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Biomedical subjects

D Hoelzer

Publications and source records attributed to D Hoelzer.

At least 217 records · Page 12Linked to original sources
PubMed1994

[Pneumonia after cytostatic drug therapy].

On account of its high mortality, pneumonia is a particularly feared infectious complication in granulocytopenic patients. One of the main reasons for the fatal outcome is the increasing rate of pulmonary mycoses. Fungal infections offer considerable problems concerning diagnostics and therapy. To improve the prognosis of pulmonary mycoses undelayed diagnostics--even by more invasive methods like bronchoalveolar lavage--and immediate start of antifungal treatment (Amphotericin B/5-Flucytosine are still considered as standard therapy) is necessary. A further problem are gram positive organisms, insufficiently prevented by the standard prophylactic regimens. Particularly pneumonia by Staphylococcus aureus and Viridans-Streptococci may show lethal outcome. The initial treatment with glycopeptides is discussed. Treatment of infections by gram negative organisms however, is less controversial. Finally pneumonias in granulocytopenic patients present serious problems in diagnostics and therapy requiring interdisciplinary co-operation of hematology, radiology, pneumology and microbiology.

Agranulocytosis↗
PubMed1994

Acute leukemia.

Within the past year substantial progress has been made in understanding the molecular changes underlying the development of acute leukemia. Development of molecular probes allowed substantial improvements in the detection of minimal residual disease. Pilot studies underlined the correlation between the expression of the multidrug resistance gene and the likelihood of response to chemotherapy. The expression of mdr-1 apparently correlates with the expression of certain surface antigens like CD34 and CD7, which by themselves are associated with the expression of bcl-2 and poor treatment response. The value of hematopoietic growth factors to overcome drug resistance has not yet been clearly demonstrated in clinical trials, but they seem to reduce early mortality in elderly patients with acute myeloid leukemia when given after chemotherapy. Substantial progress has been made in the understanding of molecular changes in acute promyelocytic leukemia. Combination of all-trans retinoic acid and chemotherapy is the treatment of choice in acute promyelocytic leukemia. Allogeneic bone marrow transplantation proved to be superior in certain high-risk groups of patients with acute leukemia, including those with acute lymphoblastic leukemia with the bcr-abl configuration. The value of allogeneic bone marrow transplantation from related and unrelated donors, as well as the value of autologous bone marrow transplantation, is increasingly defined in randomized trials.

Acute Disease↗
PubMed1993

[Pleomorphic T-cell lymphoma. The diagnostic problems, therapeutic possibilities and infection-induced complications].

A 30-year-old man complained of high fever, resistant to antibiotics, and progressive loss of strength for five weeks. The peripheral blood showed pancytopenia (leucocytes 2200/microliters, platelets 45,000/microliters, haemoglobin 10.7 g/dl). There was also hepatosplenomegaly, abdominal lymph node enlargement, pleural and pericardial effusions and slight excess of lymphocytes in the cerebrospinal fluid. Histological examination of the bone marrow suggested a small-cell pleomorphic T-cell lymphoma, but Hodgkin's disease was also considered. Splenectomy was performed to confirm the diagnosis and treat the pancytopenia. The blood count rapidly returned to normal and the suggestion of Hodgkin's disease was excluded. Intensive chemotherapy (BMFT-ALL protocol) was followed by regression of nearly all the abnormalities, but marrow infiltration persisted. This treatment was discontinued after phase II of induction. After an intercurrent cytomegalovirus infection maintenance treatment with alpha-interferon (up to 5 million units daily) was started. The partial remission remained stable for 22 months. The lymphoma then relapsed but was held in check by further chemotherapy (Dexa-PAMB protocol). For the past 11 months the patient has remained in stable partial remission on treatment with alpha-interferon (3 million units every other day). Frequent infections (sinusitis, diarrhoea, abscess) require close supervision.

Adult↗
PubMed1993

Simultaneous administration of granulocyte colony-stimulating factor (Filgrastim) and induction chemotherapy in acute lymphoblastic leukemia. A pilot study.

The present study was designed to determine whether Filgrastim, a neutrophil-specific hematopoietic growth factor, could be administered simultaneously with intensive induction chemotherapy for adult acute lymphoblastic leukemia (ALL). The effect of Filgrastim on the severity of chemotherapy-induced neutropenia, fever, and infections was assessed in 15 patients treated according to the protocol of the German multicenter ALL (GMALL) trial 04/89. Filgrastim (5 micrograms/kg/day) was given concurrently with successive cycles of cyclophosphamide, cytosine-arabinoside (ara-C), 6-mercaptopurine (6MP), prednisone (PRD), intrathecal methotrexate, and prophylactic cranial irradiation. During the study period the median total duration of severe neutropenia (< 0.5 x 10(9)/l) in 13 evaluable patients was 8 days, individual periods of neutropenia typically were short. Infections occurred in six patients; seven patients remained fever-free during treatment with Filgrastim. We conclude that simultaneous treatment with Filgrastim and chemotherapy in this specific setting is feasible and well tolerated. The efficacy of this treatment approach in terms of overall treatment results requires further testing in a randomized trial.

Adolescent↗
PubMed1993

Analysis of lymphocyte subsets in patients with aplastic anemia before and during immunosuppressive therapy.

To define the contribution of T-lymphocyte subsets in the development of aplastic anemia (AA), T-cell subpopulations including alpha beta T cells, gamma delta T cells, and delta TCS1-positive gamma delta T cells, were analyzed by cytophotometry in the peripheral blood (PB) and bone marrow (BM) of patients with AA before and after 6 weeks of therapy with anti-lymphocyte globulin (ALG), methylprednisolone, and cyclosporin A (CSA). In nine patients with AA a significant decrease of PB- and BM-derived T cells was observed after 6 weeks of therapy as compared with normal controls. At diagnosis, the CD4/CD8 ratio in PB and BM of the patients did not differ from the ratio in the control population; however, a reversed ratio (< 1) was present in PB as well as in BM after weeks of therapy. Interestingly, lymphocytes expressing the gamma delta T-cell receptor (TCR tau delta) were significantly decreased both before (PB 1.2 +/- 0.1%; BM 0.8 +/- 0.1%) and after 6 weeks of therapy (PB 0.7 +/- 0.1%; BM 0.7 +/- 0.1%) as compared with healthy controls (PB 2.4 +/- 0.2%; BM 2.3 +/- 0.2%). However, the proportion of the gamma delta-T-cell subpopulation expressing the delta TCS1 phenotype was markedly increased before (PB 42 +/- 3.5%; BM 31 +/- 3%) and especially after 42 days of therapy (PB 77 +/- 12%; BM 45 +/- 2%) as compared with that in normal subjects (PB 19 +/- 2%; BM 9.7 +/- 0.8%). At present, follow-up is under evaluation to correlate these findings with hematological response. The pathophysiological significance of the observed alterations within the T-cell subsets and especially the gamma delta T-cell populations will require further functional analyses, in particular since delta TCS1-positive gamma delta T cells exhibit autoimmunological capacity.

Anemia, Aplastic↗
PubMed1993

Immunosuppressive effects and clinical response of fludarabine in refractory chronic lymphocytic leukemia.

BACKGROUND: Fludarabine monophosphate is a new adenine nucleoside analogue with a promising efficacy in B-cell chronic lymphocytic leukemia (B-CLL) with response rates, including hematological complete remissions, of 50%-60% in previously treated and 75%-80% in previously untreated patients. PATIENTS AND METHODS: Here, the clinical experience with and side effects of fludarabine are reported in 19 patients with refractory CLL (17 B-CLL, 2 T-CLL). All patients were pretreated with one to four different regimens and had progressive disease. Fludarabine was administered at a dosage of 25 mg/m2 daily for 5 days as a 30-minute intravenous infusion. This course was repeated every fifth week. Dosage and time course were adapted to toxicity. RESULTS: 12/18 (67%) evaluable patients achieved partial remissions (PR), 1/18 (6%) had stable disease (SD) and 5/18 (28%) were progressive. The median duration of partial remission until relapse or death was 6 months. Most responses to fludarabine occurred within two treatment courses. Major toxic effects included infections in 11 patients and nausea in 8 (mainly grade 1). Meanwhile, three patients died of progressive disease and 8 of pneumonias or other infections. Two patients had pneumocystis carinii pneumonias and one an aspergillus pneumonia. The high infection rate may be due not only to hypogammaglobulinaemia or fludarabine-induced granulocytopenia but also to a remarkable decrease of CD4(+)-cells during fludarabine therapy. In one case a tumor lysis syndrome was observed. No CNS toxicity was noted. CONCLUSION: It is concluded that fludarabine is effective even in patients with advanced chronic lymphocytic leukemia refractory to multiple chemotherapy regimens. However, fludarabine has a remarkable suppressive effect on T-lymphocytes, predominantly CD4(+)-lymphocytes. Long-term antibiotic prophylaxis is recommended.

Adult↗
PubMed1993

Induction of TNF-alpha in patients with myelodysplastic syndromes undergoing treatment with interleukin-3.

The study was undertaken to analyse whether the presence or the induction of TNF-alpha, a potent inhibitor of haemopoiesis, might affect the clinical response to treatment with interleukin-3 in patients with myelodysplastic syndromes. A total of 15 patients were treated with IL-3. Baseline serum TNF-alpha levels were elevated in MDS patients (14.2 +/- 2.4 pg/ml) compared to healthy controls (9.1 +/- 1.1 pg/ml). During IL-3 therapy TNF-alpha levels remained unchanged in 3/14 patients in whom platelet counts increased, while in non-responders TNF-alpha levels increased 1.9-fold (P < 0.025). These findings indicate that TNF-alpha not only is induced during IL-3 therapy in MDS patients but that this elevation might be associated with a poor platelet response to therapy.

Adult↗
PubMed1993

Restoration of impaired cytokine secretion from monocytes of patients with myelodysplastic syndromes after in vivo treatment with GM-CSF or IL-3.

Cytokine treatment in patients with myelodysplastic syndrome (MDS) aims to overcome the maturation defects of myeloid lineage cells associated with cytopenia and cellular dysfunction of mature cells. Since phagocytes play a major role in host defense against microbial infection, we investigated cytokine secretion and oxygen radical release (ORR) from peripheral blood monocytes (PBMC) in a total of 16 MDS patients, 12 patients with refractory anemia (RA) and four patients with RA and excess of blasts (RAEB). Interleukin (IL-6), tumour necrosis factor alpha (TNF alpha), IL-1 beta, and IL-8 secretion from monocytes in response to lipopolysaccharide (LPS) was significantly reduced in the 12 patients with RA compared to 12 healthy controls, whereas no difference was seen in ORR. We further assessed cytokine secretion from monocytes of 10 MDS patients before and after therapy with granulocyte-macrophage colony-stimulating factor (GM-CSF), IL-3, or a combination therapy with GM-CSF and cytosine arabinoside (AraC). In all 10 patients, secretion of IL-1 beta, IL-6, and TNF alpha from PBMC increased after cytokine therapy, whereas IL-8 secretion increased only in five patients with GM-CSF or IL-3 therapy receiving a dosage > or = 250 micrograms/m2 per day but decreased in all other patients. ORR increased in all patients on either GM-CSF or IL-3 therapy. These data indicate that the ability of monocytes to secrete secondary cytokines is impaired in MDS patients but can be restored by in vivo administration of GM-CSF and IL-3.

Aged↗
PubMed1993

Cumulative chemotherapy increases mafosfamide toxicity for normal progenitor cells in AML patients: rationale for cryopreserving adapted-dose purged marrow early in first complete remission.

To evaluate whether conditions for adapted dose mafosfamide (mafo) purging vary with accumulating chemotherapy, we studied the sensitivity of bone marrow CFU-GM in a total of 30 patients at different stages of treatment. We determined the dose of 95% CFU-GM growth-inhibition by mafo (ID95) in 23 patients with acute myeloid leukemia (AML) and 7 patients with lymphoid malignancies in first or second complete remission (CR). Sixteen AML patients were studied in early first CR prior to intensive consolidation with high-dose cytarabine (HDAC) and had a median ID95 of 130 (range 90-190) micrograms mafo/ml; the median ID95 in 3 of 7 AML-CR1 and 4 of 7 AML-CR2 patients who previously had HDAC therapy was 75 (range 55-110) micrograms/ml whereas a control group of 7 patients with lymphoid malignancies in CR1 showed a median ID95 of 100 (range 80-160) micrograms/ml. In AML the difference between patients in CR1 prior to HDAC and patients in CR1 after HDAC late consolidation or in CR2 was highly significant (p = 0.0006). We conclude that accumulating chemotherapy pre-treatment, in particular HDAC intensive consolidation, increases mafo toxicity for non-leukemic bone marrow CFU-GM and conversely decreases the mafo concentration applicable for adjusted-dose purging to eliminate residual leukemic cells. Hence mafo purging appears to be more efficient when done in early CR1 compared with later stages of disease.

Adult↗