ISSN:0098-1532    

DOI:10.1002/mpo.2950200702

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractSeveral glycoproteins that control blood formation have recently been characterized. Through their overlapping, synergizing, and antagonistic effects, they regulate hematopoiesis in a highly differentiated network. Large scale production of these colony stimulating factors (CSFs) has been made available by recombinant DNA technology, and a series of clinical studies in a variety of indications has been finished. In general, the subcutaneous application seems to be superior to the intravenous injection and causes less toxicity. Erythropoietin has been shown to be a highly effective treatment for anemia in patients with chronic renal failure. Granulocyte colony stimulating factor and granulocyte‐macrophage colony stimulating factor are capable of ameloriating the chemotherapy induced neutropenia, and to abbreviate the time span of myeloaplasia after bone marrow transplantation. The potentials of other colony stimulating factors like Interleukin 1 and Interleukin 3, and combination regimens of several CSFs will be discussed. © 1992 Wiley‐Liss,

ISSN:0098-1532    

DOI:10.1002/mpo.2950200703

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractProliferation and differentiation of hematopoietic progenitor cells are regulated by a network of stimulatory and inhibitory cytokines. An understanding of the molecular mechanisms of growth control may provide a physiologic basis for the innovative therapy of bone marrow disorders. Among various accessory cells, bone marrow T lymphocytes are capable of stimulating, as well as inhibiting, hematopoietic progenitor cells. We have now elucidated molecular mechanisms regulating the differential expression of T cell genes encoding for the stimulatory and inhibitory hematopoietic programs. Stimulation of hematopoiesis requires granulocyte‐macrophage colony stimulating factor (GM‐CSF), whereas inhibition requires interferon‐γ (IFγ). Both cytokines can be induced by interleukin‐2 (IL‐2). The T cell IL2 receptor consists of a 75 kD chain (p75) mainly expressed on a subset of resting T cells and a 55 kD chain (p55) which is strongly expressed upon T cell activation. P55 and p75 associate on activated T cells to form a dimeric receptor molecule exhibiting high affinity for IL2. The p75 monomer has an intermediate affinity for IL2. Expression of p55 in the context of the high affinity IL2 receptor constitutes a requirement for T cell IFg release. In contrast, p75 alone is capable of mediating the production of GM‐CSF. Thus, T cells may be capable of selective production of cytokines with specific effects in hematopoietic growth control. Utilizing a human peripheral blood leukocyte genomic library, we identified various clones containing the entire GM‐CSF gene, including coding and regulatory regions. Cloning of the GM‐CSF gene allowed clinical studies utilizing recombinant DNA‐derived GM‐CSF. Chemotherapy‐induced neutropenia contributes to both complications of cytotoxic therapy as well as increased relapse incidence of underlying disease. In a prospective randomized study, we have demonstrated that GM‐CSF abrogates neutropenia following aplasiogenic chemotherapy in children and adolescents with solid tumors, and that GM‐CSF may reduce the duration of infectious episodes after cytotoxic therapy. Next, we escalated the cumulative doses of cytotoxic therapy in an ablative regimen followed by hematopoietic stem cell transplantation to treat patients with poor prognosis pediatric tumors. Morbidity of this highly toxic ablative regimen depends on the duration of myeloid aplasia. Median duration of aplasia following hyper‐VAMP was 13 days with GM‐CSF and 29 days without GM‐CSF. In addition, we have employed p55 blocking monoclonal antibody for prevention of graft vs. host disease in bone marrow transplantation. The understanding of specific molecular mechanisms of hematopoietic immuno‐regulation can thus be utilized to provide novel approaches to the treatment of bone marrow failure

ISSN:0098-1532    

DOI:10.1002/mpo.2950200704

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractGM‐CSF is a major regulator of myelopoiesis. Recombinant human GM‐CSF (250 μg/m2per day i.v.) was used prior to chemotherapy (“3 + 7” scheme) to recruit leukemia blasts in vivo (de novo AML patients, n = 20) into the chemotherapy sensitive phases of the cell cycle. The stimulatory effect of GM‐CSF on peripheral blood AML blasts was associated with a rapid redistribution of leukemia blood cells and with an increase in “S‐phase positive” cells. Standard induction chemotherapy (“3 + 7”) following GM‐CSF induced complete aplasia in 19/20 patients. In the same patients, rhGM‐CSF (given after chemotherapy) was found to shorten the time of complete aplasia compared to historical controls whereas post‐chemotherapy‐ and follow‐up data suggest no significant differences for CCR and survival. Together, our studies show that GM‐CSF can safely be administered to AML patients in combination with induction chemotherpay to recruit leukemia cells into the ce

ISSN:0098-1532    

DOI:10.1002/mpo.2950200705

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractApplication of erythropoietin during intensive chemotherapy for acute lymphoblastic leukemia in a 5 year old boy was effective in preventing transfusions of red blood cells. © 1992 Wiley‐Liss, I

ISSN:0098-1532    

DOI:10.1002/mpo.2950200706

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe toxicity and efficacy of recombinant human granulocyte‐macrophage colony‐stimulating factor (rhuGM‐CSF) is established in adults [1–4], but limited information is available on its use in children [5, 6]. The profound myelotoxicity induced by cisplatin (40 mg/m2daily × 5) and etoposide (150 mg/m2daily × 3) provides a model to test the clinical value of recombinant human granulocyte‐macrophage colony‐stimulating factor in pediatric cancer patients; myelosuppression occurred (absolute neutrophil count [ANC]<500/μL) during 99 of 118 (84%) courses given to 44 children with refractory solid tumors. Fifty‐nine courses (50%) resulted in hospitalizations for fever. Subsequently, rhuGM‐CSF was added to this treatment regimen to: (i) determine the dose‐limiting toxicity of this agent in children; and (ii) to determine whether it can decrease the duration and severity of neutropenia and attendant complications. Here we summarize and update our experience with this glycoprotein in children with relapsed solid tumors. ©

ISSN:0098-1532    

DOI:10.1002/mpo.2950200707

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractRhGM‐CSF is a hematopoietic growth factor which stimulates the proliferation, differentiation and functional activity of neutrophils, monocytes and macrophages [1]. It also stimulates proliferation of endothelial cells [2]and induces the production of other cytokines, such as interleukin (IL‐1), tumor necrosis factor (TNF), interferon, prostaglandin E2, and plasminogen activating factor which affects both hematopoietic and non‐hematopoietic cell activities [3]. Initial clinical studies in 1987 generally excluded experimental therapy with rhGM‐CSF in pediatric patients (age ± 17 years) unless life threatening illness related to neutropenia and infection developed (i.e., patients with graft failure). Serious complications of patients undergoing autologous bone marrow transplantation (BMT) related to pancytopenia include infection and hemorrhage. Other regimen related complications include venoocclusive disease, pneumonitis and mucositis. As a result of these complications, patients require intensive medical support including antibiotics and hyperalimentation. Initial hospital duration following marrow reinfusion is generally 4 to 5 weeks. Hematopoietic growth factors have been administered to patients undergoing autologous BMT as an attempt to reduce regimen related toxicity. © 1992 Wiley

ISSN:0098-1532    

DOI:10.1002/mpo.2950200708

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe multilineage hematopoietic effects of IL‐3 appear to be most important for its clinical use comprising especially leucocyte and platelet responses. This was demonstrated to be dose dependent characterising doses of 250 to 500 μg/m2/day subcutaneously as hematopoietic effective and well tolerable. Since preclinical data suggest synergism between IL‐3 and GM‐CSF hematopoietic effects of their sequential administration were evaluated in 15 patients with preserved hematopoietic function. An enhanced stimulation of megakaryopoiesis combined with more pronounced stimulation of granulopoiesis than IL‐3 alone could be demonstrated. The cytokine combination of IL‐3 and GM‐CSF was thus used during chemotherapy induced myelosuppression. Data indicates beyond the known amelioration of myelosuppression by GM‐CSF additional chances to enhance platelet recovery which can be of important clinical impact. © 1992

ISSN:0098-1532    

DOI:10.1002/mpo.2950200709

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0098-1532    

DOI:10.1002/mpo.2950200701

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY