Efficacy of Antiviral Prophylaxis up to 6 or 12 Months From Completion of Rituximab in Resolved Hepatitis B Patients: A Multicenter, Randomized Study

Background@#Rituximab occasionally induces reactivation of hepatitis B virus (HBV) in patients with resolved HBV, at times with fatal consequences. The optimal duration of prophylactic antiviral therapy in this situation is unclear. We aimed to investigate the difference in HBV reactivation according to the duration of prophylactic tenofovir disoproxil fumarate (TDF) in patients with resolved HBV and receiving rituximab. @*Methods@#A multicenter, randomized, open-label, prospective study was conducted in hepatitis B surface antigen-negative and anti-HBc-positive non-Hodgkin’s lymphoma patients treated with rituximab-based chemotherapy. A total of 90 patients were randomized and received prophylactic TDF from the initiation of rituximab until 6 months (the 6-month group) or 12 months (the 12-month group) after the completion of rituximab. The primary outcome was the difference in HBV reactivation and the secondary outcomes were the difference in hepatitis flare and adverse events between the two groups. @*Results@#In an intention to treat (ITT) analysis, HBV reactivation occurred in 1 of 43 patients (2.3%; 95% confidence interval [CI], 0.41–12%) at a median of 13.3 months in the 6-month group and 2 of 41 patients (4.9%; 95% CI, 1.4–16%) at a median of 13.7 months in the 12-month group. In a per protocol (PP) analysis, HBV reactivation occurred in 1 of 18 patients (5.6%; 95% CI, 0.99–26%) at 13.3 months in the 6-month group and 1 of 13 patients (7.7%; 95% CI, 1.4–33%) at 9.7 months in the 12-month group. The cumulative incidence of HBV reactivation was not significantly different between the two groups in ITT and PP analyses (P = 0.502 and 0.795, respectively). The occurrence of adverse events was not significantly different between the two groups in ITT (9.3% in the 6-month group, 22.0% in the 12-month group, P = 0.193) and PP analyses (5.6% in the 6-month group, 7.7% in the 12-month group, P > 0.999). @*Conclusion@#Prophylactic TDF up to 6 months after completion of rituximab-based chemotherapy is sufficient in terms of the efficacy and safety of reducing HBV reactivation in patients with resolved HBV.Trial Registration: ClinicalTrials.gov Identifier: NCT02585947

Treatment outcome and prognostic factors of Korean patients with chronic lymphocytic leukemia: a multicenter retrospective study

Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.

Acute cor pulmonale due to pulmonary tumor thrombotic microangiopathy in two patients with breast cancer

No abstract available.

Prediction of survival by applying current prognostic models in diffuse large B-cell lymphoma treated with R-CHOP followed by autologous transplantation

BACKGROUND: Among the currently available prognostic models for diffuse large B-cell lymphoma (DLBCL), we investigated to determine which is most adoptable for DLBCL patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) followed by upfront autologous stem cell transplantation (auto-SCT). METHODS: We retrospectively evaluated survival differences among risk groups based on the International Prognostic Index (IPI), the age-adjusted IPI (aaIPI), the revised IPI (R-IPI), and the National Comprehensive Cancer Network IPI (NCCN-IPI) at diagnosis in 63 CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT. RESULTS: At the time of auto-SCT, 74.6% and 25.4% of patients had achieved complete remission and partial remission after R-CHOP, respectively. As a whole, the 5-year overall (OS) and progression-free survival (PFS) rates were 78.8% and 74.2%, respectively. The 5-year OS and PFS rates according to the IPI, aaIPI, R-IPI, and NCCN-IPI did not significantly differ among the risk groups for each prognostic model (P-values for OS: 0.255, 0.337, 0.881, and 0.803, respectively; P-values for PFS: 0.177, 0.904, 0.295, and 0.609, respectively). CONCLUSION: There was no ideal prognostic model among those currently available for CD20-positive DLBCL patients treated with R-CHOP followed by upfront auto-SCT.

Metastatic Pulmonary Calcification in a Patient with Adult T-Cell Leukemia/Lymphoma / 대한내과학회지

Adult T-cell leukemia/lymphoma (ATLL) is a highly aggressive disease that is geographically clustered, mirroring areas endemic for human T-cell lymphotropic virus type 1 infection. Most patients with ATLL present with aggressive manifestations such as severe hypercalcemia, lymphadenopathy, hepatosplenomegaly, and bone marrow involvement with progressive thrombocytopenia. We herein report a case of a patient with ATLL exhibiting increased uptake in both lungs as shown on a bone scan using 99mTc-methylene diphosphonate. This finding is thought to have been caused by metastatic calcification associated with ectopic parathyroid hormone production.

R-CHOP chemoimmunotherapy followed by autologous transplantation for the treatment of diffuse large B-cell lymphoma

BACKGROUND: We investigated factors that influence outcomes in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab combined with the CHOP regimen (R-CHOP) followed by upfront autologous stem cell transplantation (Auto-SCT). METHODS: We retrospectively evaluated survival differences between subgroups based on the age-adjusted International Prognostic Index (aaIPI) and revised-IPI (R-IPI) at diagnosis, disease status, and positron emission tomographic/computerized tomographic (PET/CT) status at transplantation in 51 CD20-positive DLBCL patients treated with R-CHOP followed by upfront Auto-SCT. RESULTS: Patients had either stage I/II bulky disease (5.9%) or stage III/IV disease (94.1%). The median patient age at diagnosis was 47 years (range, 22-66 years); 53.3% and 26.7% had high-intermediate and high risks according to aaIPI, respectively. At the time of Auto-SCT, 72.5% and 27.5% experienced complete (CR) and partial remission (PR) after R-CHOP, respectively. The median time from diagnosis to Auto-SCT was 7.27 months (range, 3.4-13.4 months). The 5-year overall (OS) and progression-free survival (PFS) were 77.3% and 72.4%, respectively. The 5-year OS and PFS rates according to aaIPI, R-IPI, and PET/CT status did not differ between the subgroups. More importantly, the 5-year OS and PFS rates of the patients who achieved PR at the time of Auto-SCT were not inferior to those of the patients who achieved CR (P=0.223 and 0.292, respectively). CONCLUSION: Survival was not influenced by the aaIPI and R-IPI at diagnosis, disease status, or PET/CT status at transplantation, suggesting that upfront Auto-SCT might overcome unfavorable outcomes attributed to PR after induction chemoimmunotherapy.

Polycythemia Vera Presenting with Generalized Chorea: A Case Report and Review of the Literature / 대한내과학회지

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis. Clinical symptoms can range in severity from headache and tinnitus to thrombohemorrhagic complications. Neurologic symptoms are common at the onset of polycythemia; however, chorea due to PV is a rare complication. We present the case of a 77-year-old female who was referred to our hospital because of choreic movement of the limbs, head and face. She was diagnosed with JAK2V617F mutation-positive PV. Her chorea was completely resolved by phlebotomy combined with hydroxyurea and aspirin.

Polycythemia Vera Presenting with Generalized Chorea: A Case Report and Review of the Literature / 대한내과학회지

Polycythemia vera (PV) is a myeloproliferative neoplasm characterized by erythrocytosis. Clinical symptoms can range in severity from headache and tinnitus to thrombohemorrhagic complications. Neurologic symptoms are common at the onset of polycythemia; however, chorea due to PV is a rare complication. We present the case of a 77-year-old female who was referred to our hospital because of choreic movement of the limbs, head and face. She was diagnosed with JAK2V617F mutation-positive PV. Her chorea was completely resolved by phlebotomy combined with hydroxyurea and aspirin.

Mushroom Poisoning by Podostroma cornu-damae: A Case Report and Review of the Literature

Podostroma cornu-damae is a rare species of fungus belonging to the Hyocreaceae family. Its fruit body is highly toxic, as it contains trichothecene mycotoxins. Unfortunately, it highly resembles Ganoderma lucidum and Cordyceps, well-known health foods; this can lead to poisoning. We experienced such a case of a 42-year old man who received mushroom poisoning by injesting Podostroma cornu-damae. The patient was presented with severe pancytopenia and infection. The patient recovered without any complications after conservative care, antibiotics therapy, and granulocyte colony stimulating factor administration. The most common complications of podostroma cornu-damae intoxication were reported pancytopenia, infection, disseminated intravascular coagulation, acute renal failure, etc. It is important to provide enough fluid therapy, use of antibiotics to infection and granulocyte colony stimulating factor administration.

Clinical features and survival outcomes of patients with diffuse large B-cell lymphoma: analysis of web-based data from the Korean Lymphoma Working Party Registry

BACKGROUND: This study aimed to survey the clinical spectrum of diffuse large B-cell lymphoma (DLBCL) in terms of epidemiology, pathologic subtypes, stage, and prognostic index as well as treatment outcomes. METHODS: In 2007-2008, 13 university hospitals evenly distributed in the Korean peninsula contributed to the online registry of DLBCL at www.lymphoma.or.kr and filed a total of 1,665 cases of DLBCL recorded since 1990. RESULTS: Our analysis showed a higher prevalence of DLBCL in male than in female individuals (M:F=958:707), and extranodal disease was more common than primary nodular disease (53% vs. 47%). Among the 1,544 patients who had been treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) or rituximab-CHOP (R-CHOP) therapy with or without radiation, 993 (63.9%) were alive, with 80% free of disease, 417 were dead (26.8%), with 13% free of disease, and 144 (9.3%) were lost to follow-up, with 23% free of disease. Age below 60 years, stage at diagnosis, international prognostic index (IPI) score regardless of age, and addition of rituximab to CHOP therapy in low- and low-intermediate-risk groups according to IPI scores significantly increased survival duration. CONCLUSION: The epidemiology, clinical spectrum, and biological behavior of DLBCL in Korea are similar to those observed in Western countries, and the advent of rituximab improved survival.

Pneumocystis carinii pneumonia in gastric cancer patients without acquired immune deficiency syndrome: 3 cases report and literature review / 대한외과학회지

Pneumocystis carinii pneumonia (PCP) has rarely been reported in solid tumor patients. It is a well-known complication in immunosuppressed states including acquired immune deficiency syndrome and hematologic malignancy. PCP has been reported in solid tumor patients who received long-term steroid treatment due to brain or spinal cord metastases. We found 3 gastric cancer patients with PCP, who received only dexamethasone as an antiemetic during chemotherapy. The duration and cumulative dose of dexamethasone used in each patient was 384 mg/48 days, 588 mg/69 days, and 360 mg/42 days, respectively. These cases highlight that the PCP in gastric cancer patients can successfully be managed through clinical suspicion and prompt treatment. The cumulative dose and duration of dexamethasone used in these cases can be basic data for risk of PCP development in gastric cancer patients during chemotherapy.

Slow, but complete, resolution of mitomycin-induced refractory thrombotic thrombocytopenic purpura after rituximab treatment / 대한혈액학회지

Thrombotic thrombocytopenic purpura (TTP) is a critical complication of treatment with mitomycin C. We retrospectively describe the case of a patient with progressive renal cell carcinoma and mitomycin-induced TTP refractory to plasma exchange and glucocorticoids; we describe the clinical course, successful management of TTP with rituximab, and follow-up of this case. Mitomycin-induced TTP resolved completely by a total of 4 infusions of rituximab 375 mg/m2 on a weekly basis, and it took up to 12 months to obtain a platelet count of >100,000/microL. Rituximab is indicated for the treatment of mitomycin-induced TTP refractory to plasma exchange and glucocorticoids, and it could improve the patient's quality of life despite the presence of underlying malignancy.

A Case of Therapy-related ALL with MLL Gene Rearrangement Following Treatment of Breast Cancer / 대한진단검사의학회지

ALL with MLL gene rearrangement secondary to chemotherapy has been rarely reported. We report a case of therapy-related ALL (t-ALL) with MLL gene rearrangement in a patient who had undergone treatment for breast cancer. A 60-yr-old woman with breast cancer underwent breast-conserving surgery followed by 6 cycles of adjuvant chemotherapy (cyclophosphamide, epirubicin, and fluorouracil) and radiation therapy (dose, 5,040 cGy to the left breast and a 1,000 cGy boost to the tumor bed). A follow-up examination performed 14 months after the chemotherapy revealed no evidence of breast malignancy. However, the patient's complete blood cell count indicated acute leukemia: white blood cell count, 174.1x10(9)/L with 88% blasts; Hb level, 12.5 g/dL; and platelet count, 103.0x10(9)/L. Examination of the bone marrow aspirate smear revealed a high percentage of blasts (85.1% of all nucleated cells); the blasts showed a pro-B immunophenotype and were positive for CD19, CD79a, HLA-DR, CD34, and terminal deoxynucleotidyl transferase (TdT). Cytogenetic and FISH analyses revealed t(4;11)(q21;q23) and MLL gene rearrangement, respectively. The patient received induction chemotherapy with cyclophosphamide, vincristine, doxorubicin, and dexamethasone and achieved complete remission. Following consolidation chemotherapy, she underwent allogenic peripheral blood stem cell transplantation and has been clinically stable. To our knowledge, this is the first reported case of t-ALL with MLL gene rearrangement following treatment of breast cancer in Korea.

A Case of Acute Lymphoblastic Leukemia Accompanied with Lactic Acidosis and Kidney Enlargement / 대한혈액학회지

There have been several reported cases of acute lymphoblastic leukemia with severe lactic acidosis in adults. In these cases, kidney and liver enlargement that was caused by leukemic infiltration frequently accompanied the acute lymphoblastic leukemia and severe lactic acidosis. Chemotherapy is the only treatment that can rapidly correct the lactic acidosis and normalize the liver and kidney enlargement. We report here on a case of acute lymphoblastic leukemia that was accompanied with severe lactic acidosis and kidney enlargement.

Blunted erythropoietin response: the common findings in various anemic patients / 대한내과학회지

BACKGROUND/AIMS: The characteristics of erythropoietin response in patients suffering with anemia of chronic disease and in the patients with various other anemias are poorly defined. Thus, we evaluated the clinical factors that influence the erythropoietin response. METHODS: We enrolled the anemic patients (hemoglobin <13 g/dL for males and <12 g/dL for females) who visited the Hematology-Oncology department of Konkuk University Hospital from Mar 2006 to April 2007. The laboratory tests, including the complete blood count, serum ferritin, serum vitamin B12/folate, the peripheral blood morphology and serum erythropoietin, were done. The erythropoietin response to anemia was assessed by the ratio of the log of the measured erythropoietin to the log of the expected erythropoietin. RESULTS: A total of 161 patients, including 42 iron-deficiency anemia (IDA) patients, were analyzed. 119 non-IDA patients were diagnosed with infection (n=46), chronic renal failure (n=27), cancer (n=20), heart failure (n=12), or with other diseases (n=14). Except for the cancer patients, all the patients with other diseases showed a blunted erythropoietin response in comparison with the IDA patients (p=0.000). Among the non-IDA patients, those patients older than 65 years showed more blunted erythropoietin response than did the younger patients (p=0.01), and the diabetics without renal dysfunction also tended to respond better to erythropoietin than did the non-diabetics (p=0.055). CONCLUSION: A blunted erythropoietin response was observed in most of the anemic patients in our study. Old age and diabetes may further blunt the erythropoietin response. The feasibility of erythropoietin testing and supplementation treatment in these patients merits further evaluation.

A Case of Essential Thrombocythemia Diagnosed During Pregnancy / 대한산부인과학회지

Essential thrombocythemia (ET) is a chronic myeloproliferative disease characterized by a markedly elevated platelet count in the peripheral blood due to excessive proliferation of bone marrow megakaryocytes. When the disease affects women during pregnancy, an adverse obstetric outcome is possible: miscarriages, intrauterine growth restriction, preterm delivery, intrauterine fetal death, preeclampsia. Maternal complications, both thrombotic and hemorrhagic, were reported relatively infrequently. Various treatments as acetylsalicylic acid, hydroxyurea, anagrelide, heparin, interferon-alpha and plateletpheresis have been proposed to improve the pregnancy. Our case was a 38 years old multiparous women at 37 weeks of gestation with preeclampsia, intrauterine growth restriction. Under the impression of oligohydramnios and fetal distress, an emergency cesarean section was performed under epidural anesthesia. During cesarean section, sudden cardiac arrest with unknown cause was developed, and successful resuscitation was done. After cesarean section, patient continued to elevate platelet count. So bone marrow aspiration and biopsy were performed and showed essential thrombocythemia. We report a case of essential thrombocythemia diagnosed during pregnancy with brief review of the literature.

Pulmonary Complications After Hematopoietic Stem Cell Transplantation

Despite advanced effective prophylaxes, pulmonary complications still occur in a high proportion of all hematopoietic stem cell recipients, accounting for considerable morbidity and mortality. The aim of our study was to describe the causes, incidences and mortality rates secondary to pulmonary complications and risk factors of such complications following hematopoietic stem cell transplantation (HSCT). We reviewed the medical records of 287 patients who underwent either autologous or allogeneic HSCT for hematologic disorders from February 1996 to October 2003 at Samsung Medical Center (134 autografts, 153 allografts). The timing of pulmonary complications was divided into pre-engraftment, early and late period. The spectrum of pulmonary complications included infectious and non-infectious conditions. 73 of the 287 patients (25.4%) developed pulmonary complications. Among these patients, 40 (54.8%) and 29 (39.7%) had infectious and non-infectious conditions, respectively. The overall mortality rate from pulmonary complications was 28.8%. Allogeneic transplant, grade II-IV acute graft-versus-host disease (GVHD) and extensive chronic GVHD were the risk factors with statistical significance for pulmonary complications after HSCT. The mortality rates from pulmonary complications following HSCT were high, especially those of viral and fungal pneumonia, diffuse alveolar hemorrhage and idiopathic pneumonia syndrome.

Dendritic Cell Based Cancer Immunotherapy: in vivo Study with Mouse Renal Cell Carcinoma Model

BACKGROUND: As a potent antigen presenting cell and a powerful inducer of antigen specific immunity, dendritic cells (DCs) are being considered as a promising anti-tumor therapeutic module. The expected therapeutic effect of DCs in renal cell carcinoma was tested in the mouse model. Established late-stage tumor therapeutic (E-T) and minimal residual disease (MRD) model was considered in the in vivo experiments. METHODS: Syngeneic renal cell carcinoma cells (RENCA) were inoculated either subcutaneously (E-T) or intravenously (MRD) into the Balb/c mouse. Tumor cell lysate pulsed-DCs were injected twice in two weeks. Intraperitoneal DC injection was started 3 week (E-T model) or one day (MRD model) after tumor cell inoculation. Two weeks after the final DC injection, the tumor growth and the systemic immunity were observed. Therapeutic DCs were cultured from the bone marrow myeloid lineage cells with GM-CSF and IL-4 for 7 days and pulsed with RENCA cell lysate for 18 hrs. RESULTS: Compared to the saline treated group, tumor growth (E-T model) or formation (MRD model) was suppressed in pulsed-DC treated group. RENCA specific lymphocyte proliferation was observed in the RENCA tumor-bearing mice treated with pulsed-DCs. Primary cytotoxic T cell activity against RENCA cells was increased in pulsed-DC treated group. CONCLUSION: The data suggest the possible anti-tumor effect of cultured DCs in established or minimal residual disease/metastasis state of renal cell carcinoma. Systemic tumor specific immunity including cytotoxic T cell activity was modulated also in pulsed-DC treated group.

Significance of Endoscopy in the Investigation of Iron Deficiency Anemia / 대한소화기내시경학회지

BACKGROUND/AIMS: There is no consensus for the role of endoscopy in the etiologic investigation of iron deficiency anemia (IDA) in Korea. We carried out a retrospective study to evaluate the role of esophagogastroduodenoscopy (EGD) and colonoscopy for their etiologic diagnosis in IDA. METHODS: Between January 1998 and September 2003, 129 patients (male:female=19:110, mean age=43.6) had been grew EGD and colonoscopy for exam for the investigation of IDA at Kangbuk Samsung Hospital and Samsung Medical Center Medical records were retrospectively reviewed: RESULTS: Significant findings were found in 8.5% (11 cases: grade B reflux esophagitis by L.A. classification (1), angiodysplasia (1), severe erosive gastritis (2), and gastric ulcer (2) and duodenal ulcer (5), while 70% (89 cases) showed some abnormality in EGD examination. Significant findings were seen in 11% (14 cases: polyps >1 cm (2), angiodysplasia (1), bleeding hemorrhoids (5), inflammatory bowel disease (4) and colon cancer (2)), among 36% (46 cases) of patients with some abnormality in colonoscopy. CONCLUSIONS: Gastrointestinal lesions were frequently found in patients with IDA and significant proportion of them could be the source of blood loss. Therefore, EGD and colonoscopy should be included in the evaluation of IDA in Korea.

The Efficacy and Safety of DA-3030 (Recombinant Human Granulocyte Colony-Stimulating Factor) in Neutropenia after the Remission Induction Chemotherapy in Patients with Acute Myelogenous Leukemia / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study was conducted to determine the efficacy and safety of DA-3030 (a recombinant methionyl human granulocyte colony-stimulating factor, rhG-CSF), after remission induction chemotherapy, in patients with acute myelogenous leukemia (AML). MATERIALS AND METHODS: After the remission induction chemotherapy, with idarubicin (12 mg/m2/day for 3 days) and cytarabine (200 mg/m2/day for 7 days), 26 patients with newly diagnosed AML were assigned to receive DA-3030 (200mug/m2/day), starting 24 hours after the completion of the remission induction chemotherapy, until their neutrophil count recovered to greater than 1, 000/muL for 3 consecutive days. RESULTS: The median time from the initiation of the chemotherapy to the neutrophil recovery of 1, 000/muL was 21 days (range, 12~41). Treatment with DA-3030 was not associated with significant adverse side effects. The most frequently reported side effects were musculo-skeletal pain (13%) and headache (13%). CONCLUSION: The DA-3030 is a safe rhG-CSF for the treatment of neutropenia after remission induction chemotherapy in patients with AML.