Late-onset neutropenia following rituximab results from a hematopoietic lineage competition due to an excessive BAFF-induced B-cell recovery

Rituximab is used in the treatment of lymphoma and autoimmune diseases, for which late-onset neutropenia (LON) were reported. LON-related mechanisms remain unclear. To obtain insights into the mechanisms, we assessed serum, peripheral blood and bone marrow (BM) samples of a patient with LON. Factors classically associated with neutropenia such as anti-neutrophil antibodies, T-LGL, soluble Fas Ligand were not detectable. We then evaluated the kinetics of various cytokines involved in B-cell and granulocyte homeostasis. We found that LON is related to a lack of granulopoiesis in the BM that coincides with a very high level of BAFF, a strong stimulator of B-cell recovery, and hypothesized a hematopoietic lineage competition due to an excessive B-cell recovery in the BM by promotion of B-cell lymphopoiesis over granulopoiesis within common developmental niches. Assessment of serum BAFF levels following rituximab could detect patients at risk of developing LON

Long-term renal function after allogenic haematopoietic stem cell transplantation in adult patients: a single-centre study

BACKGROUND: Reported data regarding chronic kidney disease (CKD) in haematopoietic stem cells transplantation (HSCT) recipients are highly discrepant. Materials and methods. We undertook a retrospective single-centre study in order to assess the rate, risk factors and outcome of HSCT-associated CKD in 123 allogeneic HSCT patients. RESULTS: Twenty-four months after HSCT, CKD [e.g. glomerular filtration rate (GFR) estimated using the MDRD formula <60 ml/min/1.73 m(2)] was noted in 49 patients (40%). Age >or= 45 years, early acute kidney injury and a baseline GFR < 90 ml/min/1.73 m(2) predicted the occurrence of CKD at 24 months after HSCT. One hundred and six patients (45 with and 61 without CKD at 24 months) were followed up for more than 36 months (range 36-142). Among the 45 patients with CKD at 24 months after HSCT, CKD persisted in 30 (67%), 10 patients (22%) showed a transient improvement in GFR but retained CKD and 10 patients (22%) had a sustained improvement of GFR. Among 61 patients without CKD at 24 months after HSCT, 3 (5%) developed CKD during the follow-up. Our data indicate that HSCT-related CKD probably includes two subsets: a frequent early-onset CKD, a consequence of ARF in older patients with pre-existent renal impairment, and a rare late-onset CKD occurring more than 2 years following HSCT. CONCLUSIONS: Careful monitoring of renal function is mandatory in patients undergoing HSCT, especially old patients with pre-existent renal impairment

Urinary tract obstruction due to extramedullary plasmacytoma: report of two cases

Extramedullary plasmacytomas (EMP) rarely occur during the course of multiple myeloma (MM). Most frequent reported sites are superior respiratory airways, pleura, lung, lymph nodes, skin, subcutaneous and soft tissues, testicles and liver. EMP involving the urinary tract are very uncommon and have been ill-described in the literature. We report two unusual cases of obstructive urinary tract EMP revealing a relapse of MM after allogeneic stem cell transplantation. Clinicians must be aware that EMP may be responsible for urinary tract obstruction even in the absence of medullary progression of MM

Influence on Busilvex pharmacokinetics of clonazepam compared to previous phenytoin historical data.

International audienceThis study investigated the effect of seizure prophylaxis on busulfan (Bu) plasma exposure. Twenty-four adult patients received an intravenous Bu-cyclophoshamide conditioning regimen prior to bone marrow transplantation. Busilvex (0.8 mg/kg) was administered every six hours during four consecutive days. Clonazepam (0.025 to 0.03 mg/kg/day as a continuous 12-h i.v. infusion) was administered at least 12 hours prior to i.v. Bu dosing and continued until 24 hours after the last dose. Pharmacokinetic (PK) data were compared with those previously collected in patients (n=127) treated with phenytoin for seizure prophylaxis. Through population PK analysis, a 10% average increase (coefficient of variation, RSE=5.35%) in total clearance of Bu was quantified when Bu was associated with clonazepam as compared to phenytoin, which was considered as not being clinically relevant. The suspected induction on Bu metabolism by phenytoin should have resulted in the opposite effect. The patient efficacy and safety profiles were comparable between the two cohorts

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

International audienceRemissions 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. The median duration of remission after autologous reconstitution was 118 (12-252) months. Although we cannot exclude the possibility that some patients were cured before allo-SCT, this retrospective analysis does strongly suggest that an efficient GVL effect can be observed without sustained donor engraftment, and that the transient presence of donor T cells might be sufficient to induce a powerful GVL effect