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1.
Article in English | WPRIM | ID: wpr-915524

ABSTRACT

Background@#In diffuse large B-cell lymphoma (DLBCL), bone marrow involvement (BMI) has an important clinical implication as a component of staging and International Prognostic Index. This study aimed to determine whether molecular analysis of immunoglobulin heavy chain (IgH) genes and positron emission tomography-computed tomography (PET/CT) could overcome the limitation of defining morphologic BMI by trephination biopsy and could increase the diagnostic accuracy or prognostic prediction. @*Methods@#A total of 94 de novo patients with DLBCL underwent PET/CT, polymerase chain reaction (PCR) test for detection of IgH gene rearrangement, and unilateral bone marrow (BM) trephination at diagnosis. @*Results@#A total of 9 patients (9.6%) were confirmed to present morphologic BMI (mBMI) based on trephination biopsy. On the other hand, 21 patients (22.3%) were confirmed to have IgH clonality (IgH BMI), while 16 (17.0%) were classified with BMI based on the assessment of PET/CT (PET BMI). Each IgH rearrangement PCR and PET/CT showed the high negative predictive value of detecting the BMI. However, the combined assessment of IgH rearrangement and PET/CT could increase the diagnostic accuracy and specificity with 87.2% and 97.0%, respectively. The survival outcome of patients with double positive PET BMI and IgH BMI was significantly worse than that with either single positive PET BMI or IgH BMI, and even less than patients with neither PET BMI nor IgH BMI (3-year PFS: 50.0% vs. 75.4% vs. 97.9%, P = 0.007, 3-year OS: 50.0% vs. 75.6% vs. 80.1%, P = 0.035, respectively). @*Conclusion@#This study suggests that the combined evaluation of PET/CT and IgH rearrangement could give additional information for predicting therapeutic outcomes in patients with negative morphologic BMI as an important part of the prognosis.

2.
Blood Research ; : S37-S42, 2020.
Article | WPRIM | ID: wpr-830982

ABSTRACT

Since the introduction of an alkylator to the treatment of multiple myeloma (MM), new effective agents have been developed, such as immunomodulatory drugs including thalidomide, lenalidomide, and pomalidomide; proteasome inhibitors including bortezomib, carfilzomib, and ixazomib; monoclonal antibodies including daratumumab and elotuzumab; and deacetylase inhibitors including panobinostat. Numerous regimens with these new agents have been developed and they have contributed in improving survival outcomes in MM patients. In addition, the recommended therapies for newly diagnosed MM change every year based on the results of clinical trials. This review will discusses the appropriate induction therapies based on recent clinical trials for patients with newly diagnosed MM.

3.
Article in English | WPRIM | ID: wpr-919157

ABSTRACT

In multiple myeloma (MM), the impaired function of several types of immune cells favors the tumor’s escape from immune surveillance and, therefore, its growth and survival. Tremendous improvements have been made in the treatment of MM over the past decade but cellular immunotherapy using dendritic cells, natural killer cells, and genetically engineered T-cells represent a new therapeutic era. The application of these treatments is growing rapidly, based on their capacity to eradicate MM. In this review, we summarize recent progress in cellular immunotherapy for MM and its future prospects.

4.
Article in English | WPRIM | ID: wpr-718012

ABSTRACT

BACKGROUND/AIMS: This study evaluated the role of hypomethylating agents (HMA) compared to best supportive care (BSC) for patients with high or very-high (H/VH) risk myelodysplastic syndrome (MDS) according to the Revised International Prognostic Scoring System. METHODS: A total of 279 H/VH risk MDS patients registered in the Korean MDS Working Party database were retrospectively analyzed. RESULTS: HMA therapy was administered to 205 patients (73.5%), including 31 patients (11.1%) who then received allogeneic hematopoietic cell transplantation (allo-HCT), while 74 patients (26.5%) received BSC or allo-HCT without HMA. The 3-year overall survival (OS) rates were 53.1% ± 10.7% for allo-HCT with HMA, 75% ± 21.7% for allo-HCT without HMA, 17.3% ± 3.6% for HMA, and 20.8% ± 6.9% for BSC groups (p < 0.001). In the multivariate analysis, only allo-HCT was related with favorable OS (hazard ratio [HR], 0.356; p = 0.002), while very poor cytogenetic risk (HR, 5.696; p = 0.042), age ≥ 65 years (HR, 1.578; p = 0.022), Eastern Cooperative Oncology Group performance status (ECOG PS) 2 to 4 (HR, 2.837; p < 0.001), and transformation to acute myeloid leukemia (AML) (HR, 1.901; p = 0.001) all had an adverse effect on OS. CONCLUSIONS: For the H/VH risk group, very poor cytogenetic risk, age ≥ 65 years, ECOG PS 2 to 4, and AML transformation were poor prognostic factors. HMA showed no benefit in terms of OS when compared to BSC. Allo-HCT was the only factor predicting a favorable long-term outcome. The use of HMA therapy did not seem to have an adverse effect on the transplantation outcomes. However, the conclusion of this study should be carefully interpreted and proven by large scale research in the future.


Subject(s)
Cell Transplantation , Cytogenetics , Humans , Leukemia, Myeloid, Acute , Multivariate Analysis , Myelodysplastic Syndromes , Retrospective Studies , Transplants
5.
Blood Research ; : 293-299, 2017.
Article in English | WPRIM | ID: wpr-21828

ABSTRACT

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.


Subject(s)
Adult , C-Reactive Protein , Calcium , Diagnosis , Disease-Free Survival , Humans , Multiple Myeloma , Multivariate Analysis , Prognosis , STAT3 Transcription Factor , Stem Cell Transplantation
6.
Article in English | WPRIM | ID: wpr-78633

ABSTRACT

The migration of dendritic cells (DCs) to secondary lymphoid organs depends on chemoattraction through the interaction of the chemokine receptors with chemokines. However, the mechanism of how lymphoid chemokines attract DCs to lymphoid organs remains unclear. Here, we demonstrate the mechanism of DC migration in response to the lymphoid chemokine CCL21. CCL21-mediated DC migration is controlled by the regulation of sarcoplasmic reticulum Ca²⁺ ATPase 2 (SERCA2) expression rather than through the activation of mitogen-activated protein kinases CCL21-exposed mature DCs (mDCs) exhibited decreased SERCA2 expression but not decreased phospholamban (PLB) or Hax-1 expression, which are known to be SERCA2-interacting proteins. In addition, CCL21 did not affect the mRNA levels of SERCA2 or its interacting protein Hax-1. Interestingly, SERCA2 expression was inversely related to DC migration in response to chemokine stimulation. The migratory capacity of CCL21-treated mDCs was decreased by the phospholipase C inhibitor U73122 and by the protein kinase C inhibitor BAPTA-AM. The migratory capacities of mDCs were increased in response to SERCA2 siRNA expression but were decreased by SERCA2 overexpression. In addition, DCs treated with a SERCA2-specific inhibitor (cyclopiazonic acid) had significantly increased migratory capacities as mDCs regardless of SERCA2 expression. Moreover, SERCA2 expression was dependent on DC maturation induced by cytokines or Toll-like receptor agonists. Therefore, the migratory capacities differed in differentially matured DCs. Taken together, these results suggest that SERCA2 contributes to the migration of CCL21-activated DCs as an important feature of the adaptive immune response and provide novel insights regarding the role of SERCA2 in DC functions.


Subject(s)
Adaptive Immunity , Adenosine Triphosphatases , Chemokine CCL21 , Chemokines , Cytokines , Dendritic Cells , Mitogen-Activated Protein Kinases , Protein Kinase C , Receptors, Chemokine , RNA, Messenger , RNA, Small Interfering , Sarcoplasmic Reticulum , Toll-Like Receptors , Type C Phospholipases
7.
Article in English | WPRIM | ID: wpr-13343

ABSTRACT

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.


Subject(s)
Aged , Aminopterin/adverse effects , Antineoplastic Agents/adverse effects , Bortezomib/adverse effects , Drug Administration Schedule , Drug Therapy, Combination , Humans , Lymphoma, T-Cell, Peripheral/diagnostic imaging , Male , Neoplasm Recurrence, Local , Neutropenia/etiology , Positron Emission Tomography Computed Tomography
8.
Article in English | WPRIM | ID: wpr-36811

ABSTRACT

BACKGROUND: To identify potential molecular prognostic markers in core binding factor (CBF) AML, we analyzed incidences and prognostic impacts of mutations in c-KIT, WT1, CEBPA, CBL, and a number of epigenetic genes in CBF AML. METHODS: Seventy one and 21 AML patients with t(8;21) and inv(16) were enrolled in this study, respectively. NPM1, CEBPA, c-KIT, IDH1/2, DNMT3A, EZH2, WT1, and CBL mutations were analyzed by direct sequencing. Patients were categorized with respect to c-KIT and WT1 mutation status, and both clinical features and prognoses were compared. RESULTS: The incidences of FLT3 internal tandem duplication (ITD), NPM1, CEBPA, IDH1/2, DNMT3A, EZH2, and CBL mutations were low (< or =5%) in CBF AML patients. However, c-KIT and WT1 mutations occurred frequently (10.9% and 13.8%, respectively). t(8;21) patients with c-KIT mutations showed significantly shorter overall survival (OS) and disease free survival (DFS) periods than those without mutations (P<0.001, for both); however, although the limited number of t(8;21) patients were analyzed, WT1 mutation status did not affect prognosis significantly. Relapse or death during follow-up occurred more frequently in t(8;21) patients carrying c-KIT mutations than in those without the mutation, although the difference was significant only in a specific patient subgroup with no WT1 mutations (P=0.014). CONCLUSIONS: The incidences of mutations in epigenetic genes are very low in CBF AML; however, c-KIT and WT1 mutations occur more frequently than others. The poor prognostic impact of c-KIT mutation in t(8;21) AML patients only applies in a specific patient subgroup without WT1 mutations. The prognostic impact of WT1 mutation in CBF AML is not evident and further investigation is required.


Subject(s)
Adolescent , Adult , Aged , Aged, 80 and over , Asian Continental Ancestry Group/genetics , CCAAT-Enhancer-Binding Proteins/genetics , Child , Core Binding Factors/genetics , Disease-Free Survival , Epigenesis, Genetic , Female , Humans , Incidence , Leukemia, Myeloid, Acute/diagnosis , Male , Middle Aged , Mutation , Prognosis , Proto-Oncogene Proteins c-cbl/genetics , Proto-Oncogene Proteins c-kit/genetics , Republic of Korea/epidemiology , Survival Rate , Translocation, Genetic , WT1 Proteins/genetics , Young Adult
9.
Blood Research ; : 167-172, 2015.
Article in English | WPRIM | ID: wpr-36728

ABSTRACT

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.


Subject(s)
Acute Kidney Injury , Critical Illness , Diagnosis , Dialysis , Follow-Up Studies , Humans , Mortality , Multiple Myeloma , Multivariate Analysis , Oliguria , Renal Insufficiency , Retrospective Studies , Thrombocytopenia
10.
Chonnam Medical Journal ; : 109-114, 2015.
Article in English | WPRIM | ID: wpr-87794

ABSTRACT

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.


Subject(s)
Education , Electrons , Humans , Induction Chemotherapy , Lymphoma , Lymphoma, Non-Hodgkin , Observer Variation , Positron-Emission Tomography , Positron Emission Tomography Computed Tomography , Prognosis
11.
Blood Research ; : 19-25, 2015.
Article in English | WPRIM | ID: wpr-104397

ABSTRACT

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 ( 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.


Subject(s)
Adult , Bone Marrow Examination , Fibrosis , Follow-Up Studies , Humans , Platelet Count , Purpura, Thrombocytopenic, Idiopathic , Receptors, Thrombopoietin , Thrombocytopenia
12.
Article in English | WPRIM | ID: wpr-133657

ABSTRACT

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.


Subject(s)
Dendritic Cells , Humans , Immunotherapy , Multiple Myeloma , Stem Cell Transplantation , T-Lymphocytes, Cytotoxic
13.
Article in English | WPRIM | ID: wpr-133656

ABSTRACT

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.


Subject(s)
Dendritic Cells , Humans , Immunotherapy , Multiple Myeloma , Stem Cell Transplantation , T-Lymphocytes, Cytotoxic
14.
Chonnam Medical Journal ; : 109-114, 2015.
Article in English | WPRIM | ID: wpr-788322

ABSTRACT

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.


Subject(s)
Education , Electrons , Humans , Induction Chemotherapy , Lymphoma , Lymphoma, Non-Hodgkin , Observer Variation , Positron-Emission Tomography , Positron Emission Tomography Computed Tomography , Prognosis
15.
Article in English | WPRIM | ID: wpr-788307

ABSTRACT

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.


Subject(s)
Dendritic Cells , Humans , Immunotherapy , Multiple Myeloma , Stem Cell Transplantation , T-Lymphocytes, Cytotoxic
16.
Article in English | WPRIM | ID: wpr-214111

ABSTRACT

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.


Subject(s)
Administration, Intravenous , Adult , Antiviral Agents/administration & dosage , BK Virus/drug effects , Cystitis/diagnosis , Cytosine/administration & dosage , Drug Administration Schedule , Female , Hematopoietic Stem Cell Transplantation/adverse effects , Humans , Immunocompromised Host , Male , Organophosphonates/administration & dosage , Polyomavirus Infections/diagnosis , Retrospective Studies , Time Factors , Transplantation, Homologous , Treatment Outcome , Tumor Virus Infections/diagnosis , Viral Load
17.
Korean Journal of Medicine ; : 406-419, 2015.
Article in Korean | WPRIM | ID: wpr-180827

ABSTRACT

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.


Subject(s)
Cell Transplantation , Comorbidity , Consensus , Cytogenetics , Cytotoxins , Hematology , Humans , Korea , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Prognosis , Protein-Tyrosine Kinases , Risk Factors , Transplants , Treatment Outcome , Dasatinib , Imatinib Mesylate
18.
Chonnam Medical Journal ; : 102-111, 2014.
Article in English | WPRIM | ID: wpr-75447

ABSTRACT

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.


Subject(s)
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
19.
Chonnam Medical Journal ; : 102-111, 2014.
Article in English | WPRIM | ID: wpr-788294

ABSTRACT

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.


Subject(s)
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
20.
Blood Research ; : 87-98, 2013.
Article in English | WPRIM | ID: wpr-74592

ABSTRACT

Azacitidine is recommended for patients with higher-risk myelodysplastic syndromes (MDS) who are not eligible for intensive therapy or for patients with lower-risk MDS who have thrombocytopenia or neutropenia or have anemia that is unresponsive to other therapies. However, standard treatment with azacitidine has not been optimized and many issues about the use of azacitidine remain unresolved. The use of azacitidine is expanding rapidly, but limited comparative clinical trial data are available to (i) define the optimal use of azacitidine in patients with higher-risk MDS or around the time of allogeneic hematopoietic stem cell transplantation, (ii) identify those patients with lower-risk MDS who may benefit from treatment, and (iii) guide physicians on alternative therapies after treatment failure. Increasing evidence suggests that the clinical features, prognostic factors, and cytogenetic profiles of patients with MDS in Asia differ significantly from those of patients in Western countries, so the aim of this review is to summarize the evidence and provide practical recommendations on the use of azacitidine in patients with MDS in the Republic of Korea. Evidence considered in this review is based on published clinical data and on the clinical experience of an expert panel from the acute myeloid leukemia/MDS Working Party of the Korean Society of Hematology.


Subject(s)
Anemia , Asia , Azacitidine , Complementary Therapies , Cytogenetics , Hematology , Hematopoietic Stem Cell Transplantation , Humans , Myelodysplastic Syndromes , Neutropenia , Practice Guidelines as Topic , Republic of Korea , Thrombocytopenia , Treatment Failure
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