Reduced-intensity and non-myeloablative allogeneic stem cell transplantation from alternative HLA-mismatched donors for Hodgkin lymphoma: a study by the French Society of Bone Marrow Transplantation and Cellular Therapy.

Allogeneic stem cell transplantation (allo-SCT) following a non-myeloablative (NMA) or reduced-intensity conditioning (RIC) is considered a valid approach to treat patients with refractory/relapsed Hodgkin lymphoma (HL). When an HLA-matched donor is lacking a graft from a familial haploidentical (HAPLO) donor, a mismatched unrelated donor (MMUD) or cord blood (CB) might be considered. In this retrospective study, we compared the outcome of patients with HL undergoing a RIC or NMA allo-SCT from HAPLO, MMUD or CB. Ninety-eight patients were included. Median follow-up was 31 months for the whole cohort. All patients in the HAPLO group (N=34) received a T-cell replete allo-SCT after a NMA (FLU-CY-TBI, N=31, 91%) or a RIC (N=3, 9%) followed by post-transplant cyclophosphamide. After adjustment for significant covariates, MMUD and CB were associated with significantly lower GvHD-free relapse-free survival (GRFS; hazard ratio (HR)=2.02, P=0.03 and HR=2.43, P=0.009, respectively) compared with HAPLO donors. In conclusion, higher GRFS was observed in Hodgkin lymphoma patients receiving a RIC or NMA allo-SCT with post-transplant cyclophosphamide from HAPLO donors. Our findings suggest they should be favoured over MMUD and CB in this setting.

Antithymocyte globulins and chronic graft-vs-host disease after myeloablative allogeneic stem cell transplantation from HLA-matched unrelated donors: a report from the Sociéte Française de Greffe de Moelle et de Thérapie Cellulaire.

This retrospective report assessed the impact of rabbit antithymocyte globulins (ATG), incorporated within a standard myeloablative conditioning regimen prior to allogeneic stem cell transplantation (allo-SCT) using human leukocyte antigen-matched unrelated donors (HLA-MUD), on the incidence of acute and chronic graft-vs-host disease (GVHD). In this series of leukemia patients, 120 patients (70%) did not receive ATG ('no-ATG' group), whereas 51 patients received ATG ('ATG' group). With a median follow-up of 30.3 months, the cumulative incidence of grade 3-4 acute GVHD was 36% in the no-ATG group and 20% in the ATG group (P = 0.11). The cumulative incidence of extensive chronic GVHD was significantly lower in the ATG group as compared to the no-ATG group (4 vs 32%, respectively; P = 0.0017). In multivariate analysis, the absence of use of ATG was the strongest parameter associated with an increased risk of extensive chronic GVHD (relative risk) = 7.14, 95% CI: 1.7-33.3, P = 0.008). At 2 years, the probability of nonrelapse mortality, relapse, overall and leukemia-free survivals was not significantly different between the no-ATG and ATG groups. We conclude that the addition of ATG to GVHD prophylaxis resulted in decreased incidence of extensive chronic GVHD without an increase in relapse or nonrelapse mortality, and without compromising survival after myeloablative allo-SCT from HLA-MUD.

Noninvasive image analysis of 3D construct mineralization in a perfusion bioreactor.

Although the beneficial effects of perfusion on cell-mediated mineralization have been demonstrated in several studies, the size of the mineralized constructs produced has been limited. The ability to quantify mineralized matrix formation non-invasively within 3D constructs would benefit efforts to optimize bioreactor conditions for scaling-up constructs to clinically relevant dimensions. In this study, we report a micro-CT imaging-based technique to monitor 3D mineralization over time in a perfusion bioreactor and specifically assess mechanisms of construct mineralization by quantifying the number, size, and distribution of mineralized particle formation within constructs varying in thickness from 3 to 9 mm. As expected, mineralized matrix volume and particle number increased with construct thickness. Analyzing multiple concentric volumes inside each construct indicated that a greater proportion of the mineral volume was found within the interior of the perfused constructs. Interestingly, intermediate-sized 6mm thick constructs were found to have the highest core mineral volume fraction and the largest mineralized particles. Two complementary mechanisms of increasing total mineral volume were observed in the 6 and 9 mm constructs: increasing particle size and increasing the number of mineralized particles, respectively. The rate of mineralized matrix formation in the perfused constructs increased from 0.69 mm(3)/week during the first 3 weeks of culture to 1.03 mm(3)/week over the final 2 weeks. In contrast, the rate of mineral deposition in the static controls was 0.01 mm(3)/week during the first 3 weeks of culture and 0.16 mm(3)/week from week 3 to week 5. The ability to monitor overall construct mineralization non-invasively coupled with quantitative analysis of mineralized particle size, number, and distribution offers a powerful tool for elucidating how mineral growth mechanisms are affected by cell type, scaffold material and architecture, or bioreactor flow conditions.

Effects of farmyard manure and fertilizers on yield, fibre quality and nutrient balance of rainfed cotton (Gossypium hirsutum).

Two-year field experiments were conducted to evaluate the effect of fertilizer with or without farmyard manure (FYM) application on cotton productivity and fibre quality. A partial nutrient balance was calculated by the difference method (nutrient applied--crop removal). Seed cotton yield was improved with addition of FYM (5 Mg ha(-1)). Application of both N and P resulted in significant improvements in seed cotton yield than the control and without N plots (PK). Uniformity ratio and ginning outturn (GOT) was greater in the FYM amended plots than the plots without FYM. Nitrogen and P balance was positive in the fertilizer-N and P applied plots whereas K balance was negative in spite of the addition of fertilizer-K. Potassium balance was positive only when FYM was applied. These studies suggest that it is advantageous to apply FYM as it improves fibre yield by way of improved GOT and maintains a positive nutrient balance.

High-dose therapy and autologous bone marrow transplantation in first complete remission for adult patients with high-grade non-Hodgkin's lymphoma: the EBMT experience. Lymphoma Working Party of the European Group for Bone Marrow Transplantation.

One hundred and eighteen patients presenting with high-grade non-Hodgkin's lymphoma, undergoing autologous bone marrow transplantation (ABMT) in first complete remission (CR), have been reported to the European Group for Bone Marrow Transplantation (EBMT). Of these, 102 were eligible for inclusion in this study following review of registration forms. Patients with lymphoblastic lymphoma were excluded. Remission induction and high-dose regimens varied between contributing centres. A maintained CR was observed in 90% of patients. Early relapse was observed in 6%, and 4% suffered toxic deaths. With a median follow-up of 45 months (3-112 months), the 5-year actuarial overall and progression-free survivals are both 70%. Nineteen (18%) patients relapsed at a median of 3.5 months (0.25-52 months) after ABMT, only 1 achieving a further durable CR. The only factor with prognostic significance was histological subtype, with diffuse small noncleaved-cell lymphoma having a significantly worse outcome. High-dose therapy and ABMT has produced effective consolidation of first remission in this group of patients, even in those with poor prognostic features at presentation.

"Active" one-carbon generation in Saccharomyces cerevisiae.

A new mutation introducing a one-carbon requirement (e.g., formate) for the glycine-supplemented growth of a serine-glycine auxotroph (ser1) was correlated with a lack of glycine decarboxylase activity. The presence of oxalate decarboxylase activity or glyoxylate decarboxylase activity did not overcome the one-carbon requirement. Another mutation characterized by the absence of oxalate decarboxylase activity did not introduce a one-carbon requirement. The presence and physiological significance of glycine decarboxylase activity in Saccharomyces are thus inferred.