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A Tichelli

Publications and source records attributed to A Tichelli.

At least 19 recordsLinked to original sources
PubMed2006

Comparison of long-term outcomes after allogeneic hematopoietic stem cell transplantation from matched sibling and unrelated donors.

Long-term survivors of hematopoietic stem cell transplants remain at risk of potentially fatal complications that detract from life quality. Long-term morbidity and mortality were compared between matched recipient cohorts surviving 2 or more years and defined by donor type, HLA matched sibling donor (MSD) or volunteer unrelated donor (URD). Patients were previously entered into the prospective multicenter International Unrelated Search and Transplant Study. Thirty-nine centers provided data on 108 URD and 355 MSD recipients surviving more than 2 years. Long-term survival, performance status, chronic GvHD (c-GvHD), secondary malignancy, endocrine dysfunction, cataracts, bone necrosis and dental pathology were compared between cohorts. Twelve year survival was 77+/-5% for the MSD and 67+/-11% for the URD cohort (P=0.1). Late death occurred in 105 of 463 recipients alive at 2 years, 73 after 355 (21%) MSD and 32 after 108 (30%) URD transplants, P=0.10. Of 105 deaths, the cause was relapse in 60 and unrelated to relapse in 45 cases. Cumulative incidence of extensive c-GvHD (P=0.002), cataracts (P=0.02) and bone necrosis (P=0.02) was higher after URD transplants. No long-term difference in endocrine dysfunction, secondary malignancy and major dental pathology was detected. This landmark study will assist physicians counseling patients pre-transplant and with their long-term care post transplant.

Adolescent↗
PubMed2006

Recommended screening and preventive practices for long-term survivors after hematopoietic cell transplantation: joint recommendations of the European Group for Blood and Marrow Transplantation, Center for International Blood and Marrow Transplant Research, and the American Society for Blood and Marrow Transplantation (EBMT/CIBMTR/ASBMT).

More than 40,000 hematopoietic cell transplants (HCTs) are performed worldwide each year. With improvements in transplant technology, larger numbers of transplant recipients survive free of the disease for which they were transplanted. However, there are late complications that can cause substantial morbidity. Many survivors are no longer under the care of transplant centers and many community health-care providers may be unfamiliar with health matters relevant to HCT. The Center for International Blood and Marrow Transplant Research (CIBMTR), European Group for Blood and Marrow Transplantation (EBMT), and American Society for Blood and Marrow Transplantation (ASBMT) have developed these recommendations to offer care providers suggested screening and prevention practices for autologous and allogeneic HCT survivors.

Delivery of Health Care↗
PubMed2006

Impact of high-resolution matching in allogeneic unrelated donor stem cell transplantation in Switzerland.

It is currently unknown what degree of human leukocyte antigen (HLA)-mismatching is acceptable in unrelated donor hematopoietic stem cell transplantation (UD-HSCT). Mismatches at some loci may be more permissive than others. We have analyzed the effect of high-resolution HLA-matching on outcome of all 214 consecutive recipients of UD-HSCT carried out in Switzerland. All typing was by the Swiss reference laboratory. Donor-recipient pairs were HLA-10/10 matched (n=130) or mismatched for either HLA-A/-B/-DRB1/multiple loci (n=33; (HLA-A/-B=10); (-DRB1=8); (multiple=15)); HLA-C (n=29) or HLA-DQ/-DRB3 (n=22; (DQ=16); (-DRB1=6)). The median follow-up was 32 months. Survival probabilities (+/-95% confidence interval) at 3 years were 57 (+/-10)% for recipients of HLA 10/10-matched transplants, 53 (+/-22)% for recipients of HLA-DQ/-DRB3-mismatched transplants, 44 (+/-20)% for recipients of HLA-C-mismatched transplants and 0% for recipients of transplants mismatched at HLA-A/-B/-DRB1/multiple loci (P<0.0001). In multivariate analyses, HLA compatibility was the variable most significantly associated with survival and treatment-related mortality. We found important differences in survival in recipients of UD-HSCT with best results for transplants from 10/10 matched donors. Single mismatches at HLA-DQ/-DRB3 were well tolerated, mismatches at HLA-C had intermediate results and mismatches at HLA-A/-B/-DRB1/multiple loci resulted in poor survival.

Adolescent↗
PubMed2006

Combination of broad molecular screening and cytogenetic analysis for genetic risk assignment and diagnosis in patients with acute leukemia.

We evaluated the impact of genetic analysis combining cytogenetics and broad molecular screening on leukemia diagnosis according to World Health Organization (WHO) and on genetic risk assignment. A two-step nested multiplex RT-PCR assay was used that allowed the detection of 29 fusion transcripts. A total of 186 patients (104 males (56%), 174 adults (94%), 12 children (6%), 155 AML (83%), 31 ALL (17%)) characterized by morphology and immunophenotyping were included. Of these 186 patients, 120 (65%) had a genetic abnormality. Molecular typing revealed a fusion transcript in 49 (26%) patients and cytogenetic analysis revealed an abnormal karyotype in 119 (64%). A total of 27 (14%) cases were genetically classified as favorable, 107 (58%) intermediate and 52 (28%) unfavorable. For 38 (20%) patients, there was a discrepancy in the genetic risk assignments obtained from broad molecular screening and cytogenetics. Cryptic fusion transcripts in nine (5%) patients changed the genetic risk assignment in four and the WHO classification in four patients. In 34 patients (18%), cytogenetics defined the risk assignment by revealing structural and numerical chromosomal abnormalities not detected by molecular screening. Broad molecular screening and cytogenetics are complementary in the diagnosis and genetic risk assignment of acute leukemia.

Acute Disease↗
PubMed2006

Concomitant hairy cell and acute myeloid leukemia.

Secondary malignancies in patients with hairy cell leukemia (HCL) are well described and treatment of HCL is discussed as their cause. We describe a 58-yr-old patient who presented with both acute myeloid leukemia (AML) and HCL at the same time. Treatment with cladribine, daunorubicin and cytosine arabinoside, followed by autologous stem cell transplantation, induced complete remission of AML and hematologic remission of HCL for 22 months, when he relapsed with AML. This concomitant occurrence of AML and HCL is suggestive of a genetic predisposition rather then coincidence or relation to purine analoga.

Antimetabolites, Antineoplastic↗
PubMed2005

Use of natural killer cells in hematopoetic stem cell transplantation.

Adoptive immunotherapy using natural killer (NK) cells may prove useful, especially in situations where infusion of T cells is impractical such as in recipients of haploidentical stem cell transplantation (HSCT) from haploidentical donors. NK cells may induce potent antileukemic and possibly antirejection activity and may even mitigate graft versus host disease (GvHD). Whether such effects are clinically important and whether they are mediated mainly or exclusively by KIR-HLA class I interactions remains to be determined. Recent advances in graft engineering provide for methods to isolate large numbers of purified NK cells. Several groups have shown that clinical grade NK cells up to a dose of 10(7)/kg may be collected and purified for the purpose of infusion to patients. Early results, in a limited number of patients, show that these cell doses may be administered without adverse events and without inducing GvHD. Whether such infusions will be useful in preventing graft rejection, or exerting graft versus leukemia effects and hastening immune recovery requires further study.

Hematopoietic Stem Cell Transplantation↗
PubMed2005

Transplant-associated microangiopathy (TAM) in recipients of allogeneic hematopoietic stem cell transplants.

We studied occurrence, risk factors and outcome of patients with transplant-associated microangiopathy (TAM) after allogeneic stem cell transplantation (HSCT). A total of 221 consecutive patients were transplanted between 1995 and 2002. TAM is defined as evidence of hemolysis and schistocytes in the first 100 days. Outcomes analyzed included TAM and overall survival. Of 221 patients, 68 had TAM. The cumulative incidence was 31 (25-38)% at 100 days. Patients with TAM had higher LDH, higher bilirubin, higher creatinine and more often neurologic symptoms. TAM was not associated with stem cell source, cyclosporine levels and was not more frequent in recent years. In multivariate analysis, risk factors for TAM included donor type, age, gender, ABO-incompatibility and acute graft-versus-host disease (aGvHD). In patients with TAM, 1-year survival was lower than in patients without TAM (27 +/- 18% for TAM with high schistocyte counts; 53 +/- 15% for TAM with low schistocyte counts; vs 78 +/- 7% in patients without TAM; P<0.0001). TAM was independently associated with mortality adjusting for donor type, age and aGvHD occurrence and severity. TAM is frequent after HSCT and is associated with mortality even after adjustment for aGvHD grade. Risk factors of TAM are similar to aGvHD. TAM may represent endothelial damage driven by donor-host interactions.

Adolescent↗
PubMed2004

High-dose chemotherapy using BEAM for tumor debulking without stem cell support followed by early allogeneic reduced intensity conditioning transplantation to induce a graft-versus-lymphoma effect in patients with high risk or refractory lymphoma.

In patients with refractory lymphoma, we tested the hypothesis that high-dose chemotherapy (BEAM) without stem cell support followed by a reduced intensity (RIC) allogeneic transplant with fludarabine and 2 Gy TBI 28 days later results in tumor debulking and establishment of a graft vs lymphoma effect, with acceptable toxicity. In a pilot protocol we treated 10 patients, 22-62 (median 47) years of age with high-risk or refractory Hodgkin's or non-Hodgkin's lymphoma. Donors were HLA identical siblings (eight) or unrelated volunteers. None died during the neutropenic phase after BEAM which lasted up to the RIC HSCT. The duration of neutropenia was 31-43 (median 36) days. All patients engrafted and nine achieved CR. All developed acute GvHD (median grade III) and all patients at risk developed chronic GvHD. Three patients died of GvHD. One relapsed and six patients are in continuous CR 10-32 (median 15) months after HSCT. This approach appears feasible and results in a high response rate. Neutropenia duration is of concern. It remains to be tested whether separation of debulking chemotherapy and induction of allogeneic effects confers an advantage.

Adolescent↗
PubMed2004

Purified donor NK-lymphocyte infusion to consolidate engraftment after haploidentical stem cell transplantation.

This pilot study tested feasibility of natural killer cell purification and infusion (NK-DLI) in patients after haploidentical hematopoietic stem cell transplantation (HSCT). The aim was to obtain >or=1.0 x 10(7)/kg CD56+/CD3- NK cells and <1.0 x 10(5)/kg CD3+ T cells. Mononuclear cells were collected by 10 l leukapheresis. A two-step ex vivo procedure was used to purify NK cells, using an immunomagnetic T-cell depletion, followed by NK-cell enrichment. Five patients with high-risk myeloid malignancies were included, presenting 3-12 months after a haploidentical HSCT with mixed chimerism (3), impending graft failure (1) or early relapse (1). The purified product contained a median of 1.61 x 10(7)/kg (range 0.21-2.2) NK cells and 0.29 x 10(5)/kg (0.11-1.1) T cells. A purity of NK cells of 97% (78-99), a recovery of 35.5% (13-75), and a T-cell depletion of 3.55 log (2.9-4.5) was achieved. Infusions were well tolerated and none of the patients developed graft-versus-host disease. We observed an increase in donor chimerism in 2/5, stable mixed chimerism, decreasing chimerism and relapse of AML in one patient each. Selection of NK-DLI is technically feasible. NK cells are well tolerated when used as adoptive immunotherapy in recipients of haploidentical HSCT.

Adolescent↗
PubMed2003

Mobilization of peripheral blood progenitor cells with vinorelbine and granulocyte colony-stimulating factor in multiple myeloma patients is reliable and cost effective.

Cyclophosphamide with granulocyte colony stimulating factor (G-CSF) is commonly used to mobilize stem cells in multiple myeloma. Timing of collection is variable and incidence and severity of side effects is substantial. To optimize timing of collection, to reduce side effects and to limit costs of the procedure, we evaluated vinorelbine, a drug shown to have activity in multiple myeloma, in combination with G-CSF as mobilizing regimen. A total of 19 consecutive patients with advanced stage multiple myeloma received one dose of vinorelbine 35 mg/m(2) intravenously on day 1 in an outpatient setting and G-CSF 10 microg/kg/day from day 4 divided in two daily doses. Median CD34+ cell blood counts measured on day 8 of mobilization were 142 x 10(6)/l (range 57-467). One 15-l apheresis on day 8 resulted in sufficient stem cells (median 11.1 x 10(6) CD34+ cells/kg, range 6.2-36.0 prior and median 7.5 x 10(6) CD34+ cells/kg, range 4.0-20.2 post-positive CD34+ cell selection) for transplantation. Hematopoietic recovery was swift with ANC >0.5 x 10(9)/l on day 11 median (range 10-15) and platelets >20 x 10(9)/l on day 12 median (range 10-15) after reinfusion of the stem cells on day 0. No episodes of febrile neutropenia were observed during mobilization. In our institutions cost reduction for the procedure was about 1700 euros compared to the mobilization with cyclophosphamide and G-CSF. Vinorelbine and G-CSF allow precise timing and harvesting of sufficient stem cells, and might be an alternative to cyclophosphamide in the mobilization of stem cells for autologous transplantation in multiple myeloma.

Aged↗
PubMed2003

Randomized comparison of interferon alpha and hydroxyurea with hydroxyurea monotherapy in chronic myeloid leukemia (CML-study II): prolongation of survival by the combination of interferon alpha and hydroxyurea.

The optimum treatment conditions of interferon (IFN) alpha therapy in chronic myeloid leukemia (CML) are still controversial. To evaluate the role of hydroxyurea (HU) for the outcome of IFN therapy, we conducted a randomized trial to compare the combination of IFN and HU vs HU monotherapy (CML-study II). From February 1991 to December 1994, 376 patients with newly diagnosed CML in chronic phase were randomized. In all, 340 patients were Ph/BCR-ABL positive and evaluable. Randomization was unbalanced 1:2 in favor of the combination therapy, since study conditions were identical to the previous CML-study I and it had been planned in advance to add the HU patients of study I (n=194) to the HU control group. Therefore, a total of 534 patients were evaluable (226 patients with IFN/HU and 308 patients with HU). Analyses were according to intention-to-treat. Median observation time of nontransplanted living patients was 7.6 years (7.9 years for IFN/HU and 7.3 years for HU). The risk profile (new CML score) was available for 532 patients: 200 patients (38%) were low, 239 patients (45%) intermediate, and 93 patients (17%) high risk. Complete hematologic response rates were higher in IFN/HU-treated patients (59 vs 32%). Of 169 evaluable IFN/HU-treated patients (75%), 104 patients (62%) achieved a cytogenetic response that was complete in 12% (n=21), major in 14% (n=24), and at least minimal in 35% (n=59). Of the 534 patients, 105 (20%) underwent allogeneic stem cell transplantation in first chronic phase. In the low-risk group, 65 of 200 patients were transplanted (33%), 30 (13%) in the intermediate-risk group, and nine (10%) in the high-risk group. Duration of chronic phase was 55 months for IFN/HU and 41 months for HU (P<0.0001). Median survival was 64 months for IFN/HU and 53 months for HU-treated patients (P=0.0063). We conclude that IFN in combination with HU achieves a significant long-term survival advantage over HU monotherapy. In view of the data of CML-study I, these results suggest that IFN/HU is also superior to IFN alone. HU should be combined with IFN in IFN-based therapies and for comparisons with new therapies.

Adolescent↗
PubMed2002

High stem cell dose will not compensate for T cell depletion in allogeneic non-myeloablative stem cell transplantation.

The best strategies for non-myeloablative stem cell transplants (NST) are not known. We hypothesized that a high stem cell dose and post-transplant donor lymphocyte infusions (DLI) in a T cell-depleted NST setting may result in stable engraftment without severe GvHD. We used conditioning with 200 mg/kg cyclophosphamide, and ATG, a high peripheral stem cell dose of >10 x 10(6) CD34(+) cells/kg, T cell-depleted to <1 x 10(5) CD3(+) cells/kg followed by incremental DLI. Ten patients, 53 (42-61) years of age with hematological malignancy (CML in 3, MDS in 2, myeloma in 3 and CLL in 2) were included. All patients achieved initial engraftment, at a median 13.5 (10-20) days. Three patients achieved complete chimerism, four achieved a complete hematologic remission. In seven patients the graft ultimately failed. Acute GvHD grade II was seen in three patients after DLI. At a median follow-up of 28 months (range 15-35), eight patients are alive, none died of treatment-related complications. NST with T cell depletion to prevent GVHD results in a high graft failure rate. High stem cell dose (> or =10 x 10(6) CD34(+)cells/kg) and post-transplant DLI will not compensate for the lack of T cells to ensure stable engraftment.

Adult↗
PubMed2002

Treatment of hairy cell leukemia with cladribine (2-chlorodeoxyadenosine) by subcutaneous bolus injection: a phase II study.

BACKGROUND: To assess the activity and toxicity of 2-chlorodeoxyadenosine (cladribine, CDA) given by subcutaneous bolus injections to patients with hairy cell leukemia (HCL). PATIENTS AND METHODS: Sixty-two eligible patients with classic or prolymphocytic HCL (33 non-pretreated patients, 15 patients with relapse after previous treatment, and 14 patients with progressive disease during a treatment other than CDA) were treated with CDA 0.14 mg/kg/day by subcutaneous bolus injections for five consecutive days. Response status was repeatedly assessed according to the Consensus Resolution criteria. RESULTS: Complete and partial remissions were seen in 47 (76%) and 13 (21%) patients, respectively, for a response rate of 97%. All responses were achieved with a single treatment course. Most responses occurred early (i.e. within 10 weeks) after start of CDA therapy, but response quality improved during weeks and even months after treatment completion. The median time to treatment failure for all patients was 38 months. Leukopenia was the main toxicity. Granulocyte nadir (median 0.2 x 10(9)/l) was strongly associated with the incidence of infections (P = 0.0013). Non-specific lymphopenia occurred early after CDA treatment, and normal lymphocytes recovered slowly over several months. No significant associations were found between infections and nadir count of lymphocytes or any lymphocyte subpopulation. No opportunistic infections were observed. CONCLUSIONS: One course of CDA given by subcutaneous bolus injections is very effective in HCL. The subcutaneous administration is more convenient for patients and care providers, and has a similar toxicity profile to continuous intravenous infusion. The subcutaneous administration of CDA is a substantial improvement and should be offered to every patient with HCL requiring treatment with CDA.

Adult↗
PubMed2001

[Anemia, neutropenia and thrombocytopenia: hematological findings and HIV].

Hematologic pathologies like anemia, neutropenia and thrombocytopenia are frequently seen in HIV-infected patients. Etiologies of cytopenias are diverse, affect all three cell lines and cause considerable and sometimes even live threatening clinical problems. Opportunistic infections may cause bone marrow suppression or specific cytopenias but also adverse events of antiretroviral drugs and drugs against opportunistic infections frequently cause marrow suppression. Morphological changes in the bone marrow of HIV-infected patients are generally unspecific. Frequently, dysplasia, dyserythropoesis, lymphocyte infiltration or plasmocytosis are seen. In the following article, relevant practical points of pathogenesis and therapy options should be discussed with three case studies.

Adult↗
PubMed2001

Stable transduction with lentiviral vectors and amplification of immature hematopoietic progenitors from cord blood of preterm human fetuses.

Umbilical cord blood (CB) from the early gestational human fetus is recognized as a rich source of hematopoietic stem cells. To examine the value of fetal CB for gene therapy of inborn immunohematopoietic disorders, we tested the feasibility of genetic modification of CD34(+) cells from CB at weeks 24 to 34 of pregnancy, using lentiviral vector-mediated transfer of the green fluorescent protein (GFP) gene. The transduction rate of CD34(+) cells was 42 +/- 9%, resulting in GFP expression in 23 +/- 4% of colonies derived from colony-forming units (CFUs) and 11 +/- 1% from primitive long-term culture-initiating cells (LTC-ICs). Cell cycle analysis demonstrated transduction and GFP expression in cells in the G(0) phase, which contains immature hematopoietic progenitors. Transduced fetal CD34(+) cells could be expanded 1000-fold in long-term cultures supplemented with megakaryocyte growth and development factor along with Flt-3 ligand. At week 10, expression of GFP was observed in 40.5 +/- 11.7% of CFU-derived colonies. While prestimulation of CD34(+) cells with cytokines prior to transduction increased the efficiency of GFP transfer 2- to 3-fold, long-term maintenance of GFP-expressing CFUs occurred only in the absence of prestimulation. The GFP gene was found integrated into the genomic DNA of 35% of LTC-IC-derived colonies initiated at week 10, but GFP expression was not detectable, suggesting downregulation of transgene activity during the extended culture period. These results indicate that human fetal CB progenitors are amenable to genetic modification by lentiviral vectors and may serve as a target for gene therapy of hematopoietic disorders by prenatal autologous transplantation.

Antigens, CD34↗