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Annals of the New York Academy of... 1985
Topics: Alkylating Agents; Drug Administration Schedule; Humans; Leukemia; Mannitol; Mitobronitol; Polycythemia Vera
PubMed: 3938195
DOI: 10.1111/j.1749-6632.1985.tb20842.x -
Lancet (London, England) Mar 2000
Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Alkylating; Charcoal; Drug Interactions; Female; Humans; Mitobronitol; Phytotherapy; Platelet Count; Thrombocythemia, Essential; Treatment Failure
PubMed: 10768466
DOI: 10.1016/s0140-6736(05)74767-x -
Magyar Onkologia Dec 2017The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines... (Review)
Review
The present review about the history of anticancer drug research in Hungary intends to call attention to the importance of studies on their mode of action. Several lines of evidence suggest that clinically usable oncopharmacological properties could be revealed by this way. Among the numerous compounds certain alkylating sugar alcohols and 2'-deoxyuridine derivatives were submitted to detailed investigations concerning their mode of action. Myelobromol with selective action on the myeloid elements of bone marrow has been justified for its application in chronic myeloid leukemia therapy and also in bone marrow ablation before transplantation. Mitolactol is able to cross bloodbrain barrier, consequently could control certain brain tumors. 5-etil-2'-deoxyuridine by reducing dihydropyrimidine dehydrogenase activity is able to increase 5-fluorouracil concentration in the blood, resulting in improved antitumor effect. In contrast, 5-hexil-2'-deoxyuridine, as an inhibitor of glycoconjugate pathway by reducing heparan sulfate production, has the ability to prevent metastasis. Noteworthy, the remarkable effects of vinca alkaloids, antiestrogens, and GNRH analogues were also presented in this review.
Topics: Antineoplastic Agents, Alkylating; Databases, Factual; Drug Design; Forecasting; Humans; Hungary; Mannomustine; Mitobronitol; Mitolactol; Pharmaceutical Research; Pharmacology, Clinical; Quality Improvement; Retrospective Studies
PubMed: 29257158
DOI: No ID Found -
Leukemia Jul 1993Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow...
Non-supralethal mitobronitol/cytarabine/cyclophosphamide conditioning without irradiation before bone marrow transplantation for accelerated chronic granulocytic leukemia: apparent absence of acute graft-versus-host disease.
Cytostatic chemotherapy instead of supralethal total body irradiation (TBI) has been increasingly used as an alternative myeloablative regimen before bone marrow transplantation (BMT). While irreversible azoospermia/amenorrhoea seems to occur less frequently with such conditioning, graft-versus-host disease (GVHD) remains unaffected. Five-year disease-free survival in accelerated chronic granulocytic leukemia (CGL), after BMT with matched sibling grafts has been 0.10-0.30. Mitobronitol, cytosine arabinoside, and cyclophosphamide were used for conditioning. Patients were transplanted with unmanipulated HLA/MLC identical sibling bone marrow. For recovery, a pathogen-low room was available without air filtering and laminar airflow. Seven of eight accelerated-CGL patients were engrafted: full allogeneic reconstitution was detected in four and mixed chimerism in three patients. Five out of the seven engrafted patients survived at least nine months (median = 42 months), two are considered cured (8-9 years survival). The four leukemia-free survivors displayed full allogeneic reconstitution and presented symptoms of chronic GVHD. One patient became a genetically verified father. Acute GVHD and veno-occlusive liver disease (VOLD) were absent in all patients, diffuse interstitial pneumonitis (IP) occurred in one case. Non-supralethal conditioning with mitobronitol/cytarabine/cyclophosphamide in accelerated-CGL allows allogeneic bone marrow reconstitution with survival and cure rates comparable to those achieved with other protocols using TBI or busulphan conditioning. Unlike the latter treatments, however, our protocol leads to fewer transplant-related complications including acute GVHD, IP, VOLD, and azoospermia/amenorrhoea.
Topics: Adult; Amenorrhea; Antineoplastic Combined Chemotherapy Protocols; Bone Marrow Transplantation; Combined Modality Therapy; Cyclophosphamide; Cytarabine; Female; Graft vs Host Disease; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Mitobronitol; Oligospermia
PubMed: 8321045
DOI: No ID Found -
Leukemia Oct 1997It has previously been reported that the use of mitobronitol (dibromomannitol, DBM) instead of busulphan (BU) for myelosuppression is associated with significantly...
Comparison of the lymphoid toxicities of mitobronitol and busulphan in mice: reduced B cell toxicity and improved thymic recovery as possible contributors to the reduced risk for complications following BMT with mitobronitol preconditioning.
It has previously been reported that the use of mitobronitol (dibromomannitol, DBM) instead of busulphan (BU) for myelosuppression is associated with significantly decreased risk for several complications of allogeneic bone marrow transplantation in accelerated chronic granulocytic leukemia. In exploring the pharmacologic basis for this observation, we have compared the acute and subacute cytotoxicities of DBM and BU on the spleen and thymus of mice. While there was comparable early (day 3) weight loss in both organs following these treatments, splenic B cells exhibited significantly less damage, and thymic regeneration (over weeks) was significantly faster following DBM treatment than with BU. These observations raise the possibility that improved post-BMT immune recovery could contribute to the clinical benefits observed with DBM-preconditioning.
Topics: Animals; Antineoplastic Agents, Alkylating; B-Lymphocytes; Bone Marrow Purging; Bone Marrow Transplantation; Busulfan; Female; Mice; Mice, Inbred BALB C; Mitobronitol; Risk Factors; Spleen; Thymus Gland
PubMed: 9324299
DOI: 10.1038/sj.leu.2400741 -
British Medical Journal (Clinical... Jul 1983
Topics: Alkylating Agents; Altretamine; Antibiotics, Antineoplastic; Antimetabolites, Antineoplastic; Antineoplastic Agents; Cisplatin; Etoposide; Humans; Mitobronitol; Mitolactol; Nitrosourea Compounds; Razoxane; Vinca Alkaloids
PubMed: 6407699
DOI: 10.1136/bmj.287.6385.110 -
Lancet (London, England) Sep 1987
Topics: Aged; Follow-Up Studies; Humans; Leukemia; Mannitol; Mitobronitol; Polycythemia Vera; Risk
PubMed: 2887907
DOI: 10.1016/s0140-6736(87)93012-1 -
Orvosi Hetilap Aug 1998A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36... (Review)
Review
A new, radiation-free, conditioning protocol, containing the original Hungarian mitobronitol (DBM) (DBM/ cytosine arabinoside/cyclosphosphamide) has been applied to 36 chronic myeloid leukemia (CML) patients followed by bone marrow transplantation (BMT) from HLA identical sibling donors between 1990-1997. In spite of some prognostically disadvantageous factors (half of them were above 40 years, 10 out of 36 patients were in accelerated phase, the disease history was longer than 2 years in average) the overall survival (30/36) and the leukemia free survival rate (26/36) were in accordance with the best international results. Transplantation-related toxicity was remarkably reduced in comparison to bone marrow transplantation performed by total body irradiation/cyclophosphamide (TBI/Cy) or busulphan/cyclophosphamide (Bu/Cy) conditioning protocols. Acute graft versus host disease was present in lower percentage (9/36) and the number of serious cases was only 2/36. Chronic GVH disease, generally known to be associated with antileukemic effect (GVL), occurred in 25 of cases. Early haematological relapse among the 34 patients with functioning graft occurred in 6 patients which rate is slightly higher than reported after TBI/Cy or Bu/Cy conditioning treatment. There was no relapse among patients transplanted within one year post-diagnosis and patients having CML with accelerated phase. The leukemia free post-transplant period was in association with the chronic GVH disease and full chimeric state.
Topics: Adolescent; Adult; Bone Marrow Transplantation; Clinical Protocols; Female; Graft vs Host Reaction; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Middle Aged; Mitobronitol
PubMed: 9745304
DOI: No ID Found -
Human Immunology Feb 2000Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The... (Review)
Review
Chimerism is an exceptional immunogenetic state, characterized by the survival and collaboration of cell populations originated from two different individuals. The prerequisits to induce chimerism are immuno-suppression, myeloablation, or severe immunodeficiency of the recipients on the one side and donor originated immuno-hematopoietic cells in the graft on the other. The pathologic or special immunogenetic conditions to establish chimerism are combined with bone marrow transplantation, transfusion, and various kinds of solid organ grafting. Different types of chimerism are known including complete, mixed and mosaic, or split chimerism. There are various methods used to detect the type of chimera state, depending on the immunogenetic differences between the donor and recipient. The induction of complete or mixed chimerism is first determinated by the effect of myeloablative therapy. The chimera state seems to be one of the leading factors to influence the course of the post-transplant period, the frequency and severity of GVHD, and the rate of relapse. However, the most important contribution of the chimeric state is in development of graft versus leukemia effect. A new conditioning protocol (DBM/Ara-C/Cy) for allogeneic BMT in CML patients and its consequence on chimera state and GVL effect is demonstrated.
Topics: Antineoplastic Agents, Alkylating; Bone Marrow Transplantation; Cyclophosphamide; Cytarabine; Graft vs Host Disease; Humans; Immunosuppressive Agents; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Mitobronitol; Transplantation Chimera; Treatment Outcome
PubMed: 10717801
DOI: 10.1016/s0198-8859(99)00143-3 -
Bone Marrow Transplantation Dec 1998Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as...
Between February 1993 and November 1997, 62 patients with severe aplastic anaemia (SAA), acute myeloid (AML), acute lymphoid (ALL), or chronic myeloid leukaemia (CML) as well as two patients with NHL underwent allogeneic marrow transplantation (BMT) from HLA-identical or one-antigen mismatched sibling or unrelated donors. Patients received preparative regimens according to the baseline disease. Patients with SAA were conditioned with ATG/Cy (2 cases) and TAI/Cy (3 cases), AML, ALL and NHL with TBI/Cy (21 cases including two retransplantations) and CML with Mitobronitol/Ara-C/Cy except two patients conditioned traditionally with Bu/Cy. For GVHD prevention, patients received cyclosporin-A (CsA) with short course methotheraxe according to the Seattle protocol. Significantly better overall survival rates were associated with the Mitobronitol (DBM)/Ara-C/Cy conditioning regarded the patients as a whole. Autologous stem cell transplantation (bone marrow and/or peripheral blood) were performed in ten cases including 2 AML, 4 non-Hodgkin's lymphoma (NHL), 3 Hodgkin's disease (HD) and 1 patient with multiple myeloma (MM). Patients with AML and two patients with NHL were conditioned with TBI/Cy and the others with BEAM combined chemotherapy. Eight out of ten patients are leukaemia- or lymphoma-free survivors. One patient relapsed having conventional chemotherapy and interferon maintenance therapy. One patient died in a rapid relapse five months post-BMT.
Topics: Antineoplastic Combined Chemotherapy Protocols; Carmustine; Cytarabine; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Histocompatibility Testing; Humans; Hungary; Leukemia; Melphalan; Podophyllotoxin; Recurrence; Transplantation Conditioning; Transplantation, Autologous; Treatment Outcome; Whole-Body Irradiation
PubMed: 9916638
DOI: No ID Found