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H Heimpel

Publications and source records attributed to H Heimpel.

At least 145 records · Page 8Linked to original sources
PubMed1989

Clonal analysis of myelodysplastic syndromes: evidence of multipotent stem cell origin.

Restriction fragment length polymorphisms (RFLPs) of the X-chromosome genes hypoxanthine phosphoribosyl transferase (HPRT) and phosphoglycerate kinase (PGK) were studied in 34 female patients with primary myelodysplastic syndromes (MDS). Twelve patients (35%) were heterozygous at the HPRT or PGK loci for BamHI or BglI RFLPs, respectively. In eight patients showing PGK polymorphisms, clonality was determined by X-chromosome inactivation analysis. These included patients from different morphologic subtypes: four with refractory anemia (RA), two with RA and ring sideroblasts (RARS), one patient with RA with excess of blasts (RAEB), and one with chronic myelomonocytic leukemia (CMML). A monoclonal pattern of X-chromosome inactivation was observed in seven cases. In a further case characterized by bone marrow hypoplasia, peripheral blood (PB) leukocytes were polyclonal in origin. Following low-dose cytarabine therapy, reversion to polyclonal hematopoiesis was observed in a case of RAEB indicating the presence of residual normal hematopoietic stem cells with the capacity for marrow reconstitution. The clonal relation of lymphoid and granulocyte/monocyte lineages was studied directly in two cases of CMML exhibiting somatic mutations of N-ras or Ki-ras oncogenes. By selective oligonucleotide hybridization to ras gene sequences amplified in vitro by the polymerase chain reaction, a mutated ras allele was demonstrated in PB granulocytes, monocytes, and B and T lymphocytes of both patients. We conclude that MDS arise from a multipotent hematopoietic stem cell with the potential for myeloid and lymphoid differentiation.

Adult↗
PubMed1989

Allogeneic bone marrow transplantation for myelodysplastic syndromes (MDS).

In the literature 63 patients with myelodysplastic syndromes (MDS) are reported who were treated with syngeneic or allogeneic bone marrow transplantation. 62 patients were prepared for BMT with TBI containing regimens or Busulfan/Cyclophosphamide. GvHD prophylaxis was heterogenous. 33/63 patients are alive and well between 4 and 132 months after BMT. 23/63 patients died due to GvHD (n = 6), interstitial pneumonitis (n = 6), other infections (n = 4), toxicity of the preparative regimen (n = 5) or graft failure (n = 2). 9/63 patients relapsed between 2 and 98 (in median 6) months after BMT. There seems to be a correlation between the subtype of the MDS and the relapse rate: only 1/18 patients with RA/RARS relapsed compared to 7/42 patients with RAEB/RAEB-T. These results indicate that marrow transplantation can induce long term survival and may result in cure of patients with MDS.

Adolescent↗
PubMed1988

Different antitumor mechanisms of interferon-alpha in the treatment of hairy cell leukemia and renal cell cancer.

There is increasing evidence for the therapeutic effectiveness of Interferon-alpha (IFN-alpha) in malignant diseases. However, the antitumor mechanisms of IFN-alpha are not known. Using two examples, hairy Cell leukemia (HCL) and renal cell cancer (RCC), it is shown that the requirements for successful IFN-alpha therapy of HCL and RCC are different. In HCL low doses of IFN-alpha are sufficient to treat the disease. The reduction of hairy cells in peripheral blood is detectable within the first week of treatment. The endogenous IFN-alpha production in these patients is impaired as demonstrated by the lack of IFN-alpha induction and by low levels of 2-5 oligoadenylate synthetase in peripheral blood mononuclear cells. A possible reason for deficient endogenous IFN-alpha production is the lack of monocytes in HCL patients. It is likely that therapy with low doses of IFN-alpha substitutes for the endogenous IFN-alpha deficiency. In RCC comparatively high doses of IFN-alpha are necessary for a clinical response. There may be differences between the effectiveness of natural and recombinant alpha interferons. High doses given within a week seem to be more important than high single doses, which therefore suggests the need of daily treatment. Responses of RCC to IFN-alpha therapy are usually seen several months after the beginning of therapy. These differences in the effectiveness of IFN-alpha therapy for HCL and RCC suggest that IFN-alpha acts differently in the treatment of each disease.

2',5'-Oligoadenylate Synthetase↗
PubMed1988

[Bone marrow transplantation as therapy in chronic myeloid leukemia].

Between April 1982 and December 1986, HLA-identical bone marrow transplantations were performed on 25 patients with Philadelphia chromosome-positive chronic myelocytic leukaemia (CML), 18 in the chronic phase, 7 in acceleration or blast crisis. Twelve of the 18 patients (67%) in the chronic phase are still alive a median period of 570 days after transplantation, but only two of the seven (29%) in acceleration or blast crisis a median period of 227 days after transplantation (P less than 0.025). The duration of the chronic phase was of great importance for survival after transplantation: 86% of patients in the chronic phase for less than two years survived, but all patients in the chronic phase for over two years died (P less than 0.001). CML relapses occurred in one patient in a late chronic phase and in two in an advanced stage of the disease. These results confirm the unfavorable outcome of bone marrow transplantation in the accelerated phase or blast crisis, as well as in the late chronic phase. Since at present there are no reliable risk factors for the occurrence of acceleration or blast crisis, bone marrow transplantation should be undertaken as early as possible in the chronic phase of CML.

Adolescent↗
PubMed1988

Blast crisis of Philadelphia chromosome-positive chronic myelocytic leukemia (CML). Treatment results of 69 patients.

We have studied the clinical courses of 69 patients with blastic crises of Philadelphia chromosome positive CML to identify parameters that were associated with an increased response rate or survival. Cytogenetic analysis at the time of blastic transformation revealed additional chromosome changes in 70% of the patients tested. Bone marrow fibrosis was detected in 58% of evaluable patients. Lymphoblastic transformation was seen in 28% of the patients tested with cell surface marker analysis. The value of 5'-nucleotidase as a marker for distinguishing lymphoid from non-lymphoid blast crisis was confirmed. Of 57 evaluable patients, 23 (40%) responded to therapy (CR/PR longer than 14 days). Median survival was 75 days. Longer survival was related to the following factors: Ph1-chromosome as the only detectable cytogenetic abnormality; lymphoblastic transformation; no bone marrow fibrosis; high percentage of blasts and promyelocytes in the bone marrow, and response to therapy. No prognostic significance was associated with age, sex, Tdt, LDH, spleen size, duration of the chronic phase of the disease, white blood cell count, Hb, platelet count and percentages of basophils, eosinophils, erythroblasts and blasts and promyelocytes in the peripheral blood. These data confirm the poor prognosis of patients with blastic crisis of CML treated by conventional chemotherapy.

Adult↗
PubMed1988

Haemolytic anaemia as initial manifestation of Wilson's disease.

Common manifestations of Wilson's disease are disorders of the liver and brain. A rare complication of this inherited disease is acute intravascular haemolytic anaemia. We report the case of a 33-year old female patient who was admitted to the hospital with acute haemolysis as the initial symptom of Wilson's disease. The haemolysis preceded the definitive diagnosis by 20 months. It is concluded that in any case of unclear haemolytic anaemia, especially in adolescents or in young adults, Wilson's disease should be considered.

Acute Disease↗
PubMed1988

Antimicrobial prophylaxis in neutropenic patients after bone marrow transplantation.

Fourty-one patients with haematological malignancies or severe aplastic anaemia underwent allogeneic or syngeneic bone marrow transplantation and received one of two forms of infection prophylaxis while granulocytopenic: total decontamination in strict reverse isolation (ITD, 26 patients) or selective decontamination of the digestive tract with barrier nursing (SD, 15 patients). The patients were evaluated for infection acquisition, fever days, days on systemic antibiotics and granulocyte transfusions from 48 hours after the beginning of the decontamination procedure until 1,000 granulocytes/microliter have been reached. Ten of 26 patients of the ITD group remained free of febrile episodes and infections, whereas all patients of the SD group acquired infections (p less than 0.001). During granulocytopenia patients of the ITD group had fewer fever days, were less frequently on systemic antibiotics and received fewer granulocyte transfusions as compared with the SD group. Both methods were obviously very effective in preventing gram-negative infections, infections caused by Staphylococcus aureus and infections due to yeasts or fungi. No death due to infection occurred in either group. However, the data of this study provide evidence that ITD is a more effective antimicrobial prophylaxis in bone marrow transplant recipients than SD.

Adolescent↗
PubMed1988

Induction of myeloperoxidase in five cases of acute unclassified leukaemia.

For further analysis of their lineage affinity the differentiation capacity of five cases of acute unclassified leukaemias were studied in vitro using 5 nM 12-O-tetradecanoyl-phorbol-13-acetate as an inducing agent. After 4 d in vitro a co-expression of both myeloid and early B-lymphoid or myeloid and early T-lymphoid antigens on the same population of cells was found. While ultrastructural analysis of the blasts prior to culture revealed the morphology of undifferentiated blasts without any specific endogenous peroxidase activity, the cultured blasts displayed monoblastic features and myeloperoxidase activity after 4 d in vitro. Since this type of peroxidase is highly specific for the myelomonocytic lineage the data indicate myelomonocytoid differentiation of all five cases studied. The co-expression of lymphoid as well as myeloid antigens and myeloperoxidase by the same blasts after culture could be indicative of bilineage differentiation capacity characterizing the original blasts as bipotential progenitor cells.

Acute Disease↗
PubMed1988

Idiopathic thrombocytopenic purpura and autoimmune hemolytic anemia in Hodgkin's disease.

Idiopathic thrombocytopenic purpura (ITP) and Coombs' positive hemolytic anemia (AIHA) were found, respectively, in 5 (1%) and 1 (0.2%) of 492 patients with Hodgkin's disease (HD). 33 cases of ITP associated with HD reported in the literature are reviewed. Of our cases, ITP was coincident with the diagnosis of HD in 1 patient. In another patient ITP preceded the diagnosis of HD by 41 months and in the remaining 3 patients the diagnosis of ITP was established after they had been successfully treated for HD. A herpes zoster infection preceded ITP by 1 month in 1 patient and another had herpes zoster at the time of diagnosis of ITP. AIHA had preceded the diagnosis of HD by 8 months in 1 case. In patients with ITP the prognosis seems to be related only to the status of the underlying HD.

Adolescent↗
PubMed1988

T-cell depletion versus methotrexate as GvHD-prophylaxis in allogeneic bone marrow transplantation for leukaemia.

Graft-versus-host disease (GvHD) prophylaxis using methotrexate (23 patients) and T-cell depletion of the graft (40 patients) was compared in 63 allogeneic bone marrow transplantations (BMT) for leukaemia. T-cell depletion significantly reduced (p = 0.001) the incidence of GvHD from 68% to 11% and the GvHD-associated mortality from 79% to 5%. Actuarial disease-free survival for low-risk patients (57% with T-cell depletion and 47% with MTX) was not significantly improved, due to graft failure and possibly due to a higher leukaemic relapse rate after T-cell depletion. Prevention of graft failure after T cell-depleted BMT is essential and could also reduce the risk of leukaemic relapse by improved engraftment.

Acute Disease↗
PubMed1988

[Intensive combined therapy for high-risk ALL patients].

In the risk-adapted multicenter trial (02/84) for adult ALL the effectiveness of a consolidation therapy consisting of VM26 and Ara-C for high-risk patients was tested. Out of a total of 442 patients in the study, 79.2% achieved a complete remission. For the 182 high-risk patients the median remission duration is 17 months and the probability of being in continuous complete remission (CCR) is 34%. Improved results were found for elderly ALL patients between 35 and 65 years of age, whose median remission duration and CCR rate are 19 months and 40% respectively, compared to 15 months and 26% in the former study 01/81. The consolidation therapy has apparently also benefited patients with the immunological subtype c-ALL, for whom the CCR rate at 3 years is 53% in comparison to the previous value of 34%.

Adolescent↗
PubMed1988

Reproductive and endocrine gonadal functions in adults following multidrug chemotherapy for acute lymphoblastic or undifferentiated leukemia.

The impact of aggressive chemotherapy on reproductive and endocrine gonadal function was studied in ten women and ten men with acute lymphoblastic leukemia (ALL) or acute undifferentiated leukemia (AUL) in complete remission. Hormone determinations, sperm analyses, measurements of basal body temperature, and interviews with a standardized questionnaire were used for diagnostic evaluation. Elevated serum follicle-stimulating hormone (FSH) levels and azoospermia were seen in all male patients after completion of induction and consolidation therapy as a result of germ cell and stem cell loss. Recovery of spermatogenesis, as indicated by normalization of serum FSH values and sperm density, occurred in the second year of maintenance therapy in all men. Serum testosterone and luteinizing hormone (LH) values remained within normal limits indicating resistance of Leydig cells to chemotherapy. All female patients showed normal serum levels of gonadal steroids and gonadotropins, as well as an adequate increase in basal body temperature after intensified chemotherapy, indicating intact follicle function and ovulation. Most patients reported normal sexual functions after induction and consolidation therapy. These results demonstrate that multidrug chemotherapy induced significant impairment of reproductive function in all male patients with early and complete recovery. In contrast, endocrine gonadal function was unaffected in men treated with ALL/AUL. In female patients, neither reproductive nor endocrine functions were influenced by aggressive chemotherapy.

Acute Disease↗
PubMed1988

Norfloxacin for prevention of bacterial infections during severe granulocytopenia after bone marrow transplantation.

48 patients treated with bone marrow transplantation (BMT) received the quinolone norfloxacin (NOR) in a total decontamination (TD-NOR, n = 36) or selective decontamination (SD-NOR, n = 12) regimen and were compared with a historical control group of 48 BMT patients receiving oral non-absorbable antibiotics (TD-NAA, n = 31 and SD-NAA, n = 17). 17/36 patients (47%) of group TD-NOR and 16/31 patients (52%) of group TD-NAA remained free of febrile episodes and infections. 4/12 patients (33%) of group SD-NOR and only 1/17 patients (6%) of group SD-NAA remained free of fever and infections. The use of norfloxacin in selective decontamination resulted in a statistically significant lower incidence of fever days than in patients receiving SD-NAA (p less than 0.001). These data suggest that norfloxacin may replace non-absorbable antibiotics in total and in selective decontamination regimens used for infection prophylaxis in BMT recipients.

Adolescent↗
PubMed1988

[Recombinant tissue-type plasminogen activator: pharmacokinetics and effect on the hemostasis system of the human].

The in vitro interaction of rt-PA with the coagulation and fibrinolytic system was investigated. After addition of rt-PA to citrated plasma prolonged clotting times for prothrombin time, partial thromboplastin time and thrombin time, decreased activities of individual clotting factors and decreases of alpha 2-antiplasmin, plasminogen and fibrinogen were measured. The alterations were dependent on incubation times and rt-PA concentrations and were mainly observed at rt-PA concentrations exceeding therapeutic levels. These in vitro phenomena could be prevented to different degrees using various inhibitors. Because of interferences with some fibrinolytic and coagulation assays aprotinin was only of limited utility as an inhibitor. PPACK lengthened clotting time assays based on generation of endogenous thrombin, but did not affect fibrinolytic assays. The most versatile inhibitor was a specific anti-rt-PA antibody which enabled correct measurements of all fibrinolytic and most coagulation assays. It is concluded that high rt-PA levels in samples taken from patients during fibrinolytic therapy induce in vitro artefacts which can be prevented by the use of suitable inhibitors. In 8 healthy male volunteers aged 32 +/- 7 years pharmacokinetic investigations were done. After infusion of 0.25 mg rt-PA/kg bw mean maximal plasma levels were 970 +/- 130 ng/ml. The elimination of rt-PA from plasma was fitted to a two compartment model and was characterized by two half lives of t1/2 alpha = 3.3 and t1/2 beta = 26 minutes.

Adult↗
PubMed1988

Concentration of bone marrow mononuclear cells for in vitro treatment and AB0-incompatible transplantation: a rapid and reproducible procedure using the haemonetics V50 cell separator.

Forty-nine allogeneic and 14 autologous bone marrow grafts were processed with the Haemonetics V50 cell separator (Haemonetics Corp., Braintree, USA) for in vitro treatment with antibodies and cryopreservation respectively. The concentration of hemopoietic progenitor cells was performed without any sedimentation or density gradient agents. The recovery is given in percent (mean +/- sd) of the original marrow values: mononuclear cells (MNC) 74 +/- 10%, polymorphonuclear cells (PMC) 48 +/- 17%, red blood cells (RBC) 12 +/- 5%, granulocyte/monocyte progenitors (CFU-GM) 83 +/- 36%, and erythroid progenitors (BFU-E) 78 +/- 38%. The recovery of nucleated cells (NC) was 90 +/- 13% and the viability 82 +/- 11% after cryopreservation. The technique described provides a simple, rapid and efficient preparation of large bone marrow volumes for in vitro treatment and AB0-incompatible transplantation.

Blood Grouping and Crossmatching↗
PubMed1988

Lymphokines as inhibitors of hematopoietic cell proliferation.

Although the identification of lymphokines negatively affecting hematopoiesis is rapidly increasing, efforts to precisely define their action even in vitro have become more and more complicated. Studies of lymphokine abnormalities in aplastic anemia exemplify the modest contribution of experimental hematology to permit access to possible pathogenic mechanisms of hematopoietic failure syndromes. Nevertheless, these results help in the interpretation of clinical observations and to develop alternative therapeutic concepts.

Animals↗
PubMed1988

Prognostic significance of additional cytogenetic abnormalities at diagnosis of Philadelphia chromosome-positive chronic granulocytic leukemia.

Of 661 patients with Philadelphia chromosome (Ph)-positive, nonblastic chronic granulocytic leukemia, 58 had cytogenetic abnormalities in addition to the Ph at the time of diagnosis. Twenty patients had reduplication of the Ph in one or more metaphases. Twenty-one patients with a single Ph exhibited hyperdiploidy in one or more metaphases. Eleven patients had two or more hypodiploid metaphases as their only numerical abnormality. The remaining six patients had a variety of abnormalities. Many patients had more than one type of abnormality. Survival of patients in the different subgroups was similar, but these 58 patients had a shorter course than the 603 patients without additional cytogenetic abnormalities (P less than .02). Survival curves for the two populations did not diverge until the 2-year point, after which the annual death rate among patients with additional cytogenetic abnormalities was approximately 40% higher than that of patients without such abnormalities. The two populations had similar relative risk values according to a hazard ratio formula previously described by the International CGL Prognosis Study Group. Thus, they would have been expected to have essentially identical survival curves. We conclude that the presence of additional cytogenetic abnormalities at the time of diagnosis constitutes an independently significant prognostic feature with an unusually delayed influence on survival.

Adolescent↗