PURPOSE: Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL) is a rare subtype of non-Hodgkin lymphoma, and asparaginase-based regimens are the best first-line treatments. Data on the role of specific circulating lymphocyte subsets in the progression of ENKTL are limited. The aim of this study was to investigate the clinical correlation and distribution of circulating absolute CD4+ T-cell counts (ACD4Cs) in ENKTL. MATERIALS AND METHODS: We retrospectively searched medical records for 70 newly diagnosed ENKTL patients treated with pegaspargase-based regimens. Comparison of ACD4Cs as a continuous parameter in different groups was calculated. Univariate and multivariate analyses were used to assess prognostic factors for overall survival (OS) and progression-free survival (PFS). RESULTS: Stage III/IV, B symptoms, elevated lactate dehydrogenase, monocytopenia, high-intermediate and high risk International Prognostic Index (IPI) and Korean Prognostic Index (KPI), high risk Prognostic Index of Natural Killer Lymphoma (PINK), and lower lymphocytes were significantly associated with low ACD4C at diagnosis. With a median follow-up time of 32 months, patients who had an ACD4C < 0.30×109/L had a worse OS. Median OS was 11 months and median PFS was 5 months in the low ACD4C cohort. There were significant differences in both OS and PFS between the two cohorts. Moreover, multivariate Cox analysis identified ACD4Cs as an independent predictor for OS and PFS. CONCLUSION: Low ACD4Cs were associated with poorer survival and could act as a negative predictor for ENKTL patients treated with asparaginase-based regimens.
Cell Count* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy* ; Follow-Up Studies ; Humans ; L-Lactate Dehydrogenase ; Lymphocyte Subsets ; Lymphocytes ; Lymphoma* ; Lymphoma, Extranodal NK-T-Cell ; Lymphoma, Non-Hodgkin ; Medical Records ; Multivariate Analysis ; Prognosis* ; Retrospective Studies ; T-Lymphocytes

BACKGROUND AND PURPOSE: Brain-derived neurotrophic factor (BDNF) is a neuronal growth factor that plays an essential role in the maintenance of the nervous system. We have evaluated the peripheral blood protein levels of BDNF and the valine-to-methionine substitution at codon 66 (Val66Met) single-nucleotide polymorphism (SNP) as potential biomarkers for the early recognition of chemotherapy-induced peripheral neuropathy (CIPN) in non-Hodgkin lymphoma and multiple myeloma patients. METHODS: CIPN was assessed in 45 patients at the diagnosis and during vincristine or bortezomib-based therapy using objective [reduced version of the Total Neuropathy Score (TNSr)] and subjective (FACT-GOG-NTx) tools. Depression was assessed using the Patient Health Questionnaire-9 (PHQ-9) questionnaire. BDNF protein levels and the Val66Met SNP were determined using ELISA and Sanger sequencing. RESULTS: The pretreatment BDNF protein level was inversely correlated with the maximum TNSr, FACT-GOG-NTx, and PHQ-9 scores in both genotypes. BDNF patients with the Val/Val genotype demonstrated significantly higher maximum FACT-GOG-NTx and PHQ-9 scores than those with the Val/Met and Met/Met genotypes (Met-BNDF carriers). Correlations between PHQ-9 and TNSr score were found only in Met-BDNF carriers, suggesting that peripheral neuropathy and depression coincide in Met-BDNF carriers. CONCLUSIONS: Determining the BDNF protein levels before initiating chemotherapy might be a useful tool for CIPN risk assessment and preemptive dose modification. The present data should be validated in larger studies that include other neurotoxic agents.
Biomarkers ; Brain-Derived Neurotrophic Factor ; Codon ; Depression ; Diagnosis ; Drug Therapy ; Enzyme-Linked Immunosorbent Assay ; Genes, vif ; Genotype ; Humans ; Lymphoma ; Lymphoma, Non-Hodgkin ; Multiple Myeloma ; Nervous System ; Neurons ; Peripheral Nervous System Diseases ; Risk Assessment ; Vincristine

Primary central nervous system lymphoma (PCNSL) is an extranodal Non-Hodgkin's lymphoma that is confined to the brain, eyes, and/or leptomeninges without evidence of a systemic primary tumor. Although the tumor can affect all age groups, it is rare in childhood; thus, its incidence and prognosis in children have not been well defined and the best treatment strategy remains unclear. A nine-year old presented at our department with complaints of diplopia, dizziness, dysarthria, and right side hemiparesis. Magnetic resonance image suggested a diffuse brain stem glioma with infiltration into the right cerebellar peduncle. The patient was surgically treated by craniotomy and frameless stereotactic-guided biopsy, and unexpectedly, the histopathology of the mass was consistent with diffuse large B cell lymphoma, and immunohistochemical staining revealed positivity for CD20 and CD79a. Accordingly, we performed a staging work-up for systemic lymphoma, but no evidence of lymphoma elsewhere in the body was obtained. In addition, she had a negative serologic finding for human immunodeficient virus, which confirmed the histopathological diagnosis of PCNSL. She was treated by radiosurgery at 12 Gy and subsequent adjuvant combination chemotherapy based on high dose methotrexate. Unfortunately, 10 months after the tissue-based diagnosis, she succumbed due to an acute hydrocephalic crisis.
Biopsy ; Brain Stem* ; Brain* ; Central Nervous System* ; Child* ; Craniotomy ; Diagnosis ; Diplopia ; Dizziness ; Drug Therapy, Combination ; Dysarthria ; Glioma ; Humans ; Incidence ; Lymphoma* ; Lymphoma, B-Cell ; Lymphoma, Non-Hodgkin ; Methotrexate ; Paresis ; Prognosis ; Radiosurgery

Spontaneous gastric perforation is a rare complication of gastric lymphoma that is potentially life threatening since it can progress to sepsis and multi-organ failure. Morbidity also increases due to prolonged hospitalization and delay in initiating chemotherapy. Therefore prompt diagnosis and appropriate treatment is critical to improve prognosis. A 64-year-old man presented to the emergency department with severe abdominal pain. Chest X-ray showed free air below the right diaphragm. Abdominal CT scan also demonstrated free air in the peritoneal cavity with large wall defect in the lesser curvature of gastric lower body. Therefore, the patient underwent emergency operation and primary closure was done. Pathologic specimen obtained during surgery was compatible to diffuse large B cell lymphoma. Fifteen days after primary closure, the patient received subtotal gastrectomy and chemotherapy was initiated after recovery. Patient is currently being followed-up at outpatient department without any particular complications. Herein, we report a rare case of gastric lymphoma that initially presented as peritonitis because of spontaneous gastric perforation.
Abdominal Pain ; Antigens, CD20/metabolism ; Antigens, CD45/metabolism ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Gastrectomy ; Humans ; Intestinal Perforation/diagnostic imaging ; Lymphoma, Large B-Cell, Diffuse/*diagnosis/drug therapy/pathology ; Lymphoma, Non-Hodgkin/*diagnosis/drug therapy/pathology ; Male ; Middle Aged ; Positron-Emission Tomography ; Stomach Neoplasms/*diagnosis/drug therapy/pathology ; Tomography, X-Ray Computed

OBJECTIVETo analyze the clinical characteristics and the course of diagnosis and therapy of PEG-asparaginase associated pancreatitis (AAP) in childhood, and to reveal the pathophysiology of AAP, enhance the ability of diagnosis and treament.

METHODData of 13 cases with AAP in childhood seen from March 2011 to March 2014 were analyzed with regard to clinical manifestations, laboratory findings, imaging feature and treatment.

RESULTAAP was found in 12 of acute lymphoblastic leukemia (ALL) and 1 of non-Hodgkin's lymphoma (NHL), 8 were boys and 5 were girls, with a mean age 6 years. In 12 cases AAP occurred during the induction-remission treatment, in 1 case during the maintenance- intensification phase. AAP occurred after a median of two doses, and 9 d (median) from the latest administration of PEG-asparaginase. The major manifestations of AAP was abdominal pain (11/13) . At the time of AAP diagnosis during the first 48 hours the median peak serum amylase and serum lipase levels were 559 U/L (range 118-1 585, upper normal limit: 125) and 934 U/L (range 221-1 673, upper normal limit: 300). Three cases with serum amylase and serum lipase levels above 3 times upper normal limit were repeatedly complicated with pancreatic pseudocyst; 11 patients had abnormal CT imaging, 8 cases revealed effusion around the pancreas, and 4 cases had pseudocyst. Therapy with ulinastatin, octreotide acetate, glucocorticoid could relieve abdominal pain significantly. Three cases underwent abdominal puncture drainage and 5 cases fulfilled nasojejunal nutrition therapy. Nine of them were cured, 4 developed pseudocyst, in 2 AAP vanished gradually and 2 died with pseudocyst.

CONCLUSIONThe major manifestations of AAP were abdominal pain, but sometimes apparent and sometimes latent. Condition of acute pancreatitis may exacerbate rapidly and easily. Early identification had significance. Pancreatic pseudocyst suggested a poor prognosis.

Acute Disease ; Asparaginase ; adverse effects ; therapeutic use ; Child ; Female ; Humans ; Lymphoma, Non-Hodgkin ; drug therapy ; Male ; Pancreatic Pseudocyst ; Pancreatitis ; chemically induced ; diagnosis ; therapy ; Polyethylene Glycols ; adverse effects ; therapeutic use ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; drug therapy

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/computed tomography scan and bone marrow examination, which may be useful for early diagnosis.
Aged ; Bone Marrow ; Bone Marrow Examination ; Diagnosis, Differential ; Drug Therapy ; Early Diagnosis ; Electrons ; Fever ; Humans ; Hypercalcemia* ; Lymphatic Diseases ; Lymphoma, B-Cell* ; Lymphoma, Non-Hodgkin ; Male ; Parathyroid Hormone-Related Protein* ; Spleen

Hepatitis C virus (HCV) is one of the main viral causes of hepatocellular carcinoma (HCC) and is associated with lymphoproliferative disorder such as non-Hodgkin's lymphoma (NHL). However, there are only few case reports on concomitantly induced NHL and HCC by HCV. Herein, we report a case of synchronous NHL and HCC in a patient with chronic hepatitis C which was unexpectedly diagnosed during liver transplantation surgery. This case suggests that although intrahepatic lymph node enlargements are often considered as reactive or metastatic lymphadenopathy in chronic hepatitis C patients with HCC, NHL should also be considered as a differential diagnosis.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*diagnosis/radiotherapy ; Drug Therapy, Combination ; Embolization, Therapeutic ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Genotype ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/complications/*diagnosis/*virology ; Humans ; Liver Neoplasms/complications/*diagnosis/radiotherapy ; Lymph Nodes/pathology ; Lymphoma, Non-Hodgkin/complications/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

BACKGROUND: Anaplastic large cell lymphoma (ALCL) is uncommon in children, accounting for approximately 15% of all cases of childhood non-Hodgkin lymphoma. Despite many studies attempting new treatment strategies, treatment outcomes have not significantly improved, and the optimal treatment for pediatric ALCL has not been established. METHODS: The records of newly diagnosed ALCL patients at our institute between July 1998 and April 2013 were reviewed. We evaluated the general characteristics of the patients, chemotherapy regimens, overall survival (OS) rates, and event-free survival (EFS) rates. RESULTS: Twenty-eight ALCL patients were eligible. The median age at diagnosis was 10.8 years. Lymph node involvement was the most common presentation (79%). CCG-5941, a multi-agent T-cell lineage chemotherapy, was the predominant treatment regimen (57%). The five-year OS and EFS rates were 88% and 69%, respectively. Stage, the presence of B symptoms, lung involvement, and bone marrow involvement were significant prognostic factors for EFS (P=0.02, 0.01, 0.01, and 0.02, respectively). Eight patients relapsed, and three died during the study period. Four of the eight patients who relapsed were treated with high-dose chemotherapy and autologous stem cell transplantation (HDCT-ASCT). Two of the four who had undergone HDCT-ASCT developed secondary relapses and were subsequently treated with allogeneic SCT or brentuximab. CONCLUSION: We found that treatment outcomes with multi-agent chemotherapy in children with ALCL were similar to those of previous reports, and that relapsed patients could be salvaged with HDCT-ASCT or allogeneic SCT. A prospective, larger cohort study is warranted to define the optimal treatment for pediatric ALCL.
Bone Marrow ; Child* ; Cohort Studies ; Diagnosis ; Disease-Free Survival ; Drug Therapy ; Humans ; Lung ; Lymph Nodes ; Lymphoma, Large-Cell, Anaplastic* ; Lymphoma, Non-Hodgkin ; Prognosis ; Recurrence ; Stem Cell Transplantation ; T-Lymphocytes

BACKGROUND: Treatment outcomes of children with non-Hodgkin lymphoma (NHL) have dramatically improved in recent years. However, there are few studies on the outcomes of pediatric NHL in Korea.METHODS: We retrospectively analyzed the outcomes of 34 children diagnosed with NHL and treated at Kosin University Gospel Hospital from Jan. 1987 to Dec. 2009, according to age, lactate dehydrogenase (LDH) level, histology, stage and involved site.RESULTS: The mean age of the subjects was 9.0 years. The abdomen and head/neck regions were the most common primary sites. On histologic classification, Burkitt lymphoma was the most common, followed by lymphoblastic lymphoma, diffuse large B-cell lymphoma, anaplastic large cell lymphoma, and unclassifiable, with respective incidences of 35.3%, 23.5%, 17.6%, 17.6%, and 5.9%. Various combination chemotherapies according to the diagnosis with mean treatment duration of 14.9 months showed 5 year event free survival (EFS) and 5 year overall survival (OS) rate of 67.7+/-8.0% and 79.3+/-7.0%, respectively. Nine out of the 34 patients relapsed, and the 5 year OS rates for those who relapsed vs. 25 patients without relapse were 44.4+/-16.6%, vs. 92.0+/-5.4%, respectively (P<0.01). Although 5 year EFS rate varied according to stage, 5 year OS rate were not different according to age, sex, LDH, stage, histology, or treatment period.CONCLUSION: The outcome of children with NHL treated in our setting was comparable to those of other large centers in Korea. No factor other than stage, including LDH, histologic subtype showed significant prognostic value.
Abdomen ; Burkitt Lymphoma ; Child ; Classification ; Diagnosis ; Disease-Free Survival ; Drug Therapy, Combination ; Humans ; Incidence ; Korea ; L-Lactate Dehydrogenase ; Lymphoma, B-Cell ; Lymphoma, Large-Cell, Anaplastic ; Lymphoma, Non-Hodgkin ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; Retrospective Studies

OBJECTIVETo analyze outcomes and prognostic factors of children with B-cell non-Hodgkin lymphoma (B-NHL).

METHODSOne hundred and four newly diagnosed B-NHL children were enrolled in protocol of B-NHL 2001. The statistics were performed by SPSS 13.0.

RESULTSOf 104 children (79 males, the median age of 7.1 years), 60, 32 and 4 patients were diagnosed with Burkitt lymphoma, diffuse large B-cell lymphoma and unclassifiable B-cell lymphoma, respectively. Four patients were in stage Ⅰ, 27 stage Ⅱ, 55 stage Ⅲ and 18 stage Ⅳ; 1, 26 and 77 patients were allocated into R1, R2 and R3 risk groups, respectively. Three patients never got complete remission (CR), 9 patients relapsed after CR with the duration of relapse from 1 to 7 months after chemotherapy. The estimated 5-year EFS of 104 patients was (86.7 ± 3.5)%. Univariable analyses identified that risk factors for recurrence were of higher staging, elevated LDH, serum ferritin and poor early response. Age, sex, pathologic diagnosis, original tumor, bone or marrow involvement, C-MYC and risk group were not found to be associated with the risk of failure to treatment. Multivariable COX regression models confirmed serum ferritin as a significant independent prognostic marker.

CONCLUSIONB-NHL 2001 protocol was reasonable for B-NHL children. Higher staging, elevated LDH, serum ferritin and poor early response increased risk for recurrence.

Adolescent ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Lymphoma, B-Cell ; diagnosis ; drug therapy ; Lymphoma, Non-Hodgkin ; diagnosis ; drug therapy ; Male ; Prognosis ; Prospective Studies ; Treatment Outcome