Granulocyte colony-stimulating factor in neutropenic, pediatric solid tumor patients following chemotherapy

Granulocyte colony-stimulating factor (G-CSF) has been used to reduce the duration and/or degree of neutropenia of different etiologies in recent years. In this study, experience with the use of G-CSF (Neupogen, Roche) after 123 courses of highly myelosuppressive chemotherapy administered to 31 (20 female, 11 male) patients with pediatric solid tumors is reported. G-CSF was initialed at a white blood cell (WBC) count of 918 ± 452/μL (100-2000), at a dose of 7.6 ± 2.3 μg/kgl/d (5-14) subcutaneously for 5.2 ± 2.4 days (2-18). G-CSF was given for afebrile neutropenia after 82 and for febrile neutropenia after 41 courses. Only in two episodes where G-CSF was given for afebrile neutropenia, fever developed. The average hospitalization period for febrile neutropenia was 9.8 ± 3.3 days (5-20). Chemotherapy could be given on scheduled time and dosage in 90% of the courses in which G-CSF was used for afebrile neutropenia. G-CSF was well tolerated. Bone pain was observed in two patients and urticaria in one patient. In conclusion, G-CSF increased the WBC count effectively, there were only two febrile episodes in 82 courses in children receiving G-CSF for afebrile neutropenia, it was well tolerated, and it was found to be feasible for use in a developing country.     

Safety, efficacy and pharmacokinetics of linezolid for treatment of resistant Gram-positive infections in cancer patients with neutropenia.

BACKGROUND: Linezolid is a recently approved oxazalidinone with extended activity against Gram-positive bacteria. We evaluated the results of linezolid therapy in neutropenic cancer patients with Gram-positive bacterial infections from a compassionate-use program. PATIENTS AND METHODS: This was a prospective, multicenter, open-label, non-comparative, non-randomized compassionate-use treatment program in patients with serious Gram-positive infections. To qualify for enrollment patients were required to have an infection resistant to available antimicrobial agents, or in whom available agents had failed or to which they were intolerant. Patients with absolute neutrophil counts (ANC) <500 cells/mm(3) or <1000 cells/mm(3) and expected to decrease to <500 cells/mm(3), and who received linezolid 600 mg twice daily were included. Plasma samples for population pharmacokinetic analysis were collected. Clinical and microbiological assessments of outcomes were made at the end of therapy and at short-term follow-up. RESULTS: Of the patients in the compassionate-use trial, 103 were neutropenic. The mean [standard deviation (SD)] age was 50.1 (17.5) years, 47% were female, and 47.6% had a baseline ANC neutropenia did not differ from the overall compassionate-use population. CONCLUSIONS: Linezolid was safe and effective in treating resistant Gram-positive infections in neutropenic cancer patients. Comparative clinical trials to evaluate further the effectiveness and safety of linezolid in this patient population are warranted.     

Chemotherapy dose intensity in non-Hodgkin's lymphoma: is dose intensity an emerging paradigm for better outcomes?

BACKGROUND: Higher chemotherapy dose intensity has been studied as a way of improving the clinical outcomes in various malignancies, including non-Hodgkin's lymphoma (NHL). METHODS: We reviewed clinical trials that have studied the relation between dose and response in cancer chemotherapy, the theory behind dose-intense chemotherapy, and the clinical results with dose-escalated and dose-dense therapy in aggressive NHL. RESULTS: Myeloablative high-dose chemotherapy with stem cell transplantation produces higher 5-year survival rates than standard salvage chemotherapy in relapsed aggressive lymphoma, but its role as initial therapy is not yet clear. Nonmyeloablative dose-escalated chemotherapy is feasible with granulocyte colony-stimulating factor (G-CSF) support, but this approach does not improve outcomes. Dose-dense (14-day) CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) with G-CSF support produces better results than 21-day CHOP in patients with previously untreated aggressive lymphoma, without additional toxicity. The addition of etoposide to dose-dense CHOP may provide further benefits in younger patients. The addition of rituximab to G-CSF-supported dose-dense CHOP is feasible. Preliminary data suggest the feasibility of dose-dense chemotherapy for NHL with the once-per-cycle G-CSF, pegfilgrastim. CONCLUSION: Dose-dense chemotherapy with G-CSF support produced better clinical outcomes in both younger and older patients. Phase 3 trials of dose-dense CHOP plus rituximab with CSF support are warranted.     

How we approach: Severe congenital neutropenia and myelofibrosis due to mutations in VPS45

Mutations in the VPS45 gene lead to a severe primary immune deficiency characterized by severe congenital neutropenia and primary myelofibrosis, leading to overwhelming infection and early death. This condition is exceedingly rare with only 16 patients previously reported, including four with successful hematopoietic stem cell transplantation. We review the pathophysiology underlying this condition and detail our approach to treatment, particularly vis‐à‐vis bone marrow transplantation and the challenges of transplanting into a diseased bone marrow niche. We provide an update on the progress of our three previously reported patients, and two additional patients transplanted at our center.     

儿童急性淋巴细胞白血病中性粒细胞缺乏伴发热单中心血流感染病原菌分析

目的 分析儿童急性淋巴细胞白血病(ALL)化疗后中性粒细胞缺乏伴发热(FN)血流感染的临床特点、危险因素和病原菌分布。方法 回顾性分析2007年1月1日至2016年12月31日上海交通大学附属儿童医院血液肿瘤科收治的ALL化疗后发生FN住院患儿的临床资料和血培养结果,分析菌株的分布及药敏特点。结果 纳入ALL患儿312例,FN1 548例次,共送检1 700例次血培养,血培养阳性率7.5%(127/1 700),血流感染发生率8.2%(127/1 548),病死率9.4%(12/127)。血流感染革兰阳性菌51.1%(65/127),革兰阴性菌47.2%(60/127),真菌1.5%(2/127)。革兰阴性菌血流感染与革兰阳性菌血流感染比较,ANC<0.1×10⁹·L^-1的患儿占比(P=0.041)和感染性休克发生率更高(P=0.002)。2012~2016年铜绿假单胞菌构成比较2007~2011年增加(χ²=4.712,P=0.030)。ALL的危险程度分层IR/HR(OR=2.560,P=0.045)和ANC<0.1×10⁹·L^-1(OR=0.754,P=0.025)是血流感染发生的独立危险因素。结论 ALL患儿发生FN时血流感染病原菌阳性率较高(8.2%),以革兰阳性菌感染为主。在严重粒细胞缺乏时以革兰阴性菌血流感染为主,铜绿假单胞菌感染有增加趋势,合并感染性休克是FN死亡的独立危险因素。     

Chemotherapy-Induced Neutropenia and Febrile Neutropenia in the US: A Beast of Burden That Needs to Be Tamed?

Neutropenia and febrile neutropenia (FN) are common complications of myelosuppressive chemotherapy. This review provides an up-to-date assessment of the patient and cost burden of chemotherapy-induced neutropenia/FN in the US, and summarizes recommendations for FN prophylaxis, including the interim guidance that was recommended during the coronavirus disease 2019 (COVID-19) pandemic. This review indicates that neutropenia/FN place a significant burden on patients in terms of hospitalizations and mortality. Most patients with neutropenia/FN presenting to the emergency department will be hospitalized, with an average length of stay of 6, 8, and 10 days for elderly, pediatric, and adult patients, respectively. Reported in-hospital mortality rates for neutropenia/FN range from 0.4% to 3.0% for pediatric patients with cancer, 2.6% to 7.0% for adults with solid tumors, and 7.4% for adults with hematologic malignancies. Neutropenia/FN also place a significant cost burden on US healthcare systems, with average costs per neutropenia/FN hospitalization estimated to be up to $40 000 for adult patients and $65 000 for pediatric patients. Evidence-based guidelines recommend prophylactic granulocyte colony-stimulating factors (G-CSFs), which have been shown to reduce FN incidence while improving chemotherapy dose delivery. Availability of biosimilars may improve costs of care. Efforts to decrease hospitalizations by optimizing outpatient care could reduce the burden of neutropenia/FN; this was particularly pertinent during the COVID-19 pandemic since avoidance of hospitalization was needed to reduce exposure to the virus, and resulted in the adaptation of recommendations to prevent FN, which expanded the indications for G-CSF and/or lowered the threshold of use to >10% risk of FN.     

急性白血病化疗后中性粒细胞缺乏患者血流感染的病原菌分布及耐药性特征分析

目的 了解急性白血病（acute leukemia, AL）化疗后中性粒细胞缺乏患者血流感染（bloodstream infection,BSI）的病原菌分布及耐药性特征,为临床及时合理选择抗菌药物、制定合理给药方案提供参考依据。方法 收集2016年1月—2021年12月中国医科大学附属盛京医院收治的AL患者化疗后中性粒细胞缺乏期经血培养确诊发生血流感染258例,对患者临床资料、病原菌及药敏结果进行分析。结果 258例患者分离病原菌268株,其中革兰阴性菌180株（67.16%）,革兰阳性菌61例（22.76%）,真菌27株（10.07%）;革兰阴性菌以肺炎克雷伯菌（53/268,19.78%）、大肠埃希菌（49/268,18.28%）、铜绿假单胞菌（41/268,15.30%）为主;革兰阳性菌以凝固酶阴性葡萄球菌（31/268,11.57%）、金黄色葡萄球菌（17/268,6.34%）为主;真菌以热带念珠菌（25/268,9.33%）为主;急性髓细胞白血病（AML）分离病原菌以大肠埃希菌（33/268,12.31%）常见,其次为铜绿假单胞菌（25/268,9.33%）、凝固酶阴性葡萄...