Role of frontline autologous stem cell transplantation in young, high-risk diffuse large B-cell lymphoma patients

BACKGROUND/AIMS: Several studies have demonstrated the effect of autologous hematopoietic stem cell transplantation (auto-HSCT) as a salvage treatment for patients with relapsed diffuse large B-cell lymphoma (DLBCL). However, the role of auto-HSCT as a frontline treatment has not been fully investigated in the rituximab era. We validated the age-adjusted International Prognostic Index (aaIPI) score for high-risk DLBCL patients and identified a possible role for frontline auto-HSCT. METHODS: We recommended frontline auto-HSCT for high-risk DLBCL patients who satisfied the criteria of both a higher Ann-Arbor stage (III to IV) and an elevated lactate dehydrogenase (LDH) level at diagnosis with an aaIPI score > or = 2. From 2006 to 2011, among the 150 DLBCL patients aged or = 2 showed inferior overall survival (OS; p = 0.040) and progression-free survival (PFS; p = 0.007) compared to the aaIPI score 0 to 1. Between the two treatment arms among the high-risk DLBCL patients, the clinical parameters were not different. The high-risk group treated with frontline auto-HSCT showed similar OS (p = 0.392) and PFS (p = 0.670) to those in the low-risk group. Thus, frontline auto-HSCT showed superior PFS (p = 0.004), but only a trend towards favorable OS (p = 0.091) compared to R-CHOP alone. CONCLUSIONS: We identified the possible role of frontline auto-HSCT for high-risk DLBCL with a higher stage (III to IV) and elevated LDH level.

SOCS1 and SOCS3 are expressed in mononuclear cells in human cytomegalovirus viremia after allogeneic hematopoietic stem cell transplantation

BACKGROUND: The expression of the SOCS genes in cytomegalovirus (CMV) viremia after hematopoietic stem cell transplantation (HSCT) remains largely unexplored. METHODS: Using quantitative RT-PCR of mononuclear cells, we conducted pairwise comparison of SOCS1 and SOCS3 expression levels among a healthy donor group (N=55), a pre-HSCT group (N=17), and the recipient subgroup (N=107), which were divided according to the occurrence of CMV viremia and acute graft-versus-host disease (aGVHD). RESULTS: Compared to that in the healthy donor group, SOCS1 expression was higher in the CMV+ subgroup, especially in the CMV+GVHD- group, but decreased in the other subgroups. When compared to the expression in the pre-HSCT group, SOCS1 expression was significantly higher in the CMV+ subgroup, especially in the CMV+GVHD+ subgroup. Meanwhile, compared to that in the healthy donor group, SOCS3 expression was significantly lower in all other groups. The CMV-GVHD- subgroup showed significantly lower SOCS3 expression compared to the CMV+ subgroup, the CMV+GVHD+ subgroup, and the CMV+GVHD- subgroup. CONCLUSION: We report differential expression of SOCS genes according to CMV viremia with acute GVHD occurrence after HSCT, suggesting that regulation of SOCS expression is associated with CMV viremia.

Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

Expression of SOCS1 and SOCS3 genes in human graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

BACKGROUND: Suppressor of cytokine signaling genes (SOCS) are regarded as pivotal negative feedback regulators of cytokine signals, including the interferon-gamma (IFN-gamma), granulocyte-colony stimulating factor, and interleukin families, released by T cells. A detailed understanding of the involvement of SOCS genes in graft-versus-host disease (GVHD) is critical to effectively manage GVHD, yet their expression patterns among recipients remain largely unexplored. METHODS: Expression levels of SOCS1 and SOCS3 were determined by real-time quantitative reverse transcription PCR (qRT-PCR) in patients with acute GVHD (aGVHD) and chronic GVHD (cGVHD), in a severity-dependent manner, after allogeneic hematopoietic stem cell transplantation (HSCT). A total of 71 recipients with AML (N=40), ALL (N=12), myelodysplastic syndromes (MDS; N=10), chronic myelogenous leukemia (CML; N=2), severe aplastic anemia (SAA; N=5), or others (N=2), who received allogeneic HSCT from human leukocyte antigen-identical siblings or unrelated donors between 2009 and 2011, were included in the present study. RESULTS: Overall, the expression levels of SOCS1 decreased in recipients with grade II to IV aGVHD and cGVHD when compared to normal donors and non-GVHD recipients. Interestingly, the expressions of SOCS1 decreased significantly more in cGVHD than in aGVHD recipients (P=0.0091). In contrast, SOCS3 expressions were similarly reduced in all the recipients. CONCLUSION: This is the first study to show that SOCS1 and SOCS3 are differentially expressed in recipients following allogeneic HSCT, suggesting a prognostic correlation between SOCS genes and the development of GVHD. This result provides a new platform to study GVHD immunobiology and potential diagnostic and therapeutic targets for GVHD.

The impact of novel therapeutic agents before and after frontline autologous stem cell transplantation in patients with multiple myeloma

BACKGROUND: Novel agents (NAs) such as thalidomide and bortezomib have been administered in combination with autologous stem-cell transplantation (ASCT) to effectively treat multiple myeloma (MM). However, whether NAs perform better as induction treatments prior to transplantation, or as post-transplant maintenance therapies remains unclear. METHODS: We retrospectively analyzed 106 consecutive patients with MM who underwent ASCT within 1 year of diagnosis as first-line therapy. RESULTS: Eighty-seven (82.1%) patients received NAs before ASCT, whereas 68 (64.2%) received NAs after ASCT. NAs were administered to each patient as follows: before ASCT alone (N=29, 27.4%), after ASCT alone (N=10, 9.4%) or both before and after ASCT (N=58, 54.7%). High-quality rates before and after ASCT were significantly higher for patients who received NAs as induction treatment compared to those who did not receive pre-transplant NAs. At a median follow-up of 37.9 months, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 42.8% and 70.2%, respectively. The PFS and OS were significantly higher in patients with NAs as post-transplant maintenance treatment (P=0.03 and P=0.04, respectively), but not in those with NAs as pre-transplant induction treatment. The PFS of patients with NAs before and after ASCT was higher than that of the patients with NAs as induction therapy alone (P=0.05). Age, serum beta2-microglobulin level, complete response after ASCT, and NA use post-ASCT independently predicted survival outcomes. CONCLUSION: These findings suggest that integration of NAs post-ASCT could benefit patients with MM undergoing ASCT. Induction therapy using NAs also improves high-quality response rates before and after ASCT.

A Case of Intracranial Involvement in Plasma Cell Myeloma / 영남의대학술지

Plasma cell myelomas generally manifest as bone or soft-tissue tumors with variable mass effects, pain, and infiltrative behavior. Extramedullary involvement occurs most commonly in the spleen, liver, lymph nodes, and kidneys, but intracranial involvement in plasma cell myeloma is a rare extramedullary manifestation. These authors recently encountered a case of intracranial involvement of plasma cell myeloma. A 69-year-old man was hospitalized for headache and mental changes. Brain CT showed subdural hemorrhage caused by plasma cell myeloma. Plasma cell myeloma with intracranial involvement has poor prognosis, and the patient in this case died from acute complications, such as subdural hemorrhage. Based on this case report, it is suggested that more effective treatment regimens of plasma cell myeloma with intracranial involvement be developed. Moreover, a screening method and decision on the appropriate time for intracranial involvement are needed for plasma cell myeloma patients.

A Case of Multiple Pulmonary Plasmacytomas after Complete Remission of Multiple Myeloma / 결핵및호흡기질환

Extramedullary plasmacytoma (EMP) is a rare disorder that typically occurs in the upper airway. Although the condition rarely arises in the lungs, a few cases have been reported. Here, we report a case of pulmonary plasmacytoma in 66-year-old man, who had been treated with VAD (vincrestine, adriamycin, dexamethasone) chemotherapy for multiple myeloma. The patient had been declared clear of multiple myeloma after 4 cycles of chemotherapy. Three months later, the patient had multiple masses visible on computed tomography (CT) and on positron emission tomography-computed tomography (PET-CT) with hot uptake. Subsequent studies using CT-guided needle biopsy and immunohistochemical stain showed pulmonary plasmacytoma. Bone marrow biopsy, serum, and urine M protein tests were repeated, showing no evidence of multiple myeloma. Pulmonary plasmacytomas, as extramedullary plasmacytomas, were considered an isolated manifestation of multiple myeloma recurrence. We treated the patient with concurrent chemoradiotherapy and the pulmonary plasmacytomas regressed dramatically.

Oral Beclomethasone Dipropionate for the Treatment of Steroid-refractory Gastrointestinal Acute Graft-versus-host Disease / 대한혈액학회지

Acute graft-versus-host disease (GVHD) is one of the most severe complications following allogeneic stem cell transplantation (SCT), and involvement of the gut has been associated with increased mortality and a poorer response to high-dose systemic corticosteroids. For over a decade, oral beclomethasone dipropionate (BDP) has been studied in the treatment of acute gastrointestinal GVHD, as a monotherapy, or in combination with systemic corticosteroids. Here we report, for the first time in Korea, the efficacy of oral BDP (8 mg/day for 25 days) in 3 adults with acute lymphoblastic leukemia who developed steroid-refractory gastrointestinal GVHD (grade III) after myeloablative conditioning SCT (1 matched sibling transplant, 2 matched unrelated transplants). All patients responded completely to oral BDP treatment. Oral BDP is safe and effective for the control of steroid-refractory acute gastrointestinal GVHD.

Secondary involvement of the skull base in malignant B-cell lymphoma / 대한내과학회지

We report a case of B-cell lymphoma with multiple asymmetrical cranial nerve palsies as the initial presentation. A 70-year-old woman complained of chin numbness, diplopia, dysarthria, and headache that had developed insidiously over the previous 2 months. The neurological examination showed multiple cranial nerve dysfunction, including right V and left VI nerve palsies. Her cerebrospinal fluid was normal, while her bone marrow biopsy revealed CD20-positive B-cell lymphoma. Five days after starting R-CHOP (rituximab-cyclophosphamide, adriamycin, vincristine, prednisolone) chemotherapy, her cranial nerve palsies and pain had improved markedly. Twenty days after starting R-CHOP chemotherapy, however, she was rehospitalized due to general worsening paralysis. In the hospital, the general paralysis progressed rapidly and she lapsed into delirium. No additional treatment was given based on the directives of her guardian and herself, and she was allowed to leave the hospital for hospice care.

Effect of the G-CSF schedule for harvesting peripheral blood progenitor cells from healthy donors / 대한내과학회지

BACKGROUND/AIMS: Peripheral blood progenitor cells (PBSC) have been used instead of bone marrow cells for allogeneic transplantation. Progenitor cells are mobilized using granulocyte colony stimulating factor (G-CSF). Kinetic studies of G-CSF have shown that the CD34+ cells peak on day 5, although the optimal time for harvesting has not been established. METHODS: We compared two mobilization schedules using G-CSF. In groups I and II, G-CSF 10 microgram/kg/day was administered subcutaneously for 3 or 4 days, respectively, and leukapheresis was performed the next day. RESULTS: In groups I and II, a respective mean number of 5.84 x 106 and 10.76 x 106 circulating CD34+ cells per kilogram of the recipient's weight was collected by leukapheresis. The yield of the two collections did not differ significantly (p=0.386). CONCLUSION: This study suggested that the two mobilization schedules are equally effective. To avoid prolonged exposure to G-CSF, the day 4 collection schedule is the preferred mobilization strategy.

Acute Hemolysis and Renal Failure caused by Hepatitis A Infection with Underlying Glucose-6-Phosphate Dehydrogenase Deficiency / 대한진단검사의학회지

Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder worldwide, it has rarely been reported among Korean. The patient was previously healthy 39 yr old male who showed severe hemolytic anemia and acute renal failure accompanied by hyperbilirubinemia after hepatitis A infection. The additional studies for differential diagnosis of hemolytic anemia showed a moderate deficiency of G6PD enzyme. Because hepatitis A infection in patient with G6PD deficiency present much more severe clinical symptoms, G6PD enzyme should be examined in patients with triggering factors of hemolysis such as hepatitis A infection.

No Associations between Schizophrenia and D22S280 Marker on Synapsin III Gene in Korean Males

OBJECTIVES: Synapsin III near VCFS region on chromosome 22q affects. It could be an interesting candidate gene for schizophrenia. D22S280 is a highly polymorphic genetic marker residing in synapsin III. We examined association of D22S280 marker on synapsin III with Korean patients with schizophrenia. METHODS: The subjects were 46 male Korean patients with schizophrenia and 60 male normal controls. Using polymerase chain reaction, gel electrophoresis, ABI 310 genetic analyzer, and GeneScan Collection 3.1 software, we confirmed genotypes of D22S280 marker. We examined Hardy-Weinberg equilibrium and case-control association using SAS/Genetic 9.1.3. RESULTS: Genotypes of both schizophrenia and control groups were in Hardy-Weinberg equilibrium. We could not find any significant statistical differences in allele-wise(chi-square=10.4, df=6, p=0.098) and genotype-wise (chi-square=22.1 df=19, p=0.258) analyses of D22S280 marker between schizophrenia and normal controls. Individual allele analyses with df=1 showed significant differences in A1(p=0.025) and A7(p=0.034) allele, which were not significant following Bonferroni corrections(A1 : p=0.177, A7 : p=0.235). CONCLUSION: We couldn't find any association between schizophrenia and the synapsin III gene. Given the small number of subjects studied, further investigations are needed.

Four Cases of Non-Hodgkin's Lymphoma in AIDS patients

The incidence of opportunistic infection has decreased since the introduction of highly active antiretroviral therapy, so lymphoma is now far and away the most lethal complication of acquired immunodeficiency syndrome. We have experienced four cases of NHL in AIDS patients. The first patient was a 37 year old male who presented with left sided hemiplegia due to CNS lymphoma. The second patient was a 40 year old male who was admitted because of jaundice; he was diagnosed as having lymphoma that exclusively involved the liver. The third patient was a 38-year-old male who presented with palpable mass in the left cervical region, which was diagnosed as lymphoma. Above three cases were confirmed as diffuse large B cell lymphoma. The fourth patient presented with a protruding swollen chest wall mass on the right side of his chest, this was determined pathologically to be the Burkitt's type. The latter case is the first report of NHL involving the chest wall musculature in a Korean AIDS patient.

A case of granulocytic sarcoma of the pancreas and kidney in a patient presenting with jaundice / 대한내과학회지

Granulocytic sarcoma is an extramedullary tumor composed of immature cells of the granulocytic series known to occur in patients with myelodysplastic syndrome, chronic myeloid leukemia, or acute myeloid leukemia. and occasionally it has been presented without overt leukemia. Involvement of pancreas and kidney is relatively rare in granulocytic sarcoma. We present an extremely rare case of granulocytic sarcoma of pancreas and kidney in a 56-year-old male patient of acute myeloid leukemia presenting with obstructive jaundice due to a pancreatic mass and peri-lymphadenopathy consisting of myeloblast and review the literatures. It should be kept in mind that granulocytic sarcoma is a possible cause of obstructive jaundice in patient with acute myeloid leukemia.

The Differences of EEG Coherence between Schizophrenia and Bipolar Disorder

OBJECTIVES: EEG coherence could imply the connectivity between two different areas of the brain, which is known to be important in the pathophysiology of bipolar I disorder(BPD I) and schizophrenia. The authors investigated EEG coherence in patients with BPD I and schizophrenia to examine the connectivity of the neural circuit. METHODS: EEGs were recorded in 15 schizophrenia and 14 bipolar disorder patients, and 14 age-matched normal control subjects from 16 electrodes with linked-ear reference. Spectral parameters and coherence were calculated for the alpha bandwidth(8-13Hz) by a multi-channel autoregressive model using 20 artifact-free 2-seconds epochs and the differences were compared among three groups by two different statistical methods; F-test and Kruskal-Wallis test. Furthermore, when there were significant differences among three groups, Scheffe's multiple comparison tests were provided and Jonckheere-Terpstra tests for the ordered alternative were given. RESULTS: In the intra-hemispheric comparison, left frontal coherence was increased in order of control, BPD I and schizophrenia. In the inter-hemispheric comparison, 1) inter-prefrontal coherence in BPD I was significantly higher than in normal controls, and 2) inter-prefrontal coherence in schizophrenia was significantly lower than in controls. CONCLUSION: These results suggest that 1) both schizophrenia and BPD I are diseases having the abnormality of neural circuit connectivity in both frontal and prefrontal lobes, and 2) the abnormality is more severe in schizophrenia than in BPD I. Furthermore, the data support that a common pathogenetic process may reside in both schizophrenia and BPD I.

Surgical Management of Chronic Lymphedema of Penis and Scrotum / 대한비뇨기과학회지

Chronic lymphedema of the penis and scrotum is a rare disease in Korea. Lymphedema can be defined as an accumulation of excessive lymph, proteins, chronic inflammation, edema and fibrosis, secondary to the impairment of the lymph vessels, which can be classified into primary, which is the result of inadequate drainage of lymph caused by agenesis and hypogenesis of lymph vessels, and secondary, which could be due to an obstruction or interruption of the lymphatic system, caused by malignancies, post-operative, post-radiation fibrosis, infection, trauma or excision. The treatment method for a lymphedema of the genitalia is determined by cause, which is crucial to the natural course of the disease. In contrast to a primary lymphedema without soft tissue changes and injury, which could be treated conservatively, surgical excision is the best method to treat a chronic lymphedema with soft tissue changes. In this article, a case of penile and scrotal chronic lymphedema of unknown cause, treated with surgical methods, is reported.

A case of subcutaneous plasmacytomas of vessel puncture site in multiple myeloma after autologous stem cell transplantation / 대한내과학회지

We report a case of a 61-year-old man with Durie-Salmon stage IB, kappa light chain type, multiple myeloma (MM), who relapsed 6 months after autologous hematopoietic stem cell transplantation (HSCT). One month after vinblastin-mitoxantrone-dexamethasone chemotherapy, he presented with multiple subcutaneous plasmacytomas. These lesions were confined to previous vessel puncture sites such as subclavian central catheter insertion site, anchoring site and sampling site. He had no past history of plasmacytoma. After additional treatment of etoposide, cisplatin, solumedrol, cytosine arabinoside, the plasmacytomas decreased or disappeared. But blasts reappeared in his peripheral blood and the size of the plasmacytomas increased. This case represents the rare report of refractory MM presenting as multiple subcutaneous plasmacytomas with specific tropism to the sites of previous trauma.

Induction Chemotherapy for Patients with Acute Myeloid Leukemia Aged over 60 Years / 대한혈액학회지

BACKGROUND: Clinical and biologic characteristics of elderly patients with acute myeloid leukemia (AML) have not been well defined yet and there is no consensus on the appropriate treatment approach. We analyzed the outcome of these patients in terms of complete remission (CR) and the long-term life expectancy. METHODS: Twenty patients received mitoxantrone at the dose range of 4~8 mg/m2/ day for 3 days according to the patients' condition based on age and performance status, low-dose cytosine arabinoside 10mg/m2 subcutaneously at every 12 hours for 10~14 days, and etoposide 100mg/day per os for 10~14 days. Most of patients achieving CR received at least 1~3 more courses of post-remission therapy with same initial regimen. Nine out of 17 patients receiving more than two courses of post-remission chemotherapy received their cryopreserved peripheral bloods stem cells after the second or third consolidation chemotherapy. RESULTS: Overall, CR was achieved in 16 (80%) out of 20 patients and the median CR duration was 6 months (range 2~17 months). The most frequent complication during the induction chemotherapy was pneumonia (55%). CONCLUSION: The induction chemotherapy regimen including mitoxantrone, cytosine arabinoside, and etoposide seems to be promising in elderly AML patients in terms of CR rate, while its duration was short. Hopefully, it is necessary to develop a new post-remission therapy to maintain long-term disease-free survival in elderly AML patients.

A case of thymic hyperplasia after high-dose chemotherapy in a patient with malignant lymphoma / 대한내과학회지

Thymic hyperplasia results from thymic regrowth after atrophy during a stressful period. Differentiation from recurrent or residual neoplasm may be an important consideration. Thymic hyperplasia is most problematic when it is observed in patients with malignant lymphoma. We report a case of thymic hyperplasia in which thymic enlargement is developed in a malignant lymphoma patient with high-dose chemotherapy and autologous peripheral blood stem cell transplantation and this condition is confirmed by the findings of serial chest computed tomography without chemotherpy.

Protein Losing Enteropathy in a Patient with Henoch-Sch nlein Purpura: Successful Treatment with Steroid / 대한신장학회잡지

Although gastrointestinal manifestations are very common in patients with Henoch-Sch nlein purpura, protein losing enteropathy is a rare complication. We here report a case of protein losing enteropathy in a patient with Henoch-Sch nlein purpura. A 52-year old woman presented with lower abdominal pain, purpura and edema on lower extremity. Serum albumin was 1.9g/dL and 24 hour urine protein was 4.7g/ day. Skin and kidney biopsy revealed leukocytoclastic vasculitis and mesangial proliferative glomerulonephritis consistent with Henoch-Sch nlein purpura, respectively. Colonoscopy showed diffuse mucosal erosion at right colon. 99mTc-human serum albumin scintigraphy and fecal alpha-1-antitrypsin clearance confirmed protein losing enteropathy. The protein losing enteropathy improved with steroid treatment.