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To assess the kinetics of lymphocyte subset recovery, 758 allografted patients were monitored by surface markers (CD3, CD4, CD8, CD56), with a 5-year follow-up. The donor was a matched sibling donor (MSD) ( n =502) or an alternative donor (family mismatched or unrelated, AD) ( n =256). The stem cell source was bone marrow for all patients. CD4+ cell recovery was influenced—in univariate analysis—by three factors: donor type, patient age and GvHD. This was not the case for CD8+ and CD56+ cells. The median CD4+ cell count on day +35 after HSCT was 86/μl. Patients achieving this CD4+ cell count had significantly lower transplant-related mortality (TRM) compared to patients who did not achieve this CD4+ cell count (20 vs 39%, P =0.00001), due to a lower risk of lethal infections (24 vs 47%, P =0.0003). In multivariate analysis MSD (RR 3.45, P =0.0001) and recipient age less than 16 years (RR 3.23, P =0.003) were significantly associated with a better CD4+ cell recovery. CD4+ counts on day +35 was predicted TRM (RR=1.97, P =0.0017) together with acute GvHD grade II–IV (RR 1.59, P =0.0097). No difference of TRM was observed for CD8+ and CD56+ cell counts.

This is a dose-finding study using foscarnet for CMV prophylaxis after allogeneic bone marrow transplantation (BMT) in 20 high risk patients (unrelated donors, or T cell depleted, and/or advanced disease). Foscarnet was started on day +1 after BMT and continued until day +100. We explored four different dose levels, patients being entered at the lowest dose level until one patient experiences CMV-reactivation, identified as two consecutive positive CMV antigenemias (CMVAg-emia). The four dose levels expressed as mg/kg/day between days 1 and 30 (induction) and between days 31 and 100 (maintenance) were respectively: dose level I = 60/30 (n = 5); dose level II = 120/60 (n = 4); dose level III = 120/90 (n = 5) and dose level IV = 120/120 (n = 6). All patients showed engraftment: PMN > or =0.5 x 109/l at a median interval of 16, 21, 17, 15 days after BMT, and Plt > or =30x10(9)/l on days 19, 16, 17, 17 respectively. CMVAg-emia was seen in 10 patients at a median interval of 53 days post-BMT (range 33-89) with a median of 10 CMV antigen+ cells (range 1-16). There was a dose effect of foscarnet on CMVAg-emia: respectively 4/5 patients (80%), 2/4 (50%), 3/5 (60%) and 1/6 (18%) at dose levels I, II, III, IV (P = 0.1). CMV disease was seen in 3/9 (33%) at dose levels I, II and 0/11 at dose levels III, IV (P = 0. 07). The median number of CMV antigen-positive cells at diagnosis of CMV infection was different: 13 in dose levels I-II and two in dose levels III-IV (P = 0.01). Increased creatininine was seen in 15 patients with a mean of 1.8 mg% (range 1.5-5.7) and was the cause of discontinuation in nine patients (45%). Renal toxicity was reversible in all nine patients. Overall actuarial TRM at 2 years was 31%: 47% for patients at dose levels I-II and 19% for patients at dose levels III-IV. In conclusion, foscarnet exhibits a dose-dependent prophylactic effect on CMVAg-emia, CMV disease and transplant-related mortality with acceptable and reversible renal toxicity.

Donor lymphocyte infusions (DLI) were given between June 1990 and March 1996 to 18 patients with chronic myeloid leukemia (CML) for the treatment of cytogenetic (n = 6) or hematologic relapse (n = 12) following an allogeneic bone marrow transplant (BMT). Patients were divided in two groups: patients in group A (n = 8) received a large dose of donor lymphocytes (> or = 1 x 10(8)/kg), whereas patients in group B (n = 10) received escalating numbers of cells (2 x 10(5) up to 2 x 10(8)/kg). The median number of DLI in group A was 2 (range 1-3); the median number of infusions in group B was 7 (range 3-9). Acute GVHD occurred in 12 patients (grades I-III) and was a major cause of death in two. The risk of developing GVHD correlated with the number of cells infused: 37%, 14%, 5% and 0% for DLI with cells > or = 1 x 10(8), 2 x 10(7)/kg, 2 x 10(6)/kg, and 2 x 10(5)/kg, respectively (P = 0.01). Median transaminase levels were found to be significantly increased in patients with, as compared to patients without, acute GVHD (GPT 412 vs 28 IU/l; P = 0.03). Severe aplasia occurred in four and was a contributing cause of death in two patients. Overall, four patients died as a consequence of DLI and all received > 1 x 10(8)/kg cells: the actuarial risk was 38% in group A and 14% in group B (P = 0.1). There were 10 complete and three partial cytogenetic responses: the actuarial probability at 5 years of being Ph negative was 69%: it was 46% for group A and 85% for group B (P = 0.1). The longest patient is now 6 years post-DLI, Ph negative, BCR-ABL negative. The actuarial 3 year survival is 38% in group A and 86% in group B (P = 0.06). The study confirms that DLI post-BMT is not innocuous and that there is a definite long-lasting antileukemic effect in patients with CML. It also suggests that: (1) the risk of developing GVHD correlates with the number of infused cells; (2) that significant elevations of serum GPT levels are associated with GVHD; and (3) that the use of escalating doses of cells may allow the identification of side-effects and discontinuation of infusions before life-threatening GVHD has developed.

A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001-2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997-2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II-IV graft-versus-host disease (GvHD) (42 vs 15%, P=0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P=0.04). The actuarial survival at 5 years is 69 vs 87%, respectively (P=0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.

To assess whether brain tissue loss occurs after profound and sustained suppression of magnetic resonance imaging (MRI) enhancement, we measured brain volume changes from 10 patients with rapidly evolving secondary progressive multiple sclerosis (MS) treated with autologous haematopoietic stem cell transplantation and followed up for 24 months. An average yearly decrease of brain volume of about 1.9% was observed despite only five enhancing lesions seen on triple dose follow up scans of two patients. This indicates that, in MS, progressive loss of tissue can occur independently of concomitant MRI-visible inflammation.

'.the leukemic stem line is a small minority within the total cell mass;. when the leukemic stem line is not exceeding the normal stem cell numbers, its proliferation may still be under partial control.' LG Lajtha, Blood Cells 1981; 7: 45-62 We performed cytogenetic analysis on fresh bone marrow cells and on progenitor cell colonies in a patient who relapsed after allogeneic BMT for CML and was subsequently treated with donor lymphocyte infusions (DLI). Two Philadelphia-positive clones were identified at relapse. One clone displayed an additional chromosomal abnormality most likely induced by radio-chemotherapy and therefore arising in a single cell. This cell displays the characteristics of a stem cell, since it was able to support 20% of Ph-positive hemopoiesis for 5 months. If the progeny of a single Ph-positive stem cell account for 20% of hemopoiesis, a very low number of leukemic stem cells may sustain relapse after allogeneic BMT. This is in keeping with two observations: (1) at relapse, long-term culture initiating cells (LTC-IC) were all donor-derived and Ph-negative; (2) on average, the pace of the disease is very slow after relapse following allogeneic-BMT. Therefore, we hypothesize that a small number of leukemic stem cells may be involved in the initial events of relapse following BMT for CML.

A bone marrow harvest is filtered either in the operating room, in the laboratory or during infusion to the patient. Filters are usually discarded. Little is known of haemopoietic progenitor cells (HPCs) trapped in the filters. The aim of the study was to evaluate HPC content in the filters and to assess the outcome of transplants with filter-discarded or filter-recovered cells. Haemopoietic progenitors were grown from filters of 19 marrow transplants. We then compared the outcome of 39 filter-recovered transplants from HLA-identical siblings (years 2001–2004) with a matched cohort of 43 filter-discarded marrow grafts (years 1997–2000). Filters contained on average 21% long-term culture-initiating cells (LTC-IC) and 15% fibroblasts colony-forming units (CFU-F) of the total progenitor cell content. Filter-discarded transplants had significantly more grade II–IV graft-versus-host disease (GvHD) (42 vs 15%, P =0.008) as compared to filter-recovered transplants, and more transplant-related mortality (TRM) (20 vs 3%, P =0.04). The actuarial survival at 5 years is 69 vs 87%, respectively ( P =0.15). This study suggests that a significant proportion of LTC-IC is lost in the filters together with CFU-F. Recovery and add back of progenitors trapped in the filters may reduce GvHD and TRM.

The income tax systems of most countries entail a favourable treatment of homeownership, compared to rental-occupied housing. Such ‘homeownership bias’ and its consequences for a wide range of economic outcomes have long been recognised in the economic literature. Although a removal of the homeownership bias is generally advocated on efficiency grounds, its distributional implications are often neglected, especially in a cross-country perspective. In this paper, we aim to fill this gap by investigating the first-order effects, in terms of distribution of income and work incentives, of removing the income tax provisions favouring homeownership. We consider six European countries – Belgium, Germany, Greece, Italy, the Netherlands and the UK – that exhibit important variation in terms of income tax treatment of homeowners. Using the multi-country tax benefit model EUROMOD, we analyse the distributional consequences of including net imputed rent in the taxable income definition that applies in each country, together with the removal of existing special tax treatments of incomes or expenses related to the main residence; thus, we provide a measure of the homeownership bias. We implement three tax policy scenarios. In the first, imputed rent is included in the taxable income of homeowners, while at the same time existing mortgage interest tax relief schemes and taxation of cadastral incomes are abolished. In the two further revenue-neutral scenarios, the additional tax revenue raised through the taxation of imputed rent is redistributed to taxpayers, through either a tax rate reduction or a tax exemption increase. The results show how including net imputed rent in the tax base might affect inequality in each of the countries considered. Housing taxation appears to be a promising avenue for raising additional revenues, or lightening taxation of labour, with no inequality-increasing side effects.

El objetivo de este trabajo será analizar y debatir acerca de los facilitadores y los obstáculos identificados en el proceso de implementación de esta estrategia innovadora de atención en salud integral comunitaria, desde el entorno virtual (2020-2022). Este proyecto se inicia con la detección de necesidades en la comunidad desde un marco institucional y se basa en la investigación acción participativa, desde un enfoque cualitativo. En el contexto de pandemia, el diseño e implementación de estrategias de extensión social y comunitaria resultó un importante desafío para los equipos interdisciplinarios que desarrollan prácticas institucionales de atención primaria. El primer desafío para nuestro equipo fue explorar y evaluar los modos de aproximarnos bajo la interacción digital, para sostener las prácticas comunitarias presenciales implementadas en el territorio nacional (2009-2019). El aislamiento físico, social y obligatorio, consecuencia de la pandemia por COVID 19, constituyó un factor de riesgo para la salud mental de la población en general, siendo la comunidad malvinera (Veteranos de Guerra de Malvinas, grupo familiar y familiares de caídos en Malvinas) un grupo vulnerable por las características socio históricas que presenta a causa de la participación directa e indirecta en el Conflicto del Atlántico Sur y las experiencias atravesadas en la Postguerra. De este modo, en este contexto de incertidumbre, se buscó minimizar los efectos del aislamiento emocional y las barreras psicosocioculturales, que obstaculizan la demanda para el acceso a los servicios de salud mental. En tal sentido, se proponen los talleres psicoeducativos y socioculturales que promueven diversos movimientos creativos, habilitadores e instituyentes, en constante producción, desde un enfoque salutogénico, implicando a los integrantes de la comunidad, a los equipos interdisciplinarios y a la propia institución desde donde se proyecta este trabajo colaborativo y en red. Por todo ello, y junto al retorno progresivo a las actividades presenciales, se evaluó la importancia de sostener esta nueva modalidad de atención orientada a la comunidad, originada por la situación de la pandemia de Covid-19, y donde la Telesalud se va constituyendo como una herramienta posible para el acceso a este tipo de servicios de salud, facilitando el encuentro entre profesionales e integrantes de la comunidad pertenecientes a diversas -e inclusive remotas-  localidades de nuestro territorio nacional, promoviendo el autocuidado y cuidado mutuo desde las diversas propuestas de talleres que se ofrecen, según las demandas de interés, personal y colectiva, que los convoca a participar. Se concluye acerca de la resignificación de las prácticas institucionales de atención integral orientada a la comunidad por medio de la Telesalud, práctica qué vinculó a 1956 participantes pertenecientes a la comunidad malvinera y a un equipo de facilitadores de diferentes regiones del país a través de 246 talleres en línea, y que sigue fortaleciendo las redes de apoyo en un sentido vital y transformador.