[Show abstract][Hide abstract] ABSTRACT: The role of interim PET/CT in peripheral T-cell lymphoma (PTCL) is less identified compared to other subtype of lymphoma. This study prospectively investigated the prognostic accuracy of sequential interim PET/CT using visual and quantitative assessment to determine whether it provided prognostic information for the treatment of PTCL.
Sixty-three patients with newly diagnosed PTCL were enrolled, and 59 patients underwent interim PET/CT after three or four courses of induction treatment. The response of interim PET/CT was assessed by three parameters: the Deauville five-point scale (5-PS), ΔSUVmax, and ΔMTV2.5.
Over a median follow up of 40.3 months, each assessment of interim PET/CT using the 5-PS, ΔSUVmax, and ΔMTV2.5 had predictive value for progression-free survival. To increase the predictive accuracy of interim PET/CT, we divided patients into three groups according to the sum of scores for three adverse responses based on the visual, SUV-based and MTV-based assessment: favorable, intermediate, and poor responder. The clinical outcome of patients in the favorable group was significantly superior to patients in the poor or intermediate group.
Visual, quantitative SUV-based, and MTV-based assessment in interim PET/CT are valuable for early treatment response assessment in patients with PTCL, and the combined approach using the three parameters was more efficient in discriminating between patients with different survival outcomes compared with single-parameter assessment.
BMC Cancer 12/2015; 15(1):198. DOI:10.1186/s12885-015-1193-1 · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Normal karyotype acute myeloid leukemia (NK-AML) with CCAAT/enhancer binding protein α (CEBPA) mutations is known to have a more favorable prognosis. However, direct comparison of the clinical significance according to consolidation therapy has not been widely performed in patients with NK-AML. A total of 404 patients with NK-AML who received intensive induction chemotherapy were included in the present study. Diagnostic samples from the patients were evaluated for CEBPA mutations by direct sequencing. CEBPA single (sm) or double mutation (dm) was observed in 27 (6.7 %) and 51 (12.6 %) patients, respectively. CEBPA (dm) was associated with GATA2 (mut), and it was less frequently associated with FLT3-ITD(pos), NPM1 (mut), and DNMT3A (mut) in comparison with CEBPA (wild) or CEBPA (sm) (all p values <0.05). On multivariate analysis, CEBPA (dm) (p = 0.007, OR 39.593) was an independent risk factor for achievement of complete remission (CR). With a median follow-up of 40.1 months, CEBPA (dm) showed a favorable overall survival (OS), event-free survival (EFS), and lower relapse incidence (RI) in comparison with CEBPA (wild) (all p values <0.005). Comparison of clinical outcome analyses (consolidation chemotherapy vs. allogeneic hematopoietic cell transplantation (HCT)) demonstrated the role of consolidation treatment in patients with CEBPA (dm). Allogeneic HCT was associated with lower EFS and RI and a trend of higher non-relapse mortality. However, there was no statistically significant difference in OS. In conclusion, CEBPA (dm) was associated with other molecular mutations. Consolidation chemotherapy alone may overcome higher relapse rates by reducing the treatment mortality and increasing survival after relapse events in patients with CEBPA (dm) in NK-AML.
Annals of Hematology 11/2015; DOI:10.1007/s00277-015-2540-7 · 2.63 Impact Factor
[Show abstract][Hide abstract] 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).
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.
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 <100×10(9)/L at diagnosis (HR 2.534, 95% CI 1.068-6.015, P=0.035), were significantly associated with overall survival.
Oliguria was significantly associated with higher mortality in MM patients with RI. Therefore, close monitoring of urine output could be important for these patients.
Blood Research 10/2015; 50(3):167. DOI:10.5045/br.2015.50.3.167
[Show abstract][Hide abstract] ABSTRACT: Overall, more than 50% of marginal zone lymphoma (MZL) patients experience a relapse within 10 years. We conducted this phase II trial to assess the efficacy and safety of oxaliplatin-prednisone (Ox-P) chemotherapy for patients with relapsed or refractory MZL. Patients received oxaliplatin 130mg/m(2) on day 1, and prednisone 100mg/day on days 1-5 of each cycle. A total of 38 patients were enrolled. The median age of the 34 (16 males, 18 females) evaluated patients was 53 (range 27-74) years. There were 7 complete response (20.6%) and 15 partial response (44.1%) (Overall response rate 64.7%). No treatment related deaths occurred. The median progression free survival was 14.2 months (95% CI, 2.1-26.3 months). 3 year overall survival rate was 77.7%. Thus, salvage Ox-P chemotherapy for patients with relapsed or refractory MZL at the stated dosage and schedule, showed moderate clinical activity and considerable in very few selected patients. (NCT01068392).
[Show abstract][Hide abstract] 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.
[Show abstract][Hide abstract] ABSTRACT: 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.
Adult refractory ITP patients (<30,000 platelets/µL) were enrolled. Eltrombopag doses were increased to achieve a target platelet count (≥50,000 cells/µL). 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.
Among 18 patients, 66.7% achieved complete response, 5.6% achieved platelet counts between 50,000 and 100,000 cells/µL, 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.
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.
Blood Research 03/2015; 50(1):19-25. DOI:10.5045/br.2015.50.1.19
[Show abstract][Hide abstract] ABSTRACT: 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.
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.
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.
Weekly intravenous low-dose cidofovir without probenecid appears to be a safe and effective treatment option for patients with BKV-associated HC.
The Korean Journal of Internal Medicine 03/2015; 30(2):212-8. DOI:10.3904/kjim.2015.30.2.212 · 1.43 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Approximately 10–25 % of patients with diffuse large B cell lymphoma (DLBCL) at the time of diagnosis exhibit bone marrow involvement (BMI). After introduction of rituximab, immunohistochemistry (IHC) markers lost to prognostic value in DLBCL patients. However, the specimens used have mainly been diagnostic tissues, not bone marrow (BM). It would thus be useful to determine the prognostic value of specific IHC markers of pathologic BM in DLBCL patients with BMI in the rituximab era. In the present study, a total of 580 DLBCL patients were analyzed 67 of whom had BMI. CD10, Bcl-6, MUM-1, Bcl-6 and Ki-67 dyeing on pathologic BM were applied. Bcl-2 positivity was more frequent in discordant BMI (P = 0.039) and high Ki-67 expression was more frequent in concordant BMI (P = 0.016). High Ki-67 expression independently predicted poor prognosis between the negative BMI group and each of the following BMI-positive groups: entire BMI (PFS, P P P = 0.024; OS, P = 0.007), and discordant BMI (PFS, P = 0.033; OS, P = 0.026). We found that Ki-67 expression in pathologic BM is a novel significant prognostic parameter of worse prognosis in DLBCL patients with BMI in the rituximab era.
International Journal of Hematology 12/2014; 101(2). DOI:10.1007/s12185-014-1719-3 · 1.92 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) regimen has been widely used for lymphoblastic lymphoma (LBL) as a primary treatment. However, there is few data about its treatment outcome in Asian patients. Thus, we conducted this study to evaluate the efficacy of hyper-CVAD induction and stem cell transplantation (SCT) consolidation in LBL patients. The treatment responses of 49 patients treated with the hyper-CVAD regimen were retrospectively analyzed in 13 institutions. Given 24 patients who responded to hyper-CVAD underwent consolidation treatment with SCT, overall survival (OS) and progression-free survival (PFS) of patients who received SCT were compared with patients who did not. The overall response rate was 79 %: 73 % (36/49) complete responses, 6 % (3/49) partial responses, and 4 % (2/49) induction deaths. The major limitation for the delivery of the planned hyper-CVAD cycles was hematological toxicity. Among 39 responders, 24 patients underwent autologous (n = 16) and allogeneic SCT (n = 8) consolidation. Their 3-year OS and PFS rates were 76 and 78 %, respectively, and there was no difference in survival outcomes between autologous and allogeneic SCT. However, 15 patients without SCT consolidation showed poorer PFS even though they all achieved complete response. Thus, only seven patients maintained their response at the time of analysis. In conclusion, the hyper-CVAD regimen is effective for remission induction in LBL, and SCT consolidation after hyper-CVAD induction produced better clinical outcomes than did continuation of hyper-CVAD.
Annals of Hematology 12/2014; 94(4). DOI:10.1007/s00277-014-2258-y · 2.63 Impact Factor
[Show abstract][Hide abstract] 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-naïve 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-naïve 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.
Chonnam Medical Journal 12/2014; 50(3):102-11. DOI:10.4068/cmj.2014.50.3.102
[Show abstract][Hide abstract] ABSTRACT: This retrospective study investigated the clinical efficacy and safety of bortezomib retreatment in patients with relapsed or refractory multiple myeloma (MM). A total of 30 patients who relapsed or progressed after ≥6 months since the last dose of their previous bortezomib therapy were included in this study. During the median 6 cycles (range: 2-12) of bortezomib retreatment, 10 (33.3%), 2 (6.7%), and 6 (20.0%) patients achieved complete response, very good partial response, and partial response, respectively. Grade 3 or 4 neutropenia (47.0%), thrombocytopenia (43.0%), anemia (10.0%), and peripheral sensory neuropathy (3.0%) were observed. The median time to progression, progression-free survival, and overall survival were 5.8 months (95% CI: 2.6-9.0), 5.5 months (95% CI: 4.2-6.8), and 13.4 months (95% CI: 6.1-20.7), respectively. Patients who received bortezomib retreatment ≥12 months from initial last therapy had a 1-year OS rate of 65.8% (95% CI: 43.5-88.1) while patients receiving retreatment after 6-12 months interval had a 1-year OS rate of 41.7% (95% CI: 13.9-69.5) (P = 0.038). In conclusion, this study demonstrates that retreatment with bortezomib is an effective strategy for patients with MM who relapsed at a long interval after initial bortezomib therapy.
BioMed Research International 10/2014; 2014:145843. DOI:10.1155/2014/145843 · 1.58 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Bortezomib-based therapy is commonly used in treatment for relapsed or refractory multiple myeloma (MM). Unfortunately, many patients show relapse or progression in heterogeneous patterns.
Patients and methods:
In this study, we retrospectively evaluated patterns of relapse or progression after bortezomib-based salvage therapy in patients with MM and analyzed prognostic significance according to patterns of relapse or progression. One hundred forty-eight patients were treated with bortezomib-based therapy between November 2004 and April 2012. Of these patients, 104 (70.3%) patients relapsed or progressed after bortezomib-based salvage therapy. We divided the patterns of relapse or progression to the 2 groups: (1) the isoform relapse or progression (group A) in 89 (85.6%) patients as disease findings at initiation of bortezomib-based therapy; and (2) transformed relapse or progression (group B) in 15 (14.4%) patients (plasmacytoma, n = 7; light chain escape, n = 6; and plasma cell leukemia, n = 2) different from initial disease findings.
Median overall survival in group A and group B were 32.7 months (95% confidence interval [CI], 21.3-44.1) and 10.7 months (95% CI, 2.0-19.4) (P < .001), respectively.
MM patients who relapsed or progressed as the transformed pattern for bortezomib-based salvage therapy have an extremely poor prognosis and might require new innovative approaches.
[Show abstract][Hide abstract] ABSTRACT: Fluoroquinolone is recommended as a prophylactic antibiotic for high-risk patients with profound neutropenia. We previously reported that multiple myeloma (MM) patients who received bortezomib-based regimens were at higher risk of severe infections (30.9 %) associated with lymphocytopenia. In the study, we evaluated whether severe infectious complications can be prevented by prophylactic administration of oral levofloxacin in MM patients treated with bortezomib-based regimens. A total of 80 patients received oral levofloxacin 500 mg daily during the median four cycles of treatment. The prophylactic group (n = 80) with levofloxacin showed significantly decreased severe infections compared to a historical control group (n = 139) without levofloxacin prophylaxis during treatment of bortezomib-based regimens (17.5 vs. 30.9 %, P = 0.037). In the prophylactic group, two patients (2.5 %) died of pneumonia and septic shock. Four patients (5 %) stopped levofloxacin due to side effects that consisted of gastrointestinal discomfort (2.5 %), itching sense (1.25 %), and QTc prolongation (1.25 %). In conclusion, prophylaxis with levofloxacin may be effective in the prevention of severe infection in MM patients receiving bortezomib-based regimens. A prospective randomized study is needed to test the prophylactic effect of levofloxacin in MM patients treated with bortezomib-based regimens.
International Journal of Hematology 09/2014; 100(5). DOI:10.1007/s12185-014-1672-1 · 1.92 Impact Factor