No abstract

Mesenchymal stem cells (MSC) are multilineage non hematopoietic progenitor cells that play a key role in supporting the lymphohematopoietic system. Their distribution in bone marrow and secondary lymphoid organs allows an intimate interaction with T and B-lymphocytes, which contribute to the normal lymph node development, but this interaction, can not be considered as a simple bi-directional cross-talk and other cell subsets, such as dendritic cells (DC), must be considered. We have analysed the effect of MSC on B-lymphocytes and the pathways involved in these effects. For these propose, we cultured B-cell with or without MSC and analysed different markers involved in the differentiation of B-cells. We found that MSC inhibited proliferation, arresting B lymphocytes in G0G1 phase of cell cycle (figure 1). However, the presence of MSC increased the viability ob B-lymphocytes (double number of viable B-cells: from 13012 to 22835 Annexin-V PE/7 ADD negative events within B-lymphocytes in absence versus presence of MSC). The exposure of B-cells to plasmocytoid DC (pDC) induced B-lymphocytes differentiation increasing both the percentage of CD38++/CD138++ cells as well as the mean fluorescence intensity of both markers (figure 2). Accordingly, different B-cell subpopulations could be identified which represented a continuum in B-cell maturation. While the levels of cytoplasmic immunoglobulin (cIg) were higher among CD38++ cells, the opposite occurred for the expression of surface Ig as well as CD19 and CCR7. Interestingly, the presence of MSC blocked B-cell differentiation. Regarding the pathways involved in these effects, the presence of MSC influenced on ERK 1/2 and p38 pathways, but these effects depended on the culture conditions. Thus, MSC induced phosphorilation of ERK 1/2 MAPK and inhibited phosphorilation of p38 in B-cells cultured with Ig plus CpG (low proliferative conditions) while the contrary occurred in B-cells cultured with TPA (highly proliferative conditions). Therefore we demonstrated that MSC increased viability and blocked cell cycle of B-lymphocytes. Furthermore the plasmocitoid dendritic cells favoured B-lymphocytes differentiation and this process in inhibited in presence with MSC. These effects are at least in part mediated through the ERK 1/2 and p38 pahtways. Figure Figure

We report the case of an 18-year-old patient who received an allogeneic bone marrow transplant from an HLA-identical unrelated donor for a Ph+ acute lymphoblastic leukemia, in his third complete remission. Cyclophosphamide and busulfan were used as conditioning treatment. Acute graft-versus-host disease developed on day +9, and the response to adequate treatment (steroids) was favourable. On day +45 the patient developed an acute severe haemorhragic cystitis, and BK polyomavirus was demonstrated in urine samples using electron microscopy and polymerase chain reaction. Urinary symptoms did not improve in spite of palliative treatment, but a response was evident after 2 weeks of cidofovir treatment.

Summary. We report on a case of pyridoxine refractory hereditary sideroblastic anaemia (HSA) in a 19-year-old man who underwent peripheral blood stem cell transplantation (PBSCT) from his HLA-identical brother. By using short tandem repeat polymorphism, 100% donor cells were observed in peripheral blood on day 121; bone marrow showed mixed chimaerism from day 121 to day 1221, when 100% cells of donor origin were observed. The patient developed extensive chronic graft-versus-host disease with favourable response to treatment. When the haemoglobin range was normal, a programme of phlebotomies reduced serum ferritin levels. Three years after transplantation, the patient has an ECOG rating of 0, with completely normal haemoglobin values (15 g/dl). To our knowledge, this is the first PBSCT reported in a case of hereditary sideroblastic anaemia.

We report an unusual case of cerebral toxoplasmosis associated with Guillain-Barré syndrome (GBS) in a 25-year-old patient diagnosed with chronic myelogenous leukaemia (CML), who underwent a mismatched allogeneic peripheral stem cell transplantation (PSCT). On day +83 he started with fever, and 7 days later tremor, muscular weakness, diplopia, dysarthria, respiratory difficulty, and universal arreflexia appeared, compatible with GBS. As the patient had a positive cytomegalovirus (CMV) antigenemia, this was the aetiology suspected for his neurologic findings, but specific treatment failed to improve his clinical situation, and he died on day +123. Necropsy demonstrated cerebral toxoplasmosis and axonal degeneration of nerve roots compatible with the axonal form of GBS. Interestingly, the polymerase chain reaction (PCR) signal for Toxoplasma gondii in two different cerebrospinal fluid (CSF) samples had been negative. In addition, this case showed unique magnetic resonance imaging (MRI) abnormalities. We conclude that a negative PCR on CSF cannot exclude toxoplasmosis in a transplant patient, and we emphasise the importance of considering Toxoplasma as an aetiology of fever and neurological symptoms in the transplant setting.

No abstract

No abstract

We have analyzed the impact of MRD monitoring (detected by flow cytometry) on the outcome of 56 patients undergoing RIC allogeneic SCT. Of them, 67% reached complete remission (CR), 11% partially responded (PR) and 22% progressed or did not respond. MRD assessment after transplant distinguished different risk populations. At day +100, 80% of patients with high MRD levels (>10−2 leukemia asocciatted immunophenotypical cells, LAIP cells) versus 27% of patients with low MRD (<10−4) had relapsed. Accordingly, 3 categories could be clearly idenitified in terms of relapse free survival (RFS) at 5 years: 62% of patients with low MRD levels (<10−4) were event free as compared to only 28% and 20% among patients with intermediate (>10−4 and <10−2) and high MRD (>10−2) (p=0.0047). In multivariate analysis, patients’ age > 60 years (HR: 4,005; 95% CI 1.1–14.1, p=0.03), advanced disease status at transplant (HR: 4,087; 95% CI 1.3–12, p=0.01), failure to develop acute (HR: 4,785; 95% CI 1.2–18, p=0.02) and chronic GVHD (HR: 8,166; 95% CI 2.5–26.1, p=<0.001) and MRD levels, ≥10−4 on day +100 (HR: 5,795; 95% CI 1.7–19.1, p=0.004) adversely influenced RFS. Our study suggests that monitoring of MRD is a useful tool for predicting risk of relapse.