The dosage of soluble programmed cell death ligand 1 (sPD-L1) protein in the blood of adults with cancer has never been performed in a prospective patient cohort. We evaluated the clinical impact of sPD-L1 level measured at the time of diagnosis for newly diagnosed diffuse large B-cell lymphoma (DLBCL). Soluble PD-L1 was measured in the plasma of 288 patients enrolled in a multicenter, randomized phase III trial that compared R-high-dose chemotherapy with R-CHOP. The median follow-up was 41.4 months. A cutoff of 1.52 ng/ml of PD-L1 level was determined and related to overall survival (OS). Patients with elevated sPD-L1 experienced a poorer prognosis with a 3-year OS of 76% versus 89% (P<0.001). Considering clinical characteristics, the multivariate analysis retained this biomarker besides bone marrow involvement and abnormal lymphocyte-monocyte score as independently related to poor outcome. sPD-L1 was detectable in the plasma and not in the serum, found elevated in patients at diagnosis compared with healthy subjects and its level dropped back to normal value after CR. The intention-to-treat analysis showed that elevated sPD-L1 was associated with a poorer prognosis for patients randomized within the R-CHOP arm (P<0.001). Plasma PD-L1 protein is a potent predicting biomarker in DLBCL and may indicate usefulness of alternative therapeutic strategies using PD-1 axis inhibitors.

Since 1986, we have treated young patients with aggressive multiple myeloma (MM) by high-dose chemotherapy (HDC) and total body irradiation (TBI) followed with autologous blood stem cell transplantation (ABSCT). To evaluate this strategy: 1) We conducted a phase II trial that included 63 patients. Within a median follow-up of five years after transplantation, overall survival was 60% and median event-free survival was four years, and 2) In the early 1990s, we initiated a prospective trial where, after collection of chemotherapy-mobilized ABSC, patients under 55 years of age with newly diagnosed MM were randomly assigned either to HDC and TBI supported with ABSCT (high-dose therapy [HDT] arm) or to a conventional vincristine, melphalan, cyclophosphamide and prednisone (VMCP) regimen (VMCP arm). In the latter, HDT with ABSCT was performed as a rescue therapy, in case of primary resistance to VMCP or at relapse in responders. As of June 1994, 167 patients have been enrolled since a median time of 26 months. Fourteen (8%) could not be randomized. Among the randomized patients (n = 153), 30 deaths were observed, 13 in the HDT group and 17 in the VMCP group (p = 0.28, two-sided log rank test). Overall survival rates at two years were estimated at 78% for all 167 patients, at 82% in the HDT group and at 67% in the VMCP group. ABSC, provided they are collected early in the disease course, allow a great majority of myeloma patients to receive HDT.(ABSTRACT TRUNCATED AT 250 WORDS)

Coronaviruses strains 229E and OC43 have been associated with various respiratory illnesses ranging from the self-resolving common cold to severe pneumonia. Although chronic underlying conditions are major determinants of severe respiratory virus infections, few data about coronavirus-related pneumonia in immunocompromised patients are available. Here we report 2 well-documented cases of pneumonia related to coronavirus 229E, each with a different clinical presentation. Diagnosis was made on the basis of viral culture and electron microscopy findings that exhibited typical crown-like particles and through amplification of the viral genome by reverse transcriptase-polymerase chain reaction. On the basis of this report, coronaviruses should be considered as potential causative microorganisms of pneumonia in immunocompromised patients.

Summary:To assess the place of allogeneic hematopoietic stem cell transplantation (HSCT) in the advanced stage of acute myeloid leukemia (AML), we retrospectively analyzed 379 consecutive patients who underwent allogeneic HSCT for advanced AML. The median follow-up of the entire cohort was 7.5 years. Sixty-nine patients (18%) were transplanted with primary resistant disease. Three hundred and ten (82%) were relapsed patients, 94 (30%) of whom were in untreated relapse, 67 (22%) in refractory relapse and 149 (48%) in 2nd or 3rd complete remission at time of transplantation. The 5-year probabilities of overall survival (OS), disease-free survival (DFS), and transplant-related mortality (TRM) were 22 ؎ 4% 20 ؎ 4%, 45 ؎ 6%, respectively. In multivariate analysis, we demonstrated the favorable impact on OS, DFS and TRM of two factors over which we have no control (age Ͻ15 years, complete remission achievement) and three factors over which we have some control (female donor, acute and chronic graftversus-host disease). The results of this study suggest that the graft-versus-leukemia effect is important in advanced AML and that new HSCT modalities are needed for some patients with this indication. Bone Marrow Transplantation (2000) 26, 1157-1163. Keywords: allogeneic; HSCT; advanced; AML The outcome of treatment in younger patients with de novo acute myeloid leukemia (AML) has improved substantially over the past decade. Complete remission (CR) rates range from 60% to 80% with long-term survival in about 50% of

Myelodysplastic syndromes are associated with a risk of severe infections. While neutropenia is likely to be the main predisposing factor, several other immune defects have been reported, including impaired neutrophil function, B-, T-and NK-cell defects and the possible consequences of iron overload due to red blood cell transfusions. The advanced age of most patients, their frequent comorbidities, and the fact that drugs such as hypomethylating agents and lenalidomide, which are effective in myelodysplastic syndromes but can transiently worsen neutropenia, may increase the risk of infection and their severity in this context. The majority of infections in myelodysplastic syndromes are bacterial, while the incidence of fungal infections is not well known and viral infections seem to be rare. No prophylactic measures against infections have demonstrated efficacy in myelodysplastic syndromes. However, pending more data, we propose here some recommendations for the management of patients with myelodysplastic syndromes. In the future, an important contribution can be made by prospective trials testing the efficacy of prophylactic and therapeutic approaches to infection in these patients, especially in the context of the new drugs available for myelodysplastic syndromes. ABSTRACTand respective bacterial, fungal, and viral causes of infection in MDS. Most of these data are retrospective. Some are compromised by inconsistencies in the definition of the infectious events or, although taken from therapeutic trials, may be biased by patient eligibility criteria. In a recent US retrospective series of 273 untreated low-or intermediate-1 risk MDS patients who died in the period from 1980 to 2004, infection was the primary cause of death, accounting for 38% of the total, followed by AML transformation (15%) and hemorrhage (13%).9 Pneumonia was the most common infection, responsible for 40% of infectious deaths. Infection, mostly of a bacterial origin, was microbiologically documented in 30% of the cases of pneumonia in these MDS patients. As this study covered three decades, it was possible to show a significant decrease in the incidence of infectious deaths over time, likely attributable to improved supportive care. Another US survey of the Medicare population (an insurance covering more than 97% of all US citizens aged 65 years or over) indicated that, in a population of 1.3 million people over the age of 65 years followed between the years 2003 and 2005, patients with MDS had a higher prevalence of infections than the non-MDS Medicare population (22.5% vs. 6.

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An inflammatory reaction could be an important source of intraindividual variability in cyclosporine pharmacokinetics, possibly through an inhibition of cytochrome P4503A-dependent enzyme activities by endogenous interleukin-6. Blood AM1 accumulation might be explained by a secondary metabolic step that is highly sensitive to the inhibitory effect of interleukin-6.

Summary An open‐label, phase II non‐randomised trial was conducted with darbepoetin (DAR), an erythropoiesis‐stimulating factor with prolonged half‐life, at a weekly dose of 300 μg subcutaneously in 62 anaemic patients with myelodysplastic syndrome (MDS) with an endogenous erythropoietin (EPO) level <500 mU/ml. Most of the patients were classified as low or intermediate 1 according to the International Prognostic Scoring System. After 12 weeks, 44 (71%) patients had an erythroid response (34 major and 10 minor), including eight of 13 patients who were previous non‐responders to conventional EPO. Two additional responses (one minor and one major) occurred, in 10 non‐responders, after the addition of granulocyte colony‐stimulating factor (G‐CSF). Thirty‐six of the 46 total responders (31/35 major and 5/11 minor) continued to respond on maintenance DAR after a median of 40 weeks (range 4–84). Median dose of DAR required to maintain response was 300 μg every 14 d. The only prognostic factors of favourable response were low endogenous EPO level and low or absent red blood cell transfusion requirement. Those results suggest that high‐dose DAR alone yields high erythroid response rates in anaemia of lower risk MDS, possibly equivalent to those obtained with conventional EPO + G‐CSF, although this will need to be confirmed in larger and randomised trials.