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Drug-induced agranulocytosis during treatment with infliximab in enteropathic spondyloarthropathy.

Agranulocytosis is a disorder characterized by a severe decrease in the number of granulocytes in blood, that frequently occurs as an adverse reaction to some drugs. By now, there are no reports in literature of agranulocytosis caused by tumur necrosis factor-alpha blockers. We describe the case of a 20-year-old Caucasian male affected by enteropathic (Crohn's disease) spondyloarthropathy HLA B27 negative, successfully treated with infliximab. After the second infliximab infusion, he was found to have a severe transient neutropenia (0.5 x 10(9)/L). Routine serum chemistry and full blood cell count (apart from neutrophil count) were normal. Serology excluded an active infection. Bone marrow needle aspirate showed a normal trilineage differentiation. Autoantibody assessment showed negative ANA, anti-dsDNA, anti-ENA, and ANCA, but positive granulocyte-bound antibodies (GBA) and neutrophil-specific (CD 16+)-bound antibodies (anti-NA). Ten weeks after infliximab infusion, neutrophil count and GBA and anti-NA assay returned spontaneously within normal range and we observed the same progress after every successive infliximab infusion we performed. These data indicated that infliximab possibly triggered production of granulocyte and neutrophil autoantibodies with resultant autoimmune agranulocytosis.

Adult↗
PubMed2005

[Neutropenia induced by taxoids and its control with granulocyte colony-stimulating factor].

Nowadays, the use of taxoid derivated compounds constitutes one of the main chemotherapeutic weapons against breast cancer, ovarian cancer and non-microcytic lung cancer. The limiting factor when determining the dose of taxoids to be administered is the occurrence of neutropenia which is a common side-effect of this therapy. That is why we propose this retrospective study in which we assessed docetaxel and paclitaxel induced neutropenia in oncologic patients by means of colony stimulating factors consumption. A systematic revision of filgastrin consumption by patients treated with taxoids during 2003 in the Infanta Cristina Hospital (Badajoz, Spain) was performed. Filgastrin consumption data were obtained individually, considering its dispensation to external patients as well as the possible administration during hospital stay. 22 out of the 140 patients treated with paclitaxel required colony stimulating factor. On the other hand, 27 out of 116 patients treated with docetaxel received filgastrin. The relation between filgastrin (micrograms) and taxoid consumption (milligrams) was 1.35 for paclitaxel and 4.17 for docetaxel. Taking into account each patient taxoids consumption (milligrams), the results were 7.09 for paclitaxel and 20.12 for docetaxel. When selecting the patients who suffer from breast cancer and lung cancer, these ratios were 0.76 for paclitaxel and 6.48 for docetaxel. The docetaxel group consumed 2.83 more colony stimulating factor than the pacitaxel group. This ratio was even greater (3.1) when ovarian cancer patients were excluded. These results showed an unfavorable relation for docetaxel, thus confirming that the use of docetaxel provokes a greater incidence and severity of neutropenia.

Antineoplastic Agents↗
PubMed2005

Amsacrine combined with etoposide and high-dose methylprednisolone as salvage therapy in acute lymphoblastic leukemia in children.

In a retrospective analysis of 24 children with refractory or multiply relapsed acute lymphoblastic leukemia (ALL), a salvage regimen comprising amsacrine, etoposide, and high-dose methylprednisolone AEP achieved a significant treatment response in 11 of 19 evaluable patients (8 complete and 3 partial remissions). Five of 9 AEP-responsive patients who underwent subsequent stem cell transplantation are alive (median follow-up: 43 months; range 10 to 91). The load of minimal residual disease prior to transplantation appears to be predictive for outcome in this very poor-prognosis subgroup of ALL.

Adolescent↗
PubMed2006

Dose-dense R-CHOP-14 supported by pegfilgrastim in patients with diffuse large B-cell lymphoma: a phase II study of feasibility and toxicity.

BACKGROUND AND OBJECTIVES: The aim of this study was to evaluate the feasibility and toxicity of CHOP-14, with rituximab (R-CHOP-14), supported by pegfilgrastim, in untreated diffuse large B-cell lymphoma (DLBCL). DESIGN AND METHODS: This study included 50 patients with DLBCL with a median age of 55 years (range: 22-70). Sixty-two percent had an International Prognostic Index score >1, 40% had bulky disease and 52% had stage IV disease. CHOP was administered every 14 days, preceded on day 1 by rituximab (375 mg/m2) and followed on day 3 by pegfilgrastim (6 mg per cycle). Toxicity was calculated over 277 cycles administered; feasibility was calculated over 227, since the first cycle in each patient was not susceptible to delay or dose-reduction. RESULTS: Therapy was delivered on time in 92% of cycles, with the relative dose intensity being 95% for doxorubicin and cyclophosphamide. Grade 4 neutropenia developed in 19% of cycles and neutropenic fever in 4% of cycles (16% of patients), with a median duration of 3 days (range: 2-10). The program was completed in 40 of 50 patients (80%); reasons for withdrawal included progression in three patients, interstitial pneumonia in four, prolonged severe neutropenia in two and septic shock in one patient. Severe adverse events occurred on 12 occasions (4% of cycles), involving 11 patients (22% of total); the most frequent severe adverse event was interstitial pneumonia which occurred in seven patients (14% of total). In three cases, Pneumocystis carinii pneumonia was documented; no cotrimoxazole prophylaxis had been given and a correlation with hypogammaglobulinemia was observed. The complete remission rate was 74%; the 2-year event-free and overall survival rates were 72% and 68%, respectively. INTERPRETATION AND CONCLUSIONS: A single dose of pegfilgrastim per cycle of R-CHOP allowed on-time delivery of this chemotherapy in DLBCL, with a low incidence of febrile neutropenia; the risk of P. carinii pneumonia makes cotrimoxazole prophylaxis essential in this setting.

Adult↗
PubMed2006

Pegfilgrastim support for full delivery of BEACOPP-14 chemotherapy for patients with high-risk Hodgkin's lymphoma: results of a phase II study.

The primary endpoint of this feasibility study was to determine whether pegfilgrastim support could enable the delivery of the full dose of BEACOPP chemotherapy every 14 days on schedule. Forty-one patients with high-risk Hodgkin's lymphoma were randomized to receive pegfilgrastim (6 mg) on day 4 or 8 of each cycle. Eighty-one percent of cycles administered were delivered at full dose and on schedule (FDOS). Response was retrospectively assessed in 27 patients at 6 months; 23 of these 27 patients (85%) achieved a complete response and one (4%) achieved a partial response. Toxicities were mostly moderate in intensity. These results support the feasibility of delivering full dose, on schedule BEACOPP-14, chemotherapy with pegfilgrastim support.

Adolescent↗
PubMed2006

Spontaneous splenic rupture in a healthy allogeneic donor of peripheral-blood stem cell following the administration of granulocyte colony-stimulating factor (g-csf). A case report and review of the literature.

Human granulocyte colony-stimulating factor (G-CSF) is a hematopoietic hormone promoting the growth, proliferation, differentiation and maturation of myeloid and leukocytic lineages. G-csfs have been used to improve granulocyte count in neutropenic patients, reduce the incidence and duration of neutropenia in patients receiving cytotoxic chemotherapy and to mobilize peripheral blood stem cells prior to leukapheresis for using in both autologous and allogeneic hematopoietic cell transplantation. In general, side-effects are mild to moderate and life threatening side-effects like splenic rupture are very rare. We herein, report a case of spontaneous splenic rupture secondary to high-dose G-CSF use (20 mcg/kg/day), in a healthy female allogeneic donor of peripheral-blood stem cell (PBSC) .

Abdominal Pain↗
PubMed2006

Effects of pegfilgrastim on normal biodistribution of 18F-FDG: preclinical and clinical studies.

UNLABELLED: The purpose of this study was to evaluate the effects of pegfilgrastim, a long-acting granulocyte colony-stimulating factor, on the normal biodistribution of (18)F-FDG in an animal model and in humans. METHODS: Two groups of 12 rats received a single subcutaneous injection of either normal saline or pegfilgrastim. One, 7, 14, and 21 d after injection, biodistribution studies were performed 1 h after (18)F-FDG injection. Sixteen breast cancer patients underwent baseline (18)F-FDG PET/CT and, approximately 1 wk after receiving 1 dose of docetaxel and adjunctive pegfilgrastim, follow-up (18)F-FDG PET/CT (scan 2). Standardized uptake values corrected for lean body mass (SUL) were determined for several normal organs before and after therapy. RESULTS: In rats, bone marrow (18)F-FDG uptake (standardized uptake value) was higher in the pegfilgrastim group 1 d after injection (mean +/- SD, 8.3 +/- 4.1 vs. 2.5 +/- 0.2, P < 0.05), whereas (18)F-FDG uptake in blood was lower (0.41 +/- 0.06 vs. 0.49 +/- 0.01, P < 0.05). In patients, mean SUL was higher in bone marrow (4.49 +/- 1.50 vs. 1.33 +/- 0.22, P < 0.0001), spleen (3.29 +/- 0.83 vs. 1.23 +/- 0.23, P < 0.0001), and liver (1.45 +/- 0.25 vs. 1.31 +/- 0.23, P = 0.01) but lower in brain (4.18 +/- 0.76 vs. 5.14 +/- 1.44, P < 0.01) on scan 2 than on the baseline scan. CONCLUSION: In both the animal model and humans, pegfilgrastim markedly increased bone marrow uptake of (18)F-FDG and reduced (18)F-FDG uptake in some normal tissues. These profound alterations in (18)F-FDG biodistribution induced by pegfilgrastim must be considered when one is evaluating quantitative (18)F-FDG PET scans for tumor response to therapy.

Animals↗
PubMed2006

[G-CSF in oncology].

Neutropenia and its subsequent infectious complications represent the most common dose-limiting toxicity of cancer chemotherapy. Febrile neutropenia (FN) occurs with common chemotherapy regimens in 25 to 40 % of treatment-naive patients, and its severity depends on the dose intensity of the chemotherapy regimen, the patient's prior history and comorbidities. Neutropenia is associated with the risk of life-threatening infections as well as chemotherapy dose reductions and delays that may compromise treatment outcome. One of the first, most important and sustained applications of recombinant DNA technology in medicine was the cloning and introduction into clinical practice of several glycoprotein factors involved in the regulation of hematopoiesis. Colony-stimulating factors (CSFs) such as granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) are now an integral part of the prevention of potentially life-threatening FN. Important uses of CSFs in oncology are prevention of FN after chemotherapy, treatment of FN, collection of CSF-mobilised peripheral stem cells and support following peripheral stem cells transplantation. This article reviews the data supporting the clearly clinical applications of CSFs in oncology.

Antineoplastic Agents↗
PubMed2006

[New generation cytokines to prevent anemia and febrile neutropenia].

Febrile neutropenia and anemia are two major complications of chemotherapy. Human recombinant cytokines as G-CSF and erythropoietin allow efficient fight against these secondary effects but require iterative injections due to a short half life. The glycosylation of natural cytokines results in enhanced stability of these molecules of new generation and makes it possible to space the injections which become concomitant of chemotherapies. With regard to the erythropoietin, the prolonged half-life form shows a similar effectiveness with the natural molecule. For the G-CSF, the glycosylated form could still show itself more effective for the prevention of febrile neutropenias. Finally, these new molecules allow an improvement of the quality of life while ensuring an optimal dose-intensity of the treatment.

Anemia↗