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Erdheim-Chester disease (ECD), also known as non-Langerhans cell histiocytosis, is a multi-systemic disease with unclear pathogenesis. Based on a small number of case studies, pegylated interferon-α (PEG-IFN-α) has been used as the front-line treatment option. However, there are limited data regarding administration of ropegylated-interferon α-2b (ROPEG-IFN-α 2b) for ECD patients. Herein, we report two cases of severe ECD treated with two types of PEG-IFN-α. One patient with heart and skeleton involvement and BRAF V600E mutation was treated with weekly PEG-IFN-α 2a. Another patient with bone involvement and no BRAF V600E mutation was administered monthly ROPEG-IFN-α 2b. The two types of PEG-IFN-α showed excellent disease control, excellent survival outcomes, and manageable toxicities in ECD patients. These results suggest that ROPEG-IFN-α 2b could be used equivalently to PEG-IFN-α 2a for management of advanced ECD.
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Purpose@#We evaluated the characteristics of CCAAT/enhancer-binding protein α (CEBPA) mutations and the significance of a basic leucine zipper in-frame mutation (bZIPin-f) of CEBPA in patients with acute myeloid leukemia with a normal karyotype. @*Materials and Methods@#Based on updated knowledge of CEBPA mutations, we conducted next-generation sequencing analyses in a previously established real-world cohort. @*Results@#Among 78 of a total of 395 patients (19.7%), 50 had bZIPin-f CEBPA, and 28 had non-bZIPin-f CEBPA. In the multivariate analysis, patients with NPM1mut, those with bZIPin-f CEBPA, and those who underwent allogeneic hematopoietic cell transplantation (allo-HCT) had favorable overall survival (OS), but FLT3-ITDmut was a poor prognostic indicator. For relapse-free survival (RFS) and cumulative incidence of relapse, bZIPin-f CEBPA, and allo-HCT were associated with favorable outcomes; FLT3-ITDpos was associated with worse outcomes. In the CEBPA double-mutated group (CEBPAdm), bZIPin-f CEBPA was associated with superior outcomes in terms of OS (p=0.007) and RFS (p=0.007) compared with non-bZIPin-f CEBPA. Of 50 patients with bZIPin-f CEBPA, 36 patients had at least one mutation. When grouped by the presence of mutations in chromatic/DNA modifiers (C), cohesion complex (C), and splicing genes (S) (CCS mutations), CCS-mutated bZIPin-f CEBPA was associated with poor OS (p=0.044; hazard ratio [HR], 2.419) and a trend in inferior RFS (p=0.186; HR, 1.838). @*Conclusion@#Only bZIPin-f CEBPA was associated with favorable outcomes in patients with CEBPAdm. However, some mutations accompanying bZIPin-f CEBPA showed inferior OS; thus, further studies with larger numbers of patients are required for clear conclusions of the significance of bZIPin-f CEBPA.
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Background/Aims@#Recent advances in the understanding of the pathophysiology of myeloproliferative neoplasms (MPN) were not paralleled with advances in treatment options; thus many questions regarding optimal MPN management remain unanswered. Here, we report the results of descriptive survey study of Korean MPN patients and their attending physicians. @*Methods@#A total of 105 Korean patients (myelofibrosis [MF], 39; polycythemia vera [PV], 25; essential thrombocythemia [ET], 41) and 30 physicians completed the Landmark Health Survey, then data from the survey were analyzed. @*Results@#Among the MPN-Symptom Assessment Form symptoms, the most severe symptom reported was ‘fatigue or tiredness’ in MF and ET patients and ‘itching’ in PV patients. The majority of the patients agreed that MPN reduced their quality of life (QoL). Interestingly, physicians gave higher scores regarding the impact of MPN on patient’s daily and social life compared to patients themselves. For patients, the most important treatment goal was symptom improvement regardless of MPN subtype, while for physicians the highest priority for treatment was better QoL regardless of MPN subtype. Generally, both patients and physicians were satisfied with the overall treatment/management of MPN and communications. However, many patients felt there was not enough time during the appointment for discussion, while many physicians felt they lacked effective drugs to offer to their patients. @*Conclusions@#Our study suggests there are room for better-standardized monitoring of symptoms and treatment options and those continuous efforts to bridge the gap between patients and physicians are necessary for better care of MPN patients.
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Background@#Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea. @*Methods@#An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph + CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response. @*Results@#During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients). @*Conclusion@#This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph + CML in routine clinical practice settings.
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Background@#Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. @*Methods@#The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). @*Results@#The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P ＜0.001). The median overall survival was 136.3 months, and the average 5- and 10-year OS rates were 82.0% and 57.4%, respectively. @*Conclusion@#This is one of the largest studies involving Korean patients with CLL. Although the patients had been treated with less favored treatment regimens, the outcomes were not different from those reported in Western studies.
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Background/Aims@#In this study, we tested whether mutations in the methylation pathway genes ten-eleven-translocation 2 (TET2) and DNA methyltransferase gene 3A (DNMT3A) improve the responses of patients with myelodysplastic syndrome (MDS) to decitabine. @*Methods@#We retrospectively sequenced the TET2 and DNMT3A genes from 70 patients diagnosed with de novo MDS between June 2008 and December 2011 and treated with a 5-day regimen of decitabine (290 cycles). We then analyzed treatment outcomes. @*Results@#Patients with hematological improvement survived longer than those without hematological improvement (22.9 months vs. 10.9 months, p = 0.006). Among the 70 patients, 12 (17.1%) carried TET2 or DNMT3A mutations. The baseline characteristics of patients with wild type or mutated genes were similar. Patients with mutations in TET2 or DNMT3A had a higher overall response rate than those with the wild type genes (82.3% vs. 46.6%, p = 0.023). Multivariate analysis demonstrated that the TET2 or DMNT3A mutation status was associated with improved treatment responses and better overall survival among patients receiving decitabine. @*Conclusions@#These results demonstrate that TET2 mutations enhance the treatment response of MDS patients to hypomethylating agents like decitabine.
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Background/Aims@#Compared with Western countries, chronic lymphocytic leukemia (CLL) rarely occurs in Asia and has different clinical characteristics. Thus, we aimed to evaluate the clinical characteristics, treatment outcomes, and prognostic significance of Korean patients with CLL. @*Methods@#We retrospectively analyzed 90 patients with CLL who had received chemotherapy at 6 centers in Korea between 2000 and 2012. @*Results@#Compared with Western patients with CLL, Korean patients with CLL express lambda (42.0%) and atypical markers such as CD22 and FMC7 (76.7% and 40.0%, respectively) more frequently. First-line chemotherapy regimens included chlorambucil (n = 43), fludarabine and cyclophosphamide (FC) (n = 20), fludarabine (n = 13), rituximab-FC (n = 4). The remaining patients were treated with other various regimens (n = 10). The 5-year overall survival (OS) and progression-free survival (PFS) rates were 79.3% and 28.1%, respectively. Multivariate analyses showed that hyperleukocytosis (≥ 100 × 103/μL), extranodal involvement, and the Binet C stage were significant negative prognostic factors for OS (hazard ratio [HR] 4.75, p = 0.039; HR 21.6, p = 0.002; and HR 4.35, p = 0.034, respectively). Cytogenetic abnormalities including complex karyotypes (≥ 3), del(11q), and del(17) had a significantly adverse impact on both OS and PFS (p < 0.001 and p = 0.010, respectively). @*Conclusions@#Initial hyperleukocytosis, extranodal involvement, complex karyotype, del(17) and del(11q) need to be considered in the risk stratification system for CLL.
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In 2016, the World Health Organization revised the diagnostic criteria for myeloproliferative neoplasms (MPNs) based on the discovery of disease-driving genetic aberrations and extensive analysis of the clinical characteristics of patients with MPNs. Recent studies have suggested that additional somatic mutations have a clinical impact on the prognosis of patients harboring these genetic abnormalities. Treatment strategies have also advanced with the introduction of JAK inhibitors, one of which has been approved for the treatment of patients with myelofibrosis and those with hydroxyurea-resistant or intolerant polycythemia vera. Recently developed drugs aim to elicit hematologic responses, as well as symptomatic and molecular responses, and the response criteria were refined accordingly. Based on these changes, we have revised the guidelines and present the diagnosis, treatment, and risk stratification of MPNs encountered in Korea.
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Background@#The global TARGET survey examined real-world management of chronic myeloid leukemia (CML) compared with international guideline recommendations. This report focused on the responses of physicians from South Korea compared with those of physicians from the rest of the world (ROW). @*Methods@#The self-administered, online survey, comprising 23 questions and clinical case scenarios, was completed between April and August 2017. It was designed to gather information on practicing physicians and local practices for CML diagnosis, disease monitoring, treatment, and adverse event (AE) management. @*Results@#While there were similarities in the mutation analysis and treatment efficacy between Korea and the ROW, there were also differences in CML management. Initial diagnostic testing was more comprehensive in Korea than in the ROW, and there was significantly better access to standardized polymerase chain reaction testing. Assessment of BCR-ABL levels during the first 12 months of treatment was excellent in Korea, and there was greater frontline use of second-generation BCR-ABL tyrosine kinase inhibitors. Korean physicians were significantly less likely to switch therapy for hematologic AEs. Treatment-free remission was not an important goal of therapy among Korean or ROW physicians. @*Conclusion@#This study identified some differences in the current CML management between Korea and the ROW; CML management in Korean patients was generally in line with the current guidelines.
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No abstract available.
Subject(s)
Adult , Child , Humans , Cytomegalovirus , Polymerase Chain ReactionABSTRACT
Splenic B-cell lymphomas (SBCLs) show characteristically pronounced splenomegaly without significant lymphadenopathy. Distinguishing hairy cell leukemia (HCL) from other SBCLs (splenic marginal zone lymphoma [SMZL], variant HCL [v-HCL], and splenic diffuse red pulp small B-cell lymphoma [SDRPL]) is essential to determine suitable treatments and prognoses. With advances in diagnostic modalities and therapies, splenectomy is not commonly performed, and thus diagnosis of HCL must be based on the results obtained using blood and bone marrow samples. Annexin A1 is known as the most specific marker for HCL. There has yet been no report of the assessment of annexin A1 immunostaining from Korea. In this study we analyzed samples from 13 Korean patients with SBCLs (three HCL, three v-HCL, six SMZL, and one SDRPL) from May 2001 to December 2016. Immunohistochemical analyses for annexin A1 and CD20 were performed using bone marrow sections; molecular analyses for detection of the BRAF V600E mutation were also performed. All HCL patients showed positive results for annexin A1 immunostaining and the presence of the BRAF V600E mutation, and negative results for other SBCLs. Our results confirmed the high specificity of annexin A1 and the BRAF V600E mutation as HCL markers. Molecular analysis requires expensive equipment and substantial manpower. Annexin A1 is a better alternative as an HCL marker than the BRAF V600E mutation in terms of cost-effectiveness.
Subject(s)
Humans , Annexin A1 , Bone Marrow , Diagnosis , Korea , Leukemia, Hairy Cell , Lymphatic Diseases , Lymphoma , Lymphoma, B-Cell , Prognosis , Sensitivity and Specificity , Splenectomy , SplenomegalyABSTRACT
BACKGROUND: Molecular genetic abnormalities are observed in over 90% of chronic myelomonocytic leukemia (CMML) cases. Recently, several studies have demonstrated the negative prognostic impact of ASXL1 mutations in CMML patients. We evaluated the prognostic impact of ASXL1 mutations and compared five CMML prognostic models in Korean patients with CMML. METHODS: We analyzed data from 36 of 57 patients diagnosed as having CMML from January 2000 to March 2016. ASXL1 mutation analysis was performed by direct sequencing, and the clinical and laboratory features of patients were compared according to ASXL1 mutation status. RESULTS: ASXL1 mutations were detected in 18 patients (50%). There were no significant differences between the clinical and laboratory characteristics of ASXL1-mutated (ASXL1+) CMML and ASXL1-nonmutated (ASXL1−) CMML patients (all P>0.05). During the median follow-up of 14 months (range, 0–111 months), the overall survival (OS) of ASXL1+ CMML patients was significantly inferior to that of ASXL1− CMML patients with a median survival of 11 months and 19 months, respectively (log-rank P=0.049). An evaluation of OS according to the prognostic models demonstrated inferior survival in patients with a higher risk category according to the Mayo molecular model (log-rank P=0.001); the other scoring systems did not demonstrate a significant association with survival. CONCLUSIONS: We demonstrated that ASXL1 mutations, occurring in half of the Korean CMML patients examined, were associated with inferior survival. ASXL1 mutation status needs to be determined for risk stratification in CMML.
Subject(s)
Humans , Follow-Up Studies , Korea , Leukemia, Myelomonocytic, Chronic , Models, Molecular , Molecular BiologyABSTRACT
BACKGROUND/AIMS: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that typically presents in the form of skin manifestations with or without lymph node and bone marrow involvement. Given its rarity and recent recognition as a distinct pathological entity, no standard of treatment exists for this aggressive disease and its prognosis is particularly dismal. METHODS: We retrospectively analyzed clinical features and treatment outcomes of patients who were diagnosed with BPDCN between 2000 and 2014. RESULTS: Ten patients had a median age at diagnosis of 41 years (range, 18 to 79), and seven patients were male. Sites of disease involvement were the skin (n = 7), lymph node (n = 5), bone marrow (n = 2), liver (n = 2), spleen (n = 2), and soft tissue (n = 1). Intensified chemotherapy regimens such as hyperCVAD regimen (cyclophosphamide, vincristine, doxorubicin, dexamethasone, methotrexate, cytarabine), and VPDL (vincristine, methylprednisolone, daunorubicin, L-asparaginase) were used as a first-line treatment. Although all patients treated with intensified chemotherapy showed an objective response (five patients with complete response) with median progression-free survival of 11.2 months (range 6.2 to 19.4), complete remission was not sustained for more than 2 years in any case. The response was relatively long-lived compared with previously reported CHOP (doxorubicin, cyclophosphamide, vincristine, prednisone)-like regimens, but the above regimens do not result in long-term remission. CONCLUSIONS: All patients treated with hyperCVAD or VPDL showed an objective response, but the duration of response was relatively short. Thus, the development of more effective induction as well as consolidation treatment strategy should be warranted to improve this rare disease entity.
Subject(s)
Humans , Male , Bone Marrow , Cyclophosphamide , Daunorubicin , Dendritic Cells , Dexamethasone , Diagnosis , Disease-Free Survival , Doxorubicin , Drug Therapy , Hematologic Neoplasms , Korea , Liver , Lymph Nodes , Methotrexate , Methylprednisolone , Prognosis , Rare Diseases , Retrospective Studies , Skin , Skin Manifestations , Spleen , VincristineABSTRACT
Allogeneic hematopoietic stem cell transplantation is the only option for chemotherapy-refractory chronic myeloid leukemia (CML). Extramedullary relapse after transplantation is rare and usually accompanies marrow relapse. Generally, the prognosis of extramedullary relapse is poor. Here, we report a man with extramedullary relapsed CML after stem cell transplantation that presented as an isolated cardiac mass, which has shown an indolent course for more than 2 years, without evolving to medullary relapse during that period. This case implies that the CML clone might contribute to the development of quiescent extramedullary relapse with a benign course.
Subject(s)
Bone Marrow , Clone Cells , Heart Neoplasms , Hematopoietic Stem Cell Transplantation , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Prognosis , Recurrence , Sarcoma, Myeloid , Stem Cell TransplantationABSTRACT
Here, we report on a 20-year-old patient with a primary nonseminomatous mediastinal germ cell tumor (MGCT) who developed myelodysplastic syndrome (MDS) 2 months following chemotherapy with cisplatin, etoposide, ifosfamide, and paclitaxel. Bone marrow examinations revealed that the MDS was a refractory anemia with excess type II blasts and complex chromosomal abnormalities. With the onset of MDS occurring rapidly following chemotherapy, it is unlikely to have been caused by the therapy. We discuss the association between primary nonseminomatous MGCTs and hematological malignancies, including the possibility of a common clonal origin.
Subject(s)
Humans , Young Adult , Anemia, Refractory , Bone Marrow Examination , Chromosome Aberrations , Cisplatin , Drug Therapy , Etoposide , Germ Cells , Hematologic Neoplasms , Ifosfamide , Myelodysplastic Syndromes , Neoplasms, Germ Cell and Embryonal , PaclitaxelABSTRACT
PURPOSE: Central retinal vein occlusion (CRVO) as a complication of acute leukemia has rarely been reported. Here, we report a favorable outcome of radiation therapy for CRVO with severe macular edema in a patient with acute lymphocytic leukemia (ALL). CASE SUMMARY: A 21-year-old female presented with acute visual loss in the left eye and headache. Best-corrected visual acuity in the left eye was 0.3. Fundus examination showed some hemorrhagic spots in the right eye and flame-shaped retinal hemorrhage, tortuous retinal vessels, and a retinal infiltrative lesion in the left eye. Fluorescein angiography revealed CRVO in the left eye and severe central macular edema was observed by optical coherence tomography. Hematologic study revealed ALL. Even after leukapheresis and commencement of systemic chemotherapy, fundus findings showed no remarkable change. She was given low dose (400 cGy) ocular external beam radiation therapy (EBRT). Three days after EBRT, macular edema, fundus infiltration, and visual acuity improved dramatically. Visual acuity improved to 0.4 and to 0.8 at 1 month and 1 year after EBRT respectively. CONCLUSIONS: Early start of EBRT after diagnosis could lead to good visual prognosis. EBRT showed rapid resolution of macular edema associated with CRVO in a patient with ALL. Low dose EBRT may be considered as a suitable treatment option for CRVO associated with leukemia.
Subject(s)
Female , Humans , Young Adult , Diagnosis , Drug Therapy , Fluorescein Angiography , Headache , Leukapheresis , Leukemia , Macular Edema , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Prognosis , Retinal Hemorrhage , Retinal Vein , Retinal Vessels , Retinaldehyde , Tomography, Optical Coherence , Visual AcuityABSTRACT
Polycythemia vera, essential thrombocythemia, and primary myelofibrosis are collectively known as 'Philadelphia-negative classical myeloproliferative neoplasms (MPNs).' The discovery of new genetic aberrations such as Janus kinase 2 (JAK2) have enhanced our understanding of the pathophysiology of MPNs. Currently, the JAK2 mutation is not only a standard criterion for diagnosis but is also a new target for drug development. The JAK1/2 inhibitor, ruxolitinib, was the first JAK inhibitor approved for patients with intermediate- to high-risk myelofibrosis and its effects in improving symptoms and survival benefits were demonstrated by randomized controlled trials. In 2011, the Korean Society of Hematology MPN Working Party devised diagnostic and therapeutic guidelines for Korean MPN patients. Subsequently, other genetic mutations have been discovered and many kinds of new drugs are now under clinical investigation. In view of recent developments, we have revised the guidelines for the diagnosis and management of MPN based on published evidence and the experiences of the expert panel. Here we describe the epidemiology, new genetic mutations, and novel therapeutic options as well as diagnostic criteria and standard treatment strategies for MPN patients in Korea.
Subject(s)
Humans , Antineoplastic Agents/therapeutic use , Asian People/genetics , Janus Kinase 2/antagonists & inhibitors , Molecular Targeted Therapy , Mutation , Myeloproliferative Disorders/diagnosis , Protein Kinase Inhibitors/therapeutic use , Republic of Korea/epidemiology , Risk Factors , Signal Transduction/drug effects , Treatment OutcomeABSTRACT
BACKGROUND/AIMS: The first edition of the Korean treatment guidelines for chronic myelogenous leukemia (CML) was published in 2006. We intend to update those guidelines to include the use of next-generation tyrosine kinase inhibitors (TKIs). METHODS: New guidelines were developed in 2012 based on the results of a survey and a consensus meeting of various Korean experts, the reports of recent clinical studies, and updated guidelines from external study groups. RESULTS: An assessment of risk factors is strongly recommended before treating newly diagnosed chronic phase CML. Imatinib, dasatinib, and nilotinib are reimbursable in Korea as first-line treatments, and the patient's age, comorbidities, and possible adverse events should be considered in the choice of treatment. Molecular studies are recommended for assessing treatment efficacy instead of invasive cytogenetic response evaluations, and an early response is believed to correlate with a good prognosis. Second-line TKIs can be considered for patients who fail or are intolerant of first-line therapy, pending analysis of ABL tyrosine kinase mutation status. For treating advanced stages, a combination of TKIs with cytotoxic agents and hematopoietic cell transplantation is recommended. The adverse effects of TKI therapy can be managed via dose reduction and supportive care, or switching to an alternate TKI. CONCLUSIONS: The use of TKIs has improved the outcome of CML treatment. Treatment-free remission after discontinuing TKIs might be possible in select patients who achieve sufficient response, indicating that curative treatment for CML can be expected in the future.