Sphingobacterium spiritivorum has been rarely isolated from clinical specimens of immunocompromised patients, and there have been no case reports of S. spiritivorum infection in Korea to our knowledge. We report a case of S. spiritivorum bacteremia in a 68-yr-old woman, who was diagnosed with acute myeloid leukemia and subsequently received chemotherapy. One day after chemotherapy ended, her body temperature increased to 38.3℃. A gram-negative bacillus was isolated in aerobic blood cultures and identified as S. spiritivorum by an automated biochemical system. A 16S rRNA sequencing analysis confirmed that the isolate was S. spiritivorum. The patient received antibiotic therapy for 11 days but died of septic shock. This is the first reported case of human S. spiritivorum infection in Korea. Although human infection is rare, S. spiritivorum can be a fatal opportunistic pathogen in immunocompromised patients.
Sphingobacterium spiritivorum; Bacteremia; Immunocompromised patient; 16S rRNA sequencing
Maximum standardized uptake value (SUVmax) and maximum tumor diameter (MTD) have been shown to reflect survival outcome in diffuse large B cell lymphoma (DLBCL). However, applying these values to primary extranodal DLBCL is difficult because they are separate nosological entities with differences in genetic origin. We therefore decided to evaluate whether SUVmax and MTD on 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18-FDG) positron emission tomography (PET) would affect the survival outcome in primary extranodal DLBCL.
From October 2005 to November 2010, 76 primary extranodal DLBCL patients receiving R-CHOP therapy were analyzed. All patients had undergone an initial 18-FDG PET/CT and conventional computed tomography (CT) of the neck, chest, abdomen, and pelvis for staging. Median follow-up period was 35 months.
The SUVmax and MTD cut-off values were 11.0 and 7.5 cm, respectively. SUVmax≥11.0 predicted a short progression free survival (PFS, P=0.002) and overall survival (OS, P=0.002). MTD≥7.5 cm was associated with poor PFS (P=0.003) and OS (P=0.003). High International Prognostic Index (IPI) was also associated with the survival outcome (PFS, P=0.046; OS, P=0.030). Multivariate analysis revealed that SUVmax≥11.0 (PFS, hazard ratio [HR]=10.813, P=0.024; OS, HR=6.312, P=0.015); MTD≥7.5 cm (PFS, HR=5.631, P=0.008; OS, HR=4.072, P=0.008); and high IPI (PFS, P=0.027; OS, P=0.046) were independent prognostic factors.
It appears that both MTD and SUVmax can be independent prognostic factors in primary extranodal DLBCL.
Lymphoma; Large B-cell; Extranodal
The objective of this study was to identify prognostic factors for survival in patients with primary diffuse large B-cell lymphoma (DLBCL) of the adrenal gland.
Thirty one patients diagnosed with primary adrenal DLBCL from 14 Korean institutions and treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) were analyzed.
Complete remission (CR) and overall response rate after R-CHOP chemotherapy were 54.8% and 87.0%. The 2-year estimates of overall survival (OS) and progression-free survival (PFS) were 68.3% and 51.1%. In patients achieving CR, significant prolongations of OS (P = 0.029) and PFS (P = 0.005) were observed. Ann Arbor stage had no influence on OS. There was no significant difference in OS between patients with unilateral involvement of adrenal gland and those with bilateral involvement. When staging was modified to include bilateral adrenal involvement as one extranodal site, early stage (I or II) significantly correlated with longer OS (P = 0.021) and PFS (P <0.001).
Contrary to prior reports, our data suggests that outcomes of primary adrenal DLBCL are encouraging using a regimen of R-CHOP, and that achieving CR after R-CHOP is predictive of survival. Likewise, our modified staging system may have prognostic value.
Primary adrenal lymphoma; Diffuse large B-cell lymphoma; Prognostic factor; R-CHOP
The objective of this study was to investigate whether metabolic tumor volume (MTV) by positron emission tomography (PET) can be a potential prognostic tool when compared with Ann Arbor stage, in stages II and III nodal diffuse large B cell lymphoma (DLBCL). We evaluated 169 patients with nodal stages II and III DLBCL who underwent measurements with PET prior to rituximab combined with cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP). Cutoff point of MTV was measured using the receiver operating characteristic (ROC) curve. During a median period of 36 months, stage II was 59.2% and III was 40.8%. Using the ROC curve, the MTV of 220 cm3 was the cutoff value. The low MTV group (<220 cm3) had longer progression-free survival (PFS) and overall survival (OS), compared with the high MTV group (≥220 cm3) (p < 0.001, p < 0.001). Stage II patients had longer survival than those in stage III (PFS, p = 0.011; OS, p = 0.001). The high MTV group had lower PFS and OS patterns, regardless of stage, compared with the low MTV group (p < 0.001, p < 0.001). Multivariate analysis revealed an association of the high MTV group with lower PFS and OS (PFS, hazard ratio (HR) = 5.300, p < 0.001; OS, HR = 7.009, p < 0.001), but not stage III (PFS, p = 0.187; OS, p = 0.054). Assessment of MTV by PET had more potential predictive power than Ann Arbor stage in the patients that received R-CHOP.
Diffuse large B cell lymphoma; Positron emission tomography; Rituximab
Autologous stem cell transplantation (ASCT) has become the treatment of choice for patients with multiple myeloma (MM). Studies have shown that maintenance treatment with interferon-alpha is associated with improved survival rates following ASCT. However, despite these recent advances in regimes, relapses are inevitable; thus, the prediction of relapse following ASCT requires assessment.
We retrospectively analyzed 39 patients who received ASCT between 2003 and 2008. All patients received chemotherapy with vincristine, adriamycin, and dexamethasone (VAD), and ASCT was performed following high-dose melphalan conditioning therapy. We evaluated the influence of the post-transplant day +14 (D+14) bone marrow plasma cell percent (BMPCp) (≥ 2 vs. < 2%), international scoring system (ISS) stage (II vs. III), response after 3 cycles of VAD therapy (complete response [CR] vs. non-CR), deletion of chromosome 13q (del[13q]) (presence of the abnormality vs. absence), and BMPCp at diagnosis (≥ 50 vs. < 50%) on progression-free survival (PFS) and overall survival (OS).
During the median follow-up of 28.0 months, the median PFS and OS were 29.1 and 42.1 months, respectively. By univariate analysis, ISS stage III at diagnosis, BMPCp ≥ 50% at diagnosis, CR after 3 cycles of VAD therapy, del (13q) by fluorescence in situ hybridization, and BMPCp ≥ 2% at post-transplant D+14 were correlated with PFS and OS. A multivariate analysis revealed that a post-transplant D+14 BMPCp ≥ 2% (PFS, hazard ratio [HR] = 4.426, p = 0.008; OS, HR = 3.545, p = 0.038) and CR after 3 cycles of VAD therapy (PFS, HR = 0.072, p = 0.014; OS, HR = 0.055, p = 0.015) were independent prognostic parameters.
Post-transplant D+14 BMPCp is a useful parameter for predicting the outcome for patients with MM receiving ASCT.
Multiple myeloma; Stem cell transplantation; Bone marrow; Plasma cell
Bortezomib has significant activity in treating multiple myeloma (MM). The risk of herpes zoster (HZ) has been reported to increase significantly with bortezomib treatment, but the predisposing factors for HZ are not clear. This study is a retrospective analysis of the relevant risk factors for HZ in Korean MM patients treated with bortezomib.
Sixty-six patients with refractory or relapsed MM who underwent chemotherapy with bortezomib were included in the study. Prophylactic antiviral drugs were not used for treatment. The following parameters were reviewed: age, gender, stage and type of MM, extent of previous treatment, history of HZ, duration from the time of diagnosis to the time of bortezomib treatment initiation, and absolute lymphocyte counts (ALC) at the time of bortezomib treatment initiation.
The incidence of HZ was 16.7%. There were no intergroup differences between the HZ-positive and the HZ-negative groups with regard to a history of HZ, number of previous treatments, and exposure to steroids before bortezomib treatment. The median duration from the time of MM diagnosis to the time of bortezomib treatment initiation in the HZ-positive group was significantly shorter than that in the HZ-negative group. The median ALC at the time of bortezomib initiation in the HZ-positive group was significantly lower than that in the HZ-negative group.
Bortezomib itself might act as a risk factor for HZ by inhibiting cell-mediated immunity, and patients with low ALC at the time of bortezomib treatment initiation were at greater risk of HZ during bortezomib treatment.
Multiple myeloma; Protease inhibitors; Herpes zoster
Post-transplant lymphoproliferative disorders (PTLD) are a heterogeneous group of lymphoproliferative disorders associated with immunosuppression and Epstein-Barr virus infection. PTLD is classified into three major categories: early lesions, polymorphic PTLD, and monomorphic PTLD. The majority of monomorphic PTLD cases are non-Hodgkin's lymphoma of B-cell origin. This retrospective study was conducted to investigate the incidence, clinical manifestation, treatment, and outcomes of monomorphic PTLD among 5,817 recipients of solid organ or allogeneic hematopoietic stem cell transplantation from five institutions. Fourteen patients with monomorphic PTLD were identified (male:female 11:3; median age 42.6 yr, range 24-60). The overall incidence rate was 0.24%. The most common disease type was diffuse large B cell lymphoma (n=7). The median time between the transplant and diagnosis of PTLD was 85.8 months. However, all cases of PTLD after allogeneic hematopoietic stem cell transplantation occurred within 1 yr after transplantation. Ten of the 14 patients had EBV-positive tumor. Fourteen patients received combination systemic chemotherapy and four patients were treated with radiation therapy. Ten patients achieved a complete response (CR) and two patients a partial response (PR). The median follow-up period for surviving patients was 36.6 months. Nine patients remain alive (eight CR, one PR). Nine of 11 solid organ transplantations preserved graft function. The present study indicates a lower incidence rate and a longer median time before the development of PTLD than those of previous reports. Careful monitoring was needed after allogeneic hematopoietic stem cell transplantation for PTLD.
Monomorphic Post-transplant Lymphoproliferative Disorders
Serum ferritin is a marker of acute phase reactions and iron storage. In addition, hematologic malignancies are associated with elevated serum ferritin levels. Other studies have suggested that ferritin is a surrogate for advanced disease and has an impact on relapse, because elevated serum ferritin predicts overall survival (OS) and relapse-free survival following autologous stem cell transplantation for lymphomas.
We studied 89 consecutive patients with newly diagnosed multiple myeloma to determine the value of serum ferritin in comparison with known prognostic factors.
The OS in the elevated serum ferritin group (≥300 ng/mL) was shorter than that in the normal serum ferritin group (<300 ng/mL, p<0.001) after a median follow-up of 25 months. In univariate analysis, elevated ferritin was correlated with poor survival in the patients (relative risk [RR], 2.588; 95% confidence interval [CI], 1.536 to 4.358; p<0.001). Furthermore, multivariate analysis showed that elevated serum ferritin was an independent predictor of mortality in patients with multiple myeloma (RR, 2.594; 95% CI, 1.403 to 4.797; p=0.002).
The serum ferritin can a prognostic parameter of survival as well as disease activity in patients with multiple myeloma.
Ferritin; Multiple myeloma; Survival
Previous reports have suggested that a high serum cyclosporine A (CsA) level could result in a lower incidence of acute-graft-versus-host disease (aGVHD). An elevated serum lactate dehydrogenase (LDH) level has been reported to be an adverse predictor of outcome in stem cell transplantation (SCT) for acute myeloid leukemia. In this study, we retrospectively analyzed the records of 24 patients who received allogeneic SCT from an HLA-matched sibling donor for acute and chronic myelogenous leukemia. Univariate analysis showed that two factors (the serum CsA level at the third week after SCT and the LDH level at the third week after SCT) were significantly associated with the incidence of aGVHD among several variables (age, sex, stem cell source, cell dose, C-reactive protein, absolute lymphocyte count, conditioning regimens, and time to engraftment). A higher serum level of CsA and lower serum LDH level at the third week after SCT were associated with a lower incidence of aGVHD (P=0.015, 0.030). In multivariate analysis, the serum CsA level (hazard ratio [HR], 0.12; 95% confidence interval [CI], 0.022-0.652, P=0.0014) and serum LDH level (HR, 6.59; 95% CI, 1.197-36.316, P=0.030) at the third week after SCT were found to be independent factors that were significantly associated with the development of aGVHD. We conclude that a high CsA level and low LDH level might predict a low cumulative incidence of aGVHD after allogeneic transplantation from a matched sibling donor.
Leukemia, Myeloid, Acute; Cyclosporine; Graft vs Host Disease
A refractory and resistant disease to conventional induction chemotherapy and relapsed disease are considered as the most important adverse prognostic factors for acute myeloid leukemia (AML). Sixty-one patients (median age, 33.6 yr) with relapsed or refractory AML were treated with the FLAG regimen that consisted of fludarabine (30 mg/m2, days 1-5), cytarabine (2.0 g/m2, days 1-5) and granulocyte colony-stimulating factor. Of the treated patients 29 patients (47.5%) achieved complete remission (CR). Higher CR rates were observed for patients with a first or second relapse as compared to patients with a primary refractory response or relapse after stem cell transplantation (HSCT). There was a significant difference in the response rates according to the duration of leukemia-free survival (pre-LFS) before chemotherapy (P=0.05). The recovery time of both neutrophils (≥500/µL) and platelets (≥20,000/µL) required a median of 21 and 18 days, respectively. Treatment-related mortality (TRM) occurred in seven patients (11.4%), of which 71.4% of TRM was caused by an invasive aspergillosis infection. After achieving CR, 18 patients underwent consolidation chemotherapy and six patients underwent allogeneic HSCT. In conclusion, FLAG chemotherapy without idarubicin is a relatively effective and well-tolerated regimen for relapsed or refractory AML and the use of FLAG chemotherapy has allowed intensive post-remission therapy including HSCT.
Leukemia, Myeloid, Acute; FLAG Chemotherapy; Toxicity
To date, an effective salvage chemotherapy regimen for the treatment of refractory or relapsing non-Hodgkin's lymphoma (NHL) has not been discovered. This study was conducted to evaluate the efficacy and safety of gemcitabine, etoposide, cisplatin, and dexamethasone in relapsed or refractory NHL patients.
All patients had histologically proven relapsed or refractory NHL. Treatments consisted of gemcitabine 700 mg/m2 by continuous i.v. on days 1 and 8; etoposide 40 mg/m2 by i.v. on days 1-4; cisplatin 60 mg/m2 by i.v. on day 1; or dexamethasone 40 mg by i.v. on days 1-4 (GEPD) every 21 days. The primary end point was the patient response rate following two cycles of treatment. After two cycles, stem cells were harvested using mobilizing regimens (ESHAP or GEPD plus filgrastim), and this was followed by autologous stem cell transplantation or four additional cycles of GEPD.
Between January 2005 and January 2006, 20 patients (13 males and 7 females) were enrolled in the study. The median age was 53 (range 16-75) years. The most common histology was diffuse large B-cell lymphoma (n=10). The median follow-up duration was 5.2 (range 1.0-16.0) months. After two cycles, the overall response rate was 50.0% (10/20), including two complete responses and eight partial responses. The dose-limiting toxicity was myelosuppression. Grade IV neutropenia and thrombocytopenia occurred in 13 (65.0%) and 6 patients (30.0%), respectively. The median number of CD34-positive cells collected was 6.0 (range, 2.8-11.6) ×106/kg. Of the 17 patients < 66 years of age, 4 (23.5%) proceeded to autologous stem cell transplantation.
GEPD chemotherapy in patients with refractory or relapsed NHL was effective as a salvage therapy and helpful for stem cell harvest followed by autologous transplantation.
Non-Hodgkin's lymphoma; Refractory or relapsed; Gemcitabine
We initiated this study to investigate whether combining Helicobacter pylori eradication with immunosuppressive therapy provides an additional benefit to patients with idiopathic thrombocytopenic purpura (ITP) that has relapsed or has not responded to steroid and/or danazol therapy in patients who have H. pylori infection. Thirty-four patients with chronic ITP that had relapsed or failed to steroid and/or danazol therapy were assessed for H. pylori infection. Of the 21 confirmed cases, 12 patients were given H. pylori eradication therapy alone (EA), while 9 patients received eradication therapy combined with immunosuppressive therapy (EI). The response rate was not significantly different between patients in the EA and those in the EI group (41.7% in the EA group vs. 66.7% in the EI group, p=0.345). The median platelet count at 6 months after therapy was higher in the EI group patients (75×109/L in the EI group patients vs. 18×109/L in the EA group patients, p=0.028). The median response duration was also longer in the EI group patients (9 months in the EI group patients vs. 3 months in the EA group patients, p=0.049). These results show that a significant benefit is gained by the use of H. pylori eradication combined with immunosuppressive therapy over the use of eradication therapy alone for patients with chronic ITP.
Helicobacter pylori; Purpura, Thrombocytopenic, Idiopathic; Eradication
The objective of the current study was to investigate the treatment outcomes for the use of cyclophosphamide, adriamycin, vincristine, and prednisolone (CHOP) chemotherapy in adult patients with hemophagocytic lymphohistiocytosis (HLH). Seventeen HLH patients older than 18 yr of age were treated with CHOP chemotherapy. A response evaluation was conducted for every two cycles of chemotherapy. With CHOP chemotherapy, complete response was achieved for 7/17 patients (41.2%), a partial response for 3/17 patients (17.6%), and the overall response rate was 58.8%. The median response duration (RD) was not reached and the 2-yr RD rate was 68.6%, with a median follow-up of 100 weeks. Median overall survival (OS) was 18 weeks (95% CI, 6-30 weeks) and the 2-yr OS rate was 43.9%. Reported grade 3 or 4 non-hematological toxicities were increased serum liver enzyme levels and stomatitis. Grade 3 or 4 hematological toxicities were leukopenia (50.8%), anemia (20%), and thrombocytopenia (33.9%). Neutropenic fever was observed in 21.6% of patients (14/65 cycles), and most of the cases were resolved with supportive care including treatment with broad-spectrum antibiotics. CHOP chemotherapy seems to be effective in adult HLH patients and the toxicities are manageable.
Lymphohistiocytosis, Hemophagocytic; Herpesvirus 4, Human; Lymphoma; CHOP Protocol
Although concurrent chemoradiotherapy (CCRT) has been considered as a standard treatment for locally advanced squamous cell carcinoma of the head and neck (SCCHN), this treament is associated with increased toxicities such as mucositis and dermatitis. As a result, the dose intensity can be reduced and interruptions of radiotherapy are more common for CCRT than for sequential treatment, especially for the elderly patients. This prospective study was performed to assess the efficacy and safety profiles of the induction chemotherapy of docetaxel and cisplatin for elderly patients with locally advanced SCCHN.
Materials and Methods
Patients over 65 years of age with locally advanced SCCHN were treated with docetaxel (70 mg/m2) and cisplatin (75 mg/m2) every 21 days. The chemotherapy consisted of two cycles with a third cycle that was administered to the responding patients. Patients who did not respond to initial chemotherapy underwent radiotherapy as a definitive local treatment.
Fifty patients were enrolled in this study and 44 patients were assessable for response and toxicity. The overall response rate was 88%, 16 patients (36%) achieved a complete response and 23 patients (52%) achieved a partial response. After a median follow-up of 24 months (range: 9~38 months) the median disease free period and overall survival period had not yet been reached. The one year and two year survival rates were 89% and 70%, respectively. The most common grade 3/4 adverse event was neutropenia, which occurred in 33 patients (75%) and 4 patients had febrile neutropenia.
Combination chemotherapy of docetaxel and cisplatin is an effective regimen with an acceptable safety profile as the induction treatment for elderly patients suffering with SCCHN.
Docetaxel; Cisplatin; Head and neck cancer; Induction chemtherapy