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A Tichelli

Publications and source records attributed to A Tichelli.

At least 37 records · Page 2Linked to original sources
PubMed2001

Anemia: an indicator for malnutrition in the elderly.

The prevalence of anemia increases with age and is frequently multifactorial. We postulated that malnutrition contributes to anemia in the elderly and is underdiagnosed. Our objective was to analyze the prevalence of anemia and its association with nutritional status in a hospitalized geriatric population. Included in this retrospective cohort study were 186 consecutive patients admitted in 1997 to a geriatric unit of a university hospital. We compared hematological and chemical blood tests routinely performed upon admission in patients with anemia (hemoglobin <120 g/l) and without anemia (hemoglobin > or = 120 g/l). Using these admission parameters, we defined a multiparameter score of malnutrition by low lymphocyte counts, decreased values of albumin, cholesterol, transferrin, cholinesterase, and zinc, iron deficiency by low transferrin saturation and normal C-reactive protein, and inflammation by increased C-reactive protein and high transferrin saturation. Of the 186 patients, 82 (44%) met the criteria for anemia on admission. In univariate analysis, patients with anemia differed significantly from patients with normal hemoglobin exhibiting lower serum values of albumin, iron, transferrin, cholesterol, cholinesterase, zinc, transferrin saturation, and lymphocyte count and higher C-reactive protein levels. Using a multiparameter score, anemia correlated significantly with parameters of malnutrition (P=0.0001) but not with iron deficiency (P=0.5) or with inflammation (P=0.08). In a multivariate logistic regression model, anemia was significantly associated with serum albumin (RR: 1.138; 95% CI: 1.056-1.227; P=0.0007), cholinesterase (RR: 1.387; 95% CI 1.122-1.714; P=0.0025), and transferrin saturation (RR: 1.05; 95% CI: 1.012-1.09; P=0.009). We conclude that malnutrition may play an important etiologic role in anemia in the elderly.

Aged↗
PubMed2001

Effect of preeclampsia on umbilical cord blood hematopoietic progenitor-stem cells.

OBJECTIVE: The aim of the present study was to determine the influence of preeclampsia on cord blood hematopoietic progenitor-stem cells obtained at delivery because cord blood is increasingly used clinically for stem cell retrieval as an alternative to bone marrow. STUDY DESIGN: Umbilical cord blood was collected from patients fulfilling the criteria for preeclampsia and from gestational age- and birth weight-matched control subjects at delivery (patient/control subjects ratio, 1:2). Cord blood volume and nucleated cell content were measured, and the number of hematopoietic progenitor-stem cells was determined by means of fluorescence-activated cell sorting with the CD34(+) epitope and by means of colony assays with different hematopoietic growth factors. In addition, the expression of adhesion molecules by CD34(+) progenitor-stem cells was examined. RESULTS: In pregnancies affected by preeclampsia, volume and nucleated cell and total CD34(+) cell contents in the collected cord blood were significantly smaller compared with those of control subjects. Furthermore, there was a trend toward a smaller relative number of CD34(+) cells and colony-forming units per nucleated cell in cord blood samples from preeclamptic patients. No difference in the expression of the cell-adhesion molecules leukocyte function-associated antigen 1, very late activation antigen 4, and L-selectin by CD34(+) cells could be found. CONCLUSION: This study shows that preeclampsia affects umbilical cord blood volume and nucleated cell and progenitor-stem cell numbers obtained at birth.

Adult↗
PubMed2000

[Single and double high-dose chemotherapy with autologous stem cell transplantation in children with advanced solid tumors: first experiences].

The disease-free survival of children with malignant disorders has increased impressively over the last three decades due to better understanding of tumour biology and the resultant improvement in diagnosis and therapy. Children with advanced and relapsed solid tumours, such as brain tumour, alveolar rhabdomyosarcoma, Ewing's sarcoma, or neuroblastoma, have not benefited from this progress. The concept of myeloablative high-dose chemotherapy (HDT) is based on the observation that certain cytostatic drugs have a steep linear dose-response curve, and thus escalating the dose may increase the tumour cell kill. The interest in HDT intensified when autologous stem cells mobilised from the peripheral blood became available, in view of the possibility of increasing the cell dose, which correlates directly with the time period of haematopoietic recovery and thus reduces therapy-associated toxicity. The aim of the study was to evaluate the feasibility of single or double HDT by autologous peripheral blood stem cell transplantation (PBSCT) after each cycle in children, and to obtain pilot data for future prospective clinical trials. 11 children aged between 2.8 and 17.2 years with brain tumours, soft tissue sarcomas, germ-cell tumours and neuroblastomas were analysed over a 2-year-period. 7 of the 11 children are in complete remission 2+ and 24+ months after HDT, 3 died of progressive disease and one child died of therapy-associated complications. The median hospital stay was 29.5 (22-104) days. An absolute neutrophil granulocyte count of 0.5 x 10(9)/l was achieved after a median stay of 11 days and a platelet count of > 20 x 10(9)/l independent of platelet transfusions was achieved after 11 days. Painful stomatitis leading to total parenteral nutrition (9 children) and intravenous morphine therapy (6 children) was the most serious toxicity. Single or double HDT with autologous PBSCT after each cycle is feasible in children and offers basic data for conducting phase III paediatric clinical studies.

Adolescent↗
PubMed2000

Myeloproliferative disorders: complications, survival and causes of death.

This retrospective single-center study compared thromboembolic and hemorrhagic complications, survival and causes of death in a cohort of 102 consecutive patients with myeloproliferative disorders (MPD). We included 17 patients with essential thrombocythemia (ET), 59 with polycythemia vera (PV), and 26 with osteomyelofibrosis (OMF). The median follow-up was 3.7 years. Estimated 8-year probability of complications for the entire cohort was 80 +/- 11% (95% confidence interval), without significant differences among MPD subgroups. The rate of thromboembolic complications, expressed as the number of events per 100 patient years, was 16.7 for patients with PV, 13.8 for OMF, and 7.5 for ET. Fifty-four percent of thromboembolic events in PV involved cerebral or limb arteries. The rate of bleeding complications was highest in patients with OMF (31.8 per 100 patient years), followed by ET and PV (11.8). Ninety percent of bleeding episodes affected the skin. mucosal membranes, and the gastrointestinal tract. Eight-year survival was highest in ET with 91 +/- 17%, followed by PV (66 +/- 18%) and OMF (40 +/- 31%) (P< 0.01). Twenty-four patients died during the observation period, and fatal thrombosis (in five patients) represented the leading cause of death. Only two patients with MPD died from fatal hemorrhage and one from acute leukemia. We conclude that survival is highest in ET and lowest in OMF. Both thromboembolic and hemorrhagic complications are frequent. However, thrombosis appears to be more often fatal than bleeding complications. Prophylaxis of thromboembolic events remains a key issue in the management of MPD.

Adolescent↗
PubMed2000

Treatment of acquired severe aplastic anemia: bone marrow transplantation compared with immunosuppressive therapy--The European Group for Blood and Marrow Transplantation experience.

Patients with severe aplastic anemia (SAA) can be successfully treated with bone marrow transplantation (BMT) or immunosuppressive therapy (IS). The current outcome using both forms of therapy among 3,669 patients treated in Europe between 1976 and 1998 is reviewed. Significant progress has been made and the overall risk of failure is now low, with survival rates greater than 80% for both treatments. Chronic graft-versus-host disease (GvHD) remains a problem for BMT patients, and carries a high risk of lethal complications. On the other hand, IS patients are exposed to late failure due to relapse or clonal/malignant diseases. First-line BMT from identical siblings is compared with IS therapy in an intent-to-treat analysis of 1,765 patients, regardless of subsequent transplant status. The outcome of SAA patients has improved considerably over time and is influenced by patient variables such as severity of the disease and age, but also by the choice of the initial treatment.

Anemia, Aplastic↗
PubMed2000

Treatment of solid tumors following allogeneic bone marrow transplantation.

Second solid tumors are well known late complications after bone marrow transplantation. Treatment strategies are ill defined. We retrospectively evaluated treatment and outcome in a single institution. From August 1974 to July 1996, six solid tumors were observed in five of 387 patients 2 to 13 years after BMT, corresponding to a probability of developing a second solid tumor of 9% (1-17%, 95 CI) at 15 years: these comprised endometrial carcinoma, carcinoma of the thyroid gland, cervical carcinoma, sarcoma of the small intestine, osteosarcoma of the tibia and ovarian carcinoma. All five patients were treated as intensively as they would be without a history of BMT. At last follow-up four of the five patients were alive and without signs of tumor. We postulate that second solid tumors after BMT should be treated as de novo tumors. Early detection based on consequent clinical follow-up of the transplant patients might explain the relatively good outcome.

Adenocarcinoma↗
PubMed2000

Increased stem cell dose, as obtained using currently available technology, may not be sufficient for engraftment of haploidentical stem cell transplants.

The best strategies for haploidentical stem cell transplants are not known. We used a standard myeloablative pretransplant conditioning regimen (30 mg/kg VP-16, 120 mg/kg cyclophosphamide, and 12 Gy of TBI in six fractions), an increased peripheral stem cell dose of > 10 x 10(6) CD34+ cells/kg, T cell depletion (with CD34+ cell selection and CD4/CD8 depletion steps) to < 1 x 10(5) CD3+ cells/kg and cyclosporine post transplant. Ten patients (7M/3F, median age 11 (3-33) years) with high-risk leukemia (AML in 4, MDS in 2, CML in 1 and T-ALL in 3) received a hemopoietic stem cell transplant (HSCT) from a haploidentical father or sibling. The median number of CD34+ cells was 12.9 (9.5-45.7) x 10(6) cells/kg; median number of CD3+ cells was 0.41 (0.09-1.89) x 10(5) CD3+ cells/kg. All patients initially achieved 0.5 x 10(9)/l neutrophils at a median 12 (10-21) days. Graft failure in two consecutive patients out of four on the original protocol led to a modification adding ATG pretransplant and OKT3 post transplant. Graft failure was observed in one out of six subsequent patients. Acute GVHD > or = grade II was observed in three patients. Three of 10 patients are alive in CR at > 24 and >3 (2) months after transplant. Seven patients died: four of transplant related complications and three of relapse. Increased stem cell dose (> or = 10 x 10(6) CD34+ cells/kg) as obtained using currently available technology may not be sufficient to ensure stable engraftment in patients with high-risk leukemia using standard myeloablative conditioning regimens.

Graft vs Host Disease↗
PubMed2000

Natural killer-type receptors for HLA class I antigens are clonally expressed in lymphoproliferative disorders of natural killer and T-cell type.

In recent years, natural killer (NK) cells, as well as subpopulations of T cells, have been found to express diverse NK receptors (NKRs) for HLA class I molecules. We have characterized NKR phenotypes in lymphoproliferative disorders of NK or T-cell type. Peripheral blood of patients with lymphoproliferative disorders (n = 9) was analysed by multiparametric immunofluorescence flow cytometry with eight different antibodies against NKRs. Abnormal neoplastic cell populations from different types of NK or T-cell lymphoproliferative disorders lacked diversity in their NKR repertoires, i.e. all or none of the abnormal cells expressed individual NKRs and this expression occurred at single levels of intensity. This pattern of expression was specific for lymphoproliferative disorders as these resticted NKR repertoires were not found either in healthy donors (n = 9) or in patients with viral or autoimmune disease (n = 5). We conclude that NKRs are clonally expressed in lymphoproliferative disorders of NK or T-cell origin. NKR repertoires may represent a novel tool in diagnosing clonal disorders of NK and T-cell type.

CD3 Complex↗
PubMed2000

Preterm birth and the availability of cord blood for HPC transplantation.

BACKGROUND: Cord blood from deliveries at term can be used for HPC transplantation. The objective of this study was to determine the amounts of cord blood nucleated cells (NCs) and HPCs that were collectable from preterm deliveries. STUDY DESIGN AND METHODS: Cord blood collected from preterm deliveries between 22 and 36 weeks of gestation was compared with regard to volume, NC count (/mL), CD34+ cell count (/mL), and the NC and CD34+ cell counts per cord blood sample and at different gestational ages. RESULTS: A correlation was found between gestational age and NC count (r = 0.52, p<0.001), and an inverse relation was found between gestational age and CD34+ cell count (r = - 0.68, p<0.001). The CD34+ cell count per cord blood sample was independent of gestational age (r = - 0.13, p = NS), and no significant difference between early (22-32 week) and late (33-36 week) preterm deliveries was found (p = 0.870). Comparison with published data from cord blood transplantations revealed that up to one-third of preterm samples contained at least as many NCs (or CD34+ cells) as the median cell dose transplanted (calculated for the median recipient weight) in the respective study. Furthermore, 77 percent of all preterm samples contained at least 1 x 10(7) NCs (and 42% at least 1 x 10(5) CD34+ cells) per kg for transplantation in a recipient of 20-kg body weight, which corresponds to the lower threshold of cells per kg in the graft recommended by Eurocord. CONCLUSION: Preterm delivery should not be a reason to exclude cord blood collection if allogeneic cord blood transplantation in a sibling is planned.

Blood Donors↗
PubMed2000

Umbilical cord blood collection before placental delivery during cesarean delivery increases cord blood volume and nucleated cell number available for transplantation.

OBJECTIVE: We sought to determine whether umbilical cord blood collection during cesarean delivery can be improved by collecting cord blood before delivery of the placenta. STUDY DESIGN: Patients undergoing cesarean delivery were randomly assigned to cord blood collection before or after placental delivery. Closed sterile collection systems were used for blood sampling. Cord blood characteristics and maternal outcome parameters were compared between the 2 groups. RESULTS: A total number of 40 patients were available for analysis. No differences in maternal and neonatal characteristics were found. A larger amount of cord blood volume (mean +/- SEM, 93 +/- 7.5 vs 66 +/- 6.6 mL; P =.013) and total nucleated cell number (11.1 +/- 1.2 vs 7.4 +/- 0.8 x 10(8) cells; P =.026) was obtained in the samples collected before compared with those collected after placental delivery. Similarly, there was a trend toward higher total CD34(+) cell number in samples collected in situ (30.0 +/- 6.0 vs 17.4 +/- 2.4 x 10(5) cells; P =.076). Estimated intraoperative blood loss, difference between prepartum and postpartum hemoglobin values, operating time, and puerperal infection rates were similar in both groups. CONCLUSION: If a cesarean delivery is performed, cord blood sampling is more efficacious if performed before delivery of the placenta. This collection method seems beneficial and safe and might therefore be preferably used for related, as well as unrelated, cord blood stem cell banking and transplantation.

Antigens, CD34↗
PubMed2000

Developmental changes in adhesion molecule expressions in umbilical cord blood CD34 hematopoietic progenitor and stem cells.

OBJECTIVE: The purpose of this study was to determine whether expressions of the cell adhesion molecules LFA-1 (CD11a), VLA-4 (CD49d), and L -selectin (CD62L ) on CD34(+) stem and progenitor cells in umbilical cord blood change during gestation. STUDY DESIGN: In a prospective observational study 3-color fluorescence-activated cell sorting was used to assess the levels of expression of CD11a, CD49d, and CD62L on CD34(+) cells in fresh cord blood samples collected at delivery between 22 and 42 weeks' gestation. RESULTS: The relative number of CD34(+) cells decreased as gestational age increased (r = -0.71; P<.001). Conversely, we found significant increases in cell adhesion molecule expression by CD34(+) cells during gestation (LFA-1, r = 0.47; P =.001; VLA-4, r = 0.33, P =.031; L -selectin, r = 0.61; P<.001). Comparisons between grouped samples from early preterm (22-32 weeks' gestation), late preterm (33-37 weeks' gestation), and term (38-42 weeks' gestation) infants confirmed this correlation and revealed that the major increases occurred between early and late preterm gestation. CONCLUSION: These results suggest a role for cell adhesion molecule expression in the process of migration and homing of circulating stem cells to the fetal bone marrow toward the end of pregnancy. The findings may have implications for the use of preterm cord blood for hematopoietic stem cell transplantation and also for prenatal gene therapy.

Adult↗
PubMed2000

C-reactive protein and fever in neutropenic patients.

The predictive value of daily C-reactive protein (CRP) monitoring to distinguish causes of fever in neutropenic patients was studied retrospectively. A total of 143 fever episodes during 113 consecutive hospitalizations were studied in 71 patients who had been referred for chemotherapy or haemopoietic stem cell transplantation (HSCT). There were, on average, 1.3 fever episodes per hospital stay, attributed to: infection (55, 27 invasive bacterial, 5 fungal, 3 viral and 20 probable infections); acute graft vs host disease (GvHD) (20); drugs (22); transfusions (7); and not attributable (39). 130 (91%) fever episodes were accompanied by a rise in CRP, 6 (4%) episodes were fatal. Maximal CRP levels (CRPmax) and maximal temperature (Tmax) were higher in invasive bacterial infections than in aGvHD and higher in aGvHD than in drug- or transfusion-related fever (p < 0.0001). Temperature and CRP rose in parallel. A total of 16 patients developed grade II-IV aGvHD by day 11 (9-21) (median, range) after allogeneic HSCT. Acute GvHD was preceded by fever for 3 d (1-7), and by CRP increase for 5 d (0-15) (p < 0.0001). CRP monitoring may be useful to distinguish between causes of fever. Very high CRP levels tend to be associated with invasive bacterial infections. CRP is not an early warning sign. An increase in CRP and fever may precede other clinical manifestations of aGvHD.

Adolescent↗
PubMed2000

Current results of bone marrow transplantation in patients with acquired severe aplastic anemia. Report of the European Group for Blood and Marrow transplantation. On behalf of the Working Party on Severe Aplastic Anemia of the European Group for Blood and Marrow Transplantation.

We have analyzed 2,002 patients grafted in Europe between 1976 and 1998 from an identical twin (n = 34), from an HLA-identical sibling (n = 1,699) or from an alternative donor (n = 269), which included unrelated and family mismatched donors. The proportions of patients surviving in these three groups are, respectively, 91, 66 and 37%: major causes of failure were acute graft-versus host disease (GvHD) (11%), infection (12%), pneumonitis (4%), rejection (4%). In multivariate Cox analysis, factors predicting outcome were patient's age (p < 0.0001), donor type (p < 0.0001), interval between diagnosis and bone marrow transplantation (BMT) (p < 0.0005), year of BMT (p = 0.0005) and female donor for a male recipient (p = 0.02). Patients were then divided in two groups according to the year of BMT: up to or after 1990. The overall death rate dropped from 43 to 24% (p < 0.00001). Improvements were seen mostly for grafts from identical siblings (from 54 to 75%, p < 0.0001), and less so for alternative-donor grafts (from 28 to 35%; p = 0.07). Major changes have occurred in the BMT protocol: decreasing use of radiotherapy in the conditioning regimen (from 35 to 24%; p < 0.0001) and increasing use of cyclosporin (with or without methotrexate) for GvHD prophylaxis (from 70 to 98%; p < 0.0001). In conclusion, the outcome of allogeneic BMT for patients with severe aplastic anemia has considerably improved over the past two decades: young patients, grafted early after diagnosis from an identical sibling, have currently an over 80% chance of long-term survival. Transplants from twins are very successful as well. The risk of complications with alternative donor transplants is still high.

Acute Disease↗
PubMed2000

Predictive factors for cure after immunosuppressive therapy of aplastic anemia.

In a previous study, we evaluated efficacy of repeated antilymphocyte globulin (ALG) treatment for patients with severe aplastic anemia not responding to an initial ALG treatment or relapsing after initial response to ALG. We now searched in the same cohort of patients for differences between patients who responded to treatment and remained free of complications and those who relapsed or developed a clonal complication. From 107 patients surviving for more than 1 year after immunosuppression, 34 remained free from complications after the first course of ALG, and 73 presented an event defined as relapse of aplastic anemia, development of a clonal complication such as paroxysmal nocturnal hemoglobinuria, myelodysplastic syndrome or leukemia, or appearance of a solid tumor. We compared these two groups for survival, clinical performance and blood counts during follow-up. Survival probability was 93% for the event-free patients, and 55% for the patients with a complication event (p = 0.0003). Event-free patients had a higher incidence of complete remission (71%), were more often free of immunosuppressive treatment (79%) and independent of transfusions (100%), and had a higher Karnofsky score (91% with a score > or =90%) as compared to the group with events (29, 37, 67, 48%; p < or = 0.0002). At 1 and 3 years, event-free patients had significantly higher leukocyte and neutrophil counts, as compared to patients with a complication (p < 0.05). However, at 3 and 5 years, event-free patients had borderline higher platelet counts (p = 0.056, p = 0.078) and hemoglobin (p = 0. 097, p = 0.061). The coefficient of variation as an expression of the variability of the results in each group was systematically lower at 3, 5 and 10 years in the group of event-free patients. Despite some differences between the two groups, our data support the hypothesis that patients with long-lasting remissions should not be considered as definitively cured of aplastic anemia.

Adolescent↗
PubMed2000

Late clonal diseases of treated aplastic anemia.

Recent progress in the treatment of aplastic anemia has dramatically changed the previously grim prognosis for these patients. Improvements in bone marrow transplantation and immunosuppression have increased the number of long-term survivors so that immediate survival is no longer the sole concern. Here, we review the major clinical studies and summarize recent analyses of risk factors for developing paroxysmal nocturnal hemoglobinuria (PNH), myelodysplastic syndrome (MDS), acute leukemia, or solid tumor after treatment for aplastic anemia. We also examine biologic clues that may shed light on the interrelationship between aplastic anemia and clonal diseases.

Anemia, Aplastic↗