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W Gassmann

Publications and source records attributed to W Gassmann.

At least 73 records · Page 4Linked to original sources
PubMed1991

High-dose cytostatic agents in allogeneic bone marrow transplantation: comparison of the engraftment promoting potential.

We investigated the potential of various cytostatic agents for preventing graft rejection following allogeneic bone marrow transplantation. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) F1(CAP x LEW) marrow cells, which are unable to induce a graft-versus-host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte counts. Due to its weak immunosuppressive activity, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, agents administered in addition to busulfan can be tested for their capacity to prevent marrow graft rejection. 120 mg/kg of cyclophosphamide, 20 mg/kg of ACNU and 240 mg/kg of ifosfamide completely prevented rejection of the allogeneic marrow. Maximum doses of BCNU applicable in conjunction with busulfan reduced the rejection rate to 12% (30 mg/kg) and 17% (40 mg/kg), whereas the antitumour agents thiotepa, melphalan, and carboplatin exhibited a very limited engraftment-promoting potential in this experimental setting. Thus, BCNU (carmustine), ACNU (nimustine), and ifosfamide might be suitable candidates for conditioning of allogeneic bone marrow graft recipients.

Animals↗
PubMed1991

Effect of post-transplant methotrexate, cyclosporin A and prednisolone on graft rejection after allogeneic bone marrow transplantation.

Methotrexate, cyclosporin A and prednisolone have been shown to improve graft survival rates in solid organ transplantation. However, little is known concerning their capacity to promote lasting engraftment of allogeneic bone marrow. Therefore, we tested these agents in LEW rats receiving MHC-mismatched marrow after pretreatment with a myeloablative dose of busulfan plus different doses of total body irradiation (TBI). To avoid mortality due to graft-versus-host reaction (GHVR), F1(CAP x LEW) marrow was transferred. Hematological parameters were determined twice weekly to monitor engraftment and rejection. The pretreatment was lethal but not sufficiently immunosuppressive to ensure lasting engraftment in all animals. Thus, post-transplant immunosuppressive protocols could be evaluated for their capacity to improve engraftment rates. Standard clinical doses of methotrexate (0.25 mg/kg i.p. day 1, 3, 6, 11, 18, 25), cyclosporin A (10 mg/kg orally day 0-28) and prednisolone (1 mg/kg i.p. day 0-28) were administered and proved to be of nearly equivalent toxicity in our system. All three agents failed to allow engraftment after busulfan alone. After additional conditioning with 1.5 Gy of TBI, methotrexate and cyclosporin A reduced the rejection rate from 100% to 59% and 70%, respectively. When 3 Gy of TBI were added to busulfan, cyclosporin A and prednisolone were able to reduce the rejection rate from 67% to 33% and 39%, respectively, whereas 0.12 and 0.25 mg/kg methotrexate completely prevented graft rejections. After cessation of cyclosporin A therapy, late secondary rejections were frequently observed. These results demonstrate that postgrafting immunosuppression with protocols conventionally used for the prophylaxis of GVHR is able to facilitate lasting engraftment of MHC-mismatched bone marrow.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1988

Fractionated total body irradiation and high-dose VP 16-213 followed by allogeneic bone marrow transplantation in advanced leukemias.

Thirty-eight patients (median age, 21 years) with acute nonlymphoblastic leukemia (ANLL) (17 patients), acute lymphoblastic leukemia/lymphoma (ALL) (18 patients), chronic myelogenous leukemia (two patients), and refractory anemia received allogeneic bone marrow transplants from HLA-identical sibling donors or a one-antigen-mismatched brother (one patient) after a preparatory regimen consisting of fractionated total body irradiation and high-dose VP 16-213 (60 to 70 mg/kg body weight). Of the 33 patients with acute leukemia who received grafts from HLA-identical donors, three patients with ANLL received transplants in first remission and one patient with standard-risk ALL received a graft while in second remission. All other patients were in more advanced stages of their disease or exhibited other high-risk features. At the time of analysis, 20 of the 33 patients were alive, with 19 of them remaining in continued complete remission for 6 to 35 months (median, 18 months). The 3-year actuarial disease-free survival rate of 56.6% +/- 9.7% (SE) and the actuarial relapse rate of 11.9% +/- 6.8% (SE) demonstrate that the combination of fractionated total body irradiation and high-dose VP 16 is an effective mode of therapy in patients with advanced leukemias. Preliminary experience cautions against the use of VP 16 instead of cyclophosphamide in any clinical situation carrying an increased risk of graft rejection because the immunosuppressive potency of VP 16 is largely untested but may be inferior to that of cyclophosphamide.

Adolescent↗
PubMed1988

Comparison of cyclophosphamide, cytarabine, and etoposide as immunosuppressive agents before allogeneic bone marrow transplantation.

Etoposide and cytarabine have been shown to exert high antileukemic activity and are currently under study as preparatory agents before allogeneic bone marrow transplantation. However, data concerning their engraftment-promoting potency are scarce. Therefore, we tested these agents in LEW rats receiving a myeloablative dose of busulfan followed by transfer of F1 (CAP X LEW) marrow, which is unable to induce a graft-v-host reaction (GVHR). Since busulfan by itself has only minor immunosuppressive potency, graft rejection ensues unless etoposide, cytarabine, or cyclophosphamide provide additional immunosuppression to facilitate durable engraftment. Before allogeneic bone marrow transplantation in humans, 120 mg/kg of cyclophosphamide, 60 mg/kg of etoposide, or 900 mg/kg of cytarabine are the standard doses given in conjunction with total body irradiation. Seventy-five percent of these doses administered in addition to busulfan resulted in rejection rates of 75% for cytarabine and 58% for etoposide, respectively, whereas no rejections were observed with cyclophosphamide. These data indicate that etoposide and cytarabine are inferior to cyclophosphamide in their rejection-preventing potential. Using either of these agents as substitutes for cyclophosphamide before allogeneic bone marrow transplantation may increase the risk of graft rejection in HLA-mismatched bone marrow transplantation and, in case of HLA identity, if T-depleted marrow is administered.

Animals↗
PubMed1987

Postinduction and preremission chemotherapy alternatives for adult AML: three multicenter studies of the AML Cooperative Group.

Major chemotherapeutic alternatives for AML have been implemented and compared in three multicenter studies, including a total of 877 adult patients of all ages. The results strongly suggest that myelosuppressive postinduction treatment is a prerequisite for the achievement of long-term remissions. In addition, it was possible to establish an important antileukemic effect of monthly maintenance chemotherapy. Initial results from an intensive two-course preremission therapy concept revealed good practicability and acceptable toxicity, as well as promising response and remission durations by this new approach.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Immune reactivity after high-dose irradiation.

Immune reactivity after total-body irradiation was investigated in rats using skin graft rejection as the indicator system. After sublethal irradiation with 10.5 Gy (approximately 50% lethality/6 weeks) the rejection of major histocompatibility complex allogeneic skin grafts was delayed significantly compared with nonirradiated control animals (28 versus 6.5 days). In contrast, skin grafts were rejected after 7.5 days in sublethally irradiated animals and 7 days in lethally irradiated animals if additional skin donor type alloantigens--namely, irradiated bone marrow cells--were given i.v. either simultaneously or with a delay of not more than 24 hr after the above conditioning regimen. These reactions were alloantigen-specific. They were observed in six different strain combinations with varying donors and recipients. Starting on day 2 after irradiation, i.v. injection of bone marrow gradually lost its effectivity and skin grafts were no longer rejected with uniform rapidity; skin donor marrow given on days 4 or 8 did not accelerate skin graft rejection at all. These data show that for approximately 1-2 days after high-dose total-body irradiation rats are still capable of starting a vigorous immune reaction against i.v.-injected alloantigens. The phenomenon of impaired rejection of skin grafted immediately after high-dose irradiation appears to result from the poor accessibility of skin graft alloantigens during the early postirradiation phase when vascularization of the grafted skin is insufficient.

Animals↗
PubMed1986

[A comparison of staging classifications of plasmacytoma].

In 152 patients treated with cytostatic agents for multiple myeloma the prognostic value of seven staging systems was evaluated: Carbone et al. Acute Leukemia Group B, Southeastern Cancer Study Group, Durie and Salmon, Alexanian, Merlini et al., British Medical Research Council. The staging systems of the ALGB and SECSG, both dividing patients into "good risk"- and "poor risk"-groups gave significantly different survival curves. Nevertheless, the differences were rather small. In the systems of Carbone et al., Merlini et al., Alexanian, and Durie and Salmon some of the differences in the survival curves were statistically significant while others were not. Our data best fitted into the British Medical Research Council staging system, the survival curves of all three stages showing significant differences with median survival time dropping from 83 months in stage A to 52 months in stage B and 26 months in stage C. Nevertheless, none of those systems was clearly superior to single risk factors especially creatinine and hemoglobin.

Evaluation Studies as Topic↗
PubMed1985

[Allogeneic bone marrow transplantation after fractionated whole body irradiation. Results at the Kiel transplantation center].

Allogeneic bone marrow transplantations were carried out between March 1983 and July 1985 in 31 patients aged 7 to 45 years (median 18 years). Acute lymphoblastic leukaemia in 1st to 5th remission was present in 8 patients, acute myeloblastic leukaemia in 1st and 2nd remission in 4 patients, chronic myeloid leukaemia, with various remission status, in 6 patients, 3 patients had severe aplastic anaemia and there were single cases of myelodysplasia and immature cell megakaryocytic myelosis. Transplantation was carried out during relapse in 8 patients with either acute myeloid or lymphoblastic leukaemia. Phenotypic HLA-identical mothers (n = 2) as well as genotypic HLA-identical siblings (n = 27), and in two cases HLA-non-identical mothers, served as bone marrow donors. In leukaemia patients the conditioning treatment consisted of fractionated total body irradiation and high dose cyclophosphamide or etoposide. Patients with severe aplastic anaemia received cyclophosphamide (4 X 50 mg/kg) and fractionated total nodal irradiation (total dose 8 Gy). 19 patients (61%) survived 14 to 605 days after bone marrow transplantation. 15 patients (48%) continue to remain in complete remission with Karnofsky indices of greater than or equal to 90%. Causes for death were infection (n = 3), interstitial pneumonia (n = 3), relapse (n = 3) as well as single cases involving acute graft-versus-host-disease, non-engraftment of donor marrow and veno-occlusive disease of the liver.

Acyclovir↗