Advantage of achieving deep response following frontline daratumumab-VTd compared to VRd in transplant-eligible multiple myeloma: multicenter study

Background@#The goal of induction therapy for multiple myeloma (MM) is to achieve adequate disease control. Current guidelines favor triplet (bortezomib-lenalidomide-dexamethasone;VRd) or quadruplet regimens (daratumumab, bortezomib-thalidomide-dexamethasone;D-VTd). In the absence of a direct comparison between two treatment regimens, we conducted this study to compare the outcomes and safety of VRd and D-VTd. @*Methods@#Newly diagnosed MM patients aged ＞18 years who underwent induction therapy followed by autologous stem cell transplantation (ASCT) between November 2020 and December 2021 were identified. Finally, patients with VRd (N=37) and those with D-VTd (N=43) were enrolled. @*Results@#After induction, 10.8% of the VRd group showed stringent complete remission (sCR), 21.6% showed complete response (CR), 35.1% showed very good partial response (VGPR), and 32.4% showed partial response (PR). Of the D-VTd group, 9.3% showed sCR, 34.9% CR, 48.8% VGPR, and 4.2% PR (VGPR or better: 67.6% in VRd vs. 93% in D-VTd, P =0.004). After ASCT, 68.6% of the VRd group showed CR or sCR, while 90.5% of the D-VTd group showed CR or sCR (P=0.016). VRd was associated with an increased incidence of skin rash (P=0.044). Other than rashes, there were no significant differences in terms of adverse events between the two groups. @*Conclusion@#Our study supports the use of a front-line quadruplet induction regimen containing a CD38 monoclonal antibody for transplant-eligible patients with newly diagnosed MM.

COVID-19 outbreak and risk factors for infection in a taekwondo gym in the Republic of Korea

Objectives@#Relatively few studies have assessed risk factors for coronavirus disease 2019 (COVID-19) in public facilities used by children and adolescents. This study presents an analysis of a COVID-19 outbreak that occurred in a taekwondo gym in Korea, predominantly among children and adolescents, with the aim of providing insights on managing COVID-19 outbreaks in similar facilities. @*Methods@#All 108 taekwondo gym students and staff received COVID-19 tests. A survey and closed-circuit television analyses were used to identify risk factors. A univariate analysis was conducted, followed by multivariate logistic regression analysis with backward elimination for variables with a significance level <0.10 in the univariate analysis. @*Results@#COVID-19 was confirmed in 30 of 108 subjects at the taekwondo gym (attack rate, 27.8%). The outbreak started in an adult class student. This student transmitted the virus to the staff, who consequently transmitted the virus to adolescent students. In the univariate analysis, the relative risk for younger age (≤9 years) was 2.14 (95% confidence interval [CI], 1.01–4.54; p=0.054), and that for food consumption inside the gym was 2.12 (95% CI, 1.04–4.30; p=0.048). In the multivariate logistic regression analysis, the odds ratio for younger age was 2.96 (95% CI, 1.07–8.20; p=0.036), and that for food consumption inside the gym was 3.00 (95% CI, 1.10–8.17; p=0.032). @*Conclusion@#Food consumption inside the facility and young age were significant risk factors for COVID-19 transmission in this taekwondo gym. Food consumption should be prohibited in sports facilities, and infection prevention education for young students is also required.

Sodium Tetradecyl Sulphate Sclerotherapy for Lateral Malleolar Bursitis of the Ankle

Background@#The aim of this study was to evaluate clinical outcomes of sodium tetradecyl sulphate (STS) sclerotherapy for conservative treatment of lateral malleolar bursitis of the ankle. @*Methods@#We reviewed data from 20 consecutive patients (20 ankles) who underwent STS sclerotherapy between August 2018 and June 2019. After aspiration of fluid from the lateral malleolar bursal sac, 2 mL (20 mg) STS was injected into the sac. Clinical outcomes and side effects and complications were evaluated at 2 weeks, 3 months, 1 year, and 2 years after sclerotherapy. Responses to treatment were assessed according to degree of fluctuation, shrinkage of the bursal sac, and soft-tissue swelling. The 36-item short form survey (SF-36) was completed for each patient before and after therapy. @*Results@#Complete response was observed in 17 patients (85%), and partial response was observed in 3 patients (15%) after STS sclerotherapy. SF-36 physical component scores improved from 62.2 (interquartile range, 5.2) before therapy to 70.0 (interquartile range, 7.9) at last follow-up (p < 0.05). One patient (5%) experienced transient hyperpigmentation at the injection site. No major complications occurred. @*Conclusions@#STS sclerotherapy was an effective and safe treatment for patients with lateral malleolar bursitis of the ankle.

Viral Hepatitis in Patients with Inflammatory Bowel Disease / 대한소화기학회지

There has been a rise in the incidence of inflammatory bowel disease (IBD) in developing countries, including South Korea. Consequently, the use of immunosuppressive agents such as immunomodulators or biologics has also increased. Due to immunosuppression, patients on these agents are at increased risk of various opportunistic infections during treatment, which may sometimes lead to serious adverse outcomes. Viral hepatitis, especially hepatitis B, is one of the infectious conditions that can be reactivated during immunosuppressive therapy, and adequate strategies for monitoring and prophylaxis are needed to prevent it. South Korea is one of the countries with intermediate endemicity for hepatitis A and B. Thus, taking adequate precautions against viral hepatitis could prevent new infections or reactivation of these conditions in patients with IBD on immunosuppressive therapy. In this review article, we have summarized the latest evidence on viral hepatitis in patients with IBD that would be of assistance in clinical practice.

2019 Tabletop Exercise for Laboratory Diagnosis and Analyses of Unknown Disease Outbreaks by the Korea Centers for Disease Control and Prevention

Objectives@#The Korea Centers for Disease Control and Prevention has published “A Guideline for Unknown Disease Outbreaks (UDO).” The aim of this report was to introduce tabletop exercises (TTX) to prepare for UDO in the future. @*Methods@#The UDO Laboratory Analyses Task Force in Korea Centers for Disease Control and Prevention in April 2018, assigned unknown diseases into 5 syndromes, designed an algorithm for diagnosis, and made a panel list for diagnosis by exclusion. Using the guidelines and laboratory analyses for UDO, TTX were introduced. @*Results@#Since September 9th , 2018, the UDO Laboratory Analyses Task Force has been preparing TTX based on a scenario of an outbreak caused by a novel coronavirus. In December 2019, through TTX, individual missions, epidemiological investigations, sample treatments, diagnosis by exclusions, and next generation sequencing analysis were discussed, and a novel coronavirus was identified as the causal pathogen. @*Conclusion@#Guideline and laboratory analyses for UDO successfully applied in TTX. Conclusions drawn from TTX could be applied effectively in the analyses for the initial response to COVID-19, an ongoing epidemic of 2019 - 2020. Therefore, TTX should continuously be conducted for the response and preparation against UDO.

Epidemiological Characteristics of COVID-19 Outbreak at Fitness Centers in Cheonan, Korea

Background@#In February 2020, a coronavirus disease 2019 (COVID-19) outbreak was reported in fitness centers in Cheonan, Korea. @*Methods@#From February 24 to March 13, an epidemiological investigation was conducted on the fitness center outbreak. All those who were screened were tested for severe acute respiratory syndrome coronavirus-2 (SARS CoV-2) using real-time reverse transcriptase polymerase chain reaction. Contacts were traced and self-isolated for 14 days. We determined the epidemiological characteristics of confirmed cases of SARS-CoV-2 infection, and estimated the time-dependent reproduction number to assess the transmission dynamics of the infection. @*Results@#A total of 116 cases were confirmed, and 1,687 contacts were traced. The source cases were 8 Zumba instructors who led aerobics classes in 10 fitness centers, and had the largest average number of contacts. A total of 57 Zumba class participants, 37 of their family members, and 14 other contacts were confirmed as cases. The attack rate was 7.3%. The contacts at Zumba classes and homes had a higher attack rate than other contacts. The mean serial interval (± standard deviation) were estimated to be 5.2 (± 3.8) days. The time-dependent reproduction number was estimated to be 6.1 at the beginning of the outbreak, but it dropped to less than 1, 2 days after the epidemiological investigation was launched. @*Conclusion@#The results suggest that the COVID-19 outbreak was effectively contained with rigorous contact tracing, isolating, and testing in combination with social distancing without a lock-down.

Predictive Role of Circulating Immune Cell Subtypes Early after Allogeneic Hematopoietic Stem Cell Transplantation in Patients with Acute Leukemia

BACKGROUND AND OBJECTIVES: Cells of innate immunity normally recover in the first weeks to months after allogenenic hematopoietic stem cell transplantation (allo-HSCT). Their relevance in terms of graft-versus-host disease (GVHD) and graft-versus-leukemia (GVL) effect is largely unknown. The predictive role of early recovery in the immune cells on acute GVHD and GVL effect after allo-HSCT was investigated in patients with acute leukemia who achieved the first complete remission. METHODS: Peripheral blood samples were taken at the median of 14 days (range, 12~29 days) after allo-HSCT. A cohort including 119 samples and characteristics of patients were analyzed. Immune cell populations were identified by flow cytometry. RESULTS: The median age was 49.0 years (range, 21~69) at transplantation. Univariate analysis showed that age less than 40 years old, lower frequencies of CD8+ T cells, invariant natural killer T (iNKT) cells, monocytic myeloid derived suppressor cells (M-MDSCs) and higher frequency of immature MDSCs were associated with occurrence of grade III–IV acute GVHD. Multivariate analyses showed that iNKT cells (hazard ratio (HR), 0.453, 95% CI, 0.091~0.844, p=0.024) and M-MDSCs (HR, 0.271, 95% CI, 0.078~0.937, p=0.039) were independent factors. Combination of higher frequencies of both cell subsets was associated with lower incidence of grade III–IV acute GVHD, whereas patients with lower frequency of iNKT cells and higher frequency of M-MDSCs showed significant higher probability of relapse. CONCLUSIONS: iNKT cells and M-MDSCs could be relevant cell biomarkers for predicting acute GVHD and/or relapse in acute leukemia patients treated with allo-HSCT.

Enhanced polo-like kinase 1 expression in myelodysplastic syndromes

BACKGROUND: Cancer is characterized by uncontrolled cellular proliferation, and Polo-like kinase 1 (PLK1), a key regulator of the cell cycle, is overexpressed in many cancers, including acute leukemia and lymphoma. However, the dynamics of PLK1 transcription in myelodysplastic syndromes (MDS) are unknown. This study aimed to investigate the transcript dynamics of PLK1 and determine its role in the pathophysiology of MDS. METHODS: PLK1 mRNA obtained from the bone marrow samples of 67 patients with MDS, 16 patients with secondary acute myeloid leukemia (sAML), and 10 healthy controls were analyzed using quantitative real-time PCR and compared according to various clinical parameters. RESULTS: The median PLK1 expression levels differed slightly, but not significantly, between MDS and sAML patients [661.21 (range, 29.38–8,987.31) vs. 1,462.05 (32.22–5,734.09), respectively], but were significantly higher (P<0.001) than the levels in the healthy controls [19.0 (1.60–49.90)]. Further analyses of PLK1 levels according to the WHO classification of MDS, prognostic risk groups, karyotype risk groups, marrow blast percentage, and depth of cytopenia did not reveal any significant associations. In patients progressing to sAML, PLK1 expression levels differed significantly according to the presence or absence of resistance to hypomethylation treatment (2,470.58 vs. 415.98, P=0.03). CONCLUSION: PLK1 is upregulated in MDS patients; however, its role in the pathophysiology of MDS is unclear. Gene upregulation in cases with pharmacotherapeutic resistance warrants further investigation.

Rhabdomyolysis and diabetic ketoacidosis after bee sting: A case report

Bee stings result in diverse clinical manifestations from localized pain, rash to life-threatening systemic allergic reactions or toxic reactions. Toxic reactions include skin necrosis, pancreatitis, acute renal failure, hemolysis or coagulopathy, while systemic allergic reactions present with IgE-mediated anaphylaxis. We experienced a 63-year-old woman who developed rhabdomyolysis and diabetic ketoacidosis after bee sting. The patient was accompanied by pulmonary edema due to acute kidney injury, which was recovered by intensive hemodialysis treatment. Here, we report a rare and serious case induced by bee sting with a review of the literature.

Epidemiology and Clinical Characteristics of Zika Virus Infections Imported into Korea from March to October 2016

Zika is a re-emerging, mosquito-borne viral infection, which has been recently shown to cause microcephaly and Guillain-Barré syndrome. Since 2015 the number of infected patients has increased significantly in South America. The purpose of this study was to identify the epidemiologic and clinical characteristics of patients with Zika virus (ZIKV) infections in Korea. Patients who had visited areas of risk and tested positive in the ZIKV reverse transcriptase polymerase chain reaction (RT-PCR) in blood, urine, or saliva specimens were included. The first Korean case of ZIKV infection was reported in March 2016, and 14 cases had been reported by October 2016. The median age of the patients was 34 years (19–64 years). Ten patients had been exposed in Southeast Asia and 4 in Latin America. Rash was the most common symptom (92.9%; 13/14), followed by myalgia (50.0%; 7/14), and arthralgia (28.6%, 4/14). There were no neurologic abnormalities and none of the patients was pregnant. Results of biochemical tests were normal. Positivity rates of RT-PCR for ZIKV in serum, urine, and saliva were 53.8%, 100.0%, and 83.3%, respectively in the first week of symptoms. In conclusion, 14 patients with ZIKV infections were reported in Korea by October 2016 and all of them had mild clinical symptoms.

Hemophagocytic Lymphohistiocytosis Occurring after Induction Chemotherapy in Acute Myelocytic Leukemia / 대한내과학회지

Hemophagocytic lymphohistiocytosis (HLH), associated with acute myelocytic leukemia (AML), is a very rare disease. We here report a case of HLH occurring after induction chemotherapy for AML. AML-associated HLH can be triggered by AML itself, by chemotherapeutic agents, or by infectious complications. Our patient developed a high-grade fever of unknown cause, bilateral pulmonary infiltrates, and shock after successful treatment of AML with induction chemotherapy, and had high serum ferritin, hypertriglyceridemia, hypofibrinogenemia, hemophagocytic histiocytes in bone marrow, low natural killer cell activity, and elevated soluble interleukin-2 receptor levels. A diagnosis of HLH was made. Dexamethasone, cyclosporine, and etoposide were given and allogeneic hematopoietic stem cell transplantation was performed. Careful suspicion of HLH may be warranted if a patient experiences fever of unknown etiology, high ferritin levels, and liver dysfunction during AML treatment.

Genetic–pathologic characterization of myeloproliferative neoplasms

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic stem cell disorders characterized by the proliferation of one or more myeloid lineages. The current study demonstrates that three driver mutations were detected in 82.6% of 407 MPNs with a mutation distribution of JAK2 in 275 (67.6%), CALR in 55 (13.5%) and MPL in 6 (1.5%). The mutations were mutually exclusive in principle except in one patient with both CALR and MPL mutations. The driver mutation directed the pathologic features of MPNs, including lineage hyperplasia, laboratory findings and clinical presentation. JAK2-mutated MPN showed erythroid, granulocytic and/or megakaryocytic hyperplasia whereas CALR- and MPL-mutated MPNs displayed granulocytic and/or megakaryocytic hyperplasia. The lineage hyperplasia was closely associated with a higher mutant allele burden and peripheral cytosis. These findings corroborated that the lineage hyperplasia consisted of clonal proliferation of each hematopoietic lineage acquiring driver mutations. Our study has also demonstrated that bone marrow (BM) fibrosis was associated with disease progression. Patients with overt fibrosis (grade ⩾2) presented an increased mutant allele burden (P<0.001), an increase in chromosomal abnormalities (P<0.001) and a poor prognosis (P<0.001). Moreover, among patients with overt fibrosis, all patients with wild-type JAK2/CALR/MPL (triple-negative) showed genomic alterations by genome-wide microarray study and revealed the poorest overall survival, followed by JAK2-mutated MPNs. The genetic–pathologic characteristics provided the information for understanding disease pathogenesis and the progression of MPNs. The prognostic significance of the driver mutation and BM fibrosis suggests the necessity of a prospective therapeutic strategy to improve the clinical outcome.

Community-acquired Methicillin-resistant Staphylococcus aureus Bacteremia Complicated by Acute Cholecystitis / 대한내과학회지

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) bacteremia is an uncommon infection in Korea. Typically, staphylococcal bacteremia is associated with various metastatic infections, such as multiple liver and spleen abscesses, infectious spondylitis, or infective endocarditis. Solitary cholecystitis as the only manifestation of CA-MRSA bacteremia has not been reported. Therefore, we report a case of CA-MRSA bacteremia complicated by acute cholecystitis.

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.

Spontaneous Neoplastic Remission of Hepatocellular Carcinoma / 대한소화기학회지

We report on a case of a 57-year-old male who underwent a curative resection for hepatocellular carcinoma (HCC) with histological confirmation of a spontaneously necrotized tumor. Initial serum AFP level was 4,778 ng/mL. A 3.7 cm hyperechoic mass in segment 6 of the liver was observed on ultrasonography and dynamic contrast-enhanced liver MRI showed a 3.7x3.1 cm sized HCC. He was scheduled to undergo curative surgical resection under the clinical diagnosis of an early stage HCC (Barcelona Clinic Liver Cancer stage A). Without treatment, the serum AFP level declined rapidly to 50 ng/mL over five weeks. He underwent curative wedge resection of segment 6 of the liver. Histology revealed complete necrosis of the mass rimmed by inflamed fibrous capsule on a background of HBV-related cirrhosis with infiltration of lymphoplasma cells. Exact pathophysiology underlying this event is unknown. Among the proposed mechanisms of spontaneous neoplastic remission of HCC, circulatory disturbance and activation of host immune response offer the most scientific explanation for the complete histologic necrosis of HCC in the resected mass seen in our patient.

Recent advances in treatment of aplastic anemia

Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.

Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

Hepatic veno-occlusive disease resulting in tacrolimus toxicity after allogeneic hematopoietic stem cell transplantation

Tacrolimus is a widely used immunosuppressive agent for the prophylaxis of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). Since tacrolimus is primarily metabolized by the liver, hepatic dysfunction may affect its metabolism. Hepatic veno-occlusive disease (VOD) is an early complication of HSCT that results in hepatic dysfunction, suggesting that VOD may affect tacrolimus metabolism. We report a case of hepatic VOD accompanied by a sustained high blood trough level of tacrolimus despite its discontinuation. The findings of this case suggest that the elimination of tacrolimus can be markedly delayed in patients with hepatic VOD, and that the clinician should carefully modulate the drug dosage for these patients.

Hepatic veno-occlusive disease resulting in tacrolimus toxicity after allogeneic hematopoietic stem cell transplantation

Tacrolimus is a widely used immunosuppressive agent for the prophylaxis of graft-versus-host disease in allogeneic hematopoietic stem cell transplantation (HSCT). Since tacrolimus is primarily metabolized by the liver, hepatic dysfunction may affect its metabolism. Hepatic veno-occlusive disease (VOD) is an early complication of HSCT that results in hepatic dysfunction, suggesting that VOD may affect tacrolimus metabolism. We report a case of hepatic VOD accompanied by a sustained high blood trough level of tacrolimus despite its discontinuation. The findings of this case suggest that the elimination of tacrolimus can be markedly delayed in patients with hepatic VOD, and that the clinician should carefully modulate the drug dosage for these patients.