therapy to prevent serious morbidity and mortality. Even those with evidence of HBV seroconversion are at risk for fatal flares without active prophylactic antiviral therapy.
Rituximab; Hepatitis B reactivation; Hepatitis B screening; Lymphoma; R-CHOP chemotherapy
Hepatitis B virus (HBV) reactivation is a well-recognized complication that occurs in lymphoma patients who undergo chemotherapy. Only very few cases of HBV reactivation in patients with isolated antibody against hepatitis B surface antigen (anti-HBs) have been reported. We present a case of a 78-year-old woman diagnosed with diffuse large B cell non-Hodgkin's lymphoma who only displayed a positive anti-HBs, as the single possible marker of occult HBV infection, before starting therapy. She was treated with several chemotherapeutic regimens (including rituximab) for disease relapses during 3 years. Forty days after the last cycle of chemotherapy, she presented with jaundice, markedly elevated serum aminotransferase levels, and coagulopathy. HBV serology showed positivity for HBsAg, anti-HBc and anti-HBs. HBV DNA was positive. Antiviral treatment with entecavir was promptly initiated, but the patient died from liver failure. A review of the literature of HBV reactivation in patients with detectable anti-HBs levels is discussed.
Anti-HBs positive; entecavir; hepatitis B virus; lymphoma; reactivation
Hepatitis B virus (HBV) can still be found within the hepatocytes after its clearance and the control of viral replication depends on the immune response. However during immunosuppression, seroconversion of HBsAg has been described followed by disease reactivation. Hepatitis B virus reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents and in particular, by the use of rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. We describe a case of a 64-year old female patient with rheumatoid arthritis and resolved HBV infection, who experienced a severe hepatitis B reactivation after the administration of rituximab.
HBV reactivation; rituximab; rheumatoid arthritis; monoclonal antibodies
Loss of HBsAg and development of surface and core antibodies represent clinical cure. However, recent evidence suggests that hepatitis B virus (HBV) persists in a latent state even in those with mounted protective antibodies. After significant immunosuppression, anti-HBs may decrease and HBsAg may reappear (reverse seroconversion). Reverse seroconversion of HBV has been observed in association with hematopoietic stem cell transplantation, renal transplantation, intensive chemotherapy, human immunodeficiency infection, or rituximab usage.
We present here a case study of a patient with a previous high titer of anti-HBs who later developed HBV reactivation following intensive chemotherapy for leukemia.
We conclude that in immunosuppressed patients with a history of HBV infection may carry a risk for reverse seroconversion and monitoring anti-HBs levels may help recognising this risk.
Hepatitis B virus; Reverse seroconversion; Immunosuppression
Rituximab is a monoclonal antibody that targets B-lymphocytes, and it is widely used to treat non-Hodgkin's lymphoma. However, its use has been implicated in HBV reactivation that's related with the immunosuppressive effects of rituximab. Although the majority of reactivations occur in hepatitis B carriers, a few cases of reactivation have been reported in HBsAg negative patients. However, reactivation in an HBsAg negative/HBsAb positive patient after rituximab treatment has never been reported in Korea. We present here an HBsAg-negative/HBsAb-positive 66-year-old female who displayed reactivation following rituximab plus CHOP chemotherapy for diffuse large B-cell lymphoma. While she was negative for HBsAg at diagnosis, her viral status was changed at the time of relapse as follows: HBsAg positive, HBsAb negative, HBeAg positive, HBeAb negative and an HBV DNA level of 1165 pg/ml. Our observation suggests that we should monitor for HBV reactivation during rituximab treatment when prior HBV infection or occult infection is suspected, and even in the HBsAg negative/HBsAb positive cases.
Rituximab; Hepatitis B virus; Lymphoma
Case report: The patient was a 42 year old woman with primary SS and associated MALT lymphoma located in the parotid gland and the hard palate. Four infusions of rituximab (375 mg/m2) weekly resulted in complete remission of the lymphoma. An incision biopsy of the parotid gland before and after treatment showed improvement of the (immuno)histopathological characteristics of SS, with possible regeneration of salivary gland tissue. Furthermore, salivary analysis showed decreased inflammatory characteristics and increased stimulated salivary flow.
Discussion: Rituximab is a promising agent in the treatment of SS associated MALT lymphoma. In addition to the effect on MALT lymphoma, B cell depletion by rituximab may also attenuate the activity of SS. This case report is the first to describe the effect of rituximab on histological and sialometric/chemical characteristics of SS. The efficacy of rituximab in the treatment of SS warrants further investigation.
Patients with chronic hepatitis C virus (HCV) can develop systemic cryoglobulinemic vasculitis. Combination of pegylated-interferon α and ribavirin is the first-line treatment of this condition. However, in case of severe or life-threatening manifestations, absence of a virological response, or autonomized vasculitis, immunotherapy (alone or in addition to the antiviral regimen) is necessary. Rituximab is to date the only biologic with a sufficient level of evidence to support its use in this indication. Several studies have demonstrated that rituximab is highly effective when cryoglobulinaemic vasculitis is refractory to antiviral regimen, that association of rituximab with antiviral regimen may induce a better and faster clinical remission, and, recently, that rituximab is more efficient than traditional immunosuppressive treatments. Some issues with regard to the optimal dose of rituximab or its use as maintenance treatment remain unsolved. Interestingly, in balance with this anti-inflammatory strategy, a recent pilot study reported the significant expansion of circulating regulatory T lymphocytes with concomitant clinical improvement in patients with refractory HCV-induced cryoglobulinaemic vasculitis using low dose of subcutaneous interleukin-2. This paper provides an updated overview on the place of immunotherapy, especially biologics, in the management of HCV-induced cryoglobulinaemic vasculitis.
Hepatitis B virus (HBV) reactivation represents an emerging cause of liver disease in patients undergoing treatment with biologic agents. In particular, the risk of HBV reactivation is heightened by the use monoclonal antibodies, such as rituximab (anti-CD20) and alemtuzumab (anti-CD52) that cause profound and long-lasting immunosuppression. Emerging data indicate that HBV reactivation could also develop following the use of other biologic agents, such as tumor necrosis factor (TNF)-α inhibitors. When HBV reactivation is diagnosed, it is mandatory to suspend biologic treatment and start antiviral agents immediately. However, pre-emptive antiviral therapy prior to monoclonal antibody administration is crucial in preventing HBV reactivation and its clinical consequences. Several lines of evidence have shown that risk of HBV reactivation is greatly reduced by the identification of high-risk patients and the use of prophylactic antiviral therapy. In this article, we discuss current trends in the management of HBV reactivation in immunosuppressed patients receiving biologic therapy, such as rituximab, alemtuzumab and TNF-α antagonists.
Hepatitis B virus; Virus reactivation; Rituximab; Tumor necrosis factor-α antagonists; Biologic agents; Antiviral drugs
Hepatitis B reactivation is a well-described complication in patients with inactive chronic hepatitis B receiving chemotherapy. Screening for HBV and preemptive therapy are recommended. However, the rates of HBV screening, prophylaxis and reactivation during rituximab-containing chemotherapy are unknown.
Patients and methods
We performed a retrospective study of patients with non-Hodgkin lymphoma (NHL) who received rituximab between August 1997 and September 2009. We evaluated patients for hepatitis B serologies, antiviral prophylaxis and hepatitis B reactivation during or up to 6 months after chemotherapy.
One thousand four hundred twenty nine patients underwent rituximab-containing chemotherapy for NHL. Hepatitis B serologies were documented in 524 (36.6%) patients. Of these, 20 (3.8 %) were HBsAg positive and 10 (50%) experienced HBV reactivation. Only half (5/10) had HBV serology documented prior to reactivation. Only 3/8 (37.5%) of patients with newly documented HBsAg positivity received antiviral prophylaxis. Virologic breakthrough occurred in 2 of the patients on chronic therapy, in one of three inactive carriers on prophylaxis and in 2 of 5 patients not receiving prophylaxis. Reactivation developed in another 5 patients not previously screened for hepatitis B. One patient developed ALF and died. Reactivation did not occur in 25 patients with isolated positive core antibody.
At tertiary care institutions hepatitis B serologies are infrequently assessed prior to rituximab-based chemotherapy and prophylaxis is uncommon. Greater adherence to recommendations for screening and prophylaxis is necessary. This suboptimal screening rate could be even lower in community hospitals and could result in significant harm to unscreened and unprophylaxed patients.
Chemotherapy; HBV Reactivation; Hepatitis B; HBV prophylaxis; Non-Hodgkin lymphoma; Rituximab
Recurrence of FSGS occurs in 30–40% of allografts. Therapies for recurrence are not well established. We retrieved all published reports depicting kidney transplant recipients with focal segmental glomerulosclerosis (FSGS) recurrence, treated with rituximab, to determine factors associated with treatment response. We found 18 reports of 39 transplant recipients who received rituximab. By univariate analysis for two outcomes (no response versus any response), fewer rituximab infusions and normal serum albumin at recurrence were associated with treatment response. For 3 outcomes (no response, partial and complete remission), male gender, fewer rituximab infusions, shorter time to rituximab treatment, and normal serum albumin were associated with remission. Multivariate analysis for both models revealed that normal serum albumin at FSGS recurrence and lower age at transplant were associated with response.
Rituximab for recurrence of FSGS may be beneficial for only some patients. A younger age at transplant and normal serum albumin level at recurrence diagnosis may predict response.
Rituximab is a biologic agent that is usually well tolerated. With its increasing use for a myriad of rheumatologic and immunologic conditions, post-marketing surveillance has revealed more side effects. Systemic inflammatory response syndrome associated with cytokine release syndrome (CRS) is a very rare entity associated with the use of rituximab and carries a very high morbidity and case fatality rate. Cases of CRS reported within the literature are of patients with a very high tumor burden leading to a catastrophic cascade of events. We report the case of a patient having post-transplant lymphoproliferative disorder who died of fatal lactic acidosis and CRS within 24 h of receiving rituximab. Understanding the pathophysiology of such cases and identifying patients at risk may help to possibly avert this life-threatening complication.
Rituximab; Cytokine release syndrome; Systemic inflammatory response syndrome; Mortality; Fatality; Lactic acidosis; Post-transplant lymphoproliferative disorder
Multicentric Castleman's Disease (MCD), a lymphoproliferative disorder associated with Human Herpes Virus-8 (HHV-8) infection, is increasing in incidence amongst HIV patients. This condition is associated with lymphadenopathy, polyclonal gammopathy, hepato-splenomegaly and systemic symptoms. A number of small studies have demonstrated the efficacy of the anti-CD20 monoclonal antibody, rituximab, in treating this condition.
We report the case of a 46 year old Zambian woman who presented with pyrexia, diarrhoea and vomiting, confusion, lymphadenopathy, and renal failure. She rapidly developed multiple organ failure following the initiation of treatment of MCD with rituximab. Following admission to intensive care (ICU), she received prompt multi-organ support. After 21 days on the ICU she returned to the haematology medical ward, and was discharged in remission from her disease after 149 days in hospital.
Rituximab, the efficacy of which has thus far been examined predominantly in patients outside the ICU, in conjunction with extensive organ support was effective treatment for MCD with associated multiple organ failure. There is, to our knowledge, only one other published report of its successful use in an ICU setting, where it was combined with cyclophosphamide, adriamycin and prednisolone. Reports such as ours support the notion that critically unwell patients with HIV and haematological disease can benefit from intensive care.
The activity of the anti-CD20 monoclonal antibody, rituximab in B-cell non-Hodgkin's lymphoma, with relatively minimal toxicity has been well established. Adverse effects such as low-grade fever, urticaria, bronchospasm, sporadic tachycardia, and hypotension have been described. However, only a single case of rituximab-related, transient conjunctivitis has been documented in literature. We report an occurrence of chronic, bilateral conjunctivitis in an 88-year-old female diagnosed with stage IV, non-Hodgkin's lymphoma (NHL), who was maintained on rituximab for 12 months. In contrast to the previously described case, our patient developed severe conjunctival inflammation approximately three to four weeks following rituximab induction. Resolution of conjunctivitis occurred within two months after cessation of rituximab treatment.
To report on the results of a randomized controlled trial of rituximab in hepatitis C virus (HCV)-associated mixed cryoglobulinemic vasculitis.
We conducted an open-label single center randomized controlled trial of rituximab (375 mg/m2 per week for 4 weeks) compared to best available therapy for treatment of patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy failed to induce remission. The primary endpoint was remission at 6 months from study entry.
A total of 24 patients were enrolled. Baseline disease activity and organ involvement were similar in the two groups. Ten patients in the rituximab group (83%) were in remission at study month 6, compared with 1 patient in the control group (8%), a result that met criterion for stopping the study (P<0.001). The median duration of remission for rituximab-treated patients reaching the primary endpoint was 7 months. No adverse effect of rituximab on HCV plasma viremia or hepatic transaminase levels was observed.
Therapy with rituximab was well tolerated and effective treatment for patients with HCV-associated cryoglobulinemic vasculitis in whom antiviral therapy fails to induce remission.
A case of de novo acute hepatitis B that showed symptoms of general malaise and anorexia during rituximab therapy with the CHOP regimen for diffuse large B cell lymphoma is reported. Lamivudine was strikingly effective, showing a rapid recovery from liver damage with jaundice. Hepatitis B virus (HBV) DNA in serum became and stayed undetectable even after the withdrawal of lamivudine, although HBsAg remained positive over 42 months from the onset. Liver biopsy showed a picture suggestive of acute viral hepatitis with multinucleated giant hepatocytes and CD38-positive plasma cell infiltration into liver parenchyma. Immunohistochemically, CD3-positive T-cells were predominant cells that infiltrated in liver parenchyma, whereas CD20-positive B cells were essentially null. Hence, it is suggested from these findings that B lymphocytes might be crucial for the continuous latency in HBV infection and may give rise to de novo acute hepatitis B if totally deleted. Moreover, the CHOP regimen might have some additive effects with the repeated on–off use of corticosteroids to the onset of the disease. In addition, significance of plasma cell infiltration in this setting is discussed.
De novo acute hepatitis B; Rituximab; Lamivudine
Muscletech Hydroxycut® (Iovate Health Sciences Research, Oakville, Ontario) was a popular weight loss supplement that was recalled by the manufacturer in May 2009 based on reports of hepatotoxicity associated with this supplement.
To characterize the clinical presentation of Hydroxycut®-associated liver injury and to adjudicate these cases for causal association with Hydroxycut®.
Academic tertiary care hospitals and FDA databases.
Assessment of causality and grading of severity of liver injury using methodology developed by the Drug-Induced Liver Injury Network (DILIN) study.
Eight patients who developed liver injury after taking Hydroxycut treated at different medical centers were identified. All were hospitalized and 3 of 8 patients required liver transplantation. Nine other cases with adequate clinical information were obtained from the FDA MedWatch database including one fatal case of acute liver failure. Usual symptoms were jaundice, fatigue, nausea, vomiting and abdominal pain. Most patients exhibited a hepatocellular pattern of injury. Adjudication for causality revealed 8 cases as definite, 5 highly likely, 2 probable and 2 were considered as possible.
Hydroxycut® has been clearly implicated as a cause for severe liver injury that may lead to acute liver failure and death. Weight loss supplements represent a class of dietary supplements that should be regarded as capable of causing severe hepatic toxicity when the usual causes of identified liver injury cannot be otherwise elucidated.
The association between hepatitis B virus (HBV) mutations and hepatocarcinogenesis remains controversial because of conflicting data in the literature. We conducted a meta-analysis of case–control and cohort studies to examine HBV PreS, enhancer II (EnhII), basal core promoter (BCP), and precore mutations in relation to the risk of hepatocellular carcinoma (HCC).
We searched databases for studies of these associations that were published in English or Chinese up to August 31, 2008. HBV mutation–specific odds ratios and relative risks were pooled by use of a random-effects model and stratified by potential confounders. All statistical tests were two-sided.
Of the 43 studies included in this meta-analysis, 40 used a case–control design. The 43 studies evaluated a total of 11 582 HBV-infected participants, of whom 2801 had HCC. Statistically significant summary odds ratios of HCC were obtained for any PreS mutation (3.77, 95% confidence interval [CI] = 2.57 to 5.52), C1653T in EnhII (2.76, 95% CI = 2.09 to 3.64), T1753V (2.35, 95% CI = 1.63 to 3.40), and A1762T/G1764A in BCP (3.79, 95% CI = 2.71 to 5.29). PreS mutations were more strongly associated with an increased risk of HCC in subjects who were infected with HBV genotype C than in those who were infected with HBV genotype B, whereas the opposite was true for A1762T/G1764A. C1653T, T1753V, and A1762T/G1764A were more strongly associated with an increased risk of HCC in hepatitis B e antigen (HBeAg)–positive subjects than in HBeAg-negative subjects. PreS mutations, C1653T, T1753V, and A1762T/G1764A accumulated during the progression of chronic HBV infection from the asymptomatic carrier state to HCC (Ptrend < .001 for each mutation). PreS mutations, C1653T, C1653T + T1753V, and A1762T/G1764A-based combinations of mutations had specificities greater than 80% for the prediction of HCC. The precore mutations G1896A and C1858T were not associated with the risk of HCC, regardless of HBeAg status and HBV genotype.
HBV PreS mutations, C1653T, T1753V, and A1762T/G1764A are associated with an increased risk of HCC. These mutations alone and in combination may be predictive for hepatocarcinogenesis.
Thrombotic thrombocytopenic purpura (TTP) is a life threatening condition associated with formation of platelet thrombi. Deficiency of ADAM TS 13 with presence of inhibitory anti-ADAM TS 13 Immunoglobulin G antibody is seen in patients with acquired TTP. TTP in patients on interferon therapy for chronic hepatitis C has rarely been reported. Furthermore, successful treatment of an initial episode of acute refractory acquired TTP, in a patient of chronic hepatitis C during interferon therapy with Rituximab, has not been previously reported. Here we describe a case of acute refractory acquired TTP associated with pegylated interferon therapy for her chronic hepatitis C infection. Initially refractory to plasmapheresis and steroids, she was successfully treated with Rituximab and plasmaphersis without any evidence of reactivation of hepatitis.
thrombotic thrombocytopenic purpura; interferon; hepatitis C; Rituximab
We describe the effect on the neonate of administration of rituximab to a woman with idiopathic thrombocytopenic purpura (ITP). Rituximab, an anti-CD20 antibody, was given weekly for 4 weeks to a woman with ITP in her third trimester of pregnancy. One month after the last rituximab administration a healthy girl was born. She had normal growth and development during the first six months. At birth, B-lymphocytes were not detectable. Rituximab levels in mother and neonate were 24000 and 6700 ng/mL, respectively. Only 7 cases of rituximab administration during pregnancy were described. No adverse events are described for fetus and neonate. We demonstrate that rituximab passes the placenta and inhibits neonatal B-lymphocyte development. However, after 6 months B-lymphocyte levels normalized and vaccination titres after 10 months were adequate. No infection-related complications occurred. Rituximab administration during pregnancy appears to be safe for the child but further studies are warranted.
Two patients with diabetic nephropathy were diagnosed with primary central nervous system posttransplant Epstein-Barr-virus-associated lymphoproliferative disorder (PTLD) 3 years after renal transplantation. The histological diagnoses of the isolated brain tumors were diffuse large B-cell lymphoma and plasmacytoma. Considerable co-morbidity precluded intensive chemotherapy. The first patient with lymphoid CD20+ PTLD had a partial resection of her tumor performed. She was treated with 4 weekly doses of rituximab, ganciclovir and prednisolone; the posttransplant immune suppression (tacrolimus) was reduced. After 4 weeks of treatment a magnetic resonance imaging (MRI) demonstrated complete regression of the CNS lesion. The patient continues to receive rituximab (every second month), valgangciclovir and low-dose prednisolone. Twenty-two months after initiation of therapy, she is still in complete remission. The second patient was only treated with craniospinal irradiation involving the medulla to the second cervical vertebra and valgangciclovir. Moreover, the posttransplant immune suppression was reduced. A new MRI two months after initiation of therapy showed a complete regression of the lesions in the CNS; this was again demonstrated by a MRI after 19 months. These 2 cases illustrate interesting alternative treatments of PTLD. To our knowledge, an EBV-associated PTLD of plasmacytic origin isolated to the CNS has never been described before.
Hepatitis B virus (HBV) reactivation is a well-recognized complication in patients with chronic HBV infection receiving cytotoxic or immunosuppressive chemotherapy. Imatinib mesylate and nilotinib are selective Bcr/Abl tyrosine kinase inhibitors, which are now widely used in the treatment of patients with chronic myeloid leukemia. Although HBV reactivation induced by imatinib mesylate has been reported, nilotinib-related HBV reactivation has not been reported in the English literature. We report here 2 cases of HBV reactivation in chronic myeloid leukemia patients receiving imatinib mesylate and a novel case of nilotinib related HBV reactivation.
Hepatitis B virus; Chronic myeloid leukemia; Imatinib mesylate; Nilotinib; Tyrosine kinase inhibitor
Occult hepatitis B virus (HBV) infection (OBI) is characterized by HBV DNA persistence even though the pattern of serological markers indicates an otherwise resolved HBV infection. Although OBI is usually clinically silent, immunocompromised patients may experience reactivation of the liver disease.
We report the case of an individual with human immunodeficiency virus (HIV) infection and anti-HBV core antibody positivity, who experienced severe HBV reactivation after discontinuation of lamivudine-including antiretroviral therapy (ART). HBV sequencing analysis showed a hepatitis B surface antigen escape mutant whose presence in an earlier sample excluded reinfection. Molecular sequencing showed some differences between two isolates collected at a 9-year interval, indicating HBV evolution. Resumption of ART containing an emtricitabine/tenofovir combination allowed control of plasma HBV DNA, which fell to undetectable levels.
This case stresses the ability of HBV to evolve continuously, even during occult infection, and the effectiveness of ART in controlling OBI reactivation in HIV-infected individuals.