Long-term follow-up results of cytarabine-containing chemotherapy for acute promyelocytic leukemia

Background/Aims@#We evaluated the feasibility and long-term efficacy of the combination of cytarabine, idarubicin, and all-trans retinoic acid (ATRA) for treating patients with newly diagnosed acute promyelocytic leukemia (APL). @*Methods@#We included 87 patients with newly diagnosed acute myeloid leukemia and a t(15;17) or promyelocytic leukemia/retinoic acid receptor alpha (PML-RARα) mutation. Patients received 12 mg/m2/day idarubicin intravenously for 3 days and 100 mg/m2/day cytarabine for 7 days, plus 45 mg/m2/day ATRA. Clinical outcomes included complete remission (CR), relapse-free survival (RFS), overall survival (OS), and the secondary malignancy incidence during a 20-year follow-up. @*Results@#The CR, 10-year RFS, and 10-year OS rates were 89.7%, 94.1%, and 73.8%, respectively, for all patients. The 10-year OS rate was 100% for patients that achieved CR. Subjects were classified according to the white blood cell (WBC) count in peripheral blood at diagnosis (low-risk, WBC < 10,000/mm3; high-risk, WBC ≥ 10,000/mm3). The low-risk group had significantly higher RFS and OS rates than the high-risk group, but the outcomes were not superior to the current standard treatment (arsenic trioxide plus ATRA). Toxicities were similar to those observed with anthracycline plus ATRA, and higher than those observed with arsenic trioxide plus ATRA. The secondary malignancy incidence after APL treatment was 2.7%, among the 75 patients that achieved CR, and 5.0% among the 40 patients that survived more than 5 years after the APL diagnosis. @*Conclusions@#Adding cytarabine to anthracycline plus ATRA was not inferior to anthracycline plus ATRA alone, but it was not comparable to arsenic trioxide plus ATRA. The probability of secondary malignancy was low.

Therapy-related acute promyelocytic leukemia in plasma cell myeloma treated with melphalan: a case report and literature review

No abstract available.

Crohn's disease and smoldering multiple myeloma: a case report and literature review

Crohn's disease (CD) is a chronic inflammatory bowel disease (IBD) that presents with abdominal pain, weight loss, and diarrhea. Although the etiology has not been fully elucidated, both environmental and genetic causes are known to be involved. In chronic inflammatory conditions such as IBD, B lymphocytes are chronically stimulated, and they induce monoclonal expansion of plasma cells, sometimes resulting in monoclonal gammopathy of undetermined significance. Immunomodulators that are commonly used to control inflammation, such as tumor necrosis factor-α (TNF-α) blockers could increase the possibility of hematologic malignancy. The pathogenesis of multiple myeloma in association with TNF-α inhibitor therapy is attributed to decreased apoptosis of plasma cell populations. Here, we describe a case of a 36-year-old male patient who was diagnosed with immunoglobulin A subtype smoldering multiple myeloma during the treatment for CD with infliximab and adalimumab. We report this case along with a review of the literature on cases of multiple myeloma that occurred in conjunction with CD.

Chronic eosinophilic leukemia with FIP1L1-PDGFRA rearrangement

No abstract available.

Plasma Cell Myeloma Initially Presenting as Lung Cancer

No abstract available.

The e8a2 fusion transcript in B lymphoblastic leukemia with BCR-ABL1 rearrangement / 대한혈액학회지

No abstract available.

Detection of RUNX1-MECOM Fusion Gene and t(3;21) in a Very Elderly Patient Having Acute Myeloid Leukemia with Myelodysplasia-Related Changes

An 87-yr-old woman was diagnosed with AML with myelodysplasia-related changes (AML-MRC). The initial complete blood count showed Hb level of 5.9 g/dL, platelet counts of 27x10(9)/L, and white blood cell counts of 85.33x10(9)/L with 55% blasts. Peripheral blood samples were used in all the tests, as bone marrow examination could not be performed because of the patient's extremely advanced age and poor general health condition. Flow cytometric analysis, chromosome analysis, FISH, and reverse transcriptase-PCR (RT-PCR) results indicated AML-MRC resulting from t(3;21) with the RUNX1-MECOM fusion gene. To our knowledge, this is the second most elderly de novo AML patient associated with t(3;21) to be reported.

Long-term outcomes of a 5-year follow up of patients with immune thrombocytopenic purpura after splenectomy / 대한혈액학회지

BACKGROUND: The long-term outcomes of adult patients with immune thrombocytopenic purpura (ITP) after splenectomy are not clear. METHODS: We retrospectively analyzed 31 patients who underwent splenectomy after diagnosis of ITP at our institution between 1990 and 2009. Long-term follow-up was defined as a follow-up that lasted 1 year or more from splenectomy to the last follow-up. RESULTS: The overall response rate to splenectomy was 84%. However, the response rate at 6 and 12 months decreased to 77% and 68%, respectively. During the 6 years of median follow-up after splenectomy, 11 patients (35%) relapsed. The long-term response rate was 55%. The long-term follow-up of 26 patients after responding to splenectomy showed that the median time from splenectomy to relapse was 19 months in the partial response (PR) group; however, there was no relapse after 9 months in the complete response (CR) group. Variables, including age, were not predictive of the long-term response after splenectomy. Additional treatment in patients who did not respond or relapsed after splenectomy was mostly effective. After a median follow-up of 7 years (range: 1-25 years) from the diagnosis, there were 2 deaths, including one due to spontaneous bleeding after repair of duodenal ulcer perforation. CONCLUSION: Although splenectomy is safe and effective, the response rate after splenectomy continuously decreases over time. The duration of response is different between the patients that achieved CR and those that achieved PR. Factors, including age, were not predictors of a response to splenectomy.

Korean Patients with Superwarfarin Intoxication and Their Outcome

This observational study aimed at evaluating recent superwarfarin intoxication of Korean patients. Ten patients were diagnosed as or highly suspicious for superwarfarin intoxication. Case report forms described by attending hematologists of the patients were collected and analyzed. Bleeding symptoms were varied among the patients. Patients uniformly showed prolonged prothrombin time (PT) and activated thromboplastin time (aPTT) with decreased activity of vitamin K dependent coagulation factors. Positive serum brodifacoum test results in 4 of 5 requested patients contributed to confirmatory diagnosis. Psychiatric interview revealed an attempted ingestion in one patient. High dose vitamin K1 therapy promptly corrected prolonged PT and aPTT, but hasty discontinuation caused repeated bleeding diathesis in 6 patients. Route of intoxication was unknown or not definite among 8 of 10 patients. Three patients had a possibility of environmental exposure considering their occupations: there might be intoxication by transdermal absorption or inhalation. Therefore, high dose and prolonged use of vitamin K1 therapy is necessary for effective detoxification. Further detailed investigation on environmental exposure and efforts to improve availability of the blood level test in clinic are requested.

Korean Guidelines for the Prevention of Venous Thromboembolism

This guideline focuses on the primary prevention of venous thromboembolism (VTE) in Korea. The guidelines should be individualized and aim at patients scheduled for major surgery, as well as patients with a history of trauma, high-risk pregnancy, cancer, or other severe medical illnesses. Currently, no nation-wide data on the incidence of VTE exist, and randomized controlled trials aiming at the prevention of VTE in Korea have yielded few results. Therefore, these guidelines were based on the second edition of the Japanese Guidelines for the Prevention of VTE and the eighth edition of the American College of Chest Physicians (ACCP) Evidenced-Based Clinical Practice Guidelines. These guidelines establish low-, moderate-, and high-risk groups, and recommend appropriate thromboprophylaxis for each group.

Complete Hematologic Response and Cytogenetic Remission after Imatinib and Dexamethasone Treatment of a Ph+ Precursor B-cell Acute Lymphoblastic Leukemia in Renal Transplantation Patient / 대한혈액학회지

In this report, we present a case of a patient with Philadelphia chromosome-positive (Ph+) B-cell acute lymphoblastic leukemia after renal transplantation. The patient, a 65-year-old man, had received a kidney transplantation 20 years prior to diagnosis with Ph+ precursor B-cell ALL. Because he was refractory to intensive chemotherapy and had refused to receive additional intensive chemotherapy, he was treated with imatinib and dexamethasone. While this patient experienced a complete hematologic and cytogenetic response, he did not show a complete molecular remission. Eighty days after imatinib combination therapy, the patient relapsed and died from intracerebral hemorrhage.

A Case of Cutaneous Plasmacytoma Treated with Bortezomib and Radiotherapy / 대한피부과학회지

Multiple myeloma is a hematologic malignancy characterized by the proliferation of monoclonal plasma cells that produce monoclonal immunoglobulins. Cutaneous involvement is very uncommon in patients with multiple myeloma. It usually appears late in the course of the disease. Bortezomib is a potent proteasome inhibitor, recently introduced in the treatment of multiple myeloma. It has proven to be safe and effective in the treatment of refractory or relapsed multiple myeloma. In this study, we show the high efficacy of a concurrent therapeutic approach with bortezomib and radiation in a patient with a cutaneous plasmacytoma.

Treatment of Bleeding in Hemophilia

The management of hemophilia patients includes the treatment of acute bleeding, prevention of bleeding, and the treatment of complications. Bleeding can be minimized by prophylactic factor maintenance, education, and lifestyle modifications. The complications in hemophilia include hemophilic arthropathy, inhibitor development, liver disease due to transfusion-transmitted infections, etc. Patients can be managed ideally in comprehensive hemophilia care centers. The management of bleeding is most important. Treatment should be given early with an appropriate amount of drugs, according to the extent and site of bleeding. This early treatment is possible by home therapy. Life-threatening bleedings such as bleeding of the central nervous system, throat, or neck should be treated as emergency, immediately before evaluation. Recently, the World Federation of Hemophilia published a guideline for the management of hemophilia, which also suggested a good standard for the care of bleeding patients. In this article, the author introduce coagulation factors available in Korea for the treatment of hemophilia patients, including bypassing agents for inhibitor patients, and discuss practical points for the treatment of hemophilia patients in Korea.

Investigation of Hemostatic Changes in Patients with Sepsis / 대한진단검사의학회지

BACKGROUND: It is known that severe infection and inflammation lead to hemostatic abnormalities. Recently, much attention is focused on the mechanisms of infection or inflammation and on how it plays a central role in effecting the coagulation system. Disseminated intravascular coagulation in particular, is a common phenomenon in patients with sepsis, but the clinical implications of this condition are not clear. Therefore we attempted to evaluate the changes of the coagulation system in patients with sepsis and studied the factors that lead to such changes. METHODS: One hundred one patients diagnosed with sepsis were enrolled in this study. The patients were clinically evaluated for underlying disease and data for inflammatory status and coagulative changes were evaluated retrospectively. RESULTS: The WBC count increased in 76% and decreased in 6% of sepsis patients in comparison to the reference interval. The platelet count decreased in 65.3%. Changes in coagulative tests such as prothrombin time, activated partial thromboplastin time, antithrombin III, and D-dimer were observed in 70.4%, 52.7%, 87.2% and 100% of the patients, respectively. Correlation between ESR and fibrinogen was the highest in relation to the other coagulation factors. CRP also showed the highest correlation with fibrinogen in contrast to the other coagulation factors. CONCLUSIONS: This study confirmed the clear activation of coagulation in patients with sepsis. Of the evaluated factors involved in coagulation and fibrinolysis, fibrinogen showed the highest correlation to indices representing the inflammatory state. However further studies on the anticoagulant pathway are necessary in elucidating this matter.

A Case of Acute Lymphoblastic Leukemia with Maturation / 대한혈액학회지

Acute lymphoblastic leukemia with maturation (ALLm) has different disease characteristics that does typical ALL. ALLm is characterized by an increased number of mature appearing leukemic cells (>20% of ANCs in the BM) having differentiation beyond the prolymphocyte stage according to light microscopic (LM) examination. It also has a worse prognosis than typical ALL. We have recently experienced a case of ALLm and we report on this case along with a literature review. A 36 year old patient showed lymphoblasts and mature appearing leukemic cells that were counted up to 15.8% and 23.0%, respectively, of the WBCs on bone marrow examination. Despite their mature appearance, these cells showed positivity for Tdt, CD10, CD19 and HLA-DR on the immunophenotypic study. Differentiating the mature-appearing leukemic cells from the hematogones or mature lymphocytes is difficult, and only through immunophenotypic examination is it possible to discriminate ALLm from typical ALL. We suggest performing a leukemic marker study that includes CD38 to effectively differentiate mature appearing leukemic cells from hematogones, especially for the follow up of leukemia with mature appearing cells.

Increased ERCC Expression Correlates with Improved Outcome of Patients Treated with Cisplatin as an Adjuvant Therapy for Curatively Resected Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: It has been reported that the overexpression of the excision repair cross-complementing 1 (ERCC1) gene, which is essential for the repair of cisplatin (CDDP)- DNA adducts, negatively influences the effectiveness of CDDP-based therapy for primary gastric cancer. We investigated whether the ERCC1 expression was associated with survival for gastric cancer patients in an adjuvant setting. MATERIALS AND METHODS: We retrospectively analyzed 44 patients who were diagnosed with stage II or higher disease after undergoing curative resection and they had also received cisplatin-based chemotherapy. The ERCC1 expression was examined by performing immunohistochemical (IHC) staining, and this was divided into two groups according to the percentage of IHC staining of the tumor cell nuclei (negative: 10% or less, positive: more than 10%). RESULTS: Among the 44 patients (ERCC1-negative/ERCC1-positive group=16/28), 32 patients were male and their median age was 52 years. There was no difference for the baseline characteristics of the two groups. The median follow-up duration was 41 months. The median disease-free survival (DFS) and the overall survival (OS) for the ERCC1-positive group were significant higher than those of the ERCC1-negative group (DFS: 40.4 vs. 14.6 months, p=0.02, OS: undefined vs. 20.4 months, p=0.008). CONCLUSION: The overall survival in gastric cancer patients who received cisplatin-based adjuvant chemotherapy after a curative resection is higher in those patients showing the overexpression of the ERCC1 gene. However, prospective studies using the ERCC1 gene expression as a prognostic marker for the DNA repair activity are needed.

Effects of the Expression of Leptin and Leptin Receptor (OBR) on the Prognosis of Early-stage Breast Cancers / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: Obesity-related leptin and leptin receptor (OBR) have a relation to the development of cancer and metastasis and also the low survival rate for breast cancer patients. Leptin has been associated with increased aromatase activity and it displays functional cross-talk with estrogen. This study was designed to determine the relationship between the expression of leptin and OBR in breast cancer tissue and the prognosis of early-stage breast cancer patients, and especially for the tamoxifen-treated patients. MATERIALS AND METHODS: Ninety-five patients with early-stage breast cancer and who had undergone surgical treatment at Kyung Hee University Hospital between January 1994 and June 2004 were analyzed. The surgical specimens underwent immunohistochemical analysis for leptin and OBR. The patients' survival and clinical characteristics were obtained from the medical records. RESULTS: Of the 95 patients, 79 (83%) and 32 (33.7%) showed the expression of leptin and OBR in breast cancer tissue, respectively. The expression of leptin and OBR in breast cancer tissue was not significantly related to the clinicopathological characteristics, including obesity, the expression of hormonal receptor, the HER-2/neu expression, menopause, stage and the nuclear grade. The expression of leptin and OBR was not significantly related to the overall disease-free survival (DFS). For the tamoxifen-treated postmenopausal obese patients, the DFS of the leptin-positive group was higher than that of the leptin-negative group (p=0.017). CONCLUSION: The expression of leptin and OBR in breast cancer tissue may be not a prognostic factor for disease-free survival of breast cancer patients. In the future, further studies are needed to determine whether leptin expression could be a predictive factor for tamoxifen therapy in the postmenopausal obese subgroup among the early breast cancer patients.

The Efficacy of a Modified Chronomodulated Infusion of Oxaliplatin, 5-Fluorouracil and Leucovorin in Advanced Colorectal Cancer (Preliminary Data) / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: To determine the efficacy and tolerability of a modified chronomodulated infusion of oxaliplatin, 5-fluorouracil (5-FU) and leucovorin in the treatment of advanced colorectal cancer. MATERIALS AND METHODS: Sixteen patients with relapsed or metastatic colorectal cancer were treated with an intravenous infusion of oxaliplatin 25 mg/m(2), 5-FU 700 mg/m(2) and leucovorin 20 mg/m(2) on days 1 to 5. The infusion of oxaliplatin was chronomodulated with a peak delivery rate at 16: 00 p.m., with 5-FU infused constantly overnight. Each course was repeated every 21 days. RESULTS: The response rate was 38.5% (95% confidence interval [CI], 13.9% to 68.4%) in the 13 measurable patients, including 1 complete response (7.7%) and 4 partial responses (30.8%). Five patients (38.5%) had a stable disease and 3 (23.0%) a progressive disease. Three patients without a measurable lesion had improved status. The median time to progression and overall survival were 29 weeks and 85 weeks, respectively. Grade 3 thrombocytopenia occurred in 2.5% (2 cycles) and grade 3 vomiting in 12.5% (2 patients). Anorexia, stomatitis, diarrhea, pruritus, alopecia and peripheral neuropathy were mild and tolerable. CONCLUSION: The modified chronomodulated infusion of oxaliplatin, 5-FU and leucovorin is effective and tolerable, but the number of patients was too small. Further study will be needed to confirm the efficacy of this regimen with a larger population of patients.

Establishment of Serum Reference Range for Free Light Chains and its Clinical Usefulness in Multiple Myeloma / 대한진단검사의학회지

BACKGROUND: M protein, as a marker for monoclonal gammopathy, has been evaluated by protein electrophoresis (PEP) and immunofixation electrophoresis (IFE). Recently a highly sensitive, automated immunonephelometric assay for measurement of free light chains (FLCs) in serum and urine has been developed for the identification and monitoring of patients with monoclonal gammopathy. METHODS: We measured the concentration of kappa and lambda FLCs in 120 healthy individuals aged 20 to 80 years to establish the reference range of kappa and lambda FLCs and kappa/lambda FLC ratio and in 61 serum and 14 urine samples from patients with multiple myeloma (MM) to examine the correlation between the amount of M protein indirectly calculated on PEP and the direct measurement of FLCs. RESULTS: The concentrations of kappa and lambda FLCs and the kappa/lambda FLC ratio in healthy individuals were not significantly related to age or sex. The 95 percentile reference ranges for kappa FLC, lambda FLC, and kappa/lambda FLC ratio were 8.5-23.7 mg/L, 9.5-23.5 mg/L, and 0.67-1.38, respectively. On the PEP performed with MM specimens, 18 cases did not show the evidence of M protein. But, they revealed abnormal FLC concentrations on FLC assay and a significant correlation was found between the amount of M protein and the concentration of kappa and lambda FLC. However, inconsistent results such as the concentra-tion of kappa+lambda FLCs being more than the total protein in urine or M protein in serum were found in 5 of the 14 urine and 1 of the 61 serum samples of MM patients. CONCLUSIONS: FLC assay showed a good correlation with PEP and was more sensitive and accurate than PEP. Therefore, FLC assay is useful for diagnosing and monitoring monoclonal gammopathy at an early stage of the disease and during a remission state after chemotherapy or peripheral blood stem cell transplantation.

Randomized Phase III Trial of Cisplatin, Epirubicin, Leucovorin, 5-Fluorouracil (PELF) Combination versus 5-fluorouracil Alone as Adjuvant Chemotherapy in Curative Resected Stage III Gastric Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The combination of cisplatin, epirubicin, leucovorin and 5-fluorouracil (PELF) administration, as adjuvant chemotherapy after curative resection for gastirc cancer, was compared with 5-fluorouracil (5-FU) administration alone. This paper reports the results of a prospective randomized comparison of the two regimens, PELF and 5-FU. METHODS: From August 1996 to July 1999, 54 patients were selected subsequent to being diagnosed with stage III cancer after a curative resection for gastric cancer. The patients were stratified according to stage IIIA/IIIB and subtotal/total gastrectomy, and then they were randomized into each treatment group, i.e. the PELF or 5-FU alone groups. RESULTS: 54 assessable patients were enrolled in this study: 28 received PELF and 26 received 5-FU alone. 12 patients relapsed in each group and the median follow-up duration was 42 months (range: 10~77 months). The overall survival rate and disease-free survival rate (DFS) were not significantly different between two groups, (5-year survival of PELF vs. 5-FU: 57% vs. 64%, 5-year DFS: 54% vs. 51%). The PELF combination was more toxic in terms of anemia, anorexia, nausea and diarrhea than the 5-FU. CONCLUSIONS: This study showed that the PELF combination, as an adjuvant therapy for gastric cancer after a curative resection, was a less effective treatment, and it had more toxic effects than the 5-FU.