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1.
S Asano K Hirashima Y Yoshida F Takaku T Miyazaki M Omine S Furusawa T Abe M Mori S Arimori 《[Rinshō ketsueki] The Japanese journal of clinical hematology》1990,31(9):1456-1462
The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on neutropenia was studied in 30 patients with aplastic anemia (AA). RhG-CSF was administered intravenously daily at a dose of 2, 5, 10, or 20 micrograms/kg/day for more than 7 days. In the patients whose absolute neutrophil counts (ANC) were more than 0.1 X 10(9)/l, the rhG-CSF injections at greater than or equal to 5 micrograms/kg/day caused rapid and selective elevation of ANC which maintained during the injection period. Most of the patients were well tolerated, and minor side effects were observed in only 3 patients. These findings suggest that daily injections of rhG-CSF at a dose of greater than or equal to 5 micrograms/kg/day may be an effective strategy for the treatment of bacterial and/or fungal infections in AA patients. 相似文献
2.
We investigated the efficacy and safety of high-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) in treating 10 children with severe aplastic anemia and fewer than 0.05 x 10(9)/L neutrophils. Doses of rhG-CSF ranging from 400 to 2,000 micrograms/m2/d were administered as a 30-minute intravenous infusion daily for 4 weeks. In 6 of the 10 children, treatment increased the neutrophil count by 10- fold to greater than 60-fold (range, 0.21 to 1.8 x 10(9)/L). Bacterial or fungal infections that were present at study entry resolved in all 6 responders, who are still alive with a median survival of more than 27 months (range, 15 to 54 months) since the initiation of treatment. Three of 4 nonresponders died of infection, whereas 1 nonresponder received a bone marrow transplant and is alive. No serious toxicity was attributable to rhG-CSF. It was well tolerated at doses up to 2,000 micrograms/m2/d and effectively stimulated granulopoiesis. This agent thus offers promise as adjuvant treatment for severe infections in children with aplastic anemia and very severe neutropenia. 相似文献
3.
The best-known adverse hematologic reaction of methimazole is agranulocytosis. Aplastic anemia is extremely rare. The prognosis within the entity of aplastic anemias is surprisingly good, despite the severe and prolonged course of the disease. The present article reports the case of a 74-yr-old female patient who exhibited aplastic anemia with severe clinical symptoms 8 weeks after the initiation of methimazole administration. The hemorrhagic symptoms were aggravated by a coumarin overdose. Supportive hemotherapy and antibiotic treatment were supplemented with recombinant human granulocyte colony-stimulating factor and high-dosage corticosteroids. The granulocyte count normalized on day 5 of treatment, the platelet count exceeded the critical value on day 11, and on day 25 the patient was discharged in remission. 相似文献
4.
Y Sonoda H Yashige H Fujii S Tsuda T Maekawa S Misawa T Abe 《European journal of haematology》1992,48(1):41-48
5 patients with refractory aplastic anemia (AA) received long-term administration (2-11 + months) of recombinant human G-CSF (rhG-CSF) in doses from 250-500 micrograms/body/day by intravenous infusion or 75-300 micrograms/body/d by subcutaneous injection. All 5 evaluable patients showed a substantial increase in absolute neutrophil count (ANC) with a recovery of myeloid components in the bone marrow after 1 to 2 months of treatment. Interestingly, 2 out of the 5 patients showed a dramatic improvement in severe anemia after 2 to 4 months of treatment accompanying a recovery of erythroid components in the bone marrow. In addition, there was no serious infection before or during therapy. Long-term administration of rhG-CSF was well tolerated because of its minimal toxicity. Clonal assay revealed a recovery of myeloid progenitors in all patients and a recovery of erythroid progenitors in 3 out of the 5 patients. These results suggest that long-term administration of rhG-CSF at least mobilizes residual myeloid as well as erythroid progenitor cells and induces a bilineage response in severe refractory AA. 相似文献
5.
X López-Karpovitch A Ulloa-Aguirre C von Eiff R Hurtado-Monroy A Alanis 《Acta haematologica》1992,87(3):148-150
The in vivo response to recombinant human granulocyte-monocyte colony-stimulating factor (rHu GM-CSF) in facilitating the reconstitution of granulomonopoiesis was evaluated in a patient with Graves' disease who developed severe aplastic anemia during methimazole therapy. After 10 days of treatment with rHu GM-CSF, the neutrophil and monocyte counts rose to 1.65 x 10(9)/l and 0.41 x 10(9)/l, respectively. However, the patient was still dependent on erythrocyte and platelet transfusions. Two days after rHu GM-CSF withdrawal, the neutrophil count dropped off to 0.41 x 10(9)/l.rHu GM-CSF was reinitiated for 2 days along with glucocorticosteroids. With this combined therapeutic approach, the neutrophil count returned to normal and remained stable, and both Hb and platelet values began to improve. It is concluded that the combination of rHu GM-CSF and glucocorticosteroids can be used as a therapeutic option that may lead to beneficial results in drug-induced aplastic anemia. 相似文献
6.
7.
Matsuda A Kishimoto K Yoshida K Yagasaki F Ito Y Sakata T Kawai N Ino H Hirashima K Bessho M 《International journal of hematology》2002,76(3):244-250
In our previous study, approximately 60% of aplastic anemia (AA) and refractory anemia (RA) patients treated with recombinant human granulocyte colony-stimulating factor (rhG-CSF) and recombinant human erythropoietin (rhEpo) showed a multilineage response. In this study, we analyzed the long-term follow-up of the multilineage responders (multi-R). In the follow-up analysis of 11 multi-R (6 AA and 5 RA), 10 patients (5 AA and 5 RA) were evaluable. The range of time from the start of treatment to the final contact was 50 to 125 months. Analysis of survival times revealed a significant difference between multi-R and non-multi-R among AA patients given this treatment (P = .016). One AA and 1 RA patient among the multi-R developed acute leukemia. Of 7 living multi-R, 3 AA and 2 RA patients did not need transfusion at final contact. Four of them maintained the target hemoglobin concentration of more than 11 g/dL for quality-of-life benefit. The findings suggested that this result is an important advantage of this treatment. 相似文献
8.
Treatment of refractory aplastic anemia with recombinant human granulocyte-macrophage-colony-stimulating factor 总被引:2,自引:0,他引:2
Fifteen patients with refractory aplastic anemia or agranulocytosis received treatment with recombinant human granulocyte-macrophage-colony-stimulating factor (rhGM-CSF) in doses from 4 to 64 micrograms/kg/d by continuous intravenous (IV) infusion. Ten of 11 evaluable patients with aplastic anemia had substantial increments in granulocytes, monocytes, and eosinophils associated with myeloid and eosinophilic hyperplasia in the bone marrow. Patients with pretreatment granulocytes greater than 0.3 x 10(9)/L had greater increments in circulating myeloid cells than patients with more severe granulocytopenia. Only one patient had improvement in erythrocytes and platelets. Blood counts fell to baseline after rhGM-CSF treatment was discontinued. Doses up to 16 micrograms/kg/d were relatively well tolerated in the absence of extreme leukocytosis. Fatigue and myalgia were common. Three patients developed pulmonary infiltrates that resolved with discontinuation of treatment. Patients tended to have recurrent inflammation in previously diseased tissues. These data indicate that rhGM-CSF will increase circulating granulocytes, monocytes, and eosinophils in patients with refractory aplastic anemia. Further studies are necessary to determine if rhGM-CSF treatment will reduce morbidity or improve survival. 相似文献
9.
Zonghong Shao Yulin Chu Yizhi Zhang Guibin Chen Yizhou Zheng 《American journal of hematology》1998,59(3):185-191
To evaluate the therapeutic potential of hematopoietic growth factors (HGFs) during immunosuppressive treatment (IST) of severe aplastic anemia (SAA), 38 patients with newly diagnosed SAA received IST alone (group I), or IST plus recombinant human erythropoietin and granulocyte-macrophage colony-stimulating factor (rhEPO + rhGM-CSF) (group II). Eleven patients in each group received antilymphocyte globulin (ALG) for IST, and eight patients in each group received cyclosporine (CSA). Complete remission rates at one year were 26% and 74% for group I and group II patients, respectively. The ALG-treated subgroup showed the greatest differences between treatments. Compared with patients receiving ALG alone, patients treated with ALG plus HGFs had significantly better one-year survival (100% vs. 54.5%, P < 0.05), complete remission rates (91% vs. 36%, P < 0.05), more rapid and complete hematologic recovery, greater reductions in transfusion requirements, and lower infection rates. The data suggest a potential role for rhEPO + rhGM-CSF therapy in SAA patients receiving IST. Am. J. Hematol. 59:185–191, 1998. © 1998 Wiley-Liss, Inc. 相似文献
10.
Pharmacokinetics of subcutaneous recombinant human granulocyte colony-stimulating factor in children. 总被引:7,自引:1,他引:7
Fifteen children (age 1.2 to 9.4 years) with advanced neuroblastoma were treated with myelosuppressive chemotherapy (cyclophosphamide, cisplatin, doxorubicin) followed by 5 (n = 5), 10 (n = 5), or 15 (n = 5) micrograms/kg recombinant granulocyte colony-stimulating factor (rG-CSF) subcutaneously (SC) once daily for 10 days, starting the day after chemotherapy. Serial serum samples obtained on days 1 and 10 were analyzed for G-CSF activity by a specific proliferation assay using NFS-60 cells. G-CSF serum concentration-time data were best described by a one-compartment model, with zero-order absorption and first-order elimination. After SC injection, absorption was prolonged, with peak concentrations of G-CSF (3 to 117 ng/mL) being reached after 4 to 12 hours. The relatively slow absorption, with a mean elimination half-life of 5.8 hours on day 1 and 4.5 hours on day 10, provided measurable G-CSF concentrations for the entire 24-hour dosing interval in all patients at each dosage level. The median apparent clearance of G-CSF on day 10 was significantly higher than on day 1 (0.57 v 0.31 mL/min/kg, P = .02), and was positively correlated with the absolute neutrophil count (ANC) (r2 = .33, P = .003). Systemic exposure to G-CSF was dose-related, but interpatient pharmacokinetic variability yielded overlap in area under the concentration-time curve (AUC) at all three dosage levels. Stepwise regression analysis showed that G-CSF AUC could be predicted by a model that includes rG-CSF dosage and ANC on the day of administration (r2 = .82, P = .0001). 相似文献
11.
K Sugimoto A Togawa K Miyazono K Itoh M Amano S Chiba M Hino H Mizoguchi F Takaku 《European journal of haematology》1990,45(2):110-111
Abstract: Two Spanish families with α thalassaemia, including 4 individuals with Hb H disease, are described. DNA mapping shows that, in addition to the common α thalassaemia determinant (-α3.7), a different and previously unreported allele is present in each family. In one, there is a deletion of 10.5–12 kb of DNA including both α genes (-SPAN). in the other, a deletion of more than 100 kb has removed the entire α globin gene complex (-BR). 相似文献
12.
13.
Nissen C; Tichelli A; Gratwohl A; Speck B; Milne A; Gordon-Smith EC; Schaedelin J 《Blood》1988,72(6):2045-2047
Four patients with very severe aplastic anemia refractory to antilymphocyte globulin were administered recombinant human granulocyte- macrophage--colony stimulating factor (GM-CSF). One patient with minimal residual myelopoiesis responded transiently to two separate courses of GM-CSF at 4 and 8 micrograms/kg/d administered intravenously and another course at 4 micrograms/kg/d administered subcutaneously. Septicemia and bilateral pneumonia that had been resistant to conventional therapy resolved. Three patients with no evidence of residual myelopoiesis did not respond to GM-CSF. In one patient, the dose was increased to 32 micrograms/kg/d with no effect on hematopoiesis. Immediate side effects were minimal at GM-CSF doses up to 16 micrograms/kg/d. GM-CSF may, however, have been involved in the pathophysiology of thrombosis of the inferior vena cava in the patient administered 32 micrograms/kg/d. We conclude that GM-CSF does not induce hematopoiesis in long-standing, severe, treatment-resistant aplastic anemia with complete myelopoietic failure. However, in patients with minimal residual myelopoiesis, GM-CSF could be a promising adjuvant therapy for severe infection. 相似文献
14.
Bessho M Hotta T Ohyashiki K Takahashi T Mizoguchi H Asano S Ikeda Y Sakurai M Tojo A Kizaki M Iwanaga M Tomonaga M Hirashima K 《International journal of hematology》2003,77(2):152-158
To elucidate the relationship between treatment with granulocyte colony-stimulating factor (G-CSF) and the development of chromosomal abnormalities and clonal evolution in adult aplastic anemia (AA) patients, we performed a prospective multicenter study. Of the 104 registered patients, 91 were found by the central review committee to have the diagnosis of AA. Of the 91 patients, 84 were determined to be evaluable in this study and were treated with regimens including G-CSF (lenograstim). A time-course study (at registration and 6 and 12 months after registration) of G-banded chromosomes, fluorescence in situ hybridization (FISH) analysis for monosomy 7, and morphological assessment of bone marrow was performed with these patients during the 1-year follow-up period. G-banding analysis demonstrated the development of cytogenetic abnormalities in 10 (16.1%) of the 62 evaluable patients. The most common aberration was monosomy 7. FISH analysis demonstrated monosomy 7 in 7 (10.4%) of the 67 evaluable patients. Evolution into myelodysplastic syndrome (MDS) was observed in 5 (7.7%) of the 65 patients who underwent morphological assessment of bone marrow. All patients who developed cytogenetic abnormalities or MDS received immunosuppressive agents and/or steroids with G-CSF. This study demonstrated that some adult AA patients exhibit evolution into MDS and development of chromosomal abnormalities such as monosomy 7. Although the incidence seems to be comparable with that found in previous studies, further long-term follow-up will be necessary to confirm the relationship between G-CSF and the development of chromosomal abnormalities and MDS. 相似文献
15.
A phase I/II trial of recombinant granulocyte-macrophage colony-stimulating factor for children with aplastic anemia 总被引:1,自引:0,他引:1
Nine pediatric patients (median age, 8 years; range, 0.7 to 19 years), eight with refractory aplastic anemia and one with newly diagnosed aplasia, were enrolled in a phase I/II trial of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) administered via continuous intravenous infusion. Doses ranged from 8 to 32 micrograms/kg/d. Six of eight evaluable patients responded with a significant rise in neutrophil count (median fourfold increase; range, 2.5- to 31-fold) during the 28-day induction period. Five patients completed 2 further months of therapy (maintenance) with persistent or improved neutrophil responses. Three patients had bone marrow aspirates suggestive of increased erythropoiesis, although only one patient had improvement in peripheral hematocrit and platelet count. In the five patients completing maintenance, three experienced a rapid return to baseline counts after rhGM-CSF was discontinued, one maintained a neutrophil response for 2 months after drug discontinuation, and one has maintained a trilineage response for greater than 1 year off study. Drug therapy was well tolerated. Toxicity was minimal at doses from 8 to 16 micrograms/kg/d. Fever and rash were more commonly seen at 32 micrograms/kg/d. No patient developed an infection during the course of rhGM-CSF administration. These results demonstrate that rhGM-CSF increases peripheral neutrophil counts in children with refractory and newly diagnosed aplastic anemia and may be able to stimulate a multilineage response in a more limited number. Randomized, prospective trials are necessary to determine if rhGM-CSF administration will impact favorably on the morbidity and mortality of severe aplastic anemia. 相似文献
16.
We administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) intravenously for 2 weeks to 2 elderly patients with severe neutropenia. The absolute neutrophil count (ANC) recovered promptly after the initiation of rhG-CSF therapy and reached a peak (greater than 10 x 10(9)/l) on the 13th day. The ANC fell rapidly after rhG-CSF was discontinued, but it remained within the normal range after therapy. There were no side effects during the entire course of treatment. Therefore, rhG-CSF seems to be a most beneficial treatment in elderly patients with severe neutropenia. 相似文献
17.
Immunosuppressive therapy using antithymocyte globulin, cyclosporine, and danazol with or without human granulocyte colony-stimulating factor in children with acquired aplastic anemia 总被引:21,自引:4,他引:21
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Kojima S Hibi S Kosaka Y Yamamoto M Tsuchida M Mugishima H Sugita K Yabe H Ohara A Tsukimoto I 《Blood》2000,96(6):2049-2054
A prospective multicenter trial of 119 children 1 to 18 years of age with newly diagnosed aplastic anemia (AA) was conducted, comparing treatment using antithymocyte globulin (ATG), cyclosporine (CyA), and danazol (DAN) with or without rhG-CSF (400 microg/m(2), day on days 1-90). All children with very severe AA received rhG-CSF (VSAA group, n = 50). The other children were randomized to receive ATG, CyA, DAN, and rhG-CSF (G-CSF+ group, n = 35) or ATG, CyA, and DAN without rhG-CSF (G-CSF- group, n = 34). After 6 months, the hematologic response rate was 71%, 55%, and 77% in the VSAA group, G-CSF+ group, and G-CSF- group, respectively. There was no difference in the incidence of febrile episodes and documented infections between the G-CSF+ and G-CSF- groups. Bone marrow transplantation (BMT) was attempted in 22 patients in whom initial immunosuppressive therapy (IST; n = 18) failed or in whom a relapse occurred after an initial response (n = 4). Nineteen of the 22 patients are alive and well after a median follow-up of 18 months (range, 3 to 66 months) since BMT. The probability of survival at 4 years was 83% +/- 7% in the VSAA group, 91% +/- 5% in the G-CSF+ group, and 93% +/- 6% in the G-CSF- group. Myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) developed in one patient in each of the three groups; the overall risk for MDS/AML was 3% +/- 2% at 4 years. Because the results of IST were encouraging, it is suggested that children with AA receive IST as first-line therapy if there is no human leukocyte antigen-matched sibling donor. 相似文献
18.
Negrin RS; Stein R; Vardiman J; Doherty K; Cornwell J; Krantz S; Greenberg PL 《Blood》1993,82(3):737-743
We treated myelodysplastic syndrome patients (MDS) with both recombinant human granulocyte colony-stimulating factor (G-CSF) and recombinant human erythropoietin (EPO) to determine whether such combination therapy resulted in improvement of their anemias. Twenty- four of 28 patients begun on study completed the protocol and were evaluable for erythroid responses. Therapy was initiated with G-CSF at 1 micrograms/kg administered by daily subcutaneous injection and adjusted to either normalize or double the neutrophil count. EPO was then administered by daily subcutaneous injection at a dose of 100 U/kg and dose-escalated to 150 and 300 U/kg every 4 weeks while continuing the G-CSF. Changes in absolute reticulocyte count, hematocrit level, and need for RBC transfusions were compared with pretreatment values as well as other blood cell counts. Ten of 24 patients (42%) had erythroid responses, whereas all patients had neutrophil responses. Six previously transfused patients no longer required RBC transfusions during the treatment period. Erythroid responses were found to be independent of patient age, French-American-British subtype, duration of disease, prior RBC transfusion requirements, or cytogenetic abnormalities at presentation. Pretreatment serum EPO levels were lower in erythroid-responding as compared with nonresponding patients (median 157 v 600 U/L; P = .05). The combined treatment modality was generally well tolerated. We conclude that a substantial percentage of MDS patients had both erythroid and myeloid responses when treated with the combination of G-CSF and EPO. 相似文献
19.
Dinçol G Aktan M Diz-Küçükkaya R Yavuz S Nalçaci M Oztürk S Palanduz S Doğan O Ağan M 《American journal of hematology》2007,82(9):783-786
Fifty-six adult patients with newly diagnosed acquired severe aplastic anemia (SAA) received horse antilymphocyte globulin (ALG), cyclosporin A (CyA), methylprednisolone (Mpred), granulocyte colony-stimulating factor (G-CSF) as first-line therapy. The median age was 34 (range, 17-72) and median neutrophil count 0.280 x 10(9)/L. Trilineage hematologic recovery (at a median interval of 105 days from treatment) was seen in 46 patients (37 complete, 9 partial) after one (n = 38) or two (n = 8) courses of ALG. Cytogenetic abnormalities were observed in three unresponders, clonal hematologic disease in three complete responders, and relapse of marrow aplasia in four complete responders. Median follow up for surviving patients was 1,668 days (range, 237-4,012). The actuarial survival at 5 years was 82%, falling to 77.1% at 7 years and was stationary at 7 and 8 years. Survival was not influenced by the neutrophil count (72% vs. 87%, for neutrophils less than vs. greater than 0.2 x 10(9)/L; P = 0.54). Immunosuppressive treatment of SAA with the 4-drug combination appears to be effective. The significant prognostic effect of an enduring increase of the white blood cell (WBC) count during G-CSF treatment may suggest complete and partial response to therapy. In nonresponders, the WBC count either did not change or elevated values gradually returned to nearly their initial levels while the patients were still under G-CSF treatment. In patients not responsive to treatment but living under CyA and G-CSF, the possibility of developing cytogenetic abnormalities does not seem to be low, despite the absence of findings attributable to manifest myelodysplastic syndrome. 相似文献
20.
Effect of recombinant human granulocyte macrophage-colony stimulating factor in long-term marrow cultures from patients with aplastic anemia. 总被引:1,自引:0,他引:1
The hematopoietic system in patients with aplastic anemia (AA) shows both quantitative and qualitative deficiencies, i.e., reduced numbers of hematopoietic progenitor cells (HPC) and impaired HPC proliferation in long-term marrow cultures (LTMC). Since recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) has been shown to be a potent stimulator of normal hematopoiesis, both in vivo and in vitro, in the present study we wanted to assess the possibility of stimulating hematopoiesis in LTMC from 17 patients with AA, by weekly addition of rhGM-CSF (10 ng/ml). In LTMC from 11 patients (group of responders), rhGM-CSF induced a significant increase (4.8-fold, compared with untreated cultures) in the levels of myeloid progenitor cells; in contrast, in six patients (group of nonresponders), myeloid progenitors were refractory to this cytokine. In the group of responders, rhGM-CSF also induced a pronounced increment in the levels of nonadherent and adherent cells (5.99- and 5.18-fold, respectively, compared with untreated cultures). Among the different myelopoietic lineages, rhGM-CSF preferentially stimulated the macrophagic lineage; this was evident both at the progenitor and mature cell levels. Interestingly, the effect of rhGM-CSF in LTMC from AA patients was only transient. Indeed, the effects mentioned above were observed only during the first three weeks of culture; afterwards, myeloid progenitor and nonadherent cell levels in treated cultures declined, practically reaching the levels observed in untreated cultures. At the moment, we do not know whether this transient stimulatory effect is due to the production of inhibitory cytokines, by macrophages generated in response to rhGM-CSF, or to the exhaustion of the HPC pool in AA cultures. In all 17 patients, rhGM-CSF had no effect on the kinetics of erythroid or multipotent progenitor cells. These results are in keeping with clinical studies in which it has been observed that most AA patients treated with rhGM-CSF show increments in circulating monocytes and granulocytes, as well as in bone marrow cellularity. However, little or no effect is observed on erythropoiesis. The actual mechanisms involved in the in vitro effects of rhGM-CSF on myeloid progenitor cells from AA bone marrow are still not completely understood. Future studies on this issue should be encouraged, since they may help to understand the in vivo (clinical) effects of this cytokine. 相似文献