[Chronic myeloproliferative diseases. New knowledge about well known diseases].
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Humans↗
Biomedical subjects
H Heimpel
Publications and source records attributed to H Heimpel.
Allogenic bone marrow transplantation or chemotherapy for patients with acute myeloid leukemia in first complete remission: a decision analysis approach.
The methodology of decision analysis was originally developed to improve clinical decisions of physicians for individual patients. However, it is also well suited to support consensus procedures. We have used this methodology to analyse the question whether allogeneic bone marrow transplantation (BMT) or consolidation chemotherapy (CCT) should be used as first line postremission treatment in patients with acute myeloid leukemia. Main risk factors relevant for the outcome after BMT and CCT are therapy-related mortality and leukemic relapse, respectively. If the possibility of salvage BMT for patients relapsing after CCT is included, the outcomes of the two strategies come rather close. However, they are clearly different in subtypes of leukemia with high or low risk of relapse, and in patients at high risk for BMT-related mortality. Sensitivity analysis considering the variation of more than one risk factor provides valuable information for decision making for both individual patients and particular subgroups of patients with acute myeloid leukemia.
Antineoplastic Agents↗
Chronic myelogenous leukemia in blast crisis: retrospective analysis of prognostic factors in 90 patients.
Ninety patients with Philadelphia chromosome-positive chronic myelogenous leukemia in blast crisis were reviewed to identify significant prognostic associations. At diagnosis of blast crisis the main clinical, laboratory, and cytogenetic data were recorded and evaluated for prognostic significance. At the time of the analysis 89 patients had died, with a median survival of 11 weeks from diagnosis of blast crisis. Patient characteristics demonstrated in the univariate analysis to have significant association with shorter survival were: thrombocythemia, leukocyte count above 20 x 10(9), Karnofsky index < 50%, nonlymphoid blast cell morphology, cytogenetic clonal evolution, the presence of a double Philadelphia chromosome or trisomy 8, and no response to therapy. In 17 of 59 patients (29%) evaluable for response to therapy a complete or partial remission was achieved. These responders had a significantly longer median survival (25 weeks) as compared with nonresponders (9 weeks). Response to therapy was significantly better in lymphoid blast crisis and in patients without clonal evolution. In a multivariate analysis containing all significant variables of the univariate analysis two parameters retained their prognostic significance: response to therapy and trisomy 8. In spite of the short overall survival in blast crisis, the determination of prognostic factors may be a useful tool for the clinician planning therapy, especially new therapeutic approaches.
Adult↗
The present state of pathophysiology and therapeutic trials in polycythemia vera.
Polycythemia vera shares basic features of pathogenesis with other subtypes of the group of chronic myeloproliferative disorders. All myelopoietic cells are derived from one transformed hemopoietic stem cell. Genetic instability of mitotic clonal cells explains the risk of leukemic transformation, which may be enhanced by cytoreductive treatment. Recent data show that erythroid hyperplasia is not due to erythropoietin hypersensitivity, but rather to abnormal stimulation by other cytokine growth factors. Treatment as established by clinical trials has almost normalized life expectancy in older patients, but the optimal strategy for subgroups of patients is still unknown. For younger patients, new and potentially curative approaches should be investigated.
Animals↗
[Simulation of a mediastinal non-Hodgkin lymphoma recurrence by a diffuse thymus hyperplasia in 18F-FDG PET scan].
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Adolescent↗
New diagnostic imaging procedures in Hodgkin's disease.
A variety of new diagnostic imaging methods have been developed in recent years for patients with Hodgkin's disease in an attempt to improve the detection of spleen and bone marrow involvement within the scope of staging and to discriminate between fibrosis and vital lymphoma after treatment. Somatostatin receptor scintigraphy has been performed only in a small number of patients to date and further studies must be conducted. Magnetic resonance imaging (MRI), as the established method, has shown its potential in several studies in detecting both spleen and bone marrow involvement; MRI investigations, however, only visualize a limited portion of the body and therefore must be performed in areas of clinically suspected disease. Immunoscintigraphy with radiolabeled antibodies is still in a preclinical or at most early clinical stage of evaluation and first results have to be confirmed in a controlled trial. Positron emission tomography (PET) with [18F]fluorodeoxy-glucose (FDG) is a technique which is still not a routine clinical procedure. However, whole-body FDG-PET seems to be a promising method in staging and follow-up of lymphoma, because it offers the unique capability of visualising metabolic activity throughout the entire body. Long-term multicenter studies are necessary to confirm these promising initial data. In the future, wholebody FDG-PET will probably be the technique of choice for immunoscintigraphic studies with radiolabeled monoclonal antibodies and studies on the pharmacokinetics of cytostatic compounds.
Hodgkin Disease↗
When should the clinician suspect a drug-induced blood dyscrasia, and how should he proceed?
Blood dyscrasias account for only a minor fraction of all adverse drug reactions (ADRs), but are relevant because of their relatively high morbidity and mortality. For the majority of drugs, the magnitude of risk is low enough to remain undetected until wider distribution of the drug takes place. Thus, only post-marketing studies, carried out with appropriate methodology and sufficient statistical power, will allow the risk of serious haematological side-effects of new drugs to be ascertained. Publication of carefully studied and thoroughly described single case studies and reports to registries are necessary to detect new associations between drugs and blood dyscrasias, while only large cohort or case-control studies are suited to quantify the risks. Physicians managing a newly detected blood dyscrasia should be aware that it may be drug-induced. They should assess the exact diagnosis, obtain and thoroughly document a detailed exposure history and follow the blood counts after withdrawal of all potentially relevant agents. The recognition and appropriate management of the problem in individual cases is the basis for both effective patient care and the quality of subsequent pharmaco-epidemiological evaluation.
Anemia, Aplastic↗
Essential thrombocythemia and pregnancy.
A review of the literature disclosed 106 pregnancies (preg.) in 57 women with essential thrombocythemia (ET). The success rate (baby alive) was 57% (60 live births/106 preg.), the rate of miscarriage 43% (46 miscarriages/106 preg.). The most frequent complication was spontaneous abortion during the first trimester in 36% (38 abortions/106 preg.). Other complications such as intrauterine death and stillbirth after the 28th week, which occurred in 5% (7/106), premature delivery in 8% (8/106), pre-eclampsia in 4% (4/106), and fetal growth retardation in 4% (4/106) were rarer events. Placental infarction due to thrombosis seems to be the most consistent pathological event as far as the fetus is concerned. Maternal hemorrhage occurred in 4% (3 minor and 1 major bleeding) and only 2 minor maternal thrombotic episodes have been observed. Interestingly, a decline in platelet count has been observed in 14 women and was associated with a successful preg, in 13/14 cases (93%). Aspirin (ASS) was the most frequently used drug in 47 of 93 recorded cases (51%). In 16 evaluable women treated with ASS the live birth rate was higher (12/16 preg., 75%) than for 21 untreated women (9/21 preg., 43%). In 5 cases interferon alpha (IFN) has been used successfully. In summary, 57% of women with ET had a live birth, maternal complications happened in 6%. Promising treatment modalities might be ASS and IFN. However, no definitive answer can be given on the ideal management for women with ET during pregnancy. A European register should be set up.
Abnormalities, Drug-Induced↗
Current aspects of drug therapy in Philadelphia-positive CML: correlation of tumor burden with survival.
One therapeutic concept in chronic myeloid leukemia (CML) assumes that a reduction of clonal genetically unstable cells also reduces the rate of secondary genetic changes and thereby postpones blast crisis. According to this concept, the degree of reduction of tumor burden should correlate with a prolongation of survival. The recent literature, in particular on controlled studies of IFN, hydroxyurea or intensive chemotherapy is reviewed and analyzed with regards to this concept. In chronic phase CML, intensity of treatment as determined by the degrees of WBC suppression, and, more recently, of cytogenetic remission, as measures of the reduction of tumor burden appear to correlate directly with survival. The superiority of a therapeutic regimen in chronic phase CML seems to primarily depend on whether its pharmacology permits a sufficiently high dosage to achieve the necessary reduction of tumor burden. The concept underlies present strategies that try to prolong survival in CML by IFN alone or in combination with intensive chemotherapy, by hydroxyurea, alone or in combination with IFN, and by high-dose chemotherapy followed by autografting.
Antineoplastic Agents, Alkylating↗
Antibodies to interferon-alpha: a novel type of autoantibody occurring after allogeneic bone marrow transplantation.
Antibodies to IFN-alpha have been recognized as a novel type of autoantibody developing after allogeneic BMT. Ninety-six patients undergoing BMT for various hematologic disorders were followed for the presence of spontaneous IFN-alpha antibodies until 12 years after transplantation. Seven of them (7.3%) developed IFN-alpha antibodies occurred late after BMT (> or = 15 months), rose to very high titers in some patients, and persisted for years despite combined immunosuppressive treatment. They were oligo- or polyclonal in nature, predominantly IgG with a broad IgG subclass distribution, and neutralized the antiviral and antiproliferative activity of various natural and recombinant IFN-alpha types including the patients' endogenous IFN-alpha in vitro. All antibody-positive recipients suffered from chronic GVHD (n = 5) or chronic viral hepatitis (n = 2), but the only significant association was with prior severe aplastic anemia (3/9, 33%; P = 0.022). There was no discernible HLA association of IFN antibody development. Although the clinical relevance of the IFN-alpha antibodies is uncertain they may interfere with cellular defence mechanisms and immune regulation after BMT.
Adolescent↗
Randomized study of the combination of hydroxyurea and interferon alpha versus hydroxyurea monotherapy during the chronic phase of chronic myelogenous leukemia (CML Study II). The German CML Study Group.
It is the long-term goal of the German CML Study Group and of the Süddeutsche Hämoblastosegruppe (SHG) to improve survival of patients with chronic myelogenous leukemia (CML). In a first randomized study (CML Study I) monotherapies with hydroxyurea or interferon alpha (IFN-alpha) were compared with a standard busulfan regimen with regard to duration of the chronic phase and survival. The main results of this study were published, 1-3 and a long-term follow up is planned. In a second randomized study the effect of the combination of IFN-alpha and hydroxyurea versus hydroxyurea monotherapy on survival is being investigated. This paper provides a first preliminary report on the study concept, patient recruitment, state of documentation and initial patients' characteristics 9 months after closure of the study.
Adult↗
Current controversies on the role of interferon-alpha for therapy of chronic myeloid leukemia.
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Antineoplastic Agents↗
Long-term interleukin-3 and intensive immunosuppression in the treatment of aplastic anemia.
We have assessed in a phase I/II clinical study the tolerability and efficacy of long-term application of recombinant human interleukin-3 (rh-IL-3) in combination with antithymocyte globulin (ATG) and cyclosporin A (CSA) in 13 patients with aplastic anemia who were refractory to or relapsed after previous immunosuppressive treatment. Four cohorts of three patients were consecutively enrolled so that they received rh-IL-3 on days 9, 6, 3 and 1 after start of ATG/CSA treatment. Yeast-derived recombinant human IL-3 was administered by daily subcutaneous injection until day 90 at a dosage of 250 micrograms/m2. Long-term application of rh-IL-3 was well tolerated. The combination of rh-IL-3 with immunosuppression did not modify the known toxicities of ATG and CSA. Incidence and severity of rh-IL-3-related adverse events was less than in other phase I/II trials of rh-IL-3 as single-agent therapy. One might speculate that co-medication with CSA alleviates rh-IL-3-induced side effects. Three of eight patients with refractory AA and all four patients with relapsed AA responded to the combined treatment within four months. The median time to response was 91.5 days. There was evidence for an rh-IL-3-dependent response in two patients. Long-term rh-IL-3 did not cause stem cell exhaustion. One patient died early during the course of the study from EBV-driven lymphoproliferative disease. Two patients developed acute myeloid leukemia 4 and 22 months after cessation of rh-IL-3. In conclusion, long-term rh-IL-3 in combination with immunosuppression is well tolerated. The response rate to the combined treatment in refractory and relapsed AA was high. Recombinant human IL-3-dependent responses suggest efficacy. A prospective randomized trial comparing immunosuppression alone versus a combination with rh-IL-3 is warranted.
Adolescent↗
[Chronic myeloid leukemia--latest aspects and practical progress in recent years].
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Adult↗
[Talking medicine contra alternative medicine?].
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Communication↗
Emergence of CD52-, phosphatidylinositolglycan-anchor-deficient T lymphocytes after in vivo application of Campath-1H for refractory B-cell non-Hodgkin lymphoma.
CD52 is a phosphatidylinositolglycan (PIG)-anchored glycoprotein (PIG-AP) expressed on normal T and B lymphocytes, monocytes, and the majority of B-cell non-Hodgkin lymphomas. We observed the emergence of CD52- T cells in 3 patients after intravenous treatment with the humanized anti-CD52 monoclonal antibody Campath-1H for refractory B-cell lymphoma and could identify the underlaying mechanism. In addition to the absence of CD52, the PIG-AP CD48 and CD59 were not detectable on the CD52- T cells in 2 patients. PIG-AP-deficient T-cell clones from both patients were established. Analysis of the mRNA of the PIG-A gene showed an abnormal size in the T-cell clones from 1 of these patients, suggesting that a mutation in the PIG-A gene was the cause of the expression defect of PIG-AP. An escape from an immune attack directed against PIG-AP+ hematopoiesis has been hypothesized as the cause of the occurrence of PIG-AP-deficient cells in paroxysmal nocturnal hemoglobinuria (PNH) and aplastic anemia. Our results support the hypothesis that an attack against the PIG-AP CD52 might lead to the expansion of a PIG-anchor-deficient cell population with the phenotypic and molecular characteristics of PNH cells.
Antibodies, Monoclonal↗
[The assessment of therapeutic success in chronic myeloid leukemia].
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Bone Marrow Transplantation↗
Autologous platelet transfusion in alloimmunized patients with acute leukemia.
Seventy-eight transfusions of autologous platelets were given to eight alloimmunized patients receiving curative chemotherapy for acute leukemia. Platelets were collected at regeneration of hematopoiesis after a chemotherapy cycle, cryopreserved with 5% dimethylsulfoxide in liquid nitrogen, and retransfused during bone marrow aplasia following the next treatment cycle. The in vitro platelet recovery after freezing, thawing, and washing was 85 +/- 4%. The in vivo corrected count increment 1 h after autologous platelet transfusions was 11 +/- 5 x 10(9)/l. With the exception of moderate urticaria and slight nausea each after one transfusion, no immediate or chronic side effects occurred. The bleeding time was shortened and hemorrhage during bone marrow aplasia was prevented in all alloimmunized patients by autologous platelet transfusions.
Acute Disease↗