Busulfan, Melphalan, and Etoposide (BuME) Showed an Equivalent Effect to Busulfan, Cyclophosphamide, and Etoposide (BuCE) as Conditioning Therapy for Autologous Stem Cell Transplantation in Patients with Relapsed or High-Risk Non-Hodgkin’s Lymphoma: A Multicenter Randomized Phase II Study bythe Consortium for Improving Survival of Lymphoma (CISL) / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is the standard management for relapsed or high-risk non-Hodgkin’s lymphoma (NHL). We reported the busulfan, melphalan, and etoposide (BuME) conditioning regimen was effective in patients with relapsed or high-risk NHL. Moreover, the busulfan, cyclophosphamide, and etoposide (BuCE) conditioning regimen has been used widely in ASCT for NHL. Therefore, based on these encouraging results, this randomized phase II multicenter trial compared the outcomes of BuME and BuCE as conditioning therapies for ASCT in patients with NHL. @*Materials and Methods@#Patients were randomly assigned to receive either BuME (n=36) or BuCE (n=39). The BuME regimen was comprised of busulfan (3.2 mg/kg/day, intravenously) administered on days –7, –6, and –5, etoposide (400 mg/m2 intravenously) on days –5 and –4, and melphalan (50 mg/m2/day intravenously) on days –3 and –2. The BuCE regimen was comprised of busulfan (3.2 mg/kg/day intravenously) on days –7, –6, and –5, etoposide (400 mg/m2/day intravenously) on days –5 and –4, and cyclophosphamide (50 mg/kg/day intravenously) on days –3 and –2. The primary endpoint was 2-year progression-free survival (PFS). @*Results@#Seventy-five patients were enrolled. Eleven patients (30.5%) in the BuME group and 13 patients (33.3%) in the BuCE group had disease progression or died. The 2-year PFS rate was 65.4% in the BuME group and 60.6% in the BuCE group (p=0.746). There were no non-relapse mortalities within 100 days after transplantation. @*Conclusion@#There were no significant differences in PFS between the two groups. Therefore, busulfan-based conditioning regimens, BuME and BuCE, may be important treatment substitutes for the BCNU-containing regimens.

Safety and efficacy of nilotinib in adult patients with chronic myeloid leukemia: a post-marketing surveillance study in Korea

Background@#Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. @*Methods@#An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. @*Results@#During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). @*Conclusion@#This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.

A Randomized, Double-Blind, Placebo-Controlled Study of the Safety and Efficacy of Olanzapine for the Prevention of Chemotherapy-Induced Nausea and Vomiting in Patients Receiving Moderately Emetogenic Chemotherapy: Results of the Korean South West Oncolog / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Data on the efficacy of olanzapine in patients receiving moderately emetogenic chemotherapy (MEC) are limited. This study aimed to evaluate and compare the efficacy of olanzapine versus placebo in controlling nausea and vomiting in patients receiving MEC. MATERIALS AND METHODS: We conducted a randomized, double-blind, placebo-controlled study to determine whether olanzapine can reduce the frequency of chemotherapy-induced nausea and vomiting (CINV) and improve the quality of life (QOL) in patients receiving palonosetron and dexamethasone as prophylaxis for MEC-induced nausea and vomiting. The primary end point was complete response for the acute phase (0-24 hours after chemotherapy). The secondary end points were complete response for the delayed (24-120 hours) and overall phase (0-120 hours), proportion of significant nausea (visual analogue scale ≥ 25 mm), use ofrescue medications, and effect on QOL. RESULTS: Fifty-six patients were randomized to the olanzapine (n=29) and placebo (n=27) groups. Complete response rates were not significantly different between the olanzapine and placebo groups in the acute (96.5% vs. 88.0%, p=0.326), delayed (69.0% vs. 48.0%, p=0.118), and overall phases (69.0% vs. 48.0%, p=0.118). However, the percentage of patients with significant nausea (17.2% vs. 44.0%, p=0.032) and the use of rescue medications (0.03±0.19 vs. 1.88±2.88, p=0.002) were lower in the olanzapine group than in the placebo. Furthermore, the olanzapine group demonstrated better QOL (p=0.015). CONCLUSION: Olanzapine combined with palonosetron and dexamethasone significantly improved QOL and vomiting control among previously untreated patients receiving MEC, although the efficacy was limited to the reduction of the frequency of CINV.

Acute Myeloid Leukemia with the 11q23 Rearrangement in a Patient with Klinefelter Syndrome / 대한내과학회지

Klinefelter syndrome is usually characterized by eunuchoidism, gynecomastia, small testes, infertility, elevated gonadotropins, mental retardation, and a constitutional extra X chromosome. Several reports have suggested an association between leukemia and Klinefelter syndrome, although two cohort studies failed to show a clear association between the two. We report the first Korean case of acute myeloid leukemia with the 11q23 rearrangement in a 27-year-old man with Klinefelter syndrome.

Bisphosphonate-related osteonecrosis of the jaw in a multiple myeloma patient: A case report with characteristic radiographic features

A 59-year-old male who had suffered from multiple myeloma for nine years and had been administered bisphosphonates for seven years visited a dental hospital for pain relief due to extensive caries in his left maxillary molars. The molars were extracted, leaving an exposed wound for three months. The radiograph showed sequestra formation and irregular bone destruction in the left maxilla. Sudden pain and gingival swelling in the right mandibular molar area occurred six months later. The interseptum of the right lower second molar was observed to be necrotic during surgery. These findings coincided with the features of bisphosphonate-related osteonecrosis of the jaw (BRONJ). In this case, the long intravenous administration of bisphosphonates and tooth extraction were likely the etiologic factors of BRONJ in a patient with multiple myeloma; moreover, the bilateral occurrence of BRONJ is a characteristic feature.

Hypoglycemic Coma in a Patient with Metastatic Renal Cell Carcinoma Treated with Sunitinib / 대한내과학회지

We present a patient with type 2 diabetes mellitus and metastatic renal cell carcinoma who developed severe hypoglycemia and metabolic encephalopathy after sunitinib treatment. Sunitinib, a multi-target tyrosine kinase inhibitor, is used to treat metastatic renal cell carcinoma. Sunitinib-induced hypoglycemia has been reported and there are rare case reports of severe hypoglycemia due to sunitinib. Therefore, glycemic control should be monitored closely in diabetic patients treated with sunitinib.

Clinical features and treatment outcomes in patients with mantle cell lymphoma in Korea: Study by the Consortium for Improving Survival of Lymphoma

BACKGROUND: We investigated the clinical features and treatment outcomes of patients with mantle cell lymphoma (MCL) in Korea. METHODS: We retrospectively analyzed the clinical characteristics and prognosis of 131 patients diagnosed with MCL between January 2004 and December 2009 at 15 medical centers in Korea; all patients received at least 1 chemotherapeutic regimen for MCL. RESULTS: The median age for the patients was 63 years (range, 26-78 years), and 77.9% were men. A total of 105 patients (80.1%) had stage III or IV MCL at diagnosis. Fifty-two patients (39.7%) were categorized with high- or high-intermediate risk MCL according to the International Prognostic Index (IPI). Eighteen patients (13.7%) were in the high-risk group according to the simplified MCL-IPI (MIPI). The overall incidence of extranodal involvement was 69.5%. The overall incidence of bone marrow and gastrointestinal involvements at diagnosis was 41.2% and 35.1%, respectively. Cyclophosphamide, doxorubicin, vincristine, prednisolone, and rituximab were used frequently as the first-line treatment (41.2%). With a median follow-up duration of 20.0 months (range, 0.2-77.0 months), the overall survival (OS) at 2 years was 64.7%, while the event-free survival (EFS) was 39.7%. Multivariate analysis showed that the simplified MIPI was significantly associated with OS. However, the use of a rituximab-containing regimen was not associated with OS and EFS. CONCLUSION: Similar to results from Western countries, the current study found that simplified MIPI was an important prognostic factor in Korean patients with MCL.

Gastric Mucosa-Associated Lymphoid Tissue Lymphoma Followed by Primary Central Nervous System Lymphoma

Mucosa-associated lymphoid tissue (MALT) lymphoma is one of the most common lymphomas and accounts for about 7% of all newly diagnosed non-Hodgkin's lymphoma (NHL). The clinical course of MALT lymphoma is relatively indolent and, in the majority of cases (50%), the lymphoma arises within the stomach. Primary central nervous system lymphoma (PCNSL), an uncommon variant of extranodal NHL, can affect any part of the neuraxis, including the eyes, brain, leptomeninges, or spinal cord. Herein, we present a rare case of PCNSL, which occurred one year after radiochemotherapy of gastric MALT lymphoma. A 62-year-old man presented with a 3-day history of left facial palsy. One year ago, he underwent antibiotic eradication therapy of Helicobacter pylori, local stomach fractional radiotherapy, and chemotherapy for gastric MALT lymphoma. Magnetic resonance imaging revealed a strong enhancing solid mass in the right frontal lobe. The tumor was completely removed, and the histological diagnosis of PCNSL developing from diffuse large B-cell lymphoma was made. Although elucidating the correlation between the first gastric MALT lymphoma and the second PCNSL seemed difficult, we have postulated and discussed some possible pathogeneses, together with a review of literature.

The Effect of an Ectopic Overexpression of MnSOD in Mouse Hematopoietic Stem Cells / 대한혈액학회지

BACKGROUND: Intracellular reactive oxygen species (ROS) have dual effects depending on their cellular level. ROS act as secondary messengers at a low concentration, although ROS exhaust the hematopoietic stem cell (HSC) compartment at a higher oxidized state. So, we investigated whether maintaining a low level of ROS could preserve the hematopoietic stem cell function according to the MnSOD over expression. METHODS: Human MnSOD cDNA was introduced into mouse HSCs and progenitor cells by using a MSCV-PGK-GFP retrovirus. The hematopoietic function of over-expressing MnSOD was evaluated in vitro on a colony-forming cell assay and in vivo in a competitive transplantation model. MnSOD-transduced, lineage negative, GFP+B6.SJL (CD45.1+) mouse bone marrow cells were transplanted into lethally irradiated C57BL/6J (CD45.2+) mice in competition with CD45.1/45.2 double positive bone marrow mononuclear cells. We also measured the basal mRNA levels of antioxidants, including MnSOD, catalase and cellular glutathione peroxidase (GPx1), of C57BL/6J HSCs. RESULTS: On the colony-forming cell assay, a MnSOD over expression significantly preserved the CFU-M with irradiation as compared with the mice without irradiation. HSCs with an MnSOD over expression showed a tendency for higher engraftment ability on the competitive transplantation assay even after 200 cGy re-irradiation, and we observed a significantly higher myeloid differentiation potential after the second serial transplantation. The basal mRNA levels of MnSOD and catalase were less than 1~2% and 2~5%, respectively, in the long-term and short-term HSCs, respectively, and these cells didn't activate in spite of radiation stress. CONCLUSION: These results show that only an over expression of MnSOD without downstream catalase activation can not augment the mouse hematopoietic stem cell repopulation activity.

Assessment of Tumor Response to Therapy in Lymphoma Using (18)F-FDG PET: Diagnostic Performance of (18)F-FDG PET and Interval Likelihood Ratio / 핵의학분자영상

In this paper, the authors intended to summarize briefly the features of lymphoma with regard to (18)F-FDG PET for assessment of tumor response to therapy, to describe why assessment of treatment response should be performed, to review what method so far has been used in monitoring treatment response, to discuss what limitations of morphologic imaging criteria for assessing tumor response are, in compared with (18)F-FDG PET, and to introduce recently proposed criteria for assessing tumor response in malignant lymphoma. And also the authors emphasize the need to understand the characteristics of diagnostic performance of (18)F-FDG PET in several clinical settings in order to interpret (18)F-FDG PET results appropriately, and to encourage the use of interval likelihood ratio to enhance clinical implications of test results which, in turns, allows referring physicians to understand the meaning of interpretation with easy. Until recently, treatment response has been assessed according to the morphologic criteria. Metabolic imaging with (18)F-FDG PET was adopted to have important role for treatment assessment in IWC+PET criteria proposed recently by IHP. To accomplish this role, we should perform and interpret (18)F-FDG PET according to IWC+PET criteria. It is important for referring physicians to understand the various limitations of (18)F-FDG PET and pitfalls in PET interpretation, and to understand that clinical information are needed by nuclear medicine physicians to optimize the interpretation of (18)F-FDG PET.

FLT3 Internal Tandem Duplication in Acute Myeloid Leukemia with Normal Karyotype / 대한혈액학회지

BACKGROUND: The presence of FLT3 internal tandem dupulication (FLT3/ITD) in patients with acute myeloid leukemia (AML) with normal karyotype was investigated in order to evaluate its clinical and prognostic significance. METHODS: The FLT3/ITD was studied by PCR assay in bone marrow samples obtained from 123 patients at diagnosis. Ninety patients who received intensive induction chemotherapy were evaluated. RESULTS: Of total 123 patients, forty-seven (38.2%) demonstrated the aberrant FLT3/ITD. Patients with FLT3/ITD had significantly higher leukocyte counts at presentation than did patients without FLT3/ITD (P=0.04). By multivariate analysis, the FLT3/ITD was an independent prognostic factor of leukemic-free survival (LFS) (P=0.01) in AML patients with normal karyotype. CONCLUSION: This study demonstrated that the presence of the FLT3/ITD was a significant factor for poor prognosis in AML patients with normal karyotype.

Parvovirus B19 infection-associated hemophagocytic lymphohistiocytosis / 대한내과학회지

Hemophagocytic lymphohistiocytosis is an unusual syndrome that's characterized by fever, hepatosplenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia and pathologic finding of hemophagocytosis in the bone marrow and other tissues. A previously healthy 16-year-old male was admitted because of fever. The cervical and axillary lymph nodes, liver and spleen were palpable. CBC revealed pancytopenia with a decreased reticulocyte count, and the bone marrow aspiration smear showed the presence of giant pronormoblasts with intranuclear inclusion bodies and an increased number of histiocytes that were engulfing blood cell. IgM antibody against Parvovirus B19 and PCR for Parvovirus B19 were positive. Thus, he was diagnosed with hemophagocytic lymphohistiocytosis that was caused by Parvovirus B19 infection. Parvovirus B19 is an agent rarely associated with hemophagocytic lymphohistiocytosis, and in most cases it occurs in those patients with an underlying disease. We report here on a case of hemophagocytic lymphohistiocytosis associated with acute Parvovirus B19 infection in healthy male.

Reduced Intensity Conditioning Regimen Followed by Allogeneic Peripheral Blood Stem Cell Transplantation for Acute Panmyelosis with Myelofibrosis / 대한혈액학회지

A 44-year-old male presented with a month history of exertional dyspnea and dizziness. A peripheral blood smear revealed a pancytopenia with 3% of blasts. We were not able to obtain a bone marrow aspirate, but a biopsy specimen showed hypercellularity, proliferation of trilineage cell lines (panmyelosis) with extensive myelofibrosis, and clusters of immature cells at the paratrabecular area. After remission induction therapy with idarubicin 12mg/m2 (D1-3) and cytosine arabinoside 100mg/m2 (D1-7), the bone marrow blast count was decreased, but the marrow fibrosis and pancytopenia persisted. Peripheral blood stem cell transplantation from his HLA-matched brother was performed after administering fludarabine 30mg/m2 for 5 days and busulfan 3.2mg/kg for 2 days. Early engraftment occurred and the bone marrow reticulin fibrosis disappeared. Full-donor chimerism was demonstrated at day 22 by performing short tandem repeats analysis and this was maintained for 1 year. The patient has survived 20 months after transplantation without any complication.

Oral Mecobalamin Treatment in Cobalamin Deficiency / 대한혈액학회지

BACKGROUND: The traditional treatment of cobalamin deficiency anemia is performed by intramuscular injections. However, it has been suggested that oral replacement of cobalamin is also effective as an intramuscular injection. We studied the effectiveness of oral mecobalamin treatment in patients with cobalamin deficiency. METHODS: Patients with newly diagnosed cobalamin deficiency (<200 pg/mL) or who were previously maintained on intramuscular injection were given 2,000 microgram of oral mecobalamin daily. RESULTS: Sixteen patients were enrolled. The common causes of cobalamin deficiency were total gastrectomy (75%) and pernicious anemia (12.5%). Twelve patients received oral mecobalamin, except for four patients who were lost from follow-up after initial diagnosis. The mean pretreatment values of serum cobalamin and hemoglobin level were 58.3+/-21.9pg/mL and 8.1+/-1.9g/dL, respectively. After one, two, and six months of oral therapy, the respective mean values were 1,691.8+/-260.4pg/mL, 1,085.8+/-1,110.3pg/mL and 990.2+/-249.8pg/mL of serum cobalamin, and 10.4+/-1.3g/dL, 11.3+/-2.2g/dL and 12.1+/-2.3g/dL of hemoglobin. Initially elevated serum homocysteine were normalized after one month of oral therapy. Symptoms such as glossitis were relieved rapidly by oral treatment. CONCLUSION: High-dose oral mecobalamin supplement was a simple and effective treatment in patients with cobalamin deficiency, especially in total gastrectomized patients.

Short-Term Effect of High Dose of Vitamin C on Coronary Flow Velocity and Coronary Flow Reserve in Healthy Young Non-Smoker Men

BACKGROUND AND OBJECTIVES: Vitamin C, water-soluble antioxidant, has been reported to restore coronary microcirculatory responsiveness and impaired coronary flow reserve in smokers. However, the effect of high dose of vitamin C on coronary circulation is unclear in nonsmokers. METHODS: We used transthoracic echocardiography to measure the coronary flow reserve, an integrated measure of coronary flow in 20 male healthy nonsmokers (26+/-3 years) before and after administration of the high dose of vitamin C. RESULTS: The coronary peak diastolic velocity was increased by 14.8% after administration of antioxidant vitamin C, whereas the coronary flow reserve did not changed. CONCLUSION: High dose of vitamin C acutely increases the coronary flow velocity without restoration of coronary flow reserve in male healthy nonsmokers.

A Case of Acute Panmyelosis with Myelofibrosis / 대한진단검사의학회지

We experienced a case of acute panmyelosis with myelofibrosis, one of the acute myeloblastic leukemia (AML) subtypes according to WHO classification. A 44 year old man presented with a laborious dyspnea, dizziness, and generalized weakness. On admission, the peripheral blood revealed pancytopenia (hemoglobin 4.0 g/dL, WBC 2, 300/microliter, platelet 92, 000/microliter) with leukoerythroblastosis. The bone marrow (BM) aspirate yielded inadequate material but histological sections showed hyper-cellularity, proliferation of trilineage cell lines (panmyelosis) with extensive myelofibrosis, and clusters of immature cells at paratrabecular area. On ultrasonographic examination, no evidence of hepato-splenomegaly or any other abnormalities were noted. The follow-up BM study after the chemotherapy with Ara C for 7 days and idarubicin for 3 days showed no significant changes in pancytopenia and myelofibrosis but revealed a significant decrease in BM cellularity and blasts. We review and report the literature on acute panmyelosis with myelofibrosis.

A case of paroxysmal nocturnal hemoglobinuria with recurrent acute renal failure / 대한내과학회지

Paroxysmal nocturnal hemoglobinuria (PNH) is a acquired clonal disorder of the hematopoietic stem cells characterized by chronic intravascular hemolysis, venous thrombosis, deficient hematopoiesis. Kidney involvement is usually benign and secondary to chronic deposition of hemosiderin. But, acute renal failure may rarely occur in association with a hemolytic crisis or thrombotic complication. Hemolytic crisis is precipitated by nonspecific factors, such as infection, surgery and transfusion. A 69-year- old man was admitted to our hospital who developed acute renal failure after operation of anal fistula. He was diagnosed with PNH accompanied with deep vein thrombosis later. After being treated by hemodialysis and oral low dose steroid, he was discharged with full recovery of renal function. But, he frequently was developed acute renal failure with crisis of PNH despite taking low dose steroid. So, we report a case of PNH with recurrent acute renal failure without precipitating factors.

A Case of Primary Pericardial Undifferentiated Sarcoma

Primary pericardial sarcomas are extremely rare. The authors report a case of a 46-yr-old woman in whom a large mediastinal mass was discovered. The patient presented with cough, dyspnea, and orthopnea. Diagnostic investigations, such as echocardiography, computed tomography, and exploratory thoracotomy provided the evidence of a large mass in the mediastinum, attached by a broad base to the superior portion of the pericardium. A excisional biopsy was performed, and histologic examination of a biopsy specimen showed undifferentiated sarcoma. However, the complete removal of the mass was impossible due to adhesion to the adjacent great vessels. After the completion of the chemotherapy the patient was completely asymptomatic. However, follow-up transesophageal echocardiography showed a residual 3x4 cm-sized mass. The patient received the radiotherapy with a total dose of 55 Gy over 6 weeks. At present, there is no evidence of disease progression.

A Case of Complete Heart Block Complicating Bacterial Endocarditis

Active infective endocarditis, involving native, is often complicated by conduction abnormalities. These conduction disturbances are considered to represent an extension of the infection from the valve to the annulus, and to the surrounding myocardium. We describe a case of a 59-year-old woman who presented with dyspnea due to staphylococcal endocarditis, which was complicated by a complete heart block.

A case of pernicious anemia with early gastric cancer / 대한내과학회지

Pernicious anemia is caused by the absence of intrinsic factor from autoimmune destruction of parietal cells. Patients with pernicious anemia are predisposed to the development of gastric cancer. We report here a case of pernicious anemia with early gastric cancer. A 65 year old woman was presented with severe anemia and glossitis. Her serum cobalamin level was low, and serologic test to anti-intrinsic factor antibody and anti-parietal cell antibody were positive. Gastroscopic examination revealed an early gastric cancer and type A atrophic gastritis. This patient underwent radical subtotal gastrectomy and received daily oral vitamin B12 replacement.