Ho Jin Shin

Alemtuzumab plus CHOP as front-line chemotherapy for patients with peripheral T-cell lymphomas : a phase II study

PurposeThe present study was conducted to evaluate the safety and efficacy of alemtuzumab plus CHOP chemotherapy for patients with peripheral T-cell lymphomas (PTCLs).Patients and methodsTwenty patients with newly diagnosed PTCLs were enrolled. The treatment consisted of classical CHOP plus alemtuzumab (10xa0mg i.v. on day 1 and 20xa0mg i.v. on day 2 in the first cycle, then 30xa0mg i.v. on day 1 in the subsequent cycles) based on 3-week intervals.ResultsThirteen complete responses (65.0%) and three partial responses (15.0%) were confirmed, giving an overall response rate of 80.0%. The estimated event-free survival at 1 year was 43.3%. The most severe hematologic adverse event was neutropenia, which occurred with a grade-4 intensity in 18 patients (90.0%). Also, febrile neutropenia was observed in 11 patients (55.0%). Five patients (25%) experienced cytomegalovirus (CMV) reactivation, while three patients developed CMV diseases, such as pneumonitis or retinitis. There were two treatment-related deaths. Based on the high incidence of the adverse infectious and hematologic events, the current study was closed after 20 of the planned 43 patients had been enrolled.ConclusionThe alemtuzumab plus CHOP chemotherapy seemed to produce active antitumor activity in terms of the complete response rates in patients with PTCLs. However, since high infectious and hematologic toxicities were observed, careful monitoring and early treatment are needed to prevent treatment-related mortality.

Measurement of tumor volume by PET to evaluate prognosis in patients with head and neck cancer treated by chemo-radiation therapy.

Abstract Purpose. To evaluate the prognostic value of the metabolic tumor volume measured on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging and other clinical factors in patients treated for locally advanced head-and-neck cancer (HNC) at a single institution. Materials and methods. Between June 2005 and August 2008, 59 patients with HNC that underwent pretreatment FDG-PET studies received neoadjuvant chemotherapy and radiation therapy. Metabolically active tumor regions were delineated on the pretreatment PET scans by a fixed SUV of 2.5. We evaluated the relationship of the 18F-fluorodeoxyglucose-PET maximum standardized uptake value (SUV) and the metabolic tumor volume (MTV) with the progression-free survival (PFS) and overall survival (OS). Results. The MTV and lymph node metastasis were predictive of the PFS and OS. The lymph node status did not correlate with the MTV. A higher MTV of 9.3 cm3 was significantly associated with an increased risk of recurrence (2.19-fold, p = 0.006) and death (1.62-fold, p = 0.051). Separation of patients with tumor volumes ≤ 9.3 cm3 and no lymph node disease vs. any other combination was strongly predictive of the PFS and the OS. Conclusions. MTV and lymph node status were prognostic values associated with survival. Quantitative measurement of tumor volume separates patients with a good prognosis from those with a poorer prognosis. A subset of patients with relatively small tumors and no lymph node involvement did very well.

Weekly rituximab followed by monthly rituximab treatment for steroid-refractory chronic graft-versus-host disease: results from a prospective, multicenter, phase II study

Background Since it was suggested that B cells play a role in the pathogenesis of chronic graft-versus-host disease, rituximab, an anti-CD20 monoclonal antibody targeting B cells, has been shown to be effective in steroid-refractory, chronic graft-versus-host disease. However, most of the data were from small numbers of patients or retrospective analyses. We, therefore, conducted a multicenter phase II study to confirm the efficacy of this treatment strategy that targets B cells. Design and Methods We diagnosed and evaluated chronic graft-versus-host disease according to the National Institute of Health criteria for clinical trials on this condition. The treatment consisted of weekly intravenous infusions of rituximab for 4 weeks followed by monthly rituximab for 4 months. We evaluated the patients’ responses and monitored their disease activity until their final visit, which was on day 365. We also assessed the patients’ subsequent quality of life and serum levels of B-cell-activating factor of the tumor necrosis factor family. Results Among 37 patients enrolled (median age, 29 years; range 8–57 years), 32 patients responded to rituximab with 8 complete and 24 partial responses. Twenty-one patients maintained their response for 1 year, so their steroid treatment was discontinued or its dose reduced (21/37, or 56.8%), and their scores representing quality of life were improved although these changes were not statistically significant. The responses were better for clinical manifestations of the skin, oral cavity and musculoskeletal system (response rate, 71.4–100%) than for other organs. However, infectious complications and primary disease relapse accounted for the majority of treatment failure. The pre-treatment serum level of B cell-activating factor of the tumor necrosis factor family was not associated with better treatment outcome (P=0.147). Conclusions Rituximab could improve clinical responses and quality of life of patients with steroid-refractory chronic graft-versus-host disease, although such patients may need active prophylaxis against infection.

Prognostic Factors and Clinical Outcomes of High-Dose Chemotherapy followed by Autologous Stem Cell Transplantation in Patients with Peripheral T Cell Lymphoma, Unspecified: Complete Remission at Transplantation and the Prognostic Index of Peripheral T Cell Lymphoma Are the Major Factors Predictive of Outcome

High-dose chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) offers a rescue option for T cell lymphoma patients with poor prognosis. However, the effectiveness of HDT/ASCT in patients with various peripheral T cell subtypes, optimal transplant timing, and the prognostic factors that predict better outcomes, have not been identified. We retrospectively investigated the clinical outcomes and prognostic factors for HDT/ASCT in 64 Korean patients with peripheral T cell lymphoma, unspecified (PTCL-U) between March 1995 and February 2007. The median age at transplantation was 44 years (range: 15-63 years). According to the age-adjusted International Prognostic Index (a-IPI) and the prognostic index of PTCL (PIT), 8 patients (12.5%) were in the high-risk group and 16 (26.6%) had the 2-3 PIT factors, respectively. After a median follow-up of 29.7 months, the 3-year overall survival (OS) and progression-free survival (PFS) rates were 53.0% +/- 7.5% and 44.3% +/- 7.0%, respectively. Univariate analysis showed that poor performance status, high lactate dehydrogenase (LDH) levels, high a-IPI score, high PIT classes, failure to achieve complete response (CR) at transplantation, and nonfrontline transplantation were associated with poor OS. Multivariate analysis showed that failure to achieve CR at transplantation (hazard ratio [HR] 2.23; 95% confidence interval [CI] 1.78-7.93) and 2-3 PIT factors (HR 3.76; 95% CI 1.02-5.42) were independent prognostic factors for OS. Failure to achieve CR at transplantation and high PIT are negative predictable factors for survival following HDT/ASCT in patients with PTCL-U.

Bortezomib and the increased incidence of herpes zoster in patients with multiple myeloma.

BACKGROUNDnBortezomib has significantly advanced the treatment of patients with multiple myeloma (MM). However, considering that most patients with MM are elderly, bortezomib-related morbidity should be thoroughly studied to ensure the safe use of this drug. Herpes zoster has been reported as a possible adverse event associated with bortezomib because a major target of bortezomib, nuclear factor-kappaB, is known to be involved with T-cell immunity.nnnPATIENTS AND METHODSnWe performed a retrospective analysis of the incidence of herpes zoster among 282 patients treated with a bortezomib-containing regimen.nnnRESULTSnDuring the patients pre-bortezomib treatment (median, 2.14 years), the incidence of herpes zoster was 11% (31 of 282 patients). However, after the patients were treated with bortezomib, the incidence increased to 22.3% (63 of 282 patients), of which almost all occurrences were within the first 3 cycles (median duration, 41 days). The time interval from diagnosis to bortezomib initiation date was shorter in herpes zoster-positive patients than in herpes zoster-negative patients (2.14 +/- 1.87 years vs. 3.38 +/- 2.95 years; P = .002). Disease duration, previous herpes zoster infection, disease stage and type of myeloma, and the type and intensity of previous treatments failed to show any relationship with herpes zoster. These findings suggest that longer history of disease and treatments did not affect the occurrence of herpes zoster, nor did the type of bortezomib regimens or their toxicities.nnnCONCLUSIONnBortezomib can increase the incidence of herpes zoster regardless of disease duration, previous treatments, and concomitantly administered drugs. Thus, the occurrence of herpes zoster should be monitored during bortezomib treatment.

Prognostic factors in primary diffuse large B-cell lymphoma of adrenal gland treated with rituximab-CHOP chemotherapy from the Consortium for Improving Survival of Lymphoma (CISL).

BackgroundThe objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.MethodsThirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.ResultsComplete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (Pu2009=u20090.029) and PFS (Pu2009=u20090.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (Pu2009=u20090.021) and PFS (P < 0.001).ConclusionsContrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.

Prognostic implications of the immunophenotype in biphenotypic acute leukemia

The present study retrospectively analyzed clinicopathological and clinical data from 43 adult patients with biphenotypic acute leukemia (BAL) from 11 Korean institutes. The incidence of BAL was 2.1% among acute leukemias. In terms of immunophenotype, 31 patients had myeloid plus B-lymphoid (M + B), 10 had myeloid plus T-lymphoid (M + T), one had myeloid plus B-lymphoid plus T-lymphoid (M + B + T), and one had B-lymphoid plus T-lymphoid (B + T). Patients with M + T phenotype had significantly lower CR rate (55.6% vs. 88.0%, P = 0.039) and lower overall survival (0% vs. 33.9% at 5 years, P = 0.028) than those with M + B phenotype. Our results suggest that immunophenotype has prognostic implications in adult patients with BAL.

Efficacy and safety of radotinib in chronic phase chronic myeloid leukemia patients with resistance or intolerance to BCR-ABL1 tyrosine kinase inhibitors

Radotinib (IY5511HCL), a novel and selective BCR-ABL1 tyrosine kinase inhibitor, has shown pre-clinical and phase I activity and safety in chronic myeloid leukemia. This phase II study investigated the efficacy and safety of radotinib in Philadelphia chromosome-positive chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors. Patients received radotinib 400 mg twice daily for 12 cycles based on results from the phase I trial. The primary end point was rate of major cytogenetic response by 12 months. A total of 77 patients were enrolled. Major cytogenetic response was achieved in 50 (65%; cumulative 75%) patients, including 36 (47%) patients with complete cytogenetic response by 12 months. Median time to major cytogenetic response and complete cytogenetic response were 85 days and 256 days, respectively. Major cytogenetic response and complete cytogenetic response rates were similar between imatinib-resistant and imatinib-intolerant patients, but were higher in patients without BCR-ABL1 mutations. Overall and progression-free survival rates at 12 months were 96.1% and 86.3%, respectively. All newly-occurring or worsening grade 3/4 hematologic abnormalities included thrombocytopenia (24.7%) and anemia (5.2%); grade 3/4 drug-related non-hematologic adverse events included fatigue (3.9%), asthenia (3.9%), and nausea (2.6%). The most common biochemistry abnormality was hyperbilirubinemia (grade 3/4 23.4%), and 12 of 18 cases were managed with dose modification. Study findings suggest radotinib is effective and well tolerated in chronic phase-chronic myeloid leukemia patients with resistance and/or intolerance to BCR-ABL1 tyrosine kinase inhibitors and may represent a promising alternative for these patients. (clinicaltrials.gov identifier: 01602952)

Clinical Features and Survival Outcomes in Patients with Multiple Myeloma: Analysis of Web-Based Data from the Korean Myeloma Registry

Aim: The Korean Multiple Myeloma Working Party performed a nationwide registration of multiple myeloma patients via a web-based data bank system. Methods: We retrospectively analyzed registered data from 3,209 patients since 1999. Results: The median overall survival (OS) was 50.13 months (95% confidence interval: 46.20–54.06 months). Patients ≤40 years demonstrated a longer OS than patients >65 years of age (median OS 71.13 vs. 36.73 months, p < 0.001). Patients who received novel agents at any time during their treatments showed a longer OS than patients who did not (median OS 42.23 vs. 55.50 months, p < 0.001). Response to treatment was associated with OS, with tandem autologous stem cell transplantation (SCT) producing longer OS than single autologous SCT. Conclusions: We demonstrated associations between survival outcomes and treatment modalities as well as baseline disease characteristics in a registry of multiple myeloma patients using a web-based data analysis.

Oral Fluoropyrimidines (Capecitabine or S-1) and Cisplatin as First Line Treatment in Elderly Patients with Advanced Gastric Cancer: A Retrospective Study

BACKGROUNDnThis study aimed to evaluate the safety and efficacy of oral fluoropyrimidines and cisplatin therapy in elderly patients with untreated advanced gastric cancer (AGC) retrospectively. In addition, we evaluated the relative activity and toxicity of these agents in this patient population.nnnMETHODSnClinical data from 72 patients with previously untreated AGC, who were treated with capecitabine/cisplatin and S-1/cisplatin, were reviewed. Oral fluoropyrimidines were administered orally twice a day on Days 1-14. The dose of capecitabine was 1250 mg/m(2) and that of S-1 was 50 mg [body surface area (BSA) < 1.5 m(3)] or 60 mg (BSA > 1.5 m(3)) twice a day. Cisplatin was administered intravenously on Day 1 (before the first dose of capecitabine or S-1) at a dose of 70 mg/m(2) over a 2 h period. The chemotherapy cycle was of 3 weeks (with oral capecitabine or S-1).nnnRESULTSnThirty-two and 40 patients received the S-1 and capecitabine regimens, respectively, and were included in the analysis. The S-1 protocol had a response rate of 40.6%, a median time-to-progression (TTP) of 5.4 months and a median survival of 9.6 months. The capecitabine had a response rate of 55%, a median TTP of 5.9 months and a median survival of 10.2 months. Each protocol had a similar incidence of Grade 3 or 4 adverse events. However, there was a higher rate of the hand-foot syndrome (6 versus 37%) and diarrhea (25 versus 32%) in the capecitabine group.nnnCONCLUSIONnOral fluoropyrimidines and cisplatin in elderly patients with untreated AGC showed encouraging results. The treatment was well tolerated with a manageable toxicity profile. The comparison of S-1 with capecitabine showed that capecitabine had a slightly higher response rate (statistically not significant) in addition to a higher rate of adverse events such as the hand-foot syndrome and diarrhea. These data should be warranted with further prospective studies.