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A Tichelli

Publications and source records attributed to A Tichelli.

At least 55 records · Page 3Linked to original sources
PubMed1999

Malignant neoplasms in long-term survivors of bone marrow transplantation. Late Effects Working Party of the European Cooperative Group for Blood and Marrow Transplantation and the European Late Effect Project Group.

BACKGROUND: Patients who receive bone marrow transplants have increased risk for new malignant conditions because of several risk factors, including conditioning with radiation and chemotherapy, immune stimulation, and malignant primary disease. The occurrence of and risk factors for malignant neoplasm in long-term survivors must be assessed. OBJECTIVE: To determine the risk and define potential risk factors for new malignant conditions in long-term survivors after marrow transplantation. DESIGN: Retrospective multicenter study. SETTING: Study of the Late Effects Working Party with 45 transplantation centers cooperating in the European Cooperative Group for Blood and Marrow Transplantation. PATIENTS: 1036 consecutive patients who underwent transplantation for leukemia, lymphoma, inborn diseases of the hematopoietic and immune systems, or severe aplastic anemia. Transplantation was done before December 1985, and patients had survived more than 5 years. MEASUREMENTS: Reports on malignant neoplasms were evaluated, and the incidence was compared to that in the general population. Patient age and sex, primary disease and status at transplantation, histocompatibility of the donor, conditioning regimen, type of prophylaxis of graft-versus-host disease, development of acute and chronic graft-versus-host disease, and treatment of chronic graft-versus-host disease were evaluated as variables. RESULTS: Median follow-up since transplantation was 10.7 years (range, 5 to 22.1 years). Malignant neoplasms were seen in 53 patients; the actuarial incidence (+/- SE) was 3.5% +/- 0.6% at 10 years and 12.8% +/- 2.6% at 15 years. The rate of new malignant disease was 3.8-fold higher than that in an age-matched control population (P < 0.001). The most frequent malignant diseases were neoplasms of the skin (14 patients), oral cavity (7 patients), uterus (including cervix) (5 patients), thyroid gland (5 patients), breast (4 patients), and glial tissue (3 patients). Median age of patients and their donors was 21 years. Malignant neoplasms were more frequent in older patients and in patients with chronic graft-versus-host disease. Older patient age and treatment of chronic graft-versus-host disease with cyclosporine were significant risk factors for new malignant neoplasms after bone marrow transplantation. CONCLUSIONS: The spectrum of neoplasms and immunosuppressive treatment with cyclosporine for chronic graft-versus-host disease as dominant risk factors indicate that immunosuppression is the major cause of malignant neoplasms in patients receiving marrow transplants.

Adolescent↗
PubMed1999

[Diagnostic and therapeutic difficulties with tertian malaria].

Diagnosis of malaria tertiana is not uncommonly missed or delayed because of a long incubation period, relapses after an unnoticed primary attack or due to suppressed parasitemia under antibiotics or antimalarials. The presently available rapid tests are not suitable for diagnosis of malaria tertiana. Malaria tertiana acquired in Southeast Asia carries a considerable risk of resistance to chloroquine. In this situation mefloquine is used in first place at total dose of 1000-1500 mg. Relapse of malaria tertiana even after primaquine have been described in travellers returning from the tropics. The efficacy of primaquine can be improved by raising the dose. Hereby an increased risk of hemolysis in concomitant glucose-6-phosphate-dehydrogenase deficiency and, more commonly, gastrointestinal side effects have to be considered.

Humans↗
PubMed1999

Prospective randomized multicenter study comparing cyclosporin alone versus the combination of antithymocyte globulin and cyclosporin for treatment of patients with nonsevere aplastic anemia: a report from the European Blood and Marrow Transplant (EBMT) Severe Aplastic Anaemia Working Party.

We report the results of the first prospective randomized multicenter study of immunosuppressive treatment in patients with previously untreated nonsevere aplastic anemia (AA) as defined by a neutrophil count of at least 0.5 x 10(9)/L and transfusion dependence. Patients were randomized to receive cyclosporin (CSA) alone or the combination of horse antithymocyte globulin ([ATG] Lymphoglobuline; Merieux, Lyon, France) and CSA. The endpoint of the study was the hematologic response at 6 months. One hundred fifteen patients were randomized and assessable with a median follow-up period of 36 months; 61 received CSA and 54 ATG and CSA. In the CSA group, the percentage of complete and partial responders was 23% and 23%, respectively, for an overall response rate of 46%. A significantly higher overall response rate of 74% was found in the ATG and CSA group, with 57% complete and 17% partial responders (P =. 02). Compared with CSA alone, the combination of ATG and CSA resulted in a significantly higher median hemoglobin level and platelet count at 6 months. Fewer patients required a second course of treatment before 6 months due to a nonresponse. In the CSA group, 15 of 61 (25%) patients required a course of ATG before 6 months because of disease progression, compared with only 3 of 54 (6%) in the ATG and CSA group. The survival probabilities for the two groups were comparable, 93% (CSA group) and 91% (ATG and CSA group), but at 180 days, the prevalence of patients surviving free of transfusions, which excluded patients requiring second treatment because of nonresponse, death, disease progression, or relapse, was 67% in the CSA group and 90% in the ATG and CSA group (P =.001). We conclude that the combination of ATG and CSA is superior to CSA alone in terms of the hematologic response, the quality of response, and early mortality, and a second course of immunosuppression is less frequently required.

Adolescent↗
PubMed1999

Effectiveness of immunosuppressive therapy in older patients with aplastic anemia. European Group for Blood and Marrow Transplantation Severe Aplastic Anaemia Working Party.

BACKGROUND: Immunosuppressive therapy has been used for successful treatment of severe aplastic anemia, but little information is available on outcome in older patients. OBJECTIVE: To evaluate outcome in patients older than 50 years of age who received immunosuppressive therapy for aplastic anemia. DESIGN: Retrospective cohort study. SETTING: 56 centers of the European Group for Blood and Marrow Transplantation (EBMT). PATIENTS: 810 patients with aplastic anemia reported between 1974 and 1997. Patients were evaluated according to age group: 60 years of age or older (n = 127), 50 to 59 years of age (n = 115), and 20 to 49 years of age (n = 568; reference group). INTERVENTION: Antilymphocyte globulin, cyclosporine, or both. MEASUREMENTS: Survival, cause of death, response to treatment, relapse rate, and risk for late complications were analyzed in all patients and by age group. RESULTS: The 5-year survival rate was 57% (95% CI, 46% to 66%) in patients 50 to 59 years of age and 50% (CI, 39% to 60%) in patients 60 years of age or older compared with 72% (CI, 68% to 76%) in patients younger than 50 years of age (P < 0.001). Response to therapy, relapse rate, and risk for clonal complications were similar in all three age groups (P > 0.2). Age was significantly associated with an increased risk for death (relative risk compared with patients 20 to 49 years of age, 1.80 [CI, 1.29 to 2.52] for patients 50 to 59 years of age and 2.57 [CI, 1.87 to 3.53] for patients > or = 60 years of age), mainly because of bleeding or infection (P = 0.02). Response to immunosuppressive therapy in all patients at 12 months was 62% (CI, 58% to 66%); no difference was seen among the age groups in multivariate analysis (P > 0.2). Sixty-six of the 379 responding patients (17%) subsequently had relapse. The risk for clonal disorders at 10 years was 20% (CI, 15% to 27%). CONCLUSIONS: Response to immunosuppression in aplastic anemia is independent of age, but treatment is associated with increased mortality in older patients.

Adult↗
PubMed1999

Dicentric translocation (9;12) presenting as refractory Philadelphia chromosome-positive acute B-cell lymphoblastic leukemia.

A 66-year-old Caucasian woman presented with a Philadelphia chromosome positive common B-cell acute lymphoblastic leukemia and a dic(9;12) involving the der(9)t(9;22), a rearrangement so far not observed in acute lymphoblastic leukemia. The patient was treated for the acute lymphoblastic leukemia, but showed refractory disease and died 6 months after initial diagnosis. This case suggests that, in the combination of t(9;22) and dic(9;12), the known poor prognostic feature of t(9;22) in acute lymphoblastic leukemia may outweigh the favorable outcome reported in patients with dic(9;12).

Aged↗
PubMed1999

Umbilical cord blood from preterm human fetuses is rich in committed and primitive hematopoietic progenitors with high proliferative and self-renewal capacity.

Human umbilical cord blood (CB) has been recognized as a source of hematopoietic stem cells for transplantation. While hematopoietic properties of neonatal CB from full-term pregnancies have been well characterized, little is known about CB from early gestational ages. We analyzed the content and the growth properties of primitive and committed hematopoietic progenitors in preterm CB from second trimester (week 16-28; n = 17) and early third trimester (week 29-34; n = 17) in comparison with term CB (n = 18). The frequency of CD34+ and CD34+CD38- cells was significantly higher in preterm than in term CB (mean, 2.51% and 0.56% vs 0.88% and 0.13%;p < 0.002). The number of colony forming units (CFU) in preterm CB was about twofold higher (230 +/- 6 vs 133 +/- 14/ 10(5) mononuclear cells; p < 0.05) and correlated with the content of CD34+ progenitors (r = 0.73). Long-term culture initiating cells (LTC-IC) were enriched about 2.5-fold (6.7 +/- 2.9 vs 2.6 +/- 1.2/10(5) cells; p < 0.05). Progenitors from preterm CB could be expanded in stroma-free liquid cultures supplemented with hematopoietic growth factors as efficiently as progenitors from term neonates. In short-term cultures containing erythropoietin (Epo), interleukin (IL)-1, IL-3, and IL-6, or granulocyte- (G-) and granulocyte-macrophage colony-stimulating factor (GM-CSF) together with stem cell factor (SCF) or Flt3 ligand (FL), expansion of CFUs was six- to eightfold at week 1. In long-term cultures containing thrombopoietin (TPO) and FL, an approximately 1000-fold expansion of multilineage progenitors was observed at week 10. In summary, we show that preterm CB compared with term CB is richer in hematopoietic progenitors, and that precursors from preterm CB can be extensively expanded ex vivo. This may have implications for the development of transplantation and gene transfer strategies targeting circulating fetal stem cells.

Antigens, CD34↗
PubMed1999

Nutritional status and growth after bone marrow transplantation (BMT) during childhood: EBMT Late-Effects Working Party retrospective data. European Group for Blood and Marrow Transplantation.

The European Group for Blood and Marrow Transplantation (EBMT) Late-Effects Working Party collected data on patients who survived more than 5 years after BMT. Height at transplant and at the latest follow-up examination were evaluated in 79/258 subjects who were below the age of 15 at BMT. A significant decrease in height-standard deviation score (SDS) was observed in leukemic children conditioned with total body irradiation (TBI) and in those who received both cranial irradiation and TBI. The majority of these patients, however, received single-dose TBI (28/41). A significant decrease in height-SDS was also seen in children who received thoraco-abdominal irradiation suggesting that the deleterious effect of irradiation on growth after BMT is not entirely due to injury to cranial neuroendocrine structures, but also probably due to damage to bone epiphyses, thyroid and gonads. A non-significant decrease in height was observed in children transplanted using chemotherapy alone. Nutritional status, expressed as body-mass index (BMI), was found unchanged in the adult group (n = 158). A significant increase in BMI was observed in the younger patients (n = 88), which parallels the normal increase in BMI observed during childhood. This suggests that on long-term analysis, a good nutritional status is maintained in patients undergoing BMT at any age.

Adolescent↗
PubMed1999

Successful treatment of refractory acquired pure red cell aplasia (PRCA) by allogeneic bone marrow transplantation.

This case describes a 16-year-old woman treated successfully by a bone marrow transplant from her HLA-identical brother for refractory acquired pure red cell aplasia. Conditioning was as for severe aplastic anaemia with cyclophosphamide 4 x 50 mg/kg and antithymocyte globulin. Complete donor type engraftment at 3 months reversed to full autologous reconstitution at 2 years with normal haemopoiesis. The potential implications on pathogenesis of the disease as well as on treatment of autoimmune disorders by stem cell transplantation are discussed.

Adolescent↗
PubMed1999

Graft-versus-myeloma after withdrawal of immunosuppression following allogeneic peripheral stem cell transplantation.

There is growing evidence for a graft-versus-myeloma effect following allogeneic stem cell transplantation. We add to this evidence by reporting complete remission achieved by withdrawal of immunosuppression in a patient with multiple myeloma progressing after HLA-identical sibling peripheral stem cell transplantation. De novo chronic graft-versus-host disease coincided with the anti-myeloma effect and responded to treatment. The patient remains in complete remission 3 years after transplant.

Adult↗
PubMed1999

Repeated peripheral stem cell mobilization in healthy donors: time-dependent changes in mobilization efficiency.

Mobilization of peripheral blood stem cells was analysed in 10 consecutive healthy donors undergoing repeated stem cell mobilization for allogeneic transplantation. Donors received recombinant G-CSF at a dose of 10 microg/kg/d for both mobilizations. Collection of stem cells was started on day 5 of G-CSF administration. To compare the efficiency of first and second mobilization, we determined the leucocyte and CD34+ cell counts in peripheral blood, and the yield of nucleated cells and CD34+ cell counts in the apheresis product. CD34+ cell numbers in peripheral blood were (median) 81.2 x 10(6)/l during the first and 50.4 x 10(6)/l during the second mobilization (P = 0.007). Likewise, CD34+ cells in the apheresis product decreased from 319.8 x 10(6) to 275.7 x 10(6) (P = 0.02). Decrease in CD34+ cell counts in peripheral blood and in the apheresis product was associated with the time interval between first and second mobilization. In a regression analysis there was a correlation between the ratios of CD34+ cell counts of first and second mobilization and the inverse of time interval between procedures (r2 = 0.51 peripheral blood; r2 = 0.74 apheresis product). Thus, stem cell yield is reduced when healthy donors receive repeated mobilization within a short time. Nevertheless, an adequate number of stem cells may repeatedly be mobilized within 2 months.

Antigens, CD34↗
PubMed1999

High incidence of transiently appearing complement-sensitive bone marrow precursor cells in patients with severe aplastic anemia--A possible role of high endogenous IL-2 in their suppression.

In a prospective long-term study on the incidence of paroxysmal nocturnal hemoglobinuria (PNH), 115 consecutive patients with severe aplastic anemia (SAA), 97 treated with antilymphocyte globulin (ALG) and 18 with bone marrow transplantation (BMT), were observed over a period of 4-18 years and tested for the presence of complement-sensitive hematopoietic precursor cells with the bone marrow (BM) sucrose test. Sixteen (14%) of the ALG-treated patients developed clinical signs of PNH between 0.5 and 8 years after treatment. Complement-sensitive BM precursors were found in 89% of the SAA patients at some time during their disease, but in none of 18 normal donors. At diagnosis, their proportion was significantly higher in patients who later developed PNH than in patients who later achieved disease-free complete remission (CR). After ALG, the abnormal population was found in both groups, but it was gradually replaced by normal precursors in remission patients. After BMT, the complement-sensitive population decreased to very low numbers in patients with a stable graft, but increased again in 3 patients upon graft rejection. Mimicking the PNH defect by enzymatic removal of glycosyl-phosphatidylinositol (GPI)-linked proteins from CD34+ cells resulted in their complement sensitivity, suggesting that the BM sucrose test identifies precursor cells carrying the PNH defect. In 66 patients, white blood cells (WBC) in peripheral blood (PB) were examined for GPI-deficient populations by flow cytometry (FACS). Ten patients with signs of clinical or laboratory PNH had over 25% complement-sensitive precursor cells in the BM and a GPI-deficient WBC population in the PB. Of 56 SAA patients without PNH, 8 had an abnormal population detectable with both tests, 26 only with the BM sucrose test, 4 only with PB FACS analysis, and in 18, no abnormal cells were detected with either test. In search for parameters which might explain why in some patients the abnormal population expands, while it regresses or disappears in others, we tested the release of IL-2 as a parameter of immune competence. At diagnosis, IL-2 release was approximately 50% of normal in patients who later developed PNH, while it was double the normal value in patients who later achieved CR. We conclude that the majority of SAA patients transiently harbor complement-sensitive precursor cells in the BM. Patients with more than 25% abnormal BM precursors and low endogenous IL-2 release are at risk of progression to clinical PNH.

Anemia, Aplastic↗
PubMed1998

Relationship between cleaved L-selectin levels and the outcome of acute myeloid leukemia.

High plasma levels of the shed form of L-selectin (sL-selectin) are frequently detectable in acute myeloid leukemia (AML). sL-selectin can inhibit blast cell adhesion to vascular endothelium and may thereby influence the phenotype of AML. In this study, we have investigated the relationship between sL-selectin levels and clinical presentation or disease outcome in 100 patients with AML. Fifty-eight patients were found to have sL-selectin levels >/=3.12 microgram/mL (>/=3 SD above the mean of healthy controls: "increased"). Patients with extramedullary disease such as lymphadenopathies, splenomegaly, hepatomegaly, and/or muco-cutaneous infiltration had significantly increased sL-selectin levels (P < .001). sL-selectin levels were significantly heterogeneous in the French-American-British subtypes (P = .0003). Patients with "normal" sL-selectin levels had higher probability of achieving complete remission (CR) than with "increased" levels: 81% versus 64%, respectively (P = .06). When adjusting for clinically relevant covariates predictive for CR (sex, age, Auer rods), "normal" sL-selectin levels were significantly associated with CR (odds ratio, 3.08; 95% confidence interval [CI], 1.10 to 8.58; P = .03). Moreover, patients with "increased" sL-selectin levels (>/=3.12 microgram/mL) had shorter event-free survival (EFS) (median 7.3 v 12 months, P = .008) and overall survival (median 1 v 2.05 years, P = .03) than patients with sL-selectin <3.12 microgram/mL. Multivariate statistical analysis (adjusted for age and presence of Auer rods) indicated that sL-selectin was an independent prognostic factor for EFS (hazard ratio [HR], 1.96; 95% CI, 1.21 to 3.17, P = .006) and overall survival (HR, 1.80; 95% CI, 1.09 to 2.98; P = .02). Thus, plasma sL-selectin may be a useful prognostic marker in the evaluation of AML at diagnosis.

Acute Disease↗
PubMed1998

[2-CDA in treatment of hairy cell leukemia: a comparison between intravenous and subcutaneous administration. Swiss Study Group of Applied Cancer Research].

2-chlorodeoxyadenosine (2-CDA) is very effective in the treatment of patients with hairy-cell leukaemia, with an overall response rate of 80-95%. The standard treatment is a continuous intravenous infusion for 7 days. The bioavailability of 2-CDA after subcutaneous injection is 100%, but the concentration-time profile is completely different compared to continuous intravenous administration. In the present study we compared the intravenous standard treatment (group 1, n = 22; 0.1 mg/kg/d for 7 days, civ.) with subcutaneous administration of 2-CDA (group 2, n = 62; 0.14 mg/kg/d for 5 days, s.c.) in patients with hairy-cell leukaemia. In group 1, 96% (21/22) of patients responded to 2-CDA (complete remission 73%, partial remission 23%) and in the second group 97% were responsive (complete response 76%, 47/62; partial remission 21%, 13/62). The percentage for moderate and severe infections in the trial with intravenous and subcutaneous treatment was 14% and 26% respectively (p = 0.37). We conclude that subcutaneous administration of 2-CDA in patients with hairy-cell leukaemia is feasible and economical and results in comparable responses and toxicity compared to the intravenous standard treatment.

2-Chloroadenosine↗
PubMed1998

[Establishing an umbilical cord blood bank for unrelated allogenic stem cell transplantation].

We report the establishment of a cord-blood bank in a routine hematological laboratory. Cord-blood collection was performed with placenta in utero by a trained team and immediately sent to the cord-blood bank. There, 6.8 ml cord-blood was used for analysis of nucleated cell counts, counts of CD34-positive cells, CFU's, complete HLA-typing, ABO and Rhesus blood groups, bacteriologic cultures and serology for HIV 1 and 2, HbsAg, HVC, CMV, syphilis and toxoplasmosis. The cord-blood collection was frozen and conserved at -192 degrees C. From each cord-blood vials of DNA, viable cells and plasma were cryopreserved. Between June 1997 and April 1998, 54 cord-bloods were collected. 40 of them were cryo-preserved, and 14 discarded because of low cell counts. The median volume was 109 ml with 1.4 x 10(9) nucleated cells. The in vitro capacity of proliferation of the cord-blood correlated well with the absolute counts of CD34-positive cells (r = 0.93), moderately with the relative counts of CD34 (r = 0.68) as well as the nucleated cells (r = 0.70), poorly with the volume (r = 0.44). Three of the 40 (7.5%) cord-blood products contained a bacterial contamination. This study shows that a cord-blood bank can be organised in a routine hematological laboratory, which is familiar with transplantation products. However, the procedure is time consuming, expensive and requires a highly qualified team and specialised technical equipment.

Blood Banks↗
PubMed1998

Correction of spurious blood cell counts in a patient with cryoglobulinemia reversed by the use of citrate-anticoagulated blood.

Cryoglobulins may interfere with automated cell counting when proteins precipitate or blood cells aggregate. This results in spurious platelet or leukocyte counts, false values for red blood cell parameters and abnormal scattergrams. Usually it can be reversed by warming blood specimens to 37 degrees C. We describe the case of a 63-year-old woman with autoimmune disease in whom the diagnosis of cryoglobulinemia was suspected due to typical changes in blood cell counts. Artifacts were resistant to warming of the sample to 37 degrees C in both EDTA- and heparin-anticoagulated blood specimens. In contrast, the use of citrate as anticoagulant allowed correct measurements. This case underlines the role of assessment of blood counts in the detection of cryoglobulinemia. Correct measurements of automated blood counts in cryoglobulinemia may depend on the use of alternative anticoagulants.

Anticoagulants↗
PubMed1998

[Optimizing plasma cell content in bone marrow aspirates].

Bone marrow samples used for flow cytometric analysis of plasma cells frequently provide a low plasma cell content. Regularly, samples used for flow cytometry are provided by second step aspiration while the first aspirate is used for cytologic examination. We investigated whether the use of secondary aspirates leads to a systematic underestimation of the bone marrow plasma cell content as a consequence of an increased blood contaminant. To test the hypothesis, plasma cell (CD38bright) percentages were established by flow cytometry in 13 pairs of primary/secondary aspirates. In all cases we found lower plasma cell contents in secondary as compared to primary aspirates (p = 0.0015). Median plasma cell counts in secondary aspirates were 57% lower compared to primary aspirates. We conclude that the use of secondary aspirates leads to systematic underestimation of the bone marrow plasma cell content.

Bone Marrow↗
PubMed1998

[Immunophenotype of blast crisis in chronic myeloid leukemia].

The blast crisis in chronic myeloid leukaemia (CML) is morphologically well defined. The aim of this report was to analyze whether immunophenotyping can divide CML blast crises into subtypes as is done in acute de novo leukaemia, and whether a specific CML pattern exists. Between 1991 and 1997 we reevaluated all the immunophenotypes of patients with CML blast crises with special regard to immunological subclassification, expression of CD34, presence of aberrant markers and number of immunological clusters. Twenty-nine CML blast crises were analyzed. Seventeen were myeloid, 11 lymphoid and one biphenotypic. The blast crises were divided into subtypes as de novo acute leukaemias: of the 17 myeloid blast crises 6 were undifferentiated, 5 differentiated and 6 had monocytic differentiation. In the lymphoid blast crises there were no pro-B, 8 common-B and 3 mature-B. No T-lymphoid blast crises were observed. In 26/29 analyses (90%) CD34 was expressed in the blasts. In 17/29 analyses (59%) one or two aberrant markers were found. In summary, immunophenotyping is important in distinguishing between myeloid and lymphoid blast crises. A subclassification, as in acute leukaemias, is possible. We found no specific immunophenotypic CML pattern. A study directly comparing immunophenotyping of CML blast crises with acute de novo leukaemia is planned.

Adolescent↗