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A randomized controlled trial to explore the safety and efficacy of irradiated buffy-coat granulocytes in pediatric patients with febrile neutropenia
Ramachandran, M., Gupta, A. K., Meena, J. P., Upadhyay, A. D., Coshic, P., Lodha, R., Seth, R.
American journal of blood research. 2023;13(5):152-161
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Abstract
BACKGROUND Transfusion of granulocytes obtained by apheresis is beneficial in febrile neutropenia (FN) but expensive and time-consuming. Buffy-coat-derived granulocytes could be an alternative. We studied the efficacy and safety of the administration of irradiated buffy-coat-derived granulocytes along with the standard of care in pediatric high-risk (HR) FN. METHODS Sixty children ≤18 years with malignancy and chemotherapy-induced HR FN were randomized to either the granulocyte transfusion (GT) arm which received irradiated buffy-coat derived granulocyte transfusion along with the standard treatment or the standard treatment (ST) arm. RESULTS Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count (ANC) >500/mm(3) in the 2 groups: 4.5 days (3-6.5) in the GT arm v/s 8 days (4-11) in the ST arm (P=0.01). CONCLUSION Buffy-coat-derived granulocyte transfusion was safe and led to early hematological recovery but was not associated with survival benefits. Future studies with earlier initiation in the intended dose could be undertaken to generate more evidence.
PICO Summary
Population
Children with malignancy and chemotherapy-induced high-risk febrile neutropenia (n= 60).
Intervention
Irradiated buffy-coat derived granulocyte transfusion along with the standard treatment (GT arm, n= 30).
Comparison
Standard treatment, including: antimicrobials, blood component support, and G-CSF as per the protocol (ST arm, n= 30).
Outcome
Baseline characteristics, day-to-defervescence, antibiotic duration, hospital stay, and mortality were comparable between the groups. A significant difference was seen in days to achieve absolute neutrophil count >500/mm(3) in the 2 groups: 4.5 days (3, 6.5) in the GT arm versus 8 days (4, 11) in the ST arm.
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Efficacy and safety of thrombopoietin receptor agonists in children with chronic immune thrombocytopenia: a meta-analysis
Guo J C, Zheng Y, Chen H T, Zhou H, Huang X H, Zhong L P, Zhou H B, Huang Y, Xie D L, Lou Y L
Oncotarget. 2018;9((6)):7112-7125.
Abstract
Background and Aim: Thrombopoietin receptor agonists (TPO-RAs) have been shown to be safe and effective for adults with chronic immune thrombocytopenia (ITP). The aim of this meta-analysis is to assess the efficacy and safety of thrombopoietin receptor agonists for children with chronic ITP. Materials and Methods: Clinical randomized controlled trials (RCTs) evaluating the efficacy and safety of TPO-RAs in pediatric ITP patients published up to June 2017 were retrieved from PubMed, Cochrane Library, and Embase databases. Relevant data were extracted, and the Physiotherapy Evidence Database scale was used to assess the methodological quality. Stata/SE 12.0 was used to perform a meta-analysis. Results: Seven RCTs were included, with 238 patients and 107 patients in the TPO-RA group and the control group, respectively. Assessing efficacy, better results were found in the TPO-RA group for the rate of overall platelet response, durable response, and rescue medication needed. Furthermore, the TPO-RA group yielded superior results in the incidence of clinically significant bleeding events but had a comparable result in the incidence of any bleeding events and severe bleeding events. No significant difference was found between the two groups in health-related quality of life and parental burden. Assessing safety, no significant difference was found between the two groups in the incidence of any adverse events and severe adverse events. Conclusions: TPO-RAs are effective and safe agents for the treatment of chronic ITP in pediatric patients. Eltrombopag appears to be better than romiplostim in terms of the rate of rescue medication needed and clinically significant bleeding events.
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The efficacy of recombinant human erythropoietin in treatment chemotherapy induced anemia in children diagnosed with a solid cancer
Hiradfar A, Banihosseinian M
Iranian Journal of Pediatric Hematology & Oncology. 2014;4((4):):151-9.
Abstract
BACKGROUND Recombinant human erythropoietin (rHuEPO) treatment can increase hemoglobin levels and decrease transfusion requirements. This study aims to investigate how blood transfusion influences Hemoglobin levels in patients receiving rHuEPO for 12 weeks. MATERIALS AND METHODS This was a case-control study of 60 patients less than 15 years with anemia and a solid tumor in any location between February 2013 and March 2014. Median age of the patients were 6.27+/-0.58 years (range, 0.9-14 years). The patients were randomly assigned in two groups of rHuEPO receiving group and control group. 29 Patients in rHuEPO group received 150 IU/kg/dose rHuEPO subcutaneously, 3 times a week, for 12 weeks. The number of patients received transfusion during the treatment period was compared in the preceding 12 weeks. Also, adverse events (AE) were recorded at the 4(th), 8(th), and 12(th) weeks. RESULTS Mean hemoglobin levels, before and after study, in rHuEPO group were 8.85+/-1.01 g/dl and 9.90+/-0.29 g/dl, respectively (p<0.001) and in control group were, 9.00+/-0.09 g/dl and 7.81+/-0.23 g/dl, respectively (p=0.25). Among 60 patients initially eligible the present study, 57 (29 in rHuEPO group and 28 in control group) completed study course.There was a significant decrease in transfusion requirements in the rHuEPO receiving group (p=0.004). 5 (17.2%) patients in the rHuEPO group needed a blood transfusion, whereas 15 (53.6%) patients needed a transfusion in the control group. rHuEPO occasioned hypertension in one patient at 4(th) week that caused to end the treatment. All other AE were transient, which did not reoccur after the transient discontinuation of the medication (p<0.05). CONCLUSIONS Results showed that the rHuEPO (150 IU/kg/day, 3 times a week) was effective in increasing hemoglobin levels as well as decreasing blood transfusion requirements in children with anemia following intensive chemotherapy. IS 2008-8892
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Double-blind, placebo-controlled study of quality of life, hematologic end points, and safety of weekly epoetin alfa in children with cancer receiving myelosuppressive chemotherapy
Razzouk BI, Hord JD, Hockenberry M, Hinds PS, Feusner J, Williams D, Rackoff WR
Journal of Thrombosis and Haemostasis. 2006;24((22):):3583-9.
Abstract
PURPOSE To evaluate the effects of once-weekly epoetin alfa (EPO) on health-related quality of life (HRQOL), hemoglobin (Hb), transfusions, and tolerability in children with cancer. METHODS Anemic patients 5 years to 18 years of age receiving myelosuppressive chemotherapy for nonmyeloid malignancies, excluding brain tumors, received intravenous EPO 600 units/kg to 900 units/kg or placebo once-weekly for 16 weeks. Patients and parents completed the pediatric health-related quality-of-life generic scales (GS) and cancer-specific scales (CS). RESULTS One hundred eleven patients received EPO and 111 patients received placebo. Mean final values for GS total score (P = . 763 among patients; P = . 219 among parents) and CS domain scores (P > or = . 238; P > or = . 081, respectively) were not significantly different between treatment groups. EPO-treated patients had greater increases in Hb overall (P = . 002) and were more likely to be transfusion free after 4 weeks (38. 7% v 22. 5%; P = . 010). Change in Hb was correlated with change in PedsQL-GCS total score in the EPO group (r = 0. 242; P = . 018), but was not in the placebo group (r = 0. 086; P = . 430). Adverse events were comparable between treatment groups. CONCLUSION This study confirmed the tolerability and hematologic benefits of once-weekly EPO in children with cancer. No significant difference in HRQOL was detected between treatment groups, but a significant positive correlation was observed between Hb changes and HRQOL changes in the EPO group. Additional studies are warranted to assess HRQOL when anemia is managed optimally in children with cancer.
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Pharmacokinetics and pharmacodynamics of intravenous epoetin alfa in children with cancer
Freeman BB, Hinds P, Iacono LC, Razzouk BI, Burghen E, Stewart CF
Pediatric Blood & Cancer. 2006;47((5):):572-9.
Abstract
BACKGROUND Epoetin alfa (EPO, PROCRIT) pharmacokinetics and pharmacodynamics were evaluated in children with malignant solid tumors receiving chemotherapy. PROCEDURE Children initially received IV EPO 600 IU/kg (max dose 40,000 IU) or placebo once weekly for 16 weeks. Dose was increased to 900 IU/kg (max dose 60,000 IU) for patients not achieving a 1 g/dl increase in hemoglobin by study week 3 or 4. Serial PK samples were collected for 24 hr after the first study dose, and after the 10th or 11th dose. Serum EPO concentrations were analyzed using an ELISA assay, and pharmacokinetics were evaluated using compartmental methods. RESULTS Twelve children participated; six (median age 15. 2 years; range 9. 3-18. 6 years) were randomized to receive EPO. All children required dosage increases to 900 IU/kg due to no response. The median (range) apparent EPO AUC0-24 and clearance (CL) were 67. 1 IU/ml. hr (13. 8-102. 6) and 0. 26 L/hr/m2 (0. 19-1. 08), respectively. After the 10th or 11th EPO dose in four of these six EPO patients, the median (range) apparent AUC0-24 and CL of EPO was 126. 5 IU/ml. hr (107. 3-161. 1) and 0. 21 L/hr/m2 (0. 15-0. 25), respectively. No significant correlations were observed between pharmacokinetic parameters and pharmacodynamic effects. CONCLUSIONS EPO disposition in our patients was similar to other pediatric patient populations or adults receiving IV EPO. Interesting but insignificant trends were noted in pharmacodynamic effects.
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Combined use of erythropoietin and granulocyte colony-stimulating factor does not decrease blood transfusion requirements during induction therapy for high-risk neuroblastoma: a randomized controlled trial
Wagner LM, Billups CA, Furman WL, Rao BN, Santana VM
Journal of Clinical Oncology. 2004;22((10):):1886-93.
Abstract
PURPOSE To evaluate the efficacy of recombinant erythropoietin (EPO) and granulocyte colony-stimulating factor (G-CSF) in reducing blood transfusion requirements and stimulating hematopoiesis in children with high-risk neuroblastoma. PATIENTS AND METHODS Thirty-eight patients given six cycles of intensive induction chemotherapy for high-risk neuroblastoma were randomized to receive G-CSF (n=20) or G-CSF + EPO (n=18). Cytokines were given subcutaneously each day, starting 24 hours after each chemotherapy cycle and continuing until 48 hours before the start of the next cycle. The primary end point was the effect of EPO on total red cell transfusion requirements during induction therapy. RESULTS Patients who received G-CSF + EPO had a higher red cell transfusion requirement (median, 161. 0 mL/kg) than did those who received G-CSF alone (median, 106. 6 mL/kg; P =. 005). In addition, among patients given transfusions for hemoglobin < or = 8 g/dL, those in the G-CSF + EPO group received more red cell transfusions than did those given G-CSF alone (median per patient, 10 v 8, respectively; P =. 044). The two treatment groups had similar cumulative durations of neutropenia, incidences of febrile neutropenia, platelet transfusion requirements, and numbers of platelet transfusions; they also received induction chemotherapy for similar durations and had similar probabilities of progression-free survival and overall survival. CONCLUSION The addition of EPO to the G-CSF regimen provides no benefit for patients receiving intensive induction chemotherapy for high-risk neuroblastoma.
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Is epoetin alfa a treatment option for chemotherapy-related anemia in children?
Buyukpamukcu M, Varan A, Kutluk T, Akyuz C
Medical & Pediatric Oncology. 2002;39((4):):455-8.
Abstract
BACKGROUND The efficacy and safety of epoetin alfa in ameliorating cancer- or chemotherapy-related anemia and reducing red blood cell (RBC) transfusion requirements have been demonstrated in numerous trials in adult patients. However, limited information is available about recombinant human erythropoietin (rHuEPO, epoetin alfa) as a treatment option in pediatric cancer patients. PROCEDURE To gain more information about the efficacy and safety of epoetin alfa in the treatment of chemotherapy-induced anemia in children with solid tumors receiving either platinum- or nonplatinum-containing chemotherapy, an 8-week randomized trial was conducted. Epoetin alfa 150 IU/kg was given 3 times a week for 8 weeks to 17 patients; 17 control patients received standard of care. RESULTS Transfusions, administered if the hemoglobin (Hb) level dropped to below 6 g/dL, were necessary for only one patient in the epoetin alfa group, as compared with eight patients in the control group (change in Hb from 8.5-10.21 g/dL in the epoetin alfa group vs. 8.48-8.41 g/dL in the control group). CONCLUSIONS The data from this study suggest that this dosing regimen of epoetin alfa is effective and safe in pediatric cancer patients with chemotherapy-related anemia. Further studies with epoetin alfa in more children with different chemotherapy regimens are needed. Copyright 2002 Wiley-Liss, Inc.
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Recombinant human erythropoietin in pediatric oncology: a review
Feusner J, Hastings C
Medical and Pediatric Oncology. 2002;39((4):):463-8.
Abstract
BACKGROUND Numerous reports on recombinant human erythropoietin (rHu EPO, epoetin alfa) treatment of cancer-related anemia in adult patients have been published to date. These have shown that epoetin increases hemoglobin levels, significantly ameliorates symptoms of anemia, and improves adult patients' quality of life. Unfortunately, less is known about the impact of epoetin on anemia in pediatric cancer patients. PROCEDURE It is the objective of this review to summarize and analyze data of clinical trials of epoetin treatment of anemia in pediatric cancer patients. RESULTS A total of 15 studies were reviewed; eight were considered for detailed analysis and demonstrated important variabilities in study methods. Four of the eight were controlled, randomized trials and four were open label. CONCLUSIONS These studies suggested an overall beneficial effect of epoetin alfa for treating anemia in children with cancer. Three large, multicenter clinical trials of the efficacy and safety of epoetin alfa in anemic children with cancer are currently underway, one in Europe and two in North America.
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Recombinant human erythropoietin treatment for chemotherapy-related anemia in children
Varan A, Buyukpamukcu M, Kutluk T, Akyuz C
Pediatrics. 1999;103((2):):E16.
Abstract
OBJECTIVE The efficacy and safety of recombinant human erythropoietin (rHuEPO) treatment in chemotherapy-induced anemia in children were investigated. rHuEPO is used to treat chemotherapy-induced anemia. Several studies recommend 150 to 300 IU/kg rHuEPO for 2 to 8 months. There are only a few controlled trials in children and no precise data about the optimal dose and duration of rHuEPO treatment is available. PATIENTS and METHODS Thirty-four patients receiving chemotherapy for treatment of their solid tumors between October 1996 and June 1997 were included in this study. Patients were randomly selected for each group. The male/female ratio was 20/14, and the median age was 5 years (range, 1-16 years). They had normal hemoglobin levels at the time of diagnosis. When hemoglobin levels decreased to levels lower than 10 g/dL, rHuEPO (150 IU/kg/d, 3 times a week, subcutaneously) was given to 17 patients for 2 months. Their renal, liver, and pulmonary functions were normal. None of the patients had hematologic disease. We did not use any other drugs such as iron or granulocyte colony-stimulating factor. There were 17 patients in the control group. Fifteen patients got chemotherapy regimens including cisplatin (CDDP), but 19 were treated with regimens without CDDP. At the end of rHuEPO treatment, all patients were examined in terms of transfusion requirements and rate of change in hemoglobin levels. RESULTS One patient in the study group needed a blood transfusion, whereas 8 patients needed a transfusion in the control group. Patients in the study group had less transfusion requirements compared with the control group. The mean hemoglobin levels before and after the study were 8.48 +/- 0.98 g/dL and 8.41 +/- 1.65 g/dL in the control group and 8.50 +/- 0.85 g/dL and 10.21 +/- 2.14 g/dL in the rHuEPO group, respectively. Optimal hemoglobin increments began in 4 weeks and continued during treatment. CDDP-receiving and CDDP-nonreceiving groups did not have any difference in pretreatment serum erythropoietin levels. rHuEPO treatment was more effective in patients treated with non-CDDP regimens. Mean hemoglobin level increased from 8.68 +/- 0.73 g/dL to 10.26 +/- 1.84 g/dL in 9 patients treated with non-CDDP chemotherapy regimens in the erythropoietin group, although it increased from 8.28 +/- 0.97 g/dL to 10.15 +/- 2.5 g/dL in 8 patients treated with CDDP-containing regimens in the erythropoietin group. rHuEPO caused high blood pressure in only 1 patient that resolved spontaneously after cessation of erythropoietin treatment for a week. CONCLUSION rHuEPO treatment (150 IU/kg/d 3 times a week) is effective and safe in children with chemotherapy-induced anemia. It decreases blood transfusion requirements in solid tumor patients. Our results show that the response to rHuEPO in CDDP-induced anemia is less than the response in non-CDDP receiving patients. Higher doses may be necessary in patients using CDDP.
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Recombinant human erythropoietin in the prevention of chemotherapy-induced anaemia in children with malignant solid tumours
Csaki C, Ferencz T, Schuler D, Borsi JD
European Journal of Cancer. 1998;34((3):):364-7.
Abstract
This prospective, randomised pilot study was designed to evaluate safety, feasibility and efficacy of recombinant human erythropoietin (rhEPO) in the prevention and treatment of chemotherapy-induced anaemia in children with solid tumours. 20 children (age 4-18 years) undergoing cyclic combination chemotherapy were randomised either to a control group or to receive rhEPO at a dose of 150 U/kg/dose subcutaneously three times/week for a minimum of 12 weeks or three chemotherapy cycles. Of 15 evaluable patients, 8 were randomised to the rhEPO group and 7 to the control group. RhEPO-treated patients showed an increase in the haematocrit over the first 8 weeks of therapy, with a significantly higher mean haematocrit at week 8 (33.2 +/- 2.1% versus 39.3 +/- 4.2% in the control and rhEPO groups, respectively, P < 0.05). Similarly, significantly higher haemoglobin concentrations could be demonstrated in the rhEPO group by week 8 (11.06 +/- 1.35 g/dl versus 13.11 +/- 1.13 g/dl in the control and rhEPO groups, respectively, P < 0.05), with higher precycle haemoglobin before chemotherapy cycles 3 and 4 and higher midcycle haemoglobin between cycles 3 and 4. There was a trend towards a reduction of transfusion requirements during the 3rd month of therapy in rhEPO patients. The results of this pilot study indicate a significant benefit of rhEPO in children treated with intensive combination chemotherapy regimens. Further studies should target issues such as appropriate dosing, timing and duration of rhEPO therapy in children with cancer.