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This study evaluates the feasibility of using post‐transplant cyclophosphamide (PTCY) prophylaxis in allo‐hematopoietic cell transplantation (HCT) for adults aged 65 and older. PTCY is increasingly used to prevent graft‐versus‐host disease (GVHD) across all donor types, but concerns remain about potential risks, especially in older patients. Fifty‐seven adults aged 65 or older with hematological malignancies, undergoing their first allo‐HCT with PTCY prophylaxis between January 2011 and January 2023 were included. Overall, 94.8% of patients achieved primary engraftment. The median durations for neutrophil and platelet engraftments were 19 and 21 days. The day +30 cumulative incidence of bacterial bloodstream infection was 43.9%. No CMV reactivations occurred within the first 100 days after letermovir implementation. The day +180 cumulative incidences of grade II–IV and III–IV acute GVHD, and the 2‐year cumulative incidence of moderate/severe chronic GVHD were 26.3%, 10.5%, and 4.8%. Eighteen patients (31.6%) relapsed, and 30 (52.6%) died, with relapse (16.4%) and infection (11.5%) being the main causes of death. The estimated 2‐year overall survival, non‐relapse mortality, cumulative incidence of relapse, and GVHD‐free relapse‐free survival rates were 45.5%, 27.1%, 33.9%, and 37.0%. Adults aged 70 or older had similar outcomes to those aged 65–69. This study confirms the safety and feasibility of PTCY‐based allo‐HCT in older adults. [ABSTRACT FROM AUTHOR]

Summary: European LeukemiaNet refined their risk classification of acute myeloid leukaemia (AML) in 2022 (ELN 2022) according to the two new myeloid classifications published the same year. We have retrospectively assessed the prognostic value of the ELN 2022 in 120 AML patients undergoing allogeneic haematopoietic cell transplantation (allo‐HCT), including 99 in first complete response (CR1) from 2011 to 2021 in our centre. Adverse risk patients (Adv) presented inferior outcome in terms of overall survival (OS) and leukaemia‐free survival (LFS) (OS [p = 0.003], LFS [p = 0.02]), confirmed in multivariate analysis (hazard ratio [HR] for OS = 2.00, p = 0.037). These results were also seen in patients allografted in CR1. Further analysis identified a subgroup named adverse‐plus (AdvP), including complex karyotype, MECOM(EVI1) rearrangements and TP53 mutations, with worse outcomes than the rest of groups of patients, including the Adv (HR for OS: 3.14, p < 0.001, HR for LFS: 3.36, p < 0.001), with higher 2‐year cumulative incidence of relapse (p < 0.001). Notably, within this analysis, the outcome of Adv and intermediate patients were similar. These findings highlight the prognostic value of ELN 2022 in patients undergoing allo‐HCT, which can be improved by the recognition of a poor genetic subset (AdvP) within the Adv risk group. [ABSTRACT FROM AUTHOR]

Letermovir for CMV prevention in CMV-seropositive adults undergoing allo-HCT was implemented at our program in 2021. This study investigates the results from the use of letermovir. The study includes all the 140 CMV-seropositive patients who underwent an allo-HCT during the years 2020, 2021, and 2022 at our institution. Thirty-eight (27.4%) of these patients received letermovir, administered from day + 7 to day + 100 and restarted if patients were on treatment with steroids. The day + 180 and 1-year cumulative incidences of CMV reactivation were 5.3% and 12.1% for patients who received letermovir and 52.9% and 53.9% for those who did not (P < 0.001) (HR 0.19, P < 0.001). Four (10.5%) of these thirty-eight patients had a CMV reactivation, but only 2 (5.3%) cases occurred during the administration of letermovir. During the first year after allo-HCT, 13 (9.2%) patients had CMV disease; the day + 180 and 1-year cumulative incidences were 2.6% and 6.0% for patients who received letermovir and 9.9% and 12.3% for those who did not (P = 0.254) (HR 1.01, P = 0.458). Two (4.2%) of the patients included in the letermovir group had CMV disease, but both of them after letermovir discontinuation. Letermovir induced a protective effect on CMV reactivation risk, but its use was not associated with a significant reduction of CMV disease. The fact that the CMV disease in patients who received letermovir occurred after the discontinuation of the drug, questions whether CMV prophylaxis should be used in patients with high risk for CMV reactivation or disease. [ABSTRACT FROM AUTHOR]

Graft‐versus‐host disease (GVHD) is a complication of allogeneic haematopoietic cell transplantation. Endothelial injury is crucial as pathophysiological substrate for GVHD. GVHD first‐line treatment is high‐dose corticosteroids, although some patients are steroid‐refractory. Through the present study, we compared the endothelial proteomic profiles in response to serum from steroid‐refractory acute GVHD (SR‐aGVHD) and steroid‐sensitive acute GVHD (SS‐aGVHD) patients. Blood samples from SR‐aGVHD (n = 4) and SS‐aGVHD (n = 8) patients were collected at aGVHD diagnosis. Endothelial cell cultures were exposed (48 h) to patients' serum. Protein extraction and proteomic analysis were performed. Differences were statistically evaluated by multivariate analysis. Forty‐four proteins contributed to separate all samples into the two study groups, among which 15 participated significantly (p < 0.05), 10 exhibiting a fold change >1.2. Differentially expressed proteins were mainly associated with oxidative phosphorylation (Cytochrome C oxidase subunit 6B1, CX6B1), inflammation and angiogenesis (Apolipoprotein D, APOD), cell survival (Rapamycin‐insensitive companion of mTOR, RICTR), and oxidative stress (Riboflavin kinase, RIFK). This pilot study used a novel approach to distinguish the aGVHD response to steroid treatment. The proteins differentially expressed could constitute potential biomarkers for steroid‐treatment response. These findings signify a step forward to identify the mechanisms of response to steroids, of high clinical relevance considering the SR‐aGVHD elevated mortality. [ABSTRACT FROM AUTHOR]

Transitioning our society to a sustainable future, with low or net-zero carbon emissions to the atmosphere, will require a wide-spread transformation of energy and environmental technologies. In this perspective article, we describe how lab-on-a-chip (LoC) systems can help address this challenge by providing insight into the fundamental physical and geochemical processes underlying new technologies critical to this transition, and developing the new processes and materials required. We focus on six areas: (I) subsurface carbon sequestration, (II) subsurface hydrogen storage, (III) geothermal energy extraction, (IV) bioenergy, (V) recovering critical materials, and (VI) water filtration and remediation. We hope to engage the LoC community in the many opportunities within the transition ahead, and highlight the potential of LoC approaches to the broader community of researchers, industry experts, and policy makers working toward a low-carbon future. [ABSTRACT FROM AUTHOR]

Patients with COVID-19 present a wide spectrum of disease severity, from asymptomatic cases in the majority to serious disease leading to critical care and even death. Clinically, four different scenarios occur within the typical disease timeline: first, an incubation and asymptomatic period; second, a stage with mild symptoms due mainly to the virus itself; third, in up to 20% of the patients, a stage with severe symptoms where a hyperinflammatory response with a cytokine storm driven by host immunity induces acute respiratory distress syndrome; and finally, a post-acute sequelae (PASC) phase, which present symptoms that can range from mild or annoying to actually quite incapacitating. Although the most common manifestation is acute respiratory failure of the lungs, other organs are also frequently involved. The clinical manifestations of the COVID-19 infection support a key role for endothelial dysfunction in the pathobiology of this condition. The virus enters into the organism via its interaction with angiotensin-converting enzyme 2-receptor that is present prominently in the alveoli, but also in endothelial cells, which can be directly infected by the virus. Cytokine release syndrome can also drive endothelial damage independently. Consequently, a distinctive feature of SARS-CoV-2 infection is vascular harm, with severe endothelial injury, widespread thrombosis, microangiopathy, and neo-angiogenesis in response to endothelial damage. Therefore, endothelial dysfunction seems to be the pathophysiological substrate for severe COVID-19 complications. Biomarkers of endothelial injury could constitute strong indicators of disease progression and severity. In addition, the endothelium could represent a very attractive target to both prevent and treat these complications. To establish an adequate therapy, the underlying pathophysiology and corresponding clinical stage should be clearly identified. In this review, the clinical features of COVID-19, the central role of the endothelium in COVID-19 and in other pathologies, and the potential of specific therapies aimed at protecting the endothelium in COVID-19 patients are addressed. [ABSTRACT FROM AUTHOR]

Background: iPSC (induced pluripotent stem cells) banks of iPSC lines with homozygous HLA (human leukocyte antigen) haplotypes (haplobanks) are proposed as an affordable and off-the-shelf approach to allogeneic transplantation of iPSC derived cell therapies. Cord blood banks offer an extensive source of HLA-typed cells suitable for reprogramming to iPSC. Several initiatives worldwide have been undertaken to create national and international iPSC haplobanks that match a significant part of a population. Methods: To create an iPSC haplobank that serves the Spanish population (IPS-PANIA), we have searched the Spanish Bone Marrow Donor Registry (REDMO) to identify the most frequently estimated haplotypes. From the top ten donors identified, we estimated the population coverage using the criteria of zero mismatches in HLA-A, HLA-B, and HLA-DRB1 with different stringencies: high resolution, low resolution, and beneficial mismatch. Results: We have calculated that ten cord blood units from homozygous donors stored at the Spanish cord blood banks can provide HLA-A, HLA-B, and HLA-DRB1 matching for 28.23% of the population. Conclusion: We confirm the feasibility of using banked cord blood units to create an iPSC haplobank that will cover a significant percentage of the Spanish and international population for future advanced therapy replacement strategies. [ABSTRACT FROM AUTHOR]

When faced with microangiopathic haemolytic anaemia, thrombocytopenia and organ dysfunction, clinicians should suspect thrombotic microangiopathy (TMA). The endothelial damage that leads to this histological lesion can be triggered by several conditions or diseases, hindering an early diagnosis and aetiological treatment. However, due to systemic involvement in TMA and its low incidence, an accurate early diagnosis is often troublesome. In the last few decades, major improvements have been made in the pathophysiological knowledge of TMAs such as thrombotic thrombocytopenic purpura [TTP, caused by ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin Type 1 motif, member 13) deficiency] and atypical haemolytic uraemic syndrome (aHUS, associated with dysregulation of the alternative complement pathway), together with enhancements in patient management due to new diagnostic tools and treatments. However, diagnosis of aHUS requires the exclusion of all the other entities that can cause TMA, delaying the introduction of terminal complement blockers, which have shown high efficacy in haemolysis control and especially in avoiding organ damage if used early. Importantly, there is increasing evidence that other forms of TMA could present overactivation of the complement system, worsening their clinical progression. This review addresses the diagnostic and therapeutic approach when there is clinical suspicion of TMA, emphasizing complement evaluation as a potential tool for the inclusive diagnosis of aHUS, as well as for the improvement of current knowledge of its pathophysiological involvement in other TMAs. The development of both new complement activation biomarkers and inhibitory treatments will probably improve the management of TMA patients in the near future, reducing response times and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Summary: Carfilzomib has been associated with the development of thrombotic microangiopathy (TMA) in relapsed/refractory multiple myeloma patients, a severe disease with no currently available aetiological treatment. We evaluated the potential role of terminal complement pathway in four patients with carfilzomib‐induced TMA. Membrane attack complex (C5b‐9) deposition on endothelial cells in culture exposed to plasma from patients during the acute phase of the disease suggests complement overactivation as a mechanism of potential endothelial damage in three out of four patients. If confirmed in larger cohorts, C5b‐9 evaluation will allow early identification of patients who could benefit from complement blockade and treatment monitoring. [ABSTRACT FROM AUTHOR]

In the emerging field of deformable microfluidics, we propose a new geometry in which the height and angle of a channel are controlled, thanks to the deformability of the microfluidic elastomer down to thicknesses of a few microns. The particularity of our set-up is that the height of the channel under study is fully closed at rest, which reveals especially well suited to address micro-nanoconfinement problems such as clogging, transport selectivity and flow rectification. Using fluorescence microscopy and light absorption, we probe the channel shape from the measurement of the PDMS-displacement field. We demonstrate that the maximal PDMS displacement can be inferred from finite elements numerical simulations and predicted reliably with simple analytical relations from elasticity continuum mechanics. [ABSTRACT FROM AUTHOR]

Allogeneic hematopoietic stem cell transplantation (allo‐HCT) is an effective therapy for the treatment of high‐risk haematological malignant disorders and other life‐threatening haematological and genetic diseases. Acute graft‐versus‐host disease (aGvHD) remains the most frequent cause of non‐relapse mortality following allo‐HCT and limits its extensive clinical application. Current pharmacologic agents used for prophylaxis and treatment of aGvHD are not uniformly successful and have serious secondary side effects. Therefore, more effective and safe prophylaxis and therapy for aGvHD are an unmet clinical need. Defibrotide is a multi‐target drug successfully employed for prophylaxis and treatment of veno‐occlusive disease/sinusoidal obstruction syndrome. Recent preliminary clinical data have suggested some efficacy of defibrotide in the prevention of aGvHD after allo‐HCT. Using a fully MHC‐mismatched murine model of allo‐HCT, we report here that defibrotide, either in prophylaxis or treatment, is effective in preventing T cell and neutrophil infiltration and aGvHD‐associated tissue injury, thus reducing aGvHD incidence and severity, with significantly improved survival after allo‐HCT. Moreover, we performed in vitro mechanistic studies using human cells revealing that defibrotide inhibits leucocyte‐endothelial interactions by down‐regulating expression of key endothelial adhesion molecules involved in leucocyte trafficking. Together, these findings provide evidence that defibrotide may represent an effective and safe clinical alternative for both prophylaxis and treatment of aGvHD after allo‐HCT, paving the way for new therapeutic approaches. [ABSTRACT FROM AUTHOR]

Endothelial dysfunction is an earlier contributor to the development of atherosclerosis in chronic kidney disease (CKD), in which the role of epigenetic triggers cannot be ruled out. Endothelial protective strategies, such as defibrotide (DF), may be useful in this scenario. We evaluated changes induced by CKD on endothelial cell proteome and explored the effect of DF and the mechanisms involved. Human umbilical cord vein endothelial cells were exposed to sera from healthy donors (n = 20) and patients with end‐stage renal disease on haemodialysis (n = 20). Differential protein expression was investigated by using a proteomic approach, Western blot and immunofluorescence. HDAC1 and HDAC2 overexpression was detected. Increased HDAC1 expression occurred at both cytoplasm and nucleus. These effects were dose‐dependently inhibited by DF. Both the HDACs inhibitor trichostatin A and DF prevented the up‐regulation of the endothelial dysfunction markers induced by the uraemic milieu: intercellular adhesion molecule‐1, surface Toll‐like receptor‐4, von Willebrand Factor and reactive oxygen species. Moreover, DF down‐regulated HDACs expression through the PI3/AKT signalling pathway. HDACs appear as key modulators of the CKD‐induced endothelial dysfunction as specific blockade by trichostatin A or by DF prevents endothelial dysfunction responses to the CKD insult. Moreover, DF exerts its endothelial protective effect by inhibiting HDAC up‐regulation likely through PI3K/AKT. [ABSTRACT FROM AUTHOR]

The first experimental evidence of polymer adsorption in natural carbonates obtained from streaming potential measurements is presented. The surface probing of the Estaillades core was realized in a highly saline environment with I ~ 3 M similar to formation water naturally found in some oil reservoirs, which are typical target for enhanced oil recovery (EOR) by Smart Water Injection Methods (SWIM) and Hybrid SWIM. A highly sensitive setup with an exceptional signal-to-noise ratio even at high salinity, allowing to discriminate voltage fluctuations below 0.1 mV, was used to probe the streaming potential coupling coefficient. The injection of partially hydrolyzed polyacrylamide Flopaam 3130S was followed by chase flooding with formation water for several pore volumes, to assure that any changes measured after the polymer flooding are due to the retained polymer. We show that the streaming potential coupling coefficient changes sign after polymer adsorption. This result not only is an unambiguous evidence for polymer adsorption but has implications on chemical EOR scenarios that need to consider wettability changes due to inversion of surface charge. [ABSTRACT FROM AUTHOR]

Angiogenesis and endothelial activation and dysfunction have been associated with acute graft-vs.-host disease (aGVHD), pointing to the endothelium as a potential target for pharmacological intervention. Defibrotide (DF) is a drug with an endothelium-protective effect that has been approved for the treatment of veno-occlusive disease/sinusoidal obstruction syndrome after allogeneic hematopoietic cell transplantation. Clinical data suggest that DF also reduces the incidence of aGVHD; however, the mechanisms of DF-mediated aGVHD regulation have not been examined. To investigate possible DF-mediated prophylactic and therapeutic mechanisms in aGVHD, we performed in vitro studies using endothelial cell (EC) lines. We found that DF significantly and dose-dependently suppressed EC proliferation and notably reduced their ability to form vascular tubes in Matrigel. To explore whether DF administered prophylactically or therapeutically has a significant effect on aGVHD endothelial dysfunction, ECs were exposed to media containing sera from patients with aGVHD (n = 22) in the absence or presence of DF and from patients that did not develop aGVHD (n = 13). ECs upregulated adhesion molecules (vascular cell adhesion molecule 1, intercellular adhesion molecule 1), the adherence junction protein VE-cadherin, von Willebrand factor (VWF), and Akt phosphorylation in response to aGVHD sera. These responses were suppressed upon treatment with DF. In summary, DF inhibits vascular angiogenesis and endothelial activation induced by sera from aGVHD patients. Our results support the view that DF has notable positive effects on endothelial biology during aGVHD. [ABSTRACT FROM AUTHOR]

Information on pharmacodynamic monitoring after allogeneic hematopoietic cell transplantation (allo-SCT) to evaluate individual responses to immunosuppressive drugs is scarce. We studied the relationship between a panel of pharmacodynamic markers monitored during the first 3 months after transplant and the occurrence of graft-versus-host disease (GVHD). Lymphocyte activation assessed by intracellular ATP concentration in CD4+ T cells, a high percentage of CD8+ effector T cells, and a low percentage of CD4+ regulatory T (Treg) cells correlated significantly with GVHD. A cutoff value of 0.5 for the CD8+ effector T/Treg ratio provided the most accurate diagnosis of GVHD (sensitivity 58.8%, specificity 91%). These pharmacodynamic markers may provide an efficient complement to standard pharmacokinetic monitoring of immunosuppressive drugs after allo-SCT. [ABSTRACT FROM AUTHOR]

Sinusoidal obstruction syndrome ( SOS), also called veno-occlusive disease of the liver, is one of the most relevant complications of endothelial origin that appears early after haematopoietic cell transplantation ( HCT). Despite its relatively low incidence and the fact that most cases of SOS resolve spontaneously, the cases that evolve to multi-organ failure ( MOF; severe SOS) have a mortality rate higher than 80% and represent one of the major clinical problems after HCT. For this reason, transplantation teams must have a pre-established policy regarding preventive measures in high-risk patients, strict daily control of weight and fluid balance during HCT, homogeneous diagnostic criteria, appropriate complementary studies for a correct differential diagnosis and measures to prevent and manage hepatorenal syndrome; in addition they must also be ready to start early treatment with defibrotide in patients with a possible severe SOS. Due to the lack of definitive evidence to enable the establishment of general recommendations in the management of SOS, this review analyses all of these aspects based on the author's personal experience. [ABSTRACT FROM AUTHOR]

Objectives Information on the efficacy of extended meropenem administration in neutropenic patients is scarce. Our objective was to determine whether the administration of meropenem in a 4 h extended infusion (EI) leads to a better clinical outcome in patients with febrile neutropenia than the conventional short infusion (SI). Methods This was a retrospective observational study. The subjects were neutropenic patients who presented with fever after receiving haematopoietic stem-cell transplantation or induction chemotherapy for acute myeloid leukaemia. The primary endpoint was the success of treatment after 5 days of meropenem therapy, defined as follows: the disappearance of fever leading to a maintained (≥24 h) feverless state; the resolution or improvement of the clinical signs and symptoms of infection; the absence of persistent or breakthrough bacteraemia; and no additional antibiotics prescribed because of an unsatisfactory clinical evolution. Results Eighty-eight patients received meropenem (1 g/8 h) in SI and 76 received the same dose in EI. Treatment success on day 5 was superior in the EI group [52/76 (68.4%) versus 36/88 (40.9%); P < 0.001]. Meropenem administered in EI was independently associated with success (OR 3.13, 95% CI 1.61–6.10). Fewer additional antibiotics were prescribed in the EI group during the first 5 days of treatment [20/76 (26.3%) versus 44/88 (50.0%); P = 0.002]. Using Kaplan–Meier survival analysis a more prompt defervescence and a faster decrease in C-reactive protein concentration were observed in the EI group (P = 0.021 and P = 0.037, respectively). There were no significant differences in the length of hospital stay and in the mortality rate. Conclusions Meropenem administration in EI results in a better clinical outcome for febrile neutropenia episodes, with fewer additional antibiotics needed. [ABSTRACT FROM PUBLISHER]

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revista Española de Quimioterapia is the property of Sociedad Espanola de Quimioterapia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Invasive mold infection (IMI) remains a major cause of mortality in high-risk hematological patients. The aim of this multicenter retrospective, observational study was to evaluate antifungal combination therapy (ACT) for proven and probable IMI in hematological patients. We analyzed 61 consecutive cases of proven (n=25) and probable (n=36) IMI treated with ACT collected from eight Spanish hospitals from January 2005 to December 2009. Causal pathogens were: Aspergillus spp (n=49), Zygomycetes (n=6), Fusarium spp (n=3), and Scedosporium spp (n=3). Patients were classified in three groups according to the antifungal combination employed: Group A, liposomal amphotericin B (L-AmB) plus caspofungin (n=20); Group B, LAmB plus a triazole (n=20), and Group C, voriconazole plus a candin (n=21). ACT was well tolerated with minimal adverse effects. Thirty-eight patients (62%) achieved a favorable response (35 complete). End of treatment and 12-week survival rates were 62% and 57% respectively, without statistical differences among groups. Granulocyte recovery was significantly related to favorable response and survival (p<0.001) in multivariate analysis. Our results suggest that comparable outcomes can be achieved with ACT in high risk hematological patients with proven or probable IMI, whatever the combination of antifungal agents used. [ABSTRACT FROM AUTHOR]

A 40-year-old man with severe chronic idiopathic CD4+ lymphocytopenia complicated with opportunistic infections was successfully treated with non-myeloablative allogeneic hematopoietic stem cell transplantation. After conditioning with fludarabine plus low dose of total-body irradiation, CD34+ peripheral blood stem cells obtained by leukapheresis from his HLA-identical sister were infused. T cell and myeloid complete chimerism was achieved at day +28 and remained stable during the follow-up period. The patient did not develop infectious complications during the procedure. At 35 months of follow-up, his CD4+ T cell count was 1019 cells per microliter. Non-myeloablative allogeneic hematopoietic stem cell transplantation should be considered a treatment option for patients with severe forms of idiopathic CD4+ lymphocytopenia. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Hematology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Sixty-one patients with refractory or relapsed Hodgkin's lymphoma (HL) underwent high-dose chemotherapy and autologous stem cell transplantation (ASCT). All patients had active HL at the time of ASCT: 13 patients had partial remission, 14 refractory disease, 18 sensitive relapse, 4 resistant relapse, and 12 nontreated relapse. Overall transplant-related mortality (TRM) was 16.4% at 1 year. Twenty-eight patients (46%) achieved complete remission (CR). Actuarial 5-year overall survival (OS) and progression-free survival (PFS) were 51% and 47%, respectively. Patients with positive gallium-67 scintigraphy at 3 - 6 months after transplantation had a worse PFS at 5 years (28%) than those with negative 67Ga scan (80%) (p = 0.016), whereas no statistical differences were observed between patients with residual mass and those in CR according to computed tomography scan. In multivariate analysis, bulky disease at diagnosis, bone marrow stem cells, and stage IV at transplant were the only adverse prognostic factors significantly influencing OS. Bulky disease at diagnosis and stage IV at transplant adversely influenced PFS. Although long-term outcome of patients with active HL at the time of ASCT is poor due to a high TRM and a low CR after transplantation, a subgroup of patients with no adverse prognostic factors at ASCT gain benefit from this treatment. [ABSTRACT FROM AUTHOR]

Extrusion rates are often limited by the surface cracks originating at the die exit. These cracks can be so severe in the case of certain polymers that the phenomenon known as “flow split” occurs. Previous work by the same authors explains the macroscopic mechanisms leading to flow split observed during the extrusion of polystyrene-block-poly(ethylene-co-buylene)-block-polystyrene block copolymers in their microphase separated state. The present paper looks at the effects of extrusion on the structure of these block copolymers at regimes showing the different characteristic defects of the fluids. The structure of extruded samples is examined by small-angle x-ray scattering (SAXS). A comparison between the relaxation times characteristic of the copolymers and the time necessary to prepare the samples shows that quenching of samples the flow of which is stable at the die exit is practically impossible with a standard capillary rheometer. Hence, in situ experiments inside the die are necessary to understand the structure changes occurring during the extrusion process. For this reason, a new capillary rheometer equipped with a beryllium die, transparent to x rays, is developed and preliminary tests are performed. The results validate the design and show the feasibility of on-line experiments. Moreover, an interpretation that relates the macroscopic defects and structure observed with SAXS experiments is proposed. [ABSTRACT FROM AUTHOR]

BACKGROUND: The de novo development of anti-D after D-mismatched allogeneic hematopoietic stem cell transplantation (AHSCT) is a possibility that must be considered. The transfusion of D− blood components after AHSCT has been recommended but anti-D alloimmunization in this setting has been studied little. Thus, the aim of this study was to analyze anti-D formation after D-mismatched AHSCT. STUDY DESIGN AND METHODS: Thirty patients with a hematologic disease who underwent D-mismatched AHSCT were retrospectively studied. Support therapy included red blood cells (RBCs) and platelet (PLT) concentrates (PCs) from whole-blood donations and PLTs from apheresis. After AHSCT, patients received D+ PCs without administering Rh immunoglobulin (RhIG). An antibody screening to detect anti-D was performed by low-ionic-strength saline-indirect antiglobulin test with the tube test. RESULTS: Fifteen D+ patients received stem cells (SCs) of D− donors and 15 D− patients received SCs of D+ donors. After AHSCT, patients received a median of 11.5 (range, 0-32) D− RBC units. D+ patients received 682 (83%) of 825 PLT units from D+ donors, and D− patients received 573 (85%) of 678 PLT units from D+ donors. None of the 30 patients developed anti-D after a median follow-up of 32 weeks (range, 4-310 weeks). CONCLUSION: Anti-D alloimmunization after performing a D-mismatched AHSCT is infrequent in patients with hematologic diseases although patients receive D−mismatched PLT transfusions without RhIG administration. [ABSTRACT FROM AUTHOR]

The graft- versus-host disease (GVHD) characteristics of 150 consecutive patients undergoing reduced intensity conditioning allogeneic (allo-RIC) transplants and 88 patients undergoing myeloablative conditioning regimen were analysed. All patients received the same GVHD prophylaxis and peripheral blood stem cells from a human leucocyte antigen identical sibling. The cumulative incidence of acute GVHD (aGVHD) was 67% and 44% in the myeloablative and allo-RIC regimen groups, respectively ( P < 0·001), and was 39% vs. 29%, respectively ( P = 0·043), for grades 2–4 aGVHD. Only conditioning type (myeloablative versus allo-RIC) significantly influenced the incidence of aGVHD in multivariate analysis: Hazard ratio (HR) = 2·16 [95% confidence interval (CI): 1·52–3·07], P < 0·0001. The cumulative incidence of chronic GVHD (cGVHD) was 63% and 71% among myeloablative and allo-RIC patients respectively ( P = 0·084). This trend was because of the higher incidence of limited cGVHD, but not extensive cGVHD among allo-RIC recipients [HR = 3·3 (95% CI: 1·42–8·08), P = 0·0017]. Moreover, among patients who developed cGVHD, the cumulative incidence of limited cGVHD was significantly lower in the myeloablative group than in the allo-RIC group (7% vs. 25%, P = 0·007). Duration of immunosuppression was shorter among allo-RIC patients (35·5% vs. 68·8% required systemic immunosuppression 36 months after transplant, P = 0·028). Although prospective controlled trials are required to further evaluate the effect of the conditioning regimen on GVHD, our results suggest that RIC modifies the incidence and characteristics of both acute and cGVHD after allogeneic transplantation, and decreases the immunosuppression requirements in long-term follow up when compared with myeloablative conditioning. [ABSTRACT FROM AUTHOR]

To examine shifts in the etiology, incidence, evolution, susceptibility, and patient mortality of bacterial and fungal bloodstream isolates (BSIs) from hematopoietic stem cell transplantation (HSCT) recipients, we reviewed the BSIs of 796 patients who underwent an HSCT in our institution during a 10-year period. Four hundred eighty-nine episodes of bacterial and fungal BSI were detected in 330 patients (41%). Three hundred ten isolates (63%) were gram-positive bacteria, 142 (29%) were gram-negative, and 18 and 19 isolates were different species of anaerobic organism andCandidaspp. (both 4%). Coagulase-negative staphylococci (CoNS), with 210 isolates, were the organism most frequently isolated in each year of study and during the three phases of immune recovery after HSCT. The ratio of gram-positive to gram-negative has declined from 3.3 (1991-1992) to 1.8 (1999-2000). Crude mortality occurred in 47 cases of 489 BSI episodes (10%). Mortality according to groups was gram-negative, 7%; gram-positive, 9%; and anaerobic bacteria, 11%.Candidaspp. was the group that accounted for the highest crude mortality, with 42%. Gram-positive microorganisms were isolated more often than gram-negative organisms, but the trend is reversing. CoNS were the leading pathogen during the 10 years of study and during the three phases of immune recovery after HSCT. Crude mortality of HSCT patients with BSI was low except for infections caused byCandidaspp. [ABSTRACT FROM AUTHOR]

Serum procalcitonin (PCT) levels have been proposed as a new discriminative marker for bacterial and fungal infections. We analysed the diagnostic relevance of PCT in febrile episodes of neutropenic adult patients after haematopoietic stem cell transplantation (HSCT). PCT was determined prospectively in 92 febrile episodes, classified according to the final diagnosis as: neutropenic fever of unknown origin ( n = 51), microbiological ( n = 26) or clinical ( n = 5) documented infection and non-infectious febrile episodes ( n = 10). On first day of fever, mean (±SD) PCT level was 0·3 ng/ml (0·2) in neutropenic fever of unknown origin, 0·5 ng/ml (0·7) in microbiologically confirmed infections, 0·2 ng/ml (0·2) in clinically documented infections and 1·7 (4·2) in non-infectious fever ( P = not significant). Five days after the antibiotic therapy was started, fever persisted in 29 neutropenic episodes (32%). Cases that were eventually diagnosed with invasive aspergillosis had PCT values significantly higher [10·1 ng/ml (6·7)] than all remaining groups ( P = 0·027; Kruskal–Wallis). Our analysis indicates that the PCT level on first day of fever did not facilitate the differential diagnosis of neutropenic febrile episode. However, when fever persisted for more than 5 d, PCT values ≥3 ng/ml had a high sensitivity and specificity for the diagnosis of invasive aspergillosis. [ABSTRACT FROM AUTHOR]

Disparity for the minor histocompatibility antigen HA-1 between patient and donor has been associated with an increased risk of acute graft-versus-host disease (GvHD) after allogeneic human leucocyte antigen (HLA)-identical sibling donor stem cell transplantation (SCT). However, no data concerning the impact of such disparity on chronic GvHD, relapse or overall survival are available. A retrospective multicentre study was performed on 215 HLA-A2-positive patients who received an HLA-identical sibling SCT, in order to determine the differences in acute and chronic GvHD incidence on the basis of the presence or absence of the HA-1 antigen mismatch. Disease-free survival and overall survival were also analysed. We detected 34 patient–donor pairs mismatched for HA-1 antigen (15·8%). Grades II–IV acute GvHD occurred in 51·6% of the HA-1-mismatched pairs compared with 37·1% of the non-mismatched. The multivariate logistic regression model showed statistical significance (P: 0·035, OR: 2·96, 95% CI: 1·07–8·14). No differences were observed between the two groups for grades III–IV acute GvHD, chronic GvHD, disease-free survival or overall survival. These results confirmed the association between HA-1 mismatch and risk of mild acute GvHD, but HA-1 mismatch was not associated with an increased incidence of chronic GvHD and did not affect relapse or overall survival. [ABSTRACT FROM AUTHOR]

To assess the influence of graft-versus-host disease (GVHD) on the outcome of patients with advanced haematological malignancies (AHM) who received a primary, unmodified allogeneic peripheral blood progenitor cells transplant (allo-PBT) from a human leucocyte antigen (HLA) identical sibling donor, we analysed 136 patients with myeloid neoplasms (n = 70) or lymphoproliferative disorders (n = 66), transplanted at 19 Spanish institutions. Median age was 35 years (range 1–61). The cumulative incidence of relapse for all patients was 34% (95% CI, 26–42%), 41% (95% CI, 33–49) for patients without GVHD and 14% (95% CI, 3–25) (P = 0·001) for patients with acute and chronic GVHD. After a median follow-up of 11 months (range 2–49), 60 (44%) patients remained alive with an actuarial probability of overall survival and disease-free survival (DFS) at 30 months of 31% (95% CI, 21–41%) and 28% (95% CI, 17–39%) respectively. In patients surviving > 100 d, the low incidence of relapse in those with acute and chronic GVHD led to a DFS of 57% (95% CI, 38–76%) compared with a DFS of 34% (95% CI, 17–51%) in the remaining patients (P = 0·03). Our results indicate a reduced incidence of relapse for patients with AHM receiving an unmodified allo-PBT and developing acute and chronic GVHD, which results in an improved DFS. [ABSTRACT FROM AUTHOR]

Abstract: The clinical syndrome of veno-occlusive disease (VOD) after hemopoietic cell transplantation is characterised by jaundice, painful liver enlargement, and fluid retention with weight gain. Cytoreductive therapy is presumably the primary cause of VOD, but several other agents (and a special susceptibility of the liver) can also play a role in its genesis. The risk of VOD can be predicted before BMT by analysing the presence or absence of the main risk factors. For the diagnosis of VOD most teams worldwide apply the clinical criteria developed by both the Seattle and Baltimore teams. Transjugular liver studies and some biological markers can help establish a correct differential diagnosis. In most cases clinical manifestations improve after several days, but 20 - 25% of patients could die of VOD. Data regarding whether or not pharmacological prophylactic measures are effective are contradictory. There a few therapeutical approaches directed towards the improvement of venular occlusion; recombinant tissue plasminogen activator and defibrotide can solve some cases of severe VOD. [ABSTRACT FROM AUTHOR]