Upfront VIP-reinforced-ABVD (VIP-rABVD) is not superior to CHOP/21 in newly diagnosed peripheral T cell lymphoma. Results of the randomized phase III trial GOELAMS-LTP95.

Peripheral T-Cell lymphomas (PTCL) are relatively rare diseases but appear to be highly aggressive and display worse remission and survival rates than B-cell lymphomas. Despite unsatisfactory results with the cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) regimen, it remains the reference front-line therapy in these diseases, but has not been challenged in phase III trials. The Groupe Ouest Est d'Etude des Leucémies et Autres Maladies du Sang (GOELAMS) devised an alternative therapeutic schedule including etoposide, ifosfamide, cisplatin alternating with doxorubicin, bleomycin, vinblastine, dacarbazine (VIP-reinforced-ABVD; VIP-rABVD) and compared it to CHOP/21 as front-line treatment in non-cutaneous PTCL.

Diagnosis and treatment of digestive cryptosporidiosis in allogeneic haematopoietic stem cell transplant recipients: a prospective single centre study.

Digestive cryptosporidiosis (DC) can mimic GVHD after allogeneic haematopoietic stem cell transplantation (HSCT), thus requiring a reduction of immunosuppressive drugs and a specific therapy, whereas GVHD requires an intensification of immunosuppression. We systematically searched for cryptosporidiosis by light microscopy, immunochromatography and PCR in HSCT recipients who presented with at least one episode of diarrhoea. Of 115 consecutive patients allografted between July 2006 and November 2008, we analysed stools in 52 of 56 patients meeting these criteria.

Persistence of lymphocyte function perturbations after granulocyte-colony-stimulating factor mobilization and cytapheresis in normal peripheral blood stem cell donors.

Background: The short-term effects of granulocyte-colony-stimulating factor (G-CSF) have been extensively studied, but recent reports of G-CSF-induced genetic perturbations raised concerns regarding its long-term safety. In this respect, duration of G-CSF-induced perturbations has been less studied than short-term effects and needs to be evaluated.

Study Design And Methods: G-CSF mobilization-induced immunologic alterations were prospectively analyzed in a cohort of 24 healthy donors.

Comparison and combination of spectroscopic techniques for the detection of counterfeit medicines.

During this study, Fourier transform infrared spectroscopy (FT-IR), near infrared spectroscopy (NIR) and Raman spectroscopy were applied to 55 samples of counterfeit and imitations of Viagra and 39 samples of counterfeit and imitations of Cialis. The aim of the study was to investigate which of these techniques and associations of them were the best for discriminating genuine from counterfeit and imitation samples. Only the regions between 1800-400 cm(-1) and 7000-4000 cm(-1) were used for FT-IR and NIR spectroscopy respectively.

False-positive Aspergillus real-time PCR assay due to a nutritional supplement in a bone marrow transplant recipient with GVH disease.

PCR screening for circulating DNA, especially when combined with antigen testing, has shown promise for the definitive diagnosis of invasive aspergillosis. False positives for Aspergillus real-time PCR assays have been described in several reports, but no sources of fungal DNA contamination could be clearly identified. We report a false-positive case for both galactomannan (GM) antigenemia and Aspergillus PCR due to nutritional supplement intake in a bone marrow transplant recipient with digestive graft-versus-host disease.

Evaluation of the (R)VAD+C regimen for the treatment of newly diagnosed mantle cell lymphoma. Combined results of two prospective phase II trials from the French GOELAMS group.

Unlabelled: Background There is currently no international consensus for first-line treatment (prior to autologous stem cell transplantation) in mantle cell lymphoma patients. Here, we investigated the efficacy and tolerance of VAD associated with chlorambucil (VAD+C) and rituximab or not before autologous stem cell transplantation.

Design And Methods: Between 1996 and 2005, 113 previously untreated mantle cell lymphoma patients were enrolled in two consecutive prospective phase II studies.

Identification of an alternative CD20 transcript variant in B-cell malignancies coding for a novel protein associated to rituximab resistance.

Human CD20 is a B-cell lineage-specific marker expressed by normal and leukemic B cells from the pre-B to the plasma-cell stages and is a target for rituximab (RTX) immunotherapy. A CD20 reverse transcriptase-polymerase chain reaction (PCR) on B-cell lines cDNA yielded a short PCR product (DeltaCD20) corresponding to a spliced mRNA transcript linking the exon 3 and exon 7 ends. We established here that this novel, alternatively spliced CD20 transcript is expressed and detectable at various levels in leukemic B cells, lymphoma B cells, in vivo tonsil- or in vitro CD40L-activated B cells, and Epstein-Barr virus (EBV)-transformed B cells, but not in resting CD19(+)- or CD20(+)-sorted B cells from peripheral blood or bone marrow of healthy donors.

Cost effectiveness of rituximab maintenance therapy in follicular lymphoma: long-term economic evaluation.

Background: Rituximab maintenance therapy was shown to significantly extend overall survival (OS) and progression-free survival (PFS) in relapsed/refractory follicular lymphoma (FL) in the pivotal EORTC 20981 trial.

Objective: To assess the long-term costs and cost effectiveness of rituximab maintenance therapy after induction therapy versus current standard practice (observation) from the French National Health Service perspective.

Methods: A lifetime transition model was developed comparing rituximab maintenance with observation.

Pharmacokinetic modelling and development of Bayesian estimators for therapeutic drug monitoring of mycophenolate mofetil in reduced-intensity haematopoietic stem cell transplantation.

Background: Mycophenolate mofetil, a prodrug of mycophenolic acid (MPA), is used during non-myeloablative and reduced-intensity conditioning haematopoetic stem cell transplantation (HCT) to improve engraftment and reduce graft-versus-host disease (GVHD). However, information about MPA pharmacokinetics is sparse in this context and its use is still empirical.

Objectives: To perform a pilot pharmacokinetic study and to develop maximum a posteriori Bayesian estimators (MAP-BEs) for the estimation of MPA exposure in HCT.

Pharmacokinetics of mycophenolic acid administered 3 times daily after hematopoietic stem cell transplantation with reduced-intensity regimen.

Mycophenolate mofetil (MMF) is an immunosuppressive drug used as a prophylactic agent to prevent acute graft-versus-host disease (aGVHD) after hematopoietic stem cell transplantation (HSCT). After reduced-intensity conditioning (RIC) regimen, administration of MMF orally 3 times a day (tid) seems to be more beneficial than twice a day (bid). However, information regarding the pharmacokinetic (PK) parameters of mycophenolic acid (MPA), the active metabolite of MMF, administered in this regimen are very limited.

Infliximab treatment for steroid-refractory acute graft-versus-host disease after orthotopic liver transplantation: a case report.

Acute graft-versus-host disease (GVHD) following orthotopic liver transplantation is a rare but severe disease with a 75% death rate in adults. Various therapeutic strategies have been proposed for steroid-refractory GVHD, but there is still no consensus. Tumor necrosis factor-alpha is a key inflammatory cytokine involved in acute GVHD physiopathology, and infliximab has shown encouraging results for the treatment of acute GVHD following hematopoietic stem cell transplantation.

[Banking and indications for cord blood grafts].

A cord blood graft is now frequently used in the context of allogeneic hematopoietic transplantation. In 2007, 27% of unrelated allotransplantations performed in France used a cord blood graft. In comparison to other sources of hematopoietic grafts, cord blood has a number of advantages (immediate availability of the graft, possibility of a lesser HLA compatibility between donor and recipient.

Evidence for anti-tumour effect of allogeneic haematopoietic SCT in cases without sustained donor engraftment.

Remissions of haematological malignancies have been reported after allo-SCT, despite donor cell rejection, suggesting that sustained allogeneic engraftment is not mandatory to obtain a lasting anti-tumour effect. To evaluate the potential benefit from transient post-allo-SCT alloreactivity, we took advantage of the Société Française de Greffe de Moëlle et Thérapie Cellulaire (SFGM-TC) registry to colligate 14 patients with an efficient and long-lasting allogeneic (GVL) effect after allo-SCT for haematological malignancies, despite transient or absent engraftment. None received a second allogeneic graft after autologous recovery.

Improved outcome of acute promyelocytic leukemia with high WBC counts over the last 15 years: the European APL Group experience.

Purpose: Acute promyelocytic leukemia (APL) with pretreatment WBC counts greater than 10,000/microL is still considered to carry a poorer prognosis than APL with WBC lower than 10,000/mL. We evaluated outcome improvement in such patients in recent years.

Patients And Methods: Nine hundred two patients with APL, including 204 patients and 68 patients with WBC counts more than 10,000/microL and more than 50,000/microL, respectively, were enrolled between 1993 and 2005 in two successive randomized trials of the European APL group (APL 93 and APL 2000) that tested, in particular, the modalities of combination of all-trans retinoic acid (ATRA) and chemotherapy, maintenance treatment, escalating doses of cytarabine, early administration of dexamethasone, and CNS prophylaxis.

Extended diagnostic criteria for plasmacytoid dendritic cell leukaemia.

The diagnosis of plasmacytoid dendritic cell leukaemia (pDCL) is based on the immunophenotypic profile: CD4(+) CD56(+) lineage(neg) CD45RA(+)/RO(neg) CD11c(neg) CD116(low) CD123(+) CD34(neg) CD36(+) HLA-DR(+). Several studies have reported pDCL cases that do not express this exact profile or expressing some lineage antigens that could thus be misdiagnosed. This study aimed to validate pDCL-specific markers for diagnosis by flow-cytometry or quantitative reverse transcription polymerase chain reaction on bone marrow samples.

Risk factors for therapy-related myelodysplastic syndrome and acute myeloid leukemia treated with allogeneic stem cell transplantation.

Background: After successful treatment of malignant diseases, therapy-related myelodysplastic syndrome and acute myeloid leukemia have emerged as significant problems.

Design And Methods: The aim of this study was to investigate outcome and risk factors in patients with therapy-related myelodysplastic syndrome or acute myeloid leukemia who underwent allogeneic stem cell transplantation. Between 1981 and 2006, 461 patients with therapy-related myelodysplastic syndrome or acute myeloid, a median age of 40 years and a history of solid tumor (n=163), malignant lymphoma (n=133), or other hematologic diseases (n=57) underwent stem cell transplantation and their data were reported to the European Group for Blood and Marrow Transplantation.

Cost effectiveness of high-dose chemotherapy with autologous stem cell support as initial treatment of aggressive non-Hodgkin's lymphoma.

The GOELAMS 072 study showed that first-line high-dose chemotherapy (HDT) with peripheral blood stem cell transplant (PBSCT) support was superior to the standard chemotherapy regimen (cyclophosphamide, doxorubicin, vincristine and prednisone; CHOP) in adults with aggressive non-Hodgkin's lymphoma (NHL). The aim of the study was to evaluate the pharmacoeconomic profile of HDT with PBSCT support relative to standard CHOP therapy as first-line treatment in adults with aggressive NHL. We performed a cost-effectiveness analysis from the French Public Health Insurance perspective, restricted to hospital costs (euro, year 2008 values).

Evaluation of orthogonal/dissimilar RP-HPLC systems sets for their suitability as method-development starting points for drug impurity profiles.

Orthogonal or dissimilar separation systems provide different selectivities and their application can facilitate the development of methods to identify and quantify impurities in a drug substance. Two sets of chromatographic systems potentially applicable for method development were evaluated using four drug/impurity profiles. The sets consist of orthogonal or dissimilar systems and systems with good overall separation properties, selected in earlier studies.

High-dose therapy followed by autologous purged stem cell transplantation and doxorubicin-based chemotherapy in patients with advanced follicular lymphoma: a randomized multicenter study by the GOELAMS with final results after a median follow-up of 9 years.

Autologous stem cell transplantation (ASCT) as first-line therapy for follicular lymphoma (FL) remains controversial. The multicenter study randomized 172 patients with untreated FL for either immunochemotherapy or high-dose therapy (HDT) followed by purged ASCT. Conditioning was performed with total body irradiation (TBI) and cyclophosphamide.

Early immune response against retrovirally transduced herpes simplex virus thymidine kinase-expressing gene-modified T cells coinfused with a T cell-depleted marrow graft: an altered immune response?

Administration of herpes simplex thymidine kinase (HSV-tk)-expressing, gene-modified T cells (GMCs) with T cell-depleted bone marrow transplantation (TCD-BMT) can allow modulation of posttransplantation alloreactivity. Twelve patients received 2 x 10(5) to 2 x 10(6) CD3+ donor GMCs per kilogram with HLA-identical sibling TCD-BMT. Despite extensive T cell depletion of bone marrow, an intensive conditioning regimen, and immunosuppressive graft-versus-host disease (GvHD) prophylaxis, infusion at the time of TCD-BMT of this low number of GMCs sufficed to induce a rapid GMC-specific immune response, as detected by interferon- enzyme- linked immunospot assay in six of eight patients, preferentially targeting HSV-tk.

[Kappa light chain deposition disease, presenting as Sjögren's syndrome, successfully treated by high-dose melphalan and autologous blood stem transplantation].

Introduction: Light chain deposition disease is a systemic disorder characterised by tissue deposition of monoclonal immunoglobulin light chains without tinctorial properties. It has been exceptionally reported with salivary involvement mimicking Sjögren's syndrome and peripheral neuropathy.

Case Report: We report a case of light chain deposition disease associated with plasma cell dyscrasia presenting as sicca syndrome with salivary glands hypertrophy and polyneuropathy successfully treated by high dose melphalan and autologous blood stem transplantation.

Allogeneic hematopoietic stem-cell transplantation for myeloid sarcoma: a retrospective study from the SFGM-TC.

Purpose: This retrospective multicenter study assessed the outcome of 51 patients with myeloid sarcoma (MS) who underwent allogeneic hematopoietic stem-cell transplantation (alloHSCT).

Patients And Methods: Most patients had MS presenting in conjunction with acute myeloid leukemia (AML) or after AML. Six patients had isolated MS.

Isotopic ratios to detect infringements of patents or proprietary processes of pharmaceuticals: two case studies.

Because of the increasing problem of drug counterfeiting and the potential danger related as well as the economic losses involved, the pharmaceutical industry and the regulatory instances are interested in the development of anti-counterfeiting and patent protection methodologies. In this paper, the evaluation of measured isotopic ratios by means of explorative chemometric techniques was performed to distinguish groups in two data sets containing samples of acetyl salicylic acid and ibuprofen, respectively. The samples in the data sets originated from different countries and manufacturers.