Clinical features and treatment outcomes of limited-stage mantle cell lymphoma: Consortium for Improving Survival of Lymphoma report

Annals of Hematology - Limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL) is an extremely rare disease. Thus, there is little data on the clinical features and treatment outcomes of...     

Serum galactomannan strongly correlates with outcome of invasive aspergillosis in acute leukaemia patients

Invasive aspergillosis (IA) remains an important cause of mortality in acute leukaemia patients. Previous studies reported that serum galactomannan (GM) levels correlate strongly with IA outcomes in patients with haematological cancers. This study aimed to clarify the usefulness of serial GM testing for outcome evaluation of IA in acute leukaemia patients. We retrospectively analysed 58 acute leukaemia patients who had IA during neutropenic period after chemotherapy and whose serum GM was serially monitored until discharge or death. The kappa correlation coefficient was used to determine the strength of correlation between GM and clinical outcome (survival or death) of IA. The correlation between clinical outcome and GM kinetics was good at week 6 [κ = 0.663, 95% confidence interval (CI): 0.465-0.861] and excellent at week 12 (κ = 0.819, 95% CI: 0.667-0.91). Survival was significantly better in patients whose GM values normalised than in patients with persistently positive GM (P < 0.0001) regardless of whether neutropenia resolved or acute leukaemia responded to chemotherapy. In neutropenic patients with acute leukaemia, serum GM correlated strongly with survival outcome of IA. This finding further supports the usefulness of the GM index as a surrogate marker for assessing IA outcome and the need for serial GM testing in therapeutic monitoring.     

Escherichia coli and Klebsiella pneumoniae bacteremia in patients with neutropenic fever: factors associated with extended-spectrum β-lactamase production and its impact on outcome

Escherichia coli and Klebsiella pneumoniae are main pathogens in neutropenic fever even if the proportion of Gram-positive cocci is increasing. Extended-spectrum β-lactamases (ESBL)-producing organisms are an emerging problem in nosocomial infection. Nevertheless, until now, information about risk factors for the acquisition and clinical outcomes of bacteremia due to ESBL-producing organisms is limited in neutropenic patients. From medical records collected between January 2007 and December 2008, we identified a total of 101 consecutive patients who developed bacteremia due to E. coli (n?=?87) or K. pneumoniae (n?=?14). Twenty-six (26 %) cases of bacteremia were caused by ESBL-producing organisms. A hospital stay of >2 weeks during the 3 months preceding bacteremia [adjusted odds ratio (OR), 5.887; 95 % confidence interval (CI), 1.572–22.041] and the use of broad-spectrum cephalosporins in the 4 weeks prior to bacteremia (adjusted OR, 6.186; 95 % CI, 1.616–23.683) were significantly related to the acquisition of ESBL. Twenty-four (92 %) of the ESBL-producing organisms were susceptible to either piperacillin–tazobactam or amikacin. Aminoglycosides (amikacin or isepamicin) were the main appropriate antimicrobial agents used against the ESBL-producing isolates during the initial empirical treatment (16/22, 73 %). However, the 30-day mortality rates for ESBL bacteremia and non-ESBL bacteremia were not significantly different (15 vs 5 %; p?=?0.199). As alternatives to carbapenem, piperacillin–tazobactam plus amikacin or isepamicin combinations may be effective empirical therapeutic options for patients with neutropenic fever who are at high risk of developing bacteremia with ESBL-producing pathogens.     

Interim <Superscript>18</Superscript>F-FGD PET/CT may not predict the outcome in primary central nervous system lymphoma patients treated with sequential treatment with methotrexate and cytarabine

¹⁸F-fluoro-2-dexoy-D-glucose-positron emission tomography (PET)/computed tomography (CT) is a useful imaging technique for monitoring the treatment response in lymphoma cases. We investigated the value of interim brain PET/CT (I-PET/CT) for monitoring the response to intensive methotrexate-based chemotherapy in primary central nervous system lymphoma (PCNSL) patients with diffuse large B cell lymphoma (DLBCL). Of the 76 PCNSL patients treated with intensive methotrexate and cytarabine chemotherapy between September 2006 and December 2012, 66 patients with DLBCL were included in this study. The patient cohort of 66 individuals comprised 43 men and 23 women with a median age of 59 years (range, 17–75 years). During chemotherapy, 36 patients (54.5%) showed a negative metabolism on I-PET/CT, and 47 (71.2%) were negative on final (F) PET/CT. The baseline characteristics were similar between I-PET/CT-negative (n = 36) and I-PET/CT-positive patients (n = 30) except ECOG performance status. After a median follow-up of 27.5 months, there was no difference in the progression-free survival (PFS; P = 0.701) or overall survival (OS; P = 0.620) between the I-PET/CT-negative and I-PET/CT-positive groups. However, PFS in the F-PET/CT-negative group was significantly longer than that in the F-PET/CT-positive group (P < 0.001) without a significant difference in OS (P = 0.892). I-PET/CT may not predict the survival outcome of PCNSL patients with DLBCL treated with intensive methotrexate and cytarabine chemotherapy. Prospective trials are required to fully evaluate the role of I-PET/CT.     

Prediction of outcomes for patients with brain parenchymal metastases from breast cancer (BC): a new BC-specific prognostic model and a nomogram

The purpose of this study is to validate the recently published Breast-Graded Prognostic Assessment (GPA) and propose a new prognostic model and nomogram for patients with brain parenchymal metastases (BM) from breast cancer (BC). We retrospectively investigated 171 consecutive patients who received a diagnosis of BM from BC during 2000-2008. We appraised the recently proposed Sperduto's BC-specific GPA in training cohort through Kaplan-Meier survival curve using log-rank test and area under the curve for the BC-GPA predicting overall survival at 1 year and developed a new nomogram to predict outcomes using multivariate Cox-regression analysis. By putting the Sperduto's Breast-GPA together with our nomogram, we developed a new prognostic model. We validated our new prognostic model with an independent external patient cohort from 2 institutes for the same period. On the basis of our Cox-regression analysis, therapeutic effect of trastuzumab and status of extracranial systemic disease control were incorporated into our new prognostic model in addition to Karnofsky performance status, age, and hormonal status. Our new prognostic model showed significant discrimination in median survival time, with 3.7 months for class I (n = 15), 7.8 months for class II (n = 82), 10.7 months for class III (n = 42), and 19.2 months for class IV (n = 32; P < .0001). The new prognostic model accurately predicted survival among patients with BC from BM in an external validation cohort (P < .0001). We propose a new prognostic model and a nomogram reflecting the different biological features of BC, including treatment effect and status of extracranial disease control, which was excellently validated in an independent external cohort.     

Clinical significance of the appearance of abnormal protein band in patients with multiple myeloma

Multiple myeloma (MM) is characterized by clonal expansion of malignant bone marrow cells producing a unique monoclonal immunoglobulin. The appearance of abnormal protein band (APB) in MM has been reported during follow-up. We aimed to evaluate the clinical characteristics and outcomes of patients with APB in a single center cohort. A total of 377 consecutive MM patients were treated at the Asan Medical Center between January 2002 and December 2012. We compared clinical characteristics and survival outcome between those with and without APB. Of the 377 patients, 34 (9 %) experienced APB. They comprised 18.2 % (27/148) of patients treated with autologous stem cell transplantation (ASCT) and 3.1 % (7/229) of those not receiving ASCT. APB occurred after a median of 7.9 months (range, 2.2–95.7 months) from diagnosis. Immunoglobulin isotypes at diagnosis were as follows: IgG (n?=?10), IgA (n?=?8), IgD (n?=?5), free κ (n?=?4), and free λ (n?=?7). Nine patients experienced a second APB. With a median follow-up of 54.1 months, the median overall survival (OS) has not been reached in patients with APB and was 38.3 months in patients without (P?<?0.001). Multivariate analysis indicated that the development of APB was a significant favorable prognostic factor for OS (hazard ratio 0.21; 95 % confidence interval 0.08–0.52). Serum β₂-microglobulin, albumin, creatinine, and ASCT were also independent prognostic factors for OS. Further investigation is required to establish the mechanisms underlying APB in MM.     

Multicenter Phase 2 Study of Reduced-Dose CHOP Chemotherapy Combined With Rituximab for Elderly Patients With Diffuse Large B-Cell Lymphoma

Introduction

Elderly patients are more prone to encounter some adverse factors when they receive chemotherapy compared to younger patients. Addition of rituximab to a reduced dose (RD) of cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) chemotherapy might improve patient outcomes with an improved toxicity profile when provided to elderly patients with diffuse large B-cell lymphoma.

Prolonged Entecavir Therapy Is Not Effective for HBeAg Seroconversion in Treatment-Naive Chronic Hepatitis B Patients with a Partial Virological Response

The aims of this study were to investigate the efficacy of prolonged entecavir (ETV) therapy in treatment-naive chronic hepatitis B (CHB) patients and to determine whether continuous ETV therapy is feasible to achieve HBeAg seroconversion, particularly in patients with partial virological response (PVR). A total of 142 treatment-naive patients with CHB were enrolled. The mean duration of treatment was 65 (range, 26 to 90) months, and 86 patients (60.6%) were HBeAg positive. PVR was defined as detectable hepatitis B virus (HBV) DNA (>116 copies/ml) at year 1. The cumulative incidence of virological response (VR) increased from 54.9% at year 1 to 98.2% at year 7. HBeAg positivity (odds ratio [OR], 4.146; P = 0.001) and initial alanine aminotransferase (ALT) (OR, 0.997; P = 0.004) were independent risk factors for PVR. Among the 64 patients with PVR, 47 patients (73.4%) achieved VR within 4 years after prolonged ETV therapy without treatment adaptation. Three patients (2.1%) experienced virological breakthrough and HBV variants with genotypic resistance. The cumulative rate of HBeAg seroconversion was significantly higher in the patients with VR than in the patients with PVR (P = 0.018). None of the PVR patients with HBV DNA at ≥5,000 copies/ml at year 1 ever experienced HBeAg seroconversion. Multivariate analysis identified VR at year 1 as the only determinant of HBeAg seroconversion (hazard ratio [HR], 3.009; P = 0.010). In conclusion, although there were patients with PVR, prolonged ETV therapy showed excellent VR, with only 2.1% emergence of viral resistance during a 7-year follow-up. However, to achieve HBeAg seroconversion, drug modification is needed for HBeAg-positive patients with PVR (especially those with HBV DNA at ≥5,000 copies/ml at year 1).     

BEAC or BEAM high-dose chemotherapy followed by autologous stem cell transplantation in non-Hodgkin’s lymphoma patients: comparative analysis of efficacy and toxicity

The treatment of choice for relapsed/refractory non-Hodgkin’s lymphoma (NHL) consists of high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT). Little is known, however, regarding the comparative toxicity and efficacy of various HDC regimens applied in NHL. We have retrospectively evaluated the clinical aspects of the BCNU, etoposide, cytarabine, and cyclophosphamide (BEAC) and BCNU, etoposide, cytarabine, and melphalan (BEAM) regimens for ASCT. Between April 1994 and February 2005, 97 NHL patients underwent HDC with BEAC (N = 69) or BEAM (N = 28), followed by ASCT, at the Asan Medical Center. We matched each BEAM patient with two BEAC patients having the same International Prognostic Index. Thus, 84 patients (56 BEAC and 28 BEAM) were analyzed. Median age was 40.5years, and baseline characteristics were well balanced between the two groups. The median time to neutrophil engraftment (>500/mm³) was significantly longer with BEAC than with BEAM (12 vs 11days, P = 0.001), as was the total amount of red blood cell transfusion (6.5 vs 3.7U, P = 0.037), but the median time to platelet engraftment (>20,000/mm³) and the total amount of platelet transfusion did not differ between the two groups. BEAM patients had significantly more frequent World Health Organization grade greater than or equal to 2 diarrhea than BEAC patients (46.4 vs 19.6%, P = 0.010), but the incidence of mucositis, nausea/vomiting, and bleeding and the number of episodes of febrile neutropenia and septicemia did not differ between the two groups. Median follow-up for survivors was 33months in the BEAM group and 89months in the BEAC group. Median overall survival and median event-free survival were not reached in the BEAM group and were 7.9 (95% confidence interval [CI], 1–14.8months, P = 0.003) and 3.7months (95% CI, 0.1–7.2months, P = 0.001), respectively, in the BEAC group. BEAM appeared to be superior to BEAC for survival. Regimen-related toxicities were similar, except that BEAM was associated with more frequent but acceptable diarrhea.