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It is an open question whether in multiple myeloma (MM) bone marrow stromal cells contain genomic alterations, which may contribute to the pathogenesis of the disease. We conducted an array-based comparative genomic hybridization (array-CGH) analysis to compare the extent of unbalanced genomic alterations in mesenchymal stem cells from 21 myeloma patients (MM-MSCs) and 12 normal donors (ND-MSCs) after in vitro culture expansion. Whereas ND-MSCs were devoid of genomic imbalances, several non-recurrent chromosomal gains and losses (>1 Mb size) were detected in MM-MSCs. Using real-time reverse transcription PCR, we found correlative deregulated expression for five genes encoded in regions for which genomic imbalances were detected using array-CGH. In addition, only MM-MSCs showed a specific pattern of ‘hot-spot’ regions with discrete (<1 Mb) genomic alterations, some of which were confirmed using fluorescence in situ hybridization (FISH). Within MM-MSC samples, unsupervised cluster analysis did not correlate with particular clinicobiological features of MM patients. We also explored whether cytogenetic abnormalities present in myelomatous plasma cells (PCs) were shared by matching MSCs from the same patients using FISH. All MM-MSCs were cytogenetically normal for the tested genomic alterations. Therefore we cannot support a common progenitor for myeloma PCs and MSCs.Leukemia (2009) 23, 1515–1527; doi:10.1038/leu.2009.65; published online 9 April 2009 [ABSTRACT FROM AUTHOR]

T-cell large granular lymphocytes (LGL) proliferations range from reactive expansions of activated T cells to T-cell leukemias and show variable clinical presentation and disease course. The vast majority of T-LGL proliferations express TCRαβ. Much less is known about the characteristics and pathogenesis of TCRγδ+ cases. We evaluated 44 patients with clonal TCRγδ+ T-LGL proliferations with respect to clinical data, immunophenotype and TCR gene rearrangement pattern. TCRγδ+ T-LGL leukemia patients had similar clinical presentations as TCRαβ+ T-LGL leukemia patients. Their course was indolent and 61% of patients were symptomatic. The most common clinical manifestations were chronic cytopenias – neutropenia (48%), anemia (23%), thrombocytopenia (9%), pancytopenia (2%) – and to a lesser extent splenomegaly (18%). Also multiple associated autoimmune (34%) and hematological (14%) disorders were found. Leukemic LGLs were predominantly positive for CD2, CD5, CD7, CD8, and CD57, whereas variable expression was seen for CD16, CD56, CD11b, and CD11c. The Vγ9/Vδ2 immunophenotype was found in 48% of cases and 43% of cases was positive for Vδ1, reflecting the TCR-spectrum of normal TCRγδ+ T-cells in adult PB. Identification of the well-defined post-thymic Vδ2-Jδ1 selection determinant in all evaluable Vγ9+/Vδ2+ patients, is suggestive of common (super)antigen involvement in the pathogenesis of these TCRγδ+ T-LGL leukemia patients.Leukemia (2006) 20, 505–513. doi:10.1038/sj.leu.2404112; published online 26 January 2006 [ABSTRACT FROM AUTHOR]

While in bone marrow allogeneic transplantation the infusion of high doses of progenitor stem cells has a favourable impact on outcome, due to a faster hematopoietic and immune recovery, in the peripheral blood allo-setting the infusion of a high number of CD34 cells increases the risk of extensive chronic graft vs. host disease (cGVHD). This higher incidence of extensive cGVHD has an adverse impact on outcome due to a higher transplant related mortality, specially among patients receiving T-cell depleted allogeneic transplantation with myeloablative conditioning. By contrast, patients undergoing reduced intensity conditioning regimen may benefit from increasing higher CD34 + cell doses, especially those categorized as high risk according to disease status at transplant. Thus, the source of progenitors cells, type of conditioning and GVHD prophylaxis, among other factors, may influence the effect of the progenitor cell dose on outcome after allogeneic transplant. [ABSTRACT FROM AUTHOR]

Summary:The aim was to analyze quality-of-life (QOL) during the first year post transplant in 47 patients undergoing reduced-intensity conditioning (RIC) allotransplantation, and to compare these with a similar subgroup of patients receiving autologous stem cell transplantation (ASCT). We used self-reported questionnaires. Each answer scored from 0 (not at all) to 4 (very much), with higher scores indicating worse functioning. Mean value of physical categories among RIC transplants ranged between 1.23 and 0.77 indicating that patients scored very low for physical symptoms. Patients undergoing ASCT had higher scores in questionnaires performed early after transplant and then gradually improved (P<0.001). Overall, when we compared physical functioning scores, allo-RIC did significantly better (P=0.049). Nevertheless, while allo-RIC scores were significantly better for the first three questionnaires, ASCT patients did better in the last two questionnaires. These findings are in accordance with the toxicities observed in both subgroups which are lower in the RIC group early after transplant. No significant differences were observed between either subgroup for any of the functional, social/family, psychological distress and satisfaction with doctor/nurse relationship items. We have observed similar QOL among patients undergoing RIC-allo as compared to ASCT although GVHD remains an important‘event’in QOL.Bone Marrow Transplantation (2004) 34, 729-738. doi:10.1038/sj.bmt.1704646 Published online 6 September 2004 [ABSTRACT FROM AUTHOR]

Summary:Studies evaluating the effects of previous chemotherapy on stem-cell yield and hematological recovery after autologous peripheral-blood progenitor-cell transplantation (PBPCT) have shown conflicting results. We have retrospectively analyzed 103 consecutive lymphoma patients treated with the BEAM regimen and autologous PBPCT. The impact of the different chemotherapeutic drugs (cumulative doses) on stem-cell yield and transplant-related toxicity was investigated. Highly significant differences in platelet recovery (>20 × 109/l) were observed between patients receiving less or more than 750?mg/m2 of etoposide before transplant (15 vs 29 days, P=0.001), and between patients receiving less or more than 1.2 × 106/kg CD34+ cells (27 vs 14 days, P<0.001). Differences in neutrophil engraftment between groups were not clinically significant. Pre-transplant cumulative doses of etoposide >750?mg/m2 were associated with low CD34+ cell collections on multivariate analysis. The actuarial incidence of transplant-related mortality (TRM) was 14% at 5 years. Pre-transplant cumulative doses of etoposide >350?mg/m2 and previous administration of procarbazine were found to be independent prognostic factors for TRM.Bone Marrow Transplantation (2004) 33, 579-587. doi:10.1038/sj.bmt.1704401 Published online 19 January 2004 [ABSTRACT FROM AUTHOR]