Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells in leukapheresis product and bone marrow for clinical transplantation: a comparison of three methods.

Flow cytometric enumeration of CD34+ hematopoietic stem and progenitor cells (HSCs) is widely used for evaluation of graft adequacy of peripheral blood and bone marrow stem cell grafts. In the present study, we review and compare the major counting techniques of stem and progenitor cells. The methods are: the Milan/Mullhouse protocol, two-platform ISHAGE (International Society of Hematotherapy and Graft Engineering) and single-platform ISHAGE analysis system. According to the Milan/Mulhouse protocol, HSCs are identified by CD34 antibody staining and easy gating strategy. The ISHAGE guidelines for detection of CD34+ cells are based on a four-parameter flow cytometry method (CD34PE/CD45PerCP staining, side and forward angle light scatter) thus employing multiparameter gating strategy. With two-platform ISHAGE protocol, an absolute CD34+ count is generated by incorporating the leukocyte count from an automated hematology analyser. The single-platform ISHAGE method to determine the absolute CD34+ count directly from a flow cytometer includes the use of Trucount tubes (Becton Dickinson) with a known number of fluorescent beads. CD34+ cells were quantified in mobilized peripheral blood, collected by leukapheresis, and bone marrow from 42 samples from patients with hematological malignancies. The differences against the means display low disagreement between the Milan/Mulhouse and ISHAGE protocols, with discrepancies of up to 2.5% (two-platform ISHAGE)--2.6% (single-platform ISHAGE) in enumeration of CD34+ cells in leukapheresis product and 4.8% (two-platform ISHAGE)--4.9% (single-platform ISHAGE) in bone marrow. Our results show high correlation among all three methods. Since the three protocols are compatible, choosing the most convenient in terms of costs, simplicity and compliance with clinical results appears to be a logical consequence

Individual quality assessment of autografting by probability estimation for clinical endpoints: a prospective validation study from the European group for blood and marrow transplantation.

The aim of supportive autografting is to reduce the side effects from stem cell transplantation and avoid procedure-related health disadvantages for patients at the lowest possible cost and resource expenditure. Economic evaluation of health care is becoming increasingly important. We report clinical and laboratory data collected from 397 consecutive adult patients (173 non-Hodgkin lymphoma, 30 Hodgkin lymphoma, 160 multiple myeloma, 7 autoimmune diseases, and 28 acute leukemia) who underwent their first autologous peripheral blood stem cell transplantation (PBSCT). We considered primary endpoints evaluating health economic efficacy (eg, antibiotic administration, transfusion of blood components, and time in hospital), secondary endpoints evaluating toxicity (in accordance with Common Toxicity Criteria), and tertiary endpoints evaluating safety (ie, the risk of regimen-related death or disease progression within the first year after PBSCT). A time-dependent grading of efficacy is proposed with day 21 for multiple myeloma and day 25 for the other disease categories (depending on the length of the conditioning regimen) as the acceptable maximum time in hospital, which together with antibiotics, antifungal, or transfusion therapy delineates four groups: favorable (≤7 days on antibiotics and no transfusions; ≤21 [25] days in hospital), intermediate (from 7 to 10 days on antibiotics and 7 days on antibiotics, >3 but 30/34 days in hospital after transplantation), and very unfavorable (>10 days on antibiotics, >6 transfusions; >30 to 34 days in hospital). The multivariate analysis showed that (1) PBSC harvests of ≥4 × 106/kg CD34 + cells in 1 apheresis procedure were associated with a favorable outcome in all patient categories except acute myelogenous leukemia and acute lymphoblastic leukemia (P = .001), (2) ≥5 × 106/kg CD34 + cells infused predicted better transplantation outcome in all patient categories (P 500 mL) (P = .002), and (5) patients with a central venous catheter during both collection and infusion of PBSC had a more favorable outcome post-PBSCT than peripheral access (P = .007). The type of mobilization regimen did not affect the outcome of auto-PBSCT. The present study identified predictive variables, which may be useful in future individual pretransplantation probability evaluations with the goal to improve supportive care

21 Analiza wczesnych i późnych powikłań w grupie chorych leczonych na ziarnicę złośliwą w Centrum Onkologii w Warszawie w latach 1994–1998

W okresie 01.01.1994 do 30.06.1998 w Klinice Radioterapii, a następnie w Klinice Nowotworów Układu Chłonnego Centrum Onkologii – Instytut w Warszawie przeprowadzono prospektywne badania kliniczne, w którym oceniono powikłania leczenia w grupie chorych na ziarnicę złośliwą w stopniach zaawansowania klinicznego I–IV.MateriałAnalizie poddano 426 chorych w tym 206 kobiet i 220 mężczyzn w wieku 15–77 lat (średnio 35). Przeważali chorzy II stopniu zaawansowania klinicznego, bez objawów ogólnych (A) oraz o stwierdzonym typie mikroskopowym ziarnicy złośliwej NS 1 (szczegółowa charakterystyka grupy zostanie przedstawiona w tabelach).MetodaAnalizowaną grupę podzielono na 3 podgrupy: samodzielna radioterapia, samodzielna chemioterapia i metoda leczenia skojarzonego (chemio-radioterapia). Leczenie chemiczne prowadzono schematami: MOPP, MOPP/ABV, EVA; natomiast napromienianie w warunkach terapii megawoltowej promieniami gamma kobaltu 60 lub fotonami X o energii 4,9 lub 15 MeV. Wszystkie badania diagnostyczne (badania laboratoryjne i hormonalne, radiologiczno - ultrasonograficzne) niezbędne tło oceny stopnia zaawansowania choroby, stanu funkcji badanych narządów poddanych ocenie powikłań stosowano wyłącznie w oparciu o bazę Centrum Onkologii w Warszawie. W każdej analizowanej podgrupie przeprowadzono analizę wczesnych i późnych powikłań stosowanego leczenia w oparciu o wiarygodną ocenę stanu chorego przed leczeniem, a powikłania oceniono według stosowanych skal WHO i EORTC / RTOG.Analizie statystycznej poddano również wpływ czynników rokowniczych ziarnicy złośliwej na występowanie powikłań i wzajemne korelacje między nimi.WynikiLeczenie ukończyło obecnie 273 chorych, 51 chorych kontynuuje leczenie z powodu nawrotu procesu chorobowego. Zmarło 48 chorych pierwszorazowych (14 kobiet i 34 mężczyzn), z powodu postępu choroby (33 chorych), powikłań stosowanego leczenia (6 chorych), drugiego nowotworu (6 chorych) oraz z innych przyczyn (3 chorych). Okres obserwacji chorych po leczeniu wynosił od 9 do 54 miesięcy. Średni czas przeżycia chorych znajdujących się w remisji po leczeniu dla całej grupy wynosi 22 miesiące.Przedstawiono szczegółową analizę najczęściej występujących powikłań wczesnych i późnych: hematologiczne, neurologiczne, hormonalne i kardiologiczne oraz analizę przyczyn zgonów wraz z metodologią prowadzonego badania prospektywnego

Measurements of π±\pi^\pm, K±^\pm, p and pˉ\bar{\textrm{p}} spectra in proton-proton interactions at 20, 31, 40, 80 and 158 GeV/c with the NA61/SHINE spectrometer at the CERN SPS

Measurements of inclusive spectra and mean multiplicities of $\pi^\pm$, K$^\pm$, p and $\bar{\textrm{p}}$ produced in inelastic p+p interactions at incident projectile momenta of 20, 31, 40, 80 and 158 GeV/c ($\sqrt{s} =$ 6.3, 7.7, 8.8, 12.3 and 17.3 GeV, respectively) were performed at the CERN Super Proton Synchrotron using the large acceptance NA61/SHINE hadron spectrometer. Spectra are presented as function of rapidity and transverse momentum and are compared to predictions of current models. The measurements serve as the baseline in the NA61/SHINE study of the properties of the onset of deconfinement and search for the critical point of strongly interacting matter

Is good clinical practice becoming poor clinical care?

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Choosing project risk management techniques. A theoretical framework

The pressure for increasing quality while reducing time and costs places particular emphasis on managing risk in projects. To this end, several models and techniques have been developed in literature and applied in practice, so that there is a strong need for clarifying when and how each of them should be used. At the same time, knowledge about risk management is becoming of paramount importance to effectively deal with the complexity of projects. However, communication and knowledge creation are not easy tasks, especially when dealing with uncertainty, because decision-making is often fragmented and a comprehensive perspective on the goals, opportunities, and threats of a project is missing. With the purpose of providing guidelines for the selection of risk techniques taking into account the most relevant aspects characterising the managerial and operational scenario of a project, a theoretical framework to classify these techniques is proposed. Based on a literature review of the criteria to categorise risk techniques, three dimensions are defined: the phase of the risk management process, the phase of the project life cycle, and the corporate maturity towards risk. The taxonomy is then applied to a wide selection of risk techniques according to their documented applications. This work helps to integrate the risk management and the knowledge management processes. Future research efforts will be directed towards refining the framework and testing it in multiple industrie

Brentuximab Vedotin with Chemotherapy for Stage III or IV Hodgkin's Lymphoma

Brentuximab vedotin is an anti-CD30 antibody-drug conjugate that has been approved for relapsed and refractory Hodgkin's lymphoma