Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

Is immunological recovery clinically relevant at 100 days after allogeneic transplantation?

Background/Aims@#Immune reconstitution following allogeneic hematopoietic stem cell transplantation (HSCT) is affected by multiple variables during the transplantation. @*Methods@#We assessed the clinical factors contributing to immune function reconstitution at 100 days post-allogeneic HSCT in 114 patients receiving fludarabine-based conditioning. Immunophenotypic analysis using flow cytometry was performed to evaluate the percentage and the absolute numbers of T-cell subsets, natural killer cells, and B-cells as clinical outcomes. @*Results@#Tacrolimus-based graft-versus-host disease (GVHD) prophylaxis, T-cell depletion, and acute GVHD were significantly associated with delayed immune reconstitution of T-cell subsets. The incidence of chronic GVHD was significantly increased in the normal recovery group compared to the abnormal group (p = 0.01). Epstein-Barr virus reactivation was more frequently observed in the abnormal group of T-cell subsets (p = 0.045). All viral reactivation events including cytomegalovirus reactivation appeared to be more frequent in the abnormal group of T-cell subsets. @*Conclusions@#The immune recovery status post-allogeneic HSCT was affected by GVHD prophylactic regimens, especially in cases receiving tacrolimus-based GVHD prophylaxis, T-cell depletion, and possibly those manifesting acute GVHD. Delayed immune reconstitution might increase the morbidity due to viral reactivation. Treatment strategies are needed to prevent infectious complications and enhance immune reconstitution based on the immune recovery status following allogeneic HSCT with fludarabine-based conditioning.

A Rare Case of Essential Thrombocythemia with Coexisting JAK2 and MPL Driver Mutations

Philadelphia-negative (Ph−) classical myeloproliferative neoplasms (MPNs) include polycythemia vera, essential thrombocythemia (ET), and primary myelofibrosis. Somatic driver mutations in the JAK2, CALR, and MPL genes serve as major diagnostic criteria of the Ph− MPNs and these mutations occur in a mutually exclusive manner. In this report, we describe the first case of ET harboring double mutations in JAK2 V617F and MPL. For MPL, the patient had multiple clones of MPL mutations: c.1543_1546delinsAGGG (p.Trp515_Gln516delinsArgGlu) and c.1546C>G (p.Gln516Glu). The JAK2 V617F allele burden in our patient is very low (4%) compared to the relatively high (17%–78%) allele frequency of MPL mutations. The low JAK2 mutant burden might be explained by preexisting clonal hematopoiesis before overt signs of MPNs, followed by the acquisition of a second oncogenic mutation of CALR or MPL leading to the MPN phenotype. This highlights that screening for a second driver mutation should be considered in patients with a low JAK2 mutant burden by reporting a 57-year-old Korean man with ET.

A Retrospective Study on the Decision to Prohibit Cardiopulmonary Resuscitation in Patients with Premenarcheal Cancer in a University Hospital

OBJECTIVE: Whether to perform cardiopulmonary resuscitation (CPR) or do-not-resuscitate (DNR) is not only a medical problem but also a decision that should be made carefully with self-autonomy in accordance with life values. We conducted a retrospective observational study to identify the characteristics of current CPR and DNR at a practical level. METHODS: We retrospectively analyzed data from medical records with regard to the clinical status of DNR decision in 356 patients with cancer who expired between October 2014 and September 2015 in Soonchunhyang University Bucheon Hospital. RESULTS: DNR was decided significantly more frequently in patients with solid cancers than in patients with hematological cancer (87.7% vs. 71.4%, P=0.003). No other significant factor influenced the DNR decision in this study. The main persons who signed the DNR consent form were mostly sons or daughters (60.7%), never the patients themselves. The median time from the DNR order to death was longer in the ward than in the intensive care unit (ICU; 3.0 days vs. 1.0 days). The mean time from the DNR order to death was 6.6 days (median, 2 days). Among the patients with a DNR order, 110 (36.7%) were hospitalized in the ICU and 73 (24.3%) were treated with ventilator support. CONCLUSION: Most patients expired 6.6 days after DNR permission was given and could not decide their treatment plan by themselves. For better end-of-life care, the sensitive DNR decision with consideration of the individualized environment of the patient for life-sustaining treatment should be settled in Korea.

Association Between c-Met and Lymphangiogenic Factors in Patients With Colorectal Cancer

PURPOSE: Animal models show a strong relationship between lymphangiogenesis and lymph node metastasis. However, the clinical significance of lymphangiogenesis in patients with colorectal cancer (CRC) remains uncertain. This study aimed to evaluate the association between c-Met and lymphangiogenic factors and to elucidate the prognostic significance of c-Met in patients with CRC. METHODS: A total of 379 tissue samples were obtained from surgically resected specimens from patients with CRC at Soonchunhyang University Cheonan Hospital between January 2002 and December 2010. The expressions of c-Met, vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, and podoplanin were examined using immunohistochemistry. The expression of c-Met and clinical factors were analyzed. RESULTS: Of the 379 tissues, 301 (79.4%) had c-Met expression. High expression of c-Met in tumor cells was significantly associated with high expression of VEGF-C (P < 0.001) and VEGFR-3 (P = 0.001). However, no statistically significant association with podoplanin (P = 0.587) or VEGF-D (P = 0.096) was found. Of the 103 evaluable patients, expression of c-Met in tumor cells was significantly associated with advanced clinical stage (P = 0.020), positive lymph node status (P = 0.038), and high expression of VEGF-C (P = 0.020). However, no statistically significant association with podoplanin (P = 0.518), VEGFR-3 (P = 0.085), VEGF-D (P = 0.203), or overall survival (P = 0.360) was found. CONCLUSION: Our results provide indirect evidence for an association and possible regulatory link of c-Met with the lymphangiogenic markers, but c-Met expression in patients with CRC is not a prognostic indicator for overall survival.

The incidence of venous thromboembolism is not lowin Korean patients with advanced pancreatic cancer

BACKGROUND: Pancreatic cancer is among the most common malignancies associated with venous thromboembolism (VTE). Asian patients are known to have a lower incidence of VTE compared to Caucasian patients. However, few studies have investigated the incidence of VTE in Asian patients with pancreatic cancer. METHODS: This retrospective review of medical records was performed on 505 patients with histopathologically proven advanced stage pancreatic cancer, from January 2006 to December 2012, at Soonchunhyang University Hospitals. RESULTS: Ninety-four patients (18.6%) had at least one pulmonary embolism (PE), deep vein thrombosis (DVT), or splanchnic vein thrombosis (SVT); 38 patients had isolated SVT; and 56 patients (11.1%) had at least one classic VTE (PE and/or DVT of lower extremities). Patients with more advanced stages of pancreatic cancer (distant metastatic stage, recurrence) or who had received chemotherapy had a higher incidence of classic VTE. Patients who were simultaneously diagnosed with pancreatic cancer and classic VTE had a poorer prognosis than patients with subsequent VTEs. There was a significant difference in overall survival (OS) between the presence and absence of a concurrent classic VTE diagnosis (median: OS, 2.1 mo vs. 10.7 mo; P < 0.001). Even when VTE included SVT, the result was similar (P < 0.001). CONCLUSION: In Korean patients with advanced pancreatic cancer, the incidence of VTEs is comparable to that of Caucasian patients. We also found that pancreatic cancer patients with concurrent VTEs had a poor prognosis compared to patients who developed VTEs later.

A Case of Chronic Myeloid Leukemia With Rare Variant ETV6/ABL1 Rearrangement

No abstract available.

Associations Between Serum Vitamin D Level and Skeletal Complications in Multiple Myeloma Patients

OBJECTIVE: Vitamin D deficiency can either cause or aggravate osteopenia and osteoporosis, and that can lead to an increased risk of fracture. We studied associations between serum vitamin D level and skeletal complications including bone pain in multiple myeloma patients. METHODS: This study reviewed the medical records of 35 multiple myeloma patients in Soonchunhyang University Bucheon Hospital from January, 2013 to May, 2014. The patients were classified as three groups according to the total vitamin D level: above 20 ng/mL as sufficient group, from 10 to 20 ng/mL as insufficient group, and below 10 ng/mL as deficient group. RESULTS: The incidence of fracture complication, the number of fracture, and the number of the cases of severe fracture that needed surgical intervention did not show statically significant difference in the three groups according to the total vitamin D level. As the results presented as graphs, the number of indicator of skeletal complications and total vitamin D level showed negative relationship. In the logistic regression analysis, analgesic use due to bone pain and the number of total analgesic use were significantly different in three groups (P=0.036, P=0.041), respectively, and showed a negative correlation between the level of vitamin D and number of analgesics had negative correlation. CONCLUSION: The measurement of serum total vitamin D level at the initial diagnosis in multiple myeloma patients and the proper treatment in the deficient patients would reduce the skeletal complications and moreover improve the quality of life.

Does anti-thymocyte globulin have a place in busulfan/fludarabine conditioning for matched related donor hematopoietic stem cell transplantation?

BACKGROUND/AIMS: There is controversy about the prophylactic effect of anti-thymocyte globulin (ATG) on graft versus host disease (GVHD) in the setting of matched related-donor hematopoietic stem cell transplantation (HSCT). This study assessed the inf luences of ATG on the incidences of acute and chronic GVHD and other clinical outcomes in matched related-donor HSCT. METHODS: Sixty-one patients received allogeneic HSCT from human leukocyte antigen-matched, related donors. Patients received busulfan/fludarabine conditioning regimens and standard GVHD prophylaxis with or without additional ATG. RESULTS: There was no significant difference in the cumulative incidences of overall acute GVHD, grade II to IV acute GVHD at day 100, and chronic GVHD during the follow-up period between the ATG and non-ATG groups. Three-year overall survival rates were very similar, but three year disease-free survival of the non-ATG group was higher than that of the ATG group (56.2% for ATG vs. 63.1% for non-ATG, p = 0.597). Relapse rate at 3 years in the ATG group was slightly higher than that of the non-ATG group (37.5% vs. 20%, p = 0.29). Non-relapse mortality rate at 3 years was lower in the ATG group (6.25% vs. 15.6%, p = 0.668). CONCLUSIONS: Although the addition of ATG doesn't guarantee a reduction in the incidences of acute and chronic GVHD, pre-transplantation ATG may result in lower non-relapse mortality in the context of matched related-donor HSCT with a busulfan/fludarabine conditioning regimen. However, caution is needed when using ATG because of a possibility to increase relapse rate.

Second-Line Chemotherapy in Advanced Biliary Tract Cancer: A Retrospective Analysis

OBJECTIVE: The evidence of 2nd line chemotherapy has not been validated. We investigated the treatment outcomes of 2nd line palliative chemotherapy in patients with biliary tract cancer (BTC) and analyzed the factors affecting response or survival. METHODS: We retrospectively reviewed and analyzed the outcomes in advanced BTC patients who underwent 2nd line chemotherapy in Soonchunhyang Universitiy Hospitals (Bucheon, Seoul, and Cheonan). RESULTS: From December 2004 to May 2014, 65 patients were enrolled. The median age was 56 years (range, 40 to 76 years) and the ratio of cholangiocarcinoma (intrahepatic or extrahepatic), gall bladder cancer, and ampulla of Vater cancer was 41 (63.1%):18 (27.7%):6 (9.25%). Half of the patients (33 patients, 50.8%) were treated with gemcitabine-based and 28 patients (43.1%) with 5-fluorouracil- based therapy. The response rate was 3.0% and disease control rate was 21.5% in intention-to-treat analysis. Median overall survival (OS) was 7.2 months (95% confidence interval [CI], 3.9 to 10.5 months) and median progression free survival (PFS) was 3.7 months (95% CI, 2.5 to 4.9 months). In multivariate analysis, patients with good performance status (PS) (P=0.001) and chemo-sensitive tumor to 2nd line chemotherapy (P=0.000) had longer PFS as compared to the others. In addition, patients with good PS (P=0.003), chemo-sensitive tumor to 1st line (P=0.046), and 2nd line chemotherapy (P=0.004) were good prognostic factors for OS. CONCLUSION: The effect of 2nd line chemotherapy in advanced BTC was modest and maybe beneficial in select patients.

Inadvertent Transmission of a Donor's Constitutional Chromosome Abnormality after Hematopoietic Stem Cell Transplantation

A pre-transplant screening work-up of donors for allogeneic hematopoietic stem cell transplantation (HSCT) is essential. Inadvertent transmission of malignancy from donors with subclinical diseases to recipients has been reported recently in several cases. A 49-year-old male was diagnosed with acute myeloid leukemia. He underwent a course of induction chemotherapy and achieved cytogenetic complete remission (CR). He was treated with an additional cycle of consolidation chemotherapy followed by full matched sibling allogeneic HSCT due to an additional deletion in 9q known as an adverse prognostic factor. Post transplantation bone marrow biopsy revealed molecular CR, but conventional cytogenetics identified the presence of 46,XY,t(1:2)(p32:q35). A cytogenetic analysis of the donor graft specimen revealed t(1:2). We confirmed the donor origin of t(1:2). We report the first case of a person with constitutional t(1;2) serving as a stem cell donor.

Primary Pulmonary Leiomyosarcoma: Could It Be Cured by Radiation Therapy?

Primary leiomyosarcoma of lung is extremely rare and often diagnosed as a mass on routine chest radiography. Although advances have been made in treatment protocols, leiomyosarcoma remains one of the more difficult soft tissue sarcomas to treat. Surgical resection is usually curative for small and well-differentiated sarcomas. For poorly differentiated and non-resectable tumors, chemotherapy and radiation therapy are used as neoadejuvant or palliative treatment options. Generally, leiomyosarcomas are known to be resistant to radiation therapy alone. The authors experienced a 68-year-old woman who was diagnosed leiomyosarcoma by routine chest radiography. Although disease progression was observed despite of chemotherapy, radiation therapy reduced the size of tumor. This paper describes the curative potential of radiation therapy for primary pulmonary leiomyosarcomas through a case report and literature review.

Rectal Squamous Cell Carcinoma in a Patient with Familial Adenomatous Polyposis / 대한내과학회지

Squamous cell carcinoma of the rectum is extremely rare, with an incidence between 0.25 and 1 case per 1,000 cases of colorectal carcinoma. In familial adenomatous polyposis (FAP), characterized by the progressive development of hundreds to thousands of adenomatous colonic polyps, unscreened patients and those who are not treated at an early stage of the disease have an extremely high risk of developing colorectal adenocarcinoma. A few reports of squamous cell carcinoma of the rectum have been published but none of the patients had FAP. Here, we report the case of a 17-year-old male with FAP who developed rectal squamous cell carcinoma.

Clinical characteristics and treatment outcome of acute myeloid leukemia in elderly patients in Korea: a retrospective analysis

BACKGROUND: The clinical characteristics of elderly patients with AML differ from those of younger patients, resulting in poorer survival and treatment outcomes. We analyzed retrospectively the clinical data of AML patients 65 years old and above to describe patients' characteristics and treatment patterns, and to define meaningful prognostic factors of survival in the Korean population. METHODS: Basic patients' characteristics, clinical outcomes according to treatments, and prognostic factors associated with survival and treatment intensity were examined in a total of 168 patients diagnosed in 5 institutes between 1996 and 2012 as having AML. RESULTS: Herein, 84 patients (50.0%) received high-intensity regimens (HIR), 18 (10.7%) received low-intensity regimens (LIR), and 66 (39.3%) received supportive care (SC) only. The median survival of all patients was 4.5 months; and median survival times with HIR, LIR, and SC were 6.8 months, 10.2 months, and 1.6 months, respectively. Median survival times with HIR and LIR were significantly longer than that with SC (P<0.0001 and P=0.006, respectively). Multivariate analysis identified age, Eastern Cooperative Oncology Group-performance status (ECOG-PS), hemoglobin (Hb) level, and serum creatinine (Cr) level as statistically significant prognostic factors for survival. In the HIR group, prognostic factors for survival were ECOG-PS, Hb level, and C-reactive protein level. CONCLUSION: Even in elderly AML patients, an intensive treatment regimen could be beneficial with careful patient selection. Further prospective studies designed to identify specific prognostic factors are required to establish an optimal treatment strategy for elderly AML patients.

Thrombotic Thrombocytopenic Purpura after Stent Insertion in Patient with Colon Cancer

Thrombotic thrombocytopenic purpura (TTP), a fatal disease, is mostly idiopathic but can occur secondary to cancer, infection, transplantation, pregnancy, surgery, or drugs. The mechanism of TTP is still unknown, however, and detection is difficult because of unclear diagnosis criteria. Colonic stent insertion is commonly used in management of malignant colon obstruction. This is a very safe procedure with a low procedure-related mortality rate, but serious complications can develop. The authors first experienced a patient with TTP when the phenomenon occurred after stent insertion for palliation of obstructive colon cancer and therefore would like to report the case.

Clinical Flow and Outcomes in Patients with Malignant Spinal Cord Compression in Korea / 대한내과학회지

BACKGROUND/AIMS: We investigated the process from the development of symptoms to treatment and analyzed the clinical characteristics, treatment outcomes, and prognostic factors related to the treatment response and survival of patients with malignant spinal cord compression (SCC). METHODS: This study retrospectively reviewed the medical records of 56 patients diagnosed with metastatic SCC using magnetic resonance imaging (MRI) from January 2002 to December 2011. RESULTS: The median age of the patients was 59.5 years, and the most common origin of metastatic SCC was lung cancer. The median interval from symptom development to visiting the hospital was 7 days, and the median interval from admission to the date of clinical diagnosis was 0 days. The median interval from clinical diagnosis to the date of MRI or therapy was 1 or 4 days, respectively. Twenty-six patients (46.4%) had ambulation dysfunction at initial presentation, and 33 patients (61.1%) had ambulation dysfunction after radiotherapy or surgery. The rate of patients regaining walking ability was 17.6% with radiotherapy and 25% with surgery. In univariate analysis, good performance status, ambulatory function, and autonomic function before therapy were favorable predictors of ambulatory function after treatment in all patients. No significant factor was found in multivariate analysis. Median overall survival (OS) was 67 days, and the significant factors for survival by multivariate analysis were performance status and the presence of prostate cancer. CONCLUSIONS: The therapeutic response of ambulatory function and OS in malignant SCC is very poor. Multidisciplinary communication is required for the prompt and optimal management of patients with malignant SCC.

Clinical and Laboratory Characteristics of Pandemic Influenza A/H1N1 2009 Infection among Patients with Malignancy in Korea / 감염과화학요법

BACKGROUND: Patients with malignancy are considered to be at high risk of severe pandemic influenza A/H1N1 2009. This study was conducted to identify the severity of pandemic influenza A/H1N1 2009 among patients with malignancy. MATERIALS AND METHODS: Between August 2009 and December 2009, we reviewed clinical data and medical records of 31 patients with malignancy and 63 hospitalized patients without malignancy. RESULTS: Eighty-three patients with laboratory-confirmed pandemic influenza A/H1N1 2009 were admitted. The rate of ICU admission was higher among patients with malignancy (without malignancy 13% vs with malignancy 35%, P=0.024). The mortality rate was higher among patients with malignancy (without malignancy 6% vs with malignancy 25%, P=0.033). Patients using immunosuppressants showed a higher rate of lower respiratory tract infection (83% vs 24%, P=0.013). CONCLUSIONS: Pandemic influenza A/H1N1 2009 in patients with malignancy was more severe than in patients without malignancy.

Pathophysiological Role of Hormones and Cytokines in Cancer Cachexia

We investigated the role of fasting hormones and pro-inflammatory cytokines in cancer patients. Hormones (ghrelin, adiponectin, and leptin) and cytokines (TNF-alpha, IFN-gamma, and IL-6) were measured by ELISA or RIA in lung cancer and colorectal cancer patients before the administration of cancer therapy, and measurements were repeated every 2 months for 6 months. From June 2006 to August 2008, 42 patients (19 with colorectal cancer and 23 with lung cancer) were enrolled. In total, 21 patients were included in the cachexia group and the others served as a comparison group. No significant difference in the initial adiponectin, ghrelin, TNF-alpha, IFN-gamma, or IL-6 level was observed between groups, although leptin was significantly lower in cachectic patients than in the comparison group (15.3 +/- 19.5 vs 80.9 +/- 99.0 pg/mL, P = 0.007). During the follow-up, the patients who showed a > 5% weight gain had higher ghrelin levels after 6 months. Patients exhibiting elevated IL-6 levels typically showed a weight loss > 5% after 6 months. A blunted adiponectin or ghrelin response to weight loss may contribute to cancer cachexia and IL-6 may be responsible for inducing and maintaining cancer cachexia.

A Case of Peliosis Hepatis Mimicking Metastatic Lesions of Increasing Size

Peliosis hepatis, an uncommon vascular condition, is characterized by multiple blood-filled cavities distributed throughout the liver. Computed tomography and magnetic resonance imaging findings of peliosis hepatis are nonspecific. A 40-year-old woman presented with multiple hepatic cystic masses. Two years later, the number and sizes of the masses had increased. We suspected metastatic hepatic disease and performed a liver biopsy. Histological examination revealed dilatation of hepatic sinusoids and multiple blood-filled cavities throughout the liver parenchyma. Thus, a diagnosis of peliosis hepatis was confirmed.

Simultaneous Translocation of Both TCR Loci (14q11) with Rare Partner Loci (Xq22 and 12p13) in a Case of T-lymphoblastic Leukemia

The most common recurrent cytogenetic abnormalities in T-lymphoblastic leukemia (T-acute lymphoblastic leukemia [T-ALL]) involve T-cell receptor (TCR) loci and a variety of partner genes, including HOX11, HOX11L2, MYC, and TAL1. In this report, we present a rare case involving simultaneous translocation of the TCR alpha/delta loci with different partner loci (Xq22 and 12p13); this resulted in a poor prognosis. Chromosomal analysis showed 46,Y,t(X;14)(q22;q11.2),t(12;14)(p13;q11.2) and FISH analysis by using a T-cell receptor alpha delta DNA probe, Split Signal (DakoCytomation, Denmark), showed translocations at the same TCR alpha/delta locus on both chromosomes. FISH with 2 bacterial artificial chromosome clones showed break apart signal, which suggests involvement of the IRS4 gene. To our knowledge, this is the first report of T-ALL in which both TCR alpha/delta loci were translocated with different partner loci, and 1 of the partner loci, Xq22, was a rare translocation partner locus that included IRS4 gene.