Oestrogen and Vibration Improve Intervertebral Disc Cell Viability and Decrease Catabolism in Bovine Organ Cultures.

Postmenopausal women are at an increased risk for intervertebral disc degeneration, possibly due to the decrease in oestrogen levels. Low-magnitude, high-frequency vibration (LMHFV) is applied as a therapeutic approach for postmenopausal osteoporosis; however, less is known regarding possible effects on the intervertebral disc (IVD) and whether these may be oestrogen-dependent. The present study investigated the effect of 17β-oestradiol (E2) and LMHFV in an IVD organ culture model.

Addition of Androgens Improves Survival in Elderly Patients With Acute Myeloid Leukemia: A GOELAMS Study.

Purpose Elderly patients with acute myeloid leukemia (AML) have a poor prognosis, and innovative maintenance therapy could improve their outcomes. Androgens, used in the treatment of aplastic anemia, have been reported to block proliferation of and initiate differentiation in AML cells. We report the results of a multicenter, phase III, randomized open-label trial exploring the benefit of adding androgens to maintenance therapy in patients 60 years of age or older.

A phase Ib GOELAMS study of the mTOR inhibitor RAD001 in association with chemotherapy for AML patients in first relapse.

The mTORC1 signaling pathway is constitutively activated in almost all acute myelogenous leukemia (AML) patients. We conducted a phase Ib trial combining RAD001 (everolimus), an allosteric inhibitor of mTORC1, and conventional chemotherapy, in AML patients under 65 years of age at first relapse (clinical trial NCT 01074086). Increasing doses of RAD001 from 10-70 mg were administrated orally on days 1 and 7 (d1 and d7) of a 3+7 daunorubicin+cytarabine conventional induction chemotherapy regimen.

Double reduced-intensity allogeneic hematopoietic stem cell transplantation: a retrospective study from the SFGM-TC.

The purpose of this paper is to describe the outcome of patients who underwent double allogeneic hematopoietic stem cell transplantation (AHSCT) with reduced-intensity conditioning regimens (RIC). Forty-five patients who received double RIC-AHSCT between 1997 and 2006 were retrospectively studied. The predominant diagnosis was acute myeloid leukemia (AML) (n = 17).

Dismal prognostic value of monosomal karyotype in elderly patients with acute myeloid leukemia: a GOELAMS study of 186 patients with unfavorable cytogenetic abnormalities.

The prognosis of acute myeloid leukemia (AML) is very poor in elderly patients, especially in those classically defined as having unfavorable cytogenetics. The recent monosomal karyotype (MK) entity, defined as 2 or more autosomal monosomies or combination of 1 monosomy with structural abnormalities, has been reported to be associated with a worse outcome than the traditional complex karyotype (CK). In this retrospective study of 186 AML patients older than 60 years, the prognostic influence of MK was used to further stratify elderly patients with unfavorable cytogenetics.

Addition of lomustine to idarubicin and cytarabine improves the outcome of elderly patients with de novo acute myeloid leukemia: a report from the GOELAMS.

Purpose: No significant improvement in treatment outcome has been seen in elderly patients with acute myeloid leukemia (AML) over the past 20 years. This retrospective analysis investigated the prognostic factors for complete remission (CR) and survival in older patients with AML.

Patients And Methods: The study involved 847 patients older than 60 years enrolled onto three trials carried out in France between 1995 and 2005.

Higher incidence of relapse in patients with acute myelocytic leukemia infused with higher doses of CD34+ cells from leukapheresis products autografted during the first remission.

The stem cell source for autologous transplantation has shifted from bone marrow to peripheral blood (PB). We previously showed that relapse incidence in patients with acute myelocytic leukemia autografted in first remission (CR1) was greater with PB than bone marrow, and a poorer outcome was associated with a shorter CR1 to PB transplantation interval (≤ 80 days). Leukemic and normal progenitors are CD34(+) and can be concomitantly mobilized; we assessed whether an association exists between the infused CD34(+) cell dose and outcome.

Acute myeloid leukemia with translocation (8;21) or inversion (16) in elderly patients treated with conventional chemotherapy: a collaborative study of the French CBF-AML intergroup.

Purpose: Acute myeloid leukemia (AML) with translocation (t) (8;21) or inversion (inv) (16) is associated with a favorable prognosis when treated with intensive chemotherapy. In elderly patients, these AML types are rare, and intensive treatments are much less tolerated. We conducted a retrospective study to evaluate the characteristics and outcome of AML with t(8;21) or inv(16) in the elderly.

Higher incidence of relapse with peripheral blood rather than marrow as a source of stem cells in adults with acute myelocytic leukemia autografted during the first remission.

Purpose: The cell source for autologous stem cell transplantation has shifted from bone marrow (BM) to peripheral blood (PB). In acute myelocytic leukemia (AML), for patients who receive transplants during first complete remission (CR1), no prospective randomized study has compared relapse incidence (RI) to cell source.

Patients And Methods: We analyzed 2,165 patients who received autografts (1,607 PB and 558 BM) from 1994 to 2006 and were reported to the European Cooperative Group for Blood and Marrow Transplantation with complete research data.

NOTCH1/FBXW7 mutation identifies a large subgroup with favorable outcome in adult T-cell acute lymphoblastic leukemia (T-ALL): a Group for Research on Adult Acute Lymphoblastic Leukemia (GRAALL) study.

Many somatic genetic abnormalities have been identified in T-cell acute lymphoblastic leukemia (T-ALL) but each individual abnormality accounts for a small proportion of cases; therapeutic stratification consequently still relies on classical clinical markers. NOTCH1 and/or FBXW7 mutations both lead to activation of the NOTCH1 pathway and are among the most frequent mutations in T-ALL. We screened 141 adult diagnostic T-ALL samples from patients treated on either the Lymphoblastic Acute Leukemia in Adults (LALA)-94 (n = 87) or the GRAALL-2003 (n = 54) trials.

Early clearance of peripheral blasts measured by flow cytometry during the first week of AML induction therapy as a new independent prognostic factor: a GOELAMS study.

An early appreciation of treatment efficacy could be very useful in acute myeloblastic leukemia (AML), and a prognostic value has been suggested for the morphological assessment of decrease in blasts during induction therapy. More sensitive, multiparametric flow cytometry (FCM) can detect far lower blast counts, allowing for a precise and reliable calculation of blast cell decrease rate (BDR). Such a multiparametric FCM four-colours/single-tube protocol, combining CD11b, CD45-ECD and CD16-PC5, was applied to peripheral blood samples from 130 AML patients, collected daily during induction chemotherapy.

Constitutive phosphoinositide 3-kinase/Akt activation represents a favorable prognostic factor in de novo acute myelogenous leukemia patients.

The phosphoinositide 3-kinase (PI3K/Akt) pathway is activated in acute myelogenous leukemia (AML) and is promising for targeted inhibition. Ninety-two patients with primary AML were analyzed for PI3K/Akt constitutive activation. Fifty percent of the patients presented with constitutive PI3K activation (PI3K (+)).

Imatinib combined with induction or consolidation chemotherapy in patients with de novo Philadelphia chromosome-positive acute lymphoblastic leukemia: results of the GRAAPH-2003 study.

The combination of imatinib with chemotherapy has been recently reported as very promising in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). During 2004 and 2005, 45 patients with newly diagnosed Ph+ ALL were treated in the Group for Research on Adult Acute Lymphoblastic Leukemia (GRAAPH) 2003 study, in which imatinib was started with HAM (mitoxantrone with intermediate-dose cytarabine) consolidation in good early responders (corticosensitive and chemosensitive ALL) or earlier during the induction course in combination with dexamethasone and vincristine in poor early responders (corticoresistant and/or chemoresistant ALL). Imatinib was then continuously administered until stem cell transplantation (SCT).

Daclizumab, an efficient treatment for steroid-refractory acute graft-versus-host disease.

In a phase II study, daclizumab was given as single second-line agent to 62 patients with steroid-refractory acute graft-versus-host disease (aGVHD). Complete resolution of aGVHD was achieved in 68.8% of patients.

Autologous stem cell transplantation in adults with acute lymphoblastic leukemia in first complete remission: analysis of the LALA-85, -87 and -94 trials.

To evaluate the results of autologous stem cell transplantation (ASCT) in a large population of adults with acute lymphoblastic leukemia (ALL) in first complete remission (CR), we performed an individual data-based overview of the last three trials from the LALA group. Overall, 349 patients with ALL prospectively randomized in the consecutive LALA-85, -87, and -94 trials to receive either ASCT or chemotherapy as post-CR treatment were analyzed. Eligibility criteria were 15-50-year-old patients without sibling donors in both LALA-85/87 trials and 15-55-year-old patients with high-risk ALL and no sibling donors in the LALA-94 trial.

Intensive therapy before or during the conditioning regimen of allogeneic marrow transplantation in adult acute lymphoblastic leukemia patients: we must choose to reduce Toxicity--a Groupe Ouest-Est d'Etude des Leucemies et Autres Maladies du Sang study.

To improve the results in the treatment of adult acute lymphoblastic leukemia patients, different strategies have been proposed. The intensification could concern the induction and early consolidation phases, the conditioning regimen before allogeneic bone marrow transplantation (alloBMT), or both. We analyzed 2 consecutive trials for adult patients in first remission and with the same prognostic features.

Better outcome of adult acute lymphoblastic leukemia after early genoidentical allogeneic bone marrow transplantation (BMT) than after late high-dose therapy and autologous BMT: a GOELAMS trial.

Various transplantation strategies have been designed to improve the poor prognosis of adult (ages 15 to 60 years) acute lymphoblastic leukemia (ALL). The GOELAL02 trial evaluated the impact of early allogeneic bone marrow transplantation (alloBMT) or delayed unpurged autologous stem cell transplantation (ASCT) for patients who had no human leukocyte antigen (HLA)-matched sibling donor or who were older than 50 years. Inclusion criteria included at least one of the following: age older than 35 years; non-T-ALL; leukocytosis greater than 30 x 10(9)/L; t(9;22), t(4;11), or t(1; 19); or failure to achieve complete remission (CR) after one induction course.

Donor lymphocyte infusion to treat relapse after allogeneic bone marrow transplantation for myelodysplastic syndrome.

Donor lymphocyte infusion has become established as a salvage therapy for patients with hematological disorders relapsing after allogeneic bone marrow transplantation (BMT). The role of donor lymphocyte infusion for patients with myelodysplastic syndrome (MDS) remains to be established. Between July 1993 and October 2001, 14 patients with MDS relapsing after allogeneic BMT received DLI as salvage therapy.

Shwachman-Diamond syndrome with late-onset neutropenia and fatal acute myeloid leukaemia without maturation: a case report.

We report on a male patient affected by Shwachman Diamond syndrome (SDS) who presented an unusual delayed neutropenia and then developed a poorly differentiated acute myeloid leukaemia (M0-AML) with trilineage myelodysplasia in adulthood. Conventional cytogenetics revealed complex karyotypic changes (monosomies 20, 21, 22, additional 15p). The patient was treated with conventional chemotherapy but never reached complete remission of leukaemia and died 18 months after diagnosis.

Hematologic recovery after autologous PBPC transplantation: importance of the number of postthaw CD34+ cells.

Background: The implementation of a quality-assurance program is a major requirement to ensure quality and safety of the final PBPC components intended for clinical use. It is not clear whether the quantification of CFU-GM and CD34+ cells should be done on fresh components and after cryopreservation, which better represents the actual composition of the graft.

Study Design And Methods: Correlation between prefreeze and postthaw MNCs, CD34+ cells, and CFU-GM collected from 126 patients undergoing BMT (n=43) or PBPC (n =83) transplantation were evaluated.

Prognosis of inv(16)/t(16;16) acute myeloid leukemia (AML): a survey of 110 cases from the French AML Intergroup.

Acute myeloid leukemias (AMLs) carrying inv(16)/t(16;16) chromosomal abnormalities are associated with a good prognosis. However, studies of this AML subtype have been hampered by the few number of patients reported, frequently collectively considered with those with AML carrying the t(8;21) translocation. We performed a retrospective study in 110 patients with inv(16)/t(16;16) AML (median age, 34 years) prospectively enrolled in 6 trials conducted in France between 1987 and 1998, with the aim to investigate prognostic factors for complete remission (CR) achievement and outcome of CR patients in this AML subtype.

[Granulocyte sarcoma of the pancreas without extra-pancreatic location].

Introduction: Granulocyte sarcoma (GS), also known as chloroma, is a localized malignant tumor composed of myeloid cells, the diagnosis of which is difficult. The pancreatic location and recurrence, aside from any context of malignant hemopathy, are exceptional.

Observation: A 31-year-old woman developed an isolated and recurrent granulocyte sarcoma of the pancreas, without any context of a malignant hemopathy.