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Biomedical subjects

P Höcker

Publications and source records attributed to P Höcker.

At least 19 recordsLinked to original sources
PubMed1992

Antigenic analysis of human haemopoietic progenitor cells expressing the growth factor receptor c-kit.

The cell surface molecule encoded by the protooncogene c-kit has recently been identified as the receptor for a growth factor variously termed stem cell factor (SCF), mast cell growth factor or steel factor. Using the c-kit antibody 17F11 we analysed, in triple staining experiments, the surface molecule profile and scatter characteristics of c-kit+CD34+ human haemopoietic progenitor cells. In 10 normal bone marrow samples we found 19-51% of CD34+ bone marrow progenitor cells to coexpress c-kit. These c-kit+CD34+ bone marrow cells turned out to represent a phenotypically heterogeneous population. A considerable proportion coexpressed CD33 (52 +/- 23%), and/or CD71 (62 +/- 26) antigens, marker molecules previously shown to be expressed by committed in vitro colony forming cells but not by their precursors. In line with a relatively differentiated phenotype c-kit+CD34+ cells also gave rise to on average higher forward and right-angle light scattering signals. The proportions of CD38 and/or HLA-D expressing cells were similar in the c-kit+ and in the c-kit- subsets of CD34+ progenitor cells. Coexpression of CD19 was found to be less frequent in the c-kit+ (4 +/- 5%) as compared to the c-kit- (17 +/- 14%) fraction of CD34+ cells. CD7+ CD34+ bone marrow cells were hardly detectable and their numbers too low to allow further subdivision in c-kit+ and c-kit- subsets.

Antigens, CD↗
PubMed1992

Treatment of infant leukemia with busulfan, cyclophosphamide +/- etoposide and bone marrow transplantation.

Infants with acute leukemia have a poor chance of being cured by conventional chemotherapy. We therefore treated cases of infant leukemia with high dose chemotherapy followed by bone marrow transplantation (BMT). Six suffered from acute leukemia and one from refractory anemia with excess of blasts (RAEB-t). The conditioning regimen consisted of busulfan (BU) and cyclophosphamide (CY), and was intensified by adding etoposide (VP) in four cases. At the time of BMT the children were 4, 5, 12, 13, 13, 14, and 20 months old. Three children were autografted, three received HLA-identical marrow from a sibling donor, and one child received matched unrelated donor marrow. All five children who were grafted in complete (CR) or partial remission (PR) are alive and well in CR 7, 13, 24, 37, and 46 months after allogeneic (two patients) or autologous (three patients) BMT, and 13, 17, 29, 42, and 53 months after initial diagnosis. The child with RAEB-t and the one transplanted in second chemotherapy-resistant relapse of acute non-lymphoblastic leukemia relapsed at 7 and 17 months respectively. The chemotherapy regimen was well tolerated. BU-CY-VP is a promising alternative treatment to regimens including total body irradiation for very young children suffering from acute leukemia.

Bone Marrow Transplantation↗
PubMed1991

[Autologous bone marrow transplantation in children with acute leukemia or non-Hodgkin's lymphoma].

More than 95% of children with acute lymphoblastic leukemia (ALL) achieve complete remission with conventional chemotherapy and 60 to 70% are cured. In contrast, only 70 to 80% of children with acute myeloid leukemia (AML) achieve remission and 30 to 40% are cured. In acute leukemia, ALL and AML, high initial white blood cell counts, poor initial response to therapy, certain structural chromosomal abnormalities, and diagnosis under 1 year of age indicate an increased risk of relapse. Prognosis is poor in children, who relapse during treatment. If no bone marrow donor is available, high dose chemo(radio)therapy and autologous stem cell rescue can be applied in these children to consolidate second remission. Furthermore, autologous bone marrow transplantation may be used to consolidate first remission of individual children, who suffer from acute leukemia with high risk criteria. 19 children with a median age of 8 years (0.5 to 19 years) underwent high dose chemo(radio)therapy and autologous bone marrow and/or blood derived stem cell rescue. 11 suffered from ALL, 4 had AML, and 4 suffered from Non Hodgkin's lymphoma (NHL). 7/13 children (54%), who were in first or second remission after early relapse, are alive in continued remission for median 24 months (9 to 44) after autografting. Children in more advanced stage of disease had no benefit from high dose therapy and autologous stem cell rescue.

Adolescent↗
PubMed1991

[Collection and transfusion of peripheral blood stem cells].

Harvesting of peripheral blood stem cells (PBSC) by cytapheresis was performed in 57 patients, who underwent chemotherapy. The best yields were obtained when the leukocyte count was above 1 x 10(9)/l and the platelet count was raised above 80 x 10(9)/l. Using a Haemonetics V-50 or a Baxter CS-3000, 374 PBSC-aphereses were performed with a median of six aphereses per patient. The median number of PBSC (CFU-GM) retransfused in 22 patients who received PBSC for hematological reconstitution only was 3.26 x 10(4)/kg. For 22 patients who received autologous bone marrow plus BPSC, the median number of retransfused PBSC was 2.14 x 10(4)/kg. Myeloid engraftment was achieved in all patients, but megakaryopoiesis was delayed when the number of PBSC was less than 5.0 x 10(4)/kg. The results demonstrate that harvesting of a sufficient number of PBSC after chemotherapy is feasible but further measures like the use of rh GM-CSF will be necessary to reduce apheresis procedures and to obtain high yields to ensure rapid and complete engraftment.

Blood Cell Count↗
PubMed1991

[The role of blood banks in bone marrow transplantation].

The transfusion service (TS) plays an important role in bone marrow transplantation (BMT). Many of the techniques and methods employed are also used in the daily work of a TS like tissue typing, apheresis techniques, handling of blood and its components under sterile conditions. In the pretransplantation phase the TS is responsible for the typing of recipient and presumptive donors, harvesting of autologous blood and selection of appropriate blood components. During BMT the TS can perform bone marrow harvesting, depletion of red cells in case of ABO-incompatibility and bone marrow manipulation when T-cell depletion or purging procedures are considered. Peripheral stem cell harvest by apheresis is also best performed by the TS experienced in such techniques. Storage of hematopoietic cells in liquid nitrogen and thawing are also techniques already used in most of the transfusion services. Post BMT, the support with blood components, irradiated and almost free of white cells to avoid TA-GVH and CMV-infection, is a major job of the TS. These facts demonstrate that a well organized transfusion service is a 'conditio sine qua non' for successful BMT.

Blood Banks↗
PubMed1991

Unusually long survival after autografting in second partial remission of translocation t(4;11) acute infant leukemia.

About 70% of children with acute lymphoblastic leukemia may be cured by conventional chemotherapy. The prognosis is considerably worse in infant leukemia with a translocation t(4;11). We report an infant with a diagnosis of cytochemically undifferentiated acute hybrid leukemia (pre pre B-ALL coexpressing one myelomonocytic marker) and t(4;11). Initial clinical presentation and the course of the disease were typical for t(4;11) acute leukemia. After an early hematologic relapse intensive chemotherapy resulted only in a second partial remission 7 months after initial diagnosis. Subsequent bone marrow transplantation with 16 mg/kg busulfan and 200 mg/kg cyclophosphamide followed by the infusion of autologous purged bone marrow resulted in a continuous second remission which has lasted 46 months so far.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1991

Is treatment intensification by adding etoposide and carboplatin to fractionated total body irradiation and melphalan acceptable in children with solid tumors with respect to toxicity?

Conventional chemotherapy results in high mortality rates in patients with solid tumors involving the bones or the bone marrow. High dose melphalan (MEL) with or without total body irradiation followed by bone marrow transplantation (BMT) has prolonged survival, but curative potential has remained disappointing. In order to improve survival 20 children with generalized or relapsed solid tumors (neuroblastoma, peripheral neuroectodermal tumor, Ewing's sarcoma, rhabdomyosarcoma) underwent autologous (n = 16) or allogeneic (n = 4) BMT. The myeloablative regimen consisted of 12 Gy fractionated total body irradiation (FTBI) and high dose MEL. In 12 of these patients this regimen was intensified by giving 60 mg/kg etoposide (1800 mg/m2 VP), and 1.5 g/m2 carboplatin (CBDCA) was added in seven of these 12 patients. The intensification of FTBI and MEL by adding VP and CBDCA was followed by acceptable toxicity. Acute liver toxicity in 15/20 patients (75%) and acute renal toxicity in 17/20 patients (85%) did not exceed WHO grade 1. The use of the conditioning regimen FTBI-MEL-VP-CBDCA during first chemotherapy response is a promising approach in treatment of children suffering from generalized solid tumors.

Adolescent↗
PubMed1991

[Supportive therapy with blood components].

An overview about the recent state of the supportive therapy with blood components in the treatment of leukemia is given. The 1st part is devoted to the procurement of blood components and the techniques of preparation and storage are described. The 2nd part includes the side effects of blood components like alloimmunization, graft-versus-host disease and CMV-transmission and discusses the possibilities of prohibition. The 3rd part deals with the dosage of the single blood components and how to judge the efficacy of transfusion. In the last part the indications for the single blood donor components are described and therapeutical strategies are outlined.

Blood Component Transfusion↗
PubMed1990

Erythropoietin treatment of anemia associated with multiple myeloma.

Anemia is a common complication of multiple myeloma. It resolves early in the disease if chemotherapy induces a complete remission, but persists if the disease progresses, causing disabling symptoms and often requiring blood transfusions. We treated 13 patients with myeloma-associated anemia by administering recombinant human erythropoietin three times a week for six months. Eleven patients (85 percent) had steady increases in hemoglobin levels and eventual correction of the anemia. Their symptoms of anemia subsided, and they reported a heightened sense of well-being. No patient had any adverse side effects, particularly episodes of hypertension. Monitoring of the serum M component showed a predominantly stable tumor load without apparent interaction between the underlying disease and the response to erythropoietin therapy. The number of erythroid burst-forming units in the bone marrow and peripheral blood and the level of erythropoiesis in bone marrow smears increased significantly during therapy. Pretreatment serum levels of erythropoietin were higher in the patients who did not respond and in those who required more than two months of treatment before they responded. Serum iron, ferritin, and transferrin concentrations reflected responses to treatment. We conclude that recombinant human erythropoietin is a promising therapeutic tool for treating myeloma-associated anemia.

Aged↗
PubMed1990

[Hemolyzing antibodies to markers of the P blood factor system as a problem in blood transfusion and pregnancy. With reference to serology, biochemistry and genetics].

The extremely rare phenotypes p, P1k and P2k (0.0005-0.0006%) of the blood group P system are usually found in consanguinous families. In the serum of these persons haemolytic antibodies with the specificity anti-PP1Pk and anti-P are found, causing severe haemolytic reactions after transfusion of incompatible blood. Because of their rarity it is difficult to find compatible blood donors. The antibodies are also associated with abortion early in pregnancy. Since 1948 at the "Institut für Blutgruppenserologie der Universität Wien" 4 persons of the phenotype p and 3 of the type P2k were observed in altogether 5 families. Two of them needed blood transfusions, the one p patient received p blood from her sister, who likewise gave blood to the other p patient. This latter patient additionally received three blood units which had been stored in liquid nitrogen and came from Austria and from the European bank of frozen blood in Amsterdam (Council of Europe). The pedigrees of three families with 5 probands out of the 7 observed cases could be reconstructed and showed consanguinity, partly some generations back. A genetic model valid at the moment for the biosynthetic pathway of the P antigens is demonstrated and the appropriate serological characteristics of the haemolytic antibodies are shown. The seven antibodies are partly IgG and partly IgM antibodies, optimally reacting using the indirect antiglobulin test or enzyme-treated red cells. The range of the antibody titres was between 1:8 and 1:1024. Absorption of Anti-PP1Pk sera with red cells of type P1 to get Anti-Pk and inhibition with hydatidcyst fluid and globoside to receive Anti-P and Anti-P1 + Pk, respectively were partly successful.

Abortion, Spontaneous↗
PubMed1990

Capillary leak syndrome during low dose granulocyte-macrophage colony-stimulating factor (rh GM-CSF) treatment of a patient in a continuous febrile state.

A 20 years old man with peripheral primitive neuroectodermal tumor involving the bone marrow received 12 Gy fractionated total body irradiation, 140 mg/m2 melphalan, 1800 mg/m2 etoposide, and 1500 mg/m2 carboplatin for consolidation of first remission. Thereafter, 250 micrograms/m2/day recombinant human granulocyte-macrophage colony-stimulating factor (rh GM-CSF) (Behring Werke) were administered as continuous infusion 4 days after infusion of autologous bone marrow and peripheral stem cells to accelerate granulocyte reconstitution for control of a continued febrile state. The clinical picture of capillary leak syndrome developed with weight gain, pleural effusions and peripheral edema. The patient's condition stabilized after discontinuation of rh GM-CSF. Eight days later he died of invasive aspergillosis. The clinical course of our patient suggests a potentially fatal toxic effect of rh GM-CSF, even in low dose, in the setting of septicemia or fungemia.

Adult↗
PubMed1990

Autologous rescue with blood-derived stem cells in a child with non-Hodgkin's lymphoma.

Autologous blood-derived stem cells were used for stem-cell rescue in a 5-year-old boy with chemotherapy-resistant B-Non-Hodgkin's lymphoma (B-NHL) involving bone marrow. The high dose chemoradiotherapy was carried out 5 months after initial diagnosis during partial remission. The preparative regimen consisted of 12 Gy fractionated, total-body irradiation (FTBI) before 60 mg/kg etoposide. There were 22.96 X 10(4)/kg body weight myeloid precursor cells, granulocyte-macrophage committed stem cells (CFU-GM) collected by intermittent blood flow separation with a Haemonetics 30R in two cytaphereses and stored in liquid nitrogen. Also 11, 82 X 10(4) CFU-GM/kg body weight were recovered and transfused after thawing. Rapid hematopoietic reconstitution ensued: Erythroid precursors were detected on day 9, 1 X 10(9)/L leucocytes were counted on day 11, and 0.5 X 10(9)/L granulocytes on day 13, respectively. The patient required 3 single-donor platelet transfusions, the last one on day 10. On day 17, 100 X 10(9)/L platelets were reached. A bone marrow aspirate on the same day showed good trilineage regeneration. The patient remained in complete remission 7 months after autografting with a normal stem cell content of the bone marrow and in the peripheral blood. On day 226, after stem cell infusion, a bone marrow relapse occurred.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1990

The median rise of leucocytes predicts the optimal days for leukapheresis in children.

22 consecutive patients with a median age of 11 years (range 3-23) underwent 103 leucaphereses after a chemotherapy induced aplasia. They suffered from various solid tumors and hematological malignancies. The stem cell yield of 69 aphereses which were done during the 8 days following the first platelet rise, was median 1.02 x 10(4) myeloid committed stem cells (CFU-GM)/kg/apheresis (range 0.02-13.3), whereas only 0.27 x 10(4) CFU-GM/kg/apheresis (range 0.01-1.11) were obtained in 34 "random" collections (p less than .05). The CFU-GM yield of 69 "well timed" collections depended on the absolute number of circulating leucocytes (p = .002) and mononuclear cells (p less than .001). The median daily increment of leucocytes was a reliable predictor of the stem cell yield (p = .002) and could be used to select the optimal days for leucaphereses during the well timed period. By careful timing alone high stem cell numbers could be collected in various malignancies without using exogenous growth factors.

Adolescent↗
PubMed1990

The median daily increment of leukocytes during hematopoietic recovery reflects the myeloid progenitor cell yield during leukapheresis in children.

Twenty-two consecutive patients with a median age of 11 years (range 3-23) underwent 103 leukaphereses for collection of peripheral stem cells. They suffered from various solid tumors and hematologic malignancies. Our aim was to collect at least 2.5 x 10(4) myeloid committed stem cells (CFU-GM) per kg body weight. This stem cell number has reliably resulted in rapid and sustained hematopoietic reconstitution after autografting in our institution. Peripheral stem cell mobilization was induced by myelosuppressive therapy alone. If the stem cell collections were started at the first platelet rise and were continued during the following 8 days, the stem cell yield of one procedure was high - median 1.02 x 10(4) CFU-GM/kg body weight (range 0.02-13.3). In 69 such 'well-timed' collections, a median of only 4 leukaphereses (range 2-6) were needed to collect high numbers of CFU-GM. The yield from leukaphereses carried out at any other time was unsatisfactory. In 34 'random' collections, a median of only 0.27 x 10(4) CFU-GM/kg body weight (range 0.01-1.11) was obtained in one procedure. In 69 well-timed collections the CFU-GM yield depended on the absolute number of circulating leukocytes (r = 0.369, p = 0.002) and mononuclear cells (r = 0.476, p less than 0.001). The median daily increment of leukocytes to the day of apheresis proved to be an excellent parameter for the prediction of the yield and could be used to select the best days for leukaphereses (r = 0.403, p = 0.002). These findings may help to make the collection of blood-derived stem cells more efficient in pediatric patients.

Adolescent↗
PubMed1989

Oral cyclosporin-A is effective treatment for untreated and also for previously immunosuppressed patients with severe bone marrow failure.

16 patients with transfusion-dependent, life-threatening bone marrow failure (14 with severe aplastic anaemia, 1 with systemic lupus erythematosus and 1 with pure red cell aplasia) were treated with cyclosporin-A (Cy-A) after either lack of response to conventional immunosuppression with antithymocyte-globulin/high-dose methylprednisolone for 95 to 1190 days (median 186.5) (group I, 8 patients) or as a primary treatment due to ineligibility for conventional immunosuppression (group II, 8 pat.). Cyclosporin-A was given orally to maintain trough levels of 200 to 300 ng/ml (RIA). In group I, 6 out of 8 patients responded 30 to 480 d (median 53) and are currently alive 627 to 1482 d (median 731) after initiation of Cy-A, respectively. In 3 of the responders Cy-A has been withdrawn, without relapse. In group II, 5 of 8 patients responded 26 to 170 d (median 63) and are currently alive 142 to 697 (median 420) d following initiation of Cy-A, respectively. These data indicate a place for cyclosporin-A in the management of patients with life-threatening bone marrow failure in whom a) immunosuppressive therapy with antithymocyte-globulin and high-dose methylprednisolone had failed and b) who are not candidates for vigorous immunosuppression or bone marrow transplantation, for medical or other reasons.

Administration, Oral↗