Shih-Feng Cho

SUV on dual-phase FDG PET/CT correlates with the Ki-67 proliferation index in patients with newly diagnosed non-Hodgkin lymphoma.

Purpose PET using 18F-FDG integrated with CT is beneficial for staging patients with non-Hodgkin lymphoma (NHL). The Ki-67 index is used to assess the proliferation potential of tumor cells. The aim of this study was to evaluate the correlation of the Ki-67 index in tissue samples with the SUV at different sites on dual-phase FDG PET/CT of patients with newly diagnosed NHL. Materials and Methods From September 2009 to March 2011, patients with newly diagnosed NHL who had received dual-phase FDG PET/CT for staging and biopsy samples that were evaluated for the Ki-67 expression were enrolled. The SUVmax of the biopsy site, the tumorous lesion sites, and 3 different bone marrow sites (right iliac crest, sternum, and L1) were measured. The SUVmean of the liver and spleen were also measured. Results There were a total of 27 patients in this study. Significant correlations were observed between the Ki-67 index and the SUVmax of the right iliac crest in patients with early-stage disease (stage I and II) patients, the SUVmax of the biopsy and whole-body lesion sites in patients with late-stage disease (stage III and IV), and the retention index of SUVmax of the right iliac crest in patients whose bone marrow were involved by lymphoma cells. Conclusions For patients with newly diagnosed NHL, the significant correlation between the Ki-67 index and the SUV in this study suggests that dual-phase FDG PET/CT may be used as a noninvasive measurement of tumor proliferation.

Higher lipocalin 2 expression may represent an independent favorable prognostic factor in cytogenetically normal acute myeloid leukemia

Abstract Several molecular markers, such as NPM1, FLT3 and CEBPA, have been incorporated into both the World Health Organization and European LeukemiaNet classifications as routine assessments for the diagnosis and evaluation of prognostic significance in acute myeloid leukemia (AML). Lipocalin 2 (LCN2) is related to cancer development and is believed to be associated with the outcome of cytogenetically normal (CN)-AML. In the present study, we analyzed the prognostic effects and interactions of LCN2 expression (by molecular analysis, quantitative real-time polymerase chain reaction [qRT-PCR]) with neucleophosmin 1, fms-related tyrosine kinase 3 (FLT3) and CCAAT/enhancer-binding protein alpha mutations in 85 patients with CN-AML receiving intensive induction chemotherapy. Our results indicate that patients with higher LCN2 mRNA expression in the bone marrow (LCN2high), especially in combination with wild type FLT3-ITD, had better prognoses. FLT3-ITD compensated LCN2-overexpression-enhanced oxidative stress-induced apoptosis in cell line studies. In conclusion, LCN2high was associated with better prognosis, and FLT3 status had an adjuvant effect on overall survival.

Utilization of 18F-FDG PET/CT as a staging tool in patients with newly diagnosed lymphoma

The aim of this study was to investigate the role of 2‐fluorine‐18‐fluoro‐2‐deoxy‐D‐glucose (18F‐FDG) positron emission tomography/computed tomography (PET/CT) in the initial staging and prediction of bone marrow involvement in patients with newly diagnosed lymphoma. A total of 185 patients with newly diagnosed lymphoma were enrolled. All patients received PET/CT and bone marrow biopsy as part of a staging work‐up. At the initial staging, 17 patients (9.2%) with occult nodal or extranodal lesions were upstaged after a review of the PET/CT studies. PET/CT was found to be useful in the differentiation of aggressive lymphoma subtypes from the indolent subtype based on higher standardized uptake value (SUV) (16.67 vs. 7.98, p < 0.001). The results of bone marrow biopsy and PET/CT in the detection of bone marrow involvement were concordant in 152 patients (82.1%); positive concordance was observed in 21 patients, and negative concordance was observed in 131 patients. A high concordance rate was found between aggressive B cell lymphoma and Hodgkins lymphoma (88.1% and 93.8%, respectively). High negative predictive values (NPVs) for excluding bone marrow involvement were observed in aggressive B‐cell lymphoma (93.2%) and Hodgkins lymphoma (100%). Diffuse bone marrow FDG uptake accurately predicted bone marrow in aggressive B‐cell lymphoma with a positive predictive value (PPV) of 100%. The concordance rate was lower in indolent B‐cell lymphoma (66.0%). In conclusion, PET/CT resulted in the upstaging of patients with occult extranodal or nodal lesions. A high SUV level can predict aggressive subtype of lymphoma and detect aggressive components in indolent lymphoma. PET/CT had a high PPV for aggressive B‐cell lymphoma with diffuse bone marrow FDG uptake and high NPVs for excluding bone marrow involvement in aggressive B‐cell lymphoma and Hodgkins lymphoma. Bone marrow biopsy may be omitted for the above subgroups of patients with medical conditions not suitable for this procedure. For patients with indolent B‐cell lymphoma, bone marrow biopsy is still an indispensable procedure for staging.

Longitudinal risk of herpes zoster in patients with non-Hodgkin lymphoma receiving chemotherapy: A nationwide population-based study.

This study investigated the incidence of and risk factors for herpes zoster in patients with non-Hodgkin lymphoma (NHL) who were receiving anti-lymphoma treatment. The overall incidence density of herpes zoster was 12.21% (472/3865); 11.79% (258/2188) of the patients received conventional chemotherapy and 12.76% (214/1677) of the patients received rituximab-containing chemotherapy. For the patients who received conventional chemotherapy, the risk factors included female gender, multiple courses of chemotherapy and autologous hematopoietic stem cell transplantation. For the patients who received rituximab-containing chemotherapy, the risk factors included female gender, diabetes mellitus, multiple courses of chemotherapy, autologous hematopoietic stem cell transplantation and higher accumulated rituximab dose. The majority of the herpes zoster episodes occurred within the first two years after the diagnosis of NHL. After adjusting for the propensity score matching, rituximab-containing chemotherapy was not associated with a higher overall incidence density of herpes zoster (P = 0.155). However, the addition of rituximab to conventional chemotherapy increased the short-term risk of herpes zoster with adjusted odd ratios of 1.38 (95% confidence intervals (CI) = 1.05–1.81, P = 0.021) and 1.37 (95% CI = 1.08–1.73, P = 0.010) during the 1-year and 2-year follow-up periods, respectively.

Hepatitis C transmission from viremic donors in hematopoietic stem cell transplant.

Transmission of hepatitis C virus (HCV) to recipients of hematopoietic stem cell transplant (HSCT) occurs frequently from HCV viremic donors and causes complications. Here, we report the outcomes of 3 cases from our 265 allogeneic HSCTs, whose donors had HCV infections. Successful prevention of HCV transmission was noted in 1 recipient by pretreatment of the donor with peginterferon/ribavirin to undetectable levels of HCV viremia before stem cell harvest. This case stressed the important role of effective antiviral therapy and HCV RNA seronegativity before cell harvest for prevention of HCV transmission in HSCT.

Donor cell-derived acute promyelocytic leukemia after allogeneic hematopoietic stem cell transplant

Dear Editor, Donor cell leukemia (DCL), a relapse of leukemia derived from donor origin, is a rare complication of hematopoietic stem cell transplant (HSCT), and the etiology is still equivocal. Herein, we reported a rare case of donor cell-derived acute promyelocytic leukemia (APML) 3 years after HLA-identical allogeneic HSCT from his sister with literature review. A 52-year-old male was diagnosed of myelodysplastic syndrome, refractory anemia with excess blasts-1 in April 2010. Bone marrow aspiration revealed dysgranulopoietic change and dyserythropoiesis with increased blast cell up to 7.6 % with normal karyotype. He had supportive care and received allogeneic peripheral blood HSCT in December 2010, from his sex-mismatched HLA-identical sister. The donor was healthy without any underlying disorder in pretransplant survey. Total body irradiation (2Gy bid for 3 days) and cyclophosphamide (60 mg/kg for 2 days) were used as conditioning regimen with cyclosporine and methotrexate (on day 1, 3, 6, and 11) for GVHD prophylaxis. A total of 10.06× 10 CD34+cells/kg was infused. He suffered from acute GVHD (grade 2) at day +28 and cytomegalovirus (CMV) infection at day +42 after HSCT. CMV was controlled by gancyclovir 400 mg for 14 days, and the acute GVHD subsided after cyclosporine therapy. Cytogenetic and chimerism studies by PCR amplification of short tandem repeats (STR) revealed full donor chimerism 1month after the transplant and at the follow-up 1 year later. The patient got stable condition for 3 years with limited chronic GVHD over oral cavity, skin, and liver with cyclosporine therapy. Unfortunately, progressive thrombocytopenia was noted in January 2014. Bonemarrow examination showedAPMLwith marked infiltration with heavily granulated promyelocytes containing Auer roods. Molecular study by RT-PCR was positive for PML/RARA transcript, whichwas not found from donor sample and patient’s samples before and after HSCT (Fig. 1) [1]. Chromosome study showed t(15,17)(q22:q21) translocation in all donor cells (46,XX), and chimerism study was still in full donor chimerism. Donor cell-derived APML was diagnosed, and the patient received induction therapy with all-trans-retinoic-acid and idarubicin. Unfortunately, patient suffered from febrile neutropenia and died of septic shock 10 days after induction. The development of true DCL after allogeneic HSCT is rare with the first case reported in 1971 [2]. Since then, several cases had been reported, but the true incidence is difficult to assess [3–5]. A large survey from the European Group for Blood andMarrowTransplantation (EBMT) reported 14 cases from 10,489 transplantations performed during a 21-year period [6]. Our case with cytogenetic and chimerism studies H.

Isolated central nervous system relapse presenting as myeloid sarcoma of acute myeloid leukemia after allogeneic peripheral blood stem cell transplantation

Dear Editor, A 27-year-old female had acute myeloid leukemia (AML), M4 of French–American–British (FAB) classification with cytogenetic abnormalities of inversion (16) and trisomy 8. Immunophenotyping was positive for CD33, CD13, CD15, CD11b, CD34, and HLA-DR. She achieved complete remission after induction chemotherapy (idarubicin 12 mg/m/day for 3 days and cytarabine 200 mg/m/day for 7 days) and four courses of consolidation therapy (cytarabine 3 g/day over 5 days). After 4 months, she had a relapse, with 60 % blast cells in the bone marrow, and received salvage chemotherapy (mitoxantron 12 mg/m/day for 3 days and etoposide 100 mg/m/day for 3 days) and again achieved complete remission. She underwent allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLAmatched, related female donor with a conditioning regimen of cyclophosphamide (60 mg/kg/day for 2 days), etoposide (60 mg/kg for 1 day), and 12 Gy total body irradiation. Prophylaxis for graft-versus-host disease (GvHD) included intravenous methotrexate (15 mg/m) and cyclosporine (1.5 mg/kg, twice daily). Bone marrow examination on the 14th day posttransplantation showed complete remission and successful engraftment. She had normal 46XX karyotype by standard Giemsa staining. Another bone marrow examination on the 120th day also showed complete remission. Chimeric study by polymerase chain reaction (PCR) to amplify short tandem repeat (STR) revealed full donor chimerism. She had stages 1–2 acute GVHD involving the hepatobiliary system that was successfully treated with cyclosporine and corticosteroids. Ten months after transplantation, she gradually developed right-sided weakness and slurred speech. Brain magnetic resonance imaging (Fig. 1a) showed a mass lesion at the right cerebellopontine angle with mild focal edema. There were no other leukemic infiltrations by physical examination, chest Xray, and abdominal sonography. The patient later underwent complete tumor excision with clear margin microscopically. Microscopically, hematoxylin and eosin staining (Fig. 1b) of the specimen demonstrated diffuse infiltration of mediumto-large cells with high nucleocytoplasmic ratio. Immunohistochemistry was positive for myeloperoxidase and CD34 (Fig. 1c, d) but negative for CD3 and CD79a. There were no leukemic cells in the cerebrospinal fluid (CSF), while bone marrow examination showed no leukemic involvement. Chimeric analysis of the tumor revealed mainly recipient component, but this was not done on the CSF. Chimeric study of peripheral blood and bone marrow showed full donor chimerism (Table 1). Isolated CNS relapse of acute myeloid leukemia was diagnosed. After post-operation radiotherapy and regular follow-up for 18 months, the patient had nearly normal daily activity with mild neurologic sequelae. Myeloid sarcoma is an unusual hematologic neoplasmwith myeloblasts as its major component [1]. It can develop as the S.-F. Cho : T.-C. Liu :C.-S. Chang (*) Division of Hematology and Oncology, Department of Internal Medicine, Kaohsiung Medical University Hospital, 100, Tzyou 1st Road, Kaohsiung 807, Taiwan e-mail: albert@kmu.edu.tw

HIV-negative disseminated Kaposi's sarcoma in a Taiwanese patient.

Kaposis sarcoma is a common malignancy associated with HIV/AIDS. Herein, we describe the case of a 26‐year‐old man who presented with bilateral neck and inguinal lymphadenopathy, a massive tumor on the gum, and a nodule over the left eye. A series of tests, including tumor biopsies, were performed, and disseminated Kaposis sarcoma with human herpesvirus 8 infection was diagnosed. To test for HIV, we used enzyme‐linked immunosorbent assay and real‐time polymerase chain reaction, but the results were negative. The patient was treated by biweekly intravenous infusion of pegylated liposomal doxorubicin (25 mg/m2), and this treatment resulted in a partial response.

Previous Exposure to Statin May Reduce the Risk of Subsequent Non-Hodgkin Lymphoma: A Nationwide Population-Based Case-Control Study

Background The purpose of this study was to investigate the association between previous exposure to statins and the risk of non-Hodgkin lymphoma (NHL). Methods This nationwide population-based case–control study was conducted using the National Health Insurance Research Database of Taiwan. The NHL group consisted of the patients with a first-time diagnosis of NHL between 2005 and 2008. The cases of the control group were pair-matched to the NHL group according to sex, year of birth and date of NHL diagnosis (index date). The statin administration data from both groups were retrospectively collected from the index date to January 1, 1996. The cumulative defined daily dose (cDDD) was estimated to evaluate the statin exposure. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariate logistic regression. Results The study population was composed of 1715 NHL patients and 16942 control subjects. The analysis revealed that previous statin administration was associated with a reduced risk of subsequent NHL with an adjusted OR of 0.52 (95% CI, 0.43–0.62). Additionally, there was a dose-response relationship between statin administration and the risk of NHL. The adjusted ORs were 0.63 (95% CI, 0.46–0.86), 0.58 (95% CI, 0.42–0.79), 0.51 (95% CI, 0.38–0.67), and 0.36 (95% CI, 0.24–0.53) for the subjects with statin administrations of fewer than 28, 28 to 90, 91 to 365, and more than 365 cDDDs, respectively, relative to the subjects without any statin administration. Conclusions The results of this study suggest that previous statin administration is associated with a lower risk of subsequent NHL. As statins are widely used medications, the magnitude of the risk reduction may have a substantial influence on public health. Further studies to confirm our findings are warranted.

Investigation on treatment strategy, prognostic factors, and risk factors for early death in elderly Taiwanese patients with diffuse large B-cell lymphoma

This study aimed to investigate the treatment strategy, prognostic factors, and risk factors of early death in elderly patients (age ≥ 65 years) with diffuse large B-cell lymphoma (DLBCL) in the rituximab era. Data from elderly patients diagnosed with DLBCL between 2008 and 2014 were collected for analysis. Patients who were younger and had a better performance status were more likely to receive intensive frontline treatment. The median progression-free survival (PFS) and overall survival were 15 and 21 months, respectively. Anthracycline-containing chemotherapy achieved a higher remission rate and showed a trend towards better overall survival but a higher risk of severe neutropenia. Multivariate analysis revealed that very old age (≥81 years), a high-risk age-adjusted international prognostic index (aaIPI) score, and bone marrow involvement were associated with poorer PFS and overall survival. Progression of lymphoma was the major cause of death in the study population. In addition, approximately 25% of patients died within 120 days of being diagnosed. The risk factors for early mortality included very old age, a high-risk aaIPI score, and bone marrow involvement. The appearance of symptoms or signs of tumour lysis syndrome at diagnosis was associated with a trend towards early death.