-
Drug Design, Development and Therapy 2020High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The...
BACKGROUND
High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available.
METHODS
A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8-32 mg/24h) or granisetron (2 x 40 µg/kg∙d) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0-24h, >24-120h, >120-240h).
RESULTS
Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0-24h (64 vs 22 events; <0.01), >24-120h (135 vs 78 events; <0.0001), >120-240h (268 vs 105 events; <0.0001), and the whole observation period 0-240h (467 vs 205 events; <0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24-120h (100% vs 74.3%) but not the other analyzed time periods (>0.05).
CONCLUSION
The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.
Topics: Adolescent; Antibiotic Prophylaxis; Antiemetics; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Morpholines; Neoplasms; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Transplantation, Autologous
PubMed: 33061297
DOI: 10.2147/DDDT.S260887 -
Biology of Blood and Marrow... Jan 2003Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of multiple myeloma (MM) is presented and critically evaluated in this... (Review)
Review
Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of multiple myeloma (MM) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality of the evidence, the strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence presented in the review were made unanimously by a panel of MM experts. Recommendations for SCT as an effective therapy for MM include the following: SCT is preferred to standard chemotherapy as de novo therapy; SCT is preferred as de novo rather than salvage therapy; autologous peripheral blood stem cell transplantation (PBSCT) is preferred to bone marrow transplantation (BMT); and melphalan is preferred to melphalan plus total body irradiation as the conditioning regimen for autologous SCT. Recommendations that SCT is not effective include the following: current purging techniques of bone marrow. Recommendations of equivalence include the following: PBSCT using CD34+ selected or unselected stem cells. No recommendation is made for indications or transplantation techniques that have not been adequately studied, including the following: SCT versus standard chemotherapy as salvage therapy, tandem autologous SCT, autologous or allogeneic SCT as a high-dose sequential regimen, allogeneic BMT versus PBSCT, a preferred allogeneic myeloablative or non-myeloablative conditioning regimen, and maintenance therapy post-autologous SCT with interferon alpha post-SCT. The priority area of needed future research is maintenance therapy posttransplantation with nothing versus interferon alpha versus other agents such as corticosteroids or thalidomide or its derivatives.
Topics: Antineoplastic Agents; Combined Modality Therapy; Evidence-Based Medicine; Hematopoietic Stem Cell Transplantation; Humans; Multiple Myeloma; Practice Guidelines as Topic; Treatment Outcome
PubMed: 12533739
DOI: 10.1053/bbmt.2003.50002 -
The Cochrane Database of Systematic... Jan 2009Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate... (Review)
Review
BACKGROUND
Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken.
OBJECTIVES
To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life.
SEARCH STRATEGY
We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications.
SELECTION CRITERIA
Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care.
DATA COLLECTION AND ANALYSIS
Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data.
MAIN RESULTS
We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia.
AUTHORS' CONCLUSIONS
There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.
Topics: Antibiotic Prophylaxis; Antineoplastic Combined Chemotherapy Protocols; Fever; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Humans; Infection Control; Neoplasms; Neutropenia; Randomized Controlled Trials as Topic
PubMed: 19160320
DOI: 10.1002/14651858.CD007107.pub2 -
British Journal of Cancer Nov 1994The morbidity of high-dose chemotherapy has been considerably reduced by the use of autologous peripheral blood progenitor cell reinfusion. Most studies have used... (Clinical Trial)
Clinical Trial Comparative Study
The morbidity of high-dose chemotherapy has been considerably reduced by the use of autologous peripheral blood progenitor cell reinfusion. Most studies have used myeloid colony-stimulating factors after stem cell reinfusion, making it difficult to determine the relative contribution of each of these variables to the early recovery of blood cells. The financial implications of colony-stimulating factor use are an area of concern as dose intensification in chemosensitive malignancies is increasingly employed. We have studied 19 consecutive patients receiving high-dose chemotherapy with and without filgrastim (Amgen, granulocyte colony-stimulating factor, G-CSF) after stem cell infusion to examine its effect on the kinetics of blood cell recovery, the complications of myelosuppression and the associated costs. Analysis of the two treatment groups reveals that administration of filgrastim 10 micrograms kg-1 day-1 following stem cell reinfusion does not further accelerate haemopoietic recovery, fails to reduce the incidence of neutropenic fever or antibiotic usage and significantly increases the cost of the procedure. The results of this study do not support the routine use of filgrastim after high-dose chemotherapy and peripheral blood stem cell reinfusion.
Topics: Adolescent; Adult; Antineoplastic Agents; Dose-Response Relationship, Drug; Female; Filgrastim; Granulocyte Colony-Stimulating Factor; Hematopoiesis; Hematopoietic Stem Cell Transplantation; Humans; Male; Middle Aged; Myeloproliferative Disorders; Neoplasms; Recombinant Proteins; Retrospective Studies
PubMed: 7524605
DOI: 10.1038/bjc.1994.425 -
Annals of Hematology Jan 2021Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical... (Comparative Study)
Comparative Study Randomized Controlled Trial
Busulfan and cyclophosphamide (BuCy) is a frequently used myeloablative conditioning regimen for allogeneic hematopoietic cell transplantation (allo-HCT). Theoretical considerations and pharmacological data indicate that application of busulfan prior to subsequent cyclophosphamide (BuCy) may trigger liver toxicity. Reversing the order of application to cyclophosphamide-busulfan (CyBu) might be preferable, a hypothesis supported by animal data and retrospective studies. We performed a prospective randomized trial to determine impact of order of application of Bu and Cy before allo-HCT in 70 patients with hematological malignancy, 33 patients received BuCy and 37 CyBu for conditioning. In the short term, there were minimal differences in liver toxicity favoring CyBu over BuCy, significant only for alanine amino transferase at day 30 (p = 0.03). With longer follow-up at 4 years, non-relapse mortality (6% versus 27%, p = 0.05) was lower and survival (63% versus 43%, p = 0.06) was higher with CyBu compared to BuCy. Other outcomes, such as engraftment (p = 0.21), acute and chronic graft-versus-host disease (p = 0.40; 0.36), and relapse (p = 0.79), were similar in both groups. We prospectively show evidence that the order of application of Cy and Bu in myeloablative conditioning in allo-HCT patients has impact on outcome.
Topics: Adult; Aged; Busulfan; Chemical and Drug Induced Liver Injury; Cyclophosphamide; Drug Therapy, Combination; Female; Hematologic Neoplasms; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Male; Middle Aged; Prospective Studies; Transplantation Conditioning; Transplantation, Homologous; Young Adult
PubMed: 33098041
DOI: 10.1007/s00277-020-04312-y -
International Journal of Hematology Sep 2011The prognosis of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for refractory acute lymphoblastic leukemia (ALL) is very poor. To improve...
The prognosis of patients receiving allogeneic hematopoietic stem cell transplantation (HSCT) for refractory acute lymphoblastic leukemia (ALL) is very poor. To improve survival rates, we attempted to intensify the conditioning regimen with daunorubicin, vincristine, prednisolone, medium-dose etoposide, cyclophosphamide, and total body irradiation (DNR/VCR/PSL plus medium-dose VP/CY/TBI). Four patients in relapse or induction failure of B-precursor ALL without other complications underwent allogeneic HSCT. Initially, chemotherapy comprising DNR 60 mg/m(2) for 3 days, VCR 1.4 mg/m(2) for 1 day, and PSL 60 mg/m(2) for 3 days was administered, which was followed by medium-dose VP/CY/TBI; some modifications were made for individual patients. All patients achieved engraftment and complete remission after HSCT. Regimen-related toxicities were tolerable and no patient died within 100 days. Two patients were alive without disease on days 563 and 1,055. The third patient relapsed on day 951, while the fourth died on day 179 without disease. Our results indicate that intensified myeloablative HSCT should be considered for patients with refractory ALL.
Topics: Adolescent; Adult; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Remission Induction; Transplantation Conditioning; Transplantation, Homologous; Treatment Outcome; Whole-Body Irradiation; Young Adult
PubMed: 21879292
DOI: 10.1007/s12185-011-0919-3 -
Bulletin Du Cancer Jan 2006Therapy for renal cell carcinoma has made considerable progress in the past few years. The aims of this review are to update the pathological classification of this... (Review)
Review
Therapy for renal cell carcinoma has made considerable progress in the past few years. The aims of this review are to update the pathological classification of this tumor and discuss predictive factors for tumor response and survival in the case of metastasis as well as the place of immunotherapy with interleukine-2 and/or interferon alpha . Furthermore, we will review new therapeutic options and current results on allogeneic stem cell transplantation with non-myeloablative conditioning and HLA genoidentical donors. Finally, we will present targeted therapy (antiangiogenic drugs and tyrosine kinase inhibitors) with the mechanisms of action, efficacy and appropriate use in the treatment of metastatic renal cell carcinoma.
Topics: Angiogenesis Inhibitors; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Renal Cell; Enzyme Inhibitors; Humans; Immunotherapy; Kidney Neoplasms; Prognosis; Protein-Tyrosine Kinases; Stem Cell Transplantation; Survival; Transplantation, Homologous; Treatment Outcome
PubMed: 16455511
DOI: No ID Found -
Bone Marrow Transplantation Aug 2002We evaluated high-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell... (Clinical Trial)
Clinical Trial
We evaluated high-dose acyclovir and pre-emptive ganciclovir to prevent cytomegalovirus disease in myeloablative and non-myeloablative allogeneic stem cell transplantation. One hundred and seventy-four consecutive patients who were at risk for CMV infection (either recipient or donor seropositive) and received either intensive chemoradiotherapy and a T cell-depleted stem cell transplant followed by delayed add-back of donor T cells (TCDT: n = 98), or a non-myeloablative preparative regimen followed by an unmanipulated peripheral blood stem cell transplant (NMT: n = 76) from an HLA-identical sibling donor were studied. All received high-dose acyclovir (HDACV) from day - 7 for 3 months post-transplant in conjunction with weekly CMV pp65 antigenemia monitoring and pre-emptive treatment with intravenous immunoglobulin (not CMV-specific) and ganciclovir. The actuarial probabilities of developing pp65 antigenemia were 83 +/- 4% after TCDT and 41 +/- 6% after NMT (P < 0.00001) with reactivation occurring earlier in the TCDT group (the median 36 days vs 55 days). We observed no reactivation of CMV in seronegative recipients with a seropositive donor (n = 23). A total of 11 patients (5 in TCDT, 6 in NMT) developed CMV disease within 400 days after transplantation, and one death was clearly attributable to CMV interstitial pneumonitis (IP). This strategy was associated with effective control of CMV antigenemia in the majority of patients and near-complete eradication of fatal CMV IP.
Topics: Acyclovir; Adolescent; Adult; Aged; Antiviral Agents; Child; Cohort Studies; Cytomegalovirus; Cytomegalovirus Infections; Drug Therapy, Combination; Female; Ganciclovir; Humans; Male; Middle Aged; Peripheral Blood Stem Cell Transplantation; Phosphoproteins; Risk Factors; Survival Analysis; Transplantation Conditioning; Transplantation, Homologous; Viral Matrix Proteins; Virus Activation
PubMed: 12203140
DOI: 10.1038/sj.bmt.1703648 -
Oncotarget Jun 2013Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell...
Myeloablative anti-CD20 radioimmunotherapy +/- high-dose chemotherapy followed by autologous stem cell support for relapsed/refractory B-cell lymphoma results in excellent long-term survival.
BACKGROUND
Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.
METHODS
Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.
RESULTS
6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.
CONCLUSION
Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.
Topics: Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Disease-Free Survival; Female; Humans; Iodine Radioisotopes; Lymphoma, B-Cell; Male; Middle Aged; Neoplasm Recurrence, Local; Peripheral Blood Stem Cell Transplantation; Radioimmunotherapy; Radiopharmaceuticals; Risk Factors; Rituximab; Survival Analysis; Transplantation, Autologous
PubMed: 23765188
DOI: 10.18632/oncotarget.1037 -
The National Medical Journal of India 1995For reinfusing autologous bone marrow cells after high-dose chemotherapy and/or radiotherapy it is necessary that an effective technique for their storage is available.... (Review)
Review
For reinfusing autologous bone marrow cells after high-dose chemotherapy and/or radiotherapy it is necessary that an effective technique for their storage is available. The traditional method uses 10% dimethyl sulphoxide as cryoprotectant, a rate-controlled computerized freezer programmed to cool the cells at a constant rate of 1 degrees C per minute and liquid nitrogen as the storage system. The method is time-consuming, expensive and requires technical expertise. Moreover, it is often associated with varying levels of clinical toxicity following infusion of the preserved cells. Processing the harvest to reduce the initial volume and the mature cells has been shown to be beneficial in reducing the volume of the cryoprotectant and the incidence of toxicity. An alternative, cost-effective method using a cryoprotectant mixture of 5% dimethyl sulphoxide, 6% hydroxyethyl starch and 4% albumin has been found to be effective even when the cells are stored at -80 degrees C without rate-controlled freezing. However, its efficacy needs to be evaluated for extended periods. The current use of purging and cell sorting methods seems to be promising.
Topics: Bone Marrow Transplantation; Cryopreservation; Hematopoietic Stem Cells; Humans; Transplantation, Autologous
PubMed: 7549853
DOI: No ID Found