Geundoo Jang

Higher infused CD34+ hematopoietic stem cell dose correlates with earlier lymphocyte recovery and better clinical outcome after autologous stem cell transplantation in non-Hodgkin's lymphoma

BACKGROUND: Lymphocyte recovery after autologous stem cell transplantation (ASCT) has been shown to be associated with positive clinical outcome in non‐Hodgkins lymphoma (NHL). This study sought to identify variables that affect lymphocyte recovery and survival after ASCT.

Dose Escalation of Imatinib After Failure of Standard Dose in Korean Patients with Metastatic or Unresectable Gastrointestinal Stromal Tumor

OBJECTIVE We evaluated the results of imatinib dose escalation in patients with advanced gastrointestinal stromal tumors (GISTs) after disease progression on standard-dose imatinib. METHODS Clinical data from patients with metastatic or unresectable GISTs whose dose of imatinib was increased after disease progression on imatinib 400 mg/day were retrospectively reviewed. RESULTS The 24 patients studied had a median age of 52 years. Imatinib dosing was escalated to 600 mg/day in 12 patients, then to 800 mg/day in four patients. The other 12 patients had dose escalation directly to 800 mg/day. Two patients (8.3%) achieved a partial response, and seven (29.2%) had stable disease. Six-month progression-free and overall survival rates were 33.3 and 70.7%, respectively. Dose escalation to 600 or 800 mg/day was generally well tolerated. CONCLUSION Imatinib dose escalation is feasible and well tolerated in patients with advanced GIST who progress on standard-dose therapy, producing clinical benefit in approximately 37% of patients.

Randomized Phase 2 Trial of S1 and Oxaliplatin-Based Chemoradiotherapy With or Without Induction Chemotherapy for Esophageal Cancer

PURPOSE To assess, in a randomized, phase 2 trial, the efficacy and safety of chemoradiotherapy with or without induction chemotherapy (ICT) of S1 and oxaliplatin for esophageal cancer. PATIENTS AND METHODS Patients with stage II, III, or IVA esophageal cancer were randomly allocated to either 2 cycles of ICT (oxaliplatin 130 mg/m(2) on day 1 and S1 at 40 mg/m(2) twice daily on days 1-14, every 3 weeks) followed by concurrent chemoradiotherapy (CCRT) (46 Gy, 2 Gy/d with oxaliplatin 130 mg/m(2) on days 1 and 21 and S1 30 mg/m(2) twice daily, 5 days per week during radiation therapy) and esophagectomy (arm A), or the same CCRT followed by esophagectomy without ICT (arm B). The primary endpoint was the pathologic complete response (pCR) rate. RESULTS A total of 97 patients were randomized (arm A/B, 47/50), 70 of whom underwent esophagectomy (arm A/B, 34/36). The intention-to-treat pCR rate was 23.4% (95% confidence interval [CI] 11.2-35.6%) in arm A and 38% (95% CI 24.5% to 51.5%) in arm B. With a median follow-up duration of 30.3 months, the 2-year progression-free survival rate was 58.4% in arm A and 58.6% in arm B, whereas the 2-year overall survival rate was 60.7% and 63.7%, respectively. Grade 3 or 4 thrombocytopenia during CCRT was more common in arm A than in arm B (35.4% vs 4.1%). The relative dose intensity of S1 (89.5% ± 20.6% vs 98.3% ± 5.2%, P=.005) and oxaliplatin (91.4% ± 16.8% vs 99.0% ± 4.2%, P=.007) during CCRT was lower in arm A compared with arm B. Three patients in arm A, compared with none in arm B, died within 90 days after surgery. CONCLUSIONS Combination chemotherapy of S1 and oxaliplatin is an effective chemoradiotherapy regimen to treat esophageal cancer. However, we failed to show that the addition of ICT to the regimen can improve the pCR rate.

Addition of rituximab to the CHOP regimen has no benefit in patients with primary extranodal diffuse large B-cell lymphoma

Background The addition of rituximab to cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy (R-CHOP) has significantly improved clinical outcomes for patients with diffuse large B-cell lymphoma (DLBCL). However, new predictors of patient response to R-CHOP have not been established. We aimed to evaluate the impact of R-CHOP compared with CHOP in patients with DLBCL and to establish clinical predictors of better outcomes in these patients. Methods We retrospectively identified 177 patients diagnosed with CD20-positive DLBCL and treated with CHOP (N=82) or R-CHOP (N=95). The response rate, event-free survival (EFS), and overall survival (OS) rates were compared between the 2 treatment groups. All patients were classified into primary extranodal lymphoma (PENL) or nodal lymphoma (NL) subgroups, and the clinical parameters of each subgroup were analyzed. Results The overall response rate was higher in R-CHOP group (95% vs. 84%, P=0.07). The 3-year EFS rate was significantly higher in R-CHOP group (71% vs. 52%, P=0.013), but the OS rate was comparable between the 2 groups (79% vs. 69%, P=0.23). A significant survival benefit was seen with R-CHOP compared to CHOP therapy in NL patients (P=0.002 for EFS and 0.04 for OS). Multivariate analyses confirmed that R-CHOP therapy is an independent prognostic factor for EFS (hazard ratio of 0.32 [0.17-0.62], P=0.001) and OS (hazard ratio of 0.4 [0.18-0.87], P=0.02) in NL patients. Conclusion Patients in the PENL group did not benefit from R-CHOP chemotherapy.

A phase I/II study of bortezomib plus CHOP every 2 weeks (CHOP-14) in patients with advanced-stage diffuse large B-cell lymphomas

Background Bortezomib targets molecular dysregulation of nuclear factor-κB activation and cell cycle control, which are characteristic features of diffuse large B-cell lymphoma (DLBCL). We evaluated the safety and efficacy of bortezomib treatment with dose-dense cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) every 2 weeks (CHOP-14). Methods Untreated DLBCL patients were enrolled. A phase I dose-escalation study with 1.0, 1.3, and 1.6 mg/m2 bortezomib administration on day 1 and 4 in addition to the CHOP-14 regimen was performed to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT). Lenograstim 5 µg/kg/d was administered on day 4-13. The bortezomib dose from the phase I study was used in the phase II study. Results Nine and 37 patients were enrolled in the phase I and phase II studies, respectively. The analysis of the phase II results (40 patients) included data of the 3 patients in the last MTD dose cohort of the phase I trial. During the phase I trial, no DLT was observed at any bortezomib dose; therefore, the recommended dose was 1.6 mg/m2. In phase II, the overall response rate was 95% (complete response: 80%; partial response: 15%). Nine out of the 40 patients showed grade 3 sensory neuropathy, and 22 required at least 1 dose reduction. Three patients could not complete the intended 6 cycles of treatment because of severe neuropathy. Conclusion Bortezomib plus CHOP-14 was highly effective for the treatment of untreated DLBCL patients, but in many cases, dose or schedule modification was required to reduce neurotoxicity.

Prospective randomized comparative observation of single-versus split-dose lenograstim to enhance engraftment after autologous stem cell transplantation in patients with multiple myeloma or non-Hodgkin's lymphoma

BACKGROUND: Granulocyte–colony‐stimulating factor (G‐CSF) is used to enhance hematopoietic recovery after autologous stem cell transplantation (ASCT). Recommendations for administration of G‐CSF during the engraftment phase of ASCT have recently changed. This study sought to compare the early engraftment profile between groups receiving single‐dose versus split‐dose lenograstim to enhance engraftment after ASCT.