Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027947 (neutropenia)
 17,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As in other malignancies, peripheral blood progenitor cells (PBPC) have almost completely replaced bone marrow as the source of stem cells for autologous transplantation in multiple myeloma. PBPC collection could be optimized either by reducing contamination by the malignant clone or by increasing hematopoietic quality of the graft. Currently, the most promising technique for purifying the harvest is CD34 cell selection. Several pilot studies have shown the feasibility of this method in MM. However controlled studies are necessary to assess the clinical impact of CD34+ cell selection. In the IFM 94 study, CD34+ selection was optional. There was no significant difference between 50 patients receiving a CD34+ selected graft and 133 patients receiving non-selected PBPC, as regards duration of neutropenia, duration of thrombocytopenia, response rate, EFS or survival. Hematopoietic recovery after transplantation is related to the number of CD34+ cells infused. The optimal regimen for mobilizing the requested CD34+ yield is not yet known. We have completed a randomized study comparing the combination of SCF plus G-CSF and G-CSF alone after priming with cyclophosphamide 4 g/m2. The median number of leukaphereses to reach the target yield of 5x10(6) CD34+ cells/kg was 1 in the SCF group (N=55) versus 2 in the G-CSF group (N=47) (p=0.008). The median number of CD34+ cells collected in the first leukapheresis was 11. 6x10(6) in the SCF group versus 4x10(6) in the G-CSF group (p=0.003). These results are in line with those observed in other trials testing the combination of SCF and G-CSF to improve PBPC collection.
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PMID:Optimizing peripheral blood progenitor cell autologous transplantation in multiple myeloma. 1036

Children with acute myelogenous leukemia (AML) have a high risk of infectious complications that might be reduced by prophylactic granulocyte colony-stimulating factor (G-CSF). However, G-CSF could induce AML blast proliferation. The prospective randomized trial AML-BFM 98 investigated the impact of G-CSF on hematopoetic recovery and infectious complications (primary endpoints) and on outcome (secondary endpoint) in children (aged 0-18 years) with de novo AML. Patients with more than 5% blasts in day-15 bone marrow or with FAB M3 were not included. Between 1998 and 2003, 161 children with AML were randomized to receive G-CSF after inductions 1 and 2, whereas 156 patients were assigned to the control group. Time of neutropenia after inductions 1 and 2 was significantly shorter in the G-CSF group (23 vs 18 days and 16 vs 11 days; P=.02 and=.001, respectively). G-CSF did not decrease the incidence of febrile neutropenia (72 and 36 patients vs 78 and 37 patients, respectively), microbiologically documented infections (27 and 25 patients vs 36 and 19 patients, respectively) and infection-associated mortality (5 vs 2 patients). Both groups had similar 5-year event-free survival (EFS; 59%+/-4% vs 58%+/-4%). Since G-CSF does not influence the risk of infectious complications or outcome in children undergoing therapy for AML, one cannot advocate the routine use of G-CSF in this patient group.
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PMID:Prophylactic human granulocyte colony-stimulating factor after induction therapy in pediatric acute myeloid leukemia. 1700 36

Dose-intensity of chemotherapy is important in the treatment of Hodgkin lymphoma (HL) and granulocyte-colony stimulating factor (G-CSF) is commonly used to maintain it. We reviewed all newly diagnosed HL patients who were treated at our institution between 1996 and 2005. Fifty-nine patients received adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy with no dose reductions, treatment delays, and without G-CSF, regardless of absolute neutrophil count (ANC). The median ANC on all ABVD treatment days (n = 658) was 0.925 x 10(9)/l, and was <0.5 x 10(9)/l on 26% of treatment days. Median normalised ABVD dose-intensity was 99.1% (range, 93-100%) and median cycle duration was 28.2 d. Incidence of bleomycin lung toxicity was 1.6%, 0.44% treatments were complicated by febrile neutropenia, and no secondary malignancies have occurred (median follow-up 48 months; range, 11-130 months). Five-year event-free (EFS) and overall survival (OS) were 92.9% and 97.4% respectively. Furthermore, the 5-year EFS and OS (87.4% and 94.1% respectively) for advanced stage patients compared favourably with a similar ABVD patient group who received routine prophylactic G-CSF (n = 23) with EFS 80.0% and OS 91.3% (P = 0.46 and 0.67 respectively). Our experience suggests that ABVD may be safely and effectively administered at >99% dose-intensity without G-CSF support, regardless of the ANC.
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PMID:G-CSF is not necessary to maintain over 99% dose-intensity with ABVD in the treatment of Hodgkin lymphoma: low toxicity and excellent outcomes in a 10-year analysis. 1745 49

ABVD remains a standard chemotherapy for Hodgkin Lymphoma (HL) despite many efforts to demonstrate the superiority of other regimens. Bleomycin was proven marginally active in this combination (J Clin Oncol 22:1532-3, 2004) but adding significant toxicity. Response to ABVD is often slow and relapse rate of 20-30% is a concern. ABVD has never been directly compared to CHOP, the other global standard for other lymphomas that is composed of agents certainly active in HL. Current study is an update on our initial report of 2004 (Blood 104, 2004). In addition to extending the follow-up, we compared outcome after CHOP in a pilot series of previously untreated patients with a retrospective results of ABVD therapy at our institution. CR/CRu rates were 88 and 62% for CHOP and ABVD, respectively. In CHOP CS III/IV group, more patients had at least three risk factors (80%) than in ABVD CS III-IV group (40%). In contrast to ABVD, there were no deaths in CHOP group, but EFS was inferior. This might result from a higher risk level in CHOP patients. Toxicity of both regimens was mild: grade 3/4 leukopenia in 9%, grade 1/2/3 peripheral neuropathy in 6% of ABVD patients, and grade 3/4 neutropenia in 7% of CHOP patients. In conclusion, CHOP-21 is an active and low-toxic regimen in HL with risk factors. A prospective comparison of CHOP with a standard chemotherapy in a randomized study will be justified.
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PMID:CHOP-21 for unfavorable Hodgkin's lymphoma. An exploratory study. 1931 2

High-dose chemotherapy followed by autologous stem cell transplant (ASCT) leads to durable remissions in approximately half of patients with chemosensitive relapsed or refractory aggressive lymphomas; however, many will relapse despite ASCT secondary to persistent minimal residual disease (MRD) or malignant graft contamination. Post-transplant rituximab may eradicate MRD. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-2 (IL-2) might enhance the efficacy of rituximab by augmenting antibody-dependent cellular cytotoxicity (ADCC). We hypothesized that given together, rituximab, GM-CSF, and IL-2 might eradicate MRD and improve event-free survival following ASCT. Forty-six patients with relapsed non-Hodgkin lymphoma (NHL) or Hodgkin lymphoma (HL) were enrolled. Stem cells were mobilized with G-CSF and GM-CSF following chemotherapy. Following BEAM conditioning, patients received GM-CSF until neutrophil engraftment. Between days + 30 and + 120, patients received one dose of rituximab 375 mg/m(2) (cycle 1), followed by three cycles of GM-CSF 250 microg/m(2)/day SQ days 1-5, IL-2 1.5 x 10(6) IU/m(2)/day SQ days 6-12, and rituximab 375 mg/m(2) IV day 9, repeated every 21 days. Thirty-eight patients were eligible for post-ASCT immunotherapy. Nine patients completed 1-2 cycles and 21 completed 3-4 cycles; eight patients did not receive post-ASCT immunotherapy. Grade 3-4 neutropenia and grade 3 thrombocytopenia were observed. With a median follow-up of 30 months, the estimated 5-year OS and EFS for all patients eligible for immunotherapy are 65% and 45%, respectively. Post-ASCT immunomodulation with rituximab, IL-2, and GM-CSF was feasible and safe, but not all patients were able to continue on to post-ASCT immunotherapy.
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PMID:Phase II study of immunomodulation with granulocyte-macrophage colony-stimulating factor, interleukin-2, and rituximab following autologous stem cell transplant in patients with relapsed or refractory lymphomas. 2049 94

High-dose chemotherapy followed by autologous stem cell transplantation (auto-SCT) is widely used as a salvage therapy in the treatment of refractory malignant lymphoma. To investigate the safety and feasibility of a high-dose MCNU, carboplatin, etoposide and cyclophosphamide (MCVC) regimen, we conducted a prospective multicenter trial. Thirty patients with relapsed/refractory/poor-risk non-Hodgkin lymphoma (NHL n = 27) or Hodgkin lymphoma (HD n = 3) were uniformly treated with an MCVC regimen and underwent auto-SCT. The median follow-up duration of the surviving patients was 67 months (56-133 months). The major toxicities were anorexia (94 %), diarrhea (80 %), nausea (79 %), febrile neutropenia (70 %), alopecia (67 %) and mucositis (60 %). Three patients developed severe left ventricular dysfunction, and two patients developed severe sinusoidal obstructive syndrome (SOS). Of these patients, two died without disease progression. Treatment-related mortality was 6.6 %. Late-onset adverse events including two cases of cytomegalovirus pneumonia and one of interstitial pneumonia were observed. In DLBCL (n = 13) and transformed FL (n = 2) patients, OS and EFS at 3 years were 72 and 46 %, respectively. These results suggest that the MCVC regimen followed by auto-SCT is a feasible and tolerable therapy for relapsed/refractory malignant lymphoma. However, cardiac toxicity due to high-dose cyclophosphamide and development of SOS can occur and should be carefully monitored. Further follow-up is needed to evaluate the long-term efficacy and safety of this regimen.
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PMID:Safety and feasibility of high-dose ranimustine (MCNU), carboplatin, etoposide, and cyclophosphamide (MCVC) therapy followed by autologous stem cell transplantation for malignant lymphoma. 2305 49

We explored activity and safety of a dose-dense/dose-intense adriamycin, bleomycin, vinblastine and dacarbazine regimen (ABVDDD-DI ) in 82 patients with advanced Hodgkin Lymphoma. Patients entered a two-stage Bryant-Day Phase II study to receive six cycles of ABVDDD-DI without consolidation radiotherapy. Cycles were supported with granulocyte colony-stimulating factor and delivered every 21 d; drugs were administered on days 1 and 11 at the same doses of standard ABVD except for doxorubicin (35 mg/m2; first four cycles only). Co-primary endpoints were complete response (CR) rate and severe acute cardiopulmonary toxicity; secondary endpoints were event-free (EFS) and disease-free survival (DFS). All patients received the four doxorubicin-intensified courses and 96% concluded all six cycles (82.3% within the intended 18 weeks). This translated into a 66.9% increase of received dose-intensity for doxorubicin and 31.8% for the other agents over standard ABVD. The CR rate was 95.1% (78/82) and 87.8% (72/82) achieved a metabolic CR after two cycles. Cardiopulmonary toxicity never exceeded grade 2 and affected 14.6% of patients. Most frequent toxicities were grade 4 neutropenia (10%) and anaemia (9%), grade 3 infection (17%) and grade 2 mucocutaneous changes (30%). Five-year EFS and DFS was 88.3% and 93.7%, respectively. ABVDDD-DI regimen was well-tolerated and ensured substantial CR and EFS rates without radiotherapy.
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PMID:A phase II study of dose-dense and dose-intense ABVD (ABVDDD-DI ) without consolidation radiotherapy in patients with advanced Hodgkin lymphoma. 2467 27

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3-4 (important), thrombocytopenia grade 3-4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28-1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3-G4 anemia and G3-G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38-38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel's final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.
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PMID:Inclusion of Platinum Agents in Neoadjuvant Chemotherapy Regimens for Triple-Negative Breast Cancer Patients: Development of GRADE (Grades of Recommendation, Assessment, Development and Evaluation) Recommendation by the Italian Association of Medical Oncology (AIOM). 3139 96

Combination regimens have shown superiority over single agents in the adjuvant treatment of resected pancreatic cancer (PC), but there are no data supporting definition of the best regimen. This work aimed to compare the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel in PC patients. A meta-analysis was performed for direct comparison between trials comparing combination regimens and gemcitabine monotherapy. Subsequently, an indirect comparison was made between trials investigating the efficacy and safety of mFOLFIRINOX, gemcitabine+capecitabine, and gemcitabine+nab/paclitaxel because of the same control arm (gemcitabine). A total of three studies met the selection criteria and were included in our indirect comparison. Indirect comparisons for efficacy outcomes showed a benefit in terms of DFS (disease-free survival)/EFS (event-free survival)/RFS (relapse-free survival) for both mFOLFIRINOX versus gemcitabine+capecitabine (HR 0.69, 95% CI 0.52-0.91) and versus gemcitabine+nab/paclitaxel (HR 0.67, 95% CI 0.50-0.90). No significant advantage was registered for OS (overall survival). Indirect comparisons for safety showed an increase in terms of G3-5 AEs (with the exception of neutropenia) for mFOLFIRINOX versus gemcitabine+capecitabine (RR 1.24, 95% CI 1.03-1.50), while no significant differences were observed versus gemcitabine+nab/paclitaxel. According to our results, mFOLFIRINOX is feasible and manageable and could represent a first option for fit PC resected patients.
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PMID:Moving the Target on the Optimal Adjuvant Strategy for Resected Pancreatic Cancers: A Systematic Review with Meta-Analysis. 3211 Sep 77

EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) is a preferred regimen for HIV-non-Hodgkin lymphomas (HIV-NHLs), which are frequently Epstein-Barr virus (EBV) positive or human herpesvirus type-8 (HHV-8) positive. The histone deacetylase (HDAC) inhibitor vorinostat disrupts EBV/HHV-8 latency, enhances chemotherapy-induced cell death, and may clear HIV reservoirs. We performed a randomized phase 2 study in 90 patients (45 per study arm) with aggressive HIV-NHLs, using dose-adjusted EPOCH (plus rituximab if CD20+), alone or with 300 mg vorinostat, administered on days 1 to 5 of each cycle. Up to 1 prior cycle of systemic chemotherapy was allowed. The primary end point was complete response (CR). In 86 evaluable patients with diffuse large B-cell lymphoma (DLBCL; n = 61), plasmablastic lymphoma (n = 15), primary effusion lymphoma (n = 7), unclassifiable B-cell NHL (n = 2), and Burkitt lymphoma (n = 1), CR rates were 74% vs 68% for EPOCH vs EPOCH-vorinostat (P = .72). Patients with a CD4+ count <200 cells/mm3 had a lower CR rate. EPOCH-vorinostat did not eliminate HIV reservoirs, resulted in more frequent grade 4 neutropenia and thrombocytopenia, and did not affect survival. Overall, patients with Myc+ DLBCL had a significantly lower EFS. A low diagnosis-to-treatment interval (DTI) was also associated with inferior outcomes, whereas preprotocol therapy had no negative impact. In summary, EPOCH had broad efficacy against highly aggressive HIV-NHLs, whereas vorinostat had no benefit; patients with Myc-driven DLBCL, low CD4, and low DTI had less favorable outcomes. Permitting preprotocol therapy facilitated accruals without compromising outcomes. This trial was registered at www.clinicaltrials.gov as #NCT0119384.
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PMID:Impact of Myc in HIV-associated non-Hodgkin lymphomas treated with EPOCH and outcomes with vorinostat (AMC-075 trial). 3243 May 7


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