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Biomedical subjects

A Tichelli

Publications and source records attributed to A Tichelli.

At least 127 records · Page 7Linked to original sources
PubMed1994

Late ocular complications after bone marrow transplantation.

The most usual late ocular complications after bone marrow transplantation (BMT) are the microvasculopathy in the ocular fundus, the cataract formation and the keratoconjunctivitis sicca syndrome. Microvascular lesions in the eye fundus were evaluated in 127 patients treated at the University Hospital of Basel, Switzerland and appeared to be cotton wool spots, retinal hemorrhages, edema of the optic disk and retinal lipoid deposits. 13 of the 127 patients (10.3%) developed ischemic lesions of the fundus 3 to 6 months after BMT. Microvasculopathy was observed exclusively in patients conditioned with total body irradiation (TBI) and treated with cyclosporine A for graft-versus-host disease (GvHD). It is therefore likely that both factors are needed for the development of the microvasculopathy and we believe that lesions observed in the fundus are not restricted to the eye but reflect a generalized process of the capillary system. Cataract formation was evaluated in 197 patients treated at the University Hospital of Basel, Switzerland. 70 of the 197 (36%) patients developed cataract and 46 (23%) patients needed a surgical repair. After single dose TBI, all patients alive at 3.5 years had a lens opacification. In patients treated with fractionated TBI the probability of developing cataract is 29% at 3.5 years but 83% at 6 years. Only 1 of 33 patients conditioned with chemotherapy alone had cataract formation. In conclusion TBI as well as the mode of irradiation are the main risk factors for the development of cataract. Preventive measures, such as lens shielding during TBI should be considered.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1993

Cataract formation after bone marrow transplantation.

OBJECTIVE: To evaluate the incidence, time course, and factors associated with cataract formation in bone marrow transplant recipients. DESIGN: Prospective cohort study. SETTING: University Hospitals, Basel, Switzerland. PATIENTS: 197 patients treated with allogeneic or autologous bone marrow grafts at least 180 days before the start of the study. INTERVENTION: Three regimens for bone marrow transplant were used: 74 patients received single-dose, total-body irradiation (TBI), 90 patients received fractionated TBI, and 33 received chemotherapy alone. RESULTS: Three and one half years after single-dose TBI, 51 of the 74 patients (69%) were alive and cataracts had developed in all of these 51 patients. Cataracts developed in 18 of the 90 (20%) patients treated with fractionated TBI, with an 83% (95% CI, 63% to 100%) risk for lens opacification at 6 years. Cataracts developed in only 1 of the 33 (3%) patients treated with chemotherapy alone. Incidence of cataracts is higher and lens opacification occurs earlier after single-dose TBI than after fractionated TBI (P < 0.01). With Cox regression analysis, the use of irradiation (relative risk, 21.0), the mode of irradiation (relative risk, 7.4), and the use of steroid treatment (relative risk, 2.9) for more than 3 months after bone marrow transplantation increased the risk for cataract formation. In contrast, age, sex, and chronic graft-versus-host disease did not influence the rate of cataract development. The probability of requiring cataract surgery after 6 years was 85% (CI, 75% to 95%) for the patients treated with single-dose TBI and 20% (CI, 0% to 49%) for those prepared with fractionated irradiation. CONCLUSIONS: Patients treated with TBI, regardless of fractionation, are likely to have cataracts within 10 years, and some will need surgical repair. Long-term steroid treatment accelerates cataract formation. Preventive measures, such as lens shielding during TBI, should be considered.

Adolescent↗
PubMed1993

Malignant tumors occurring after treatment of aplastic anemia. European Bone Marrow Transplantation-Severe Aplastic Anaemia Working Party.

BACKGROUND AND METHODS: Recent studies have shown that long-term survivors of acquired aplastic anemia may be at high risk for malignant diseases. We assessed the risk of cancer after aplastic anemia was treated with immunosuppression or bone marrow transplantation and sought to identify risk factors according to treatment. The study population consisted of 860 patients treated by immunosuppression and 748 patients who had received bone marrow transplants for the treatment of severe aplastic anemia. The risk of cancer was analyzed overall and according to treatment relative to the risk in the general population. In calculating relative risk, we excluded patients with myelodysplastic syndromes or acute leukemias arising less than 6 months after treatment, and solid cancers arising less than 12 months after treatment, because of a possible association with aplastic anemia itself rather than with the treatment received. RESULTS: Forty-two malignant conditions were reported in the 860 patients who received immunosuppressive therapy: 19 cases of myelodysplastic syndrome, 15 cases of acute leukemia, 1 case of non-Hodgkin's lymphoma, and 7 solid tumors. Nine were reported in the 748 patients who received bone marrow transplants: two cases of acute leukemia and seven solid tumors. After the exclusions listed above, the overall relative risk of cancer was 5.50 (P < 0.001) as compared with that in the general European population; the risk was 5.15 (P < 0.001) after immunosuppressive therapy and 6.67 (P < 0.001) after transplantation. The 10-year cumulative incidence rate of cancer was 18.8 percent after immunosuppressive therapy and 3.1 percent after transplantation. The risk factors for myelodysplastic syndrome or acute leukemia after immunosuppressive therapy included the addition of androgens to the immunosuppressive treatment (relative risk = 0.28), older age (relative risk = 1.03), treatment in 1982 or later, as compared with 1981 or earlier (relative risk = 3.01), splenectomy (relative risk = 3.65), and treatment with multiple courses of immunosuppression (relative risk = 2.26). Risk factors for solid tumors after bone marrow transplantation were age (relative risk = 1.11 per year) and the use of radiation as a conditioning regimen before transplantation (relative risk = 9.56); such tumors occurred only in male patients. CONCLUSIONS: Survivors of aplastic anemia are at high risk for subsequent malignant conditions. Myelodysplastic syndrome and acute leukemia tend to follow immunosuppressive therapy, whereas the incidence of solid tumors is similar after immunosuppression and after bone marrow transplantation.

Acute Disease↗
PubMed1993

Levels of soluble stem cell factor in serum of patients with aplastic anemia.

Aplastic anemia (AA) is a rare bone marrow (BM) disorder characterized by an unexplained failure of hematopoietic precursors to proliferate. In vitro growth of AA BM cells can be improved by the addition of the hematopoietic growth factor SCF (stem cell factor), which suggests that deficiency of SCF may be one of the underlying causes of the disease. In this study, we measured the concentration of SCF in sera of patients with severe AA. One hundred twenty-eight serum samples from 32 patients, at diagnosis and following therapy, were analyzed. Before treatment, SCF levels varied between 0.33 and 6.1 ng/mL; no correlation between hematopoietic function and SCF serum levels was apparent. Therapy with antilymphocyte globulin (ALG) or bone marrow transplantation (BMT) did not result in a recognizable pattern of changes in SCF levels. However, serum concentration of SCF in many patients with AA was at the low range of control serum levels determined in healthy blood donors. Of 128 AA serum samples tested before and after therapy, 107 were below the mean normal value of 3.3 ng/mL, including 26 samples below the minimum normal value of 1.3 ng/mL, as estimated in 267 controls. We also found that SCF levels in peripheral blood serum correlate well with factor concentrations in the BM plasma. Clinical observations suggest that higher SCF serum levels are often associated with a better clinical status of the patients in terms of survival and transfusion requirements. The data indicate that a deficient production of soluble SCF may contribute to AA in some patients; thus, suggesting a potential therapeutic benefit of SCF in this disorder.

Adolescent↗
PubMed1993

Factors associated with transfusion requirements during treatment for acute myelogenous leukemia.

Supportive care is a prerequisite for intensive chemotherapy in leukemic patients. Little has been published about quantitative aspects of red blood cell and platelet transfusions. We evaluated transfusion requirements and factors associated with observed differences in 206 patients undergoing initial induction consolidation chemotherapy for newly diagnosed acute myelogenous leukemia. All patients were treated during a 5-year period in 12 hospitals on a common protocol of the Swiss Study Group for Clinical Cancer Research (SAKK). Protocol 30/85 comprises a double induction and one course of consolidation. Of 206 registered patients, 199 were evaluable; 118 of 199 (59%) patients entered completed all three cycles of chemotherapy. These 118 patients received a median (range) of 18 (3-44) units of red blood cells and 12 (2-61) platelet transfusions during 112 (70-129) days of hospitalization. Patients with a hemoglobin > 10 g/l, platelets > 100 x 10(9)/l, and white blood cell counts < 5 x 10(9)/l at diagnosis received fewer transfusions than patients with less favorable blood counts during the first cycle of chemotherapy (p < 0.05). Patients with FAB subtype M3 received more platelet transfusions during the first cycle. Female patients received more platelet transfusions than male patients. In multivariate analyses the participating center was the most important single factor associated with the number of red cell and platelet concentrates given per patient and cycle (p < 0.05), the number of days in hospital (p < 0.05), and the risk of premature withdrawal from the study. These data define factors associated with transfusion requirements in patients treated for newly diagnosed AML. They include severity and subtype of disease at diagnosis, age and sex of the patients, and the participating institution. Results suggest that medical decision-making varies from center to center. The participating institution is strongly associated with differences in transfusion requirements, hospitalization time, and premature withdrawal from study. Leukemia trials tend to focus on the prospective evaluation of chemotherapy or growth factors. Our results suggest that other variables, such as management strategies, should be included for prospective analysis.

Adolescent↗
PubMed1993

Cytokine serum levels during treatment with high-dose recombinant human IL-3 in a patient with severe aplastic anemia.

A 37-year-old woman with severe aplastic anemia (SAA), who had relapsed 6 years after antilymphocyte globulin therapy, was treated with intravenous recombinant human IL-3 (4 micrograms/kg/d) for 21 days. Subsequently, long-term therapy with subcutaneous rhIL-3 at the highest dose level tested so far (16 micrograms/kg/d) was initiated in order to maintain growth-factor response. Therapy was discontinued on day 73 due to progressive thrombocytopenia and increased petechial bleeding. Both treatment schedules resulted in a transient increase in leukocytes (twofold) due to an increase in monocytes, neutrophils, and eosinophils. RhIL-3 had no effect on hemoglobin values or platelet counts and only marginally improved colony formation of bone marrow CFU-GM in response to rhGM-CSF. Side effects of both treatment schedules were mild and did not exceed WHO grade II. Steady-state serum concentrations of IL-3, which are able to stimulate hematopoiesis in vitro (i.e. > 1 ng/ml), were achieved by both low- and high-dose treatment, although high-dose treatment resulted in markedly higher serum levels of IL-3. On measuring cytokine serum levels (neopterin, IL-1 beta, IL-6, sIL-2R, GM-CSF, TNF-alpha, IFN-gamma) we noticed a different cytokine pattern with both treatment modalities, resulting in a moderate induction of TNF-alpha and IFN-gamma during low-dose, intravenous treatment, whereas during subcutaneous, high-dose treatment a profound increase of IL-6, sIL-2R, and, to a lesser extent, neopterin was detected. These results in a single patient with SAA indicate that further studies on IL-3 serum levels and IL-3-induced secondary cytokines in a larger group of patients are needed to optimize growth-factor treatment and to better understand the in vivo biological activity of IL-3.

Adult↗
PubMed1993

Gender and response to antilymphocyte globulin (ALG) for severe aplastic anaemia.

We have evaluated the speed of haematological recovery in 103 severe aplastic anaemia (SAA) patients treated with antilymphocyte globulin (ALG) and followed at our institution for 3-15 years. We found that haemopoietic recovery was significantly delayed in six girls under the age of 10 years. This slow recovery in girls might be explained by their relative inability to release haemopoietic growth factors, granulocyte colony stimulating activity and burst promoting activity, compared to all other sex and age groups. This defect is not explained by disease severity at presentation and thus indicates a functional abnormality of monocytes/macrophages and T-lymphocytes in addition to the deficiency of haemopoietic stem cells. In a multivariate analysis, low factor production and low pretreatment reticulocyte counts turned out to be strong predictors of slow haemopoietic recovery. We conclude that young girls have a particular form of SAA characterized by low haemopoietic factor production and delayed recovery after ALG. They are preferential candidates for early bone marrow transplantation or, if they are not eligible, for treatment with recombinant human haemopoietic growth factors.

Adolescent↗
PubMed1992

[Swiss Register for unrelated bone marrow donors: preliminary results].

Bone marrow transplantation from the unrelated volunteer donor is today a realistic possibility for patients lacking an HLA-identical family donor. In 1988, the Swiss Unrelated Bone Marrow Donor Registry was founded to coordinate such bone marrow transplants and create the Swiss volunteer donor registry. Thus for a search has been initiated for 71 patients and 16 transplants have been performed. Donor and recipient were HLA-A-, -B- identical by serology and HLA-Dr-identical by DNA-oligotyping. 10 of the 16 patients are alive without signs of basic disease 2 weeks to 2 years and 4 months after the transplant. These results illustrate that unrelated donor transplantation, using careful selection criteria, is a realistic new therapeutic modality.

Adolescent↗
PubMed1992

Morphology in patients with severe aplastic anemia treated with antilymphocyte globulin.

One hundred and seventeen patients with severe aplastic anemia (SAA) were treated at our institution between 1976 and 1990 with antilymphocyte globulin (ALG) therapy. Seventy-nine (68%) are alive and probability of survival at 14 years, according to Kaplan and Meier, is 62% +/- 12%. Twenty-six patients developed a late clonal complication: 11 had a myelodysplastic syndrome (MDS) and 17 had paroxysmal nocturnal hemoglobinuria (PNH); two patients had both. The cumulative risk at 10 years is 42%. The development of MDS/PNH after SAA directly affects survival. The probability of being alive at 14 years is 81% +/- 10% for patients with stable disease and 36% +/- 13% for those with clonal evolution (P = .001). To look for predictive signs, we reevaluated peripheral blood and bone marrow cytomorphology at presentation, during regeneration, and in remission. We examined the peripheral blood values for hemoglobin, reticulocytes, granulocytes, thrombocytes, mean corpuscular volume (MCV), and fetal hemoglobin, as well as bone marrow for cellularity, erythropoiesis, myelopoiesis, and megakaryopoiesis. ALG therapy induces slow and incomplete recovery. Although in "remission," ALG patients have lower hemoglobin values, higher reticulocyte counts, lower granulocyte and platelet values, and a higher MCV and fetal hemoglobin than normal controls. They retain a reduced number of megakaryocytes and a persistence of atypical monocytes in bone marrow morphology as stigmata of their disease. Patients with late clonal complications show distinct morphologic abnormalities: patients with PNH have higher MCVs, higher granulocyte and reticulocyte counts, and more dyserythropoiesis at diagnosis and a lower hemoglobin with an increased proportion of erythroblasts in the bone marrow in "remission." Patients who later developed MDS are not different from the total patient population at diagnosis. After therapy, these patients are characterized by the presence of ring sideroblasts and atypical monocytes during regeneration and by a persistent increase in MCV, a higher fetal hemoglobin, lower granulocyte values, and megakaryocytic dysplasia during "remission." Thus, routine morphologic follow-up examination of blood and bone marrow can discover patients at risk for late hematologic complications after ALG therapy.

Adult↗
PubMed1992

Stem cell factor stimulates the in vitro growth of bone marrow cells from aplastic anemia patients.

Aplastic anemia (AA) is a rare human bone marrow disorder of unknown etiology manifested by a strongly impaired growth of hematopoietic precursors. In this study, we examined the ability of recombinant human stem cell factor (SCF) to stimulate proliferation in vitro of bone marrow cells from 15 AA patients. All patients had been previously treated with antilymphocyte globulin (ALG). SCF, in combination with erythropoietin (Epo), interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor (GM-CSF), and granulocyte colony-stimulating factor (G-CSF), increased the number of hematopoietic colonies formed in a semisolid medium by AA marrows. Maximal colony numbers reached 30% of the numbers observed with normal bone marrow cells. Proliferation of AA cells cultured in a liquid medium containing SCF together with Epo, IL-3, GM-CSF, and G-CSF approached 70% of the control level, as measured by 3H-thymidine incorporation. The effect of the combination of SCF with the other growth factors was more than 10 times stronger than that of the growth factors alone. The most marked effect of SCF was on the generation of erythroid colonies by precursor cells. The results demonstrate synergism between CSF and other hematopoietic growth factors, resulting in the most efficient stimulation of the in vitro growth of AA bone marrow cells described to date. Use of SCF, either alone or in combination with other factors, may be of potential value in treatment of AA.

Adolescent↗
PubMed1992

[Iron-deficiency anemia: diagnosis and therapy].

Iron deficiency is the most frequent cause of anemia. The correct diagnosis is based on history, peripheral blood findings and investigations of the iron status. Anemia occurs only when iron stores are empty. Iron deficiency anemia is a microcytic, hypochromic anemia. Red blood cells show poikilo- and anisocytosis with predominance of small erythrocytes. In one third of the patients the anemia is accompanied by slight leukopenia. The platelet counts may be normal, increased or decreased. Iron deficiency is documented by decreased serum iron, increased transferrin and decreased iron saturation. Ferritin below 15 ng/ml confirms the depletion of iron. Once the diagnosis of iron deficiency is established, its cause must be investigated. Pregnancy and bleeding are the most frequent conditions leading to iron deficiency. Therapy of iron deficiency involves treatment of the underlying condition as well as reestablishment of iron stores. Oral therapy is the most safe and economical method of correcting iron deficiency. Parenteral therapy should be confined to exceptional situations.

Anemia, Hypochromic↗
PubMed1992

[Significance of the automated blood count].

Modern hematology depends on rapid and accurate determination of quantitative and qualitative blood counts. Fully automated analyzers based on the principles of flow cytometry have replaced the traditional blood smear in the routine laboratory. They count the number of red cells, platelets and leukocytes with high precision. In addition, they divide the cells into different populations according to their physical or chemical properties. This population distribution pattern mimics a "differential" blood smear. Normality can be assessed with a high degree of accuracy, rapidly and reproducibly. The qualitative changes frequently provide pointers to the final diagnosis. In case of abnormalities the reports are flagged. A microscopic analysis should be added according to internal laboratory guidelines. It clarifies pathological findings and is essential in the search for specific abnormalities such as malaria. This underlines the need for exchange of information between physician and laboratory.

Autoanalysis↗
PubMed1991

[Health status and late complications following allogeneic bone marrow transplantation. A review].

Better results following bone marrow transplantation (BMT) have increased the number of patients in longterm follow-up. Health status and late effects are therefore of increasing interest. We discuss here the incidence and follow-up of late complications after allogenic BMT. Any conditioning regimen including TBI in postpubertal women introduces a postmenopausal status. In contrast, normal function is found after BMT without irradiation. In men, there is usually permanent azoospermia after TBI but not following chemotherapy alone. Thyroid dysfunction after BMT with TBI has been reported in about 40% of patients. In most of them compensated hypothyroidism with elevated TSH is found. BMT with TBI induces growth retardation in children. Decreased growth hormone levels are observed and substitution can induce normal height development. Interstitial pneumonitis (IP) is a major cause of death. It occurs on average three months after BMT but late onset IP's are increasingly reported. Cataracts are common after BMT. The risk of cataracts in patients given single dose TBI attains 80-100% after four years. Under treatment with cyclophosphamide alone, the risk of lens opacification is less than 20%. So far, patients treated with fractionated TBI have not developed more cataracts than those treated with chemotherapy alone. Impaired renal function is common early post-transplant. Risk factors include cyclosporine (CSA) nephrotoxic antibiotics and antifungal drugs. So far, few secondary malignancies have been reported in humans after BMT. However, actual observation time is still too short for final evaluation. Prevention or treatment is instituted for common complications. It is expected that other types of tissue damage will be recognized.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

[Emergency therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF)].

Granulocyte-macrophage colony stimulating factor (GM-CSF) has been tested for tolerability and efficacy on a compassionate need case basis in 17 patients (5 females, 12 males aged 4-72 years, median 35 years). GM-CSF was given at the rate of 3.5-32 micrograms/kg for 2-64 days as a continuous infusion for the following indications: impending rejection following bone marrow transplantation (5 patients), severe neutropenia secondary to chemotherapy in tumor patients (5), severe aplastic anemia (3), immune granulocytopenia (2) and accidental overdose with cytostatic agents (2 patients). Tolerance of GM-CSF was good in regard to doses of up to 16 micrograms/kg. Fever, myalgia and eosinophilia were the most frequent side effects. The patient treated with 32 micrograms/kg developed thrombosis of the vena cava. Efficacy is more difficult to assess in this heterogenous population, but 11 of 17 patients showed increased granulocyte counts and 3 patients clearly recovered from severe neutropenia. The role of GM-CSF in this recovery, however, cannot be proven. The results further indicate that GM-CSF cannot reverse ongoing rejection following allogenic BMT and cannot correct immune neutropenia. The value of GM-CSF therapy in patients with severe aplastic anemia and in the context of chemotherapy still needs to be defined. It is certainly indicated in patients with an accidental overdose of chemotherapeutic agents.

Adolescent↗