Three reports address the protection of the vulnerable population of patients with hematologic malignancies in the face of the ongoing COVID pandemic. The reports suggest that some patients who fail to mount a B-cell response to vaccine may nevertheless have protective T cell responses. As a group, these reports suggest that patients should continue to be immunized with additional doses to attempt to improve immune response but that they need to maintain the precautions recommended for the unvaccinated.

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The main problem encountered with serodiagnostic tests for Candida infections is their failure to differentiate between invasive and superficial candidosis. Recent immunoblotting studies suggested that the use of selective somatic proteins of Candida albicans as antigens might be a promising approach toward developing a new generation of serodiagnostic assays. In this study major cytoplasmic protein antigens with molecular weights of 47,000 (47K), 46,000 (46K), 45,000 (45K), and 29,000 (29K) were identified as potential marker antigens for antibody detection in invasive candidosis. Continuous-flow isoelectric focusing was employed to enrich the proteins in two fractions, one of them containing the 47K and 29K proteins and the other one containing predominantly the 47K and 45K major proteins. These antigens and a whole somatic antigen extract were used to establish enzyme immunoassays (EIAs) for antibody detection. Whereas all tests were able to discriminate between patients with invasive candidosis (n = 27) and normal healthy volunteers (n = 167), as proved by graphic marker analysis, the selective antigen EIAs were highly superior to the whole somatic antigen EIA and two serological standard assays (indirect immunofluorescence assay and indirect hemagglutination assay) when a panel of sera from patients with superficial candidosis (n = 34) was used as a negative control group. The use of the 47K-29K antigen fraction allowed the best differentiation between invasive and noninvasive candidosis. The corresponding immunoglobulin G class-specific EIA had a sensitivity of 81.5% and a specificity of 97% for both negative control groups as well.

For patients with diffuse large B cell lymphoma without the involvement of the CNS, the addition of rituximab to standard chemotherapy has significantly improved survival. In this single-center, retrospective analysis, a total of 81 primary CNS lymphoma (PCNSL) patients treated in our institution between 2000 and 2011 were included. Beside first-line chemotherapy with or without rituximab, we evaluated the impact of age (≤/>60 years), autologous stem cell transplantation (ASCT +/-), and other factors upon overall survival (OS) and progression-free survival (PFS). In patients treated with rituximab (n = 27), 3-year OS was 77.8 % (95 % confidence interval (CI) 62-93 %). In contrast, in patients treated without rituximab (n = 52), 3-year OS was only 39.9 % (CI 27-53 %, Fig. 1). The difference in OS was significant in the univariate (p = 0.002) as well as in the multivariate analysis (p = 0.049, hazard ratio (HR) = 0.248). Patients ≤60 years of age (n = 28) had a 3-year OS of 78.2 % (CI 63-94 %); in patients >60 years (n = 51), 3-year OS was 38.7 % (CI 25-52 %). Patients who received high-dose therapy and ASCT had a 3-year OS of 85.2 % (CI 72-99 %), and 65.1 % were alive up to the time of analysis (range 9-131 months). Without ASCT, median OS was only 16 months (CI 11-21) and 3-year OS was 35.2 % (CI 22-48 %). Age and ASCT were significantly associated with better OS in univariate (p = 0.002 and p < 0.001) as well in multivariate analysis (p = 0.004, HR = 0.023 and p = 0.001, HR = 0.014). Rituximab treatment, ASCT, and age are independent prognostic factors for OS in the first-line treatment of PCNSL.

Renal involvement in patients with lymphoma is rare but associated with poor prognosis. We analyzed characteristics and outcome of 22 patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL) and renal involvement treated with a rituximab-containing regimen in curative intent. The majority of patients presented in advanced disease, 86% were Ann Arbor stage ≥ III and had an IPI score ≥ 3. Renal impairment was present in 32%. Outcome was poor with three-year progression-free survival (PFS) 44% and three-year overall survival (OS) 52% and significantly worse compared to DLBCL without renal involvement (p < 0.01). Patients with high-risk IPI had a significantly inferior prognosis compared to intermediate-risk IPI (three-year OS 0% vs. 75%, p = 0.01) as did those with renal impairment. A high rate of central nervous system (CNS) relapse (8/22) was observed. Intravenous high-dose methotrexate and intrathecal therapy showed a trend toward prolonged time to CNS relapse. Implementation of CNS prophylaxis might therefore be considered in these high-risk patients.

BackgroundSkeletal involvement (SI) is observed at low prevalence in patients with diffuse large B-cell lymphoma (DLBCL). Due to the rareness of this particular condition, prospective trials for these patients are scarce.MethodsWe analyzed clinical characteristics and outcome of 75 patients with DLBCL and SI in order to identify factors with prognostic impact towards progression-free survival (PFS) and overall survival (OS).ResultsLimited stage disease (Ann Arbor stage IE-IIE) was present in 34 patients (45%), 41 patients (55%) had advanced stage disease (Ann Arbor stage IIIE-IVE). Outcome was generally favorable for patients with DLBCL and SI with 3-year OS of 83%. The international prognostic index (IPI) was able to distinguish between different risk groups within this specific entity. Additionally, hypercalcemia showed to be a factor significantly associated with inferior survival. In regard to first-line treatment modalities, consolidative radiotherapy was positively associated with prolonged PFS and OS while intensification of chemotherapy had no significant impact.ConclusionsIn our cohort of patients with DLBCL and SI, high-risk IPI as well as presence of hypercalcemia were associated with inferior outcome. Consolidative radiotherapy had a positive impact on survival.

PURPOSE of this analysis was to provide 10-year follow-up of the GCLLSG CLL3X trial which aimed at evaluating reduced-intensity conditioning (RIC) HSCT in patients with poor-risk CLL. DESIGN: The CLL3X trial included 100 patients (median age 53 (27-65) years), of whom 90 patients were allografted with blood stem cells from related (40%) or unrelated donors (60%) using fludarabine-alkylator-based RIC regimens. 24% had refractory CLL at HSCT, and 37% had a TP53 deletion and/or mutation. The 6-year follow-up of the trial including the observation that genetic risk factors such as TP53 lesions and SF3B1 and NOTCH1 mutations had no prognostic impact has been previously reported (Blood 2013;119:4851). Survival and relapse information was requested for all patients who underwent HSCT within the CLL3X trial in 9 German centres (the Canadian centre was unavailable for follow-up) and were alive at the 6-year follow-up. RESULTS: Follow-up information was received for 33/44 patients (75%) alive at the 6-year follow-up. Of these, 2 patients had experienced non-relapse mortality (NRM; 1 chronic GVHD, 1 secondary cancer) and another 2 had CLL recurrence 9.3 and 9.7 years post HSCT, respectively. With a median follow-up of survivors of 9.3 (0.6-15.5) years, 10-year NRM, relapse incidence (REL) event-free survival (EFS), and overall survival (OS) of all 90 patients allografted was 26%, 57%, 32%, and 51%, respectively. Absence of minimal residual disease (MRD) at the 12-month landmark post HSCT was highly predictive for an increased relapse risk (10-year REL 25% vs 80% if MRD was present at the 12-month landmark, p <0.0001), in particular if MRD eradication occurred only after immunosuppression withdrawal, suggesting of effective graft-versus-leukemia activity (GVL; 10-year REL 12%). In the 33 patients who were event-free at the 6-year landmark, NRM, REL, EFS, and OS 4 years after the 6-year landmark was 4%, 24%, 74%, and 93% (median follow-up after 6-year landmark 4.1 (0.1-8.5) years) without any effect of TP53 lesions on relapse risk. Notably, no relapse event occurred beyond 10 years post HSCT. Only one out of 33 patients included in the 6-year landmark analysis died from CLL, 4 relapsed patients are currently responding to pathway inhibitors, and the remaining patient with CLL recurrence still does not need treatment. CONCLUSIONS: Long-term observation of patients allografted in the CLL3X trial confirms that RIC HSCT can provide GVL-mediated sustained disease control in a sizable proportion of patients with poor-risk CLL independent of the TP53 status. Patients who are in MRD-negative remission one year after HSCT have a 75% probability of remaining disease-free at least for 10 years. However, late relapses do occur but may benefit from strategies involving innovative pathway inhibitors. Disclosures Krämer: Gilead: Other: Travel grants; MSD: Honoraria. Stilgenbauer:AbbVie: Consultancy, Honoraria, Other: Travel grants, Research Funding; Hoffmann-La Roche: Consultancy, Honoraria, Other: Travel grants , Research Funding; Janssen: Consultancy, Honoraria, Other: Travel grants , Research Funding; Novartis: Consultancy, Honoraria, Other: Travel grants , Research Funding; Genzyme: Consultancy, Honoraria, Other: Travel grants , Research Funding; Pharmacyclics: Consultancy, Honoraria, Other: Travel grants , Research Funding; Boehringer Ingelheim: Consultancy, Honoraria, Other: Travel grants , Research Funding; Amgen: Consultancy, Honoraria, Other: Travel grants, Research Funding; Genentech: Consultancy, Honoraria, Other: Travel grants , Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants , Research Funding; Mundipharma: Consultancy, Honoraria, Other: Travel grants , Research Funding; GSK: Consultancy, Honoraria, Other: Travel grants , Research Funding; Celgene: Consultancy, Honoraria, Other: Travel grants , Research Funding; Sanofi: Consultancy, Honoraria, Other: Travel grants , Research Funding. Böttcher:Hoffmann-LaRoche: Honoraria, Other: Travel grants, Research Funding; Celgene: Research Funding; AbbVie: Honoraria, Research Funding. Ritgen:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding. Hegenbart:Jansen Cilag: Honoraria, Other: financial support of conference participation. Hallek:F. Hoffmann-LaRoche: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Janssen-Cilag: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; Mundipharma: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau; AbbVie: Consultancy, Honoraria, Other: travel support, Research Funding, Speakers Bureau. Kneba:Amgen: Research Funding; Gilead: Consultancy, Honoraria, Other: Travel grants, Research Funding; Glaxo-SmithKline: Other: Travel grants; Roche: Consultancy, Honoraria, Other: Travel grants, Research Funding; AbbVie: Consultancy, Honoraria, Other: Travel grants; Janssen-Cilag: Consultancy, Honoraria, Other: Travel grants. Dreger:Gilead: Consultancy; Novartis: Consultancy; Gilead: Speakers Bureau; Novartis: Speakers Bureau; Janssen: Consultancy; Roche: Consultancy.