BACKGROUND: Patients with paroxysmal nocturnal hemoglobinuria (PNH) often have concurrent aplastic anemia (AA). This study aimed to determine whether eculizumab-treated patients show clinical benefit regardless of concurrent AA. METHODS: We analyzed 46 PNH patients ≥18 years of age who were diagnosed by flow cytometry and treated with eculizumab for more than 6 months in the prospective Korean PNH registry. Patients were categorized into two groups: PNH patients with concurrent AA (PNH/AA, N=27) and without AA (classic PNH, N=19). Biochemical indicators of intravascular hemolysis, hematological laboratory values, transfusion requirement, and PNH-associated complications were assessed at baseline and every 6 months after initiation of eculizumab treatment. RESULTS: The median patient age was 46 years and median duration of eculizumab treatment was 34 months. Treatment with eculizumab induced rapid inhibition of hemolysis. At 6-month follow-up, LDH decreased to near normal levels in all patients; this effect was maintained until the 36-month follow-up regardless of concurrent AA. Transfusion independence was achieved by 53.3% of patients within the first 6 months of treatment and by 90.9% after 36 months of treatment. The mean number of RBC units transfused was significantly reduced, from 8.5 units during the 6 months prior to initiation of eculizumab to 1.6 units in the first 6 months of treatment, for the total study population; this effect was similar in both PNH/AA and classic PNH. CONCLUSION: This study demonstrated that eculizumab is beneficial in the management of patients with PNH/AA, similar to classic PNH.
Anemia, Aplastic* ; Cohort Studies* ; Flow Cytometry ; Follow-Up Studies ; Hemoglobinuria, Paroxysmal* ; Hemolysis ; Humans ; Prospective Studies*

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is not only a key signaling molecule in the regulation of growth but is also involved in malignant transformation. We investigated the prognostic significance of STAT3 expression in 94 non-elderly adult patients (aged 38 to 65 yr) with newly diagnosed multiple myeloma (MM). METHODS: Tumor cell-specific phosphotyrosine-STAT3 (PY-STAT3) expression at the time of diagnosis was evaluated with dual immunohistochemical (IHC) staining for PY-STAT3 and CD138. RESULTS: PY-STAT3 positivity was detected in 10 patients (10.6%), including three who showed strong expression. PY-STAT3-positive patients had higher serum C-reactive protein and calcium levels at diagnosis than did PY-STAT3-negative patients. PY-STAT3 positivity had predictive value for poor progression-free survival (PFS; P=0.001) and overall survival (OS; P=0.003). Among the 60 patients who received frontline autologous stem cell transplantation, PY-STAT3-positive patients had poorer PFS than did PY-STAT3-negative patients (4.2 vs. 19.2 mo, respectively; P=0.013). Multivariate analysis identified PY-STAT3 expression as an independent prognostic factor for PFS (relative risk [RR]=2.706, P=0.014) and OS (RR=3.091, P=0.044). CONCLUSION: These data show that PY-STAT3 positivity, as determined using dual IHC, is a marker of poor prognosis in non-elderly adult patients with MM.
Adult* ; C-Reactive Protein ; Calcium ; Diagnosis ; Disease-Free Survival ; Humans ; Multiple Myeloma* ; Multivariate Analysis ; Prognosis ; STAT3 Transcription Factor ; Stem Cell Transplantation

Extended-release osmotic extended-release oral delivery system (OROS) hydromorphone is a strong synthetic opioid designed to maintain a constant blood concentration by once daily dosing. The objective of this observational study was to investigate the clinical usefulness of OROS hydromorphone in patients with cancer pain of moderate to severe intensity. Patients with cancer pain who required strong opioids were administered with OROS hydromorphone for 4 weeks. We assessed changes in pain intensity using a numerical rating scale (NRS) as well as levels of sleep disturbance, breakthrough pain, end-of-dose failure, patient satisfaction, and overall assessment of drug effectiveness based on investigator evaluation. Of the 648 enrolled patients, 553 patients were included in the full analysis set. The mean pain intensity was significantly decreased from the NRS value of 5.07 ± 1.99 to 2.75 ± 1.94 (mean % change of 42.13 ± 46.53, P < 0.001). The degree of sleep disturbance significantly improved (mean NRS change of 1.61 ± 2.57, P < 0.001), and the incidence of breakthrough pain was significantly decreased (mean NRS change of 1.22 ± 2.30, P < 0.001). The experience of end-of-dose failure also significantly decreased from 4.60 ± 1.75 to 3.93 ± 1.70, P = 0.007). The patient satisfaction rate was 72.7%, and 72.9% of investigators evaluated the study drug as effective. OROS hydromorphone was an effective and tolerable agent for cancer pain management. It effectively lowered pain intensity as well as improved sleep disturbance, breakthrough pain, and end-of-dose failure (Identifier: NCT 01273454).
Analgesics, Opioid ; Breakthrough Pain ; Chronic Pain ; Humans ; Hydromorphone* ; Incidence ; Observational Study ; Pain Management ; Patient Satisfaction ; Research Personnel

Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with poor prognosis. Elderly (age ≥ 65years) patients generally have impaired bone marrow function, altered drug metabolism, comorbidities, and poor functional status. Thus, treatment of elderly patients with relapsed or refractory PTCL remains a challenge for clinicians. A recent study disclosed that pralatrexate has a synergistic effect in combination with bortezomib. Weekly pralatrexate and bortezomib were administered intravenously for 3 weeks in a 4-week cycle. Of 5 patients, one achieved complete response after 4 cycles which has lasted 12 months until now. Another patient attained partial response after 2 cycles. Only 1 patient experienced grade 3 thrombocytopenia and neutropenia. Two patients suffered from grade 3 mucositis. Combination therapy with pralatrexate and bortezomib may be used as a salvage therapy for relapsed or refractory PTCL in the elderly with a favorable safety profile.
Aged ; Aminopterin/adverse effects/*analogs & derivatives/therapeutic use ; Antineoplastic Agents/adverse effects/*therapeutic use ; Bortezomib/adverse effects/*therapeutic use ; Drug Administration Schedule ; Drug Therapy, Combination ; Humans ; Lymphoma, T-Cell, Peripheral/diagnostic imaging/*drug therapy/pathology ; Male ; Neoplasm Recurrence, Local ; Neutropenia/etiology ; Positron Emission Tomography Computed Tomography

BACKGROUND: A change in urine output has been recently recognized as a valuable biomarker of acute kidney injury that is associated with mortality in critically ill patients. We investigated the prognostic impact of oliguria for survival outcomes in multiple myeloma (MM) patients presenting with renal impairment (RI). METHODS: Retrospective data on 98 patients with MM and RI, who received initial treatment with novel therapies, were analyzed. Oliguria was defined as a urine output of <0.5 mL/kg/h. RESULTS: The baseline median eGFR was 39.7 mL/min (range, 5.1-59.8). Achievement of renal complete response (CR) was observed in 39.8% of patients. Nine patients (9.2%) presented with oliguria at initial diagnosis, and 4 initially required dialysis. Over a median follow-up period of 17.1 months (range, 1.7-100.0), the median overall survival (OS) was 38.7 months (95% CI 25.0-52.5). Multivariate analyses indicated that oliguria at diagnosis [hazard ratio (HR) 3.628, 95% CI 1.366-9.849, P=0.011], and thrombocytopenia <100x10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival. CONCLUSION: Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.
Acute Kidney Injury ; Critical Illness ; Diagnosis ; Dialysis ; Follow-Up Studies ; Humans ; Mortality* ; Multiple Myeloma* ; Multivariate Analysis ; Oliguria* ; Renal Insufficiency ; Retrospective Studies ; Thrombocytopenia

BACKGROUND: Eltrombopag is a thrombopoietin receptor agonist with excellent treatment outcomes in immune thrombocytopenia (ITP). Here, we analyzed the dose of eltrombopag required to achieve and maintain safe platelet counts in Korean ITP patients. METHODS: Adult refractory ITP patients (<30,000 platelets/microL) were enrolled. Eltrombopag doses were increased to achieve a target platelet count (> or =50,000 cells/microL). After achieving the target platelet count, the dose of concomitant ITP medications and eltrombopag was reduced to identify the lowest effective dose required to maintain the platelet count. RESULTS: Among 18 patients, 66.7% achieved complete response, 5.6% achieved platelet counts between 50,000 and 100,000 cells/microL, and 27.8% failed to achieve the target platelet count. The median ITP duration was significantly shorter in patients who achieved the target platelet count. The initial dose required to achieve the target platelet count was 25 mg/d. The adjusted maintenance doses were 25 mg twice per week or 25 mg/d. After discontinuation, 83.3% relapsed, and the median relapse-free survival was 15 days. Two relapsed and 1 failed patient switched to romiplostim. The response to romiplostim was similar to eltrombopag. During eltrombopag treatment, 38.9% showed hepatobiliary laboratory anomalies. Among 9 follow-up bone marrow examinations, 1 revealed fibrosis after 1 year of treatment. CONCLUSION: Eltrombopag was well tolerated with excellent treatment outcomes in refractory adult ITP patients. Low-dose eltrombopag effectively maintained the target platelet count. However, some patients required longer or higher-dose treatment to maintain the target platelet count, especially in heavily pretreated or longer ITP cases.
Adult* ; Bone Marrow Examination ; Fibrosis ; Follow-Up Studies ; Humans ; Platelet Count ; Purpura, Thrombocytopenic, Idiopathic ; Receptors, Thrombopoietin ; Thrombocytopenia*

BACKGROUND/AIMS: BK virus (BKV) has been associated with late-onset hemorrhagic cystitis (HC) in recipients of hematopoietic stem cell transplantation (HSCT). Cidofovir has been used at higher doses (3 to 5 mg/kg/wk) with probenecid prophylaxis; however, cidofovir may result in nephrotoxicity or cytopenia at high doses. METHODS: Allogeneic HSCT recipients with BKV-associated HC are treated with 1 mg/kg intravenous cidofovir weekly at our institution. A microbiological response was defined as at least a one log reduction in urinary BKV viral load, and a clinical response was defined as improvement in symptoms and stability or reduction in cystitis grade. RESULTS: Eight patients received a median of 4 weekly (range, 2 to 11) doses of cidofovir. HC occurred a median 69 days (range, 16 to 311) after allogeneic HSCT. A clinical response was detected in 7/8 patients (86%), and 4/5 (80%) had a measurable microbiological response. One patient died of uncontrolled graft-versus-host disease; therefore, we could not measure the clinical response to HC treatment. One microbiological non-responder had a stable BKV viral load with clinical improvement. Only three patients showed transient grade 2 serum creatinine toxicities, which resolved after completion of concomitant calcineurin inhibitor treatment. CONCLUSIONS: Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.
Administration, Intravenous ; Adult ; Antiviral Agents/*administration & dosage/adverse effects ; BK Virus/*drug effects/immunology ; Cystitis/diagnosis/*drug therapy/immunology/virology ; Cytosine/administration & dosage/adverse effects/*analogs & derivatives ; Drug Administration Schedule ; Female ; Hematopoietic Stem Cell Transplantation/*adverse effects ; Humans ; Immunocompromised Host ; Male ; Organophosphonates/*administration & dosage/adverse effects ; Polyomavirus Infections/diagnosis/*drug therapy/immunology/virology ; Retrospective Studies ; Time Factors ; Transplantation, Homologous ; Treatment Outcome ; Tumor Virus Infections/diagnosis/*drug therapy/immunology/virology ; Viral Load

Although the introduction of stem cell transplantation and novel agents has improved survival, multiple myeloma (MM) is still difficult to cure. Alternative approaches are clearly needed to prolong the survival of patients with MM. Dendritic cell (DC) therapy is a very promising tool immunologically in MM. We developed a method to generate potent DCs with increased Th1 polarization and migration ability for inducing strong myeloma-specific cytotoxic T lymphocytes. In this review, we discuss how the efficacy of cancer immunotherapy using DCs can be improved in MM.
Dendritic Cells ; Humans ; Immunotherapy ; Multiple Myeloma ; Stem Cell Transplantation ; T-Lymphocytes, Cytotoxic

The prognostic value of whole-body positron emission tomography/computed tomography (PET/CT) with 18F-fluoro-2-deoxy-D-glucose (FDG) shortly after the onset of induction chemotherapy or mid treatment could help to predict long-term clinical outcomes in patients with Hodgkin's or Non-Hodgkin's lymphoma. However, FDG is not a tumor-specific substance, and it may accumulate to the point of being detected in a variety of benign conditions or at physiologic anatomical sites, which may give rise to false-positive interpretation. In an attempt to standardize the reporting criteria for interim PET/CT, the First International Workshop on Interim PET in Lymphoma suggested visual response criteria with the Deauville five-point scale, and the standardized uptake value (SUV) has been investigated in comparison with this visual system. A quantitative approach using the measurement of maximal SUV (SUVmax) or the reduction rate of SUVmax (DeltaSUVmax) might be more appropriate in early-response PET/CT for reducing false-positive rates or for decreasing interobserver variability in interpretation. In this review, the predictive efficacy of PET/CT is discussed for the treatment of aggressive lymphoma, especially in terms of an interim PET/CT-based prognostic model.
Education ; Electrons ; Humans ; Induction Chemotherapy ; Lymphoma ; Lymphoma, Non-Hodgkin ; Observer Variation ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Prognosis

This study explored drug transporter expression levels and their impact on clinical response to imatinib and second-generation tyrosine kinase inhibitors (TKIs) in imatinib- resistant chronic myeloid leukemia (CML). Imatinib-resistant chronic phase CML patients treated with dasatinib (n=10) and nilotinib (n=12) were enrolled. The mRNA expression of the OCT-1, ABCG2, and ABCB1 genes was quantified by using paired bone marrow samples obtained before administering imatinib and at the point of detecting imatinib resistance (just before starting second-generation TKIs). The expression levels of OCT-1 and ABCG2 were lower in follow-up than in imatinib-naive samples. ABCB1 revealed highly variable expression levels before and after imatinib treatment. In addition, median ABCB1 expression in follow-up samples was lower in patients achieving complete cytogenetic response or major molecular response during imatinib treatment than in failed patients. Higher ABCG2 expression in imatinib-exposed samples showed a negative impact on optimal response to dasatinib. Patients with higher ABCG2 expression in imatinib-exposed samples also had shorter progression- free survival with dasatinib treatment. However, no significant correlation was found between these drug transporter expression levels in imatinib-naive or imatinib- exposed samples and responses to nilotinib. In imatinib-resistant CML, OCT-1 and ABCG2 mRNA expression decreased after imatinib treatment. Patients with higher ABCG2 expression in imatinib-exposed samples showed poor treatment outcome with dasatinib. On the other hand, a higher expression level of ABCB1 in imatinib-exposed samples did not affect second-generation TKI responses but was correlated with poor imatinib responses.
Bone Marrow ; Cytogenetics ; Follow-Up Studies ; Hand ; Humans ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive ; Leukemia, Myeloid ; Protein-Tyrosine Kinases ; RNA, Messenger ; Treatment Outcome ; Dasatinib ; Imatinib Mesylate