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A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 19 recordsLinked to original sources
PubMed2007

Results of the EBMT activity survey 2005 on haematopoietic stem cell transplantation: focus on increasing use of unrelated donors.

This EBMT activity report documents the haematopoietic stem cell transplantation (HSCT) activity in Europe in 2005. It provides numbers of HSCT by indication, donor type and stem cell source, lists the new practice of planned double transplants with allogeneic after autologous HSCT and concentrates on the increasing role of unrelated transplants over the last years. In 2005, there were 24,168 first HSCT, 8890 allogeneic (37%), 15,278 autologous (63%) and 3773 additional re- or multiple transplants reported from 597 centres in 43 participating countries. Main indications were leukaemias (7404 (31%; 82% allogeneic)); lymphomas (13,825 (57%; 89% autologous)); solid tumours (1655 (7%; 92% autologous)) and non-malignant disorders (1131 (5%; 93% allogeneic)). A total of 671 planned allogeneic after autologous HSCT were reported; the majority for myeloma (52%), lymphoma (28%) and acute myeloid leukaemia (11%). Compared to 2004, there was a 20% increase in allogeneic HSCT; numbers of autologous HSCT remained constant. The most noticeable increase was in unrelated HSCT, which comprise 41% of all allogeneic HSCT. Unrelated HSCT were preferentially performed for leukaemias and in countries with high income according to World Bank criteria. These data illustrate the current experience in Europe and form the basis for patient counselling and decisions making at health care institutions.

Data Collection↗
PubMed2006

High-dose rituximab and anti-MAG-associated polyneuropathy.

Rituximab has been administered successfully in patients with polyneuropathy associated with antibodies to myelin-associated glycoprotein (anti-MAG). The authors present a follow-up study with high-dose rituximab. Increase of rituximab from 375 mg/m2 to a dose of 750 mg/m2 was well tolerated and led to clinical improvement in four of eight patients, along with improvement of nerve conduction velocities and a reduction of anti-MAG antibody titers.

Aged↗
PubMed2006

Haematopoietic stem cell transplantation in Switzerland. Report from the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) Registry 1997-2003.

In 1997, the Swiss Transplant Working Group Blood and Marrow Transplantation (STABMT) initiated a mandatory national registry for all haematopoietic stem cell transplants (HSCT) in Switzerland. As of 2003, information was collected of 2010 patients with a first HSCT (577 allogeneic (29%) and 1433 autologous (71%) HSCT) and 616 additional re-transplants. This included 1167 male and 843 female patients with a median age of 42.4 years (range 0.2-76.6 years). Main indications were leukaemias (592; 29%) lymphoproliferative disorders (1,061; 53%), solid tumours (295; 15%) and non-malignant disorders (62; 3%). At the time of analysis 1,263 patients were alive (63%), 747 had died (37%). Probability of survival, transplant related mortality or relapse at 5 years was 52%, 21%, 36% for allogeneic and 54%, 5%, 60% for autologous HSCT. Outcome depended on indication, donor type, stem cell source and age of patient. HSCT is an established therapy in Switzerland. These data describe current practice and outcome.

Adolescent↗
PubMed2006

Allogeneic and autologous transplantation for haematological diseases, solid tumours and immune disorders: definitions and current practice in Europe.

The Accreditation Subcommittee of the EBMT regularly publishes special reports on current practice of haemopoietic stem cell transplantation for haematological diseases, solid tumours and immune disorders in Europe. Major changes have occurred since the first report was published in 1996. Haemopoietic stem cell transplantation today includes grafting with allogeneic and autologous stem cells derived from bone marrow, peripheral blood and cord blood. With reduced intensity conditioning regimens in allogeneic transplantation, the age limit has increased, permitting the inclusion of older patients. New indications have emerged such as autoimmune disorders and AL amyloidosis for autologous, and solid tumours for allogeneic transplants. The introduction of alternative therapies has challenged well-established indications such as imatinib for chronic myeloid leukaemia. An updated report with revised tables and operating definitions is presented here.

Europe↗
PubMed2006

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

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

Adolescent↗
PubMed2006

EBMT activity survey 2004 and changes in disease indication over the past 15 years.

This fifteenth annual European Group for Blood and Marrow Transplantation activity report lists the transplant activity in Europe in 2004 and documents the changes in indication over the past 15 years. In 2004, there were 22 216 first hematopoetic stem cells (HSCT), 7407 allogeneic (33%), 14 809 autologous (67%) and 4378 additional re- or multiple transplants reported from 592 centres in 38 European and five affiliated countries. Main indications were leukemias (7045 (32%; 78% allogeneic)); lymphomas (12 310 (55%; 94% autologous)); solid tumors (1759 (8%; 93% autologous)) and nonmalignant disorders (1015 (5%; 92% allogeneic)). In comparison, 145 teams from 20 countries performed 4234 HSCT (2137 allogeneic, 50%; 2097 autologous, 50%) in 1990. The overall increase was accompanied by major changes. Stem cell source changed from bone marrow to peripheral blood. More than one-third of allogeneic HSCT are now from unrelated donors. Reduced intensity conditioning is employed for one-third of allogeneic HSCT. Leukemias for allogeneic and lymphoproliferative disorders for autologous HSCT continue to increase. The decline in HSCT for chronic myeloid leukemia appears to level off for the first time since 1999. These data are informative for patient counselling and decision making for health care professionals.

Europe↗
PubMed2006

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

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

Acute Disease↗
PubMed2006

Cytogenetic response to prior treatment with interferon-alpha is predictive for survival after allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia.

We investigated the impact of a cytogenetic response (CyR) to IFN prior to and at the time of allogeneic hematopoietic stem cell transplantation (HSCT) on transplant-related mortality (TRM), relapse rate and survival probability after HSCT in 162 transplanted patients with chronic myeloid leukemia. One-hundred-one patients (62.3%) achieved a CyR prior to HSCT. Survival probabilities were higher in patients, who achieved any CyR prior to HSCT than in patients without CyR (63.6 vs 49.2%: P = 0.019). Survival probabilities in patients, who achieved a major CyR were better than in patients with minimal and minor CyR or in patients with no CyR (69.4 vs 58.8% vs 49.2%: P = 0.040). TRM and survival of chronic phase patients without CyR at the time of HSCT were similar to that of patients transplanted in advanced phase. Both groups combined had an outcome inferior to patients with at least minimal CyR (TRM, Gray test: P = 0.016, survival, log-rank test: P = 0.002). Univariate and multivariate analyses identified CyR prior to or at HSCT as a strong and independently favorable prognostic factor. We therefore conclude that allogeneic HSCT in CyR should be investigated prospectively as an alternative treatment option in defined patient groups.

Hematopoietic Stem Cell Transplantation↗
PubMed2006

Concomitant hairy cell and acute myeloid leukemia.

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

Antimetabolites, Antineoplastic↗
PubMed2005

Galactomannan does not precede major signs on a pulmonary computerized tomographic scan suggestive of invasive aspergillosis in patients with hematological malignancies.

BACKGROUND: Detection of serum galactomannan (GM) antigen and presence of the halo sign on a pulmonary computerized tomographic (CT) scan have a high specificity but a low sensitivity to diagnose invasive aspergillosis (IA) in patients at risk for this disease. To our knowledge, the relationship between the time at which pulmonary infiltrates are detected by CT and the time at which GM antigens are detected by enzyme immunoassay (EIA) has not been studied. METHODS: In a prospective study, tests for detection of GM were performed twice weekly for patients with hematological malignancies who had undergone hematopoetic stem cell transplantation (HSCT) or had received induction and/or consolidation chemotherapy. A pulmonary CT scan was performed once weekly. Infiltrates were defined as either major or minor signs. IA was classified as proven, probable, or possible, in accordance with the definition stated by the European Organization for Research and Treatment of Cancer-Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group. RESULTS: We analyzed 161 episodes of infection in 107 patients (65 allogeneic HSCT recipients, 30 autologous HSCT recipients, and 66 induction and/or consolidation chemotherapy recipients). A total of 109 episodes with no IA, 32 episodes with possible IA, and 20 episodes with probable or proven IA were identified. Minor pulmonary signs were detected by CT in 70 episodes (43%), and major pulmonary signs were detected by CT in 11 episodes (7%). Univariate and multivariate analyses revealed no significant association between detection of GM by EIA and detection of abnormal pulmonary signs by CT. A significant association was found between GM levels and receipt of piperacillin-tazobactam. GM test results were not positive before major signs were seen on CT images. Only 7 (10%) of 70 patients with minor pulmonary signs had positive GM test results before detection of the greatest pathologic change by CT. CONCLUSIONS: We show that detection of GM by EIA does not precede detection of major lesions by pulmonary CT. In the clinical setting, the decision to administer mold-active treatment should based on detection of new pulmonary infiltrates on CT performed early during infection, rather than on results of EIA for detection of GM.

Adolescent↗
PubMed2005

Use of intrathecal prophylaxis in allogeneic haematopoietic stem cell transplantation for malignant blood diseases: a survey of the European Group for Blood and Marrow Transplantation (EBMT).

SUMMARY: A survey was carried out among EBMT centres to describe the current practice concerning intrathecal (i.t.) prophylaxis in allogeneic stem cell transplantation for malignant diseases in patients with no central nervous system (CNS) manifestations of the disease at any time. A total of 90 centres reported their practice: 42 centres (47%) never used pre-transplant i.t. prophylaxis as part of the conditioning, whereas 48 centres (53%) gave i.t. prophylaxis to selected groups. The main indications were acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), and lymphoma (53, 33, and 23% of all centres, respectively). Prophylaxis was usually given to all patients with ALL, but often restricted to high-risk patients in AML and lymphoma. Of the 90 centres, 29 (32%) gave prophylactic i.t. treatment after the transplantation, mainly for the same indications as pre-transplant. This survey illustrates the heterogeneity in the current practice of i.t. prophylaxis in allogeneic transplantation for malignant blood disorders in Europe. The documentation in the literature to support the use of i.t. prophylaxis as part of transplantation for malignant diseases in patients without preceding CNS involvement is sparse. Based on the rarity of isolated CNS relapse after allogeneic stem cell transplantation, EBMT does not recommend routine i.t. prophylaxis to patients without prior CNS involvement.

Antineoplastic Agents↗
PubMed2005

Autologous hematopoietic stem cell transplantation for autoimmune diseases.

Experimental data and early phase I/II studies suggest that high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (HSCT) can arrest progression of severe autoimmune diseases. We have evaluated the toxicity and disease response in 473 patients with severe autoimmune disease treated with autologous HSCT between 1995 and 2003, from 110 centers participating in the European Group for Blood and Marrow Transplantation (EBMT) autoimmune disease working party database. Survival, transplant-related mortality, treatment response and disease progression were assessed. In all, 420 patients (89%; 86+/-4% at 3 years, median follow-up 20 months) were alive, 53 (11%) had died from transplant-related mortality (N=31; 7+/-3% at 3 years) or disease progression (N=22; 9+/-4% at 3 years). Of 370 patients, 299 evaluable for response (81%) showed a treatment response, which was sustained in 213 (71% of responders). Response was associated with disease (P<0.001), was better in patients who received cyclophosphamide during mobilization (relative risk (RR)3.28 (1.57-6.83)) and was worse with increasing age (>40 years, RR0.29 (0.11-0.82)). Disease progression was associated with disease (P<0.001) and conditioning intensity (high intensity, RR1; intermediate intensity, RR1.81 (0.96-3.42)); low intensity, RR2.34 (1.074-5.11)). These data from the collective EBMT experience support the hypothesis that autologous HSCT can alter disease progression in severe autoimmune disease.

Autoimmune Diseases↗
PubMed2005

Change in stem cell source for hematopoietic stem cell transplantation (HSCT) in Europe: a report of the EBMT activity survey 2003.

This EBMT activity survey presents the status of hematopoietic stem cell transplantation (HSCT) in Europe 2003 and focuses on changes in stem cell source over the last decade. There were 21 028 first HSCT, 7091 allogeneic (34%), 13 937 autologous (66%) and 4179 additional re- or multiple transplants reported from 597 centers in 42 European countries in the year 2003. Main indications were leukemias (6613 (31%; 78% allogeneic)); lymphomas (11 571 (55%; 93% autologous)); solid tumors (1792 (9%; 92% autologous)) and nonmalignant disorders (898 (5%; 93% allogeneic)). In 1991, the vast majority of autologous and all allogeneic HSCT were still bone marrow (BM) transplants. Stem cell source changed rapidly to peripheral blood (PB) for autologous HSCT between 1992 and 1996. In 2003, 97% of autologous HSCT were PB derived. The change to PB for allogeneic HSCT followed 3 years later and occurred at a lower rate. In 2003, 65% of all allogeneic HSCT were PB derived. The change in stem cell source was not homogeneous. It was associated with donor type, main diagnosis, disease stage and it differed between European countries. In 2003, bone marrow remains a significant source of stem cells in some European countries for autologous HSCT and for nonmalignant disorders in allogeneic HSCT.

Bone Marrow Transplantation↗
PubMed2005

Cause of death after allogeneic haematopoietic stem cell transplantation (HSCT) in early leukaemias: an EBMT analysis of lethal infectious complications and changes over calendar time.

We analysed a large homogeneous group of 14,403 patients transplanted for early leukaemia from an HLA-identical sibling and reported to the EBMT in four time cohorts: 1980-1989 (24%), 1990-1994 (26%), 1995-1998 (30%) and 1999-2001 (20%). We focused on death from infection. End points were survival, death from relapse and transplant-related mortality (TRM), which was subdivided into death from graft-versus-host disease (GvHD) (1315 patients; 25% of deaths), infection (597 patients; 11% of deaths) or 'other' causes (1875 patients; 34% of deaths). Survival increased from 52% at 5 years in the first to 62% in the third cohort (P<0.05) and TRM decreased from 36 to 26% (P<0.05) due to a reduction in death from infection (P<0.001). GvHD, 'other' causes and relapse did not improve. The relative proportions of bacteria (217 patients; 36%), viruses (183 patients; 31%), fungi (166 patients; 28%) or parasites (32 patients; 5%) as cause of infectious death (cumulative incidence of death at 5 years 1.8, 1.6, 1.4 and > or = 0.3%, respectively) and median time to death from infections (3 months (range 0-158 months)) did not change. Death from infections has been reduced significantly, but it still represents an ongoing risk after HSCT and draws attention to the time beyond the initial period of neutropenia.

Adolescent↗
PubMed2005

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

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

Adolescent↗