Trends of Mortality and Cause of Death among HIV-Infected Patients in Korea, 1990-2011

Although a decrease in acquired immunodeficiency syndrome (AIDS)-related mortality has been documented in highly active antiretroviral therapy (HAART) era, there are no published data comparing specific causes of death between pre-HAART and HAART era in Korea. Mortality and cause of death were analyzed in three treatment periods; pre-HAART (1990-1997), early-HAART (1998-2001), and late-HAART period (2002-2011). The patients were retrospectively classified according to the treatment period in which they were recruited. Although mortality rate per 100 person-year declined from 8.7 in pre-HAART to 4.9 in late-HAART period, the proportion of deaths within 3 months of initial visit to study hospital significantly increased from 15.9% in pre-HAART to 55.1% in late-HAART period (P < 0.001). Overall, 59% of deaths were attributable to AIDS-related conditions, and Pneumocystis pneumonia (PCP) was the most common cause of death (20.3%). The proportion of PCP as cause of death significantly increased from 8.7% in pre-HAART to 31.8% in late-HAART period (P < 0.001). Despite of significant improvement of survival, there was still a high risk of early death in patients presenting in HAART era, mainly due to late human immunodeficiency virus (HIV) diagnosis and late presentation to care.

Causes of Death and Risk Factors for Mortality among HIV-Infected Patients Receiving Antiretroviral Therapy in Korea

A retrospective study was conducted to determine the mortality, causes and risk factors for death among HIV-infected patients receiving antiretroviral therapy (ART) in Korea. The outcomes were determined by time periods, during the first year of ART and during 1-5 yr after ART initiation, respectively. Patients lost to follow-up were traced to ascertain survival status. Among 327 patients initiating ART during 1998-2006, 68 patients (20.8%) died during 5-yr follow-up periods. Mortality rate per 100 person-years was 8.69 (95% confidence interval, 5.68-12.73) during the first year of ART, which was higher than 4.13 (95% confidence interval, 2.98-5.59) during 1-5 yr after ART. Tuberculosis was the most common cause of death in both periods (30.8% within the first year of ART and 16.7% during 1-5 yr after ART). During the first year of ART, clinical category B and C at ART initiation, and underlying malignancy were significant risk factors for mortality. Between 1 and 5 yr after ART initiation, CD4 cell count < or = 50 cells/microL at ART initiation, hepatitis B virus co-infection, and visit constancy < or = 50% were significant risk factors for death. This suggests that different strategies to reduce mortality according to the time period after ART initiation are needed.

Predictive Value of Post-Transplant Bone Marrow Plasma Cell Percent in Multiple Myeloma Patients Undergone Autologous Transplantation

BACKGROUND/AIMS: Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment. METHODS: We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (> or = 2 vs. or = 50 vs. or = 50% at diagnosis, CR after 3 cycles of VAD therapy, del (13q) by fluorescence in situ hybridization, and BMPCp > or = 2% at post-transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp > or = 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters. CONCLUSIONS: Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.

The risk factors for herpes zoster in bortezomib treatment in patients with multiple myeloma

BACKGROUND: Bortezomib has significant activity in treating multiple myeloma (MM). The risk of herpes zoster (HZ) has been reported to increase significantly with bortezomib treatment, but the predisposing factors for HZ are not clear. This study is a retrospective analysis of the relevant risk factors for HZ in Korean MM patients treated with bortezomib. METHODS: Sixty-six patients with refractory or relapsed MM who underwent chemotherapy with bortezomib were included in the study. Prophylactic antiviral drugs were not used for treatment. The following parameters were reviewed: age, gender, stage and type of MM, extent of previous treatment, history of HZ, duration from the time of diagnosis to the time of bortezomib treatment initiation, and absolute lymphocyte counts (ALC) at the time of bortezomib treatment initiation. RESULTS: The incidence of HZ was 16.7%. There were no intergroup differences between the HZ-positive and the HZ-negative groups with regard to a history of HZ, number of previous treatments, and exposure to steroids before bortezomib treatment. The median duration from the time of MM diagnosis to the time of bortezomib treatment initiation in the HZ-positive group was significantly shorter than that in the HZ-negative group. The median ALC at the time of bortezomib initiation in the HZ-positive group was significantly lower than that in the HZ-negative group. CONCLUSION: Bortezomib itself might act as a risk factor for HZ by inhibiting cell-mediated immunity, and patients with low ALC at the time of bortezomib treatment initiation were at greater risk of HZ during bortezomib treatment.

Primary Diffuse Large B Cell Lymphoma of the Bladder

Primary malignant lymphoma of the urinary bladder is a rare disease, and it accounts for only 0.2% of all the cases of extranodal lymphoma. The prognosis of primary bladder lymphoma has been favorable, with many patients being alive and well several years after treatment. We report here on a case of primary diffuse large B cell lymphoma of the urinary bladder in a 75-year-old man patient who presented with a one-month history of persistent dysuria. The abdominal CT revealed a mass at the posterior wall of the urinary bladder. The tissue obtained by transurethral cystoscopy showed an atypical lymphoid proliferation, which was consistent with diffuse large B cell lymphoma. The patient received systemic chemotherapy of rituximab and CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) and he achieved a significant partial remission.

A Case of Acute Biphenotype Leukemia after Diagnosis of Pulmonary Alveolar Proteinosis

We present the case of a 34-year-old man with acute biphenotype leukemia that co-expressed B-lymphoid and myeloid antigen after the diagnosis of pulmonary alveolar proteinosis (PAP). The diagnosis of PAP was established by Periodic Acid-Schiff reaction staining on the Video Associated Thoracoscope guided lung biopsy and biphenotype leukemia was revealed by immunohistochemical stains of the blasts harvested from the bone marrow biopsy. Supposedly, PAP follows a hematologic malignancy, yet this case shows the reverse sequence.

A Case of Acute Myeloblastic Leukemia in a Patient with Behcet's Disease

Behcet's disease is a relapsing inflammatory disorder characterized by vasculitis of unknown cause and has been reported rarely in association with malignant diseases. In most cases the autoimmune nature of Behcet's disease and the long-term immunosuppressive therapy for disease control have been proposed to be responsible for malignant transformation. Although a few cases of various solid tumor and myelodysplastic syndrome have been reported in association with Behcet's disease, acute leukemia has seldom been associated with Beh?et's disease in Korea. We report a case of 38-year-old man with acute myeloblastic leukemia association with a Behcet's disease who had not received long-term treatment.

Post-operative Bleeding due to Acquired Hemophilia Successfully Treated with Recombinant Factor VIIa: Case Report

Acquired hemophilia is a rare but potentially life-threatening hemorrhagic disorder caused by the development of autoantibodies against coagulation factor VIII. Concentrates of human factor VIII, desmopressin, activated prothrombin complex concentrates, recombinant activated factor VII can all be used to control episodes of acute bleeding. The recent availability of bypassing agents like recombinant activated factor VII has been shown to be clinically safe and effective as treatment for acute bleeding. In this case report, a 67 year-old male patient with Rh negative blood type developed gross hematuria and bleeding after transurethral resection due to prostatic hypertrophy. After vesicocutaneous fistular reduction operation, post-operative bleeding was presented. The acute bleeding was controlled successfully by the combined treatment with recombinant activated factor VII (Novo seven(R)) and prednisone.

Influence of Lactate Dehydrogenase and Cyclosporine A Level on the Incidence of Acute Graft-versus-host Disease After Allogeneic Stem Cell Transplantation

Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor.

Gemcitabine, Etoposide, Cisplatin, and Dexamethasone in Patients With Refractory or Relapsed Non-Hodgkin's Lymphoma

BACKGROUND/AIMS: To date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients. METHODS: All patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m2 by continuous i.v. on days 1 and 8; etoposide 40 mg/m2 by i.v. on days 1-4; cisplatin 60 mg/m2 by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD. RESULTS: Between January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The doselimiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6)x10(6)/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation. CONCLUSIONS: GEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.

Elevation of Serum Ferritin is Associated with the Outcome of Patients with Newly Diagnosed Multiple Myeloma

BACKGROUND/AIMS: Serum ferritin is a marker of acute phase reactions and iron storage. In addition, hematologic malignancies are associated with elevated serum ferritin levels. Other studies have suggested that ferritin is a surrogate for advanced disease and has an impact on relapse, because elevated serum ferritin predicts overall survival (OS) and relapse-free survival following autologous stem cell transplantation for lymphomas. METHODS: We studied 89 consecutive patients with newly diagnosed multiple myeloma to determine the value of serum ferritin in comparison with known prognostic factors. RESULTS: The OS in the elevated serum ferritin group (> or =300 ng/mL) was shorter than that in the normal serum ferritin group (<300 ng/mL, p<0.001) after a median follow-up of 25 months. In univariate analysis, elevated ferritin was correlated with poor survival in the patients (relative risk [RR], 2.588; 95% confidence interval [CI], 1.536 to 4.358; p<0.001). Furthermore, multivariate analysis showed that elevated serum ferritin was an independent predictor of mortality in patients with multiple myeloma (RR, 2.594; 95% CI, 1.403 to 4.797; p=0.002). CONCLUSIONS: The serum ferritin can a prognostic parameter of survival as well as disease activity in patients with multiple myeloma.

Clinical characteristics and prevalence of toxoplasma infection in human immunodeficiency virus-infected patients in South Korea / 대한내과학회지

BACKGROUND/AIMS: Toxoplasmic encephalitis (TE) is one of the most common causes of focal brain lesions, which complicate the course of acquired immunodeficiency syndrome (AIDS). There is wide geographic variation in the prevalence of toxoplasma infection. This study was performed to characterize toxoplasma infection in human immunodeficiency virus (HIV)-infected patients in South Korea. METHODS: We retrospectively examined the incidence and clinical characteristics of TE in 683 HIV-infected patients who were enrolled between 1990 and 2008 at four university hospitals in Busan, Korea. We also assessed the seroprevalence of IgG antibodies to Toxoplasma gondii, risk factors for toxoplasma seropositivity, and seroconversion rates during the course of HIV infection. RESULTS: Among 683 HIV-infected patients, six (0.9%) patients were diagnosed with TE. The incidence of TE was 0.34 per 100 person-years (py) during the study period. Of the 414 patients who had undergone serological examinations for Toxoplasma gondii, 35 (8.5%) patients were seropositive. Univariate analysis showed that the risk factors associated with toxoplasma seropositivity included increased age, heterosexual transmission, marriage, and a history of overseas residence (p<0.05). Of these factors, a history of overseas residence was a significant risk factor in a multivariate analysis (p<0.05). A total of 95 patients who were seronegative on their initial screen showed serial toxoplasma IgG antibodies (mean duration of follow-up, 2.1 years). Among these patients, only two (2.1%) acquired IgG antibodies to Toxoplasma gondii during the follow-up period. CONCLUSIONS: The seroprevalence of anti-toxoplasma IgG antibodies in HIV-infected patients in Korea was 8.5%. A history of overseas residence was a significant risk factor for toxoplasma seropositivity. The incidence of TE was 0.34/100 py, which is lower than that reported in other countries. Toxoplasma seroconversion was also uncommon (2.1%).

Trends in cancer risk among South Korean patients infected with Human Immunodeficiency Virus / 대한내과학회지

BACKGROUND/AIMS: The prevalence of malignancies associated with human immunodeficiency virus (HIV) is rapidly increasing. The aim of the present study was to identify clinical features associated with malignancies in South Korean patients infected with HIV. METHODS: From January 1990 to June 2007, we reviewed an electronic database containing pathological reports obtained from HIV-infected patients and then retrospectively analyzed a total of 27 malignancy cases treated at four different institutions. RESULTS: Among 683 patients infected with HIV, malignant diseases were diagnosed in 27 cases (4.0%). Twenty-five of these patients were male, and the median age was 48 (range; 24-76). At the time of diagnosis, the median CD4+ lymphocyte count was 42/uL (range 3-339). Acquired immune deficiency syndrome (AIDS)-defining malignancies were diagnosed in 13 patients (48%) and non-AIDS-defining malignancies were diagnosed in 14 patients (52%). Two patients each were diagnosed with AIDS-defining and non-AIDS-defining malignancies during the pre-highly active anti-retroviral therapy (HARRT) period. In contrast, 11 patients (48%) and 12 patients (52%) were diagnosed with AIDS-defining and non-AIDS-defining malignancies during the HARRT period, respectively. Among AIDS-defining malignancies, non-Hodgkins lymphoma was the most frequently observed (9/13), followed by Kaposi's sarcoma (4/13). Among the 9 patients with non-Hodgkins lymphoma, diffuse large B-cell lymphoma was most common (5/9), followed by primary CNS lymphoma (3/9) and Burkitt's lymphoma (1/9). Gastrointestinal (GI) malignancies [i.e., gastric cancer (3/14), rectal cancer (3/14), and esophageal cancer (1/14)] and hepatocellular carcinoma (3/14) were the most commonly observed among the non-AIDS-defining malignancies. Other observed non-AIDS-defining malignancies were thyroid cancer (1/14), tonsillar cancer (1/14), angiosarcoma (1/14), and eccrine cancer (1/14). Finally, median CD4+ lymphocyte counts at the time of diagnosis were significantly different (18 vs. 114/uL, p=0.001) between AIDS-defining malignancies and non-AIDS-defining malignancies. CONCLUSIONS: Malignancies were diagnosed in 4.0% of patients infected with HIV. This study showed similar rates of incidence between AIDS-defining and non-AIDS-defining malignancies. Non-Hodgkins lymphoma was the most frequently observed malignancy, whereas GI malignancies and hepatocellular carcinoma were common among non-AIDS-defining malignancies.

The Efficacy and Adverse Effect of Hydroxyurea as Compared with Anagrelide in Essential Thrombocythemia

BACKGROUND: Although the platelet count may not always correlate with the risk of thrombosis, there is evidence that a strict control of the platelet count decreases the incidence of thrombotic and hemorrhagic complications. However, it is difficult to select an appropriate platelet-lowering agent. This retrospective study was performed to assess the efficacy and adverse effect of the use of hydroxyurea and anagrelide for patients with essential thrombocythemia. METHODS: Sixty patients with essential thrombocythemia received either hydroxyurea (n=30) or anagrelide (n=30). Early responses and adverse effects of hydroxyurea and anagrelide in the patients were retrospectively analyzed. RESULTS: Treatment with anagrelide or hydroxyurea resulted in a rapid decrease of the platelet count within two weeks. The response rates after treatment with hydroxyurea and anagrelide were 83% and 77%, respectively. As compared with patients treated with hydroxyurea, patients treated with anagrelide presented with adverse effects such as headache palpitation was also frequently noticed (P=0.001). However, serious hemorrhage (n=2) and transformation to leukemia (n=1) occurred in patients treated with hydroxyurea. CONCLUSION: Both anagrelide and hydroxyurea were effective and well-tolerated agents for the reduction of the platelet count. Long-term efficacy and adverse effects of the drugs remain to be determined.

Reverse Seroconversion of Hepatitis B following Allogenic Hematopoietic Stem Cell Transplantation from a Hepatitis Immune Donor in a Multiple Myeloma Patient

A 52-yr-old male with multiple myeloma underwent autologous stem cell transplantation in June 2002. In August 2004, the multiple myeloma had recurred. The patient received allogenic stem cell transplantation in September 2005. Before undergoing transplantation, the presence of HBsAb and the absence of HBsAg were noted. The patient underwent allogenic peripheral blood stem cell transplantation (PBSCT) from a sibling donor who was hepatitis surface antibody (HBsAb) positive and hepatitis surface antigen (HBsAg) negative. Nineteen months after the PBSCT, the liver function tests showed elevation of the aminotransferases. The patient was HBsAg positive and HBsAb negative. The liver biopsy specimen revealed hepatitis. The reactivation of a hepatitis B virus infection, in a hepatitisB immune patient, referred to as reverse seroconversion, is a rare complication of hematopoietic stem cell transplantation.

A Case of Granulocytic Sarcoma in the Brain of a Patient with Acute Erythroleukemia

Granulocytic sarcoma is a localized tumor that's composed of immature granulocytic cells and this is more common in patient with 8;21 translocation. We present here a case in a 64-year-old man who was diagnosed with acute myelogenous leukemia (erythroleukemia) that had a complex hyperdiploid karyotype. While he underwent chemotherapy, he developed nausea, vomiting, headache and dysarthria. After several diagnostic work-ups, granulocytic sarcoma in the cerebellum and leptomeningeal metastasis of his leukemia were found on the magnetic resonance imaging and the cerebrospinal fluid cytology.

Treatment Outcomes with CHOP Chemotherapy in Adult Patients with Hemophagocytic Lymphohistiocytosis

The objective of the current study was to investigate the treatment outcomes for the use of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy in adult patients with hemophagocytic lymphohistiocytosis (HLH). Seventeen HLH patients older than 18 yr of age were treated with CHOP chemotherapy. A response evaluation was conducted for every two cycles of chemotherapy. With CHOP chemotherapy, complete response was achieved for 7/17 patients (41.2%), a partial response for 3/17 patients (17.6%), and the overall response rate was 58.8%. The median response duration (RD) was not reached and the 2-yr RD rate was 68.6%, with a median follow-up of 100 weeks. Median overall survival (OS) was 18 weeks (95% CI, 6-30 weeks) and the 2-yr OS rate was 43.9%. Reported grade 3 or 4 non-hematological toxicities were increased serum liver enzyme levels and stomatitis. Grade 3 or 4 hematological toxicities were leukopenia (50.8%), anemia (20%), and thrombocytopenia (33.9%). Neutropenic fever was observed in 21.6% of patients (14/65 cycles), and most of the cases were resolved with supportive care including treatment with broad-spectrum antibiotics. CHOP chemotherapy seems to be effective in adult HLH patients and the toxicities are manageable.

Outcome of Immunosuppressive Therapy with Helicobacter pylori Eradication Therapy in Patients with Chronic Idiopathic Thrombocytopenic Purpura

We initiated this study to investigate whether combining Helicobacter pylori eradication with immunosuppressive therapy provides an additional benefit to patients with idiopathic thrombocytopenic purpura (ITP) that has relapsed or has not responded to steroid and/or danazol therapy in patients who have H. pylori infection. Thirty- four patients with chronic ITP that had relapsed or failed to steroid and/or danazol therapy were assessed for H. pylori infection. Of the 21 confirmed cases, 12 patients were given H. pylori eradication therapy alone (EA), while 9 patients received eradication therapy combined with immunosuppressive therapy (EI). The response rate was not significantly different between patients in the EA and those in the EI group (41.7% in the EA group vs. 66.7% in the EI group, p=0.345). The median platelet count at 6 months after therapy was higher in the EI group patients (75X10(9)/L in the EI group patients vs. 18x109/L in the EA group patients, p=0.028). The median response duration was also longer in the EI group patients (9 months in the EI group patients vs. 3 months in the EA group patients, p=0.049). These results show that a significant benefit is gained by the use of H. pylori eradication combined with immunosuppressive therapy over the use of eradication therapy alone for patients with chronic ITP.

A Case of Bicytopenia Combined with Littoral Cell Angioma

Littoral cell angioma is a recently described vascular tumor of spleen with an unknown etiology. We present a case in a 74-year-old woman with severe anemia, thrombocytopenia and palpable splenomegaly. The computed tomography of abdomen showed well-defined multiple nodules in spleen. Splenectomy was performed and the histological and immunohistochemical features of splenic tumor were consistent with a littoral cell angioma. The patients had persistent anemia and thrombocytopenia after splenectomy. We suggest hepatic destruction or other autoimmune mechanism contributes persistent bicytopenia. This case illustrated the refractory bicytopenia combined with littoral cell angioma.

A Case of Henoch-Schonlein Purpura Associated with Diffuse Large B Cell Lymphoma

A 69-year-old female was referred to our institution due to abdominal pain and palpable purpura on both buttocks and legs. A skin biopsy of her purpura revealed granulocyte infiltration and leucocytoclasia around the arterioles and venuoles at the dermis, as well as an elevated serum immunoglobulin A level, hematuria and proteinuria. Therefore she was diagnosed with Henoch-Schonlein purpura. She had been diagnosed with diffuse large B cell lymphoma after a biopsy of her left inguinal lymph node 12 years ago and received 6 cycles of CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) chemotherapy, which was followed by a complete remission. Abdominal and chest CT revealed multiple lymph node enlargement and bowel wall thickening at the ileocecal area, and lesions were observed in a whole body PET CT scan. Recurrence of the diffuse large B cell lymphoma was confirmed by a biopsy of the ileocecal area via colonoscopy. The purpura was improved after oral prednisolone therapy and etoposide, oxaliplatin and ifosfamide salvage combination chemotherapy was used to treat the lymphoma.