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J Gmür

Publications and source records attributed to J Gmür.

At least 19 recordsLinked to original sources
PubMed2004

Mycobacterial infection: a difficult and late diagnosis in stem cell transplant recipients.

The Infectious Diseases Working Party of the European Blood and Marrow Transplant Group conducted a survey to obtain information about the frequency, presentation, and treatment of mycobacterial infection (MBI) in stem cell transplant (SCT) recipients. Among 29 centers, MBI was diagnosed in 0.79% of 1513 allogeneic and 0.23% of 3012 autologous SCT recipients during 1994-1998 a median of 160 days after transplantation. The mean interval between first symptoms and diagnosis was 29 days and was still longer for patients with atypical MBI or recipients of corticosteroid therapy. The prevalence of MBI was highest among those who received matched unrelated or mismatched STCs from related donors. Of 31 patients, 20 had tuberculosis, 8 had atypical MBI, and 3 had diagnoses based on histological findings only. Five patients (16%) died, all of whom had received an allogeneic SCT. Because of the increased numbers of unmatched donors and transplantation programs in countries with a high prevalence of tuberculosis, constant vigilance is required to early detect MBI in SCT recipients.

Adolescent↗
PubMed2002

Consequences of ABO incompatibility in allogeneic hematopoietic stem cell transplantation.

Aside from causing hemolytic reactions the ABO blood group system does not have an impact on outcome after allogeneic bone marrow or peripheral blood stem cell transplantation (SCT). However, only a few studies have addressed the effect of ABO incompatibility on the incidence of GVHD, time to engraftment, relapse and survival. Therefore, we performed a retrospective two-center analysis of 562 consecutive patients receiving allogeneic SCT, including 361 ABO-identical, 98 minor, 86 major and 17 bidirectional ABO-incompatible SCT. In multivariate analysis adjusted for potential confounders survival was significantly associated with ABO incompatibility (P = 0.006). Compared to ABO-identical SCT, bidirectional ABO incompatibility increased the risk significantly (RR, 2.8; 95% CI, 1.5-5.1; P = 0.0009), whereas survival of patients with minor (RR, 1.2; 95% CI, 0.9-1.7; P = 0.27), or major ABO-incompatible SCT (RR, 1.3; 95% CI, 0.9-1.8; P= 0.18) was not significantly different. RBC engraftment was delayed in major ABO-incompatible SCT (RR, 0.66; 95% CI, 0.51-0.85; P = 0.001). The incidence of acute GVHD (grade I-IV) was higher in minor ABO-incompatible SCT as compared to ABO identity (RR, 2.8; 95% CI, 1.3-5.9, P = 0.009). This difference was limited to mild GVHD; in moderate-to-severe GVHD (grade II-IV) no significant difference was found among the groups (P = 0.53). The relapse rate was not influenced by ABO incompatibility (P = 0.78). In conclusion, these results suggest that ABO incompatibility represents a risk factor not only for post-transplant hemolysis, but also for survival and the rate of mild GVHD after allogeneic SCT.

ABO Blood-Group System↗
PubMed2001

Graft-versus-host disease and survival after ABO-incompatible allogeneic bone marrow transplantation: a single-centre experience.

The effect of ABO-incompatibility on graft versus host disease (GVHD) and survival was evaluated in 173 consecutive patients receiving allogeneic bone marrow transplantation (BMT). Thirty-four percent of the patients developed GVHD and univariate analysis suggested a higher incidence of GVHD in minor ABO-incompatibility than in ABO-identity (14/30, 47% versus 37/112, 33%; P = 0.02). However, using logistic regression adjusted for potential confounders, the GVHD risk did not differ significantly. During a mean follow-up time of 59 months, the mortality was 37% and survival was significantly dependent on ABO-compatibility (P = 0.004). In particular, patients with bidirectional ABO-incompatibility had an excess mortality rate (RR, 7.6; 95% CI, 2.5-23.2; P = 0.0004). Taken together, these results suggest that ABO-incompatibility may represent a risk factor in allogeneic BMT.

ABO Blood-Group System↗
PubMed2000

Bone marrow transplantation with unrelated donors: what is the probability of identifying an HLA-A/B/Cw/DRB1/B3/B5/DQB1-matched donor?

Patients transplanted with marrow from an HLA-ABDR serologically matched unrelated donor suffer from more post-transplant complications than those who are transplanted with marrow from an HLA-identical sibling. This is most likely due to either HLA-ABDR incompatibilities not resolved by standard techniques and/or HLA polymorphisms not tested for by routine tissue typing (HLA-Cw,-DQ). By resolving these incompatibilities by molecular techniques combined with the in vitro cytotoxic T lymphocyte precursor frequency (CTLpf) test, we have shown that a high degree of HLA compatibility is associated with increased patient survival. However, higher requirements for HLA matching decrease the number of available donors. We have estimated the probability of finding an HLA-A/B/Cw/DRB1/DRB3/DRB5/DQB1 compatible donor based on 104 consecutive unrelated bone marrow donor searches initiated between January 1995 and December 1997, with December 1998 as the endpoint. For 96 patients (92.3%), one or more ABDR-identical donors were listed in the Bone Marrow Donor Worldwide Registry (BMDW). After contacting the registries, we obtained at least one (mean, 5.36; range, 1-20; total, 461) blood sample for 86 patients. A highly compatible donor was identified for 33/86 patients (38.4%), after testing an average number of 4.5 donors/patients (range, 1-13). However, by accepting an HLA-DRB3 or -DQB1 or -Cw incompatibility, this number would be as high as 68.6%. Approximately half of the patients (n = 40) for whom a search had been initiated have been transplanted: 22 patients with a perfectly matched donor, 15 patients with an HLA-DRB3 or -DQB1 or -Cw mismatch and three with other mismatches. The average time needed to identify the most compatible donor was 4 months. Extremely long searches seemed to be less useful, because after testing the first seven, a more compatible donor was seldom found. These results show that even when requirements for compatibility are high, the chances of finding a donor remain considerably low.

Bone Marrow Transplantation↗
PubMed1999

[Common variable immunodeficiency: a rare humoral immunodeficiency with frequent later change of diagnosis].

Common variable immunodeficiency (CVIS) is a condition associated with a deficiency of humoral immunity. The typical patient is an adolescent or adult with a history of recurrent upper respiratory tract infections over many years. Despite the long history the illness is not readily recognised and diagnosis is usually delayed until the patient is admitted to hospital for a severe respiratory tract infection and is being worked up for causes of immunodeficiency. The diagnosis of CVIS is based on the finding of an immunoglobulin deficiency in immunoelectrophoresis or documentation of reduced IgG subclasses. Typically this leads to upper respiratory tract infections and malabsorption, as illustrated by the case reports. Pathophysiologically this disease is characterised by malfunction of B cells with defective gammaglobulin production or secretion. 7 patients were substituted with IgG, leading to decreased susceptibility to infection and a reduction in hospital admissions due to severe infections.

Adult↗
PubMed1999

Sequencing of two HLA-A blank alleles: implications in unrelated bone marrow donor matching.

BACKGROUND: DNA-based methods can type for HLA antigens with no or very low cell surface expression. The role of such serological blank antigens in bone marrow donor selection is unknown. METHODS: HLA-A serological blank antigens detected in two leukemic patients were cloned and sequenced from genomic DNA. mRNA expression and exon 3 splicing were determined by reverse transcriptase-polymerase chain reaction (PCR). RESULTS: Two patients typed A2/x and A3/x by serology were revealed to be A*01/A*0201 and A*03/A*24 by DNA typing. The HLA-A*O1 blank antigen was identified as the A*0104N allele with a C insertion in exon 4, which results in a stop codon. The HLA-A*24 blank antigen was identified as the A*2402102L allele characterized by a mutation in intron 2 leading to impaired splicing of mainly exon 3. As a consequence, functional A24 mRNA was reduced to less than 5% compared with the other HLA-A allele. For both patients, a search for an unrelated donor was initiated on the basis of the functional absence of the serologically blank allele. The second patient with the A*24 blank antigen could undergo transplantation with marrow from a "fully A/B/C/DRB1/DRB5/DQB1-compatible" donor, homozygous for the A antigen. Donor T cells did not react against the patient in a pretransplantation cytotoxic T lymphocyte precursor frequency test known to detect all class I incompatibilities. However, despite this functional pretransplantation compatibility, the patient died 44 days after bone marrow transplantation, suffering from graft-versus-host disease grade IV. The presence of potentially functional A*2402 mRNA could be demonstrated by reverse transcriptase-PCR and sequencing: 50% of the A24 mRNA molecules were estimated to contain exon 3 with a correct splice site. CONCLUSIONS: These findings show that serological blank antigens with low mRNA expression might still be recognized after bone marrow transplantation. The determination of such alleles by molecular methods and the assessment of mRNA expression should therefore be included in the unrelated bone marrow donor search protocol.

Alleles↗
PubMed1999

A restrictive platelet transfusion policy allowing long-term support of outpatients with severe aplastic anemia.

The threshold for prophylactic platelet transfusions in patients with hypoplastic thrombopenia generally recommended in the standard literature is 20,000 platelets/microL. A more restrictive transfusion policy may be indicated in patients with chronic severe aplastic anemia (SAA) in need of long-term platelet support. We evaluated the feasibility and safety of a policy with low thresholds for prophylactic transfusions (</=5,000 platelets/microL in stable patients; 6,000 to 10,000 platelets/microL in cases with fever and/or hemorrhagic signs) combined with progressive lengthening of transfusion intervals (up to at least 7 days irrespective of the interim course of platelet counts). The study was based on a retrospective analysis of a total of 18,706 patient days with platelet counts </=10,000/microL in patients with chronic SAA treated (for more than 3 months) on an outpatient basis. Altogether, 1,135 platelet transfusions were given, 88% at counts </=10, 000/microL and 57% at counts </=5,000/microL. The mean transfusion interval was 10 days. During the period of observation, three major nonlethal bleeding complications occurred, which could be well controlled. We conclude that the restrictive policy with low transfusion thresholds and prolonged transfusion intervals proved feasible and safe in chronic SAA patients.

Adolescent↗
PubMed1999

Peripheral blood stem cell transplantation as an alternative to autologous marrow transplantation in the treatment of acute myeloid leukemia?

The clinical use of autologous marrow transplantation in acute myeloid leukemia (AML) has been hampered by the inability to collect adequate numbers of cells after remission induction chemotherapy and the notably delayed hematopoietic regeneration following autograft reinfusion. Here we present a study in which the feasibility of mobilizing stem cells was investigated in newly diagnosed AML. Among 96 AML patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with low dose and high dose schedules of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. A median of 2.0 x 10(6) CD34+ cells/kg (range 0.1-72.0) was obtained in a median of three leukaphereses following a low dose G-CSF schedule (150 microg/m2) during an average of 20 days. Higher dose regimens of G-CSF (450 microg/m2 and 600 microg/m2) given during an average of 11 days resulted in 28 patients in a yield of 3.6 x 10(6) CD34+ cells/kg (range 0-60.3) also obtained following three leukaphereses. The low dose and high dose schedules of G-CSF permitted the collection of 2 x 10(6) CD34-positive cells in 46% and 79% of cases respectively (P = 0.01). Twenty-eight patients were transplanted with a peripheral blood stem cell (PBSC) graft and hemopoietic repopulation was compared with the results of a previous study with autologous bone marrow. Recovery of granulocytes (>0.5 x 10(9)/l, 17 vs 37 days) and platelets (>20 x 10(9)/l; 26 vs 96 days) was significantly faster after peripheral stem cell transplantation compared to autologous bone marrow transplantation. These results demonstrate the feasibility of PBSCT in the majority of cases with AML and the potential advantage of this approach with respect to hemopoietic recovery.

Acute Disease↗
PubMed1999

Delaying treatment with granulocyte colony-stimulating factor after allogeneic bone marrow transplantation for hematological malignancies: a prospective randomized trial.

The use of granulocyte colony-stimulating factor (G-CSF) has been established to improve hematological recovery after allogeneic bone marrow transplantation (BMT). The optimal timing to start with G-CSF has not been determined. This study investigates whether delayed use of G-CSF starting on day 6 is as safe and efficient as starting treatment with G-CSF immediately after BMT. Thirty-eight patients undergoing allogeneic BMT were randomized to either receive post-transplant G-CSF treatment starting at day 1 or at day 6. The time to hematological recovery was monitored and the groups were compared with respect to peritransplant morbidity and mortality. Recovery of the neutrophil granulocyte counts (PMN) to >100/microl, >500/microl and >1000/microl was comparable in both groups. The nadir of the PMN counts after stopping G-CSF was also similar. There was no difference in the recovery of red blood cells and platelet counts and no difference between the two groups with respect to the number of febrile episodes, number of days with antibiotics or number of documented bacterial, fungal or viral infections. Delayed treatment with G-CSF resulted in a reduction of G-CSF treatment from 19 days to 14 days (P = 0.0017). Reducing the length of treatment by 5 days lowered G-CSF treatment costs by 26.3%. Therefore, postponing treatment with G-CSF has no influence on the hematological recovery after allogeneic BMT. There is an economical benefit of postponing G-CSF use without any clinical disadvantages.

Adolescent↗
PubMed1998

[10 years Swiss bone marrow donor registry].

The Swiss Bone Marrow Donor Registry was established 1988 as a project of Swiss Transplant. Up to the end of 1997, 13,500 unrelated volunteer donors have been added to the central registry in Bern in cooperation with the regional transfusion centers of Switzerland. During this period, the registry responded to over 15,000 international search requests. 67 matching Swiss donors were found for patients all over the world. On the other hand, 77 Swiss patients received unrelated bone marrow transplantation from international donors. In 1997, 24 donors were selected from the Swiss registry and 21 bone marrow transplantations were performed, which is more than in any year before. The most recent developments are peripheral blood stem cell donation and the creation of cord blood banks.

Bone Marrow Transplantation↗
PubMed1998

Use of intravenous immune globulin in addition to antiviral therapy in the treatment of CMV gastrointestinal disease in allogeneic bone marrow transplant patients: a report from the European Group for Blood and Marrow Transplantation (EBMT). Infectious Diseases Working Party of the EBMT.

The best treatment of CMV gastrointestinal disease has been controversial, with some centers adding intravenous (i.v.) Ig to antiviral chemotherapy. The aim of this retrospective survey was to compare the outcome of antiviral chemotherapy with or without i.v. Ig. A questionnaire was sent to centers belonging to the EBMT. Thirty-three patients with CMV gastrointestinal disease were reported, 22 patients were given antiviral chemotherapy alone and 11 patients a combination of antiviral chemotherapy and i.v. Ig. Eighteen of 33 (55%) patients responded to therapy, 13 of those treated with antiviral chemotherapy alone and five (45%) of those treated with the combination (P = NS). Patients with acute GVHD of grades II-IV had significantly worse outcomes than patients with acute GVHD grades 0-I. In a Cox proportional hazards model corrected for acute GVHD there was no difference in outcome of CMV gastrointestinal disease with or without addition of Ig. Survival at 100 days after diagnosis of CMV gastrointestinal disease was 64%. There was no difference in survival in patients treated with or without i.v. Ig. The results of this retrospective survey indicate that addition of i.v. Ig to antiviral chemotherapy might not improve outcome in patients with biopsy-proven CMV gastrointestinal disease.

Adolescent↗
PubMed1997

Hepatic lesions of chronic disseminated candidiasis may become invisible during neutropenia.

We describe the phenomenon of waning of focal hepatic and/or splenic lesions on abdominal computed tomographic (CT) scan during neutropenia in patients with chronic disseminated candidiasis. After observation of the phenomenon in one patient, a total of five cases were prospectively monitored with serial CT scans. After the diagnosis of disseminated candidiasis, hepatic lesions decreased in size and conspicuousness in three patients, while in two others they disappeared completely during a subsequent chemotherapy-induced neutropenia. After recovery of the neutrophils, the lesions reappeared or increased in conspicuousness in all five patients. Of three patients treated with a second cycle of myeloablative chemotherapy, lesions again decreased in two patients during neutropenia and increased again in one patient after neutrophil recovery. In all five patients, candidiasis eventually resolved after prolonged antifungal treatment. In chronic disseminated candidiasis, hepatic or splenic lesions may transiently disappear during neutropenia. Thus, antifungal therapy should not be discontinued on the basis of radiologic findings alone.

Adolescent↗
PubMed1997

Detection of 16 p deletions by FISH in patients with inv(16) or t(16;16) and acute myeloid leukemia (AML).

Deletions of sequences centromeric to the p-arm breakpoint have been described in a subset of patients with inv(16) and acute myeloid leukemia (AML) and reported to be associated with a relatively good prognosis. We have investigated 16 p deletions in a cohort of 15 patients with AML and inv(16) or t(16;16) and compared non-deletion and deletion patients in terms of clinical course. Patients were studied by fluorescence in situ hybridization (FISH) using cosmid zit14 as a probe to detect the presence of 16 p deletions in metaphase chromosomes of leukemic cells. While seven patients (47%) revealed no evidence of a deletion, five patients (33%) presented 16 p deletions, thus bringing further support to the relatively frequent occurrence of this event in inv(16) patients. Remarkably, two patients with inv(16) and one patient with t(16;16) showed a mosaicism of deletion and non-deletion metaphases suggesting the presence of two distinct leukemic cell populations. Results let us assume that 16 p deletions are not restricted to inv(16) and may occur subsequently to inv(16) or t(16;16). The presence of a 16 p deletion in a case of inv(16) associated with CBFB-MYH11 transcript type E indicates that deletions are not limited to CBFB-MYH11 transcript type A rearrangements. Survival of deletion patients was compared with that of non-deletion and mosaic ones. No significant differences were observed. The advantage of FISH for enumerative and quantitative assessment of submicroscopic rearrangements of clinical significance is further emphasized.

Adolescent↗
PubMed1997

Value of different modalities of granulocyte-macrophage colony-stimulating factor applied during or after induction therapy of acute myeloid leukemia.

PURPOSE: The hematopoietic growth factors (HGFs) introduced into induction chemotherapy (CT) of acute myeloid leukemia (AML) might be of benefit to treatment outcome by at least two mechanisms. HGFs given on days simultaneously with CT might sensitize the leukemic cells and enhance their susceptibility to CT. HGFs applied after CT might hasten hematopoietic recovery and reduce morbidity or mortality. MATERIALS AND METHODS: We set out to evaluate the use of granulocyte-macrophage colony-stimulating factor (GM-CSF; 5 microg/kg) in a prospective randomized study of factorial design (yes or no GM-CSF during CT, and yes or no GM-CSF after CT) in patients aged 15 to 60 years (mean, 42) with newly diagnosed AML. GM-CSF was applied as follows: during CT only (+/-, n = 64 assessable patients), GM-CSF during and following CT (+/+, n = 66), no GM-CSF (-/-, n = 63), or GM-CSF after CT only (-/+, n = 60). RESULTS: The complete response (CR) rate was 77%. At a median follow-up time of 42 months, probabilities of overall survival (OS) and disease-free survival (DFS) at 3 years were 38% and 37% in all patients. CR rates, OS, and DFS did not differ between the treatment groups (intention-to-treat analysis). Neutrophil recovery (1.0 x 10(9)/L) and monocyte recovery were significantly faster in patients who received GM-CSF after CT (26 days v 30 days; neutrophils, P < .001; monocytes, P < .005). Platelet regeneration, transfusion requirements, use of antibiotics, frequency of infections, and duration of hospitalization did not vary as a function of any of the therapeutic GM-CSF modalities. More frequent side effects (eg, fever and fluid retention) were noted in GM-CSF-treated patients predominantly related to the use of GM-CSF during CT. CONCLUSION: Priming of AML cells to the cytotoxic effects of CT by the use of GM-CSF during CT or accelerating myeloid recovery by the use of GM-CSF after CT does not significantly improve treatment outcome of young and middle-aged adults with newly diagnosed AML.

Acute Disease↗
PubMed1996

Additional inhibitory effects of intravenous immunoglobulins in combination with cyclosporine A on human T lymphocyte alloproliferative response in vitro.

Intravenous immunoglobulins (IvIgG) are often used in patients receiving a basic immunosuppressive therapy with CsA either for prevention of infectious complications or as an additional prophylaxis of graft versus host disease in clinical bone marrow transplantation. As far as we know, the combined in vitro immunosuppressive effects of these 2 drugs have not been investigated yet. In this study, we compared the effect of CsA, IvIgG, and CsA combined with IvIgG on the proliferative capacity of peripheral blood mononuclear cells in a mixed lymphocyte culture system. The concentration-dependent inhibition of peripheral blood mononuclear cell proliferation in the mixed lymphocyte culture system by CsA is a well established phenomenon. By adding IvIgG to the cultures (n=20) containing CsA, we were able to show a significantly (P<0.0002) higher inhibition compared with the inhibitory capacity of CsA alone. Cyclosporine A was added to the cultures at concentrations ranging from 25 to 400 ng/ml, and IvIgG was added in 3 different fixed concentrations: 1.25, 2.5, and 5 mg/ml. These are all concentrations which one usually obtains in patients during therapy with these drugs. Even with a minimal concentration of CsA (25 ng/ml) plus IvIgG (1.25 mg/ml), we achieved a mean inhibition of 77.7 +/- 7.9%, which is in the range of the mean inhibition (84.3 +/- 4.7%) with the highest concentration of CsA (400 ng/ml tested. Our in vitro results could suggest that the additional therapy with IvIgG in patients receiving CsA might cause a CsA sparing effect. This might lead to a combined therapeutic regimen with a good immunosuppressive efficacy and minimal drug associated adverse effects.

Cell Survival↗
PubMed1996

[Successful syngeneic transplantation using G-CSF-stimulated peripheral hematopoietic progenitor cells combined with post-transplant administration of G-CSF in a patient with acute lymphatic leukemia].

A 45-year-old male with acute lymphoblastic leukemia in first remission was successfully transplanted with G-CSF (filgrastim)-mobilized syngeneic PBPC (peripheral blood progenitor cells). Conditioning regimen consisted of high-dose etoposide, cyclophosphamide and total body irradiation. For PBPC mobilization the patient's healthy syngeneic brother was subcutaneously stimulated with 16 micrograms/kg/day G-CSF for 5 consecutive days. Only mild adverse effects (myalgia, transient changes of laboratory test) were observed. PBPC-apheresis was performed three times without complications on days 4, 5 and 6 after the start of G-CSF application. The unmanipulated PBPC (total 5.75 x 10(8)/kg mononucleated cells) were transfused immediately after each collection. Engraftment under administration of G-CSF (5 micrograms/kg/day subcutaneously) from day 0 to +12 was very rapid. Neutrophils exceeded 1.0 x 10(9)/l on day +9, platelet counts reached 50 x 10(9)/l on day +13. On day +27 the patient was discharged from the hospital with normal blood counts except mild anemia (Hb 9.5 g%). Bone marrow aspiration was repeatedly normocellular with normal differential count and no leukemia. We demonstrate that G-CSF-mobilized syngeneic PBPC transplantation after myeloblative chemoradiotherapy results in rapid and so far stable hematologic reconstitution with an actual follow-up of more than 15 months. This experience may be of relevance for future allogeneic G-CSF-mobilized PBPC transplantation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1996

[Current status of therapy and prognosis in acute adult leukemia].

In the last two decades complete remission [CR] rates for adults with acute leukemia has increased to 60 to 80%. In acute myelogenous leukemia [AML], this is due to the application of intensive induction therapies, comprising an anthracycline and a cytarabine. In acute lymphoblastic leukemia [ALL], the introduction of intensive early consolidation and CNS prophylaxis played an additional important role. These myeloablative treatments became feasible because of considerable improvements in the management of infectious and bleeding complications. The standard induction for AML further on remains the '3 + 7' schedule [daunorubicin 45 to 60 mg/m2/day x 3, I.V. and Ara-C 100 to 200 mg/m2/day x 7, 24-h infusion]. In ALL, prednisone, vincristine, L-asparaginase and an anthracyeline are the backbone of the induction therapy. Unfortunately, there has been less improvement for overall long-term survival, which is about 15 to 20% in AML and 20 to 35% in ALL beyond 5 years. More intensive post-remission regimens which include high-dose Ara-C in AML and intermediate-dose methotrexate and cyclophosphamide in ALL seem to improve these results to some extent. Allogeneic bone marrow transplantation has the most powerful anti-leukemic potential; however, because of the high peritransplant mortality [20 to 25%], its use in first CR tends to be restricted to patients with adverse prognostic features predicting early relapse, while good-risk patients are transplanted at the first signs of relapse or in second CR. In both AML and ALL, the optimal form of post-remission treatment needs to be defined.

Adult↗