Myung Hee Chang

Whole blood Epstein-Barr virus DNA load as a diagnostic and prognostic surrogate: extranodal natural killer/T-cell lymphoma.

We investigated the value of Epstein-Barr virus (EBV) DNA load in unfractionated whole blood for the diagnosis and prognosis of EBV-associated lymphoma. From July 2004 to July 2007, we compared EBV DNA loads in 101 patients with lymphoma and 105 control individuals. The median copy number of EBV was higher in patients with EBV-positive lymphoma (p<0.001). In patients with natural killer (NK)/T-cell lymphomas, the median EBV DNA load at presentation was significantly related to the stage (p = 0.011) and response (p = 0.026). The newly proposed classification model for NK/T cell lymphoma showed EBV DNA load differed significantly between patients with upper and extra-upper aerodigestive tracts (p = 0.017). In 16 patients with NK/T-cell lymphoma monitored serially, EBV DNA load correlated well with the treatment response and clinical course. Further prospective studies are required to evaluate the diagnosing and monitoring role of whole blood EBV DNA for uniformly treated patients.

Imatinib withdrawal syndrome and longer duration of imatinib have a close association with a lower molecular relapse after treatment discontinuation: the KID study.

The aim of the Korean Imatinib Discontinuation Study was to identify predictors for safe and successful imatinib discontinuation. A total of 90 patients with a follow-up of ≥12 months were analyzed. After a median follow-up of 26.6 months after imatinib discontinuation, 37 patients lost the major molecular response. The probability of sustained major molecular response at 12 months and 24 months was 62.2% and 58.5%, respectively. All 37 patients who lost major molecular response were retreated with imatinib therapy for a median of 16.9 months, and all achieved major molecular response again at a median of 3.9 months after resuming imatinib therapy. We observed newly developed or worsened musculoskeletal pain and pruritus in 27 (30%) patients after imatinib discontinuation. Imatinib withdrawal syndrome was associated with a higher probability of sustained major molecular response (P=0.003) and showed a trend for a longer time to major molecular response loss (P=0.098). Positivity (defined as ≥ 17 positive chambers) of digital polymerase chain reaction at screening and longer imatinib duration before imatinib discontinuation were associated with a higher probability of sustained major molecular response. Our data demonstrated that the occurrence of imatinib withdrawal syndrome after imatinib discontinuation and longer duration of imatinib were associated with a lower rate of molecular relapse. In addition, minimal residual leukemia measured by digital polymerase chain reaction had a trend for a higher molecular relapse. (Trial registered at ClinicalTrials.gov: NCT01564836).

Predictors of response to immunosuppressive therapy with antithymocyte globulin and cyclosporine and prognostic factors for survival in patients with severe aplastic anemia

Background:  Immunosuppressive therapy (IST) with antithymocyte globulin (ATG) plus cyclosporine (CSA) is standard therapy in patients with severe aplastic anemia (SAA) who do not have an available HLA‐matched sibling donor.

Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy

Kim KH, Do I‐G, Kim HS, Chang MH, Kim HS, Jun HJ, Uhm J, Yi SY, Lim DH, Ji SH, Park MJ, Lee J, Park SH, Kwon GY, Lim HY. Excision repair cross‐complementation group 1 (ERCC1) expression in advanced urothelial carcinoma patients receiving cisplatin‐based chemotherapy. APMIS 2010; 118: 941–8.

Rituximab-induced acute thrombocytopenia: a case report and review of the literature

Rituximab is a chimeric monoclonal antibody directed against the phosphoprotein CD20. Because of its efficacy and acceptable toxicity profile, rituximab is now commonly used for the treatment of CD20-positive B-cell malignancies, including B-cell non-Hodgkin’s lymphoma. However, rituximab-induced acute thrombocytopenia is an extremely rare side effect. We report a case of acute thrombocytopenia occurring immediately after rituximab infusion in a mantle cell lymphoma patient with bone marrow involvement and massive splenomegaly. Although the mechanism of thrombocytopenia is still unclear, it is possible that tumor burden, bone marrow involvement, the presence of infusion-related symptoms, and mantle cell histology are related to this rare complication of rituximab therapy. Hence, rituximab should be used with caution in patients who have these factors, and clinicians must be aware of this rare, but serious, side effect.

Change of health-related profiles after Imatinib cessation in chronic phase chronic myeloid leukemia patients.

The aim of this study was to investigate the changes in health-related profiles including quality-of-life (HRQoL) in the chronic myeloid leukemia (CML) patients who discontinued imatinib (IM). An HRQoL survey composed of 43 parameters about IM-related adverse events (AEs), physical health-related and mental health-related was provided at baseline and 6 months post-discontinuation. A total of 55 patients with a sustained UMRD over 6 months were analyzed. Although the majority of IM-related AEs were significantly improved, unexpectedly pruritus and musculoskeletal pain worsen or newly develop in 29.1% and 21.8% of patients, respectively. The improvements in physical and mental health condition were variable in individual patients. In addition, rapid restorations of the hematological and biochemical parameters were observed. The results showed the changes of HRQoL and laboratory tests in treatment-off patients and the necessity of continuing physical and mental support for some patients in tyrosine kinase inhibitor (TKI)-off studies.

High-Dose Ifosfamide as Second- or Third-Line Chemotherapy in Refractory Bone and Soft Tissue Sarcoma Patients

Introduction: For patients with refractory bone and soft tissue sarcoma (STS), treatment options have been limited. Ifosfamide is an alkylating agent with well-demonstrated efficacy against STS, and dose-dependent activity. The aim of this retrospective study was to evaluate the response rate, progression-free survival (PFS), progression-free rate (PFR), and median duration of response to high-dose ifosfamide (HDI) as at least second-line chemotherapy for patients with advanced bone sarcoma and STS. Patients and Methods: Thirty metastatic, unresectable sarcoma patients who were treated with HDI chemotherapy between May 1999 and November 2007 were included in the analysis. In total, 106 cycles (median 3 cycles; range 1–8 cycles) were administered. Twenty-one patients received treatment as second-line chemotherapy, and 9 patients as third-line treatment. HDI was given at a dose of 2 g/m2 over 3 h, and at a dose of 2 g/m2 per day; continuous infusion was administered on 6 consecutive days (2 g/m2/6 days) every 3 weeks. Results: After a median follow-up of 49 months (range 10–114), median PFS was 2.9 months (range 0.4–9.3) and median overall survival 8.7 months (range 0.4–57.8). The 3- and 6-month PFR were 47% (SE 9.1%) and 20% (SE 7.3%), respectively. Median response duration of HDI was 2.9 months (range 0.7–7.6). Of the 28 evaluable patients, 2 (7%) achieved complete response, 5 (18%) partial response, and 4 (14%) stable disease, and overall disease control was 39%. Two responders out of 7 (28.5%) and 4 patients out of 11 (36%) with controlled disease by HDI had a synovial sarcoma. Two patients were not evaluable because they were switched to another treatment due to ifosfamide-induced encephalopathy. Grade 3–4 neutropenia was seen in 13 (43%) patients, and treatment-related death was observed in one patient. Conclusion: HDI at a total dose of 14 g/m2 with mesna is still an active salvage regimen, particularly in patients with synovial sarcomas.

Prognostic role of insulin-like growth factor receptor-1 expression in small cell lung cancer.

Chang MH, Lee J, Han J, Park YH, Ahn JS, Park K, Ahn M‐J. Prognostic role of insulin‐like growth factor receptor‐1 expression in small cell lung cancer. APMIS 2009; 117: 861–9.

Prognostic role of integrin β1, E‐cadherin, and rac1 expression in small cell lung cancer

Chang MH, Lee K, Lee K‐Y, Kim YS, Kim YK, Kang J‐H. Prognostic role of integrin β1, E‐cadherin, and rac1 expression in small cell lung cancer. APMIS 2012; 120: 28–38.

Comparison of therapeutic outcomes between surgical resection followed by R-CHOP and R-CHOP alone for localized primary intestinal diffuse large B-cell lymphoma.

Objectives:There is no confirmed treatment strategy for primary intestinal diffuse large B-cell lymphoma (DLBL). In this retrospective study, the purpose is to find an appropriate treatment strategy in patients with primary intestinal DLBL undergoing surgery followed by chemotherapy or chemotherapy alone. Methods:Seventy-six patients were newly diagnosed with DLBL and received treatment between March 2004 and June 2011. Forty-seven patients were treated with surgical resection followed by rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisolone (R-CHOP), and 29 patients were treated with R-CHOP chemotherapy alone. Results:The characteristics of the patients were as follows: the median age was 56.5 years (range, 15 to 85 y) with a female to male ratio of 1.00:1.45. There was no significant difference in patient characteristics between the 2 groups. The estimated 3-year progression-free survival rates (PFS) and overall survival rates (OS) of surgery followed by R-CHOP (surgery/R-CHOP) and R-CHOP alone (R-CHOP) groups were 92.2% and 74.8% (P=0.009) and 94.2% and 80.7% (P=0.049), respectively. In univariate analysis, significant differences were seen in estimated PFS and OS rates when comparing Lugano stages I and II1 with II2 and IIE (P=0.006 and 0.036), low and low-intermediate risk with high-intermediate risk (P=0.004 and 0.000), and surgery/R-CHOP group with R-CHOP group (P=0.009 and 0.049), respectively. In multivariate analysis, there were no independent predictive factors for survival. Conclusions:Patients treated with surgery followed by R-CHOP seemed to have a higher survival rate than those treated with R-CHOP alone. There were no significant prognostic factors for survival, but there were possible prognostic factors such as Lugano stage, International Prognostic Index risk, and treatment modality for PFS and OS.