A phase II dose-escalation trial was conducted to ascertain low-dose thalidomide safety and response in patients with advanced myelofibrosis with myeloid metaplasia (MMM).
Thalidomide was ...administered together with current therapy to 63 patients, starting at 50 mg daily and increasing to 400 mg as tolerated.
Half of the patients sustained daily doses more than 100 mg and the drop-out rate was 51% at 6 months: the drop-out rate was lower in patients with high baseline fatigue score. At efficacy analysis, anemia was ameliorated in 22% of the patients and transfusions were eliminated in 39% of transfusion-dependent patients. Platelet count increased by 50 x 10(9)/L or more in 22% of patients with an initial count lower than 100 x 10(9)/L. Splenomegaly decreased by more than 50% of the initial size in 19% of patients. Reduction of an overall disease severity score occurred in 31% of patients and was associated with a significant reduction of fatigue. Disease severity amelioration was independently predicted by a high baseline myeloproliferative index (ie, large splenomegaly, thrombocytosis, or leukocytosis).
Low-dose thalidomide displays an acceptable toxicity profile and provides an objective and subjective advantage to a relevant portion of MMM patients.
* Laboratoire dHématologie,
° Service dHématologie Clinique
# Service de Chirurgie Cardio-Vasculaire
@ UMR CNRS 6101, CHU Dupuytren et Faculté de Médecine, Université de Limoges, France
...Correspondence: Jean Feuillard, Laboratoire d'Hématologie et UMR CNRS 6101, CHU Dupuytren, 2 Avenue Martin Luther King, 87042 Limoges Cedex, France. Phone: international +33.0555.056740. Fax: international +33.0555.056185. E-mail: jean.feuillard{at}chu-limoges.fr
Using a very simple flow cytometry protocol, we found that CD36 and CD117 on granulocytes and CD56 on monocytes were the major bone marrow phenotypic aberrations in patients with myelodysplasia, including CMML. CD56 on monocytes was associated with CMML. Importantly, phenotypic aberrations were lost on blood cells, except for CD56.
We treated 5 patients with polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome and multifocal bone lesions or diffuse bone marrow plasmacytic ...infiltration with high-dose therapy (HDT) and autologous blood stem cell transplantation. In all cases, the treatment produced remission of plasma cell proliferation associated with marked improvement in the patients' performance status, neurologic symptoms, and other manifestations of the syndrome. HDT with stem cell support should be investigated further as a therapeutic option in patients with POEMS syndrome and disseminated plasma cell dyscrasia.
mPGES-1 in leukemic cells of AML patients Rouaud, Pauline; Guerin, Estelle; Bordessoule, Dominique ...
International journal of hematology,
2012/1, Letnik:
95, Številka:
1
Journal Article
Abstract
Hepatocyte growth factor (HGF) is a pro-angiogenic cytokine activated by tissue-type plasminogen activator (tPA) that might play a role in the progression of multiple myeloma (MM). ...Preliminary studies indicated that serum HGF levels were higher in patients with AL amyloidosis (AL) compared to those with MM. The aim of the present study was to determine whether HGF is a relevant marker of diagnosis and prognosis in AL. HGF serum levels were measured at diagnosis in patients with monoclonal gammopathy (MG) without AL (76 controls), or with biopsy-proven systemic AL (69 patients). HGF serum levels were significantly higher in patients with AL compared to controls, respectively, 11.2 ng/mL min: 0.95-max: 200.4 versus 1.4 ng/mL min: 0.82-max: 6.2 (p < 0.0001). The threshold value of 2.2 ng/mL conferred optimal sensitivity (88%) and specificity (95%) to differentiate AL and monoclonal gammopathy of undetermined significance (MGUS) patients. Serum HGF concentrations were correlated positively with the severity of cardiac involvement and the serum level of monoclonal light chains. These data suggest that HGF measurement could be used in patients with MG to detect AL or to reinforce a clinical suspicion of AL and to guide indications for diagnostic tissue biopsies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Introduction. FibroScan, a non-invasive tool for measuring liver stiffness (LS), is not specific to liver fibrosis. Other extra-hepatic conditions may modify the LS value.
Objectives. Our aim was to ...examine whether amyloid deposition in the liver may modify LS.
Methods. LS was measured prospectively in 41 patients with systemic AL amyloidosis (AL) in the French AL Reference Center, comprising: 5 patients with liver involvement (LI) and no cardiac involvement (CI), 11 with CI and no LI, 12 with both LI and CI and 13 with neither (2005 consensus criteria); 26 negative controls, 50 patients infected with Hepatitis C virus (HCV)-infected and 18 AL-free patients with right-sided heart disease ('cardiac controls') were also examined.
Results. Median LS was significantly higher in patients with AL with liver involvement 27.4 (10.3-75) kPa than in negative controls 4.8 (2.8-11.9) kPa (p < 0.0001), and patients infected with HCV (6.8 (2.9-69.1) kPa (p = 0.001), and tended to be higher than in the 'cardiac controls' 11 (4.1-75) kPa (p = 0.08). A cut-off value of 17.3 kPa, prioritising specificity, is proposed for routine diagnosis of significant AL liver infiltration.
Conclusion. LS > 17.3 kPa is suggestive of AL hepatic disease in patients with non-fibrotic liver changes, and may have diagnostic value in patients with known AL.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Admission of patients with hematological malignancies to intensive care unit (ICU) raises recurrent ethical issues for both hematological and intensivist teams. The decision of transfer to ICU has ...major consequences for end of life care for patients and their relatives. It also impacts organizational human and economic aspects for the ICU and global health policy. In light of the recent advances in hematology and critical care medicine, a wide multidisciplinary debate has been conducted resulting in guidelines approved by consensus by both disciplines. The main aspects developed were (i) clarification of the clinical situations that could lead to a transfer to ICU taking into account the severity criteria of both hematological malignancy and clinical distress, (ii) understanding the process of decision-making in a context of regular interdisciplinary concertation involving the patient and his relatives, (iii) organization of a collegial concertation at the time of the initial decision of transfer to ICU and throughout and beyond the stay in ICU. The aim of this work is to propose suggestions to strengthen the collaboration between the different teams involved, to facilitate the daily decision-making process, and to allow improvement of clinical practice.
Based on the encouraging activity and manageable safety profile observed in a phase 1 study, the ECHELON-2 trial was initiated to compare the efficacy and safety of brentuximab vedotin, ...cyclophosphamide, doxorubicin, and prednisone (A+CHP) versus cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) for the treatment of CD30-positive peripheral T-cell lymphomas.
ECHELON-2 is a double-blind, double-dummy, randomised, placebo-controlled, active-comparator phase 3 study. Eligible adults from 132 sites in 17 countries with previously untreated CD30-positive peripheral T-cell lymphomas (targeting 75% with systemic anaplastic large cell lymphoma) were randomly assigned 1:1 to receive either A+CHP or CHOP for six or eight 21-day cycles. Randomisation was stratified by histological subtype according to local pathology assessment and by international prognostic index score. All patients received cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 on day 1 of each cycle intravenously and prednisone 100 mg once daily on days 1 to 5 of each cycle orally, followed by either brentuximab vedotin 1·8 mg/kg and a placebo form of vincristine intravenously (A+CHP group) or vincristine 1·4 mg/m2 and a placebo form of brentuximab vedotin intravenously (CHOP group) on day 1 of each cycle. The primary endpoint, progression-free survival according to blinded independent central review, was analysed by intent-to-treat. This trial is registered with ClinicalTrials.gov, number NCT01777152.
Between Jan 24, 2013, and Nov 7, 2016, 601 patients assessed for eligibility, of whom 452 patients were enrolled and 226 were randomly assigned to both the A+CHP group and the CHOP group. Median progression-free survival was 48·2 months (95% CI 35·2–not evaluable) in the A+CHP group and 20·8 months (12·7–47·6) in the CHOP group (hazard ratio 0·71 95% CI 0·54–0·93, p=0·0110). Adverse events, including incidence and severity of febrile neutropenia (41 18% patients in the A+CHP group and 33 15% in the CHOP group) and peripheral neuropathy (117 52% in the A+CHP group and 124 55% in the CHOP group), were similar between groups. Fatal adverse events occurred in seven (3%) patients in the A+CHP group and nine (4%) in the CHOP group.
Front-line treatment with A+CHP is superior to CHOP for patients with CD30-positive peripheral T-cell lymphomas as shown by a significant improvement in progression-free survival and overall survival with a manageable safety profile.
Seattle Genetics Inc, Millennium Pharmaceuticals Inc, a wholly owned subsidiary of Takeda Pharmacuetical Company Limited, and National Institutes of Health National Cancer Institute Cancer Center.
Extranodal NK/T-cell lymphoma, nasal type, is a rare and highly aggressive disease with a grim prognosis. No therapeutic strategy is currently identified in relapsing patients. We report the results ...of a French prospective phase II trial of an L-asparaginase-containing regimen in 19 patients with relapsed or refractory disease treated in 13 centers. Eleven patients were in relapse and 8 patients were refractory to their first line of treatment. L-Asparaginase–based treatment yielded objective responses in 14 of the 18 evaluable patients after 3 cycles. Eleven patients entered complete remission (61%), and only 4 of them relapsed. The median overall survival time was 1 year, with a median response duration of 12 months. The main adverse events were hepatitis, cytopenia, and allergy. The absence of antiasparaginase antibodies and the disappearance of Epstein-Barr virus serum DNA were significantly associated with a better outcome. These data confirm the excellent activity of L-asparaginase–containing regimens in extranodal NK/T-cell lymphoma. L-Asparaginase–based treatment should thus be considered for salvage therapy, especially in patients with disseminated disease. First-line L-asparaginase combination therapy for extranodal NK/T-cell lymphoma warrants evaluation in prospective trials. This trial is registered at www.clinicaltrials.gov as #NCT00283985.
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