Flow cytometry (FCM) is more sensitive than conventional cytology for detection of occult leptomeningeal lymphoma; however, some FCM-negative patients show central nervous system (CNS) recurrence. ...Here, we evaluated the cerebrospinal fluid (CSF) levels of 13 B-cell–associated markers and their contribution to the diagnosis of CNS lymphoma in 91 diffuse large B-cell lymphomas (DLBCL) and 22 Burkitt lymphomas (BLs). From all markers tested, CD19 was the most informative. Thus, higher soluble CD19 (sCD19) levels were associated with a greater frequency of neurological symptoms in DLBCL and BL and with parenchymal CNS lymphoma in DLBCL; sCD19 emerged as a powerful predictor of event-free and overall survival in DLBCL and BL, particularly when combined with FCM detection of CNS disease. These results support the utility of combined FCM detection of lymphoma cells and assessment of sCD19 levels in CSF, for more accurate identification of CNS disease in DLBCL and BL patients.
•Increased levels of sCD19 protein in the CSF are associated with CNS disease in DLBCL and BL patients at risk of CNS lymphoma.•Presence of lymphoma cells by FCM and/or increased CSF sCD19 levels are related with a poorer EFS and/or OS in DLBCL and BL patients.
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•Three new tetranuclear Al, Ga, Zn complexes of polynucleating N,O ligand were prepared.•Al complex shows highest activity in the ring-opening polymerization of rac-lactide for this ...family of catalysts.•Polylactide obtained was predominantly isotactic when Al complex was used as catalyst.•Cooperativity between metal centers in the ring-opening polymerization of rac-lactide was not observed.
A polynucleating ligand (L-H4) containing four N,O bidentate sites was cleanly metallated by four equivalents of AlMe3, GaMe3 and ZnEt2 resulting in tetranuclear complexes L(MMe2)4 (M = Al (1), Ga (2)) and L(ZnEt(CH3CN)0.5)4 (3). The Al complex shows the best catalytic activity for the ring-opening polymerization (ROP) of rac-lactide (rac-LA) in the present family of tetranuclear compounds. Polymerization studies indicate the lack of cooperativity between metal centers in the ROP of rac-LA, despite having a ligand platform which binds to four metal centers.
The circulation patterns in the confluence of the North Atlantic subtropical and tropical gyres delimited by the Cape Verde Front (CVF) were examined during a field cruise in summer 2017. We ...collected hydrographic data, dissolved oxygen (O2) and inorganic nutrients along the perimeter of a closed box embracing the Cape Verde Frontal Zone (CVFZ). The detailed spatial (horizontal and vertical) distribution of water masses, O2 and inorganic nutrients in the CVF was analyzed, allowing for the independent estimation of the transports of these properties in the subtropical and tropical domains down to 2000 m. Overall, at surface and central levels, a net westward transport of 3.76 Sv was observed, whereas at intermediate levels, a net 3 Sv transport northward was obtained. We observed O2 and inorganic nutrient imbalances in the domain consistent with O2 consumption and inorganic nutrient production by organic matter remineralization, resulting in a net transport of inorganic nutrients to the ocean interior by the circulation patterns.
To develop a predictive model based on inflammatory gene mRNA expression in conjunctival cells of graft versus host disease (GvHD)-associated dry eye (DE) patients, as well as to find meaningful ...correlations between gene signals and clinical signs.
Twenty GvHD-DE patients and 14 healthy controls were recruited. Patients discontinued medications for 1 week before examination. Dry eye-related symptoms and signs were recorded, and conjunctival epithelial cells were collected by impression cytology after spending 20 minutes under standard conditions within a Controlled Environmental Research Laboratory. Gene expression of inflammatory molecules was determined by polymerase chain reaction, and the results were correlated with clinical signs. Shrinkage discriminant analysis, support vector machine, and k-nearest neighbor classifier methods were used to develop predictive models that were validated considering accuracy, calibration, and discriminant capability.
Out of the 84 genes analyzed, 34 showed significant differences in expression. IL-6, IL-9, CCL24, CCL18, IL-10, IFN-γ, and CCL2 were highly increased (>6-fold); 26 genes were moderately upregulated (2- to 6-fold), whereas EGFR was downregulated (2.63 fold) in GvHD-DE samples. A panel based on EGFR, IL-6, IL-9, and NAMPT had an area under the receiver operating characteristic curve of 0.994, a sensitivity of 100%, and a specificity of 92.9%. EGFR expression correlated negatively with ocular surface damage markers, while IL-6, IL-9, and NAMPT correlated positively with these tests.
EGFR, IL-6, IL-9, and NAMPT have the greatest potential as diagnostic biomarkers, with excellent sensitivity, specificity, and clinical relevance to the ocular surface status of GvHD.
Patients with chronic lymphocytic leukemia (CLL) and 17p deletion (17p-) have a poor prognosis. Although allogeneic hematopoietic stem-cell transplantation (HCT) has the potential to cure patients ...with advanced CLL, it is not known whether this holds true for patients with 17p-CLL.
Baseline data from patients, for whom information on the presence of 17p-CLL was available, were downloaded from the European Group for Blood and Marrow Transplantation database. Additional information on the course of CLL and follow-up was collected with a questionnaire.
A total of 44 patients with 17p-CLL received allogeneic HCT between March 1995 and July 2006 from a matched sibling (n = 24) or an alternative donor (n = 20). 17p-CLL had been diagnosed by fluorescent in situ hybridization in 82% of patients and by conventional banding in 18% of patients. The median age was 54 years. Before HCT, a median of three lines of chemotherapy had been administered. At HCT, 53% of patients were in remission. Reduced-intensity conditioning was applied in 89% of patients. Acute, grade 2 to 4 graft-versus-host disease (GVHD) occurred in 43% of patients, and extensive chronic GVHD occurred in 53% of patients. At last follow-up, 19 patients were alive, with a median observation time of 39 months (range, 18 to 101 months). Three-year overall survival and progression-free survival rates were 44% and 37%, respectively. The cumulative incidence of progressive disease at 4 years was 34%. No late relapse occurred in nine patients with a follow-up longer than 4 years.
Allogeneic HCT has the potential to induce long-term disease-free survival in patients with 17p-CLL.
Summary
The current study was designed to assess the safety and efficacy of bortezomib in combination with fludarabine and melphalan as reduced intensity conditioning before allogeneic stem cell ...transplantation in patients with high risk multiple myeloma. Sixteen patients were evaluable. The median number of previous line of treatment was 3; all patients had relapsed following a prior autograft and 13 had previously received bortezomib. Fifteen of them either remained stable or improved disease status at day +100 post‐transplant, including 11 patients with active disease. More specifically, nine patients (56%) and five patients (31%) reached complete remission and partial response, respectively. 25% developed grade III acute graft‐versus‐host disease. The cumulative incidence of non‐relapse mortality, relapse and overall survival were 25%, 54% and 41%, respectively, at 3 years. Regarding the non‐haematological toxicity (grade>2), two patients developed peripheral neuropathy, two patients liver toxicity and 1 pulmonary toxicity early post‐transplant. The haematological toxicity was only observed during the first three cycles mostly related to low haemoglobin and platelet levels. The current trial is the first one evaluating the safety and efficacy of bortezomib as part of a reduced intensity conditioning regimen among patients with high risk multiple myeloma.
1 BMT Unit, Bristol Childrens Hospital, UK
2 Clinical Hematology Division, Hospital Santa Creu i Sant Pau, Barcelona, Spain
3 Lymphoma Working Party of the EBMT, Barcelona, Spain
4 Department of ...Hematology, Nottingham City Hospital, UK
5 Hematology Service, Hospital Clínico, Salamanca, Spain
6 Department of Hematology, Ospedale San Martino, Genova, Italy
7 Servicio Hematologia, Hospital U. Marques de Valdecilla, Santander, Spain
8 Department of Hematology, St Jamess University Hospital, Leeds, UK
9 Department of Hematology, Royal Liverpool University Hospital, UK
10 Department of Hematology, Hôpital St. Louis, Paris, France
11 Institute of Hematology and Medical Oncology, Bologna University, Italy
12 Department of Hematology, Ospedale di Careggi, Firenze, Italy
13 BMT Unit, Hôpital E. Herriot, Lyon, France
14 Christie Hospital, Manchester, UK
15 Department of Hematology, University Hospital Gasthuisberg, Leuven, Belgium
16 Department of Internal Medicine, Hôpitaux Universitaires de Geneve, Geneva, Switzerland
17 Department of Hematology, University of Birmingham, UK and
18 Department of Hematology, AK-St Georg, Hamburg, Germany
Correspondence: Stephen Paul Robinson, BMT Unit, Bristol Childrens Hospital, Upper Maudlin Street, Bristol BS2 8BJ, United Kingdom. E-mail: stephen.robinson{at}ubht.swest.nhs.uk
Background: The role of reduced intensity conditioning allogeneic stem transplantation (RICalloSCT) in the management of patients with Hodgkins lymphoma remains controversial.
Design and Methods: To further define its role we have conducted a retrospective analysis of 285 patients with HL who underwent a RICalloSCT in order to identify prognostic factors that predict outcome. Eighty percent of patients had undergone a prior autologous stem cell transplantation and 25% had refractory disease at transplant.
Results: Non-relapse mortality was associated with chemorefractory disease, poor performance status, age >45 and transplantation before 2002. For patients with no risk factors the 3-year non-relapse mortality rate was 12.5% compared to 46.2% for patients with 2 or more risk factors. The use of an unrelated donor had no adverse effect on the non-relapse mortality. Acute graft versus host disease (aGVHD) grades II–IV developed in 30% and chronic GVHD in 42%. The development of cGVHD was associated with a lower relapse rate. The disease progression rate at one and five years was 41% and 58.7% respectively and was associated with chemorefractory disease and extent of prior therapy. Donor lymphocyte infusions were administered to 64 patients for active disease of whom 32% showed a clinical response. Eight out of 18 patients receiving donor lymphocyte infusions alone had clinical responses. Progression-free and overall survival were both associated with performance status and disease status at transplant. Patients with neither risk factor had a 3-year PFS and overall survival of 42% and 56% respectively compared to 8% and 25% for patients with one or more risk factors. Relapse within six months of a prior autologous transplant was associated with a higher relapse rate and a lower progression-free.
Conclusions: This analysis identifies important clinical parameters that may be useful in predicting the outcome of RICaIICalloSCT in Hodgkins lymphoma.
Key words: Hodgkins lymphoma, allogeneic transplantation, prognosis.
This phase II clinical trial evaluated the efficacy, safety and pharmacokinetics of plitidepsin 3.2 mg/m(2) administered as a 1-hour intravenous infusion weekly on days 1, 8 and 15 every 4 weeks in ...67 adult patients with relapsed/refractory aggressive non-Hodgkin's lymphoma. Patients were divided into two cohorts: those with non-cutaneous peripheral T-cell lymphoma (n=34) and those with other lymphomas (n=33). Efficacy was evaluated using the International Working Group criteria (1999). Of the 29 evaluable patients with non-cutaneous peripheral T-cell lymphoma, six had a response (overall response rate 20.7%; 95% confidence interval, 8.0%-39.7%), including two complete responses and four partial responses. No responses occurred in the 30 evaluable patients with other lymphomas (including 27 B-cell lymphomas). The most common plitidepsin-related adverse events were nausea, fatigue and myalgia (grade 3 in <10% of cases). Severe laboratory abnormalities (lymphopenia, anemia, thrombocytopenia, and increased levels of transaminase and creatine phosphokinase) were transient and easily managed by plitidepsin dose adjustments. The pharmacokinetic profile did not differ from that previously reported in patients with solid tumors. In conclusion, plitidepsin monotherapy has clinical activity in relapsed/refractory T-cell lymphomas. Combinations of plitidepsin with other chemotherapeutic drugs deserve further evaluation in patients with non-cutaneous peripheral T-cell lymphoma. (clinicaltrials.gov identifier: NCT00884286).
Chronic graft-versus-host disease (cGVHD) remains a major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Aim is to identify risk factors for the ...development of cGVHD in a multicenter setting. Patients transplanted between 2000 and 2006 were analyzed (
n
= 820). Donors were HLA-identical siblings (57%), matched unrelated donors (30%), and HLA-A, B or DR antigen mismatched (13%). Reduced intensity conditioning (RIC) was given to 65% of patients. Overall incidence of cGVHD was 46% for patients surviving more than 100 days after HSCT (
n
= 747). Older patient age HR 1.15,
p
< 0.001, prior acute GVHD 1.30,
p
= 0.024, and RIC 1.36,
p
= 0.028 increased overall cGVHD. In addition, RIC 4.85,
p
< 0.001, prior aGVHD 2.14,
p
= 0.001 and female donor to male recipient 1.80,
p
= 0.008 increased the risk of severe cGVHD. ATG had a protective effect for both overall 0.41,
p
< 0.001 and severe cGVHD 0.20,
p
< 0.001. Relapse-free survival (RFS) was impaired in patients with severe cGVHD. RIC, prior aGVHD, and female-to-male donation increase the risk of severe cGVHD. ATG reduces the risk of all grades of cGVHD without hampering RFS. GVHD prophylaxis may be tailored according to the risk profile of patients.
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