Kim Sw

Efficacy of epidermal growth factor receptor tyrosine kinase inhibitors for brain metastasis in non-small cell lung cancer patients harboring either exon 19 or 21 mutation

Non-small cell lung cancer (NSCLC) harboring an activating epidermal growth factor receptor (EGFR) mutation shows good and rapid response to EGFR tyrosine kinase inhibitors (TKIs). We prospectively evaluated the efficacy of EGFR TKI for metastatic brain tumors in NSCLC patients harboring EGFR mutation. This was an open-label, single-institution, phase II study. Patients diagnosed with NSCLC harboring EGFR mutation and measurable metastatic brain tumors were eligible. They received either erlotinib or gefitinib once a day. Out of total 28 patients enrolled, 23 patients (83%) showed a partial response (PR) and 3 patients (11%) did stable disease (SD), giving a disease control rate of 93%. Median progression free survival (PFS) and overall survival (OS) were 6.6 months (95% CI, 3.8-9.3 months) and 15.9 months (95% CI, 7.2-24.6 months), respectively. There was no difference in PFS and OS according to EGFR TKIs used. After discontinuation of the treatment, 14 patients (50%) received local therapy for metastatic brain tumors during their disease course, either whole brain radiotherapy or radiosurgery, giving a local therapy-free interval of 12.6 months (95% CI, 7.6-17.6 months). EGFR TKI therapy might be the treatment of choice for metastatic brain tumors in NSCLC patients harboring an activating EGFR mutation.

Lymphocyte recovery as a positive predictor of prolonged survival after autologous peripheral blood stem cell transplantation in T-cell non-Hodgkin's lymphoma

Summary:We performed a retrospective study on recovery and survival of patients with T-cell NHL after autologous peripheral blood stem cell transplantation (APBSCT). Of a total of 39 patients with high-risk T-cell NHL, 33 were analyzed. Six patients who experienced early treatment mortality without full lymphocyte recovery were excluded. We chose absolute lymphocyte count (ALC) recovery as 1000 cells/μl as a cutoff value. ALC recovery day was defined as the first of 3 consecutive days with ALC above 1000 cells/μl. Univariate analysis revealed that age younger than 45 years, good international prognostic index, chemosensitive disease prior to APBSCT, and early ALC recovery (1000 cells/μl within 25 days of APBSCT) were predictors of prolonged survival. Multivariate analyses confirmed that chemosensitive disease prior to APBSCT and early ALC recovery were strongly associated with better overall survival (OS) (P=0.005 and 0.011, respectively) and progression-free survival (PFS) (P<0.001 and P=0.013, respectively). Our finding, that ALC recovery ⩾1000 cells/μl is an independent predictor of OS and PFS in T-cell NHL after APBSCT, suggests that earlier immune recovery may contribute to longer survival.

ESHAP plus G-CSF as an effective peripheral blood progenitor cell mobilization regimen in pretreated non-Hodgkin's lymphoma: comparison with high-dose cyclophosphamide plus G-CSF

Summary:The ESHAP (etoposide, methylprednisolone, high-dose cytarabine, and cisplatin) regimen has been shown to be effective as an active salvage therapy for lymphoma. Mobilizing stem cells following ESHAP should decrease time to transplantation by making separate mobilizing chemotherapy (MC) unnecessary, while controlling a patients lymphoma. We therefore assessed the mobilization potential of ESHAP plus G-CSF in 26 patients (ESHAP group) with non-Hodgkins lymphoma (NHL) and compared these results with those of 24 patients with NHL who received high-dose (4 g/m2l) cyclophosphamide (HDCY) as MC (HDCY group). The age, sex, and radiotherapy to the axial skeleton were well matched between groups, but the number of patients with poor mobilization predictors was higher in the ESHAP group. Significantly higher numbers of CD34+ cells (× 106/kg) (17.1±18.8 vs 5.8±5.0, P=0.03) and apheresis day 1 CD34+ cells (× 106/kg) (5.5±6.6 vs 1.7±2.0, P=0.014) were collected from the ESHAP group than from the HDCY group, and the number of patients who achieved an optimal CD34+ cell target of 5 × 106/kg was higher in the ESHAP group (81 vs 50%, P=0.022). Log-rank test revealed that time to target peripheral blood progenitor cell collection (⩾5 × 106/kg) was shorter in the ESHAP group (P=0.007). These results indicate that ESHAP plus G-CSF is an excellent mobilization regimen in patients with relapsed and poor-risk aggressive NHL.

Feasibility of BU, CY and etoposide (BUCYE), and auto-SCT in patients with newly diagnosed primary CNS lymphoma: a single-center experience

We investigated the feasibility of i.v. BU, CY and etoposide (BUCYE), followed by auto-SCT (ASCT) in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). The planned treatment consisted of induction chemotherapy with five cycles of high-dose MTX and two cycles of high-dose cytarabine followed by conditioning with BUCYE (BU 3.2 mg/m2, day −7 to day −5; CY 50 mg/kg, day −3 to day −2 and etoposide 200 mg/m2, twice a day, days −5 and −4) and then ASCT. Between May 2005 and November 2008, 11 consecutive PCNSL patients were treated. All patients completed the treatment as planned, with no cases of treatment-related death or veno-occlusive disease. After BUCYE and ASCT, 10 patients achieved complete response (CR) or unconfirmed CR (CRu). Two patients, one partial response and one CRu, received further whole-brain radiotherapy, with all achieving CR. At a median follow-up of 25.0 months (8.8–50.7 months), six patients had relapsed, with a median event-free interval of 15.0 months (95% confidence interval, 4.5–25.6 months). Median survival time was not reached yet with a 2-year survival rate of 88.9%. The current treatment was feasible with a favorable tolerance profile. However, further regimen optimization is necessary because of high relapse rate.

The role of prophylactic antimicrobials during autologous stem cell transplantation: a single-center experience

The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p<0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p<0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p=0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p=0.056 and p=0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.The aim of this study was to investigate the efficacy of antibiotic prophylaxis in patients undergoing autologous stem cell transplantation (ASCT) for multiple myeloma and non-Hodgkin lymphoma. Among 232 ASCT cases performed at the Asan Medical Center, 114 cases underwent treatment with ciprofloxacin, fluconazole, and acyclovir (between January 2001 and August 2005), while 118 cases were performed without antimicrobial prophylaxis (between February 2004 and June 2008). The two-rate χ2 test was applied to accommodate the differences in neutropenia duration. The incidence of febrile episodes was 9.8 cases per 100 person-days in the prophylactic group, while it was 16.2 cases in the no-prophylactic group (p < 0.001). The rate of unexplained fever was 8.0 cases per 100 person-days in the prophylactic group, while it was 13.8 cases in the no-prophylactic group (p < 0.001). The rate of clinically and microbiologically documented infection was 1.7 cases per 100 person-days in the prophylactic group, while it was 2.3 cases in the no-prophylactic group (p = 0.404). There were fewer cases of methicillin-susceptible Staphylococcus aureus infection and a greater number of quinolone-resistant Escherichia coli in the prophylactic group compared with the no-prophylactic group (p = 0.056 and p = 0.040, respectively). The prophylactic antimicrobials reduced the incidence rate of febrile episodes, especially unexplained fever, despite there being no difference in the incidence of documented infection. Resistant microbe infection occurred more frequently in the prophylactic group.

Optimal timing of G-CSF administration for effective autologous stem cell collection

The best time of G-CSF administration for PBPC collection remains to be defined. We aimed to identify optimal G-CSF administration timing for efficient autologous stem cell collection. A total of 262 lymphoma or multiple myeloma patients, who underwent PBPC collection from January 2000 to March 2008, were included. PBPCs were mobilized with chemotherapy followed by lenograstim at 10 μg/kg/day. Patients received lenograstim at 2000 hours, about half a day before leukapheresis (PM group) before November 2004, and at 0600 hours, 3 h before apheresis (AM group) subsequently. In the AM group, the median number of total collected CD34+ cells/kg was greater over a shorter duration of apheresis, and the median number of collected CD34+ cells/kg at first leukapheresis was larger. Stem cell collection efficacy (ratio of total collected CD34+ cells/kg per number of leukapheresis procedures) was higher, and proportion of patients who yielded an optimum harvest was larger. The statistically significant between-group difference was observed only in patients with high-dose CY chemotherapy for stem cell mobilization in subgroup analysis. The present study showed that G-CSF injection 3 h before apheresis improved the efficacy of autologous stem cell collection.

Idiopathic Thrombocytopenic Purpura: Better Therapeutic Responses of Patients with B- or T-Cell Clonality than Patients without Clonality

Results of recent studies of the pathogenesis of idiopathic thrombocytopenic purpura (ITP) have suggested activated helper T-cells drive B-lymphocytes to produce antibodies. Twenty-eight children and 85 adults with ITP entered this study. We performed polymerase chain reaction (PCR) using framework III variable region (VH FRIII)- and joining region (JH)-specific primers to analyze immunoglobulin heavy-chain gene rearrangement (IgH GR) for B-cell clonality. We used multiplex PCR to analyze T-cell receptor (TCR) γ-chain gene rearrangement (TCRγ GR) for T-cell clonality. We diagnosed 10 cases as acute ITP and 97 cases as chronic ITP. The IgH GR result was positive in 77.8% of the acute-form cases and in 58.8% of the chronic-form cases. The TCRγ GR result was positive in 11.1% of the acute cases and in 10.6% of the chronic cases. There was no dif-ference in frequency of clonality between the acute and chronic forms. After treatment the platelet count normalized in 81.8% (36/44) of the chronic ITP cases with B-cell clonality and in 88.9% (8/9) of the chronic ITP cases with T-cell clonality, compared with a normalized platelet count in 46.2% (12/26) of the chronic ITP cases without clonality. The patients with T- or B-cell clonality appeared to have better therapeutic responses than patients without clonality. In conclusion,T- and B-cell clonality may play a positive role in determining therapeutic response.