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Biomedical subjects

B Netzel

Publications and source records attributed to B Netzel.

At least 19 recordsLinked to original sources
PubMed1984

Autologous bone marrow transplantation in leukemia.

In patients without HLA-identical donors autologous bone marrow transplantation should be considered as an alternative to conservative treatment of recurrent malignancies. Any patient in complete remission is suitable for an autologous bone marrow transplantation. Bone marrow is aspirated from the patient during complete remission, frozen, and stored at -196 degrees C, and it can be used for hematopoietic reconstitution after high-dose chemotherapy and radiotherapy of the patient. In patients with solid malignant tumors or leukemia the elimination of clonogenic tumor cells from the graft by means of physical separation techniques has not been successful. However, studies in mice and more recently in patients indicate that antibodies destroy residual leukemic cells of the bone marrow transplant without jeopardizing the capacity for regeneration. During our first study in children with acute lymphoblastic leukemia, bone marrow was taken from 50 patients in remission and cryopreserved. Preservation time ranged from 1 to 60 months and the mean number of aspirated nucleated bone marrow cells was 4 X 10(8)/kg body weight (1.9 - 7.4 X 10(8)/kg). After cryopreservation the stem cell viability of the standard samples was 80% - 100%. Autologous bone marrow was transplanted in five patients with common ALL (cALL). The transplant was prepared by incubation with specific antisera of high cytotoxic, selective activity against cALL cells. Our preliminary results show that bone marrow cells aspirated in remission and prepared with antileukemic antisera stimulate repopulation of the recipient's bone marrow and effect hematopoietic regeneration.

Animals↗
PubMed1983

Therapy of acute lymphocytic leukemia in childhood with intermediate dose methotrexate and CNS irradiation. A report of the ALL 77-02 study group.

One hundred and eight children with acute lymphocytic leukemia (ALL) were admitted to a prospective therapeutic regime. Remission induction was achieved in 94% of the cases with vincristine, L-asparaginase, adriamycine and prednisone. One hundred and one patients received three intermediate dose methotrexate (MTX) infusions combined with intrathecal MTX, followed by L-asparaginase 24 h later. High risk (HR) patients (n = 50) were treated in addition with high dose cyclophosphamide and Ara-C over 3 weeks. One hundred and one patients received cranial irradiation (1,800 rads standard risk (SR)-patients, 2,400 rads HR-patients) and intrathecal MTX. Maintenance therapy was performed with the usual two drug combination of daily 6 mercaptopurine (6 MP) and weekly MTX orally. Based on phenotyping 67% of patients had common type ALL, and pre-T or T-cell type in 18%. Six per cent of the patients had leukemic blasts expressing both common ALL and T-cell markers (c/T-type); 9% had acute undifferentiated leukemia (AUL). Out of 108, 101 achieved a complete remission, 6 patients died during induction therapy, 1 was a non-responder and 9 patients relapsed. Of these Four patients died in continuous complete remission (CCR). For 101 patients the 30 months probability of CCR is 0.85 (+/- 0.05). For 51 patients with standard risk CCR probability is 0.98 (+/- 0.03), for 50 patients with high risk indices it is 0.65 (+/- 0.11). Patients with c-ALL have a CCR survival of 0.85 (+/- 0.07), those with T- or pre-T-ALL 0.88 (+/- 0.09), all 5 patients with c/T-ALL alive in CCR. In our study pediatric AUL patients have the most unfavourable prognosis.

Acute Disease↗
PubMed1981

[Bone marrow transplantation for aplastic anaemia (author's transl)].

From March 1975 until May 1980 twelve patients with severe aplastic anemia were grafted with bone marrow from HLA-identical siblings by the Munich Cooperative Group for Bone Marrow Transplantation. Six patients are alive between 10 months and more than 5 years after grafting with normal blood values and marrow. One patient is treated as an out patient for chronic localized graft-versus-host disease (GvHD), five patients are well and without treatment. Six patients have died, one patient with a cerebral hemorrhage the day before transplantation, three patients following rejection of grafts 32, 40 and 55 days after grafting, one patient with severe GvHD 85 days after grafting and one patient, probably with interstitial pneumonia, following cerebral hemorrhage. Three of 6 patients who were conditioned with Cyclophosphamide (CY) only died following rejection of the graft. Two adults who were conditioned with CY and "total lymphoid irradiation" and three children, who wer given unirradiated leukocyte concentrates from the marrow donor after grafting, did not reject their grafts. The results of the Munich-Cooperative Group for Bone Marrow Transplantation are comparable to those of large, specialized centers for bone marrow transplantation, they indicate possibilities of cure of severe aplastic anemia by marrow grafts from HLA-identical siblings. They confirm that better results are obtained with earlier transplantation in the course of the disease.

Adolescent↗
PubMed1981

[Bone marrow transplantation in acute leukemias: antibody treatment for suppression of graft-versus-host disease (author's transl)].

Anti-human-thymocyte globulin (AHTZG) was applied to prevent GvHD in clinical bone marrow transplantation. AHTZG produced by absorption with several cell preparations reacted specifically with T-lymphocyte populations and was no longer inhibitory to human CFUc and bone marrow growth in diffusion chambers. Marrow grafts of 14 patients with ALL were incubated in vitro with AHTZG and transferred to the recipients conditioned with antileukemic chemotherapy and total body irradiation of 1000 rad. Ten patients were transplanted after relapse, four patients during remission. The patients tolerated the marrow without side effects and a hemopoietic engraftment was seen in 12 cases. Three patients showed signs of GvHD on the skin, two of them showed later on also manifestations in the liver. In the other cases no GvHD could be detected. Five out of 14 patients are still alive between 144 and 964 days post transplantation in remission.

Acute Disease↗
PubMed1981

[Initial treatment of acute childhood leukemia with extreme leukocytosis by blood exchange transfusion -- rheological aspects (author's transl)].

In leukemia patients with extremely high leukocytosis the great number of poorly deformable lymphoblasts compared to normally deformable red cells greatly influences the flow properties of leukemic blood. The increased blood viscosity implies a great risk of disturbance of the microcirculation by leukostasis and bleeding. Removal of large amounts of leukemic cells by exchange transfusion with fresh blood diminished leukemic cell burden and reduced the initial elevated leukocyte counts by more than 50% in 3 patients. In addition, anemia and thrombocytopenia improved and the disturbed plasma coagulation returned to normal. One of the patients with additional risk factors treated by exchange transfusion died 8 months after diagnosis in hematologic release. The two other patients perform well without relapse six and nine months after diagnosis, respectively. Exchange transfusion with 150 ml/kg of fresh blood is considered to be of value to avoid severe early complications as e.g. massive intracerebral hemorrhage observed in 3 other patients and to correct hematological and rheological abnormalities in childhood leukemia with extreme leukocytosis. Possible favourable effects as to long term prognosis have to be awaited.

Blood Viscosity↗
PubMed1980

Immunological conditioning of bone marrow for autotransplantation in childhood acute lymphoblastic leukaemia.

Samples of bone marrow from 32 leukaemic children were removed during remission and stored in liquid nitrogen for retransplantation during relapse. Subsequently two children in advanced stages of common acute lymphoblastic leukaemia (cALL) were transplanted with their own cryopreserved marrow cells, after intensive combination chemotherapy and high doses of radiation therapy. Before grafting, the marrow cells were treated with purified heterologous antibodies prepared against cALL antigens, to remove any residual tumour cells. The antibodies showed high cytotoxic activity against leukaemic cells of cALL type without interfering with normal haemopoietic stem cells. Evidence of take was obtained in one patient, who died on day 7 with cardiac failure. In the other patient the dose of nucleated marrow cells grafted was 1.9 x 10(8)/kg (86 000 CFU-C/kg). The patient achieved complete haematological recovery on day 27 and a normal platelet count after day 50 and is now in complete remission. Marrow cells collected during remission and treated with antileukaemic antibodies can repopulate bone marrow after conditioning of the recipient with high doses of radiation.

Antibodies, Neoplasm↗
PubMed1980

Antibody incubation of human marrow graft for prevention graft versus host disease.

An in vitro incubation of incompatible donor bone marrow by xenogenic anti-T-cell globulin (ATG) suppressed an otherwise lethal GvH reaction in animal models. An application of this principle to clinical bone marrow transplantation was successfully tried in three patients with acute lymphoblastic leukemia. Preparation of the specific anti-human T-cell globulin (ATCG-H) was carried out by absorption of anti-human thymocyte globulin with liver-kidney homogenate, chronic lymphocytic leukemia cells of B-cell type, and erythrocytes. Subsequent testing revealed that the serum still reacted with human T-cells but no longer reduced the number of colony-forming units in culture (CFU-C). All three bone marrow recipients were treated by chemotherapeutic conditioning and total body irradiation followed by grafting of in vitro treated bone marrow from HLA-identical siblings. The transplantation of the bone marrow was well tolerated and no major side effects were encountered. No patient so far (24, 7, 6 months) has shown any signs of GvHD. The in vitro pretransplantation treatment of bone marrow with anti T-globulin may be a new approach to the prevention for GvHD in man.

Adolescent↗
PubMed1980

Rhesus incompatibility and aplastic anemia as the consequence of split chimerism after bone-marrow transplantation for severe combined immunodeficiency.

A patient with severe combined immunodeficiency received three transplants of bone marrow from the HLA-B- and -D-identical mother. The first transplantation led to a severe graft-versus-host reaction followed by immunological reconstitution. A split chimerism was found with engraftment only of the maternal lymphocytes. Five months after the transplantation an autoimmune hemolytic anemia was observed which was due to rhesus incompatibility as well as polyspecific antibodies. At the same time agranulocytosis developed and 9 mth after the first transplantation the child suffered from aplastic anemia. Two further attempts failed to engraft the maternal hematopoiesis. The child died during the treatment with cyclophosphamide as conditioning for a third transplantation.

Agranulocytosis↗