Intensive Immunosuppressive Therapy Research Articles

Posaconazole

Posaconazole (Noxafil®) is an oral, second-generation, extended-spectrum triazole whose approved indications include prophylaxis of invasive fungal disease (IFD) in immunocompromised patients. In pivotal head-to-head trials, posaconazole was significantly more effective in preventing IFD than standard azole therapy (i.e. oral fluconazole or itraconazole) in chemotherapy-induced neutropenic patients with acute myelogenous leukaemia (AML) or myelodysplastic syndromes (MDS) and was noninferior to treatment with fluconazole in patients with graft-versus-host disease (GVHD) who were receiving intensive immunosuppressive therapy following haematopoietic stem cell transplantation. In both indications, prophylactic posaconazole was associated with significantly lower rates of IFD-related mortality. The overall tolerability profile of posaconazole was generally similar to that of the other prophylactic treatments. The large body of modelled cost-effectiveness analyses from a healthcare payer perspective on the use of prophylactic posaconazole suggest that it is a dominant or cost-effective option relative to prophylaxis with standard azole therapy in neutropenic patients with AML/MDS, and fluconazole in patients with GVHD. Based on clinical trial data in these patient groups, antifungal prophylaxis with posaconazole was predicted to be a dominant or cost-effective option relative to prophylaxis with standard oral azoles, with regard to the incremental cost per QALY gained, life-year (LY) gained and/or other outcomes in cost-effectiveness analyses in numerous countries. In those analyses in which posaconazole did not dominate the comparator, posaconazole was considered cost effective, as the incremental cost per QALY or LY gained with posaconazole was lower than assumed willingness-to-pay thresholds. Sensitivity analyses consistently demonstrated that these results were robust to plausible changes in key model assumptions. In conclusion, prophylactic treatment with posaconazole is clinically effective in preventing IFD in neutropenic patients with AML/MDS and patients with GVHD. Available pharmacoeconomic data from several countries, despite some inherent limitations, support the use of posaconazole as a dominant or cost-effective prophylactic antifungal treatment relative to prophylaxis with standard oral azoles in these patient populations at high risk of developing IFD.

Majocchi's granuloma in solid organ transplant recipients

Superficial fungal infections are fairly prevalent in transplant recipients and the incidence increases with more intense graft-conserving immunosuppressive therapy. Majocchi's granuloma is a deep folliculitis caused by dermatophytes that involves deeper layers of the dermis. Only a few case reports of the condition have been documented in transplant recipients. After an extensive review of the medical literature, 21 cases were retrieved and are summarized here, together with a new case that occurred in a recent heart transplant recipient from our institution. This report aims to provide a comprehensive analysis of Majocchi's granuloma in solid organ transplant (SOT) recipients, with special focus on potential risk factors, offending pathogens, clinical presentation, therapeutic approaches, and outcome. General observations are presented emphasizing the relevance of close clinical and dermatologic follow-up in high-risk SOT patients with specific comments regarding treatment regimens and outcomes.

Circulating myeloid dendritic cells are increased in individuals with severe aplastic anemia

The objectives of the study were to investigate the number of myeloid dendritic cells (mDC) and plasmacytoid dendritic cells (pDC) present in peripheral blood mononuclear cells (PBMC) from severe aplastic anemia (SAA) patients before and after intensive immunosuppressive therapy (IST) and to assess the expression of co-stimulatory molecules (CD80, CD86, and CD40) expressed by dendritic cells (DC) from SAA patients. The quantities of mDC and pDC and ratios of mDC to pDC in PBMC were measured in 38 SAA patients at active phase, 19 patients at recovery phase, and 17 normal controls. The surface expression of CD80, CD86, and CD40 on DCs and B lymphocytes was analyzed in 16 SAA patients and 15 normal controls. The percentages of mDC and the ratio of mDC:pDC of SAA patients at active phase increased compared to that of healthy controls [0.65% (range 0.10-2.19%) vs. 0.40% (range 0.11-1.54%), 2.64% (range 1.07-4.33%) vs. 1.56% (range 0.89-2.27), respectively (P<0.05)]. The percentages of mDCs in recovered SAA patients decreased to 0.43% (range 0.06-0.80), and the ratio of mDC:pDC decreased to 1.78% (range 0.49-3.07). The percentages of mDC and pDC in 10 SAA patients were 0.87% (range 0.10-1.85) and 0.35% (range 0.05-0.65) before IST, which decreased to 0.24% (range 0.06-0.52) and 0.14% (range 0.01-0.28) after IST (P<0.05). The percentages of CD86 expression on DC of SAA patients increased compared to that of healthy controls [29.84% (range 20.28-39.40) vs. 11.97% (range 0.02-24.15), respectively (P<0.05)]. The number of mDCs increased in SAA patients, which was associated with stage of disease. The increased number of mDCs and the high expression of costimulatory molecules (CD86) on these DCs may contribute to abnormal activation of T lymphocytes in these patients and subsequent immune system-mediated bone marrow failure.

Intensive Immunosuppressive Therapy Improves Pulmonary Hemodynamics and Long-Term Prognosis in Patients With Pulmonary Arterial Hypertension Associated With Connective Tissue Disease

Pulmonary arterial hypertension (PAH) remains a serious disease characterized by elevated pulmonary artery pressure (PAP) and increased pulmonary vascular resistance (PVR). Among its subtypes, PAH associated with connective tissue disease (CPAH) has the worse prognosis, because of resistance to conventional vasodilator therapy. We hypothesized that intensive immunosuppressive therapy (IIT) could improve the pulmonary hemodynamics in CPAH. In our pulmonary hypertension (PH) cohort of 182 patients, we evaluated 13 consecutive patients with CPAH who received IIT combined with cyclophosphamide and glucocorticosteroids (IIT group, mean age 45 ± 8 years, 12 females and 1 male). We compared them with 8 historical controls (control group: mean age 52 ± 18 years, 8 females) for pulmonary hemodynamics and prognosis. Both groups were treated with conventional vasodilator therapy. Although the mean PAP (mPAP) remained unchanged in the control group, IIT significantly decreased mPAP (40 ± 9 to 29 ± 11 mmHg, P < 0.01) and tended to decrease PVR (700 ± 434 to 481 ± 418 dyne·s·cm⁻⁵, P=0.07). Importantly, in 6 of the 13 patients in the IIT group, mPAP was almost normalized (< 25 mmHg) and remained stabilized for more than 1 year. Furthermore, the IIT group showed significantly better prognosis compared with the control group (P<0.01). These results suggest that IIT as well as conventional vasodilator therapy improves the pulmonary hemodynamics and long-term prognosis of patients with CPAH.

A Case of Cytomegalovirus Infection Presenting as Pericarditis and Lupus Nephritis Flare-up

Cytomegalovirus (CMV) infection is associated with an exacerbations of systemic lupus erythematosus (SLE), but the role of CMV in disease pathogenesis remains unclear. CMV infection is often severe and difficult to diagnose in patients with SLE. Only a few cases of opportunistic CMV interstitial pneumonitis infection occurring in patients with SLE after intensive immunosuppressive therapy have been described. We report a case of CMV infection presenting with massive pericarditis and aggravating lupus nephritis

Recent Progress in the Management of Pulmonary Hypertension

Pulmonary hypertension (PH) is a fatal disease caused by small pulmonary artery obstruction from vascular proliferation and remodeling. PH is characterized by elevated pulmonary arterial pressure and increased pulmonary vascular resistance, frequently leading to right-sided heart failure and death. The classification of PH has been recently updated to include 5 major categories of the disorder, are as: Group 1, pulmonary arterial hypertension (PAH); Group 2, PH due to left heart disease; Group 3, PH due to lung diseases and/or hypoxia; Group 4, chronic thromboembolic PH (CTEPH); and Group 5, others. Recently, significant progress has been made in the understanding of the pathophysiology, diagnosis and treatment of PH. Regarding the pathophysiology of the disorder, direct evidence for Rho-kinase activation in the pulmonary artery from PAH patients has been provided. Regarding diagnosis, optical coherence tomography is useful as a new differential diagnostic tool for distal type CTEPH vs. PAH. Regarding treatment, in addition to the conventional therapy, several new drugs are under clinical trial, including fasudil (a Rho-kinase inhibitor), riosiguat (a soluble guanylate cyclase activator), and imatinib (a tyrosine kinase inhibitor). In addition, pulmonary angioplasty and intensive immunosuppressive therapy may be effective for CTEPH and connective tissue disease-associated PAH, respectively. We briefly review the recent progress in the management of PH.

Advances in Hemophagocytic Lymphohistiocytosis: Pathogenesis, Early Diagnosis/Differential Diagnosis, and Treatment

Hemophagocytic lymphohistiocytosis (HLH) is a histiocytic disorder characterized by a highly stimulated, but ineffective, immune response to antigens, which results in life-threatening cytokine storm and inflammatory reaction. Considerable progress has been made during the past 2 decades. Detection of molecular genetic abnormalities in genes involved in immune response pathways, such as PRF1, STX11, UNC13D, STXBP2, RAB27A, LYST, AP3B1, SH2D1A, and BIRC4, is confirmatory for the diagnosis. Clinical diagnosis is largely made according to HLH-2004 criteria. However, a new finding of the Th1/Th2 cytokine pattern (significant increase of IFN-γ and IL-10 with slightly increased or normal level of IL-6) is a useful biomarker for the early diagnosis, differential diagnosis, and the monitoring of the disease. Intensive immunosuppressive therapy is generally accepted as treatment for the relief of clinical symptoms/signs, while allogeneic hematopoietic stem cell transplantation is currently the only potentially curative therapy option for severe familial forms of HLH.

Successful bosentan therapy in a case of pulmonary arterial hypertention developed during immunosuppressive therapy for lupus nephritis.

We report a 43-year-old female who developed pulmonary arterial hypertension (PAH) during intensive immunosuppressive therapy for systematic lupus erythematosus (SLE). She was diagnosed as SLE at the age of 32 years based on serological and hematological abnormalities, oral ulcers, and facial erythema. She experienced frequent flare-ups of disseminated discoid lupus between the ages of 33 and 36 years and developed immune thrombocytopenia at the age of 39 years. In 2007 when she was 43 years old, she developed lupus nephritis (LN) with elevated serum anti-double stranded DNA antibodies and urine protein of less than 1 g/day. Combination therapy for the LN with 35 mg/day prednisolone and intravenous cyclophosphamide (IVCY) led to renal remission. After the seventh monthly session of IVCY, she developed dyspnea on exertion. PAH was diagnosed based on enlarged main pulmonary arteries on the chest x-ray, right ventricular outflow and a peak tricuspid regurgitant pressure gradient exceeding 45 mmHg on echocardiography, an elevated plasma brain natriuretic peptide (BNP) level of 260 pg/ml, the exclusion of pulmonary thromboembolism, and no lung fibrosis. The PAH was treated successfully with bosentan. At present the tricuspid regurgitation has disappeared, and the plasma BNP level has normalized.

Hepatitis B Virus (HBV) Reactivation In Anti-HB Core Antigen (anti-HBc) Positive Patients with Hematological Malignancies: A Prospective Multicenter Study

AbstractAbstract 4911Patients with haematological malignancies and overt hepatitis B (HB) infection defined by the presence of HB surface antigen (HBsAg) are at risk of hepatitis reactivation, and antiviral prophylaxis is generally recommended. HBV reactivation can also occur during immunosuppressive therapy in patients who are HBsAg negative, but are positive for antibodies to HB core antigen (anti-HBc) which suggests prior contact with HBV and potential occult infection. The risk of HBV reactivation for these patients who have evidence of viral clearance (HBV-DNA negative) and developed potential immunity (anti-HBs positive) is not clear, and there are no clear guidelines for prophylaxis in this subset of patients. We therefore performed a multicenter prospective observational study to determine the risk of HBV seroreversion in anti-HBc positive patients with or without anti-HBs and with hematological malignancies undergoing intensive immunosuppressive chemotherapy and/or hematopoietic stem cell transplantation (HSCT). Patients underwent monitoring of HBV serum markers including HBV-DNA serum levels, while patients who started antiviral prophylaxis concomitant to the cytotoxic therapy were excluded. Between 1/2008 and 12/2008, 25 consecutive HBsAg -/antiHBc +/antiHBs + patients (pts) from 3 hematological centers were enrolled into the study (20 pts with lymphoma, 2 pts with acute myeloid leukaemia, 3 with myeloma). Before starting anticancer therapy, all pts had undetectable HBV-DNA levels, 21 were anti-HBs positive, and 12 had also anti-HBe. Moreover, 3 pts had HCV co-infection. All patients underwent intense immunosuppressive therapy including rituximab in 15 pts, and HSCT in 10 pts (7 autologous and 3 allogeneic). HBV markers were monitored during immunosuppressive treatment and for 18 months after end of therapy. At present, 18 pts have completed the planned follow-up period, and other 7 pts have at least 12 months of post-treatment follow-up. Among the 25 patients, we observed 3 cases of seroreversion with positive HBV-DNA levels. All 3 seroversions occurred in patients following allogeneic HSCT despite high anti-HBs levels at baseline. The 3 seroreverted patients showed a progressive decline in anti-HBs titers during the phase of monitoring, and HBV reactivated between the 7th and 9th month after allogeneic HSCT. The pts responded to treatment with antinucleoside analogues (entecavir in 2 cases, lamivudine in 1 case), i.e. HBV-DNA decreased of at least 1 log within three months from treatment start. Moreover, we detected one case of transient anti-HBs disappearance, and one case of persistent anti-HBe loss without seroreversion. None of the HCV co-infected pts presented acute hepatitis. No seroreversions were observed in 15 lymphoma patients undergoing immunochemotherapy including rituximab. In conclusion, patients with occult HBV infection are at risk of HBV reactivation during continuous immunosuppressive therapy following allogeneic HSCT even in the presence of anti-HBs levels at baseline, while the risk appears low in patients undergoing transient immunosuppressive therapy, as immunochemotherapy including rituximab, for the treatment of lymphoma. Disclosures:No relevant conflicts of interest to declare.

Listeria monocytogenes meningitis in a young woman with systemic lupus erythematosus

Listeria meningitis, a rare but life-threatening infection in patients with systemic lupus erythematosus, often represents a diagnostic and therapeutic challenge because of its rarity and non-representative manifestations. L. monocytogenes is an intracellular pathogen capable of spreading directly from cell to cell without exposure to the extracellular humoral immune system. With the evolving trend of intense immunosuppressive therapy, patients with SLE usually have abnormal cell-mediated immunity and are susceptible to L. monocytogenes infections. The gastrointestinal tract is usually the portal of entry, and a transient gastroenteritis may precede the full-blown meningitides. Ampicillin and penicillin G are the drugs of choice. For patients who are allergic to penicillin, trimethoprim-sulfamethoxazole is an eligible alternative. Delay in diagnosis and inappropriate antibiotics are detrimental to the outcome. Herein, we report a young woman with systemic lupus erythematosus who developed listeria meningitis. Clinicians are advised to be aware of the clinical presentations of this disease.

Parvovirus-B19-associated fulminant myocarditis successfully treated with immunosuppressive and antiviral therapy

Fulminant myocarditis is a rare inflammatory heart disease affecting relatively young adults. We describe a case of a 27-year-old male with acute onset severe heart failure. A rapid and accurate diagnostic approach suggested parvovirus B19 as the most probable cause for this fulminant viral myocarditis. Initial haemodynamic support, intensive immunosuppressive and antiviral therapy resulted in a complete recovery within 2 weeks. This case demonstrates the importance of a detailed diagnosis, allowing better classification of the underlying pathology and subsequent targeted treatment.

Hyperacute graft rejection during heart transplantation for giant cell myocarditis: A case report

We report the case of a patient with giant cell myocarditis who was bridged to transplantation with mechanical circulatory support and developed a fatal perioperative hyperacute rejection. The patient had received abundant transfusions that had raised her anti-HLA antibody titers. The cross-match test was positive. No pre-transplantation immunosuppressive therapy had been administered given concomitant infection. The severity and acuteness of the rejection in this case likely reflect the combined effect of preformed anti-HLA antibodies in the context of an active organ-specific immune process at the time of transplantation. This case raises the questions of the need for intensive immunosuppressive therapy before transplantation in giant cell myocarditis and of the management of patients with positive cross-match in the context of a giant cell myocarditis.

Biomarkers for Lupus Nephritis: A Critical Appraisal

Kidney disease is one of the most serious manifestations of systemic lupus erythematosus (SLE). Despite the improvement in the medical care of SLE in the past two decades, the prognosis of lupus nephritis remains unsatisfactory. Besides exploring more effective but less toxic treatment modalities that will further improve the remission rate, early detection and treatment of renal activity may spare patients from intensive immunosuppressive therapies and reduce renal damage. Conventional clinical parameters such as creatinine clearance, proteinuria, urine sediments, anti-dsDNA, and complement levels are not sensitive or specific enough for detecting ongoing disease activity in the lupus kidneys and early relapse of nephritis. Thus, novel biomarkers are necessary to enhance the diagnostic accuracy and sensitivity of lupus renal disease, prognostic stratification, monitoring of treatment response, and detection of early renal flares. This paper reviews promising biomarkers that have recently been evaluated in longitudinal studies of lupus nephritis.

Postexposure Prophylaxis of H1N1 With Oseltamivir in a Newly Transplanted Kidney Recipient Receiving Intense Immunosuppressive Therapy

Solid organ transplant recipients undergoing immunosuppressive therapy are considered to be at high risk for serious infectious complications. Recently in the United States, a pandemic of H1N1 flu infection has been reported with serious complications. We describe H1N1 infection in a living kidney donor and the 42-year-old kidney transplant recipient exposed to this kidney donor and undergoing intense immunosuppressive therapy. Postexposure prophylaxis with oseltamivir was effective to prevent H1N1 influenza A virus in a donor and a recipient.

Ineffectiveness of infliximab therapy in severe infantile Crohn's disease

Crohn's disease is extremely rare in infancy and can be present in severe forms. Infants with Crohn's disease might require intensive immunosuppressive therapy. Infliximab is a chimeric mouse/human monoclonal IgG1 antibody against tumor necrosis factor-α, and completely neutralizes its biologic activity. Though widely used in the treatment of pediatric Crohn's disease, there are few data regarding its applicability in infancy. We therefore report herein our experiences with infliximab therapy in two infantile patients with Crohn's disease who were resistant to conventional therapies; one patient showed a partial response while there was no response in the second. We were unable to achieve satisfactory results from infliximab therapy. It remains to be determined whether inflammatory bowel disease starting in infancy represents a separate pathogenetic subgroup and whether the inflammatory bowel disease diagnosis should follow the exclusion of an immunodeficiency state. Studies in larger series are needed to further clarify the efficacy, safety and timing of infliximab therapy for infantile Crohn's disease patients.

Atypical Hemolytic Uremic Syndrome Associated With Complement Factor H Autoantibodies and CFHR1/CFHR3 Deficiency

Although genetic defect of complement factor H (CFH) is a common cause of atypical hemolytic uremic syndrome (aHUS), development of autoantibodies to CFH (CFH-Ab) is also known to be an acquired cause of aHUS. Recently, a correlation between the development of CFH-Ab and the deficiency of the CFH-related proteins, CFHR1 and CFHR3, was identified. In this study, plasma complement profiles were measured and genetic analysis of the CFH, CFI, MCP, CFHR1, and CFHR3 genes were performed in three female patients diagnosed with aHUS with positive CFH-Ab. Acute stage plasmas of all the three patients revealed low C3, low or low-normal CFH antigenic levels, and high titers of CFH-Ab. All the patients also showed complete plasma CFHR1 deficiency and homozygous genomic deletion of CFHR1/CFHR3, but none had CFH, CFI, or MCP mutations. All the patients were treated with plasmapheresis, and two patients required additional immunosuppressive therapy. These patients had a novel subgroup of aHUS characterized by a combination of genetic (a homozygous deletion of CFHR1/CFHR3) and acquired (development of CFH-Ab) factors. Patients with this disease may need intensive immunosuppressive therapy in addition to plasmapheresis. Screening for CFH-Ab and the CFHR1/CFHR3 deficiency should be included in the diagnostic tests for patients with aHUS.

Brazilian experience with two conditioning regimens in patients with multiple sclerosis: BEAM/horse ATG and CY/rabbit ATG

Studies have shown that autologous hematopoietic SCT (HSCT) can be used as an intensive immunosuppressive therapy to treat refractory patients and to prevent the progression of multiple sclerosis (MS). This is a prospective multicentric Brazilian MS trial comparing two conditioning regimens: BEAM/horse ATG and CY/rabbit ATG. Most (80.4%) of the 41 subjects in the study had the secondary progressive MS subtype and the mean age was 42 years. The baseline EDSS score in 58.5% of the subjects was 6.5 and 78% had a score of 6.0 or higher, respectively. The complication rate during the intra-transplantation period was 56% for all patients: 71.4% of the patients in the BEAM/hATG group and 40% in the CY/rATG group (P=0.04). Three subjects (7.5%) died of cardiac toxicity, sepsis and alveolar hemorrhage, all of them in the BEAM/ATG group. EFS was 58.54% for all patients: 47% in the BEAM/hATG group and 70% in the CY/rATG group (P=0.288). In conclusion, the CY/rATG regimen seems to be associated with similar outcome results, but presented less toxicity when compared with the BEAM/hATG regimen. Long-term follow-up would be required to fully assess the differences in therapeutic effectiveness between the two regimens.

Herpes Simplex Virus Infection and Pemphigus

Pemphigus is a group of autoimmune blistering diseases of the skin and/or mucous membranes caused by the presence of antibodies against adhesion molecules on the cell surface of keratinocytes. In genetically predisposed patients, several factors, including drugs, physical agents, neoplasms, hormones, and viruses, notably herpes simplex virus (HSV), have been hypothesized to trigger or exacerbate the disorder. To clarify whether HSV infection represents an aetiopathogenetic factor for pemphigus or a consequence of the immunosuppressive treatment, skin and/or mucosal swabs from 35 patients with pemphigus vulgaris or pemphigus foliaceus were tested for HSV by polymerase chain reaction. Twenty-three of these patients were newly diagnosed, while the remaining 12 had had a previous diagnosis and were under treatment with low-dosage oral corticosteroids. Repeat swabs were taken two weeks after starting intensive immunosuppressive therapy in 8 HSV-negative patients. All skin swabs (n=27) resulted negative for both HSV-1/2, while oral swabs (n=30) were positive for HSV-1 in 5 out of the 12 patients who were being treated with oral corticosteroids, but in none (n=19) of the non-treated group (p=0.0067, X2 test). Five out of the 8 patients with repeat swabs became positive for HSV-1, prompting us to start antiviral therapy. In conclusion, HSV is unlikely to be a triggering factor for pemphigus, but its presence in pemphigus lesions seems to be a frequent and early complication of immunosuppression.

Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis

The objectives of the study are to investigate the clinical features and renal outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN). Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal outcomes were investigated. There were 84 females and 10 males, with a mean age of 27.9 ± 10.7 years old. They represented: hypertension in 73 cases (77.7%), rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic syndrome needed dialysis therapy. There were 25 cases received repeated renal biopsy. Their histological examination showed the decreasing of active lesions and the increasing chronic lesions. All patients were more than 6 months follow-up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time of follow-up (3 months), the renal function, proteinuria, and anemia were improved significantly in all of cases received intensive immunosuppressive therapy. At the last time of follow-up (56.1 ± 18.8 months), only four patients eventually developed to the end-stage renal failure and five died with normal renal function. The lupus patients with DCGN presented more severe clinical syndromes, which were similar to those patients of type II of DCGN. The relative good renal outcomes were observed in those lupus patients, to which may be contribute to the effective induction therapy.

How I treat and monitor viral hepatitis B infection in patients receiving intensive immunosuppressive therapies or undergoing hematopoietic stem cell transplantation

AbstractHepatitis B virus (HBV) reactivation is a serious but preventable complication of immunosuppression. Full HBV serologic profile must be obtained from all patients receiving intensive immunosuppressive therapy. In general, preemptive anti-HBV therapy is more effective than giving treatment after development of reactivation. Prompt lamivudine therapy should be given to at-risk patients who are hepatitis B surface antigen (HBsAg)–positive. It is recommended that lamivudine be continued until at least 6 months after the cessation of immunosuppression. Some patients requiring a longer duration of lamivudine therapy are at risk of developing drug resistance. The newer anti-HBV agents are effective in overcoming lamivudine resistance. Early use of these agents may be considered. HBV reactivation was observed in HBsAg-negative patients with occult HBV infection (HBV DNA-positive) who are on heavy immunosuppression. The optimal management of this group of patients is unclear. For patients receiving allogeneic HSC transplants, the HBV status of the donors requires special attention. To minimize the risk of transmission of infection to recipients, HBsAg-positive donors should receive adequate anti-HBV therapy before HSC donation. As the result of adoptive immune transfer, clearance of HBsAg is observed in HBsAg-positive patients receiving HSC transplants from donors who are positive for hepatitis B surface and core antibodies.