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1.
Article in English | WPRIM | ID: wpr-915455

ABSTRACT

Immune thrombocytopenia (ITP) is an autoimmune condition characterized by platelet destruction through antibody-mediated mechanism. ITP is one of the manifestations of a coronavirus disease, as well as an adverse event occurring after vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Several cases of ITP have been described after vaccination with two mRNA-based vaccines—BTN162b2 (Pfizer-BioNTech) and mRNA-1273 (Moderna)—against SARS-CoV-2. Herein, we report a case of ITP occurring after vaccination with ChAdOx1 adenovirus vector nCoV-19 (AstraZeneca) vaccine in Korea. A 66-year-old woman presented with multiple ecchymoses on both upper and lower extremities and gingival bleeding, appearing 3 days after receiving the first dose of ChAdOx1 nCoV-19. Her laboratory results showed isolated severe thrombocytopenia without evidence of combined coagulopathy. She was diagnosed with ITP and successfully treated with high-dose dexamethasone and intravenous immunoglobulin. Clinical suspicion to identify vaccinerelated ITP is important to promptly initiate appropriate treatment.

2.
Article in English | WPRIM | ID: wpr-899944

ABSTRACT

Background@#This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). @*Methods@#We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. @*Results@#Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. @*Conclusion@#Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

3.
Article in English | WPRIM | ID: wpr-892240

ABSTRACT

Background@#This study presents outcomes of management in graft failure (GF) after allogeneic hematopoietic stem cell transplantation (HCT) and provides prognostic information including rare cases of autologous reconstitution (AR). @*Methods@#We analyzed risk factors and outcomes of primary and secondary GF, and occurrence of AR in 1,630 HCT recipients transplanted over period of 18 years (January 2000– September 2017) at our center. @*Results@#Primary and secondary GF occurred in 13 (0.80%), and 69 patients (10-year cumulative incidence, 4.5%) respectively. No peri-transplant variables predicted primary GF, whereas reduced intensity conditioning (RIC) regimen (relative risk [RR], 0.97–28.0, P < 0.001) and lower CD34 + cell dose (RR, 2.44–2.84, P = 0.002) were associated with higher risk of secondary GF in multivariate analysis. Primary GF demonstrated 100% mortality, in the secondary GF group, the 5-year Kaplan-Meier survival rate was 28.8%, relapse ensued in 18.8%, and AR was observed in 11.6% (n = 8). In survival analysis, diagnosis of aplastic anemia (AA), chronic myeloid leukemia and use of RIC had a positive impact. There were 8 patients who experienced AR, which was rarely reported after transplantation for acute leukemia. Patient shared common characteristics such as young age (median 25 years), use of RIC regimen, absence of profound neutropenia, and had advantageous survival rate of 100% during follow period without relapse. @*Conclusion@#Primary GF exhibited high mortality rate. Secondary GF had 4.5% 10-year cumulative incidence, median onset of 3 months after HCT, and showed 5-year Kaplan-Meier survival of 28.8%. Diagnosis of severe AA and use of RIC was both associated with higher incidence and better survival rate in secondary GF group. AR occurred in 11.6% in secondary GF, exhibited excellent prognosis.

5.
Blood Research ; : 288-293, 2018.
Article in English | WPRIM | ID: wpr-718482

ABSTRACT

BACKGROUND: Although allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment option for myelodysplastic syndrome (MDS), a substantial number of patients experience relapse. We reviewed the clinical outcomes of patients with MDS who relapsed after allogeneic HCT. METHODS: Thirty patients who experienced relapse or progression after allogeneic HCT for MDS between July 2000 and May 2016 were included in this retrospective analysis. RESULTS: The median time from HCT to relapse was 6.6 (range, 0.9–136.3) months. Donor lymphocyte infusions (DLIs) were administered to four patients: one achieved complete remission (CR) and survived disease free, while three did not respond to DLI and died. Hypomethylating agents were administered to seven patients: one who had stable disease continuously received decitabine, while six died without response to treatment. Six patients received AML-like intensive chemotherapy, and three achieved CR: two underwent second HCT and one DLI. One patient receiving second HCT survived without disease, but the other two relapsed and died. Three, four, and eight patients who did not respond to intensive chemotherapy, low-dose cytarabine, and best supportive care, respectively, died. One patient who underwent second HCT following cytogenetic relapse survived disease free. Median overall survival after relapse was 4.4 months, and relapse within 6 months after HCT was associated with shorter survival. CONCLUSION: Outcomes of MDS patients relapsing after allogeneic HCT were disappointing. Some patients could be saved using DLI or second HCT.


Subject(s)
Cell Transplantation , Cytarabine , Cytogenetics , Drug Therapy , Humans , Lymphocytes , Myelodysplastic Syndromes , Recurrence , Retrospective Studies , Tissue Donors , Transplants
6.
Immune Network ; : e2-2018.
Article in English | WPRIM | ID: wpr-714036

ABSTRACT

The detailed kinetics of the cytomegalovirus (CMV)-specific T cell response in hematopoietic stem cell transplant (HCT) recipients have not yet been fully assessed. We evaluated these kinetics of CMV-specific T cell response and factors associated with high CMV-specific T cell responses 1 year after HCT. In HCT recipients, CMV pp65 and IE1-specific ELISPOT assay were performed before HCT (D0), and at 30 (D30), 90 (D90), 180 (D180), and 360 (D360) days after HCT. Of the 51 HCT recipients with donor-positive (D+)/recipient-positive (R+) serology, 26 (51%) developed CMV infections after HCT. The patterns of post-transplantation reconstitution for CMV-specific T cell response were classified into 4 types: 1) an initial decrease at D30 followed by gradual T cell reconstitution without CMV infection (35%), 2) an initial decrease at D30 followed by gradual T cell reconstitution preceded by CMV infection (35%), 3) failure of gradual or constant T cell reconstitution (26%), and 4) no significant T cell reconstitution (4%). There was no significant difference between ELISPOT counts of D360 and those of D0. High CMV-specific T cell responses at D360 were not associated with high CMV-specific T cell response at D0, CMV infection, ganciclovir therapy, graft versus host disease (GVHD), and immunosuppressant use. In conclusion, there are 4 distinct patterns of reconstitution of the CMV-specific T cell response after HCT. In addition, reconstituted donor-origin CMV-specific T cell responses appeared to be constant until day 360 after HCT, regardless of the level of the pre-transplant CMV-specific T cell response, CMV infection, and immunosuppressant use.


Subject(s)
Cytomegalovirus , Enzyme-Linked Immunospot Assay , Follow-Up Studies , Ganciclovir , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Kinetics , Theophylline
8.
Korean Journal of Medicine ; : 546-551, 2017.
Article in Korean | WPRIM | ID: wpr-103595

ABSTRACT

A 37-year-old female presented to our hospital with a history of bleeding episodes (excessive bleeding after tooth extraction, gum bleeding, easy bruising, and excessive menstruation) and severe thrombocytopenia (2,000/µL). She had no family history of bleeding tendency or thrombocytopenia. No peripheral lymphadenopathy or splenomegaly was noted. The patient's white blood cell count was normal; hemoglobin was 9.7 g/dL. A peripheral blood smear showed markedly decreased platelets, with occasional giant or large platelets. Bone marrow examination found increased megakaryocytes. The patient also complained of hearing difficulty; a hearing test indicated sensory-neural hearing impairment. Her thrombocytopenia was refractory to treatment with glucocorticosteroids, intravenous gamma-globulin, and danazol. In the 13 years following her initial presentation, the patient required anti-hypertensive treatment, a hearing-aid for progressive hearing loss, and started maintenance kidney dialysis. Her clinical history of refractory thrombocytopenia, progressive hearing impairment, and renal failure suggested myosin heavy chain 9 gene-related congenital syndrome (Epstein syndrome), which was confirmed by the presence of a heterozygous deletion mutation, c.221_223del, (p.Lys74del) in peripheral leukocyte deoxyribonucleic acid.


Subject(s)
Adult , Bone Marrow Examination , Danazol , Dialysis , DNA , Female , gamma-Globulins , Gingiva , Hearing , Hearing Loss , Hearing Loss, Sensorineural , Hearing Tests , Hemorrhage , Humans , Kidney , Leukocyte Count , Leukocytes , Lymphatic Diseases , Megakaryocytes , Myosin Heavy Chains , Renal Insufficiency , Renal Insufficiency, Chronic , Sequence Deletion , Splenomegaly , Thrombocytopenia , Tooth Extraction
9.
Article in English | WPRIM | ID: wpr-770946

ABSTRACT

BACKGROUND: Administering extracorporeal membrane oxygenation (ECMO) to critically ill patients with acute respiratory distress syndrome has substantially increased over the last decade, however administering ECMO to patients with hematologic malignancies may carry a particularly high risk. Here, we report the clinical outcomes of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO. METHODS: We performed a retrospective review of the medical records of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO at the medical intensive care unit of a tertiary referral hospital between March 2010 and April 2015.


Subject(s)
Adult , APACHE , Critical Illness , Extracorporeal Membrane Oxygenation , Hematologic Neoplasms , Hemorrhage , Humans , Intensive Care Units , Intracranial Hemorrhages , Lung Injury , Male , Medical Records , Respiratory Distress Syndrome , Respiratory Insufficiency , Retrospective Studies , Tertiary Care Centers , Weaning
10.
Article in English | WPRIM | ID: wpr-728449

ABSTRACT

The objective of this study was to externally validate a new dosing scheme for busulfan. Thirty-seven adult patients who received busulfan as conditioning therapy for hematopoietic stem cell transplantation (HCT) participated in this prospective study. Patients were randomized to receive intravenous busulfan, either as the conventional dosage (3.2 mg/kg daily) or according to the new dosing scheme based on their actual body weight (ABW) (23×ABW(0.5) mg daily) targeting an area under the concentration-time curve (AUC) of 5924 µM·min. Pharmacokinetic profiles were collected using a limited sampling strategy by randomly selecting 2 time points at 3.5, 5, 6, 7 or 22 hours after starting busulfan administration. Using an established population pharmacokinetic model with NONMEM software, busulfan concentrations at the available blood sampling times were predicted from dosage history and demographic data. The predicted and measured concentrations were compared by a visual predictive check (VPC). Maximum a posteriori Bayesian estimators were estimated to calculate the predicted AUC (AUC(PRED)). The accuracy and precision of the AUC(PRED) values were assessed by calculating the mean prediction error (MPE) and root mean squared prediction error (RMSE), and compared with the target AUC of 5924 µM·min. VPC showed that most data fell within the 95% prediction interval. MPE and RMSE of AUCPRED were -5.8% and 20.6%, respectively, in the conventional dosing group and −2.1% and 14.0%, respectively, in the new dosing scheme group. These fi ndings demonstrated the validity of a new dosing scheme for daily intravenous busulfan used as conditioning therapy for HCT.


Subject(s)
Adult , Area Under Curve , Behavior Therapy , Body Weight , Busulfan , Drug Dosage Calculations , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Pharmacokinetics , Prospective Studies
11.
Article in English | WPRIM | ID: wpr-81004

ABSTRACT

BACKGROUND/AIMS: Cytomegalovirus (CMV) surveillance and preemptive therapy is a widely-used strategy for preventing CMV disease in transplant recipients. However, there are limited data on the incidence and patterns of CMV disease during the preemptive period. Thus, we investigated the incidence and pattern of tissue-invasive CMV disease in CMV seropositive kidney transplantation (KT) and hematopoietic stem cell transplantation (HCT) recipients during preemptive therapy. METHODS: We prospectively identified patients with tissue-invasive CMV disease among 664 KT (90%) and 496 HCT (96%) recipients who were D+/R+ (both donor and recipient seropositive) during a 4-year period. RESULTS: The incidence rates of CMV disease were 4.1/100 person-years (4%, 27/664) in KT recipients and 5.0/100 person-years (4%, 21/496) in HCT recipients. Twenty-six (96%) of the KT recipients with CMV disease had gastrointestinal CMV, whereas 17 (81%) of the HCT recipients had gastrointestinal CMV and 4 (19%) had CMV retinitis. Thus, CMV retinitis was more common among HCT recipients (p = 0.03). All 27 KT recipients with CMV disease suffered abrupt onset of CMV disease before or during preemptive therapy; 10 (48%) of the 21 HCT recipients with CMV disease were also classified in this way but the other 11 (52%) were classified as CMV disease following successful ganciclovir preemptive therapy (p < 0.001). CONCLUSIONS: The incidence of CMV disease was about 4% in both KT and HCT recipients during preemptive therapy. However, CMV retinitis and CMV disease as a relapsed infection were more frequently found among HCT recipients.


Subject(s)
Cytomegalovirus , Ganciclovir , Hematopoietic Stem Cell Transplantation , Hematopoietic Stem Cells , Humans , Incidence , Kidney Transplantation , Kidney , Prospective Studies , Retinitis , Tissue Donors , Transplant Recipients
12.
Article in English | WPRIM | ID: wpr-67125

ABSTRACT

BACKGROUND: Administering extracorporeal membrane oxygenation (ECMO) to critically ill patients with acute respiratory distress syndrome has substantially increased over the last decade, however administering ECMO to patients with hematologic malignancies may carry a particularly high risk. Here, we report the clinical outcomes of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO. METHODS: We performed a retrospective review of the medical records of patients with hematologic malignancies and severe acute respiratory failure who were treated with ECMO at the medical intensive care unit of a tertiary referral hospital between March 2010 and April 2015. RESULTS: A total of 15 patients (9 men; median age 45 years) with hematologic malignancies and severe acute respiratory failure received ECMO therapy during the study period. The median values of the Acute Physiology and Chronic Health Evaluation II score, Murray Lung Injury Score, and Respiratory Extracorporeal Membrane Oxygenation Survival Prediction Score were 29, 3.3, and -2, respectively. Seven patients received venovenous ECMO, whereas 8 patients received venoarterial ECMO. The median ECMO duration was 2 days. Successful weaning of ECMO was achieved in 3 patients. Hemorrhage complications developed in 4 patients (1 pulmonary hemorrhage, 1 intracranial hemorrhage, and 2 cases of gastrointestinal bleeding). The longest period of patient survival was 59 days after ECMO initiation. No significant differences in survival were noted between venovenous and venoarterial ECMO groups (10.0 vs. 10.5 days; p = 0.56). CONCLUSIONS: Patients with hematologic malignancies and severe acute respiratory failure demonstrate poor outcomes after ECMO treatment. Careful and appropriate selection of candidates for ECMO in these patients is necessary.


Subject(s)
Adult , APACHE , Critical Illness , Extracorporeal Membrane Oxygenation , Hematologic Neoplasms , Hemorrhage , Humans , Intensive Care Units , Intracranial Hemorrhages , Lung Injury , Male , Medical Records , Respiratory Distress Syndrome , Respiratory Insufficiency , Retrospective Studies , Tertiary Care Centers , Weaning
13.
Article in English | WPRIM | ID: wpr-210698

ABSTRACT

Mutations in the calreticulin gene, CALR, have recently been discovered in subsets of patients with essential thrombocythemia (ET) or primary myelofibrosis (PMF). We investigated Korean patients with ET and PMF to determine the prevalence, and clinical and laboratory correlations of CALR/JAK2/MPL mutations. Among 84 ET patients, CALR mutations were detected in 23 (27.4%) and were associated with higher platelet counts (P=0.006) and lower leukocyte counts (P=0.035) than the JAK2 V617F mutation. Among 50 PMF patients, CALR mutations were detected in 11 (22.0%) and were also associated with higher platelet counts (P=0.035) and trended to a lower rate of cytogenetic abnormalities (P=0.059) than the JAK2 V617F mutation. By multivariate analysis, triple-negative status was associated with shorter overall survival (HR, 7.0; 95% CI, 1.6-31.1, P=0.01) and leukemia-free survival (HR, 6.3; 95% CI, 1.8-22.0, P=0.004) in patients with PMF. The type 1 mutation was the most common (61.1%) type among all patients with CALR mutations, and tended toward statistical predominance in PMF patients. All 3 mutations were mutually exclusive and were never detected in patients with other myeloid neoplasms showing thrombocytosis. CALR mutations characterize a distinct group of Korean ET and PMF patients. Triple-negative PMF patients in particular have an unfavorable prognosis, which supports the idea that triple-negative PMF is a molecularly high-risk disease.


Subject(s)
Adult , Aged , Aged, 80 and over , Calreticulin/genetics , Disease-Free Survival , Female , Gene Frequency , Genetic Association Studies , Humans , Janus Kinase 2/genetics , Male , Middle Aged , Mutation/genetics , Primary Myelofibrosis/genetics , Receptors, Thrombopoietin/genetics , Republic of Korea , Thrombocythemia, Essential/genetics , Young Adult
14.
Blood Research ; : 227-234, 2015.
Article in English | WPRIM | ID: wpr-40795

ABSTRACT

BACKGROUND: Efforts to overcome poor outcomes in patients with adult acute lymphoblastic leukemia (ALL) have focused on combining new therapeutic agents targeting immunophenotypic markers (IPMs) with classical cytotoxic agents; therefore, it is important to evaluate the clinical significance of IPMs. METHODS: Baseline characteristics and clinical outcomes of patients with adult ALL were retrospectively analyzed. The percentage of blasts expressing IPMs at diagnosis was measured by multicolor flow cytometry analysis. Samples in which > or =20% of blasts expressed an IPM were considered positive. RESULTS: Among the total patient population (N=230), almost all (92%) were in first or second hematological complete remission (HCR) and 54% received allogeneic hematopoietic cell transplant (allo-HCT). Five-year hematologic relapse-free survival (HRFS) and overall survival (OS) rates were 36% and 39%, respectively, and 45.6% and 80.5% of patients were positive for the IPMs CD20 and terminal deoxynucleotidyl transferase (TdT), respectively. Expression of CD20, CD13, CD34, and TdT was associated with HRFS rate, and expression of CD20 and CD13 was associated with OS rate, as was the performance of allo-HCT. In multivariate analysis, positivity for CD20 (HRFS: hazard ratio [HR], 2.21, P<0.001; OS: HR, 1.63, P=0.015) and negativity for TdT (HRFS: HR, 2.30, P=0.001) were both significantly associated with outcomes. When patients were categorized into three subgroups according to positivity for CD20 and TdT, there were significant differences in HRFS and OS among the subgroups. CONCLUSION: Positivity for CD20 and TdT expression and clinical risk group were prognostic factors in adult ALL.


Subject(s)
Adult , Cytotoxins , Diagnosis , DNA Nucleotidylexotransferase , Flow Cytometry , Humans , Multivariate Analysis , Precursor Cell Lymphoblastic Leukemia-Lymphoma , Retrospective Studies , Transplants
15.
Korean Journal of Medicine ; : 474-477, 2015.
Article in Korean | WPRIM | ID: wpr-153838

ABSTRACT

Pseudoxanthoma elasticum (PXE)-like disorder with multiple coagulation factor deficiency is a genetic disease characterized by dystrophic mineralization of the connective tissue in multiple organs such as the skin, arteries, and retina. Patients with this disorder have excessive folding and sagging of the skin with loss of recoil, as well as coagulopathy. Crohn's disease is a chronic inflammatory condition of the gastrointestinal tract, which primary affects the small intestine, often leading to malnutrition. Here, we describe the case of a 25-year-old woman who presented with these diseases. We found that nutrient deficiency due to long-term Crohn's disease aggravated the coagulopathy associated with PXE-like disorder.


Subject(s)
Adult , Arteries , Blood Coagulation Factors , Connective Tissue , Crohn Disease , Female , Gastrointestinal Tract , Humans , Intestine, Small , Malnutrition , Pseudoxanthoma Elasticum , Retina , Skin
16.
Korean Journal of Medicine ; : 464-468, 2015.
Article in English | WPRIM | ID: wpr-194216

ABSTRACT

Evans syndrome is a rare complication that develops in adults after liver transplantation. The possible etiologies include ABO mismatch, viral infection, post-transplantation lymphoproliferative disease, graft-versus-host disease, and the use of certain immunosuppressive drugs (e.g., calcineurin inhibitors). Here, we present a case of Evans syndrome that developed after an ABO-matched liver transplant. Glucocorticosteroid, intravenous immunoglobulin, and alternative immunosuppressant therapies all failed. Weekly rituximab (375 mg/m2) was then administered for 4 weeks. The cytopenia improved transiently after the second dose of rituximab, but soon worsened again. However, the cytopenia normalized after a splenectomy.


Subject(s)
Adult , Anemia, Hemolytic, Autoimmune , Calcineurin , Graft vs Host Disease , Humans , Immunoglobulins , Liver Transplantation , Liver , Purpura, Thrombocytopenic, Idiopathic , Splenectomy , Rituximab
17.
Article in English | WPRIM | ID: wpr-178239

ABSTRACT

BACKGROUND: The presence of significant dysplasia in bone marrow (BM) aspirates helps to distinguish between hypocellular myelodysplastic syndrome (hMDS) and aplastic anemia (AA). Occasionally, diluted BM aspirates make it difficult to recognize dysplastic changes and can also negatively affect the detection of cytogenetic abnormalities in hMDS. We evaluated the usefulness of CD34 and p53 immunoreactivity for discriminating between hMDS and AA and for estimating survival outcomes in hMDS patients. METHODS: BM clot section (BMC) or BM biopsy (BMB) specimens were obtained from 64 hMDS/AA patients (33 with hMDS and 31 with AA) and seven controls. Immunohistochemical (IHC) staining for CD34 and p53 was performed by using the EnVision detection system (Dako, Denmark). We compared the results of IHC staining, BM findings, and chromosomal analyses, and determined overall survival outcomes. RESULTS: The number of CD34- and p53-positive BM cells was higher among the patients with hMDS than among the patients with AA (P<0.001 and P=0.001, respectively). hMDS patients with increased CD34-positive cells had significantly poorer survival outcomes compared with those with normal number of CD34-positive cells (P=0.013). CONCLUSIONS: CD34 and p53 IHC stains of BMC or BMB provide useful information for differentiating between hMDS and AA. CD34 IHC staining of BMC or BMB also provides useful information for estimating survival outcomes in hMDS patients.


Subject(s)
Adolescent , Adult , Anemia, Aplastic/diagnosis , Antigens, CD34/metabolism , Bone Marrow/metabolism , Child , Chromosome Aberrations , Diagnosis, Differential , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Myelodysplastic Syndromes/diagnosis , ROC Curve , Tumor Suppressor Protein p53/metabolism
18.
Article in English | WPRIM | ID: wpr-8783

ABSTRACT

PURPOSE: The purpose of this study is to assess the efficacy and safety of everolimus in Korean patients with metastatic renal cell carcinoma (mRCC) for whom initial treatment with a vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) has failed. MATERIALS AND METHODS: Eligible patients with mRCC (any histology) who had progressed on or were intolerant of VEGFr-TKI therapy received oral everolimus (10 mg dose once daily). Tumor response was reassessed according to Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS: This study included 100 patientswith a median follow-up duration of 10.2 months, a median progression-free survival (PFS) of 4.2 months (95% confidence interval [CI], 3.4 to 5.0 months), and an overall survival of 10.1 months (95% CI, 6.9 to 13.3 months). The most common grade 3 or greater adverse events (AEs) overall were anemia (13%), pneumonitis (9%), hyperglycemia (8%), and stomatitis (6%). While the incidence of pneumonitis was similar (26 cases, 26%) to the reported incidence in Western patients, the Korean presentations were more severe: 10 patients permanently discontinued everolimus due to pneumonitis, including two deaths on treatment. Statistically significant relationships were established between biologic toxicities, hyperglycemia and anemia, and PFS (hyperglycemia vs. non-hyperglycemia: hazard ratio [HR], 0.61; p=0.055 and anemia vs. non-anemia: HR, 0.51; p=0.021). CONCLUSION: Everolimus was effective in Korean patients with mRCC who had failed initial VEGFr-TKI therapy. While everolimus was well tolerated in general and the AE incidence of this study was similar to those of previous reports, severe pneumonitis was common. Hyperglycemia and anemia showed significant correlation with PFS and thus may be potentially useful as prognostic indicators.


Subject(s)
Anemia , Carcinoma, Renal Cell , Disease-Free Survival , Follow-Up Studies , Humans , Hyperglycemia , Incidence , Phosphotransferases , Pneumonia , Stomatitis , Treatment Failure , Treatment Outcome , Vascular Endothelial Growth Factor A , Everolimus
20.
Blood Research ; : 178-184, 2013.
Article in English | WPRIM | ID: wpr-172220

ABSTRACT

BACKGROUND: In adults, the 2 main types of myelodysplastic/myeloproliferative neoplasms (MDS/MPN) are chronic myelomonocytic leukemia (CMML) and atypical chronic myeloid leukemia (aCML). Both are associated with a poor prognosis. Allogeneic hematopoietic cell transplantation (HCT) is the only known curative treatment modality for these diseases, but data on outcomes following such treatment are limited. We analyzed the outcomes of patients with MDS/MPN after allogeneic HCT. METHODS: This retrospective study included 10 patients with MDS/MPN who received allogeneic HCT at Asan Medical Center from 2002 to 2010. Of these 10 patients, 7 had CMML, 2 had aCML, and 1 had unclassifiable MDS/MPN. Five patients received a myeloablative conditioning (MAC) regimen (busulfan-cyclophosphamide), and 5 received reduced-intensity conditioning (RIC) regimen. RESULTS: Neutrophil engraftment was achieved in all patients. After a median follow-up of 47.5 months among surviving patients, 4 had relapsed and 5 had died. There was only 1 treatment-related death. The 5-year rates of overall, relapse-free, and event-free survival were 42.2%, 51.9%, and 46.7%, respectively. Relapse was the leading cause of treatment failure, and all relapses were observed in patients who had received RIC and who did not develop chronic graft-versus-host disease. CONCLUSION: Allogeneic HCT can induce durable remission in patients with MDS/MPN, but RIC cannot replace MAC in patients eligible for myeloablative treatments.


Subject(s)
Adult , Cell Transplantation , Disease-Free Survival , Follow-Up Studies , Humans , Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative , Leukemia, Myelomonocytic, Chronic , Neutrophils , Prognosis , Recurrence , Retrospective Studies , Transplants , Treatment Failure
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