Patients with acquired brain injury (ABI) may present physical, cognitive, and/or behavioral problems that may impact driving ability. In Western countries, on-road training conducted in real traffic ...conditions has been identified as an important aspect of driver rehabilitation for the ABI patients who showed some problems on on-road driving assessment. In Japan, however, the intervention of on-road training has not been conducted. The authors have developed the system of on-road driving training in Koriyama district. So far 31 patients with ABI received the training lessons. Thirty patients passed the on-road reassessment after 2 to 10 lessons and successfully returned to drive. Preliminary follow-up survey revealed that their driving performance was comparable with that of those who passed the initial on-road assessment. Little evidence, however, as to the efficacy of on-road driving training has been established. Further investigation of the full randomized controlled trial should be necessary.
Purpose
Diffuse large B‐cell lymphoma (DLBCL), the most common non‐Hodgkin lymphoma, is a heterogeneous lymphoma with different clinical manifestations and molecular alterations, and several markers ...are currently being measured routinely for its diagnosis, subtyping, or prognostication by immunohistochemistry (IHC). Here, the utility of a reverse‐phase‐protein‐array (RPPA) as a novel supportive tool to measure multiple biomarkers for DLBCL diagnosis is validated.
Experimental design
The expression of seven markers (CD5, CD10, BCL2, BCL6, MUM1, Ki‐67, and C‐MYC) is analyzed by RPPA and IHC using 37 DLBCL tissues, and the correlation between the two methods is determined. To normalize tumor content ratio in the tissues, the raw RPPA values of each marker are adjusted by that of CD20 or PAX‐5.
Results
The CD20‐adjusted data for CD5, MUM1, BCL2, Ki‐67, and C‐MYC has better correlation with IHC results than PAX‐5‐adjusted data. Receiver operating characteristic (ROC) analysis reveals that CD5, MUM1, BCL2, and C‐MYC exhibit a better sensitivity and specificity >0.750. Furthermore, the CD20‐adjusted C‐MYC value strongly correlates with that of IHC, and has a particularly high specificity (0.882).
Conclusions and clinical relevance
Although further investigation using a large number of DLBCL specimens needs to be conducted, these results suggest that RPPA could be applicable as a supportive tool for determining lymphoma prognosis.
We evaluated the kinetics of immune reconstitution (IR) after allogeneic hematopoietic cell transplantation (HSCT) and analyzed the clinical effect of IR on posttransplant outcomes. Absolute ...lymphocyte and its subset counts were measured using flow cytometry on days 28, 100, 180, 365, and 730 after transplantation in 358 adult patients who underwent HSCT between 2009 and 2017. On day 100 after HSCT, 310 surviving patients were analyzed. Bone marrow transplantation (BMT), peripheral blood stem cell transplantation (PBSCT), and cord blood transplantation (CBT) were performed in 119, 55, and 136 patients, respectively. Mature B-cell and differentiated natural killer (NK) cell subset counts significantly increased after CBT. The 2-year overall survival (OS), nonrelapse mortality (NRM), cumulative incidence of relapse, and chronic GVHD in BMT, PBSCT, and CBT were 62%, 67%, and 76% (P = .021); 17%, 17%, and 13% (P = .82); 33%, 40%, and 27% (P = .063); and 43%, 45%, and 28% (P = .025), respectively. Multivariate analysis showed that higher CD16+CD57− NK cell counts correlated with lower disease relapse, whereas higher CD20+ B-cell counts correlated with lower NRM. OS-favoring factors were higher CD16+CD57− NK cell count (hazard ratio, 0.36; 95% confidence interval, 0.22-0.60; P < .001) and CD20+ B-cell count (hazard ratio, 0.53; 95% confidence interval, 0.30-0.93; P < .001) and lower Disease Risk/HCT-Specific Comorbidity index score. Collective contribution of graft source-specific and event-related immune reconstitution might yield better posttransplant outcomes in CBT.
•NK cell IR robustness leads to lower disease recurrence, whereas CD20+ B cells and CD8+CD11b− T cells lead to lower NRM.•Collective contributions of posttransplant event-related IR and graft source type might yield better posttransplant outcomes in CBT.
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Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive T-cell lymphoma. A 63-year-old man was diagnosed with AITL. He received 6 cycles of CHOP therapy, but showed progressive disease. ...Subsequently, he received ESHAP chemotherapy; however, it was not effective. He received mogamulizumab (an anti-CCR4 monoclonal antibody). After 4 cycles, his respiratory condition worsened and he was diagnosed with cytomegalovirus (CMV) pneumonia. Despite antiviral and antibiotic therapy, he died. We speculate that the combination of progressive lymphoma with mogamulizumab and chemotherapy likely caused CMV pneumonia. Because mogamulizumab therapy causes immunosuppression, if CMV pneumonia is suspected, then rapid treatment should be initiated.
Objective: Useful prognostic biomarkers for diffuse large B-cell
lymphoma (DLBCL) patients have been reported. To determine the
prognostic value of hemoglobin (Hb) level in DLBCL patients, we
...performed a retrospective study.
Materials and Methods: We evaluated disease outcome, progressionfree
survival (PFS), overall survival as the endpoint, and clinical and
laboratory factors affecting the outcome of 185 DLBCL patients who
had received rituximab, cyclophosphamide, doxorubicin, vincristine,
and prednisolone therapy during 2004-2014.
Results: The study group included 121 men and 64 women with a
median age of 66 years minimum-maximum: 21-83 years. In univariate
analysis, factors independently associated with worse PFS were Eastern
Cooperative Oncology Group performance status ≥2, Ann Arbor stage III
or IV, anemia with Hb levels of <10 g/dL, and serum albumin of <3.5 g/
dL. In multivariate analysis, anemia with Hb levels of <10 g/dL and Ann
Arbor stage III or IV were found to be international index-independent
prognostic factors (hazard ratio: 2.4; p=0.04).
Conclusion: Anemia is an independent prognostic marker of poor
outcome in DLBCL patients. Hb can be an easily available prognostic
marker for risk stratification in these patients.
Central nervous system (CNS) events, including CNS relapse and progression to CNS, are known to be serious complications in the clinical course of patients with lymphoma. This study aimed to evaluate ...the risk of CNS events in patients with diffuse large B‐cell lymphoma in the rituximab era. We performed a retrospective survey of Japanese patients diagnosed with diffuse large B‐cell lymphoma who underwent primary therapy with R‐CHOP chemoimmunotherapy between September 2003 and December 2006. Patients who had received any prophylactic CNS treatment were excluded. Clinical data from 1221 patients were collected from 47 institutions. The median age of patients was 64 years (range, 15–91 years). We noted 82 CNS events (6.7%) and the cumulative 5‐year probability of CNS events was 8.4%. Patients with a CNS event demonstrated significantly worse overall survival (P < 0.001). The 2‐year overall survival rate after a CNS event was 27.1%. In a multivariate analysis, involvement of breast (relative risk RR 10.5), adrenal gland (RR 4.6) and bone (RR 2.0) were identified as independent risk factors for CNS events. We conclude that patients with these risk factors, in addition to patients with testicular involvement in whom CNS prophylaxis has been already justified, are at high risk for CNS events in the rituximab era. The efficacy and manner of CNS prophylaxis in patients for each involvement site should be evaluated further. (Cancer Sci 2012; 103: 245–251)
A soluble form of suppression of tumorigenicity 2 (sST2) has emerged as a biomarker for acute graft-versus-host disease (GVHD) and non-relapse mortality (NRM). We prospectively monitored sST2 levels ...during the early phase of hematopoietic stem cell transplantation (HSCT) and evaluated the clinical association with transplant-related complications including acute GVHD.
Thirty-two adult Japanese patients who received a first allogeneic HSCT were enrolled in this study. Levels of sST2 were measured at fixed time points (pre-conditioning, day 0, day 14, day 21, and day 28).
The median age was 50.5 years (range=16-66). With a median follow-up of 21.5 months (range=0.9-35.4), 9 patients developed grade II-IV acute GVHD. Median sST2 levels on the day of HSCT were higher than baseline and reached the maximum value (92.7 ng/mL; range=0-419.7) on day 21 after HSCT. The optimal cut-off value of sST2 on day 14 for predicting grade II-IV acute GVHD was determined as 100 ng/mL by ROC analysis. The cumulative incidence of acute GVHD was 56.7% and 16.5% in the high- and low-sST2 groups, respectively (p<0.01). Multivariate analyses showed that high sST2 levels at day 14 were associated with a higher incidence of acute GVHD (hazard ratio=9.35, 95% confidence interval=2.92-30.0, p<0.01). The cumulative incidence of NRM was increased in the highs-ST2 group (33% vs 0%, p<0.01), but all the patients died of non-GVHD complications. Among 6 patients in the high-sST2 group without grade II-IV GVHD, 5 patients developed veno-occlusive disease (VOD) and one also had thrombotic microangiopathy (TMA).
The early assessment of sST2 after HSCT yielded predictive values for the onset of acute GVHD and other transplant-related complications including VOD and TMA.
Central nervous system (CNS) involvement is a serious complication in patients with diffuse large B-cell lymphoma (DLBCL) and evaluating CNS risk is an important issue. Using the standard ...international prognostic index (IPI) and CNS-IPI, a recently proposed model including IPI risk factors and adrenal/kidney involvement, we assessed CNS risk in 1220 untreated DLBCL patients who received R-CHOP without prophylaxis. According to the standard IPI, the cumulative incidences of CNS involvement at 2 years were 1.3, 4.6, 8.8, and 12.7% in the low-, low-intermediate-, high-intermediate-, and high-risk groups, respectively (p <.001). This result is comparable with that of the CNS-IPI. Patients with breast involvement tended to have lower risk according to the standard IPI but showed frequent CNS involvement, similar to patients with testis involvement. The standard IPI is also a useful predictor of CNS involvement. Patients with breast/testis involvement would be candidates for prophylaxis regardless of the standard IPI risk.
We performed a retrospective analysis of DLBCL with breast involvement to compare the prognosis of primary breast lymphoma (PBL) to secondary breast lymphoma (SBL; especially in limited stage cases). ...We retrospectively reviewed records of 25 diffuse large B-cell lymphoma (DLBCL) patients with breast involvement who received chemotherapy between January 2000 and August 2012. We compared clinical features and prognosis among patients with PBL (
n
= 11), limited stage SBL (LSBL;
n
= 6), and advanced stage SBL (ASBL,
n
= 8). The PBL group had significantly lesser patients with breast tumours (BTs) > 5 cm than the SBL group (
P
= 0.02). After a median follow-up of 71.3 months, we observed significantly better 5-year overall survival (OS) in the PBL group (90.0%) than in the LSBL (33.3%,
P
= 0.01) group, but not for progression-free survival (PFS). Patients with BT > 5 cm had worse OS (
P
= 0.01) and PFS (
P
= 0.04) than those with BT ≤ 5 cm. PBL had a better prognosis than SBL among limited stage DLBCL.
Objective Fludarabine plus melphalan (FM) and fludarabine plus busulfan (FB) are two major conditioning regimens for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methods We ...retrospectively analyzed patients who underwent allo-HSCT after a conditioning regimen consisting of FM or FB with/without total body irradiation for hematological malignancies between 2005 and 2014. Results There were 41 patients who met the criteria. The median follow-up time for the survivors was 3 years. Thirty-two patients received allo-HSCT after the FM regimen and nine patients received allo-HSCT after the FB regimen. Patients who received FB were older than those who received FM (p=0.041). There was no significant difference in the 3-year overall survival between patients who had received FB and those who had received FM (29.6% vs. 56.5%, p=0.267). The 3-year cumulative incidence of relapse was significantly higher in patients who had received FB than that in patients who had received FM (66.7% vs. 17.8%, p=0.004), and FB was an independent prognostic factor for relapse by a multivariate analysis (hazard ratio, 9.8; 95% confidential interval, 2.5-39.3; p=0.001). When we restricted the evaluation to patients with acute myeloid leukemia and myelodysplastic syndrome, the 3-year cumulative incidence of relapse was also significantly higher in patients who had received FB than that in patients who had received FM (75.0% vs. 16.1%, p=0.004). Conclusion The results suggest that FM may provide better disease control than FB.
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