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A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 199 records · Page 11Linked to original sources
PubMed1996

Results of allogeneic bone marrow transplantation for acute leukemia have improved in Europe with time--a report of the acute leukemia working party of the European group for blood and marrow transplantation (EBMT).

To evaluate whether the results of bone marrow transplantation have improved in Europe with time, we analyzed the outcome for 2195 patients with acute leukemia. 1405 had acute myeloid leukemia (AML) and 790 had acute lymphoblastic leukemia (ALL), and were allografted in first complete remission between September 1979 and December 1991 with marrow from an HLA-identical sibling donor. We found a continuing improvement more evident since 1987 for AML and since 1986 for ALL. A substantial reduction in the 3 years transplant related mortality (TRM): 26 vs 39% for AML (P = 10(-4)), and 25 vs 39% for ALL (P = 10(-4)), has resulted in an increase of the 5-year actuarial leukemia-free survival (LFS). 57 vs 45% for AML (P < 10(-4)) and 54 vs 45% (P = 10(-4)) for ALL. Four important changes have occurred. (1) Graft-versus-host disease (GVHD) prevention has involved an increased use of cyclosporin A (CsA) alone and subsequently its use in combination with methotrexate: this was associated with lower TRM both in AML and ALL; (2) Use of total body irradiation as pretransplant regimen has decreased; (3) a shorter interval from remission to BMT is more common; (4) an older population of patients has undergone BMT. Multivariate analyses were performed separately in AML and ALL. In AML four variables significantly influenced TRM favorably: year of BMT (P = 10(-4)), younger age at BMT (P = 10(-4)), prevention of GVHD including CsA (P = 0.008), sex match other than female donor to male recipient (P = 0.002). The relapse incidence (RI) was lower in patients with FAB M1-2-3 vs M4-5 (P = 0.0004). The LFS improved by year of BMT (P = 0.0004), younger age at BMT (P = 10(-4)), prevention of GVHD including CsA (P = 0.01), FAB M1-2-3 (P = 0.03). In ALL, three variables were associated with a lower TRM: year of BMT (P = 10(-4)), younger age at BMT (P = 10(-4)), sex combination other than female to male (P = 0.008). The LFS was better after 1986 (P = 0.0004) and in younger patients (P = 10(-4)). However a better outcome after 1986/87 was observed in patients receiving the same GVHD prophylaxis: therefore, other unidentified factors resulting in better patient care have also contributed to this. The improved results of allogeneic BMT are entirely related to a reduction in TRM without loss of the antileukemic effect since relapse incidence has not changed over the years.

Adolescent↗
PubMed1996

Allogeneic peripheral blood precursor cell transplants in rabbits.

This report summarizes a series of experiments undertaken to evaluate the role of mobilized peripheral blood precursor cells (PBPC) for transplantation across a major histocompatibility barrier. Adult outbred red Burgundy rabbits were used as donors, New Zealand white rabbits of the opposite sex as recipients. Conditioning consisted of single dose total body irradiation (TBI) of 10 Gy supported by a short course of cyclosporine to enhance engraftment. Human recombinant G-CSF at a dose of 10 micrograms/kg was used for mobilization of precursor cells. Three methods of PBPC transplants were tested initially in 5 animals each. PBPC were collected and infused at once on day 0; collected initially, cryopreserved for one month, infused on day 0 and followed by 3 additional fresh donations or collected and infused on 6 occasions between days 0 and + 11. 13 animals engrafted, 2 became complete, longterm chimeras. Survival was best in the group given repetitive infusions (39 days median, 12 days to > 180 days, range). 10 additional animals were transplanted as in the last group and the number of transplanted nucleated cells (10.5 x 10(8)/kg median, 7.3 - 15.7 x 10(8)/kg range) and colony forming units CFU-GM (42 x 10(4)/kg median, 12.3 - 176.8 x 10(4)/kg range), were compared with outcome. Median survival of the 10 animals was 29 days (12 - 55 days range; 1 autologous reconstitution). Survival did not correlate with total nucleated cells per kg (r = 0.10; p = 0.79), but there was a trend to prolong survival with higher numbers of CFU-GM per kg (r = 0.47; p = 0.19). These data show that allogeneic PBPCT can engraft across a major histocompatibility barrier, that the high number of CFU-GM per kg might be advantageous, but also that additional methods are warranted to reduce acute GvHD.

Animals↗
PubMed1996

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders. Current practice in Europe in 1996 and proposals for an operational classification. Accreditation Sub-Committee of the European Group for Blood and Marrow Transplantation (EBMT).

The indications and techniques employed for haematopoietic stem cell transplants performed in Europe differ substantially. The Accreditation Sub-Committee of the EBMT has consulted widely and has attempted to describe practice in Europe current in 1996 and in particular to define whether a particular procedure should be regarded as 'Routine' or whether it should be carried out preferably in the context of a Clinical Research Protocol or as part of a 'Developmental' pilot study. It is recognised that a classification of this kind must be imperfect and will require revision at frequent intervals.

Adolescent↗
PubMed1996

Granulocytic sarcoma after allogeneic bone marrow transplantation: a retrospective European multicenter survey. Acute and Chronic Leukemia Working Parties of the European Group for Blood and Marrow Transplantation.

In a retrospective analysis we assessed occurrence, contributing factors and outcome of patients experiencing granulocytic sarcoma as a localized extramedullary relapse after allogeneic BMT. EBMT members were asked to report the number of patients transplanted for leukemia between January 1981 and December 1992 and the number of patients with granulocytic sarcoma. Of a total of 5824 patients transplanted for AML, CML or MDS by 86 teams, granulocytic sarcoma was observed in 26 patients (0.45% occurring 4-56 months after BMT. Granulocytic sarcoma occurred after allogeneic BMT in 20 out of 3071 patients grafted for AML (0.65%), and in the CML/MDS subgroup in six out of 2753 grafted patients (0.22%). Granulocytic sarcoma can involve any site of the body, presenting as a soft tissue mass; it occurred in body cavities (eg pleural cavity, abdominal cavity, spinal canal, stomach and bladder), the head and neck region (orbit, ear, skull base, peripheral nerves), the trunk and limbs, and mammary and sex glands. Granulocytic sarcoma predicts an additional hazard to outcome after BMT. Nine of 26 patients (33%) were alive 15-151 months after the onset of granulocytic sarcoma. Advanced disease stage at grafting adversely affected survival and all patients died. The best treatment option still needs to be defined.

Adolescent↗
PubMed1996

Allogeneic bone marrow transplantation for chronic myeloid leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation (EBMT).

Results of 3000 patients transplanted for chronic myeloid leukemia in Europeere used to assess outcome and main risk factors for survival (SURV), leukemia free survival (LFS), relapse incidence (RI) and transplant related mortality (TRM). More than one third (39%) of all patients are alive at + 10 years. SURV at 10 years is better for patients transplanted in first chronic phase (49%) than in accelerated phase (19%) or blast crisis (0%) due to both decreased TRM (41% versus 67% versus -) and RI (35% versus 51% versus -). For those patients transplanted in first chronic phase from an HLA-identical sibling donor with non-T-cell depleted bone marrow, modern conditioning and GVHD prevention method, median SURV has not been reached at +10 years and exceeds 55%. Other risk factors are discussed.

Acute Disease↗
PubMed1996

Late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation: incidence and risk factors. European Group or Blood and Marrow Transplantation (EBMT) Working Party on Late Effects.

The incidence, time course and risk factors associated with late-onset keratoconjunctivitis sicca syndrome after bone marrow transplantation (BMT) was evaluated in a multicenter retrospective cohort study conducted by the European Group for Blood and Marrow Transplantation (EBMT) Working Party on Late Effects. Data were requested from participating European centers on all patients transplanted up to December 1980 and on all patients treated during the year of 1984. Twenty-eight centers reported data on 258 patients and 248 could be evaluated for keratoconjunctivitis. Forty-eight of the 248 (19%) patients developed a keratoconjunctivitis sicca syndrome between 3 and 127 months (13.8 months) after BMT. The actuarial probability of developing dry eyes was 21 +/- 3% at 15 years. Thirty-three of the 48 (69%) patients with sicca syndrome had graft-versus-host disease (GVHD) compared to 60 of 200 (30%) patients without keratoconjunctivitis (P < 0.0001). The probability of developing keratoconjunctivitis sicca syndrome at 15 years was 38 +/- 6% for patients with and 10 +/- 3% (P < 0.0001) for those without chronic GVHD. Factors associated with an increased risk for late-onset of keratoconjunctivitis are chronic GVHD (relative risk 3.5; CI, 1.9-6.9), female patients (5.6; CI, 1.6-18.8), age older than 20 years (3.1; CI, 1.6-5.6), single dose irradiation for preparation to BMT (3.8; CI, 1.3-11.3) and methotrexate for prevention of GVHD (3.6, CI, 1.05-12.8). Late-onset kerato- conjunctivitis is a frequent ocular complication of BMT. With adequate treatment, severe corneal defects can be avoided. It occurs more frequently in patients with chronic GVHD, but, independent of chronic GVHD, more frequently in older patients and in females as it is observed in de novo Sjögren's syndrome. These data support the current concept that chronic GVHD is a reaction of both, allo- and autoimmunity.

Adolescent↗
PubMed1996

HLA-identical sibling bone marrow transplants vs chemotherapy for acute myelogenous leukemia in first remission.

There is controversy whether adults with acute myelogenous leukemia (AML) in first remission are best treated with chemotherapy or an HLA-identical sibling bone marrow transplant. We studied 1097 adults, 16-50 years old, with AML in first remission. Results of transplants from HLA-identical siblings reported to the International Bone Marrow Transplant Registry (IBMTR; n = 901) were compared with results of chemotherapy in comparable persons treated by the German AML Cooperative Group (GAMLCG; n = 196). Preliminary analyses identified subject- and disease-related variables differing between the cohorts and associated with treatment outcome within each cohort. We adjusted for these variables and differences in time-to-treatment in subsequent comparisons of treatment-related mortality, relapse, survival and leukemia-free survival (LFS). Five-year probability of treatment-related mortality was greater for transplants than chemotherapy (43% (95% confidence interval, 37-49%) vs 7% (3-11%); P< 0.0001). Five-year relapse probability was less for transplants than chemotherapy (24% (20-28%) vs 63% (55-71%); P< 0.0001). Five-year probability of survival was similar with transplants and chemotherapy (48% (43-53%) vs 42% (33-51%); P = 0.24). Five-year LFS probability was higher for transplants than chemotherapy (46% (42-50%) vs 35% (28-41%); P= 0.01). These data indicate that bone marrow transplants from HLA-identical siblings result in comparable survival but greater LFS than chemotherapy in adults with AML in first remission.

Adolescent↗
PubMed1995

[Bone marrow transplantation].

Bone marrow transplantation (BMT) has evolved from an experimental undertaking to an established therapeutic strategy for hematological neoplasias, severe aplastic anemia, congenital immunological and metabolic disorders and some solid tumors. This report summarizes the main indications for autologous and allogenic transplants, the prerequisites and potential techniques, early and late complications as well as preventive and therapeutic strategies. The results of 397 BMT, 357 allogeneic and 40 autologous transplants, performed in Basel between 1973 and 1995, illustrate the present potential and main prognostic factors: stage of disease, age and histocompatibility. 50% of the patients treated with an allogeneic BMT from an HLA-identical sibling early in the disease are alive 15 years post BMT, 80% free of disease and reintegrated into work and family. New strategies are testing the use of unrelated HLA-compatible volunteer donors and the potential of mobilized peripheral blood precursor cells instead of bone marrow for allogeneic and autologous transplants.

Bone Marrow Transplantation↗
PubMed1995

Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation.

Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia-free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.

Acute Disease↗
PubMed1995

[Flow cytometry identification of CD34-positive cells].

In the present study three clinical applications of flow-cytometric quantification of CD34-positive cells in the field of blood and marrow transplantation are evaluated. By daily determination of CD34-positive cells in the peripheral blood after mobilization of stem cells with chemotherapy or growth-factors it is possible to set the optimal time for collection of the transplant material. Thereafter the yield of CD34-positive cells within the harvested material is determined. Finally, the efficacy of positive CD34 selection using a biotin-avidin column is evaluated. Initial experience is presented here.

Antigens, CD↗
PubMed1995

[Hydroxyurea, erythrocyte volumes and hemoglobin F].

Hydroxyurea is used in the treatment of sickle cell anemia and beta-thalassemia major to increase the content of hemoglobin F (HbF) and presumably ameliorate clinical symptoms. Under therapy with hydroxyurea an increase of the mean corpuscular volume (MCV) of the erythrocytes can be observed. To evaluate a possible estimation of the content of HbF using the increase of MCV under treatment with hydroxyurea, we measured MCV and HbF during therapy with hydroxyurea. The median MCV before therapy was 87.8 fl (range 74.3-95.7) and under hydroxyurea 104.1 fl (81.0-139.5), and the median HbF 1.8% (0.1-5.4). Although both MCV and HbF increased under treatment with hydroxyurea, a linear correlation between these two parameters was not detectable. Therefore, MCV cannot replace the measurement of HbF.

Erythrocyte Indices↗
PubMed1995

[Late idiopathic pneumopathy following bone marrow transplantation].

4 of the 198 patients treated by bone marrow transplantation in Basel, Switzerland, with a follow-up of more than one year after therapy, developed a severe restrictive pneumopathy. In none of the 4 patients could an infectious pathogen be isolated, but all of them had signs of a chronic graft-versus-host disease. The 4 cases are described in detail.

Adolescent↗
PubMed1995

[Activation of endothelium-dependent hemostatic factors following bone marrow transplantation].

Changes in hemostatic factors after bone marrow transplantation (BMT), with or without thrombotic complications, have already been described. The endothelium seems to be actively involved in such processes. Over a period of 2 years we evaluated various hemostatic factors, associated or not with endothelial stimulation, in 44 patients with BMT (40 leukemias and 4 aplastic anemias). Factor VIII activity (VIII:C), von Willebrand factor antigen (vWF:Ag), tissue plasminogen activator antigen (tPA), plasminogen activator inhibitor activity (PAI-1), antithrombin III, protein C and protein S were assayed before and 1, 3, 6, 12, 18, and 24 months after BMT. Factor VIII:C, vWF and tPA were found to be significantly increased 1-6 months after BMT, returning to normal later. Patients with acute graft versus host disease, fever or cyclosporin treatment had significantly higher VIII:C, vWF and tPA. The increase in these factors implies lasting stimulation of their release and/or synthesis from endothelial cells that is enhanced by some complications of BMT. The degree and character of these changes could favor activation of thrombotic processes.

Adolescent↗