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Biomedical subjects

K H Pflüger

Publications and source records attributed to K H Pflüger.

At least 37 records · Page 2Linked to original sources
PubMed1993

Sustained trilineage response in a patient with ALG-resistant severe aplastic anaemia after treatment with G-CSF, erythropoietin and cyclosporin A: association of recovery with marked elevation of serum alkaline phosphatase.

Aplastic anaemia is characterized by multilineage bone marrow failure resulting in pancytopenia. We have successfully treated a young woman with severe aplastic anaemia (SAA) who was resistant to antilymphocyte globulin (ALG) and corticosteroids, with a combination therapy consisting of erythropoietin, cyclosporin A and granulocyte-colony stimulating factor (G-CSF). The patient received erythropoietin and CSA for a period of 10 months without success before G-CSF treatment was started. After 6 weeks of G-CSF therapy she responded with a sustained trilineage recovery. This suggests that immunosuppression together with haemopoietic growth factors may be an effective treatment in patients with SAA who are ALG resistant and cannot be treated by BMT.

Adolescent↗
PubMed1993

Altered expression of the human retinoblastoma gene in monocytic leukaemias.

Inactivation of the retinoblastoma growth suppressor gene (RB) is responsible for the development of retinoblastomas and occurs frequently in osteosarcomas and small cell lung carcinoma. Knowledge about the involvement of RB in the pathogenesis of myeloid leukaemias is still scarce. In this study we looked at the expression of the retinoblastoma gene product (p105) in 20 primary myelomonocytic and monoblastic leukaemias by Western blotting and immunocytochemistry using the anti-p105-monoclonal antibody PMG3-245. We found absence of or barely detectable levels of p105 in 11 patients (55%). Absence of or low levels of p105 were correlated with a higher leucocyte count at presentation (133 x 10(9)/l v 83 x 10(9)/l) and with the occurrence of extramedullary leukaemia (8/10 v 2/10). We conclude that abnormal expression of RB with absence of p105 or strongly reduced p105 levels occurs frequently in myelomonocytic and monoblastic leukaemias and that this may be correlated with a more malignant course of the disease.

Aged↗
PubMed1993

Biochemical characterization of a novel autocrine transferrin-like growth factor in acute myeloblastic leukemia.

Serum-free conditioned media (CM) of acute myelogenous leukemia cell lines induce growth stimulation of other leukemic cell lines. A transferrin (Tf)-like iron binding kD 50 protein was found to be the main growth factor of these CM's. Purification and further characterization of this protein was performed by chromatographic methods, SDS-PAGE, peptide mapping and amino acid analysis. In addition m-RNA of leukemic cell lines was analysed by Northern blot analysis with oligonucleotide probes specific for human serum Tf and melanotransferrin (p97) respectively. No hybridization signals for these probes have been detected. Biochemical results show significant differences between human serum Tf and kD 50 growth factor with respect to retention time on reversed phase FPLC, pattern of digestion peptides in SDS-PAGE and amino acid composition, which suggests, that this protein is an additional tumor associated member of the transferrin superfamily.

Amino Acids↗
PubMed1992

[Recurrence of Hodgkin's disease after advanced primary stages. German Hodgkin's Study Group].

In a multicentre study on the treatment of Hodgkin's disease, 88 out of 297 patients with primary advanced stages IIIB/IV failed to respond to alternating COPP/ABVD chemotherapy +/- radiotherapy. They may be broken down as follows: tumour progression under current therapy (PD) 23/28, partial remission at the end of treatment (PR) 28/88, early nodal recurrence 13/88, late nodal recurrence 15/88, extranodal recurrence 7/88, unclear localisation 1/88. Thirty-six months after noting failure of treatment, 45% of all patients were still alive. The prognosis was poorest in the case of primary PD. Only 1/23 of these patients experience lasting complete remission thanks to salvage treatment (cCR). Eleven patients with an exclusively nodal recurrence experienced a cCR on treatment with radiation alone, and may be considered a low-risk recurrence group. For a high-risk recurrence group (n = 57), indication for high-dose chemotherapy with subsequent autologous bone marrow transplantation (HDC/ABMT) should have been recognized on the basis of the present definition. The survival probability of these patients, who only received conventional salvage treatment, was 38% after 30 months (95% confidence limit, 22 to 54%). These data would not appear to be appreciably poorer than those reported in the literature for comparable patients receiving HDC/ABMT. Only a randomized comparison would be capable of showing whether HDC/ABMT is superior to high-dose conventional chemotherapy with haematopoietic growth factors. It is proposed that such a therapeutic trial should be initiated as soon as possible.

Adolescent↗
PubMed1992

[Osteoporotic vertebral fractures in systemic mastocytosis without skin involvement].

Radiological investigation of the vertebral column in two patients with low-back pain (53-year-old woman and a 52-year-old man) revealed unusually marked osteoporosis and sintering fractures of the 3rd, and 1st and 4th lumbar vertebrae, respectively. Biochemical tests failed to provide any evidence about metabolic or endocrinological abnormality. Iliac crest biopsy showed mastocytosis. There were no skin changes in either patient. Additional examinations excluded involvement of any internal organs. Despite treatment with calcium, sodium fluoride, vitamin D3 and calcitonin in the woman, and aspirin and chromoglycinic acid in the man the osteoporosis has slowly progressed during the last 7 and 5 years, but the disease has remained limited to the skeletal system. In a case of unusually marked osteoporosis, mastocytosis should be included in the differential diagnosis even in the absence of urticaria pigmentosa.

Aspirin↗
PubMed1992

Pharmacokinetics of high-dose etoposide after short-term infusion.

The pharmacokinetics of high-dose etoposide (total dose, 2100 mg/m2 divided into three doses given as 30-min infusions on 3 consecutive days) were studied in ten patients receiving high-dose combination chemotherapy followed by autologous bone marrow transplantation. In addition to etoposide, all subjects received 2 x 60 mg/kg cyclophosphamide and either 6 x 1,000 mg/m2 cytosine arabinoside (ara-C), 300 mg/m2 carmustine (BCNU), or 1,200 mg/m2 carboplatin. Plasma etoposide concentrations were determined by 252Cf plasma desorption mass spectrometry. In all, 27 measurements of kinetics in 10 patients were analyzed. According to graphic analysis, the plasma concentration versus time data for all postinfusion plasma etoposide values were fitted to a biexponential equation. The mean values for the calculated pharmacokinetic parameters were: t1/2 beta, 256 +/- 38 min; mean residence time (MRT), 346 +/- 47 min; AUC, 4,972 +/- 629 micrograms min ml-1 (normalized to a dose of 100 mg/m2); volume of distribution at steady state (Vdss), 6.6 +/- 1.2 l/m2; and clearance (CL), 20.4 +/- 2.4 ml min-1 m-2. A comparison of these values with standard-dose etoposide pharmacokinetics revealed that the distribution and elimination processes were not influenced by the dose over the range tested (70-700 mg/m2). Also, the coadministration of carboplatin did not lead to significant pharmacokinetic alterations. Although plasma etoposide concentrations at the time of bone marrow reinfusion (generally at 30 h after the last etoposide infusion) ranged between 0.57 and 2.39 micrograms/ml, all patients exhibited undelayed hematopoietic reconstitution.

Adult↗
PubMed1992

Felty's syndrome: favorable response to granulocyte-macrophage colony-stimulating factor in the acute phase.

We report a case of Felty's syndrome in which infectious complications due to severe neutropenia could be overcome by short-term treatment with recombinant human granulocyte-macrophage colony-stimulating factor (GM-CSF, 7 micrograms/kg/day s.c.). Leukocyte counts rose from 1,050/mm3 at presentation to 4,470/mm3 after 15 days of treatment. A flare-up of arthritis was not noted. Defects in granulocyte function and clinical improvement prior to leukocyte rise suggest that the beneficial effect of GM-CSF is mainly due to an improvement of granulocyte function.

Acute Disease↗
PubMed1992

Concomitant primary low grade non-Hodgkin's lymphoma of the spleen and breast carcinoma.

A case is described of a 71 year old woman with scirrhous breast cancer and multiple hypoechogenic lesions in the spleen. The patient was treated successfully by mastectomy and splenectomy. Morphologic examination of the spleen showed a primary, centroblastic-centrocytic, low grade non-Hodgkin's lymphoma. Eight months after splenectomy the patient still remains in complete remission.

Aged↗
PubMed1991

Hematopoietic reconstitution after high-dose chemotherapy and autologous nonfrozen bone marrow rescue.

The kinetics of marrow engraftment were analyzed in 50 patients with acute leukemia (21), malignant lymphoma (15), and solid tumors (14) after high-dose multiagent chemotherapy followed by autologous bone marrow transplantation (ABMT) with nonfrozen bone marrow. Unseparated heparinized whole bone marrow was stored in 10% CPDA1 at 4 degrees C for 72 h, then filtered and reinfused. The median number of nucleated cells reinfused was 1.6 x 10(8)/kg (range 0.5-3.8 x 10(8)/kg). All patients had a full hematopoietic reconstitution. Median time to achieve a neutrophil count greater than 500/microliters was 20 days (range 12-39) and median time to achieve an unsupported platelet count greater than 20,000/microliters was 20 days (range 10-55). The main factor associated with delayed engraftment was the number of prior chemotherapy cycles. We conclude that high-dose chemotherapy with nonfrozen ABMT is a safe procedure, without the requirement for costly cryopreservation facilities.

Acute Disease↗
PubMed1990

Treatment of refractory Hodgkin's disease with high-dose cytosine arabinoside and mitoxantrone in combination. Results of a clinical phase II study of the German Hodgkin Study Group.

In the present study, the activity and side effects of high-dose cytosine arabinoside (HD-Ara-C) in combination with mitoxantrone (mitox) (HAM) was evaluated in 32 heavily pretreated patients with refractory Hodgkin's disease. Therapy consisted of HD-Ara-C 3 g/m2 every 12 hours days 1 and 2 and mitox 10 mg/m2/d days 3 to 5. In subsequent steps, HD-Ara-C was escalated to six and eight doses for 3 and 4 days, respectively, and mitox to four doses on days 2 to 5. Thirty-two patients 17 to 55 years of age entered the study. Twenty-five cases presented with extranodal disease and disseminated organ involvement and 21 revealed systemic (B) symptoms. Eighteen patients (56%) responded with five complete and 13 partial remissions, ten patients (31%) had refractory disease, and four patients died from infections during treatment-induced cytopenia. The predominant toxicity was severe myelosuppression in all patients with major infections occurring during 55% of treatment courses. Ten of the responding 18 patients underwent subsequent autologous (n = 9) or allogeneic bone marrow transplant (BMT). Seven of these cases are currently alive at 5+ to 22+ months, six of them without evidence of disease. Among the remaining eight patients not receiving BMT, three are alive at 6+ to 19+ months from the initiation of HAM, two of them in ongoing remissions of 2+ and 5+ months' duration. Two patients died from transplant-related complications and six patients succumbed to progressive disease following relapse. The median survival for all treated patients is 6.2 months. These data indicate that HAM has a significant activity in refractory Hodgkin's disease. However, the substantial side effects and the lack of an obvious superiority to alternative, less intensive regimens limits the further application of the two-drug combination in its present form. Modifications in timing and dosage and the addition of hematopoietic growth factors will be evaluated in subsequent trials.

Adolescent↗
PubMed1990

Multiple myeloma of the bladder and vagina.

A case is described of multiple myeloma with involvement of the urinary bladder and vagina. The patient was admitted with hematuria and postrenal obstruction. She was treated successfully with local radiotherapy and combination chemotherapy with vincristine, Adriamycin (doxorubicin), and dexamethasone (VAD).

Aged↗