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A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 145 records · Page 8Linked to original sources
PubMed1998

Blood and marrow transplantation activity in Europe 1996. European Group for Blood and Marrow Transplantation (EBMT).

Transplant activity by members of the European Group for Blood and Marrow Transplantation (EBMT) and related European teams is reported for 1996 by indication, donor type and stem cell source. Bearing in mind reports from previous years, the annual numbers of transplants for each indication, transplant rates for each participating country, changes in transplant rates by indication and changes in donor types and stem cell sources are described. A total 14,593 blood or marrow transplants, performed in Europe by 382 teams from 31 countries, were reported in 1996. Of these, 4393 (30%) were allogeneic and 10,200 (70%) were autologous transplants. Of the autologous transplants, 978 (10%) were bone marrow derived, 9222 (90%) from peripheral blood stem cells or combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 3252 (74%) were bone marrow and 1141 (26%) were peripheral blood stem cell transplants. Main indications in 1996 were leukemias with 4961 transplants (34%), 70% allogeneic and 30% autologous; lymphomas with 5505 transplants (38%), 6% allogeneic and 94% autologous; solid tumours with 3484 transplants (24%), 1% allogeneic and 99% autologous; non-malignant disorders with 643 transplants (4%), 92% allogeneic and 8% autologous. There are major differences between countries. Transplant rates per 10m inhabitants per country ranged from 0 to >500 (median 202 per 10 m inhabitants). The most pronounced increase since 1990 for new indications in autologous transplants was observed in multiple myeloma and carcinoma of the breast. These data reflect recent changes and present status of blood and marrow transplantation in Europe. They provide a basis for patient counselling and health care planning.

Bone Marrow Transplantation↗
PubMed1998

Double allogeneic peripheral stem cell transplants for patients at high risk of relapse.

Patients with chronic myeloid leukemia (CML) relapsing in blast crisis after HLA-identical sibling bone marrow transplantation (BMT) are difficult to treat. Infusion of donor lymphocytes or retransplantation are unlikely to result in long-term disease-free survival. Treatment intensification with allogeneic double-BMT, made possible by using repeatedly mobilized peripheral blood stem cells, offers a new treatment option. We report two patients with Philadelphia chromosome positive CML transplanted in chronic phase, relapsing with CML in myeloid blast crisis. Both received intensive induction chemotherapy (ICE) followed by a first, T cell-depleted peripheral stem cell transplant from the initial donor. Both patients engrafted rapidly (day 15). Upon hematologic recovery, a second G-CSF mobilized non-T cell-depleted peripheral stem cell transplant from the same donor was given after pretransplant conditioning with busulphan and cyclophosphamide. Again, engraftment was rapid (days 18 and 16) and both patients are alive and disease-free 18 and 21 months after allogeneic double-BMT. G-CSF mobilized peripheral stem cells allow new ways of treatment intensification with double-BMT in refractory leukemias relapsing post-transplant. This approach warrants further study.

Adult↗
PubMed1998

Clinical consequences of sensitisation to minor histocompatibility antigens before allogeneic bone marrow transplantation.

To study sensitisation to minor histocompatibility antigens (mHag) before and after BMT, we measured antidonor CTL activity in five patients who had rejected their graft, and in a control group of 10 leukemic patients who engrafted without complications. All patients were transplanted with marrow from an HLA-identical sibling. Fourteen patients were conditioned with cyclophosphamide (120 mg/kg) and TBI (1350 cGy) and received a T cell-depleted graft, while one patient with aplastic anaemia received cyclophosphamide alone and unmanipulated marrow. Before transplantation, anti-donor CTL activity was detected in two of the 15 patients. These patients rejected their grafts at days 21 and 58, respectively. In the other three patients who rejected their grafts at days 41, 60 and 250, CTL activity was found only after transplantation. In contrast, no anti-donor CTLs could be detected at any time in the 10 patients who engrafted permanently. We have identified some of the mHags recognised during graft rejection by cloning and subsequent specificity analysis of the recipient CTLs. In the patient who rejected at day 41 without detectable immunisation before BMT, the response was directed against HA-1, a minor antigen known to play a role in GVHD. In the other combinations, a significant part of the CTL activity was directed against the male antigen H-Y. In the patient who rejected the marrow of her HLA-identical brother at day 250, two clones recognised H-Y, while five others recognised at least three distinct autosomal mHags. This patient had an HLA-identical sister who expressed only one autosomal mHag that had been recognised by one single T cell clone. After re-transplantation with the marrow of this second donor, the CTL activity could no longer be detected and the patient engrafted without further complications.

Bone Marrow Transplantation↗
PubMed1998

Repeated treatment with horse antilymphocyte globulin for severe aplastic anaemia.

In a single-centre study the feasibility and efficacy of repeated antilymphocyte globulin (ALG) for patients with severe aplastic anaemia (SAA) not responding to an initial ALG treatment or relapsing after initial response to ALG was evaluated. 139 consecutive patients with newly diagnosed SAA were treated with ALG between 1976 and 1995. 89 patients responded to a first course; 50 patients did not become transfusion independent. Of the 89 responders, 66 remained in remission, 23 relapsed. 43 patients received a second or subsequent course of ALG for failure to respond (n = 25) or relapse (n = 18) and were given a total of 53 courses. Acute reactions in the multiply exposed patients occurred during the first ALG treatment in 11 (26%) and during subsequent exposures in 16/53 courses (30%; P > 0.2). Incidence of serum sickness was 63% (27/43) after the initial course compared to 57% (30/53) after subsequent courses (P > 0.2), but clinical signs of serum sickness occurred earlier after repeated (median 6 d) as compared to initial exposure (13d; P = 0.008). Transfusion-independent haemopoiesis was achieved in 27/43 (63%) and survival probabilities for the 43 patients receiving multiple courses of ALG was 52 +/- 8% at 10 years. The probability of developing a late clonal disorder was 53 +/- 10% after multiple, as compared to 34 +/- 7% after single exposure (P = 0.15). No difference in results was observed between patients retreated for failure to first ALG or for relapse. ALG of the same species can be repeated without increased risks of side-effects in patients with SAA. A second or subsequent course of ALG from the same source can be effective when the first course has failed.

Adolescent↗
PubMed1998

Lung resection for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases.

Invasive pulmonary aspergillosis (IPA) is associated with a high mortality. In 27 consecutive neutropenic patients who underwent lung resection for suspected IPA, we analyzed preoperative diagnostic evaluation, operative procedure, perioperative management, histological findings, outcome concerning recurrence of aspergillosis, and survival to evaluate the morbidity and mortality of a surgical treatment of IPA. Seventeen patients with hematologic diseases had previously undergone high-dose chemotherapy and four stem cell transplantation. Six patients with aplastic anemia were treated with antilymphocyte globulin. IPA was suspected if localized infiltrates developed on thoracic CT scan, and fever persisted under antibiotic therapy in neutropenic patients. In only one case a diagnosis of IPA could be made preoperatively. Twenty patients underwent lobectomy and seven wedge resection. At day of surgery the neutrophil count was below 500 x 10(9)/L in 78% of patients, and the platelet count below in 50 x 10(9)/L in 58% of patients. Invasive fungal infection was confirmed histologically in 22 of 27 patients (81.5%); in five patients no fungal infection was documented. The median duration of surgery was 120 min. Postoperatively, patients stayed one night in the intensive care unit, and chest tubes were removed after 2 d. Within 7 d a median of four erythrocyte packs and two platelet packs per patient were replaced. Major surgical complications occurred in two patients (bronchial dehiscence; pleural aspergillosis). Minor surgical complications included prolonged chest tube drainage (recurrent pneumothorax, n = 2; air leakage, n = 1; hematothorax, n = 1), pleural effusion (n = 4), and seroma (n = 2). Postoperatively, two patients suffered from histologically proven disseminated aspergillosis (pleural aspergillosis, renal aspergilloma) and another patient from suspected orbital aspergillosis. At 30 d postoperative mortality was 11% and 3-mo survival was 77%. After lung resection, seven patients underwent stem cell transplantation without recurrence of IPA. In conclusion, we suggest lung resection is a therapeutic option for invasive pulmonary aspergillosis in neutropenic patients with hematologic diseases and is associated with a low surgery-related morbidity and mortality.

Adolescent↗
PubMed1997

Autologous bone marrow transplantation for patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS. Chronic and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation.

Intensive chemotherapy followed by autologous bone marrow transplantation (ABMT) may provide an alternative therapy for young patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia following MDS (sAML) lacking a suitable donor. We report the results for 79 patients with MDS/sAML transplanted with autologous marrow in first complete remission (CR). Within the total group of 79, a cohort of 55 patients for whom the duration of first CR was known were compared with a matched control group of 110 patients with de novo AML. The 2-year survival, disease-free survival (DFS), and relapse rates for the 79 patients transplanted in first CR were 39%, 34%, and 64%, respectively. The relapse risk was greater than 55% for all stages and all disease categories. Patients younger than 40 years had a significantly (P = .04) better DFS (39%) than patients older than 40 years (25%). The DFS at 2 years was 28% for the cohort of 55 patients transplanted for MDS/sAML and 51% for those transplanted for de novo AML (P = .025). Relapse rates were 69% for patients with MDS/sAML and 40% for those with de novo AML (P = .007). ABMT for MDS or secondary leukemia results in a lower DFS when compared with similarly treated patients with de novo AML due to a higher relapse rate. The DFS of 28% for these patients suggests that autotransplantation may be a valuable therapy for this disease. The low treatment-related mortality rate of less than 10% supports the view that sufficient numbers of hematopoietic stem cells are present in patients with MDS to allow adequate repopulation after autologous stem-cell transplantation.

Acute Disease↗
PubMed1997

Allogeneic blood stem cell transplantation: considerations for donors.

Allogeneic transplantation of cytokine-mobilized peripheral blood stem cells (PBSCs) is now being increasingly performed, but safety considerations for hematologically normal PBSC donors have not been fully addressed. Progenitors are generally mobilized for collection from normal donors using recombinant human granulocyte colony-stimulating factor (rhG-CSF). Although the short-term safety profile of rhG-CSF seems acceptable, experience remains limited and its optimal dose and schedule have not been defined. Minimal data exist regarding long-term safety of rhG-CSF, primarily derived from experience in patients with chronic neutropenia or cancer. An "ad hoc" workshop was recently convened among a group of investigators actively involved in the field of allogeneic stem cell transplantation to discuss the safety issues pertaining to normal PBSC donors. There was agreement on the following points: (1) On the basis of available data, it appears that rhG-CSF treatment and PBSC collection have an acceptable short-term safety profile in normal donors. However, the need for continued safety monitoring was recognized. (2) rhG-CSF doses up to 10 microg/kg/d show a consistent dose-response relationship with the mobilization (and collection) of CD34+ progenitor cells, and this dose is acceptable for routine clinical use. Whether higher doses are superior (or cost effective) remains to be determined, and they may produce more severe side effects. The potential risks of marked leukocytosis (arbitrarily defined as a leukocyte count of more than 70 x 10(9)/L) have been a concern, and rhG-CSF dose reduction is performed by many centers to maintain leukocyte counts below this level. (3) Transient post donation cytopenias, involving granulocytes, lymphocytes, and platelets, may occur and are at least partly related to the leukapheresis procedure. These are generally asymptomatic and self-limited; follow-up blood counts are not necessarily required. Reinfusion of autologous platelet-rich plasma should be considered for donors with expected postdonation thrombocytopenia (platelet count < 80 to 100 x 10(9)/L). (4) Donors should meet the eligibility criteria which apply to donors of apheresis platelets, with the exception that pediatric donors may also be considered. Any deviation from these criteria should have supporting documentation. There is insufficient information at this time to clearly establish definite contraindications for PBSC collection in a hematologically normal donor. Potential contraindications include the presence of inflammatory, autoimmune, or rheumatologic disorders, as well as atherosclerotic or cerebrovascular disease. (5) The creation of an International PBSC Donor Registry is desirable to facilitate monitoring the long-term effects of the procedure. Individual institutions or donor centers are encouraged to establish their own PBSC donor follow-up system, preferably with a standardized approach to data collection.

Adult↗
PubMed1997

Recognition of major histoincompatibilities after transplantation with marrow from HLA closely matched donors.

BACKGROUND: To determine the extent to which major histoincompatibilities are recognized after bone marrow transplantation, we characterized the specificity of the cytotoxic T lymphocytes isolated during graft-versus-host disease. We studied three patients transplanted with marrow from donors who were histoincompatible for different types of HLA antigens. METHODS: Patient 1 was mismatched for one "ABDR-antigen" (HLA-A2 versus A3). Two patients were mismatched for antigens that would usually not be taken into account by standard selection procedures: patient 2 was mismatched for an "HLA-A subtype" (A*0213 versus A*0201), whereas patient 3 was mismatched for HLA-C (HLA-C*0501 versus HLA-C*0701). All three HLA class I mismatches were detected by a pretransplant cytotoxic precursor test. RESULTS: Analysis of the specificity of the cytotoxic T lymphocyte clones isolated after transplantation showed that the incompatibilities detected by the pretransplant cytotoxic precursor assay were the targets recognized during graft-versus-host disease. CONCLUSIONS: Independent of whether the incompatibility consisted of a "full" mismatch, a "subtype" mismatch, or an HLA-C mismatch, all clones recognized the incompatible HLA molecule. In addition, some of these clones had undergone antigen selection and were clearly of higher specificity than the ones established before transplantation, indicating that they had been participating directly in the antihost immune response.

Adolescent↗
PubMed1997

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

Herein we report on the feasibility of mobilizing peripheral blood progenitor cells (PBPC) in a prospective study of the HOVON-SAKK Groups in 96 cases with newly diagnosed acute myeloid leukemia (AML). Among 96 patients, 76 patients (79%) entered complete remission. Mobilization was undertaken with variable dosages of G-CSF in 63 patients, and 54 patients (87%) were leukapheresed. The comparative yields of pheresis following the G-CSF schedules and hematopoietic recovery data are presented and discussed. PBPC transplantation results in faster hematopoietic regeneration compared to autologous marrow grafting in the prior AML HOVON study.

Acute Disease↗
PubMed1997

Diagnostic and therapeutic thoracic surgery in leukemia and severe aplastic anemia.

BACKGROUND: Pulmonary complications often occur in patients with leukemia and severe aplastic anemia. Particularly in patients having undergone bone marrow transplantation, respiratory diseases account for a significant number of deaths. In a retrospective study, we evaluated 41 patients with leukemia and severe aplastic anemia who were operated on consecutively from 1980 to 1995. METHODS: Fourteen open lung biopsies, four video-assisted lung biopsies, and 24 lung resections were performed in 24 male and 17 female patients. Mean age was 32.2 years. RESULTS: Eleven (27%) early deaths occurred (30-day mortality): ten in patients after lung biopsy (56%) and one after lung resection (4%) (p < 0.001). Perioperative morbidity relating to pulmonary disease or operation included 10 (24.4%) cases of prolonged (> 24 hours) postoperative mechanical ventilation and two (4.8%) cases of bleeding or hematoma. In one (2.4%) patient a slowly developing, contained bronchial stump insufficiency appeared after lobectomy, which was successfully operated on 3 weeks later. CONCLUSION: We conclude that resection of localized pulmonary lesions, be it for diagnostic or therapeutic (or combined) purposes, can be carried out with low morbidity and mortality in patients with leukemia and severe aplastic anemia. However, early mortality is high after open or thoracoscopic lung biopsies in patients with acute-onset diffuse pulmonary disease, and little therapeutic benefit is realized in these cases.

Adolescent↗
PubMed1997

Post-remission therapy of adult acute myeloid leukaemia: one cycle of high-dose versus standard-dose cytarabine. Leukaemia Project Group of the Swiss Group for Clinical Cancer Research (SAKK).

BACKGROUND: Intensification of post-remission therapy improves the cure rate of acute myeloid leukemia (AML) but is often accompanied by unacceptable toxicity. From 1985 to 1992 the Swiss Group for Clinical Cancer Research (SAKK) performed a randomized phase III trial to evaluate the effectiveness of one single postremission course of high-dose cytarabine (HDAC) in terms of leukaemia-free and overall survival in adults with de novo AML. PATIENTS AND METHODS: Adult (15-65 years) AML patients in remission after two induction courses were randomly assigned to one consolidation course either with standard (SDAC: 100 mg/sqm 24 hours infusion over seven days) or with high-dose cytarabine (HDAC: 3000 mg/sqm every 12 hours as one-hour-infusion for six days). In addition, both arms included daunorubicin (45 mg/sqm daily on days 1 to 3). Thereafter, patients were observed without maintenance until relapse. RESULTS: After two induction courses 208/276 eligible patients achieved remission (CR: 169, 61%, PR: 39, 14%), 41 were resistant (15%) and 20 died early (7%). Seventy-one patients in remission were not randomized. One hundred thirty-seven were randomized in CR/PR (67 SDAC, 70 HDAC). 4/70 patients randomized to HDAC did not receive it. Treatment-related mortality in HDAC was 1.4% (1/66). WHO grade 3-4 toxicities occurred in 14/67 SDAC and in 38/66 HDAC patients (P < 0.0001). The median event free survival was 10.8 (SDAC) vs. 12.2 months (HDAC; P = 0.18). The median overall survival was 24.6 (SDAC) vs. 32.6 months (HDAC; P = 0.07). Although statistically uncertain, HDAC reduced the hazard of progression (hazard ratio: 0.69, P = 0.08) and of death (hazard ratio: 0.70, P = 0.13). For 112 patients stratified as CR the estimated four-year disease-free survival was 25% (+/-6%) with SDAC and 37% (+/-6%) with HDAC (P = 0.09). The overall survival rates at four years were 38% (+7%) and 48% (+7%), respectively (P = 0.10). In multivariate analysis HDAC significantly reduced the hazard of relapse by 39% compared to SDAC (hazard ratio = 0.61, 95% CI: 0.37-0.99; P = 0.049). CONCLUSIONS: We conclude that early consolidation of adult AML in CR with a single course of HDAC is superior in terms of outcome to one cycle of SDAC. The results of our intensive, single course HDAC group compare favourably with less intensive, repetitive HDAC cycles, suggesting that Ara-C dose intensity may be more important than total dosage. In addition, our treatment strategy is much less toxic and less expensive.

Acute Disease↗
PubMed1997

Blood and marrow transplantation activity in Europe 1995. European Group for Blood and Marrow Transplantation (EBMT).

In 1995, a total of 12,101 blood or marrow transplants, performed in Europe by 343 teams from 31 countries, were reported to the European Group for Blood and Marrow Transplantation (EBMT). Of these, 3858 (32%) were allogeneic, 8243 (68%) autologous transplants. Of the autologous transplants 1384 (17%) were bone marrow derived, 6504 (79%) from peripheral blood stem cells and 355 (4%) combined bone marrow and peripheral blood stem cell transplants. Of the allogeneic transplants, 571 (15%) were peripheral blood stem cell transplants, the remainder, 3287 (85%) bone marrow transplants. Main indications were leukemias with 4408 transplants (36%), 2977 allogeneic (68%) and 1431 autologous (32%); lymphomas with 4671 transplants (39%), 272 allogeneic (6%) and 4399 autologous (94%); severe aplastic anemia with 237 transplants (2%), 237 allogeneic (100%) and 0 autologous (0%); solid tumors with 2399 transplants (20%), 17 allogeneic (1%) and 2382 autologous (99%); and congenital disorders with 294 transplants (2%), 294 allogeneic (100%) and 0 autologous (0%) and others with 92 transplants (1%), 61 allogeneic (66%) and 31 autologous (34%). There were major differences between participating countries. The absolute numbers of teams and transplants per country differ widely and range from 0.2 to 33.3 teams per 10 million inhabitants (median 5.8); 3.2 to 733.3 total transplants per 10 million (median 200); 0.7 to 210 allogeneic transplants per 10 million (median 65); 0.3 to 700 autologous transplants per 10 million (median 122); 0 to 47.7 unrelated transplants per 10 million inhabitants (median 8.7). There is also a difference in the relative number of transplants for the individual indications. The coefficient of variation for selected diseases was calculated for those 14 countries with a minimum of 100 transplants. A narrow coefficient of variation indicates consensus amongst grafting physicians. It is narrowest for chronic myeloid leukemia in allogeneic transplants (36.7%) and for Hodgkin's disease in autologous transplants (44.8%). These data reflect the present status of blood and marrow transplantation in Europe and provide a basis for patient counselling and health care planning.

Anemia, Aplastic↗