The effect of the response to the coronavirus disease pandemic on treatment outcomes in patients with lymphoma and multiple myeloma

Background/Aims@#Relatively little data are available on how the response to the coronavirus disease 2019 (COVID-19) pandemic has affected treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. We aimed to determine the effect of COVID-19 countermeasures on treatment outcomes in this patient population. @*Methods@#We retrospectively analyzed data on patients treated for lymphoma or multiple myeloma in two tertiary hospitals in Seoul. Patients were divided into two groups: group 1 included patients who received chemotherapy between September and December 2019 (the control period), and group 2 included patients who received chemotherapy between September and December 2020 (the study period). Countermeasures to COVID-19 were applied to the patients in group 2. The countermeasures implemented included mask wearing and regular handwashing at home and in hospital; COVID-19 risk assessments on all hospital visitors; and pre-emptive COVID-19 screening for all newly hospitalized patients and their resident guardians. @*Results@#No differences in treatment outcomes, including treatment response, incidence and duration of neutropenia or neutropenic fever, delays in chemotherapy, or number of deaths during chemotherapy, were observed between the g roups. None of the patients in group 2 tested positive for COVID-19, and there were no COVID-19-related deaths during the study period. @*Conclusions@#Countermeasures to COVID-19 did not affect treatment outcomes in patients receiving chemotherapy for lymphoma or multiple myeloma. Data on the effect of countermeasures to COVID-19 on treatment outcomes should continue to be analyzed to ensure that treatment outcomes are not adversely affected.

A Diagnostic Roadmap for Polycythemia / 대한내과학회지

Polycythemia could be defined as an elevation in hemoglobin or hematocrit levels above normal. To figure out what induces polycythemia is very important since the causes of polycythemia are very variable and the approaches for the treatments are basically different. Polycythemia can be primary or secondary in origin. The secondary causes are all associated with increase in erythropoietin (EPO) levels. If serum EPO levels are elevated, one try to differentiate whether the elevation is a physiologic response to hypoxemia or is related to autonomous production. Patients with low arterial O2 saturation (< 92%) should be further evaluated for the presence of heart or lung disease. Patients without hypoxemia who are smokers may have elevated EPO levels because of CO displacement of O2. If carboxyhemoglobin levels are elevated, the diagnosis is smoker’s polycythemia. Patients without hypoxemia who do not smoke, either could be diagnosed as high oxygen affinity hemoglobinopathy or have EPO producing tumors. If EPO levels are low, the patients most likely have polycythemia vera which has almost JAK2 mutation.

The role of platelet function analyzer-200 in predicting perioperative bleeding risk

Background/Aims@#Various preoperative screening tests, such as platelet count, prothrombin time, activated partial thromboplastin time, and bleeding time, have been widely used to evaluate the risk of bleeding during surgery. Use of platelet function analyzer (PFA)-100/200 for assessing platelet function instead of bleeding time is increasing. However, its role in predicting the perioperative risk of bleeding remains controversial. @*Methods@#Data of 703 patients who underwent surgery under general anesthesia were retrospectively analyzed. Preoperative platelet function was measured using PFA-200 system and the association with intraoperative bleeding was assessed. Additionally, other variables that could affect PFA-200 results were assessed by logistic regression analysis. @*Results@#Collagen/epinephrine (COL/EPI) test was prolonged in 199/703 (28.3%) patients (EPI group), while 99/212 (46.7%) patients showed COL/adenosine diphosphate test abnormalities. Bleeding over 300 mL during surgery occurred in 14.3% and 20.1% of patients in the normal and EPI groups, respectively (p = 0.058). In addition, red blood cell transfusion within 72 hours after surgery rate was significantly higher in the EPI group than in the normal group (31.7% vs. 23.4%,p= 0.024). In multivariate logistic analysis, prolongation closure time with COL/EPI (p = 0.068) was marginally associated with risk of bleeding during surgery. Furthermore, PFA-200 results were influenced by various factors, such as nonsteroidalanti-inflammatory drug use, blood group, hematocrit, and time of blood collection. @*Conclusions@#Preoperative PFA-200 test may be helpful in predicting the risk of perioperative bleeding. However, its results should be carefully interpreted becausethey are affected by several factors.

Impact of subsequent chemotherapy on the survival of elderly patients with extensive stage small cell lung cancer

Background/Aims@#The prognosis of small cell lung cancer (SCLC) is still poor because of rapid recurrence, despite good response to initial chemotherapy. Additionally, patients’ old ages and comorbidities are often obstacles that make it difficult to apply subsequent treatment after initial treatment. This retrospective study analyzed the correlation of post-progression survival (PPS) with overall survival (OS), and prognostic factors including comorbidities to figure out impact of subsequent chemotherapy on OS in elderly extensive disease SCLC. @*Methods@#We analyzed 101 patients of age 65 years or older who were recently diagnosed with extensive disease SCLC (ED-SCLC) in Korea University Medical Center between January 1995 and December 2015. The degree of comorbidity was scored using simplified comorbidity score (SCS). Correlation between PPS, progression-free survival (PFS) and OS was analyzed using a Pearson correlation coefficient. Cox proportional hazards regression was employed to examine the influence of clinical variables on survival. @*Results@#Median age of patients was 71 years old (range, 65 to 83). Median OS was 8.7 months (range, 0.3 to 42.7). PPS was a reliable factor on OS than PFS (R2 = 0.852, p 4 cycles of first line chemotherapy and subsequent second line chemotherapy. @*Conclusions@#PPS was more correlated with OS than PFS in elderly patients with ED-SCLC. The most important prognostic factors for PPS and OS included SCS and second line chemotherapy. Patients receiving subsequent treatment had increased OS regardless of degree of comorbidity.

Immature platelet fraction based diagnostic predictive scoring model for immune thrombocytopenia

Background/Aims@#The diagnosis of immune thrombocytopenia (ITP) is based on clinical manifestations and there is no gold standard. Thus, even hematologic malignancy is sometimes misdiagnosed as ITP and adequate treatment is delayed. Therefore, novel diagnostic parameters are needed to distinguish ITP from other causes of thrombocytopenia. Immature platelet fraction (IPF) has been proposed as one of new parameters. In this study, we assessed the usefulness of IPF and developed a diagnostic predictive scoring model for ITP. @*Methods@#We retrospectively studied 568 patients with thrombocytopenia. Blood samples were collected and IPF quantified using a fully-automated hematology analyzer. We also estimated other variables that could affect thrombocytopenia by logistic regression analysis. @*Results@#The median IPF was significantly higher in the ITP group than in the non-ITP group (8.7% vs. 5.1%). The optimal cut-off value of IPF for differentiating ITP was 7.0%. We evaluated other laboratory variables via logistic regression analysis. IPF, hemoglobin, lactate dehydrogenase (LDH), and ferritin were statistically significant and comprised a diagnostic predictive scoring model. Our model gave points to each of variables: 1 to high hemoglobin (> 12 g/dL), low ferritin (≤ 177 ng/ mL), normal LDH (≤ upper limit of normal) and IPF ≥ 7 and < 10, 2 to IPF ≥ 10. The final score was obtained by summing the points. We defined that ITP could be predicted in patients with more than 3 points. @*Conclusions@#IPF could be a useful parameter to distinguish ITP from other causes of thrombocytopenia. We developed the predictive scoring model. This model could predict ITP with high probability.

Modified dose of melphalan-prednisone in multiple myeloma patients receiving bortezomib plus melphalan-prednisone treatment

BACKGROUND/AIMS@#Bortezomib plus melphalan-prednisone (VMP) is a standard treatment for multiple myeloma, particularly for patients who are ineligible for high-dose therapy. However, early discontinuation or treatment modification is often needed owing to adverse events. The aim of this study was to investigate the clinical outcomes of modifying the dose of melphalan-prednisone (MP) in patients receiving VMP.@*METHODS@#We examined 67 patients who received a modified dose of MP, and 38 patients who received the regularly planned dose of MP. We then analyzed clinical differences between the groups.@*RESULTS@#Although there was no difference in the proportion of discontinuation due to adverse events between dose groups, more patients in the planned-dose group experienced earlier discontinuation in general. The overall response rate (ORR) was 81.0% and complete response (CR) rate was 30.5%. After a median 15.7 months of follow-up, the median progression-free survival (PFS) and overall survival (OS) were 25.0 and 47.8 months, respectively. There was no significant difference in the ORR, CR, PFS, and OS of the two dose groups. A median of four cycles were delivered, and the median cumulative bortezomib dose was 41.6 mg/m². The median PFS in patients with doses ≥ 41.6 mg/m² was longer than that in patients with doses < 41.6 mg/m² (35.1 months vs. 9.6 months). However, when MP was < 50% of the planned dose, PFS and OS were poor.@*CONCLUSIONS@#Modifying the dose of MP might be a feasible and effective therapeutic approach for multiple myeloma patients receiving VMP treatment.

Analysis of Overall Survival According to Bone Marrow Aspiration Results in Non-Hodgkin's Lymphoma Patients / 대한내과학회지

BACKGROUND/AIMS: The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods. METHODS: We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis. RESULTS: Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003). CONCLUSIONS: This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.

Usefulness of Chromosomal Microarray in Hematologic Malignancies: A Case of Aggressive NK-cell Leukemia with 1q Abnormality

A variety of clonal cytogenetic abnormalities have been reported in aggressive natural killer (NK)-cell lymphoma and leukemia. Recent chromosomal microarray studies have shown both gain and loss of 1q and loss of 7p as recurrent abnormalities in aggressive NK-cell leukemia. Here, we report a case of aggressive NK-cell leukemia with complex chromosomal gains and losses, as confirmed by chromosomal microarray analysis. The patient showed an aggressive clinical course, which was complicated by hemophagocytic lymphohistiocytosis. Conventional cytogenetic analysis revealed trisomy 3 and 1q gain only. However, chromosomal microarray analysis detected an additional gain of 1q21.1–q24.2 and a loss of 1q24.2–q31.3. These abnormal lesions might play a role in the pathogenesis of aggressive NK-cell leukemia by inactivating tumor suppressor genes or by activating oncogenes. These results suggest that chromosomal microarray analysis may be used to provide further genetic information for patients with hematological malignancies, including aggressive NK-cell leukemia.

Analysis of Overall Survival According to Bone Marrow Aspiration Results in Non-Hodgkin's Lymphoma Patients / 대한내과학회지

BACKGROUND/AIMS@#The staging work-up for patients with non-Hodgkin's lymphoma includes bone marrow aspiration and biopsy. Consistent results of both procedures can clarify the diagnosis. However, no clear guidelines have been established regarding positive results for bone marrow aspiration alone. The aim of this study was, therefore, to analyze the overall survival (OS) for the clinical diagnoses of these patients using morphological methods.@*METHODS@#We performed a retrospective analysis of patients who were consecutively enrolled in the Korea University Lymphoma Registry from 1991 to 2016. OS was compared according to the bone marrow group: without bone marrow involvement (BMA−/BMBx−), with positive results for aspiration and negative results for biopsy (BMA+/BMBx−), and with bone marrow involvement in biopsy (BMBx+). OS was assessed using the Kaplan-Meier method and multivariate analysis.@*RESULTS@#Of 1,735 patients, 1,326 were analyzed and 409 were excluded. In the Kaplan-Meier survival analysis, OS was significantly worse for patients in the BMBx+ group compared with those in the BMA−/BMBx− group (p < 0.001). However, there was no significant difference in OS between patients in the BMA+/BMBx− group and those in other groups (vs. BMA−/BMBx−, p = 0.163; BMBx+, p = 0.292). In multivariate analysis, by adjusting survival-related variables, the BMA+/BMBx− group showed marginal significance compared to the BMA−/BMBx− group (p = 0.081), and showed significance in the subgroup of indolent non-Hodgkin's lymphoma patients (p = 0.003).@*CONCLUSIONS@#This study suggested that even if there are positive results in bone marrow aspiration alone in patients with non-Hodgkin lymphoma, attention to patient characteristics, involving significance as a poor prognosis for OS, is required.

Myeloma prognostic index at diagnosis might be a prognostic marker in patients newly diagnosed with multiple myeloma

BACKGROUND/AIMS: The aims of this study were to identify the value of inflammatory markers as pretreatment prognostic factors for patients with multiple myeloma (MM) and to estimate the value of a prognostic index including these markers at diagnosis. METHODS: A total of 273 newly diagnosed MM patients undergoing active treatment were analyzed in this study. The prognostic values for survival of the pretreatment inflammatory markers were investigated. A myeloma prognostic index (MPI) was derived using prognostic factors determined to be independently significant on multivariate analysis. RESULTS: A high pretreatment neutrophil-lymphocyte ratio (NLR), low platelet count, and high C-reactive protein (CRP) level had independently unfavorable significance for overall survival (OS). The MPI was derived based on these factors. Per the MPI, 1 point each was assigned to high NLR, low platelet count, and high CRP. Risk categories were stratified into low- (score 0), intermediate- (score 1), and high-risk (score 2 or 3) groups. The MPI demonstrated independent statistical significance for OS on multivariate analysis ([intermediate: hazard ratio (HR), 1.91; 95% confidence interval (CI), 1.12 to 3.24] and [high: HR, 3.37; 95% CI, 2.00 to 5.69]; p < 0.001). Moreover, this significance could be observed regardless of age, renal function, and exposure to novel agents. In addition, the International Staging System risk group could be further significantly stratified using the MPI. CONCLUSIONS: The MPI, consisting of pretreatment inflammatory markers, NLR, platelet count, and CRP, might be effective in predicting the survival of newly diagnosed MM patients undergoing active treatment.

Clinicopathological characteristics of extremely young Korean multiple myeloma patients: therapeutic implications

BACKGROUND/AIMS: Although multiple myeloma (MM) is typically a disease of the elderly, a certain subset of extremely young patients exists. It is necessary to establish clinicopathological characteristics for this population. METHODS: We reviewed the medical records of MM patients whose age was 40 years or younger at diagnosis. RESULTS: A total of 32 patients were analyzed (male to female ratio 19:13, median age 37 years). According to International Staging System, 29%, 48%, and 16% were in stage I, II, and III, respectively. Light chain myeloma accounted for 30%. Clinically significant anemia, hypercalcemia, azotemia, and hypoalbuminemia were present in 29%, 28%, 13%, and 28%, respectively. Three or more lytic bone lesions were detected in 45% of the patients, whereas 13% had no lytic bone lesions. Regarding treatment, 79% of patients received autologous hematopoietic stem cell transplantation. After a median follow-up duration of 64 months, the 1-, 3-, and 5-year overall survival (OS) rates were 84%, 62%, and 54%, respectively. The median OS was 61 months for the entire cohort. CONCLUSIONS: In our study, MM patients aged 40 years or younger at diagnosis showed no superior survival compared to those of the moderately elderly patients based on historical data.

A Case of Therapy-related Acute Lymphoblastic Leukemia with t(11;19)(q23;p13.3) and MLL/MLLT1 Gene Rearrangement / 대한진단검사의학회지

Therapy-related ALL (t-ALL) is a rare secondary leukemia that develops after chemotherapy and/or radiotherapy for primary malignancies. Chromosomal 11q23 abnormalities are the most common karyotypic alterations in t-ALL. The t(11;19)(q23;p13) aberration is extremely rare and has not been confirmed at the molecular genetic level. Here, we report a case of t-ALL with t(11;19)(q23;p13.3) and MLL-MLLT1 (alias ENL) gene rearrangement confirmed by cytogenetic analysis, multiplex reverse transcription-PCR (multiplex RT-PCR), and DNA sequencing in a patient who had undergone treatment for breast cancer. A 40-yr-old woman developed acute leukemia 15 months after undergoing 6 cycles of adjuvant chemotherapy (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2), radiation therapy (dose, 5,900 cGy), and anticancer endocrine therapy with tamoxifen. The complete blood cell counts and bone marrow examination showed increased blasts and the blasts showed B lineage immunophenotype (positive for CD19, CD34, and cytoplasmic CD79a). Cytogenetic analysis revealed the karyotype 47,XX,+X,t(11;19)(q23;p13.3)[4]/46,XX[16]. FISH analyses, multiplex RT-PCR, and DNA sequencing confirmed the MLL-MLLT1 gene rearrangement. The patient underwent induction chemotherapy with fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (Hyper-CVAD) and achieved complete remission. Subsequently, she underwent consolidation chemotherapy, but died of brain ischemia in the pons and the region of the middle cerebral artery. To our knowledge, this is the first case report of t-ALL with t(11;19)(q23;p13.3) and the MLL-MLLT1 gene rearrangement.

Bortezomib and melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma / 대한혈액학회지

BACKGROUND: High-dose melphalan (200 mg/m2) with autologous stem cell transplantation (ASCT) is the standard treatment for young patients with multiple myeloma (MM). However, the response rates after ASCT are often unsatisfactory. We performed a pilot study by using bortezomib-melphalan as conditioning regimen for ASCT in Korean patients with MM. METHODS: The conditioning regimen consisted of administration of intravenous infusion of bortezomib 1.0 mg/m2 on days -4 and -1 and melphalan 50 mg/m2 (day -4) and 150 mg/m2 (day -1). In this study, we enrolled 6 newly diagnosed patients and 2 patients with relapse. RESULTS: The disease status of the 6 newly diagnosed patients at ASCT was as follows: 1 complete remission (CR), 1 very good partial remission (VGPR), and 4 partial remissions (PRs). The disease status of the 2 relapsed patients at ASCT was PR. All patients except 1 showed adequate hematologic recovery after ASCT. The median time for the absolute neutrophil counts to increase over 500/mm3 was 13 days (range, 10-19 days). Six patients with VGPR or PR at the time of transplantation showed an improvement in response to CR after ASCT. The patients were followed up without any maintenance treatment after ASCT except 1 patient who died during ASCT. During the follow-up period, CR was maintained in 3 newly diagnosed patients, but the other 4 patients, including 2 newly diagnosed patients, relapsed. CONCLUSION: Conditioning regimen consisting of bortezomib and melphalan may be effective for ASCT in MM; however, the feasibility of this regimen should be further evaluated in large study populations.

Stemness Evaluation of Mesenchymal Stem Cells from Placentas According to Developmental Stage: Comparison to Those from Adult Bone Marrow

This study was done to evaluate the stemness of human mesenchymal stem cells (hMSCs) derived from placenta according to the development stage and to compare the results to those from adult bone marrow (BM). Based on the source of hMSCs, three groups were defined: group I included term placentas, group II included first-trimester placentas, and group III included adult BM samples. The stemness was evaluated by the proliferation capacity, immunophenotypic expression, mesoderm differentiation, expression of pluripotency markers including telomerase activity. The cumulative population doubling, indicating the proliferation capacity, was significantly higher in group II (P<0.001, 31.7+/-5.8 vs. 15.7+/-6.2 with group I, 9.2+/-4.9 with group III). The pattern of immunophenotypic expression and mesoderm differentiation into adipocytes and osteocytes were similar in all three groups. The expression of pluripotency markers including ALP, SSEA-4, TRA-1-60, TRA-1-81, Oct-4, and telomerase were strongly positive in group II, but very faint positive in the other groups. In conclusions, hMSCs from placentas have different characteristics according to their developmental stage and express mesenchymal stemness potentials similar to those from adult human BMs.

A Case of Nonclassifiable Interstitial Pneumonia after Allogeneic Hematopoietic Stem Cell Transplantation / 결핵및호흡기질환

Despite the improvements in supportive care, early and late hematopoietic stem cell transplantation-related complications still remain a significant cause of morbidity and mortality. Pulmonary complications occur in 40~60% of patients who undergo allogeneic hematopoietic stem cell transplantation. Late-onset noninfectious pulmonary complications can occur months and even years after transplantation. Interstital lung disease has also been reported to be a late post-transplant complication. Exposure to cytotoxic drugs and/or irradiation has been implicated as a cause of pulmonary toxicity including pulmonary fibrosis. We report a case of an 18-year-old female with non-classifiable interstitial pneumonia that manifested eight and a half years after allogeneic hematopoietic stem cell transplantation. The condition worsened rapidly and the patient eventually died.

Reversible Posterior Leukoencephalopathy Syndrome in a Patient with Relapsed Hodgkin's Disease: A Case Report / 대한혈액학회지

Reversible posterior leukoencephalopathy syndrome (RPLS) is a distinctive clinicoradiological entity that's characterized by headache, confusion, seizure and frequent visual disturbances. It is associated with certain neuro-radiological findings, and predominantly white matter abnormalities of the parieto-occipital lobes. RPLS has been identified mostly in patients with malignant hypertension, pre-eclampsia and renal insufficiency and in those patients who are using immunosuppressive agents or cytotoxic drugs. We report here on a case of RPLS in a patient who was undergoing chemotherapy. A 49-year-old woman presented with abrupt mental changes and visual disturbances five days after the administration of a chemotherapeutic agent. MRI showed hyper-intense signals on the magnetic resonance (MR) diffusion images in the bilateral temporal, parietal and occipital lobes. The clinical manifestations completely resolved after one week of treatment that consisted of blood pressure control, a negative intake-output balance and the best supportive care. These radiological changes and the reversible clinical manifestations were consistent with RPLS.

Clinical Factors Related to Suspected Second Primary Lung Cancer Development in Patients with Head and Neck Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: The rate of second primary lung cancer development for patients with head and neck cancer (HNC) has been noted. The aim of our study was to evaluate the incidence and clinical features of suspected second primary lung cancer that developed in patients with primary HNC. MATERIALS AND METHODS: We conducted a retrospective study of 469 patients who were newly diagnosed with HNC at the Korea University Medical Center between January 2000 and December 2006. RESULTS: A total of 469 patients were included (389 men and 80 women). Eighteen patients (3.8%) had suspected second primary lung cancers. Statistically significant clinical variables for lung cancer development included the origin site for the primary HNC (oro-hypopharynx and larynx) (p=0.048), abnormal chest x-ray findings (p=0.027) and the histological HNC type (squamous cell carcinoma) (p=0.032). When the second primary lung cancers were combined with HNCs, the adjusted overall survival of patients with a second primary lung cancer was 16 months (p<0.001). CONCLUSIONS: Considering the relative risk factors for a second primary lung cancer developing in patients with HNC, advanced diagnostic tools, such as chest CT or PET CT scan, should be applied for the early detection of a second primary lung cancer.

Treatment Outcomes and Toxicities of ABVD Combination Chemotherapy Compared with CVPP in Hodgkin's Disease / 대한혈액학회지

BACKGROUND: We retrospectively evaluated the treatment outcomes and toxicities of Hodgkin's disease (HD) patients treated by ABVD (adriamycin, bleomycin, vinblastine, and dacarbazine) combination chemotherapy, and compared them with those of a historical group treated with a CVPP (cyclophosphamide, vinblastine, procarbazine, and prednisone) regimen. METHODS: The medical records of patients who had been diagnosed with HD histologically and treated by either ABVD or CVPP from 1997 to 2006 at the Korea University Medical Center were retrospectively reviewed. RESULTS: Thirty patients were eligible. Nineteen patients received ABVD and eleven patients were treated with CVPP. The response rates for ABVD and CVPP were 84.21% and 54.55%, respectively. Median overall survival was 43.17 months for ABVD and 43.27 months for CVPP (P=.570). Median event-free survival was 39.03 months for ABVD and 16.73 months for CVPP (P=.088). There was no significant difference in median survival or in event-free survival between the two regimens. Hematologic toxicities were significantly more common in the CVPP group than in the ABVD group. Grade 3 or 4 neutropenia was observed in 72.72% of the CVPP group and in 36.84% of the ABVD group (P=.050). CONCLUSION: ABVD for HD showed significantly lower hematologic toxicities and moderately better treatment outcomes than did CVPP.

Persistent Anemia in a Patient with Diffuse Large B Cell Lymphoma: Pure Red Cell Aplasia Associated with Latent Epstein-Barr Virus Infection in Bone Marrow

We report a case of pure red cell aplasia (PRCA), which was initially suspected as a result of bone marrow involvement of diffuse large B cell lymphoma. Persistent anemia without an obvious cause was observed in a 47-yr-old man diagnosed with relapsed diffuse large B cell lymphoma. The bone marrow study showed only erythroid hypoplasia without the evidence of bone marrow involvement with lymphoma cells, thus PRCA was suggested. However, parvovirus infection was excluded as a potential cause of PRCA because of negative IgM anti-parvovirus B19 antibody and negative parvovirus PCR in the serum. Latent Epstein-Barr virus (EBV) infection of bone marrow was suggested by in situ hybridization with EBV-encoded small RNA (EBER) that showed a strong positive expression in bone marrow cells. Thus, PRCA was thought to be associated with latent EBV infection in bone marrow cells. Although the finding of unexplained anemia is a possible predictor of bone marrow involvement with lymphoma cells, PRCA as a result of a viral infection including EBV should be considered in lymphoma patients. This is the first report of the occurrence of PRCA associated with latent EBV infection in a patient with non-Hodgkin's lymphoma.

Differentiation Culture of Hematopoietic Stem Cells from Embryonic Stem Cells / 대한혈액학회지

BACKGROUND: This study was designed to verify the effective culture condition for the differentiation of human hematopoietic stem cells from SNU-3 embryonic stem cell line. METHODS: Control group was that of which embryonic stem cells were directly cultured to LTC-IC assay. Study group was that of which an embryonic body manufactured from embryonic stem cells was cultured to LTC-IC assay. CD34+ cells were separated by MACS method at 1, 3, 5, 7, 10, 14, 21 days of LTC-IC assay in both groups. Thereafter, CD34+ cell were cultured to semisolid methyl-cellulose media to count CFUs. CD34+CD45- cell percentage was measured with FACS method at 5 days of LTC-IC assay. This study was repeated for 14 times. RESULTS: In control group, CD34+ cells were hardly separated in any period of LTC-IC assay. In study group, the median count of CD34+ cells was 0.7 (0.4-1.2)x10(4), 1.8 (1.4-2.6)x10(4), 0.6 (0.5-0.7)x10(4) and the median count of CFUs was 0.5 (0.2-0.8)x10(2), 1.0 (0.6-1.3)x10(2), 0.2(0.1-0.4)x10(2) at 3, 5, 7 days of LTC-IC assay, respectively. Median CFUs count per CD34+ cell was 0.0071, 0.0056, 0.0033 at 3, 5, 7 days of LTC-IC assay, respectively. In study group, the count of CD34+ cells and CFUs was significantly higher at 5 days of LTC-IC assay than at any other days (P<0.01). CFUs count per CD34+ cell was significantly higher at 3 days of LTC-IC assay than at any other days (P<0.01). CD34+CD45- cells detected by FACS method of study group(1.16%(0.92-1.97) was significantly higher than that of control group (0.09% (0.00-0.23)) (P<0.01). CONCLUSION: The differentiation of hematopoietic stem cells from SNU-3 embryonic stem cell line is effective in the condition of which an embryonic body manufactured from embryonic stem cells is cultured to LTC-IC assay. The period of which embryonic stem cells differentiate to hematopoietic stem cells is between 3 to 7 days of LTC-IC assay.