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) T he central nervous system (CNS) is thought to be a sanctuary for lymphoma cells from systemic chemoimmunotherapy, such as rituximab (R) plus CHOP (cyclophosphamide [CPA], doxorubicin [adriamycin, ADR], vincristine [VCR] and prednisolone [PSL]), because standard doses of these drugs do not adequately penetrate the CNS. Occurrence of a CNS event, defined as CNS relapse during systemic complete remission or CNS progression during concurrent systemic active lymphoma, is associated with extremely poor prognosis, with median survival of <6 months.(1-6) Many studies concerning CNS prophylaxis have been conducted; however, the efficacy of such prophylaxis in preventing CNS events is controversial. (5,(7)(8)(9)(10)(11)(12) The discrepancies between reports might be due to the differences in the various subtypes of lymphoma histology and the variability of treatment of CNS prophylaxis. (13)(14)(15)(16) In addition, R has had a substantial impact on outcomes in patients with diffuse large B-cell lymphoma (DLBCL).(17) It is thus necessary to re-evaluate the risk of CNS events in the R era.The present study comprises a multicenter retrospective analysis of patients with uniform DLBCL histology who have undergone uniform treatment with R-CHOP, widely accepted as the standard therapy in the R era. Patients who received any CNS prophylactic treatment, such as intrathecal chemotherapy, intraveneous high-dose methotrexate or whole brain irradiation, were excluded to evaluate the natural risk of CNS events in R-CHOP therapy. This study also took particular note of the evaluation ...

The incidence of CNS involvement does not decrease in rituximab-era.

We retrospectively studied the association between iron overload and bloodstream infections (BSI) in the 100-day period following allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia or myelodysplastic syndromes. Serum ferritin was measured before transplantation to evaluate iron overload. Of 114 adult patients who underwent transplantation between 2000 and 2008, 36 (32%) developed BSI. Of the 44 isolates, 63% were Gram-positive bacteria, 32% were Gram-negative bacteria, and 4% were fungi. The median time to the onset of the first BSI was day 28 (range day 0-95) after transplantation. Univariate analysis revealed a significantly higher incidence of BSI in the high (≥ 1,000 ng/ml, n = 57) than in the low (< 1,000 ng/ml, n = 57) ferritin group (42.1 versus 21.1%, respectively, P = 0.017). Peripheral blood stem cell transplantation (PBSCT) (n = 23) showed a greater protective effect against BSI compared with bone marrow (n = 71) and cord blood (n = 20) transplantation. Pretransplantation serum ferritin (HR = 2.844, 95% CI: 1.180-6.859, P = 0.020) and PBSCT (HR = 0.135, 95% CI: 0.025-0.717, P = 0.019) were significant factors on multivariate analysis. In conclusion, pretransplantation serum ferritin significantly predicts BSI within the 100-day period after allo-HSCT.

The maximum standard uptake value (SUVmax) of the whole body on 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) reflects the tumor aggressiveness in non-Hodgkin lymphoma (NHL). To clarify the correlation between SUVmax at the biopsy site and the proliferation potential of tumor cells, we studied 36 patients with untreated NHL and five with untreated Hodgkin lymphoma (HL) by measuring the Ki-67 proliferation index (MIB-1 labeling index) in biopsy specimens. The measured MIB-1 labeling index was categorized into seven levels: nearly 0%, 5-20%, 21-40%, 41-60%, 61-80%, 81-95%, and nearly 100%. Twenty-four lymph nodes (LNs) and 17 extranodal (EN) sites were biopsied. The reviewed diagnosis was eight indolent lymphomas, two mantle-cell lymphomas, 26 aggressive lymphomas, and five HLs. A positive correlation was observed between the SUVmax at the biopsy site and the MIB-1 labeling index in the 36 patients with NHL (r = 0.69, p < 0.001). The correlations were also observed in LN group (r = 0.60, p = 0.006) and EN group (r = 0.87, p < 0.001), respectively. In the five patients with HL, the MIB-1 labeling index was uniformly categorized in nearly 100%. The SUVmax correlates with the proliferation potential in the case of NHL.

The LMR at diagnosis, as a simple index which reflects host systemic immunity, predicts clinical outcomes in DLBCL patients treated with R-CHOP.