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1.
Cancer Research and Treatment ; : 1355-1362, 2023.
Article in English | WPRIM | ID: wpr-999832

ABSTRACT

Purpose@#This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL). @*Materials and Methods@#Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy. @*Results@#Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016). @*Conclusion@#Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

2.
Cancer Research and Treatment ; : 693-703, 2023.
Article in English | WPRIM | ID: wpr-976718

ABSTRACT

Purpose@#A three-drug combination of cyclophosphamide, bortezomib, and dexamethasone (CVD) shows significant efficacy and manageable toxicity as induction therapy in patients with multiple myeloma. @*Materials and Methods@#In this phase II study, we enrolled 45 patients who achieved a very good partial response (VGPR) or partial response (PR) after autologous stem cell transplantation (ASCT) and evaluated the efficacy and toxicity of CVD consolidation. CVD consolidation comprised three cycles of cyclophosphamide 300 mg/m2 orally on days 1, 8, and 15, and bortezomib 1.3 mg/m2 subcutaneously on days 1, 8, 15, and 22, along with dexamethasone 20 mg orally or intravenously on days 1 and 2, 8 and 9, 15 and 16, and 22 and 23. @*Results@#At enrollment, 39 patients (86.7%) showed VGPR, and nine (13.3%) presented with PR. Nineteen patients (45.2%) achieved a complete response or better as their best response after the end of consolidation. Overall, 22 of 42 patients (52.4%) experienced an improved response status with CVD consolidation. Three-year overall survival and progression-free survival rates were 89.0% and 42.7%, respectively. The most common non-hematologic toxicities were peripheral neuropathy and infection (20.5%), with no grade ≥ 3 neuropathy observed. @*Conclusion@#These results showed that CVD consolidation therapy improved the response with reasonable toxicity in patients with residual disease after ASCT. This trial was registered with the Clinical Research Information Service, Republic of Korea (KCT0001327).

3.
Cancer Research and Treatment ; : 684-692, 2023.
Article in English | WPRIM | ID: wpr-976690

ABSTRACT

Purpose@#We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients. @*Materials and Methods@#Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL. @*Results@#A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS. @*Conclusion@#The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

4.
The Korean Journal of Internal Medicine ; : 734-746, 2023.
Article in English | WPRIM | ID: wpr-1003070

ABSTRACT

Background/Aims@#We performed a prospective study to determine the efficacy and safety of rituximab including chemotherapy in CD20-positive acute lymphoblastic leukemia (ALL). @*Methods@#Patients with newly diagnosed ALL, aged ≥ 15 years, were eligible for the study if their leukemic blast cells in bone marrow expressed CD20 ≥ 20% at the time of diagnosis. Patients received multiagent chemotherapy with rituximab. After achieving complete remission (CR), patients received five cycles of consolidation with concomitant rituximab. Rituximab was administered monthly from day 90 of transplantation for patients who received allogeneic hematopoietic cell transplantation. @*Results@#In patients with Philadelphia (Ph)-negative ALL, 39 of 41 achieved CR (95.1%), the 2- and 4-year relapse-free survival (RFS) rates were 50.4% and 35.7%, and the 2- and 4-year overall survival (OS) rates were 51.5% and 43.2%, respectively. In the group with Ph-positive ALL, all 32 patients achieved CR, the 2- and 4-year RFS rates were 60.7% and 52.1%, and the 2- and 4-year OS rates were 73.3% and 52.3%, respectively. In the Ph-negative ALL group, patients with higher CD20 positivity experienced more favorable RFS (p < 0.001) and OS (p = 0.06) than those with lower CD20 positivity. Patients who received ≥ 2 cycles of rituximab after transplantation had significantly improved RFS (hazard ratio [HR], 0.31; p = 0.049) and OS (HR, 0.29; p = 0.021) compared with those who received < 2 cycles. @*Conclusions@#The addition of rituximab to conventional chemotherapy for CD20-positive ALL is effective and tolerable (Clinicaltrials. gov NCT01429610).

5.
Cancer Research and Treatment ; : 325-333, 2023.
Article in English | WPRIM | ID: wpr-966481

ABSTRACT

Purpose@#Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal. @*Materials and Methods@#We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation. @*Results@#Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529). @*Conclusion@#In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

6.
The Korean Journal of Internal Medicine ; : 179-189, 2022.
Article in English | WPRIM | ID: wpr-919195

ABSTRACT

Background/Aims@#Veno-occlusive disease/sinusoidal obstruction syndrome (VOD/SOS) is one of the most fatal complications of hematopoietic cell transplantation (HCT), and defibrotide is the only curative drug. We conducted this study to confirm the survival rate of VOD/SOS patients diagnosed in Korea and assess the efficacy of defibrotide. @*Methods@#Patients diagnosed with VOD/SOS after allogenic HCT between 2003 and 2020 were enrolled. We investigated day +100 survival rates and associated risk factors in patients who satisfied the modified Seattle criteria within 50 days of HCT. @*Results@#A total of 110 patients satisfied the modified Seattle criteria, of which 65.5% satisfied the Baltimore criteria. Thirty-seven patients were treated with defibrotide. The day +100 survival rate of the 110 patients was 65.3%. The survival rates in patients who did not meet the Baltimore criteria and in those who did were 86.8% and 53.7%, respectively (p = 0.001). The day +100 survival rate of patients treated with defibrotide was 50.5%. Among the patients receiving defibrotide, those whose creatinine levels were more than 1.2 times the baseline had a significantly lower survival rate at 26.7% (p = 0.014). On multivariate regression analysis, the hazard ratio of satisfaction of the Baltimore criteria was 4.54 (95% confidence interval [CI], 1.69 to 12.21; p = 0.003). In patients treated with defibrotide, the hazard ratio was 8.70 (95% CI, 2.26 to 33.45; p = 0.002), when creatinine was more than 1.2 times the baseline on administration. @*Conclusions@#The day +100 survival rate was significantly lower when the Baltimore criteria were satisfied, and when there was an increase in creatinine at the time of defibrotide administration.

7.
Journal of Korean Medical Science ; : e55-2021.
Article in English | WPRIM | ID: wpr-892277

ABSTRACT

Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT.

8.
Journal of Korean Medical Science ; : e85-2021.
Article in English | WPRIM | ID: wpr-892134

ABSTRACT

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.

9.
Blood Research ; : 243-251, 2021.
Article in English | WPRIM | ID: wpr-913728

ABSTRACT

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.

10.
Journal of Korean Medical Science ; : e55-2021.
Article in English | WPRIM | ID: wpr-899981

ABSTRACT

Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT.

11.
Journal of Korean Medical Science ; : e85-2021.
Article in English | WPRIM | ID: wpr-899838

ABSTRACT

Acute myeloid leukemia (AML) is a complicated disease characterized by genetic heterogeneity and simultaneous alterations in multiple genes. For decades, its only curative method has been intensive induction chemotherapy with or without allogeneic hematopoietic stem cell transplantation, and this approach cannot be applied to elderly patients, who make up more than 50% of AML patients. Recent advances in genomics facilitated the elucidation of various mutations related to AML, and the most frequent mutations were discovered in epigenetic regulators. Alterations to epigenetic modifications that are essential for normal cell biology, including DNA methylation and histone acetylation, have been identified. As epigenetic dysregulation is an important carcinogenic mechanism and some epigenetic changes are reversible, these epigenetic alterations have become targets for novel drug development against AML. This review summarizes the recent advances in epigenetic therapies for AML and discusses future research directions.

12.
Annals of Laboratory Medicine ; : 312-316, 2020.
Article in English | WPRIM | ID: wpr-811099

ABSTRACT

Angiogenesis is important for the proliferation and survival of multiple myeloma (MM) cells. Bone marrow (BM) microvessel density (MVD) is a useful marker of angiogenesis and an increase in MVD can be used as a marker of poor prognosis in MM patients. We developed an automated image analyzer to assess MVD from images of BM biopsies stained with anti-CD34 antibodies using two color models. MVD was calculated by merging images from the red and hue channels after eliminating non-microvessels. The analyzer results were compared with those obtained by two experienced hematopathologists in a blinded manner using the 84 BM samples of MM patients. Manual assessment of the MVD by two hematopathologists yielded mean±SD values of 19.4±11.8 and 20.0±11.8. The analyzer generated a mean±SD of 19.5±11.2. The intraclass correlation coefficient (ICC) and Bland-Altman plot of the MVD results demonstrated very good agreement between the automated image analyzer and both hematopathologists (ICC=0.893 [0.840–0.929] and ICC=0.906 [0.859–0.938]). This automated analyzer can provide time- and labor-saving benefits with more objective results in hematology laboratories.

13.
Cancer Research and Treatment ; : 374-387, 2020.
Article | WPRIM | ID: wpr-831060

ABSTRACT

Purpose@#The treatment outcome of brentuximab vedotin (BV) has not been related with CD30 expressionin previous studies enrolling patients with a wide range of CD30 expression level.Thus, this study explored the efficacy of BV in high-CD30–expressing non-Hodgkin lymphoma(NHL) patients most likely to benefit. @*Materials and Methods@#This phase II study (Clinicaltrials.gov: NCT02280785) enrolled relapsed or refractory high-CD30–expressing NHL, with BV administered intravenously at 1.8 mg/kg every 3 weeks.The primary endpoint was > 40% disease control rate, consisting of complete response(CR), partial response (PR), or stable disease. We defined high CD30 expression as ! 30%tumor cells positive for CD30 by immunohistochemistry. @*Results@#High-CD30-expressing NHL patients (n=33) were enrolled except anaplastic large cell lymphoma.The disease control rate was 48.5% (16/33) including six CR and six PR; six patients(4CR, 2PR) maintained their response over 16 completed cycles. Response to BV and survivalwere not associated with CD30 expression levels. Over a median of 29.2 months offollow-up, the median progression-free and overall survival rates were 1.9 months and 6.1months, respectively. The most common adverse events were fever (39%), neutropenia(30%), fatigue (24%), and peripheral sensory neuropathy (27%). In a post-hoc analysis forthe association of multiple myeloma oncogene 1 (MUM1) on treatment outcome, MUM1-negative patients showed a higher response (55.6%, 5/9) than MUM1-positive patients(13.3%, 2/15). @*Conclusion@#BV performance as a single agent was acceptable in terms of disease control rates and toxicityprofiles, especially MUM1-negative patients.

14.
Annals of Laboratory Medicine ; : 147-154, 2018.
Article in English | WPRIM | ID: wpr-713684

ABSTRACT

BACKGROUND: JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden. METHODS: Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as a diagnostic work-up. The same samples were used for ddPCR to determine the correlation between assays and establish a detection sensitivity cut-off. Clinical and hematologic aspects were reviewed. RESULTS: Forty-two (75%) and 46 (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR, respectively. The mean mutated allele frequency at diagnosis was 37.5±30.1% and was 40.7±31.2% with ddPCR, representing a strong correlation (r=0.9712, P < 0.001). Follow-up samples were available for 12 patients, including eight that were JAK2 V617F-positive. Of these, mutational burden reduction after treatment was observed in six patients (75%), consistent with trends of hematologic improvement. CONCLUSIONS: Quantitative analysis of the JAK2 V617F mutation using ddPCR was highly correlated with pyrosequencing data and may reflect the clinical response to treatment.


Subject(s)
Humans , Bone Marrow , Diagnosis , DNA , Follow-Up Studies , Gene Frequency , Polymerase Chain Reaction
15.
Gut and Liver ; : 278-287, 2018.
Article in English | WPRIM | ID: wpr-714613

ABSTRACT

BACKGROUND/AIMS: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. METHODS: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. RESULTS: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. CONCLUSIONS: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall.


Subject(s)
Humans , Male , Bone Marrow Examination , Bone Marrow , Diagnosis , Follow-Up Studies , Helicobacter pylori , Korea , Lymph Nodes , Lymphoid Tissue , Lymphoma , Lymphoma, B-Cell, Marginal Zone , Prevalence , Prognosis , Retrospective Studies , Risk Factors , Stomach
16.
Cancer Research and Treatment ; : 222-238, 2018.
Article in English | WPRIM | ID: wpr-739613

ABSTRACT

PURPOSE: Regional differences in the incidence of lymphoid malignancies have been reported worldwide, but there has been no large-scale epidemiologic analysis in Korea. The aim of this study was to provide a nationwide population-based statistical analysis of Korean patients with lymphoid malignancies. MATERIALS AND METHODS: The Korea Central Cancer Registry analyzed the incidence and survival of patients with lymphoid malignancies from the Korean National Cancer Incidence Database. Diseases were grouped by clinically relevant categories based on the 2008 World Health Organization classification. RESULTS: Overall 65,948 lymphoid diseases were identified between 1999 and 2012. The incidence of most subtypes increased with age, except for precursor cell neoplasms. Male predominance (male:female ratio=1.28:1) was observed. In 2012, annual age-standardized incidence rates per 100,000 persons of Hodgkin’s lymphoma, mature B-cell neoplasm, mature T/natural killer (NK)–cell neoplasm, and precursor cell neoplasm were 0.46, 6.60, 0.95, and 1.50, respectively, and they increased yearly from 1999. Composite Hodgkin’s and non-Hodgkin’s lymphomas were extremely rare. Survival improvement estimated using 5-year relative survival rate was observed in patients with Hodgkin’s lymphoma (71.1%-83.0%), diffuse large B-cell lymphoma (49.5%-61.5%), plasma cell neoplasms (20.2%-36.9%), and lymphoblastic lymphoma/leukemia (41.5%-56.3%) between 1993 and 2012. However, survival rates of T/NK-cell lymphoma (excluding cutaneous T-cell lymphoma) ranged from 40.5%-43.5% during the study period. Survival rates decreased with age in most subtypes. CONCLUSION: This report presented the subtype-specific statistical analysis of lymphoid malignancies in the Korean population, showing increasing incidences and survival rates in most subtypes.


Subject(s)
Humans , Male , B-Lymphocytes , Classification , Epidemiology , Hematologic Neoplasms , Incidence , Korea , Lymphoma , Lymphoma, B-Cell , Neoplasms, Plasma Cell , Republic of Korea , Survival Rate , T-Lymphocytes , World Health Organization
17.
Annals of Laboratory Medicine ; : 327-330, 2017.
Article in English | WPRIM | ID: wpr-186608

ABSTRACT

Peripheral blood stem cell (PBSC) transplantation following myeloablative therapy is a mainstay of treatment for various types of malignancies. This study aimed to evaluate the differences between the Optia MNC and COBE Spectra MNC systems (Terumo BCT, Japan) according to apheresis procedures and the parameters of apheresis, products, and collection. The clinical data of 74 patients who underwent autologous PBSC collection from July 2012 to July 2015 were reviewed retrospectively. The patients comprised 48 (65%) men and 26 (35%) women with a median age of 56 yr (range, 23–66 yr). Of 216 procedures, 111 (51%) and 105 (49%) were processed by using COBE and Optia MNC, respectively. PBSC collection rates, throughput, numbers of stem cells retrieved, collection efficacy, and platelet loss were compared. There were no significant differences in the median CD34+ cell counts of collected products (0.61×10⁸ vs 0.94×10⁸), CD34 collection efficiency (43.5% vs 42.1%), and loss of platelets (40.1% vs 44.7%). The Spectra Optia MNC apheresis system was comparable to the COBE Spectra system in collecting autologous CD34+ hematopoietic stem cells and retention of platelets.


Subject(s)
Female , Humans , Male , Blood Component Removal , Blood Platelets , Cell Count , Hematopoietic Stem Cells , Retrospective Studies , Stem Cells
18.
Genomics & Informatics ; : 87-97, 2017.
Article in English | WPRIM | ID: wpr-175151

ABSTRACT

Multiple myeloma (MM) is a malignant disease caused by an abnormal proliferation of plasma cells, of which the prognostic factors include chromosomal abnormality, β-2 microglobulin, and albumin. Recently, the term chromothripsis has emerged, which is the massive but highly localized chromosomal rearrangement in response to a one-step catastrophic event. Many studies have shown an association of chromothripsis with the prognosis in several cancers; however, few studies have investigated it in MM. Here, we studied the association between chromothripsis-like patterns and treatment resistance or prognosis. First, we analyzed nine MM cell lines (U266, MM.1S, RPMI8226, KMS-11, KMS-12-BM, KMS-12-PE, KMS-28-BM, KMS-28-PE, and NCI-H929) and bone marrow samples of four patients who were diagnosed with MM by next-generation sequencing-based copy number variation analysis. The frequency of the chromothripsis-like pattern was observed in seven cell lines. We analyzed the treatment-induced chromothripsis-like patterns in KMS-12-BM and KMS-12-PE cells. As a result, breakpoints and chromothripsis-like patterns were increased after drug treatment in the relatively resistant KMS-12-BM. We further analyzed the patients’ results according to the therapeutic response, which was divided into sensitive and resistant, as suggested by the International Myeloma Working Group. The chromothripsis-like pattern was more frequently observed in the resistant group. In the sensitive group, the frequency of the chromothripsis-like pattern decreased after treatment, whereas the resistant group showed increased chromothripsis-like patterns after the treatment. These results suggest that the chromothripsis-like pattern is associated with treatment response in MM.


Subject(s)
Humans , Bone Marrow , Cell Line , Chromosome Aberrations , Drug Resistance , Multiple Myeloma , Plasma Cells , Prognosis
19.
Blood Research ; : 207-211, 2017.
Article in English | WPRIM | ID: wpr-38721

ABSTRACT

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.


Subject(s)
Humans , Anemia, Aplastic , Cohort Studies , Flow Cytometry , Follow-Up Studies , Hemoglobinuria, Paroxysmal , Hemolysis , Prospective Studies
20.
Experimental & Molecular Medicine ; : e360-2017.
Article in English | WPRIM | ID: wpr-153375

ABSTRACT

Donor lymphocyte infusion (DLI) followed by hematopoietic stem cell transplantation has served as an effective prevention/treatment modality against the relapse of some hematologic tumors, such as chronic myeloid leukemia (CML). However, the therapeutic efficacies of DLI for other types of leukemia, including acute lymphocytic leukemia (ALL), have been limited thus far. Therefore, we examined whether increasing the reactivity of donor T cells by gene modification could enhance the therapeutic efficacy of DLI in a murine model of ALL. When a CTLA4-CD28 chimera gene (CTC28) in which the intracellular signaling domain of CTLA4 was replaced with the CD28 signaling domain was introduced into CD4 and CD8 T cells in DLI, the graft-versus-tumor (GVT) effect was significantly increased. This effect was correlated with an increased expansion of donor CD8 T cells in vivo, and the depletion of CD8 T cells abolished this effect. The CD8 T cell expansion and the enhanced GVT effect were dependent on the transduction of both CD4 and CD8 T cells with CTC28, which emphasizes the role of dual modification in this therapeutic effect. The CTC28-transduced T cells that expanded in vivo also exhibited enhanced functionality. Although the potentiation of the GVT effect mediated by the CTC28 gene modification of T cells was accompanied by an increase of graft-versus-host disease (GVHD), the GVHD was not lethal and was mitigated by treatment with IL-10 gene-modified third-party mesenchymal stem cells. Thus, the combined genetic modification of CD4 and CD8 donor T cells with CTC28 could be a promising strategy for enhancing the therapeutic efficacy of DLI.


Subject(s)
Humans , Chimera , Graft vs Host Disease , Hematologic Neoplasms , Hematopoietic Stem Cell Transplantation , Interleukin-10 , Leukemia , Leukemia, Myelogenous, Chronic, BCR-ABL Positive , Lymphocytes , Mesenchymal Stem Cells , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Recurrence , T-Lymphocytes , Tissue Donors
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