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Biomedical subjects

A Gratwohl

Publications and source records attributed to A Gratwohl.

At least 163 records · Page 9Linked to original sources
PubMed1997

A survey of the prophylaxis and treatment of acute GVHD in Europe: a report of the European Group for Blood and Marrow, Transplantation (EBMT). Chronic Leukaemia Working Party of the EBMT.

A survey was carried out among EBMT (European Group for Blood and Marrow Transplantation) centres of the practical details of the prophylaxis and treatment of acute GVHD. The emphasis was on the prophylactic use of cyclosporine A and methotrexate and their combination, and on the initial treatment of acute GVHD. Eighty-seven centres sent a report. This survey demonstrated that marked differences exist between centres in the practices of GVHD prophylaxis and treatment despite superficially similar protocols. These differences may have an impact on the results obtained.

Acute Disease↗
PubMed1997

Haploidentical family member transplants for patients with chronic myeloid leukaemia: a report of the Chronic Leukaemia Working Party of off European Group for Blood and Marrow Transplantation (EBMT).

Within the registry of the chronic leukaemia working party of the European Group for Blood and Marrow Transplantation, data were available from 103 patients with chronic myeloid leukaemia who were treated by bone marrow transplantation from haploidentical family members. The patients of median age 30 years were transplanted between 1983 and 1994 in 25 European centres. The overall probabilities of survival and leukaemia-free survival (LFS) at 5 years were 32 and 25%, respectively. In univariate analysis, two factors were identified which affected survival and LFS, ie the state of disease at the time of transplant and the degree of HLA disparity. Fifty-nine patients were transplanted in first chronic phase and the probability of survival at 2 years was 47%. Forty-four patients received their transplants for advanced disease and their probability of survival at 2 years was 25% (P = 0.004). Donor bone marrow was HLA-mismatched for 0-1 antigens in 54 patients (group 1) and for 2-3 antigens in 49 patients (group 2). At 2 years, the probabilities of survival for groups 1 and 2 were 46 and 27% (P < 0.02) and the probabilities of LFS were 43 and 24% (P < 0.03), respectively. Multivariate analysis confirmed the prognostic importance of the disease stage and of the HLA disparity. Patients transplanted in first chronic phase from a donor mismatched for 0-1 HLA antigens had a probability of survival of 52% at 2 years compared with 19% for patients transplanted in advanced disease stage from donors mismatched for 2-3 HLA antigens.

Adolescent↗
PubMed1997

European results of matched unrelated donor bone marrow transplantation for chronic myeloid leukemia. Impact of HLA class II matching. Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

We have retrospectively analyzed the impact of prognostic factors on the outcome of serologically HLA-matched unrelated donor (UD) BMT for CML. For this purpose, we have studied a cohort of 366 patients transplanted in Europe between January 1985 and December 1994. The median age of the 211 males and 155 females was 34 years; 238 patients were transplanted in first chronic phase and 116 in advanced phases. The median interval from diagnosis to BMT was 827 days. GVHD prophylaxis consisted of CsA and MTX in 202 patients or of ex vivo or in vivo T cell depletion (TCD) in 129. Recently, DNA-based methods of HLA-class II typing have been used to improve donor selection. We obtained complete data on 300 donor/recipient (D/R) pairs. Among them, we have identified three groups of patients, according to specific HLA-DRB1 D/R compatibility. Two hundred and ten patients received marrow from donors identical for HLA-DRB1 (group 1). Thirty-one patients received BMT from a donor who was HLA-DRB1 mismatched (group 2) and 59 from a donor in whom specific HLA-DRB1 typing was not performed (group 3). The overall survival was 37 +/- 3% at 2 years and leukemia-free survival (LFS) was 31 +/- 3%. In univariate analysis, five variables had a favorable effect on LFS: transplant in first chronic phase (P = 0.0001), time interval from diagnosis to BMT shorter than the median (P = 0.01), prophylaxis of GVHD without TCD (P + 0.001), acute GVHD < grade III (P = 0.0009) and HLA-DRB1 D/R matching (P = 0.0001). Transplant-related mortality (TRM) was 49 +/- 4% in group 1, 79 +/- 8% in group 2 and 80 +/- 6% in group 3 (P = 0.0001). Multivariate analysis confirmed that HLA-DRB1 matching was the most significant factor influencing survival (P = 0.04), LFS (P = 0.013) and TRM (P = 0.0049). From these results, we have defined a 'good risk' group, ie patients transplanted in first chronic phase, from an HLA-DRB1 matched donor, without TCD as prophylaxis against GVHD. The 2 year LFS, TRM and relapse incidence for this group were 51 +/- 5%, 47 +/- 5% and 2 +/- 2%, respectively. This suggests that the long-term outcome of patients with favorable prognostic features can approach that of patients transplanted from geno-identical siblings. In contrast, the TRM for patients transplanted for advanced disease from non HLA-DRB1-identical donors was 94%. Such a high TRM clearly indicates that UD BMT is not justifiable for these individuals.

Adolescent↗
PubMed1997

Celiac disease transmitted by allogeneic non-T cell-depleted bone marrow transplantation.

We observed the occurrence of celiac disease following allogeneic bone marrow transplantation in a patient transplanted for acute leukemia. The marrow donor was his HLA-identical sister, who had suffered from celiac disease since birth. The post-transplant period was characterized by recurrent episodes of diarrhea. Detailed workup showed atrophic intestinal mucosa on histology and anti-gliadin and anti-endomysium antibodies in the serum, features that were not present before transplantation. GVHD was absent at that time. The patient remains free of symptoms on gluten-free diet and slight immunosuppression. This case suggests transmission of celiac disease by bone marrow transplantation and supports the T cell concept in celiac disease.

Acute Disease↗
PubMed1997

Long-term results after allogeneic bone marrow transplantation for chronic myelogenous leukemia in chronic phase: a report from the Chronic Leukemia Working Party of the European Group for Blood and Marrow Transplantation.

The purpose of this study was to determine the long-term results of allogeneic bone marrow transplantation for chronic myeloid leukemia. A retrospective analysis was carried out of the outcome of 373 consecutive transplants performed at 38 European institutions between 1980 and 1988 and reported to the registry of the European Group for Blood and Marrow Transplantation. All transplants were carried out for first chronic phase of chronic myelogenous leukemia using unmanipulated marow cells from HLA-identical sibling donors. The probability of survival and leukemia-free survival at 8 years were 54% (95% CI: 49-59) and 47% (95% CI: 41-52) respectively. The probabilities of developing acute GVHD (II-IV) at 100 days and chronic GVHD at 4 years after transplant were 47% (95% CI: 41-53) and 52% (95% CI: 46-58) respectively. The probabilities of transplant-related mortality and leukemic relapse 8 years after BMT were 41% (95% CI: 36-48) and 19% (95% CI: 14-25), respectively. Transplant within 12 months of diagnosis was associated with reduced transplant-related mortality (34 vs 45%, P = 0.013) and resulted in improved leukemia-free survival (52 vs 44%, P = 0.03). The probability of relapse was significantly reduced in patients who developed chronic GVHD (RR = 0.33, P = 0.004). The probability of relapse occurring more than 2 years after transplant was increased more than five-fold in patients transplanted from a male donor (RR = 5.5, P = 0.006). Sixty-seven patients in hematologic remission were studied for residual disease by two-step RT/PCR for BCR-ABL mRNA and 61 (91%) tested negative. We conclude that bone marrow transplantation can induce long-term survival in approximately one-half of CML patients; the majority of survivors have no evidence of residual leukemia cells when studied by molecular techniques. The probability of late relapse is increased with use of a male donor.

Adolescent↗
PubMed1997

Allogeneic bone marrow transplantation for acute leukemia in patients over the age of 40 years. Acute Leukemia Working Party of the European Group for Bone Marrow Transplantation (EBMT).

Extension of allogeneic transplants to older patients has been limited by a high risk of transplant-related death and graft-versus-host disease. To evaluate the feasibility in older patients, a retrospective analysis of the procedure was performed for first remission acute leukemia in 192 patients aged over 40 years and compared with a group of 1119 recipients aged from 16 to 40 years reported to the EBMT from 1986 to 1992. Patient-, disease-, and treatment-related variables were compared between the two age groups using the chi2 statistical method for categorical variables. Variables differing significantly or recognized as potential prognostic factors were included in a multivariate analysis. Leukemia-free survival and relapse were comparable among the age groups in the two types of leukemias. Incidence of graft-versus-host disease was higher in the older group of ALL patients. Older patients with AML in first remission had a higher treatment-related mortality incidence, with no influence on survival. A pair-matched analysis of AML patients did not show any statistical difference in the probability of LFS, RI, TRM, and survival for the two age cohorts of patients. These results suggest that BMT should be considered for patients over 40 years of age.

Acute Disease↗
PubMed1997

IBMTR Severity Index for grading acute graft-versus-host disease: retrospective comparison with Glucksberg grade.

Acute graft-versus-host disease (GVHD) severity is graded by pattern of organ involvement and clinical performance status using a system introduced by Glucksberg and colleagues 21 years ago. We examined how well Glucksberg grade predicted transplant outcome and constructed a Severity Index not requiring subjective assessment of performance in 2881 adults receiving an HLA-identical sibling T-cell-depleted (n = 752) or non-T-cell-depleted (n = 2129) bone marrow transplant for leukaemia between 1986 and 1992. Relative risks (RR) of relapse, treatment-related mortality (TRM) and treatment failure (TF) (relapse or death) were calculated for patients with (Glucksberg Grade I, II or III/IV acute (GVHD) versus those without acute GVHD and for patients with distinct patterns of organ involvement regardless of Glucksberg grade. Using data for non-T-cell-depleted transplants, a Severity Index was developed grouping patients with patterns of organ involvement associated with similar risks of TRM and TF. Higher Glucksberg grade predicted poorer outcome; however, patients with the same grade but different patterns of skin, liver or gut involvement often had significantly different outcomes. The revised Severity Index groups patients in four categories, A-D. Compared to patients without acute GVHD, RRs (95% confidence interval) of TF were 0.85 (0.69, 1.05) for patients with Index A, 1.21 (1.02, 1.43) with B, 2.19 (1.78, 2.71) with C, and 5.69 (4.57, 7.08) with D. Prognostic utility of the Index was tested in patients receiving T-cell-depleted transplants; similar RRs of TF were observed. An acute GVHD Severity Index is proposed to enhance design and interpretation of clinical trials in the current era of allogeneic blood and bone marrow transplantation.

Adolescent↗
PubMed1997

Autologous peripheral blood stem cell transplantation in a patient with chronic autoimmune thrombocytopenia.

Immunoablation by high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (PBSCT) is one approach currently under discussion for the treatment and possible cure of patients with severe autoimmune diseases. Chronic immune thrombocytopenic purpura (ITP) can be refractory to current therapies and in severe cases may constitute a life-threatening condition. We performed autologous PBSCT with T-cell depletion in a patient with severe chronic ITP but observed no effect on platelet levels. This contrasts with a recent report where complete remission was induced by a similar regimen in two patients with ITP Further studies will be necessary to identify subgroups of patients who might benefit from this form of therapy.

Adult↗
PubMed1997

Hemopoietic blood and marrow transplants in the treatment of severe autoimmune disease.

The past year of activities represents virtually the first year of activities in hemopoietic blood and marrow transplants in the treatment of severe autoimmune disease. The concept of profound hematoimmunoablation followed by blood or marrow transplants for severe autoimmune disease is not new, but the first publications of such cases treated for autoimmune disease alone occurred only in late 1996. Other case reports followed, and the activity has expanded rapidly such that over 40 treated patients have been described, 35 of whom have been entered into a recently created European League Against Rheumatism/European Group for Blood and Marrow Transplantation database (now extended to include data from Australasia and the United States). Four international meetings have been held, the published proceedings of which have formed the basis for an ongoing international collaborative effort. Although very early, some trends have been observed: the majority of patients (mostly with multiple sclerosis or scleroderma) have clinically improved or stabilized; the toxicity of the procedure (mostly autologous bone marrow transplantation) was as observed previously in other disorders; and better results are suggested in patients achieving significant T-cell depletion, either through conditioning, graft purging, or both. These impressions must be confirmed by prospective comparative studies using a limited number of regimens.

Animals↗
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

Flt3 ligand level reflects hematopoietic progenitor cell function in aplastic anemia and chemotherapy-induced bone marrow aplasia.

Flt3 ligand (flt3L) is a member of a small family of cytokines acting as tyrosine kinase receptor ligands that stimulate the proliferation of primitive hematopoietic progenitors in vitro. To gain insight into the physiological role of flt3L in early hematopoiesis, levels of flt3L were determined in serum of patients with multilineage bone marrow failure and related to the severity of stem cell depletion. In patients with aplastic anemia (AA) and in cancer patients with chemotherapy-induced transient suppression of hematopoiesis, flt3L fluctuated in an inverse relationship to the degree of bone marrow failure. In severe AA at diagnosis, levels of circulating soluble flt3L were highly elevated (2,653 +/- 353 pg/mL) as compared with normal blood serum values of 14 +/- 39 pg/mL. Flt3L returned to near normal levels within the first 3 months following successful bone marrow transplantation and in autologous remission induced by immunosuppressive therapy with antilymphocyte globulin (ALG; 100 +/- 31 and 183 +/- 14 pg/mL, respectively). In contrast, rejection of the graft or relapse of the disease after ALG was accompanied by an increase to high pretreatment concentrations of the circulating cytokine (3,770 +/- 2,485 and 1,788 +/- 233 pg/mL, respectively). Flt3L in serum inversely correlated with the colony-forming ability of AA bone marrow precursors in vitro (R = -.86), indicating that the concentration of the ligand reflects hematopoiesis at the progenitor cell level. Flt3L increased to 2,500 pg/mL in the serum of leukemia patients during chemoradiotherapy-induced bone marrow suppression and returned to normal values along with hematopoietic recovery. Expression of the membrane-bound form of flt3L was significantly elevated in mononuclear bone marrow and peripheral blood cells from patients with severe pancytopenia, suggesting de novo synthesis of the factor in response to bone marrow failure. The data provide a strong argument for the involvement of flt3L in the regulation of early hematopoiesis in vivo.

Anemia, Aplastic↗
PubMed1996

Outbreak of invasive mycoses caused by Paecilomyces lilacinus from a contaminated skin lotion.

BACKGROUND: Invasive mycoses are an important cause of illness and death in immunocompromised patients. Infections with molds other than aspergilli have been increasingly seen in patients with hematologic cancers, but epidemics of these infections have not yet been reported. OBJECTIVE: To describe an outbreak of invasive mycoses with Paecilomyces lilacinus in severely neutropenic patients. DESIGN: An outbreak investigation. SETTING: The hematology-oncology isolation and bone marrow transplantation unit of the University Hospital, Basel, Switzerland. PATIENTS: 25 consecutive patients admitted between 17 August 1993 (the date of the first manifestation of P. lilacinus infection) and 31 October 1993 (when the unit was closed). MEASUREMENTS: Clinical and microbiological data, including histologic findings; cultures from several patient sites; and environmental examinations of potential airborne, parenteral, enteric, and horizontal routes of transmission. Infections were defined by the isolation of P. lilacinus from clinically evident skin eruptions. RESULTS: 12 of the 25 patients (48%) were infected or colonized. Nine patients (36%), including all bone marrow transplant recipients, had documented invasive P. lilacinus infections. All 9 infected patients had papular, pustular, or necrotic skin eruptions. Two patients with severe graft-versus-host disease died with refractory fungal disease; 1 also had microbiologically documented endophthalmitis and kidney infiltrates. Seven affected patients no longer had P. lilacinus after recovery of bone marrow function. The organism was resistant in vitro to amphotericin B, itraconazole, and fluconazole. Patients did not respond clinically to these agents. The outbreak was ultimately traced to a contaminated, commercially available, pharmaceutically prepared skin lotion. The outbreak ended after the skin lotion was recalled and has not recurred after a follow-up period of 2 years. CONCLUSION: Contaminated skin lotion is a potential cause of opportunistic fungal infections in immunocompromised hosts. Paecilomyces lilacinus is a common saprophytic mold that can cause, by direct cutaneous inoculation, invasive infections associated with illness and death.

Adolescent↗
PubMed1996

[Oral All-transretinoic acid administration in intubated patients with acute promyelocytic leukemia].

In acute promyelocytic leukemia (APL), disseminated intravascular coagulation is frequently observed. Massive alveolar bleeding can lead to respiratory insufficiency, requiring tracheal intubation and mechanical ventilation. Today all-transretinoic acid (ATRA) is part of induction chemotherapy in acute promyelocytic leukemia. The administration of ATRA is oral. No intravenously administered form is available. ATRA can be administered to intubated patients in the following manner: the daily amount of ATRA is placed in a sterile 50 ml tube. After addition of about 20 ml of sterile water the tube is heated in a waterbath to a temperature of 37 degrees C until the capsules melt and the suspension is completely liquid. The resulting oily fluid is then administered via nasogastric tube. We have treated 2 patients with acute promyelocytic leukemia intubated due to massive alveolar bleeding in this manner, and have observed a differentiation of promyelocytes to granulocytes and complete remission in both patients, indicating that the ATRA administered had been resorbed intestinally.

Adolescent↗
PubMed1996

[Bernard-Soulier thrombocytopenia: clinical significance of a rare disorder].

We present 5 cases with thrombocytopenia and abnormal platelet function. The diagnosis of Bernard-Soulier syndrome was suspected in some subjects of advanced age on the ground of morphologic changes in the thrombocytes and of low platelet counts with or without prolonged bleeding time. The platelets showed normal aggregation with adrenalin, ADP and collagen but abnormal agglutination with ristocetine. All patients had normal von Willebrand factor levels in plasma. Flow cytometry demonstrated on thrombocytes lack of GP Ib expression of varying degree in comparison to normal controls, using various anti-GP Ib-antibodies (CD42b). The combination of these findings confirmed the diagnosis of Bernard-Soulier syndrome with varying expression of GP Ib. Flow cytometry and the use of specific monoclonal antibodies may be a rapid and reliable diagnostic tool. Differential diagnosis and treatment strategies are discussed. A congenital thrombopathy should always be considered in patients with thrombocytopenia of unknown origin and abnormal platelet morphology.

Adult↗
PubMed1996

High resolution HLA matching associated with decreased mortality after unrelated bone marrow transplantation.

As compared with related HLA-identical sibling donors, bone marrow transplantation (BMT) with phenotypically HLA ABDR-compatible unrelated donors is associated with increased mortality. This may be due to hidden HLA incompatibilities not detected by conventional typing. We have analyzed 44 unrelated patient-donor pairs who were matched for HLA-A, -B, and -DR by routine tissue typing. Our comprehensive HLA typing approach consisted of serology, cytotoxic T-cell precursor (CTLp) tests, T-cell cloning, oligotyping, and DNA sequencing. Using these techniques, we identified numerous HLA allele mismatches not detected by the previously applied routine typing. Twenty-four patient-donor pairs were highly matched and had a low CTLp frequency, whereas the remaining 20 pairs were allele-mismatched for HLA-A, -B, -C, -DR, -DQ antigens and/or had a positive result of the CTLp test. Patient and donor age, diagnosis, and treatment did not differ significantly between the matched and mismatched transplants. The probability for severe acute graft-versus-host disease grades III-IV was 21% in the matched and 47% in the mismatched patients (P = .0464). Transplant-related mortality was 21% and 57% (P = .0072) and actuarial patient survival rates at 3 years were 61% and 13% (P = .0005). We conclude that both HLA class I and class II allele mismatches between unrelated phenotypically ABDR-compatible patient-donor pairs are frequent and associated with increased incidence of posttransplant complications.

Alleles↗
PubMed1996

[Skin manifestations of graft-versus-host reaction following bone marrow transplantation].

We review the cutaneous manifestations of acute and chronic graft versus host disease (GvHD). Acute GvHD is characterized by initial itching, pain on pressure and erythema which begins on posterior auricular skin, palms and soles. The disease evolves into a typical but nonspecific maculopapular rash. Confluent rashes and follicular erythema may occur. Erosive oral lesions usually develop. The most severe variant of GvHD is toxic epidermal necrolysis, which often has a fatal outcome. The onset of chronic GvHD usually occurs more than 100 days after bone marrow transplantation and may be preceded by the acute form. The spectrum of skin changes includes lichenoid pruritic lesions with violaceous color and scleroderma-like skin involvement. Investigation of unknown rashes in these patients includes skin biopsy, which clearly differentiates leukocytoclastic vasculitis and erythema exsudativum multiforme with lymphocytic vasculitis from cutaneous manifestations of GvHD. Special stains may reveal bacteria and fungus in septicemic patients. The therapeutic options are discussed.

Acute Disease↗