Risk factors for lower respiratory tract disease and outcomes in allogeneic hematopoietic stem cell transplantation recipients with influenza virus infection.

INTRODUCTION: Influenza virus infection (IVI) is frequent in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients, and reports from several countries indicate high morbidity and mortality from progression to lower respiratory tract disease (LRTD). However, there have been no reports on IVI clinical characteristics, treatment outcomes, and risk factor for progression to LRTD among allo-HSCT recipients in Japan. METHODS: We retrospectively reviewed the medical charts of allo-HSCT recipients who developed IVI between 2012 and 2019. RESULTS: Forty-eight cases of IVI following allo-HSCT were identified at our institution. The median age was 42 years, and median time from allo-HSCT to IVI was 25 months. Thirty-seven patients (77.1%) were administered neuraminidase inhibitors (NAIs) as antiviral therapy within 48 h of symptom onset (early therapy), whereas 11 (22.9%) received NAI over 48 h after onset (delayed therapy). Subsequently, 12 patients (25.0%) developed LRTD after IVI. Multivariate analysis identified older age (hazard ratio [HR], 7.65; 95% confidence interval [CI], 2.22-26.3) and bronchiolitis obliterans (HR, 5.74; 95% CI, 1.57-21.0) as independent risk factors for progression to LRTD. Moreover, land-mark analysis showed that early therapy prevented progression to LRTD (11.8% vs. 45.5%, P = 0.013). The IVI-related mortality rate was 2.1%. CONCLUSIONS: Early NAI treatment is recommended for reducing the risk of LRTD progression due to IVI in allo-HSTC recipients, particularly for older patients and those with bronchiolitis obliterans.

Composite Follicular Lymphoma and CD5-Positive Nodal Marginal Zone Lymphoma.

Composite CD10-positive low-grade B-cell and CD5-positive low-grade B-cell lymphoma is extremely rare. We report a case of a composite follicular lymphoma (FL) and CD5-positive nodal marginal zone lymphoma (NMZL) in a resected inguinal lymph node of a 72-year-old Japanese male. Histologically, multiple follicles had reactive-germinal centers with tingible body macrophages, a thin mantle zone and a wide marginal zone. The wide marginal zone consisted of medium-sized cells having slightly indented nuclei and clear cytoplasm, indicating monocytoid cells with CD5-positive B-cells. Several follicles had germinal centers filled with many centrocytes, with CD10-positive B-cells. Polymerase chain reaction/sequence analysis of the immunoglobulin heavy chain gene obtained from microdissected regions of CD5-positive NMZL and FL showed different sequences within the CDR3 region. To our knowledge, this is the first report of FL and CD5-positive NMZL.

Cladribine combined with rituximab (R-2-CdA) therapy is an effective salvage therapy in relapsed or refractory indolent B-cell non-Hodgkin lymphoma.

Although cladribine has been reported to be an active purine analog against indolent B-cell non-Hodgkin lymphoma (B-NHL), there are few reports of combination use of cladribine and rituximab. This multicenter phase II study evaluated the efficacy and toxicity of cladribine with rituximab (R-2-CdA) therapy in relapsed or refractory indolent B-NHL. Twenty patients with the median age of 58.5 yrs (range, 42-72) were enrolled and received R-2-CdA therapy from April 2005 to July 2007. The median number of prior regimens was 2 (range, 1-3), and fifteen patients (75%) were previously treated with rituximab-containing regimens. Disease histology included follicular lymphoma in 16 patients, MALT lymphoma in two patients, nodal marginal B-cell lymphoma in one patient, and lymphoplasmacytic lymphoma in one patient. The overall response rate (ORR) was 90%, with a complete response rate (CRR) of 70%. Estimated median progression-free survival (PFS) time was 22.4 months (95%CI, 10.9-32.6 months) at a median follow-up time of 27 months (range, 12-43). Two-year PFS and 2-yr overall survival (OS) were 52.6% (95%CI, 31.0-73.2%) and 89.5% (95%CI, 66.1-97.3%), respectively. Grade 3 or grade 4 toxicities were neutropenia in 74% and thrombocytopenia in 11%. R-2-CdA therapy was demonstrated to have a high activity with durable PFS and acceptable toxicity in relapsed or refractory indolent B-NHL mostly pretreated with rituximab-containing therapy. Although a large-scale trial is needed for confirmation, R-2-CdA therapy could be a good salvage therapy option in relapsed or refractory indolent B-NHL.

Prognostic analysis and a new risk model for Hodgkin lymphoma in Japan.

The Japan Clinical Oncology Group conducted two multicenter phase II trials in 200 patients with advanced Hodgkin lymphoma (HL) in the 1990s. Among 181 patients whose histopathological specimens were available and reviewed by 6 hematopathologists, 167 (92.3%) were diagnosed with HL. Five-year overall survival (OS) among these 167 patients was 88.3%, including 89.2% among nodular sclerosis and 82.2% among mixed cellularity cases. International prognostic score was not closely associated with OS. Seven unfavorable prognostic factors for OS on univariate analysis were male, B symptoms, clinical stage of III or IV, elevated serum LDH, elevated alkaline phosphatase, elevated beta2-microglobulin, and pathological subtype (mixed cellularity and lymphocyte depletion). On multivariate analysis, male [HR 3.30 (95% CI 1.15-9.52, p = 0.027)] and elevated serum LDH [HR 2.41 (95% CI 1.07-5.43, p = 0.034)] were independent factors for OS. Based on these prognostic factors, the 5-year OS was 95.7% in the low-risk group (no adverse factor), 87.9% in the intermediate-risk group (1 adverse factor) and 73.3% in the high-risk group (2 adverse factors). This simple prognostic model for HL warrants further validation studies.

Irinotecan hydrochloride for the treatment of recurrent and refractory non-Hodgkin lymphoma: a single institution experience.

BACKGROUND: Irinotecan hydrochloride (CPT-11) has a broad range of antitumor activity and has demonstrated little cross-resistance with doxorubicin or vincristine. In the current study, the authors investigated the efficacy and adverse effects of irinotecan in the treatment of recurrent and refractory non-Hodgkin lymphoma, for which current therapies appear to be unsatisfactory. METHODS: Irinotecan was administered by intravenous infusion at a dose of 40 mg/m(2)/day for 3 days, and this regimen was repeated 2-3 times at weekly intervals, followed by 2 weeks off therapy. The subjects were 48 patients with recurrent or refractory non-Hodgkin lymphoma. The histologic classification (Working Formulation) was low grade in 8 patients, intermediate grade in 36 patients, high grade in 1 patient, and other (angiocentric lymphoma, Ki-1 lymphoma, and unidentified) in 3 patients. RESULTS: Forty-five patients were determined to be evaluable. Therapy resulted in a complete disease remission in 2 patients and a partial remission in 15 patients. The response rate was 37.8%. The median duration of response was 64 days and the median time to disease progression was 77 days. The median survival time was 422 days. Major adverse reactions included myelosuppression and gastrointestinal toxicity. Leukopenia, anemia, and thrombocytopenia of Grade 3 or 4 (according to the National Cancer Institute Common Toxicity Criteria) was observed in 63.0%, 30.4%, and 6.5% of the patients, respectively, and Grade 3 or 4 diarrhea occurred in 30.4% of patients. Treatment was withdrawn because of diarrhea in three patients. Because of myelosuppression and diarrhea, approximately 67% of the patients required changes to the regimen, including dose reduction, prolongation of the interval between treatments, and reducing the number of days of consecutive treatment. CONCLUSIONS: The results of the current study suggest the activity of irinotecan as salvage therapy for patients with recurrent and refractory non-Hodgkin lymphoma. However, the optimum dosing schedule remains to be determined.