Haematopoietic growth factor in antithyroid-drug-induced agranulocytosis

Drug-induced agranulocytosis (DIA) is often caused by antithyroid drugs. We retrospectively studied the use of granulocyte colony-stimulating factor (G-CSF) therapy in antithyroid-DIA. Data for 20 patients (10 treated with G-CSF) with antithyroid-DIA (neutrophil count <0.5x10(9)/l) were extracted from a cohort study of DIA patients (n=110). G-CSF (300 microg/day subcutaneously) was used where the neutrophil count was <0.1x10(9)/l, or the patient was aged >70 years, or there were severe features of infection or underlying disease. Mean patient age was 62 years (range 34-87); sex ratio (M/F) was 0.05. Carbimazole (n=19) and benzylthiouracile (n=1) were the causative drugs, at mean doses of 30 mg/day (range 20-60) and 100 mg/day (range 50-150), respectively, for a mean of 37 days (range 31-90). Antithyroid drugs were prescribed for Graves' disease (n=8), thyrotoxicosis related to amiodarone intake (n=6) and multinodular goitre (n=6). Clinical features included isolated fever (n=7), pneumonia (n=5), septicaemia or septic shock (n=5) and acute tonsillitis (n=3). Mean neutrophil count was 0.07+/-0.1x10(9)/l. No patient died. Mean durations of haematological recovery, antibiotic therapy and hospitalization were significantly reduced with G-CSF: 6.8+/-4 days vs. 11.6+/-5; 7.5+/-3.8 days vs. 12+/-4.5; and 7.3+/-4.8 days vs. 13+/-6.1, respectively (all p<0.05). G-CSF induced flu-like symptoms in 30% of patients, but reduced overall costs.     

Hematopoietic colony-stimulating factors for neutropenic patients in the ICU

OBJECTIVE: To assess whether adjunct hematopoietic colony-stimulating factor (H-CSF) accelerates neutrophil recovery and improves survival. DESIGN: A retrospective study. SETTING: Medical/surgical intensive care unit (ICU). PATIENTS: 30 neutropenic patients admitted to the ICU and treated with H-CSF. Controls were the preceding 30 neutropenic patients not treated with H-CSF. MEASUREMENTS AND RESULTS: Patient admission characteristics were reviewed. Endpoints were neutrophil recovery ( > 1.0 x 10(9)/l), length of ICU stay and survival. Depth and duration of neutropenia (0.267 +/- 0.04 x 10(9)/l for 12 +/- 1.7 days vs 0.293 +/- 0.05 x 10(9)/l for 15 +/- 1.9 days; p = 0.67 and 0.21), and the Acute Physiology and Chronic Health Evaluation II and organ system failure scores were similar. Systemic candidiasis was lower in the H-CSF group (20 vs 3 %; p > 0.05). In 11 (36.6 %) and 10 (33.3 %) patients neutrophil count recovered ( > 1.0 x 10(9)/l); H-CSF did not reduce the duration of neutropenia (7.8 +/- 1.4 vs 5.7 +/- 1.3 days; p = 0. 28), the length of ICU stay (7.8 +/- 1.1 vs 8.9 +/- 1.5 days; p = 0. 55) or improve survival (23 vs 10 %; p = 0.168). CONCLUSION: H-CSF for treatment of neutropenia in patients admitted to the ICU did not accelerate neutrophil recovery or improve survival.     

自体外周血干细胞移植治疗恶性血液病临床疗效观察

目的　对４９ 例自体外周血干细胞移植（ＡＰＢＳＣＴ） 治疗的恶性血液病患者有关材料进行总结分析。方法　ＡＰＢＳＣＴ治疗恶性血液病患者４９ 例,计５１ 例次,其中急性髓系白血病（ＡＭＬ）１８ 例,急性淋巴细胞白血病（ＡＬＬ）１０ 例,多发性骨髓瘤（ＭＭ）１４ 例（ 其中２ 例行２ 次移植） ,非霍奇金淋巴瘤（ＮＨＬ）６ 例,骨髓增生异常综合征ＲＡＥＢｔ１ 例。结果　与常规化疗相比,ＡＰＢＳＣＴ可延长移植患者的无病生存期及总生存期,３ 年及５ 年生存率在ＡＭＬ、ＮＨＬ组分别为７４．７８％ 和８３．３３％ ,ＭＭ 组为３８ ．００ ％ 和１９ ．００ ％ ,ＡＬＬ组为４０ ．００ ％ 和０ 。移植后造血重建时间,未用ＧＣＳＦ组干细胞回输后平均第１７ ．６ 天外周血白细胞恢复至＞０ ．５×１０９／Ｌ,用ＧＣＳＦ组平均１１．１４ 天。４９ 例患者移植相关死亡率为零,至今随访７ 年,死亡２１ 例,其中２０ 例死于复发,主要为ＡＬＬ和ＭＭ 患者。移植相关并发症以发热、肝功能受损和低钾最常见,经治疗可好转。结论　ＡＰＢＳＣＴ是治疗血液系统肿瘤,改善其预后的重要手段之一。     

第二次移植治疗异基因造血干细胞移植后复发白血病的临床研究

目的　评价第二次异基因造血干细胞移植 (allo HSCT)治疗allo HSCT后复发白血病的疗效。方法　回顾分析因allo HSCT后复发而进行第二次allo HSCT的 1 0例白血病患者临床资料。其中急性髓系白血病 5例 ,急性淋巴细胞白血病 4例 ,慢性髓系白血病 1例。第一次HSCT后中位复发时间 1 4 1d(34～ 5 4 5d)。第二次HSCT时预处理方案包括 :以中剂量阿糖胞苷 (Ara C)为主的联合化疗 5例 ;以白消安为主的联合化疗 3例 ;含常规剂量Ara C的联合化疗 1例 ;氟达拉宾 /马法兰 1例。移植物抗宿主病 (GVHD)预防方案 :单用环孢菌素 (CsA) 2例 ,CsA 短疗程甲氨蝶呤 1例 ,短疗程他克莫司 1例 ,6例未预防。输注外周血单个核细胞中位数 6 .1× 1 0 8/kg[(1 .9～ 1 1 .8)× 1 0 8/kg]。 结果　可评价的 8例患者均造血重建 ,达中性粒细胞绝对值 >0 .5× 1 0 9/L、血小板 >2 0× 1 0 9/L中位时间分别为移植后 1 1d(3～ 1 7d)、1 2d(9～ 2 3d)。发生Ⅰ度急性GVHD 4例 ,Ⅱ度急性GVHD 3例。可评价的 6例中 5例发生局限型慢性GVHD。 2例无病生存 986d和 1 91 3d。移植相关死亡 5例。复发 3例 ,均死亡。 2年实际无病生存率、移植相关死亡率、复发率分别为 2 0 %、5 0 %和 30 %。结论　第二次allo HSCT是治疗allo HSCT后复发白血病的有效     

Efficacy of colony-stimulating factors in acute leukemia

OBJECTIVE: To evaluate the literature describing the safety and efficacy of the hematopoietic colony-stimulating factors (CSFs) for the management of treatment-related adverse effects in patients with acute leukemia. DATA SOURCES: A systematic MEDLINE search of the English-language literature (1995-April 2000) was performed to identify all randomized trials evaluating CSF use in acute leukemia. The following search terms were used: granulocyte colony-stimulating factor, filgrastim, granulocyte-macrophage colony-stimulating factor, sargramostim, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), acute nonlymphocytic leukemia, and acute myeloid leukemia. The references from relevant literature were also examined in order to identify reports not discovered in the MEDLINE search. DATA SYNTHESIS: Six randomized trials in pediatric ALL, nine in adult AML, and four in adult ALL have examined the safety and efficacy of the CSFs. Two of the pediatric trials supported a reduction in either the duration of hospitalization or in the incidence of febrile neutropenia when a CSF was employed during the consolidation or intensification phase of chemotherapy. The remaining pediatric trials failed to demonstrate a clinical benefit. In adult AML, eight of the nine trials showed a significant decrease in the time to neutrophil recovery when a CSF was used. Only one of these trials demonstrated a decrease in hospital stay and none showed a decreased incidence of infection for patients who received a CSF. Three of the four trials in adult ALL demonstrated the efficacy of a CSF in decreasing the number of days to neutrophil recovery. Only one trial demonstrated that a CSF led to a reduction in the number of hospital days. Trials in children or adults have not demonstrated that the CSFs influence the long-term outcome of patients with acute leukemia. CONCLUSIONS: The published studies document a decrease in the time to recovery from neutropenia when patients with acute leukemia are treated with a CSF. However, a consistent reduction in infectious complications or in the duration of hospitalization has not been demonstrated when a CSF is used for either pediatric or adult patients. Very limited data exist to support the premise that CSFs meet the criteria established by the American Society of Clinical Oncology for demonstrating the value of these agents. Further careful study focused on resource utilization and pharmacoeconomics may help to elucidate how healthcare institutions may most effectively employ CSFs to treat patients with acute leukemia.     

Time course changes in the count of peripheral granulocytes in children with acquired aplastic anemias treated with antithymocyte globulin,cyclosporin A and granulocytic colony stimulating factor

AIM: To examine the pattern of changes in the count of peripheral granulocytes in children with aplastic anemias (AA), receiving a combined immunosuppressive therapy with antithymocytic globulin (ATG) and cyclosporin A in combination with granulocytic colony-stimulating factor (G-CSF). MATERIALS AND METHODS: 31 children (17 boys and 14 girls) aged 2-15 years (median 9 years) with newly diagnosed severe and very severe acquired AA took a combined immunosuppressive therapy with ATG and cyclosporin A in combination with G-CSF in an initial dose of 10 micrograms/kg a day. RESULTS: A three-linear and response was recorded in 19 (61%) children, an isolated granulocytic response was in 26 (84%). The interval median before the recovery of granulocytes to 1.5 x 10(9)/l and 5 x 10(9)/l was 19 and 38 days, respectively. CONCLUSION: Use of G-CSF may increase the count of granulocytes in the vast majority of patients with AA, without dramatic influence on the frequency of a three-linear response. Intermittent use of G-CSF may maintain the count of granulocytes long at the safe level and reduce the cost of treatment.     

Factors influencing collection and engraftment of CD34+ cells in patients with breast cancer following high-dose chemotherapy and autologous peripheral blood progenitor cell transplantation

Although autologous PBPC transplantation is being used increasingly for the treatment of breast cancer, there are few data on factors influencing mobilization and engraftment in these patients. We have analyzed these factors in 70 patients with advanced or metastatic breast cancer undergoing autologous PBPC transplantation. All patients were mobilized after stimulation with G-CSF, and a median of 3.16 x 10(6)/kg CD34+ cells (range 0.75-23.33) were infused. All patients received conditioning with a combination of cyclophosphamide, thiotepa, and carboplatin, and postinfusion G-CSF was administered to 60 patients. The median times to reach 0.5 x 10(9)/L and 1 x 10(9)/L neutrophils were 10 and 11 days, respectively. The median times to obtain 20 x 10(9)/L and 50 x 10(9)/L platelets were 12 and 18 days, respectively. An analysis of factors that influence CD34+ cell collection was performed by linear regression. Previous radiation therapy and increasing age were associated with lower numbers of CD34+ cells collected. Those variables that could influence the tempo of engraftment were examined by multivariate analysis using Cox regression models. The number of CD34+ cells infused was found to influence both neutrophil and platelet recovery. The use of G-CSF after transplant, accelerated neutrophil recovery, and having more than six cycles of previous chemotherapy was an unfavorable factor for recovering >50 x 10(9)/L platelets.     

Ceftriaxone plus once daily aminoglycoside with filgrastim for treatment of febrile neutropenia: early hospital discharge vs. Standard In-patient care

BACKGROUND: In febrile neutropenic patients, ceftriaxone plus an aminoglycoside is effective for the treatment of infection, while filgrastim reduces the extent and duration of neutropenia. Because the once daily dosing regimen of this combination permits ambulatory treatment, there is a need to test criteria for early hospital discharge. METHODS: Hospitalized adult patients with febrile neutropenia (following chemotherapy) considered to be potentially treatable on a follow-up out-patient basis were entered into this open-label, multinational study. Patients received a once daily combination of ceftriaxone for > or =5 days, aminoglycoside for > or =2 days, and filgrastim until the absolute neutrophil count was > or =1.0x10(9)/l for 2 days. Those initially responding to therapy (reduction of fever by > or =1 degrees C within 72 h, and clinical improvement) were randomized into standard in-patient or follow-up out-patient treatment groups, the latter patients being discharged from hospital early, after meeting defined criteria. RESULTS: 105 patients were enrolled, of whom 21 initial non-responders were not randomized. Efficacy was evaluable in 80 patients. Success (resolution of fever and symptoms, maintained for 7 days after cessation of therapy, and eradication of infecting pathogens) was similar among in-patients (40/42, 95%) and out-patients (34/38, 89%). The duration of hospitalization was shorter for out-patients than in-patients (median of 4 vs. 6 days, respectively). No hospital readmissions were necessary in out-patients. All other efficacy parameters assessed were comparable in both groups, as was tolerability/safety. One potentially drug-related death was reported. CONCLUSIONS: Patients who satisfy prospectively defined criteria for early discharge can be treated safely on an out-patient basis with a regimen of once daily ceftriaxone plus an aminoglycoside with filgrastim. In addition to reducing healthcare costs, it may improve patients' quality of life. Copyright Copyright 1999 S. Karger AG, Basel.     

Granulocyte transfusions from G-CSF-stimulated donors for the treatment of severe infections in neutropenic pediatric patients with onco-hematological diseases

From March 1994 to January 2001, 15 courses of granulocyte transfusion (GTX) were administered to 13 neutropenic patients (6 male and 7 female patients; median age 7 years, range 3 months to 14 years) affected by: acute lymphoblastic leukemia (ALL) in 6 cases, acute myeloid leukemia (AML) in 5, very severe aplastic anemia in 1, and familial erythrophagocytic lymphohistiocytosis (FEL) in 1. Infections were classified as microbiologically defined and clinically defined infections in 8 and 7 episodes, respectively. Before the GTX transfusions, broad-spectrum antibacterial and antifungal therapy had been administered for a median of 12 (range 5-28) and 8 days (range 2-50), respectively, with no improvement. G-CSF was administered prior to GTX in 9 episodes of infection, with a median of 9 days of treatment (range 4-30). Leukapheresis was obtained from 15 related donors (father, 10; mother, 3; sister, 1; aunt, 1) after s.c. stimulation with G-CSF, 300 micro g daily, starting from day -3 (where day 0 was the day of the first granulocyte collection) and continuing throughout the period of GTX treatment. The donors' median white blood cell (WBC) count at leukapheresis was 31.6 x 10(9)/l (range 12-56), and the median yield was 31.39 x 10(9) WBC (range 2.96-64.73 x 10(9)), with a proportion of PMN of 90-95%. Overall, 70 GTX were administered, with a median of 4 GTX per episode of infection (range 2-11). The combination of GTX with antimicrobial therapy led to complete or partial recovery in 6 and in 3 of 15 episodes (60%), respectively. Priming of the donor with G-CSF was well tolerated, the most common side-effects being bone pain, malaise and paresthesia. All donors are alive and well after a median of 4.5 years (range 0.8-7.7) from donation. We conclude that GTX is potentially useful when the severity of the infection and the host's immunodeficiency make any other antimicrobial treatment ineffectual. Long-term safety data on the stimulation of donors with G-CSF have been reassuring to date. Further controlled studies are needed to assess the exact role of GTX in the outcome of neutropenic patients with severe infection and any criteria for patient selection and the timing of GTX administration.     

IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.     

Factors influencing mobilization and engraftment in patients with metastatic breast cancer undergoing PBSC transplantation.

Factors influencing mobilization and engraftment of PBSC were analyzed in 38 patients with metastatic breast cancer who were undergoing PBSC transplantation. None of these patients had had previous chemotherapy for metastatic disease. PBSC were mobilized with cyclophosphamide (CY) and G-CSF (n = 21) or CY and etoposide (CY-etoposide) and G-CSF (n = 17). All received cyclophosphamide 6000 mg/m2, thiotepa 500 mg/m2, and carboplatin 800 mg/m2 (CTCb) as preparative regimen. PBSC infusion was followed by G-CSF at 5 microg/kg in 30 patients or 10 microg/kg in 8 patients. A median number of 27 x 10(6) CD34+ cells/kg was obtained with a median of four aphereses. Previous chemotherapy, radiation therapy, marrow disease, time from previous chemotherapy to mobilization, and type of mobilization regimen did not have a statistically significant effect on collection efficiency (CE). CE was defined as the total number of CD34+ collected/number of collections. Engraftment was rapid, with patients reaching a neutrophil count of 0.5 x 10(9)/L a median of 9 days (range 7-23) and a platelet count of 20 x 10(9)/L a median of 12 days (range 8-28) after transplantation. Shorter times to platelet recovery were associated with a higher number of CD34+ cells infused (p = 0.012), CY mobilization (p = 0.033), and a lower number of prior chemotherapy cycles (p = 0.022). When the number of CD34+ cells was included in the proportional hazard model, no other variables were found to be significant predictors of platelet engraftment. Time to neutrophil recovery was negatively associated with the dose of G-CSF used after transplantation (p = 0.036) CD34 cell dose is an important predictor of engraftment kinetics. A posttransplant dose of G-CSF improves neutrophil recovery. For patients with metastatic breast cancer and no previous chemotherapy for metastatic disease, we have no evidence for a difference between CY and CY-Etoposide as the mobilization regimen.     

白血病患儿接受父/母单倍相合未去T细胞骨髓移植的临床观察

为探讨单倍相合未去T细胞的骨髓移植治疗儿童白血病的临床疗效及可行性,对8例白血病儿童（1.9岁-9岁）接受父/母单倍体相合骨髓移植疗效进行了评价。对5例患儿采用了含全身照射（TBI）的预处理方案,它包括阿糖胞苷＋环磷酰胺＋全身照射（Ara-C/CTX/TBI）;对另外3例不加TBI,单用马利兰＋阿糖胞苷＋环磷酰胺（Bu/Ara-C/CY）预处理方案。移植物抗宿主病（GVHD）的预防措施包括供者用粒细胞集落刺激因子（G-CSF）及受者接受环孢菌素A（CsA）、氨甲蝶呤（MTX）、抗胸腺细胞球蛋白（ATG）、CD25单克隆抗体和霉酚酸酯（MMF）联合治疗。结果显示：8例患者移植后均获得造血重建,中性粒细胞数大于0.5×109/L的平均天数是16天,血小板数大于20×109/L的平均天数是17天,骨髓植活的直接证据检测证实为完全供者造血。移植后急性重度GVHD的发生率低,仅1例发生急性肠道Ⅱ-Ⅲ度GVHD（1/8）;5例出现慢性GVHD,其中4例为局限性慢性GVHD,1例为泛发性（合并有肺部GVHD）。在180天内无移植相关死亡,期间无致死性严重感染发生,髓系造血和免疫功能恢复较快。中位随访33个月（范围7-56月）,2例死亡,均死于白血病复发,其中1例移植后22月死于供者源复发。结论：对儿童白血病进行单倍相合未去T细胞骨髓移植时采用上述预处理方案和GVHD预防措施是安全、可行、有效的。     

The role of diagnosis in patients failing peripheral blood progenitor cell mobilization

BACKGROUND: Failure to mobilize PBPCs for auto-logous transplantation has mostly been attributed to previous therapy and poses therapeutic problems. STUDY DESIGN AND METHODS: The role of underlying disease was analyzed in 17 of 73 (23%) patients with PBPC mobilization failure, and secondary mobilization with high-dose filgrastim was attempted. RESULTS: Of 16 patients with acute leukemia, 13 (81%) mobilized poorly. In contrast, of 57 patients with non-Hodgkin's lymphoma, Hodgkin's lymphoma, multiple myeloma, and solid tumor, 53 (93%, p < 0.001) showed good PBPC mobilization. Relapsed disease did not predispose to poor mobilization. As secondary mobilization attempt, 7 patients received 25 micro g per kg per day filgrastim without chemotherapy leading to a 3.7 +/- 2.8-fold (SD) increase in the maximum number of circulating CD34+ cells (p = 0.104). PBPC apheresis yielded 3.3 (+/-0.5) x 10(6) CD34+ cells per kg of body weight in 5 patients. Four poor mobilizers received 50 micro g per kg per day filgrastim as second or third mobilization attempt. Circulating CD34+ cells in these patients increased by 1.5 (+/-0.7) compared with the primary G-CSF application. CONCLUSION: Selective PBPC mobilization failure was seen in patients with acute leukemia whereas remarkably good mobilization was seen in other malignancies. Increasing the filgrastim dose to 25 micro g per kg per day may allow PBPC collection in patients failing PBPC mobilization.     

Impact of colony-stimulating factor therapy on clinical outcome and frequency rate of nosocomial infections in intensive care unit neutropenic patients

OBJECTIVES: To determine whether the use of recombinant human granulocyte colony-stimulating factor (G-CSF, filgrastim) reduces the mortality rate and the frequency rate of nosocomial infections in neutropenic patients requiring intensive care unit (ICU) admission. DESIGN: Retrospective consecutive case series analysis. SETTING: Medical ICU of a teaching hospital. PATIENTS: We compared two groups of patients, according to whether or not they received G-CSF. In the ICU, 28 leukopenic patients received filgrastim (5 microg of body weight per day intravenously). In all these patients, G-CSF was continued until recovery from leukopenia, defined as a leukocyte count >1,000/mm3. A total of 33 ICU leukopenic patients did not receive G-CSF. End points included leukocyte count, bone marrow recovery, frequency of ICU nosocomial infections (pneumonia, urinary tract, and catheter-related infections), and mortality rate. MEASUREMENTS AND MAIN RESULTS: There were no differences in number of patients who recovered from leukopenia or in whom blood leukocyte count increased. Nosocomial infections occurred in the same percentage in both groups. The percentage of patients who died was identical in both groups. The percentage of patients with and without filgrastim therapy who recovered from leukopenia but died, was 86% and 78%, respectively. CONCLUSION: In the ICU, clinical outcome of neutropenic patients was not changed by G-CSF therapy. It is possible that G-CSF therapy may not be helpful in improving the ICU clinical outcome of neutropenic patients. Additional controlled studies designed to address this question are warranted.     

CD34+ cell dose requirements for rapid engraftment in a sequential high-dose chemotherapy regimen of paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) with PBPC support in metastatic breast cancer

Sequential high-dose chemotherapy may increase the threshold dose of CD34+ cells necessary for rapid and successful hematologic recovery. There are limited data regarding the pharmacodynamics and threshold CD34+ cell dose required for engraftment following high-dose paclitaxel. To determine the dose of CD34+ PBPC sufficient for rapid engraftment, 65 women with metastatic breast cancer undergoing a sequential high-dose paclitaxel, melphalan, and cyclophosphamide, thiotepa, and carboplatin (CTCb) chemotherapy regimen were evaluated. The intertreatment interval was a median of 27 days. Paclitaxel was escalated from 400 to 825 mg/m2, infused continuously (CI) over 24 h on day -4 with PBPC reinfusion on day 0. Following marrow recovery, 90 mg/m2/day of melphalan was given over 30 min on days -2 and -1, with PBPC reinfusion on day 0. On recovery, patients received CTCb on days -7 to -3, with PBPC reinfusion on day 0. G-CSF was administered after each cycle until WBCC recovery. For paclitaxel, an ANC >0.5 x 10(9)/L occurred at a median of 6 days (range 0-7 days) after PBPC reinfusion. The median nadir platelet count was 63 x 10(9)/L (range 6 x 10(9)/L-176 x 10(9)/L). Eight patients (12%) had platelet nadir <20 x 10(9)/L, and all recovered their counts to >20 x 10(9)/L on day 7. There was no clinical difference in days to engraftment between women receiving <2 or > or =2 x 10(6) CD34+ PBPC/kg following paclitaxel. All patients recovered neutrophil and platelet counts within 7 days after reinfusion of > or =1 x 10(6) CD34+ cells/kg and G-CSF. The data suggest that a paclitaxel dose of 825 mg/m2 is not myeloablative. For melphalan, median days to ANC >0.5 x 10(9)/L was 10 days (range 9-15), and platelet recovery to >20 x 10(9)/L was 13 days (range 0-28) after PBPC reinfusion. Median time to engraftment was more rapid in patients receiving > or =2 x 10(6) CD34+/kg versus <2 x 10(6)CD34+/kg, for both neutrophils (11 days versus 10 days, p = 0.05) and platelets (14 days versus 12 days, p < 0.01). Ninety-eight percent of patients infused with > or =2 x 10(6) CD34+/kg engrafted within 21 days. Following CTCb in this sequential regimen, a dose of > or =2 x 10(6) CD34+ cells/kg provided for significantly more rapid neutrophil engraftment than <2 x 10(6) CD34+ cells/kg (9 days versus 10 days,p = 0.01), but a dose > or =3 X 10(6) CD34+ cells/kg is necessary for reliable, rapid, and sustained neutrophil and platelet engraftment by day 21.     

Collection efficiency on the fenwal CS3000 when using filgrastim (recombinant methionyl human granulocyte colony-stimulating factor) as a peripheral blood stem cell mobilization agent

The collection efficiency (CE) of the Fenwal CS3000 in collecting peripheral blood stem cells during post-chemotherapy recovery phase ranges from 58% to 73%. Recently filgrastim (recombinant methionyl human granulocyte colony-stimulating factor [G-CSF]) has also been shown to be effective as a mobilization agent although mobilization occurs during elevated and not low normal leukocyte counts. We compared the mononuclear cell (MNC) CE and the myeloid progenitor cell (CFU-GM) CE among 11 patients with G-CSF mobilization (33 procedures) and 19 patients during recovery following myelosuppression chemotherapy (93 procedures). Pre-apheresis leukocyte, neutrophil, MNC, and PB CFU-GM counts were significantly higher in the G-CSF group, while the granulocyte percentage in the apheresis products was similar in both groups. Both MNC CE (81.8 ± 4.5% vs. 64 ± 2.4%) and CFU-GM CE (79.5 ± 10.5% vs. 55.8 ± 3.5%) were higher in the G-CSF group. Only the pre-apheresis MNC count showed an independently significant correlation for both CE (P <.001). The higher CE in the G-CSF group can only be partly explained by a rise in MNC count during apheresis. These data suggest that the blood cell separator works better with leukocytosis, and especially with a higher MNC count. The improvement in CE is another benefit of G-CSF mobilization over chemotherapy mobilization. © 1994 Wiley-Liss, Inc.     

The effect of granulocyte colony-stimulating factors on survival parameters in pediatric patients with acute lymphoblastic leukemia: a retrospective study

ObjectiveThere is a paucity of data concerning the use of granulocyte colony-stimulating factors (G-CSFs) in pediatric patients with acute lymphoblastic leukemia (ALL). The aim of the present study was to evaluate the effect of G-CSF use on relapse-free and overall survival in 358 consecutive, newly diagnosed pediatric ALL patients uniformly treated at the same institution between April 2012 and April 2020.Materials and MethodsPatients were evaluated in two separate periods, based on the G-CSF treatment approach. All patients who underwent ALL treatment between April 2012 and December 2016 received G-CSF (G-CSF⁺ arm; n: 245) in the course of the protocol for reducing the risk of febrile neutropenia and/or inducing neutrophil recovery to prevent any treatment delay. No patients after December 2016 received G-CSF, even if they belonged to the high-risk group, and these were included in the G-CSF^? arm (n: 113).ResultsEstimated mean relapse-free (106.5 months; 95 % CI 102?110.8 vs 82 months 95 % CI 75.2?88.9; p: 0.794) and overall survival (111.4 months; 95 % CI 108?114.8 vs 85 months 95 % CI 80.4?89.8; p: 0.431) rates were similar between the G-CSF⁺ and G-CSF^? groups.ConclusionsOur findings indicate that G-CSF use during ALL treatment had no effect on relapse rates or overall survival.     

无血缘关系脐血移植治疗血液系统恶性疾病的临床研究

目的　观察无血缘脐血移植 (UCBT)治疗儿童和成人血液系统恶性疾病的植入率、移植物抗宿主病 (GVHD)的发生和生存情况。方法　血液系统恶性疾病患者 17例 ,其中儿童 13例 ,成人 4例。 12例接受单份脐血 (CB) ,5例接受 2份CB。脐血与受者HLA 6个位点相合 6例 ,4～ 5个位点相合11例。 10例患者移植时处于疾病稳定期 ,7例处于复发或难治白血病阶段。预处理多数采用BU CY或CY TBI方案 ,同时应用抗胸腺细胞球蛋白。GVHD预防采用环孢菌素A(CsA)为主的方案。结果　14例存活超过 4 0d的患者进行了脐血植入率的评价。至移植后 6 0天 ,12例 (86 % )患者白细胞达到了植入标准 ,植活时间为 (2 1.0± 1.3)d ;10例 (71% )血小板达到植活水平 ,植活时间为 (39.0± 10 .3)d。 4例患者发生Ⅱ度急性GVHD ,2例发生慢性GVHD。 17例患者 11例存活 ,其中无事件生存 (EFS) 8例。10例处于疾病稳定期患者 ,2年总生存概率 (OS)为 90 % ,无事件生存率 (EFS)为 70 % ;7例处于复发或难治白血病阶段的患者 ,只有 2例存活而无复发。 4例成人患者 2例达到了持久植入 ,目前EFS分别为 18和 14个月。结论　初步结果表明 ,HLA相合及 1～ 2位点不合的UCBT是可行的 ,尤其是移植前处于疾病稳定状态的患者。对于 1份脐血有核细胞不足的成人患者 2     

重组人白细胞介素11治疗急性白血病化疗后血小板减少的疗效和机制研究

目的观察重组人白细胞介素11(rhIL-11)治疗急性白血病(AL)患者化疗后血小板减少的疗效、安全性及其可能的机制。方法AL患者60例,其中32例在化疗结束后BPC≤30×109/L时用rhIL-11治疗,1.5mg/d皮下注射,连用7～14d或至血小板较用药前升高50×109/L以上时停药。观察rhIL-11的疗效及不良反应,ELISA法检测用药前血清IL11水平,RTPCR法检测单个核细胞IL-11受体α(IL11Rα)基因的表达,分析三者关系。以28例未用rhIL11治疗的患者作对照。结果①rhIL-11用药患者组(完全缓解26例,部分缓解2例,未缓解4例)用药后1周、2周血小板计数分别为(63.40±7.24)×109/L、(98.70±9.37)×109/L;对照组(完全缓解20例,部分缓解3例,未缓解5例)为(42.50±6.38)×109/L、(70.30±7.12)×109/L;rhIL11用药患者组较对照组血小板恢复时间缩短(P<0.05)。rhIL11用药患者组10例需要输注血小板,平均为16～32U;对照组19例,平均为32～48U。常见不良反应为轻度乏力、肌肉疼痛,5例出现短暂房性心律失常,减量或停药后消失。显效组用药前平均IL11水平为(21.81±1.88)ng/L,低于无效组(35.75±2.10)ng/L(P<0.05);其IL-11Rα相对水平为0.3552±0.0224,高于无效组(0.1692±0.0066)(P<0.05)。用药前血清IL-11、单个核细胞IL-11Rα水平与血小板计数均无相关性;用药后IL-11水平与骨髓巨核细胞计数无相关性。结论rhI-11治疗AL患者化疗后引起的血小板减少安全有效;检测用药前血清IL-11水平和单个核细胞IL-11Rα的表达对预测rhIL-11疗效有一定意义。     

Factors influencing haematological recovery after allogeneic bone marrow transplantation in leukaemia patients treated with methotrexate-containing GVHD prophylaxis

 In the present single institution study of 66 leukaemia patients (28 AML, 23 ALL, 15 CML), the factors influencing haematological recovery after allogeneic bone marrow transplantation (alloBMT) were analysed retrospectively to identify the optimal conditions required for rapid haematological recovery after alloBMT. All patients received GVHD prophylaxis with cyclosporine A plus methotrexate. The mean number of days required to achieve a neutrophil count ≥0.5×10⁹/l after alloBMT was 17 (range 9–27), 19 patients (28.8%) had rapid neutrophil recovery within 15 days after alloBMT. Haematological recovery was more rapid in the 38 patients without GVHD or with only grade I GVHD. Also, 50% and 40% of patients receiving 10 (n=18) or 5 (n=20) μg/kg G-CSF per day, respectively, had rapid neutrophil recovery within 15 days after alloBMT, as against only 7.1% of patients not receiving G-CSF after the transplant (n=28);P<0.001. The neutrophil recovery was similar in patients receiving either fresh or cryopreserved allografts and either a TBI-containing or a busulfan-containing conditioning regimen. A significant correlation was found between the neutrophil recovery and either the MNCs or CFU-GM contents of the allografts. The mean number of days required for neutrophil recovery was only 16 (range 9–24) in patients receiving allografts containing >1×10⁵ CFU-GM/kg (n=28), as against 19 (range 13–27) in patients receiving allografts containing ≤1×10⁵ CFU-GM/kg (n=35). Three patients receiving allografts containing <0.5×10⁵ CFU-GM/kg had primary neutrophil engraftment failure. The mean number of days required to achieve a platelet count ≥20×10⁹/l was 21 (range 11–50), and 30 patients (46.9%) had platelet recovery within 20 days after alloBMT. The platelet recovery after alloBMT was not affected by the type of leukaemia, conditioning regimen, or G-CSF administration. The mean number of days required for platelet recovery after alloBMT was 20 in patients receiving allografts containing >1.0×10⁵ BFU-E/kg (n=35), as against 23 days in patients receiving allografts containing ≤1.0×10⁵ BFU-E/kg (n=24). Seven patients receiving allografts containing <0.5×10⁵ BFU-E/kg had primary platelet engraftment failure. The present study has identified the high number of progenitor cells in the allografts infused and the daily administration of G-CSF posttransplant as the optimal combination for rapid neutrophil recovery after alloBMT. More significantly, the number of BFU-E in allografts was the most significant determining factor in platelet recovery after alloBMT. The development of GVHD of grade II or more during the first weeks after alloBMT was associated with slower haematological recovery, a longer period of fever during neutropenia and longer hospitalization.