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H Heimpel

Publications and source records attributed to H Heimpel.

At least 19 recordsLinked to original sources
PubMed1992

Host-specific interleukin-2-secreting donor T-cell precursors as predictors of acute graft-versus-host disease in bone marrow transplantation between HLA-identical siblings.

BACKGROUND: Acute graft-versus-host disease (GVHD) is a serious complication of allogeneic bone marrow transplantation from an HLA-identical sibling. There is no practical test before transplantation that gives sufficient information to predict the degree of allogeneic reactivity between HLA-identical siblings. METHODS: We determined the frequency with which host-specific interleukin-2-secreting donor T-cell precursors occurred in 16 consecutive pairs of HLA-identical siblings before they underwent marrow grafting. The results were correlated with the development of acute GVHD after transplantation. RESULTS: High frequencies of host-specific T-cell precursors (> or = 1 per 100,000) were detectable before transplantation in eight donors whose siblings later had severe (grade II or III) acute GVHD. Among the donors to eight patients with mild (grade 0 or 1) acute GVHD, low frequencies (< 1 per 100,000) were found. CONCLUSIONS: Analysis of the frequency of such cells before transplantation may be a useful predictor of severe acute GVHD in allogeneic bone marrow transplantation between HLA-identical siblings. It is possible that the patients at risk for serious acute GVHD after marrow grafting may benefit from some alternative form of immunosuppressive therapy.

Acute Disease↗
PubMed1992

[Severe tetraparesis as the first manifestation of a chronic lymphatic leukemia].

Uncertain gait and weakness on standing, progressing to flaccid paraparesis of both legs, developed in a 76-year-old woman. Proprioceptor reflexes of both legs were absent and there was pallaesthesia up to the pelvic rim. Electromyography pointed to polyneuritis. Administration of prednisone, 1 mg/kg daily for 10 days, was ineffective, as was one-time plasmapheresis. An incomplete tetraparesis developed. Blood white-cell count increased within 2 weeks by 10,400/microliters (52% lymphocytes) to 17,400/microliters. Blood smear, bone-marrow cytology and histology, as well as immunocytology, revealed lymphoplasmocytoid immunocytomas (chronic lymphocytic leukemia). Oral cytoreductive treatment was started with chlorambucil, 0.1 mg/kg daily, and prednisone, 100 mg daily. After 19 days the patient was able to walk with support, after 28 was walking unaided. Treatment was continued over eight cycles (14 days' treatment, 14 days' interval per cycle). 17 weeks after onset of treatment paraesthesias of the legs required renewed administration of chlorambucil, 0.1 mg/kg per day, for 3 months. The patient has now been free of symptoms during a follow-up period of 12 months.

Aged↗
PubMed1992

Thrombotic thrombocytopenic purpura in early pregnancy with maternal and fetal survival.

Thrombotic thrombocytopenic purpura (TTP) is a hematologic disorder which is clinically characterized by thrombocytopenia, microangiopathic hemolytic anemia, fever, neurologic symptoms, and cardiac and renal involvement. The pathogenic mechanisms of this disease are poorly understood. It is well known that TTP is associated with pregnancy and that prognosis for the mother and child is poor. We present the first case of a severe TTP diagnosed in the first trimester of pregnancy (13th week of gestation) with maternal survival and birth of a healthy child which required continuous and intensive treatment with plasma therapy until delivery. During a period of 24 weeks several attempts to discontinue plasma therapy failed because of continuous active disease, and it became evident that plasma infusions were not as effective as plasma exchanges. The fact that the patient entered into remission soon after delivery of a healthy child by cesarean section in the 37th gestational week shows that in this case pregnancy activated an unknown factor which does not cross the placenta and which can be removed by plasmapheresis.

Adult↗
PubMed1992

Cryopreserved autologous platelet transfusions in alloimmunized patients with acute leukemia.

Autologous platelets of 5 alloimmunized patients with acute leukemia in remission were cryopreserved with 5% dimethylsulfoxide in liquid nitrogen and retransfused in the following therapy-induced thrombocytopenic phase. The mean platelet recovery after freezing, thawing and washing was 85 +/- 6%. The mean corrected 1-hour increment in platelet counts was 11 (4-27) x 10(9)/l, i.e. 61% in comparison with fresh platelet transfusions in other patients. In vivo function of frozen platelets was documented by improvement of the posttransfusion bleeding time. Cryopreserved autologous platelets function hemostatically and can be used even for completely refractory patients and thus permit curative antileukemic therapy.

Adult↗
PubMed1992

ABO-incompatible bone marrow transplantation.

In the past 10 years 201 HLA-identical bone marrow transplantations (BMT) were performed with major ABO incompatibility in 41 (20%) and minor ABO incompatibility in 35 (18%) patients. ABO compatibility between donor and recipient showed no influence on granulocyte and platelet recovery after BMT. Erythrocyte reconstitution was significantly (p < 0.01) delayed for about 1 week in major ABO-incompatible BMT. In addition, a pure red cell aplasia lasting for 2-5 months occurred in 6 out of 21 blood group 0 patients who received transplants of group A. The rate of graft rejection, incidence of graft-versus-host disease as well as the leukemic relapse rate were similar in ABO-compatible and ABO-incompatible BMT. The probability of a 10-year survival after BMT is independent of ABO compatibility between donor and recipient.

ABO Blood-Group System↗
PubMed1992

Chronic myelogenous leukemia: recent developments in prognostic evaluation and chemotherapy. The German CML Study Group.

Recent developments in CML research are illustrated by the results of one large randomized multicenter study carried out by the German CML Study Group. From July 1983 to January 1991, a total of 703 CML patients were recruited; 624 patients were randomized to compare hydroxyurea and interferon alpha (IFN) with busulfan. The median survival of Ph+ patients by now is 3.95 years, that of Ph- patients 1.1 years. Some difference in survival is recognizable between the treatment arms, but this is not yet significant. Fewer adverse effects are being observed in the hydroxyurea group. Ph-negative patients tend to have lower white blood cell and platelet counts. Patients (164) were randomized to receive IFN. In 50 patients (30%) IFN had to be terminated because of adverse effects, therapy resistance, or other reasons. Reduction of the Ph-chromosome was observed in 20% of evaluable patients. In 3 patients complete cytogenetic remissions were observed. Clinically relevant neutralizing antibodies were detected in 9 cases. Prospectively evaluated age, organomegaly related symptoms, Karnofsky index, extramedullary manifestations, erythroblasts, and percent of circulating blasts proved to be of prognostic significance. A prognostic score (score 1) was determined and compared to Sokal's score. It is expected that the study results will allow statements as to the advantages or disadvantages of the use of busulfan, hydroxyurea and IFN in the treatment of CML as well as to the reliability of prognostic markers.

Bone Marrow Transplantation↗
PubMed1991

Treatment of aplastic anemia with antilymphocyte globulin and methylprednisolone with or without cyclosporine. The German Aplastic Anemia Study Group.

BACKGROUND AND METHODS: Immunosuppression is the most effective treatment for patients with aplastic anemia, except for bone marrow transplantation. The best results are achieved with antilymphocyte globulin or cyclosporine. Patients have been treated successfully with a combination of both agents, but there has been no controlled evaluation of its efficacy. We conducted a randomized, multicenter trial in 84 patients not eligible for bone marrow transplantation, comparing treatment with antilymphocyte globulin and methylprednisolone (41 patients--the control group) with antilymphocyte globulin, methylprednisolone, and cyclosporine (43 patients--the cyclosporine group). RESULTS: At three months significantly more patients in the cyclosporine group had a complete or partial remission in response to treatment than did patients in the control group (65 percent vs. 39 percent, P less than 0.03); this difference was confirmed at six months (70 percent vs. 46 percent, P less than 0.05). The superior results of the regimen including cyclosporine were most evident in the patients with severe or very severe aplastic anemia, whose response rate at six months was 65 percent, as compared with 31 percent of such patients in the control group (P less than 0.02). Granulocyte and hemoglobin levels became normal in most patients who responded, but platelet counts continued to be subnormal in 61 percent of the patients. Ten of 52 patients with responses (3 in the cyclosporine group and 7 in the control group) relapsed 4 to 37 months after treatment. The actuarial survival of all patients at 41 months is 64 percent in the cyclosporine group and 58 percent in the control group (P = 0.16); among the patients with severe or very severe disease, survival is 80 percent and 44 percent, respectively (P = 0.077). Cyclosporine had substantial but reversible side effects. CONCLUSIONS: Immunosuppressive treatment of aplastic anemia with antilymphocyte globulin, methylprednisolone, and cyclosporine appears to be more effective than a regimen of antilymphocyte globulin and methylprednisolone without cyclosporine and may thus represent a treatment of choice for patients who are not eligible for bone marrow transplantation.

Adult↗
PubMed1991

Functional criteria for staging and treatment of hairy cell leukemia.

The determination of clinical stage in hairy cell leukemia is hampered by the lack of common criteria. Furthermore, clinical stages in which the disease should be treated have not yet been defined. In this paper we propose common criteria for the clinical staging of all hairy cell leukemia patients (treated or untreated), as well as for the assessment of responses to therapy. These criteria are absence or presence of disease-related symptoms and disease progression. Based on these criteria we propose that hairy cell leukemia patients in the most favorable stage of the functional system, non-symptomatic Stable Disease (nsSD), do not require treatment. Only in patients with disease-related symptoms and/or signs of disease progression is treatment justified and necessary. No symmetry was observed between the functional stages and Jansen's stages. For evaluation of responses to treatment, our stages were more sensitive than the Leeds criteria. Experimental evidence enables the differentiation of patients with non-symptomatic stable disease from those with symptomatic and/or progressive disease.

Adult↗
PubMed1991

[Multicenter prospective controlled study of therapy of chronic myeloid leukemia. Comparison of busulfan, hydroxyurea and interferon alpha (April 1990 status)].

In a multicenter study it is being determined, whether the use of hydroxyurea or of interferon alpha instead of busulfan prolongs the chronic phase of Philadelphia-positive CML. Additional goals are the examination, whether the types of disease evolution and the terminal phases differ between the treatment groups, and the prospective recognition of prognostic criteria for the duration of the chronic phase of CML. By September 5, 1990, 593 CML-patients had been randomized, 221 for busulfan, 228 for hydroxyurea and 144 for interferon alpha. The average age is about 51 years. By April 30, 1990, 106 patients had reached the end of the chronic phase, 126 had died. The median survival of Philadelphia-positive patients was 3.95 years, that of all patients 3.75 years. The median observation time of all patients was 1.34 years (mean 1.60 years). At present, no significant difference in survival is recognizable between the three treatment arms, although fewer adverse effects have been observed in the hydroxyurea arm.

Busulfan↗
PubMed1990

Essential thrombocythemia in two sisters originating from different stem cell levels.

We report the rare occurrence of essential thrombocythemia (ET) in two sisters. In one patient, the clinical phenotype of the disease evolved from ET to polycythemia vera (PV) after 4 years of follow-up. Clonal hematopoiesis was established in both cases by X-chromosomal inactivation analysis using a DNA polymorphism of the phosphoglycerate-kinase (PGK) gene. Cell separation studies suggested a common ancestor for granulocytes, monocytes, and T lymphocytes in one patient; however, in her sister, monoclonality could only be demonstrated convincingly for the granulocyte fraction. Our data indicate that ET may originate from heterogenous stem cell levels.

Aged↗
PubMed1990

Establishment and characterization of a new Epstein-Barr virus transformed cell line from a human B cell lymphoma.

We have established a new cell line from a patient with centrocytic B cell lymphoma. Highly purified peripheral blood B cells from patient DUL (WBC counts 158,000/microliters) were infected in vitro with Epstein-Barr virus (EBV), and CD20+ B cells were cloned into 96 well culture plates with the aid of a cell sorter autoclone device. As shown by GTG-banding and Southern blot analysis, out-growing EBV-positive clones had the same chromosomal abnormalities and identical monoclonal IgH gene rearrangement as the original EBV-genome-negative leukemic B cell clone. Surface marker analysis with a panel of monoclonal antibodies revealed identical patterns on EBV-negative and -positive clones, with the exception of PCA1 (reactive with plasma cells) which was negative on freshly explanted leukemic B cells but positive on EBV-converted clones.

Antigens, Surface↗
PubMed1990

Transient pancytopenia. A report from the International Agranulocytosis and Aplastic Study.

From a population-based study on the incidence of potentially drug-associated blood dyscrasias 28 cases were identified with pancytopenia. Who recovered within 90 days after diagnosis. Early recovery occurred more frequently in patients showing normal or increased cellularity of the bone marrow than in patients with bone marrow hypoplasia. Median recovery times of leukocytes were 14 and 10 days and of platelets 21 and 9 days in patients with and without bone marrow hypoplasia, respectively. Age and sex distribution were similar in both groups. Of 28 patients, 11 reported a period of fever before onset of pancytopenia. Sixteen patients in whom information on drug use was available had taken a median of 4 drugs before the onset of symptoms that were related to pancytopenia. From these results we present the hypothesis that transient pancytopenia with or without marrow hypoplasia can be the expression of the same type of bone marrow injury and that drugs or viral infections should be considered as etiological factors.

Agranulocytosis↗
PubMed1990

Aggressive polychemotherapy for acute myelofibrosis.

Acute myelofibrosis is a rare and still ill-defined disease. Based on morphological observation, immunophenotyping and ultrastructural analysis, we support the assumption that acute myelofibrosis is a malignant disorder mainly of the megakaryocytic lineage and is closely related to acute megakaryocytic/blastic leukaemia. Consequently, the 11 patients reported here were treated with aggressive polychemotherapy with combinations including daunorubicin and cytosine arabinoside and 6-thioguanin or VP16-213. 4 complete remissions, 2 partial remissions and 1 minor response were observed. Duration of aplasia was not significantly prolonged. These findings indicate that the use of aggressive polychemotherapy is feasible in acute myelofibrosis and results in a significant number of remissions.

Acute Disease↗
PubMed1990

Antilymphocyte immunoglobulins stimulate peripheral blood lymphocytes to proliferate and release lymphokines.

Five different preparations of antilymphocyte immunoglobulins (ATG) and antithymocyte immunoglobulins (ALG) with good or little clinical response were compared for their hematopoietic and immunological activities. All ATG/ALG lots demonstrated complement-mediated cytotoxicity on peripheral blood mononuclear cells. They had different titers of antibody specificities against lymphocyte cell membrane antigens. Neither clinically effective nor ineffective lots demonstrated any apparent colony stimulating activity on bone marrow mononuclear cells. Purified Natural Killer cells failed to be stimulated by ATG/ALG in liquid culture. ATG/ALG demonstrated potent T-cell stimulating activity comparable to phytohemagglutinin. This stimulation was blocked by anti-IL-2 receptor monoclonal antibodies, and was inhibited dose-dependently by cyclosporin-A. Some clinically ineffective ATG/ALG lots also stimulated T cells to release lymphokines. The differences in these characteristics among ATG/ALG lots provide some clues to guide further efforts to elucidate a key mechanism of therapeutic effectiveness.

Anemia, Aplastic↗
PubMed1990

[Evaluation of 196 patients with chronic myeloid leukemia based on a standard prognosis model].

The clinical course of 196 patients with chronic myelocytic leukemia (CML) was studied. Prognostic factors were analyzed using a standard prognostic model. From a univariate analysis of patients with nonblastic Philadelphia chromosome-positive CML, splenomegaly, bone marrow fibrosis, percentage of blasts and promyelocytes in the peripheral blood and LDH activity were shown to be factors with a significant negative influence on survival. However, age and the platelet count did not influence survival. The standard prognostic model, generated with the 4 variables (1) percentage of blasts and promyelocytes, (2) spleen size, (3) platelet count and (4) age did not provide a useful representation of risk status in this heterogenous patient population. However, the addition of further variables (LDH, additional chromosomal aberrations, percentage of basophiles/eosinophiles and percentage of bone marrow blasts) to the standard model allowed a separation into 2 patient groups: one with low and the other with intermediate to high risk. Our data support the general validity of the prognostic model; however, the applicability of the model may be compromised in hematologic centers with a heterogenous CML population due to the selection of high-risk patients. In this situation additional risk factors may have to be added to the prognostic formula.

Biomarkers, Tumor↗