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.     

Polymorphisms in cytokine genes as prognostic markers in diffuse large B cell lymphoma patients treated with (R)-CHOP

To investigate whether cytokine genetic polymorphisms influence the outcome of diffuse large B cell lymphoma (DLBCL), we tested 337 consecutive DLBCL treated with CHOP or rituximab-CHOP (R-CHOP) from interleukin 10 (IL10), Bcl-2, and tumor necrosis factor (TNF)-α polymorphisms. Patients who carried the IL10 rs1800871 TT or rs1800872 AA genotype showed higher complete response (CR) and overall response rate (ORR) significantly. A longer progression-free survival (PFS) was observed in patients with IL10 rs1800871 TT (P?=?0.017) or rs1800872 AA (P?=?0.017) genotype after rituximab-based chemotherapy, and better PFS was also noted with Bcl-2 rs1801018 AA genotype in the CHOP group (P?=?0.048). Furthermore, the R-CHOP group patients who carried the IL10 non-CCA haplotype had longer PFS (P?=?0.030). Cox proportional hazards analyses demonstrated that the genotype TT of IL10 rs1800871 and AA plus AC of rs1800872 were predictive of longer PFS and event-free survival (EFS) in DLBCL patients treated with R-CHOP. And the Bcl-2 rs2279115 AA plus AC genotypes and rs1801018 GG genotype were risk factors for EFS in DLBCL patients treated with CHOP. In conclusion, the results reminded us those DLBCL patients with IL10 rs1800871 TT, rs1800872 AA, or IL10 non-CCA haplotype are likely to benefit from the therapy of rituximab-based chemotherapy.     

Tumor necrosis could reflect advanced disease status in patients with diffuse large B cell lymphoma treated with R-CHOP therapy

Tumor necrosis (TN) can lower responsiveness to chemotherapy and confer basic resistance to anti-cancer therapy. We investigated the association of TN with poor clinical features and outcome in diffuse large B cell lymphoma (DLBCL). We examined the presence or absence of TN in 476 DLBCL patients of who received rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy. Eighty-nine (18.7 %) patients had TN at diagnosis. Patients with TN had a progression-free survival (PFS) and overall survival (OS) of 39.3 and 46.7 %, whereas patients without TN had a PFS and OS of 73.4 and 82.6 %. Adverse clinical factors of poor Eastern Cooperative Oncology Group performance status ≥ grade 2 (p?=?0.005), elevated lactate dehydrogenase ratio >1 (p?<?0.001), advanced Ann Arbor stage (p?=?0.002), and bulky disease (p?=?0.026) were more prevalent in the TN group than the non-TN group. Cox regression model analysis revealed TN as an independent prognostic factor for PFS and OS in DLBCL (PFS, hazard ratio [HR]?=?1.967, 95 % confidence interval [CI]?=?1.399–2.765, p?<?0.001; OS, HR?=?2.445, 95 % CI?=?1.689–3.640, p?<?0.001). The results indicate that TN could reflect adverse clinical features and worse prognosis in DLBCL patients receiving R-CHOP therapy.     

Clinical outcomes in patients with diffuse large B cell lymphoma with a partial response to first-line R-CHOP chemotherapy: prognostic value of secondary International Prognostic Index scores and Deauville scores

After introducing a rituximab-containing chemoimmunotherapy (R-CHOP) for diffuse large B cell lymphoma (DLBCL), a partial response (PR) which is regarded as treatment failure is still observed. To investigate the prognostic factors for the DLBCL patients with a PR to R-CHOP, we retrospectively evaluated 758 newly diagnosed DLBCL patients. After R-CHOP, 88 (11.6%) achieved a PR. Three-year progression-free and overall survival rates measured from the date of PR achievement (PFS2 and OS2) were 57.4 and 67.8%, respectively. The secondary International Prognostic Index (IPI2) scores after R-CHOP were low (0–1) in 68.2% and high (2–3) in 31.8% of the patients. The Deauville scores from 18-fluorodeoxyglucose positron emission tomography after R-CHOP showed low (2–3) in 58.0% and high (4) in 42.0% of the patients. High IPI2 and high Deauville scores were associated with worse PFS2 (P < 0.001 and P = 0.009) and OS2 (P = 0.013 and P = 0.067). The high-risk group defined by the IPI2 and Deauville scores, whose scores were both high, showed significantly lower 3-year PFS2 (P < 0.001) and OS2 (P = 0.006) rates compared with those of the other groups. In multivariate analyses, the IPI score of ≥?3 at diagnosis and bone marrow involvement at diagnosis were independent prognostic factors. In addition, high IPI2-Deauville score after R-CHOP was significantly associated with poor PFS2 (P = 0.009) and demonstrated a trend toward inferior OS2. In conclusion, DLBCL patients who partially responded to R-CHOP are still a heterogeneous group, for which IPI2 and Deauville scores should be evaluated for prediction of prognosis.     

Hyperfibrinogenemia is a poor prognostic factor in diffuse large B cell lymphoma

Diffuse large B cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphomas worldwide. Previous studies indicated that hyperfibrinogenemia was a poor predictor in various tumors. The purpose of our study was to evaluate the prognostic effect of hyperfibrinogenemia in DLBCL. Data of 228 patients, who were diagnosed with DLBCL in our hospital between May 2009 and February 2016, were analyzed retrospectively. The Kaplan-Meier method and Cox regression were performed to find prognostic factors associated with progression-free survival (PFS) and overall survival (OS). Receiver operator characteristic (ROC) curve and the areas under the curve were used to evaluate the predictive accuracy of predictors. Comparison of characters between groups indicated that patients with high National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) score (4–8) and advanced stage (III–IV) were more likely to suffer from hyperfibrinogenemia. The Kaplan-Meier method revealed that patients with hyperfibrinogenemia showed inferior PFS (P?<?0.001) and OS (P?<?0.001) than those without hyperfibrinogenemia. Multivariate analysis showed that hyperfibrinogenemia was an independent prognostic factor associated with poor outcomes (HR?=?1.90, 95% CI: 1.15–3.16 for PFS, P?=?0.013; HR?=?2.65, 95% CI: 1.46–4.79 for OS, P?=?0.001). We combined hyperfibrinogenemia and NCCN-IPI to build a new prognostic index (NPI). The NPI was demonstrated to have a superior predictive effect on prognosis (P?=?0.0194 for PFS, P?=?0.0034 for OS). Hyperfibrinogenemia was demonstrated to be able to predict poor outcome in DLBCL, especially for patients with advanced stage and high NCCN-IPI score. Adding hyperfibrinogenemia to NCCN-IPI could significantly improve the predictive effect of NCCN-IPI.     

Pneumothorax in Patients with Pulmonary Langerhans Cell Histiocytosis

Introduction

Pneumothorax often develops in pulmonary Langerhans cell histiocytosis (PLCH), but some patients take a long time to be correctly diagnosed.

Objectives

This study assessed the frequency of pneumothorax in PLCH and analysed the role of chest computed tomography (CT) in the prompt diagnosis.

Patients and material

Of the 90 patients with PLCH seen from 2000 to 2015, 29 (32%) had pneumothorax as the initial finding. In this group, 18 (62%) patients were diagnosed within 1 month, whereas the diagnosis was delayed for 4–120 months in 11 (38%) patients.

Results

Patients who had pneumothorax as the initial sign of PLCH tended to be younger (mean age 27.7?±?7.92 vs. 39.9?±?13.21 years; P?=?0.0001), male (69% vs. 43%; P?=?0.028), smoked less (mean pack/years 8.4?±?6.85 vs. 19?±?17.16; P?=?0.003), and had a significantly lower mean FVC (77.96?±?19.62 vs. 89.47?±?21.86% pred.; P?=?0.015) and FEV₁ (68.6?±?19.93 vs. 79.4?±?21.48% pred.; P?=?0.03 than patients who had no pneumothorax. Recurrent pneumothorax was diagnosed more frequently in the group with a delayed diagnosis (82% vs. 39%; P?=?0.02). CT was performed in all of the patients who were diagnosed promptly, but in none of the patients with a delayed diagnosis.

Conclusions

Patients who had pneumothorax as the initial sign of PLCH were younger, more frequently men, and had greater respiratory impairment than those who had no pneumothorax. CT in patients with pneumothorax led to a correct diagnosis of this disease.

     

Peripheral blood lymphocyte/monocyte ratio following completion of first-line therapy predicts early relapse in patients with diffuse large B cell lymphoma

To investigate whether the post-therapy lymphocyte/monocyte ratio (ALC/AMC ratio or LMR) predicts early relapse in patients with diffuse large B cell lymphoma (DLBCL), we enrolled 125 consecutive patients with DLBCL and followed up from 2005 to 2015 in our hospital. The LMR was measured following completion of first-line therapy. We found that the LMR following completion therapy was a strong predictor of early relapse, which is less than 12 months after diagnosis. A low LMR was significantly associated with early relapse in both univariate [odds ratio (OR)?=?8.8; P?=?0.006] and multivariate analysis (OR?=?8.951; P?=?0.011). The low-LMR group (<2.9) had poorer outcomes than the high-LMR group (≥2.9), with a lower 2-year progression-free survival rate (78.9 versus 97.1 %, P?=?0.002) and 2-year OS rate (82.5 versus 98.5 %, P?=?0.002). This study suggests that a lower LMR following completion of first-line therapy can be used as a marker to predict early relapse in patients with DLBCL.     

Patients with primary breast and primary female genital tract diffuse large B cell lymphoma have a high frequency of <Emphasis Type="Italic">MYD88</Emphasis> and <Emphasis Type="Italic">CD79B</Emphasis> mutations

This study is to retrospectively evaluate the prevalence of MYD88 and CD79B mutations and the clinicopathologic characteristics of patients with primary diffuse large B cell lymphoma (DLBCL) of the female genital tract and breast. The characteristics, treatments, and outcomes of 19 patients diagnosed with primary DLBCL of the female genital tract and breast, who had formalin-fixed and paraffin-embedded tissues obtained from diagnostic samples diagnosed between January 2004 and June 2016, were analyzed retrospectively. Nineteen female patients (7 with primary breast and 12 with primary female genital tract DLBCL) were included in this retrospective study. Eleven patients (57.9%) carried a MYD88 mutation, including 10 with MYD8 L265P and 1 with the MYD88 L265S mutation. Seven patients (36.8%) harbored a CD79B mutation, which included two cases with CD79B Y196H, two cases with CD79B Y196N, one case with CD79B Y196D, one case with CD79B Y196F, and one case with CD79B Y196X. Four cases had both MYD88 and CD79B mutations. The clinicopathologic parameters, progression-free survival (PFS), and overall survival (OS) of the MYD88 mutation-carrying group were not significantly different from those of the MYD88 wild-type group except for higher LDH levels. Six patients received cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP), while 13 patients received rituximab plus CHOP, and 13 patients received central nervous system prophylaxis. The median OS and PFS were 73 and 56 months, respectively. Patients with primary breast and primary female genital tract DLBCL have a high frequency of MYD88 and CD79B mutations. The presence of these mutations does not affect survival but may offer additional therapeutic options.     

Autologous stem cell transplantation in first remission is associated with better progression-free survival in multiple myeloma

Autologous stem cell transplant (ASCT) is standard consolidation therapy in management of multiple myeloma (MM) patients. We reviewed records of all consecutive MM patients who underwent ASCT with high-dose melphalan at our center from year 2002 to 2016. A total of 141 ASCT were conducted (90 males and 51 females) with median age of 55 years (23–68 years). Median time from diagnosis to transplant was 7 months (3–79), with majority of patients underwent transplant in first remission, while 17 (12%) patients received transplant beyond first remission. Eighty-three percent patients obtained CR/VGPR post-ASCT. Transplant-related mortality was 2.1%. At a median follow up of 54 months, mean overall survival (OS) and progression-free survival (PFS) group were 128.3 months (95% C.I. 111.9–144.7 months) and 73.8 months (95% C.I. 57.7–89.9 months), respectively. On univariate analysis, OS was adversely affected by renal insufficiency (p?=?0.024), while OS was better with CR/VGPR post-ASCT (p?<?0.001) and lenalidomide maintenance therapy (p?=?0.009). PFS was affected by CR/VGPR pre-ASCT (p?=?0.021), CR/VGPR post-ASCT (p?<?0.001), and transplant in first remission (p?=?0.034). On multivariate analysis, lenalidomide maintenance (versus thalidomide) (p?=?0.007) and CR/VGPR response post-ASCT (p?=?0.0003) were found to be predictors for better OS and CR/VGPR response at transplant for better PFS (p?=?0.038). Transplant in first remission versus beyond first remission showed a trend for better PFS (p?=?0.073). Conclusion: Majority of patients obtained CR/VGPR post-ASCT. Longer PFS was seen with patients who were transplanted in first remission.     

Geriatric nutritional risk index as a prognostic factor in patients with diffuse large B cell lymphoma

The geriatric nutritional risk index (GNRI) is a simple and well-established nutritional assessment tool that is a significant prognostic factor for various cancers. However, the role of the GNRI in predicting clinical outcomes of diffuse large B cell lymphoma (DLBCL) patients has not been investigated. To address this issue, we retrospectively analyzed a total of 476 patients with newly diagnosed de novo DLBCL. We defined the best cutoff value of the GNRI as 96.8 using a receiver operating characteristic curve. Patients with a GNRI <?96.8 had significantly lower overall survival (OS) and progression-free survival (PFS) than those with a GNRI ≥?96.8 (5-year OS, 61.2 vs. 84.4%, P?<?0.001; 5-year PFS, 53.7 vs. 75.8%, P?<?0.001). Multivariate analysis showed that performance status, Ann Arbor stage, serum lactate dehydrogenase, and GNRI were independent prognostic factors for OS. Among patients with high-intermediate and high-risk by National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI), the 5-year OS was significantly lower in patients with a GNRI <?96.8 than in those with a GNRI ≥?96.8 (high-intermediate risk, 59.5 vs. 75.2%, P?=?0.006; high risk, 37.4 vs. 64.9%, P?=?0.033). In the present study, we demonstrated that the GNRI was an independent prognostic factor in DLBCL patients. The GNRI could identify a population of poor-risk patients among those with high-intermediate and high-risk by NCCN-IPI.     

Delayed wound healing and postoperative surgical site infections in patients with rheumatoid arthritis treated with or without biological disease-modifying antirheumatic drugs

Biological disease-modifying antirheumatic drugs (bDMARDs) have become more popular for treating rheumatoid arthritis (RA). Whether or not bDMARDs increase the postoperative risk of surgical site infection (SSI) has remained controversial. We aimed to clarify the effects of bDMARDs on the outcomes of elective orthopedic surgery. We used multivariate logistic regression analysis to analyze risk factors for SSI and delayed wound healing among 227 patients with RA (mean age, 65.0 years; disease duration, 16.9 years) after 332 elective orthopedic surgeries. We also attempted to evaluate the effects of individual medications on infection. Rates of bDMARD and conventional synthetic DMARD (csDMARD) administration were 30.4 and 91.0 %, respectively. Risk factors for SSI were advanced age (odds ratio [OR], 1.11; P?=?0.045), prolonged surgery (OR, 1.02; P?=?0.03), and preoperative white blood cell count >10,000/μL (OR, 3.66; P?=?0.003). Those for delayed wound healing were advanced age (OR, 1.16; P?=?0.001), prolonged surgery (OR, 1.02; P?=?0.007), preoperative white blood cell count >10,000/μL (OR, 4.56; P?=?0.02), and foot surgery (OR, 6.60; P?=?0.001). Risk factors for SSI and medications did not significantly differ. No DMARDs were risk factors for any outcome examined. Biological DMARDs were not risk factors for postoperative SSI. Foot surgery was a risk factor for delayed wound healing.     

Prevalence and factors associated with disturbed sleep in outpatients with ankylosing spondylitis

Sleep disturbance is prevalent among patients with ankylosing spondylitis (AS) and is considered a multifactorial issue. The study was designed to investigate sleep disturbance and its associated factors in AS outpatients in Southwest China. Patients were recruited by convenience sampling in this cross-sectional study. The Pittsburgh Sleep Quality Index (PSQI), the Bath AS Disease Activity Index (BASDAI), the Bath AS Functional Index (BASFI), the Bath AS Patient Global Score (BAS-G), and the Hospital Anxiety and Depression Scale (HADS) were used to assess sleep quality, disease activity, function status, global well-being, depression, and anxiety. Spearman’s correlation, t test, ANOVA, and multiple linear regression analysis were used to explore the associated factors of sleep disturbance. Of the 281 outpatients included in the study, 190 (67.6%) patients had sleep disturbance. The married patients, the patients with extra-spinal manifestation, depression and anxiety, longer duration of diagnostic delay, higher disease activity, worse functional status and global well-being, high level of pain, and fatigue, had poorer sleep quality (P?<?0.05). Multiple linear regression analysis revealed age (β?=?0.087, P?=?0.102), BAS-G (β?=?0.181, P?=?0.003), fatigue (β?=?0.170, P?=?0.002), anxiety (β?=?0.151, P?=?0.002) and nocturnal back pain (β?=?0.192, P?=?0.001), extra-spinal manifestation (β?=?0.120, P?=?0.012), and duration of diagnostic delay (β?=?0.174, P?=?0.001) were the contributors to PSQI. Sleep disturbance is common in AS patients in Southwest China. It may be useful to keep regular exercise, strengthen the management of pain, relieve anxiety, and prevent and treat extra-spinal manifestation for improving sleep quality.     

Ultrasound of knee osteoarthritis: interobserver agreement and correlation with Western Ontario and McMaster Universities Osteoarthritis

The aim of this work was to assess the reproducibility of ultrasound findings of knee osteoarthritis and to correlate ultrasound findings with Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Prospective study was conducted upon 80 patients (56 F, 24 M; mean age 57 years) with primary osteoarthritis of knee joint. All patients underwent clinical assessment with calculation of WOMAC and high-resolution ultrasound of the knee joint. The ultrasound images were analyzed for cartilage thinning, osteophytes, synovial effusion, synovial proliferation, popliteal cyst, and meniscal protrusion. Image analysis was performed by two readers and linear regression analysis was used to determine association of ultrasound findings with WOMAC. There was excellent inter-observer agreement of both readers for cartilage thinning (k?=?0.99, P?=?0.001), osteophytes (k?=?0.94, P?=?0.001), synovial effusion (k?=?0.98, P?=?0.001), synovial thickening (k?=?0.96, P?=?0.001), popliteal cyst (k?=?1.00, P?=?0.001), and meniscal protrusion (k?=?0.86, P?=?0.001). There was significant association of WOMAC with cartilage changes (t?=?3.406, 3.302, P?=?0.001), osteophytes (t?=?3.841, 3.006, P?=?0.001), and synovial effusion (t?=?4.140 and 2.787, P?=?0.05) of both readers. We concluded that ultrasound is a reproducible method for assessment of knee osteoarthritis and well correlated with WOMAC.     

Bendamustine and rituximab (BR) versus dexamethasone,rituximab, and cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia

The treatment approaches for Waldenstrom macroglobulinemia (WM) are largely based upon information from single-arm phase II trials, without comparative data. We compared the efficacy of two commonly used regimens in routine practice (bendamustine-rituximab (BR) and dexamethasone, rituximab plus cyclophosphamide (DRC)) and evaluated their activity with respect to the patients’ MYD88^L265P mutation status. Of 160 consecutive patients, 60 received BR (43 with relapsed/refractory WM) and 100 received DRC (50 had relapsed/refractory WM). In the treatment-naïve setting, overall response rate (ORR) was 93% with BR versus 96% with DRC (p?=?0.55). Two-year progression-free survival (PFS) with BR and DRC was 88 and 61%, respectively (p?=?0.07). In salvage setting, ORR was 95% with BR versus 87% with DRC, p?=?0.45; median PFS with BR was 58 versus 32 months with DRC (2-year PFS was 66 versus 53%; p?=?0.08). Median disease-specific survival was not reached with BR versus 166 months with DRC (p?=?0.51). The time-to-event endpoints and depth of response were independent of the MYD88 mutation status. Grade ≥?3 adverse events of both regimens were comparable. A trend for longer PFS was observed with BR although the regimens have comparable toxicities. The activity of BR and DRC appears to be unaffected by patients’ MYD88 mutation status.     

Impact of front line relative dose intensity for methotrexate and comorbidities in immunocompetent elderly patients with primary central nervous system lymphoma

Primary central nervous system lymphomas (PCNSL) are non-Hodgkin lymphomas strictly localized to the CNS, occurring mainly in elderly patients with comorbidities. Current treatment in fit patients relies on high-dose methotrexate and high-dose cytarabine. The aim of this study was to evaluate the efficacy and feasibility of this treatment in elderly patients and to assess potential prognostic factors associated with survival. We conducted a retrospective study in two centers between January 2008 and September 2015 including 35 elderly immunocompetent patients who received first-line treatment with high-dose methotrexate. With a median follow-up of 19.8 months (range: 1.7–73.4 months), median overall survival (OS) was 39.5 months (95% confidence interval (95% CI): 18.3–60.7) and median progression-free survival (PFS) was 25.8 months (95% CI: 5.2–46.4). In univariate analysis, administration of high-dose cytarabine and achieving a relative dose intensity for methotrexate >?75% were associated with increased OS (p?=?0.006 and p?=?0.003, respectively) and PFS (p?=?0.003 and p?=?0.04, respectively) whereas comorbidities, defined by a CIRS-G score ≥?8, were associated with decreased OS and PFS (p?=?0.02 and p?=?0.04, respectively). A high MSKCC score was associated with decreased OS (p?=?0.02). In multivariate analysis, administration of high-dose cytarabine was associated with increased OS and PFS (p?=?0.02 and p?=?0.007, respectively). Comorbidities and relative dose intensity for methotrexate are important for the prognosis of elderly patients with PCNSL. These results must be confirmed in prospective trials.     

The prognostic value of positron emission tomography/computed tomography in rheumatoid arthritis patients with methotrexate-associated lymphoproliferative disorders

Recently, methotrexate-associated lymphoproliferative disorders (MTX-LPDs) in rheumatoid arthritis (RA) have been found to commonly occur in association with iatrogenic immunodeficiency. Several factors have been reported to be related to the prognosis. We herein investigate the efficacy of 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) in predicting the prognosis of MTX-LPD. We performed a retrospective analysis of the clinical features, characteristics, and outcomes of 18 patients with MTX-LPDs who were treated from 2004 to 2015. All of the patients were diagnosed with MTX-LPD based on the histological examination of biopsy specimens. Spontaneous regression was detected after the cessation of MTX in 5 of 18 cases (28%). The maximum standardized uptake value (SUVmax) of the FDG uptake on PET/CT was significantly lower, and the maximum size of the LPD-associated tumor was significantly smaller among the patients who showed spontaneous regression (p?=?0.01, p?=?0.04, respectively). Both the SUVmax and the maximum tumor size were related to better overall survival (p?=?0.02, p?=?0.04, respectively). Thus, PET/CT can be used to predict spontaneous regression and the prognosis at the diagnosis of MTX/LPD. Cases that showed spontaneous regression never relapsed during the follow-up period, despite the usage of several anti-rheumatoid arthritis drugs, including biological agents. The early detection of LPDs and the early cessation of MTX are important for the management of RA patients. An evaluation by F-FDG-PET/CT can be useful for predicting spontaneous regression and the prognosis.     

Pooled analysis of the reports of carfilzomib/ixazomib combinations for relapsed/refractory multiple myeloma

We sought to evaluate the activity and safety of carfilzomib-/ixazomib-containing combinations for patients with relapsed/refractory multiple myeloma (RRMM). We searched published reports including carfilzomib-/ixazomib-containing combinations for RRMM. Finally, we identified 11 prospective studies covering 2845 relapsed/refractory patients. Carfilzomib- and ixazomib-containing combinations respectively resulted in an impressive overall response rate (ORR 77 vs. 64%, P?=?0.14), very good partial response or better (≥ VGPR 48 vs. 21%, P?=?0.001), complete response or better (≥ CR 14 vs. 7%, P?=?0.23), and clinical benefit rate (CBR 84 vs. 59%, P?=?0.0002). Subgroup analysis showed that the carfilzomib (CFZ) +lenalidomide (LEN) + dexamethasone (DEX) triplet regimen resulted into similar response outcomes to those from CFZ + DEX doublet regimen in ORR (77 vs. 78%, P?=?0.91), ≥VGPR (50 vs. 53%, P?=?0.84), and ≥ CR (13 vs. 12%, P?=?0.96) analysis in these previously heavily pretreated population. And, there were no statistically significant differences between IXA + LEN + DEX triplet regimen and CFZ + LEN + DEX triplet regimen in ORR (85 vs. 78%, P?=?0.55), ≥ VGPR (37 vs. 53%, P?=?0.19), and ≥ CR (18 vs. 12%, P?=?0.70) analysis. There were favorable trend towards proteasome inhibitors (PIs) + IMiDs + DEX in comparison with PIs + alkylating agent + Dex in ORR (79 vs 49%, P?<?0.00001), ≥ VGPR analysis (36 vs. 16%, P?=?0.008), and ≥ CR (16 vs. 3%, P?<?0.00001). Compared with current standard chemotherapy, carfilzomib containing combinations clearly improved overall survival (HR, 0.79; P?=?0.01), progression free survival (HR, 0.61; P?=?0.0001). Carfilzomib-/ixazomib-containing combinations produced clinical benefit for patients with R/RMM. PIs + IMiDs + DEX triplet regimens could be good options for such relapsed/refractory patients.     

Knee pain during activities of daily living and its relationship with physical activity in patients with early and severe knee osteoarthritis

This study aimed to investigate whether knee pain during various activities of daily living (ADLs) is associated with physical activity in patients with early and severe knee osteoarthritis (OA). We hypothesized that the painful ADLs associated with decreased physical activity differ according to disease severity. This cross-sectional study enrolled 270 patients with medial knee OA, assigned to either the early (Kellgren Lawrence [K/L] grade 1–2) or the severe group (K/L grade 3–4). Physical activity was assessed using a pedometer. Knee pain during six ADLs (waking up in the morning, walking on a flat surface, ascending stairs, etc.) was evaluated using a questionnaire. We performed multiple regression and quantile regression analysis to investigate whether knee pain during each ADL was associated with physical activity. In the early group, the more knee pain they experienced while ascending stairs, the lower their physical activity was (75th regression coefficient?=??1033.70, P?=?0.018). In the severe group, the more knee pain they experienced while walking on a flat surface or bending to the floor or standing up, the lower their physical activity was (unstandardized coefficients?=??1850.87, P?=?0.026; unstandardized coefficients?=??2640.35, P?=?0.010). Knee pain while ascending stairs and while walking on a flat surface or bending to the floor or standing up was a probable limiting factor for physical activity in early and severe knee OA, respectively. These findings suggested that a reduction in task-specific knee pain according to disease severity could improve physical activity levels.     

The impact of R-VACOP-B and interim FDG-PET/CT on outcome in primary mediastinal large B cell lymphoma

The choice of a rituximab-based regimen and the prognostic significance of interim 2-[fluorine-18]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (FDG-PET/CT) in primary mediastinal large B cell lymphoma (PMBCL) are debatable. We evaluated the clinical features and outcomes of 95 consecutive patients with PMBCL who were treated between 1985 and 2009. Forty-three patients received rituximab-based chemotherapy, R-VACOP-B (N?=?30) or R-CHOP21 (N?=?13), whereas 52 patients were treated with VACOP-B (N?=?47) or CHOP21 (N?=?5). Radiotherapy was not given. Patients who received rituximab had a 5-year progression-free survival (PFS) of 79 % and overall survival (OS) of 97 % compared with 58 % (p?=?0.06) and 88 % (p?=?0.2), respectively, without rituximab. Five-year PFS in patients treated with R-VACOP-B, R-CHOP21, VACOP-B, and CHOP21 were 83, 69, 62, and 20 %, respectively (p?=?0.039). However, direct comparison showed that the difference between PFS rates in patients receiving R-VACOP-B compared to R-CHOP21 was not statistically significant (p?=?0.3). None of the standard clinical risk factors predicted for PFS and OS in patients receiving rituximab (R)-chemotherapy. Mid-interim FDG-PET/CT scans were performed in 30/43 patients who received R-chemotherapy. The negative predictive values of mid-PET activity were high (100 % for R-VACOP-B and 86 % for R-CHOP21) while the positive predictive values (PPV) were relatively low (30 and 75 %, respectively). Despite the low PPV, the 5-year PFS for mid-PET-negative patients (N?=?16) was significantly higher (94 %) than that for mid-PET-positive (N?=?14) patients (57 %, p?=?0.015). This retrospective analysis demonstrates that the superiority of VACOP-B over CHOP21 for treatment of PMBCL disappeared once rituximab was added. The potential benefit of using interim PET activity as a guide for continuing therapy in patients with PMBCL remains unclear due to the relatively low PPV.     

Impact of hematopoietic stem cell transplantation in patients with relapsed or refractory mantle cell lymphoma

Rituximab has been shown to improve outcomes in patients with B-cell lymphoma. However, patients with relapsed or refractory (R/R) mantle cell lymphoma (MCL) still have a poor prognosis, and the choice between high-dose therapy with autologous hematopoietic cell transplantation (HCT) and allogeneic HCT remains controversial in these patients. We retrospectively analyzed the risk factors for outcomes in 162 R/R MCL patients who received autologous (n?=?111) or allogeneic (n?=?51) HCT between 2004 and 2014. The median overall survival (OS) rates were 48 and 65 months in the autologous and allogeneic HCT groups, respectively (P?=?0.20). Significant risk factors for overall survival in R/R MCL patients after autologous HCT were >?60 years of age at HCT (P?=?0.017), higher score of HCT-specific comorbidity index at HCT (P?=?0.033), and receiving MCEC (ranimustine?+?carboplatin?+?etoposide?+?cyclophosphamide) regimen (P?=?0.017), while higher performance status at HCT (P?=?0.011) and longer interval from diagnosis to HCT (P?=?0.0054) were risk factors after allogeneic HCT. Strategies that carefully select R/R MCL patients for autologous HCT may allow the identification of individuals suitable for allogeneic HCT.