Non-cryopreserved peripheral blood progenitor cells collected by a single very large-volume leukapheresis: a simplified and effective procedure for support of high-dose chemotherapy

High-dose chemotherapy with autologous peripheral blood progenitor cell (PBPC) support has become a widely used treatment strategy. In order to simplify the procedure, a single very large-volume leukapheresis programme combined with short-term refrigerated storage of the PBPC was developed. Seventy-two patients suffering from various relatively chemosensitive malignancies received high-dose chemotherapy, consisting of agents with short in vivo half-lives and 24 to 48 hours later, the refrigerated PBPC were reinfused. A single very large-volume apheresis was sufficient to obtain at least 2 x 10(6)/kg CD34+ cells in 58 patients (81%), and 63% had at least 2.5 x 10(6) CD34+ cells/kg. Only two patients (3%) were transplanted with less than 1 x 10(6) CD34+ cells/kg. In three patients (4%) leukapheresis was repeated because of insufficient number of PBPC. The median CD34+ cell count was 3 x 10(6)/kg. A median of 38.5 L blood (range, 21 to 59) was processed, which accounted for a median of 9 x patient's total blood volume. Very large-volume leukapharesis was well tolerated with symptomatic hypocalcemia being the most common (18%) side-effect. The median time to neutrophils >1.5 x 10(9)/L, and to self-supporting platelet count >25 x 10(9)/L, was 10 and 12 days after reinfusion of PBPC graft, respectively. There were no treatment-related deaths. Our results indicate that this simplified approach of PBPC transplantation can be associated with prompt hematologic recovery in most patients and that it can be useful in settings where facilities are limited or for certain diseases where conditioning regimens with short half-life are appropriate. J. Clin. Apheresis, 15:236-241, 2000.     

Accelerated immune red cell destruction in the absence of serologically detectable alloantibodies

Two patients are described in whom clinically significant red blood cell alloantibodies could be demonstrated only by in vivo 51chromium (51Cr) survival studies. The first patient had experienced a severe delayed hemolytic transfusion reaction to four units of crossmatch compatible blood. Serial phenotype studies suggested the presence of a serologically undetectable anti-c (hr') antibody. 51Cr survival of c- positive red blood cells was one per cent at 24 hours, while survival of c-negative red blood cells was 80 per cent at 24 hours. The second patient had multiple red blood cell alloantibodies. An anti-c antibody was suspected but could not be convincingly demonstrated by in vitro techniques. 51Cr survival of c-positive red blood cells, however, was 57 per cent at 24 hours and 17 per cent at 48 hours. 51Chromium red blood cell survival studies should be considered whenever an unexplained hemolytic transfusion reaction occurs, or when an expected red blood cell alloantibody cannot be demonstrated by in vitro laboratory studies.     

Activated Notch1 signaling promotes tumor cell proliferation and survival in Hodgkin and anaplastic large cell lymphoma

Notch signaling controls cell fate decisions of hematopoietic progenitors by inhibiting certain steps of differentiation and inducing either self-renewal or differentiation toward lymphoid or myeloid lineages. In addition, truncated Notch1 alleles could be associated with 10% of all cases of human T lymphoblastic leukemia and, when introduced into mouse bone marrow stem cells, cause T-cell neoplasms. However, functional links between the abundant expression of intact Notch1 and oncogenesis are still lacking. Here we show that Notch1 is highly expressed in B- and T-cell-derived tumor cells of Hodgkin and anaplastic large cell lymphoma. We demonstrate a novel mechanism for the oncogenic capacity of Notch1 by showing that the interaction between intact Notch1 on tumor cells and its ligand Jagged1 dramatically induces proliferation and inhibition of apoptosis in vitro. We further provide evidence that in Hodgkin and anaplastic large cell lymphoma, Jagged1 is expressed in malignant and in bystander cells colocalizing with Notch1-positive tumor cells. Notch1 signaling may therefore be activated in tumor cells by Jagged1 through homotypic or heterotypic cell-cell interactions, and it seems likely that these interactions contribute to lymphomagenesis in vivo. Thus, our data suggest that activated Notch1 signaling plays an important role in the pathobiology of Hodgkin and anaplastic large cell lymphoma and that it might be a potential new target for treatment.     

Higher myocardial strain rates during isovolumic relaxation phase than during ejection characterize acutely ischemic myocardium

OBJECTIVES: The aim of this study was to define an index that can differentiate normal from ischemic myocardial segments that exhibit postsystolic shortening (PSS). BACKGROUND: Identification of ischemia based on the reduction of regional systolic function is sometimes challenging because other factors such as normal nonuniformity in contraction between segments, tethering effect, pharmacologic agents, or alterations in loading conditions can also cause reduction in regional systolic deformation. The PSS (contraction after the end of systole) is a sensitive marker of ischemia; however, inconsistent patterns have also been observed in presumed normal myocardium. METHODS: Twenty-eight open-chest pigs underwent echocardiographic study before and during acute myocardial ischemia induced by coronary artery occlusion. Ultrasound-derived myocardial longitudinal strain rates were calculated during systole (S(SR)), isovolumic relaxation (IVR(SR)), and rapid filling (E(SR)) phases in both ischemic and normal myocardium. Systolic strain (epsilon(sys)) and postsystolic strain (epsilon(ps)) were calculated by integrating systolic and postsystolic strain rates, respectively. RESULTS: During ischemia, S(SR), E(SR), and epsilon(sys) in ischemic segments were significantly lower (in magnitude) than in nonischemic segments or at baseline. However, some overlap occurred between ischemic and normal values for all three parameters. At baseline, 18 of 28 animals had negative IVR(SR) (i.e., PSS) in at least one segment. During coronary artery occlusion, IVR(SR) became negative and larger in magnitude than S(SR) in all ischemic segments. The IVR(SR)/S(SR) and epsilon(ps) best differentiated ischemic from nonischemic segments. CONCLUSIONS: In the presence of reduced regional systolic deformation, a higher rate of PSS than systolic shortening identifies acutely ischemic myocardium.     

Sutureless technique to support anastomosis during thoracic aorta replacement

Background  

In aortic replacement procedures the aortic wall and Teflon strips form a double layer, with the use of continuous sutures. Surgical glues may or may not be used to enhance the durability of the anastomoses. In this technical report a modification of the aortic stumps preparation is devised.     

Acute heart failure: is there a role for surgery?

Many of the disorders and lesions leading to acute heart failure can be treated surgically. Modern surgical techniques like the off pump coronary surgery, newer techniques for the surgical treatment of the mechanical complications of acute MI and valvular reparative techniques have been added to the surgical armamentarium in recent years. Modern ventricular assist devices have started their career in the clinical arena promising to be less invasive. At the same time the spectrum of indications for mechanical circulatory support continues to witness a rapid expansion. Technical advances have led to an evolution of surgical strategies. Heart failure surgery is now in a position to offer improved outcomes, avoidance of recurrence of acute heart failure or the development of advanced chronic heart failure.     

Quality and safety of fresh-frozen plasma inactivated and leucoreduced with the Theraflex methylene blue system including the Blueflex filter: 5 years' experience

BACKGROUND AND OBJECTIVES: The objective of this paper is to present 5 years' experience of pathogen inactivation of fresh-frozen plasma with the methylene blue system in a blood centre in Athens. MATERIALS AND METHODS: Eight thousand and five hundred units treated by methylene blue and 54 435 untreated were issued for transfusion in four hospitals during the period 2000-2005. Eighty-eight units were evaluated for changes in coagulation factor activity and cytokine concentrations following treatment. RESULTS: Coagulation factor losses were in the accepted range. Adverse reactions were 1 : 8500 with treated and 1 : 2177 with untreated units. The five serious reactions were all in untreated units. No seroconversions for infectious diseases were reported. CONCLUSIONS: Methylene-blue-treated fresh-frozen plasma is safer than the untreated product even in patients who require large quantities of plasma transfusion.