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A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 127 records · Page 7Linked to original sources
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

[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

[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↗
PubMed1998

HA-1 and the SMCY-derived peptide FIDSYICQV (H-Y) are immunodominant minor histocompatibility antigens after bone marrow transplantation.

BACKGROUND: Allogeneic bone marrow donors can be incompatible at different levels. Even HLA-identical pairs will be still incompatible for numerous minor histocompatibility antigens (mHag). Nevertheless, some incompatibilities are found to be associated with an increased risk of graft-versus-host disease (GVHD), which could be related to the way the immune system recognizes these antigens. METHODS: We determined the specificity of cytotoxic T-cell clones isolated during acute GVHD or during bone marrow graft rejection in patients (n=14) transplanted with marrow from donors who were histoincompatible for different minor and/or major histocompatibility antigens. RESULTS: We found a clear hierarchy among the different types of histoincompatibilities. In three combinations mismatched for a class I allele, all 27 clones isolated during GVHD were specific for the incompatible HLA molecule. In the 11 class I-identical combinations, 14 different mHags were recognized. The mHag HA-1, known to have a significant impact on the development of GVHD, was recognized in the two HA-1-incompatible combinations. In one of these combinations, which was sex mismatched, all 56 clones analyzed were directed against HA-1, demonstrating the dominance of this mHag. In the four HA-1-compatible, sex-mismatched combinations, the anti-H-Y response was directed against one immunodominant epitope rather than against multiple Y-chromosome-encoded epitopes. All male specific cytotoxic T lymphocytes (n=15) recognized the same high-performance liquid chromatography-purified peptide fraction presented by T2 cells. Moreover, all cytotoxic T lymphocytes tested (n=6) were specific for the SMCY-derived peptide FIDSYICQV, originally described as being the H-Y epitope recognized in the context of HLA-A*0201. CONCLUSIONS: Some histocompatibility antigens are recognized in an immunodominant fashion and will therefore be recognized in the majority of mismatched combinations. Only for such antigens, correlations between mismatches and the occurrence of GVHD or graft rejections will be found.

Bone Marrow Transplantation↗
PubMed1998

Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

BACKGROUND: Transplantation of blood or bone-marrow stem cells is the treatment of choice for selected patients with chronic myeloid leukaemia (CML). Transplantation is used with increasing frequency and success, but remains associated with substantial risks of morbidity and mortality. Other treatments with satisfactory short-term outcome are available. For appropriate counselling of patients, a rapid and simple way to assess risk is needed. METHODS: Data from 3142 patients (1873 [60%] male, 1269 [40%] female; mean age 34 years, range <1-60 years) treated with allogeneic blood or marrow transplants for CML between 1989 and 1997, reported to the European Group for Blood and Marrow Transplantation (EBMT), were used to develop and test a simple risk score based on previously reported major pretransplant risk factors: histocompatibility, stage of disease at time of transplantation, age and sex of donor and recipient, and time from diagnosis to transplantation. We analysed probabilities of survival, leukaemia-free survival, transplant-related mortality, and relapse incidence with respect to these risk factors. FINDINGS: At the time of analysis, 1922 (61%) of the 3142 patients were alive-1567 (65%) of those with HLA-identical sibling donors and 417 (57%) of those with unrelated donors. 1682 (54%) were alive without relapse. 1220 (39%) patients had died, 1013 (83%) of transplant-related causes, 207 (17%) of relapse. 447 (14%) patients had relapsed. The final scoring system was highly predictive for leukaemia-free survival, survival and transplant-related mortality. Survival at 5 years was 72%, 70%, 62%, 48%, 40%, 18%, and 22% for patients with scores 0, 1, 2, 3, 4, 5, and 6, respectively. Risk of transplant-related mortality was 20%, 23%, 31%, 46%, 51%, 71%, and 73%. Data showed the same trends for HLA-identical sibling transplants and unrelated transplants for transplants done in 1989-93 and 1994-96. INTERPRETATION: Pretransplant risk factors are cumulative for individual patients with CML having blood or marrow transplantation. A simple system based on five main factors gives adequate risk assessment for counselling of patients and taking decisions.

Adolescent↗
PubMed1998

FLT-3 ligand provides hematopoietic protection from total body irradiation in rabbits.

Several hematopoietic cytokines have been investigated for their potential to provide protection from the lethal consequences of bone marrow aplasia after total body irradiation (TBI). Some can increase the dose of irradiation tolerated by the animals; none allow endogenous recovery after doses such as administered in clinical blood or marrow transplantation. We tested the radioprotective potential of FLT-3 ligand, an early acting hematopoietic cytokine, alone and in combination with a late acting cytokine, granulocyte-colony stimulating factor (G-CSF). Adult outbred New Zealand White rabbits were submitted to TBI of 1,200 or 1,400 cGy by a Co60 source. Recombinant human (rh) FLT-3 ligand at a dose of 500 microg/kg and/or rhG-CSF at a dose of 10 microg/kg were administered for 14 days subcutaneously daily, beginning either 2 days before or the day after TBI. All control animals given no growth factors died of aplasia at day 10 (range, 5 to 16). All 8 animals given G-CSF had severe aplasia and 7 died at day 8 (range, 5 to 10); 1 animal survived, with G-CSF being administered before TBI. In contrast, 11 of 12 animals given FLT-3 ligand, with or without G-CSF, survived. Radioprotection was best in the group given FLT-3 ligand together with G-CSF before TBI. In these animals median platelet counts were never <10 x 10(9)/L and median white blood cell counts never <0.5 x 10(9)/L. These data show that hematopoietic recovery can occur after 1,400 cGy TBI in rabbits, if protected by FLT-3 ligand, and suggest a radioprotective clinical potential of this cytokine.

Anemia, Aplastic↗
PubMed1998

[Umbilical cord blood transplantation: acceptance of umbilical cord blood donation by pregnant patients].

BACKGROUND/OBJECTIVE: Umbilical cord blood is an alternative source for allogeneic transplantation of hematopoietic stem cells from related and unrelated donors. It can easily be collected, cryopreserved and stored in cord blood banks for later use. In Switzerland, cord blood banks for related and unrelated stem cell transplantation are being established. The aim of the study was to evaluate previous knowledge of the possible medical use of cord blood and acceptance of cord blood banking in pregnant women. METHODS: We performed a prospective open study using a structured, anonymous questionnaire at the University of Basel Women's Hospital pregnancy outpatient clinic. After concise information on the use of cord blood for transplantation, questions were asked concerning previous knowledge of the use of placenta and cord blood in general, concerning the attitude to donation of cord blood for transplantation, and the respondent's willingness to donate cord blood of her own child. Women of different ethnic background were compared. RESULTS: From 300 questionnaires handed out to pregnant women of different ethnic background attending our outpatient clinic, 250 (83%) were returned, and 245 could be evaluated for final analysis. Only 40% indicated that they did know what usually happens to the placenta after birth. In contrast, the vast majority (95%) supported the idea of umbilical cord blood for banking and later use for stem cell transplantation. Similarly, 93% stated that they would agree to donate the cord blood from their own child for this purpose, while no statistically significant differences could be identified either between women with or without previous knowledge or of different ethnic background. CONCLUSIONS: This study shows the high acceptance of umbilical cord blood donation for banking and stem cell transplantation purposes in pregnant women, irrespective of previous knowledge. As there are no major differences between women of different ethnic background, a high degree of diversity of HLA-types of donated cord blood samples can be expected and may offset the underrepresentation of ethnic minorities in bone marrow donor registries.

Blood Banks↗
PubMed1998

Cutaneous manifestations of Paecilomyces lilacinus infection induced by a contaminated skin lotion in patients who are severely immunosuppressed.

BACKGROUND: New opportunistic fungal infections cause significant morbidity and death in patients who are severely immunocompromised. Cutaneous lesions may be the first clinical manifestation and give the clue to early diagnosis. OBJECTIVE: The purpose of this study was to describe the clinical and histologic manifestations of Paecilomyces lilacinus infection in patients who are severely immunosuppressed. METHODS: Within a 3-month period, we observed 5 patients with allogenic bone marrow transplantation and 4 patients with aplasia after chemotherapy for hematologic malignancies who developed skin eruptions caused by invasive P lilacinus. RESULTS: The skin lesions began in 7 cases during or shortly after recovery of pancytopenia. Most of the skin lesions were located on the lower extremities. The cutaneous manifestations were highly variable including erythematous macules, nodules, pustules, vesicular lesions, and necrotic crusts. In 3 biopsy specimens, histologic examination revealed hyphae in periodic acid-Schiff-stained sections. In all patients P lilacinus was isolated from skin tissue samples. P lilacinus was identified from all lesions either by skin biopsy or needle aspiration from clinically evident lesions. In 3 additional cases, the patient's hands were colonized without skin lesions. The source of the epidemic outbreak was finally traced down to several contaminated lots of a topical moisturizing agent. Two patients died; one patient had septic lesions in the eye and kidney as the result of P lilacinus. CONCLUSION: Clinical and histologic findings of P lilacinus infection with cutaneous manifestations in patients who are severely immunosuppressed are summarized. P lilacinus is resistant to all systemic antimycotics available, and in general, recovery of immunosuppression is necessary to eradicate the mold. Contaminated topical dermatologic agents should be included in the differential diagnosis as a source for severe epidemic cutaneous manifestations of fungal infection in patients who are severely immunosuppressed. This fact implies that additional safety guidelines are necessary for topical dermatologic agents used for patients who are severely immunosuppressed.

Adolescent↗
PubMed1998

Bone marrow transplantation from HLA-identical siblings as first-line treatment in patients with myelodysplastic syndromes: early transplantation is associated with improved outcome. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

Allogeneic bone marrow transplantation (BMT) offers a potential cure for younger patients with myelodysplastic syndromes (MDS) or secondary acute myeloid leukemia (sAML). More than 600 patients from 50 European centers have now been reported to the European Group for Blood and Marrow Transplantation (EBMT). We retrospectively analyzed 131 patients reported to the Chronic Leukemia Working Party of the EBMT who underwent BMT from HLA-identical siblings without prior remission induction chemotherapy. At the time of BMT 46 patients had refractory anemia (RA) or RA with ringed sideroblasts, 67 patients had more advanced MDS subtypes and 18 patients had progressed to sAML. The 5-year disease-free (DFS) and overall survival (OS) for the entire group of patients was 34 and 41%, respectively. Fifty patients died from transplant-related complications, most commonly graft-versus-host disease and/or infections. Relapse occurred in 28 patients between 1 and 33 months after BMT, resulting in an actuarial probability of relapse of 39% at 5 years. DFS and OS were dependent on pretransplant bone marrow blast counts. Patients with RA/RARS, RAEB, RAEB/T and sAML had a 5-year DFS of 52, 34, 19 and 26%, respectively. The 5-year OS for the respective patient groups was 57, 42, 24 and 28%. In a multivariate analysis, younger age, shorter disease duration, and absence of excess of blasts were associated with improved outcome. From these data we conclude that patients with myelodysplasia who have appropriate marrow donors, especially those aged less than 40 years and those with low medullary blast cell count should be treated with BMT as the primary treatment early in the course of their disease. Transplantation early after establishing the diagnosis of MDS may improve prognosis due to a lower treatment-related mortality and a lower relapse risk.

Adolescent↗
PubMed1998

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: current practice in Europe in 1998. Accreditation Sub-Committee of the European Group for Blood and Marrow Transplantation.

In 1996, the Accreditation Sub-Committee of the EBMT published a special report summarising current practice in Europe in relation to haemopoietic stem cell transplants for haematological diseases, solid tumours and immune disorders. An updated report is presented here. The major change has been the recognition that transplant practice is appreciably different between children and adults, who should therefore be considered in separate categories. The autoimmune disorders for which autografting may be useful are now specified. Non-CML myeloproliferative disorders and AL amyloidosis have been added to the list of indications for transplant procedures in adults. Other changes have been incorporated into the revised tables.

Adolescent↗
PubMed1998

Allogeneic bone marrow transplantation vs filgrastim-mobilised peripheral blood progenitor cell transplantation in patients with early leukaemia: first results of a randomised multicentre trial of the European Group for Blood and Marrow Transplantation.

In a multicentre trial involving 20 transplant centres from 10 countries haematopoietic stem cells were obtained either from the bone marrow of 33 sibling donors or from the peripheral blood of 33 such donors after administration of filgrastim (10 microg/kg/day). The haematopoietic stem cells were infused into their HLA-identical recipients suffering from acute leukaemias in remission or chronic myeloid leukaemia in chronic phase. PBPC donors tolerated filgrastim administration and leukapheresis well with the most frequent side-effects being musculoskeletal pain, headache, and mild increases of LDH, AP, Gamma-GT or SGPT. Pain and haematoma at the harvest site and mild anaemia were the most frequent complaints of BM donors. Severe or life-threatening complications were not seen with any type of harvest procedure. Time to platelet recovery greater than 20 x 10(9)/l was 15 days (95% confidence interval (CI) 13-16 days) in the PBPCT group and 19 days (CI 16-25) in the BMT group. Time to neutrophil recovery greater than 0.5 x 10(9)/l was 14 days (CI 12-15 days) in the PBPCT group as compared to 15 days (CI 15-16 days) in the BMT group. The numbers of platelet transfusions administered to PBPCT and BMT patients were 12 (range: 1-28) and 10 (range: 3-39), respectively. Sixteen patients (48%) transplanted with bone marrow and 18 patients (54%) transplanted with PBPC developed acute GVHD of grades II-IV; acute GVHD of grades III or IV developed in six (18%) and seven (21%) patients, respectively. Kaplan-Meier plots for transplant-related mortality until day 100 and leukaemia-free survival at a median of 400 days after BMT or PBPCT showed no significant differences. Administration of filgrastim and leukapheresis in normal donors were feasible and well tolerated. The number of days with restricted activity and of nights spent in hospital was lower in donors of PBPC. Transplantation of PBPC to HLA-identical siblings with early leukaemia resulted in earlier platelet engraftment. The incidence of moderate to severe acute GVHD, transplant-related mortality, and leukaemia-free survival did not show striking differences. Further investigation of allogeneic PBPCT as a substitute for allogeneic BMT is warranted.

Adolescent↗
PubMed1998

Influence of protective isolation on outcome of allogeneic bone marrow transplantation for leukemia.

Various isolation strategies are used to prevent infections during bone marrow transplantation; data on their efficacy are lacking. We studied whether use of high efficiency particulate air filtration (HEPA) and/or laminar airflow (LAF) units affect transplant-related mortality (TRM) or survival in the first year after allogeneic transplantation. 5065 patients with leukemia receiving bone marrow transplants from an HLA identical sibling (n = 3982) or alternative related or unrelated donors (n = 1083) between 1988 and 1992 were reported to the International Bone Marrow Transplant Registry by 222 teams. Two types of isolation were considered: (1) conventional protective isolation with single patient room and any combination of hand-washing, gloves, mask and gown; and (2) HEPA and/or LAF. Cox proportional hazards regression models were used to determine the relative risks (RRs) of transplant-related mortality (TRM) and of deaths from any cause in patients treated in HEPA/LAF units compared to patients treated in conventional isolation. HLA-identical sibling and alternative donor transplants were analyzed separately. Risks of TRM and overall mortality in the first 100 days post-transplant were significantly lower among patients treated in HEPA/LAF units than in those treated conventionally. RRs of TRM were 0.76 (P = 0.009) for recipients of HLA-identical sibling transplants and 0.65 (P = 0.003) for recipients of alternative donor transplants. Correspondingly RRs of overall mortality were 0.80 (P = 0.02) and 0.65 (P = 0.0006). Decreased risks of TRM and of death in the first 100 days post-transplant resulted in significantly higher 1-year survival rates in patients treated in HEPA/LAF rather than in conventional isolation units. Use of HEPA and/or LAF to prevent infections decreases TRM and increases survival after allogeneic bone marrow transplants for leukemia.

Adolescent↗
PubMed1998

Unrelated bone marrow transplantation in patients with myelodysplastic syndromes and secondary acute myeloid leukemia: an EBMT survey. European Blood and Marrow Transplantation Group.

The Chronic Leukemia Working Party of the EBMT has collected data on 118 patients of median age 24 years (range 0.3 to 53 years) who underwent an allogeneic bone marrow transplantation from unrelated donors for treatment of MDS or secondary AML (RA/RARS, n = 24; RAEB, n = 26; RAEB-t, n = 34; CMML, n = 12; sAML, n = 22) between 1986 and 1996. The data were reported by 49 EBMT centers. Thirty-four of 118 patients are alive, relapse was the cause of death in 19 of 84 patients and the remaining patients died of transplant-related mortality. For the whole group the actuarial probability of survival at 2 years is 28%, disease-free survival 28%, relapse risk 35% and transplant-related mortality is 58%. The transplant-related mortality is significantly influenced by the age of the recipient (<18 years 40%, 18-35 years 61%, >35 years 81%). The relapse rate after BMT is influenced by FAB classification of the disease at BMT. Patients with a low blast count (RA, RAEB) have a lower probability of relapse (13%, 15%) compared to patients with RAEB-t or sAML (29%, 45%). Furthermore, we found evidence of a graft-versus-leukemia effect in MDS/sAML. Patients with acute GVHD, grade II-IV, had a probability of relapse of 26% vs 42% in patients with no acute GVHD or grade I only. Allogeneic transplantation with an HLA-matched, unrelated donor may be offered to younger patients (age <35 years) with poor risk myelodysplasia or secondary AML.

Adolescent↗