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Progenitor cell mobilization by granulocyte colony-stimulating factor controlled by loci on chromosomes 2 and 11.

Granulocyte colony-stimulating factor (G-CSF) can effectively mobilize hematopoietic stem and progenitor cells from bone marrow into blood, thereby allowing peripheral blood stem cells (PBSCs) to be used for transplantation. The efficiency of PBSC mobilization response to G-CSF is a multigene trait. DBA/2 (high-responder) and C57BL/6 (low-responder) mice were used for a genetic analysis of G-CSF-induced progenitor release. Significant linkages were found on chromosome 2 by analyzing segregation distortion among the high responders of 500 backcross mice and on chromosome 11 by using the quantitative trait locus analysis of 26 strains of BXD recombinant inbred mice. (Blood. 2000;95:1872-1874)

Animals↗

[Granulocyte colony-stimulating factor in the treatment of febrile neutropenia].

PURPOSE: To determine whether granulocyte colony-stimulating factor (G-CSF) used in addition to antibiotic therapy, in patients with chemotherapy-induced febrile neutropenia shortens the period of fever, neutropenia and hospitalization. PATIENTS AND METHODS: The study was prospective. Patients with lymphoblastic acute leukemia (LAL) were included. They received intensive chemotherapy of induction, intensification, or consolidation. At random, a group received amikacin-ceftriaxone; if no had response after 3 days, we added vancomicin and, after 7 days, amphotericin. The other group received in addition these antibiotics, granulocyte colony-stimulating factor. RESULTS: The groups were comparable in the magnitude of the initial neutropenia (< 0.5 x 10(9)/L), site of the infection, chemotherapy received germs isolated, age, and sex. The patients of the group that received FEC-G were cured in the course of 3.1 days; in the group without FEC-G, this occurred in 7.2 days (p = 0.0001). At the end of the infectious episode, the number of neutrophils, in the group with FEC-G, was of 1.9 x 10(9)/L versus 0.7 x 10(9)/L (p = 0.0009). The mortality was of one and two cases (p = 0.46). The global mortality was 7.5%. CONCLUSIONS: The addition of FEC-G to the treatment with antibiotics, in febrile neutropenia, decreases duration of days with fever, hospitalization and neutropenia. However, the frequency of cure is not augmented.

Adolescent↗

Outpatient sequential high dose alkylation with stem cell support for patients with advanced breast cancer: a phase I-II study.

We evaluated the feasibility of administering, in an out-patient setting, a sequential high dose alkylating regimen with hematopoietic growth factor (HGF) and stem cell support to patients with advanced breast cancer. Peripheral blood stem cells (PBSC) were previously collected after chemotherapy and HGF. Two consecutive cycles of alkylating agents were planned: Thiotepa (T) then, 15 days later, BCNU (B). Three dose levels of each agent were administered in cohorts of consecutive patients: 400, 500 and 600 mg/m2 respectively. HGF and reinfusion of PBSC followed both cycles. Toxicity and response were evaluated according to the WHO recommendations. From April 1996 to August 1988, 30 women were enrolled: 8 in the first, 12 in the second and 10 in the third dose level. In all cases, B was administered after T with a median delay of 25 days because of grade 3/4 hematological toxicity. 4 patients did not receive B because of previous lung radiotherapy, persistent tricytopenia or insufficient PBSC collection. 19 patients with measurable lesions were considered for response. The objective response rate was 48% (11% CR, 37% PR). We recommended T and B at a dose of 600 mg/m2 to conduct a phase II study in metastatic breast cancer and even to administer B before T.

Antineoplastic Agents, Alkylating↗

Increased false negative sentinel node biopsy rates after preoperative chemotherapy for invasive breast carcinoma.

BACKGROUND: Sentinel lymph node dissection (SLND) has been a promising new technique in breast carcinoma staging, but could be unreliable in certain patient subsets. The current study assessed whether age, preoperative chemotherapy, tumor size, and/or previous excisional biopsy influenced the identification of sentinel nodes (SLNs) or the reliability of a node-negative SLND in predicting a node negative axilla. METHODS: Eighty-two patients who had clinically negative axillae underwent SLND followed by Level I/II axillary lymph node dissection (ALND). SLNDs were performed using both technetium-99m (Tc-99m) labeled colloid and isosulfan blue dye. SLNs were analyzed by hematoxlyin and eosin and immunocytochemical techniques. RESULTS: SLNs were successfully identified in 80% of patients. Mapping success was decreased among postmenopausal women but was not influenced by preoperative chemotherapy, large tumor size, or previous excisional biopsy. Of the 31 successfully mapped, node positive patients, 5 had false negative (FN) SLNDs (overall FN rate = 16%). Of the 9 successfully mapped patients who had received preoperative chemotherapy and had positive axillary nodes, 3 had FN SLND (FN rate = 33%). The presence of clinically positive lymph nodes before chemotherapy did not predict which patients would have a subsequent FN SLND. T3 tumor size, but not previous excision, was associated significantly with increased FN rate, although the FN rate for previous excision was 11%. No FN SLND occurred with T1/T2 tumors that were not excised previously and had not received preoperative chemotherapy. CONCLUSIONS: Preoperative chemotherapy was associated with an unacceptably high FN rate for SLND. While larger tumor size also was associated with FN SLND, this effect might have been due to preoperative chemotherapy use in these patients. Small sample size precluded determining whether excisional biopsy before mapping increased FN SLND rates independently.

Adult↗

Results of IDA-FLAG programme in the treatment of recurrent acute myeloblastic leukaemia--preliminary report.

BACKGROUND: Unsatisfactory treatment results of acute myeloblastic leukaemia inspire the search for new drugs, characterised by higher efficiency and lower toxicity. The aim of the study was the assessment of the efficiency and side effects associated with the implementation of IDA-FLAG protocol. MATERIAL AND METHODS: The assessment of treatment results and undesirable effects was based on the material of 4 children with the relapse of acute myeloblastic leukaemia, after a total of 6 IDA-FLAG protocols. RESULTS: Complete remission was obtained in 2 (50%) children, with mean remission time of 13.5 months. One of the children underwent the transplantation of haematopoietic cells from unrelated donor. The main side effect observed was bone marrow aplasia. Leucopenia, granulocytopenia, thrombocytopenia and anaemia persisted for approx. 20 days. Apart from haematological symptoms, the following were also observed: the symptoms of intolerance after ARA-C, aspergillosis of paranasal sinuses and lungs and severe coagulation disorders. CONCLUSION: IDA-FLAG protocol may be recommended for use in children with AML relapse and the undesirable effects observed are acceptable.

Adolescent↗

Recombinant granulocyte colony-stimulating factor (G-CSF) in infectious diseases: still a debate.

Granulocyte colony-stimulating factor (G-CSF), a central mediator of the endogenous response to infection and inflammation, is approved for use in the prevention of infection-related complications in patients with nonmyeloid malignancies during antineoplastic therapy associated with high risk of severe neutropenia. Administration of granulocyte colony-stimulating factor results in improvement of host defence paired with anti-inflammatory effects. There is evidence from animal and clinical studies that administration of granulocyte colony-stimulating factor may also be beneficial in non-neutropenic infections. This review focuses mainly on the results of different animal and clinical studies of granulocyte colony stimulating factor used in the treatment of severe infections and sepsis.

Animals↗

[Possibilities of immune prevention of pyo-septic complications in cancer patients by granulocytic colony stimulating factors].

The study was carried out during the postoperative period in 75 patients with cancer of the esophagus and cardial portion of the stomach and 40 patients with lung cancer; 64 of these patients received immunoprophylactic treatment with neipogen, granulocytic colony-stimulating factor. Immune prevention resulted in a 2-fold decrease in the incidence and severity of pyoseptic and visceral complications and 1.5 times decrease in the duration of hospital treatment and mortality during the early postoperative period. Neipogen therapy was conductive to a 2-fold increase in the leukocyte count during the postoperative period in comparison with the control. The range of "safe" values of the major mediators of inflammations (TNF-alpha, IL-1, IL-8), characteristic of uneventful course of the postoperative period, was determined. About 75% pyoseptic complications were associated with mediator levels below this range. The levels of inflammation mediators in the patients treated with neipogen were within the safe range.

Adult↗

Collection of Philadelphia-negative stem cells using recombinant human granulocyte colony-stimulating factor in chronic myeloid leukemia patients treated with alpha-interferon.

BACKGROUND AND OBJECTIVES: Autologous stem cell transplantation is a therapeutic option for chronic myeloid leukemia (CML) patients who are not candidates for allogeneic transplant. To reduce the risk of post-autografting disease recurrence, different strategies of stem cell selection have been attempted. The results of using recombinant human granulocyte colony-stimulating factor (rHuG-CSF) for harvesting hematopoietic progenitors in CML patients treated with interferon-a (IFN) are reported. DESIGN AND METHODS: Twenty-one CML patients who received IFN for a median of 21 (8-68) months were mobilized with rHuG-CSF (10 mg/kg/day). Twelve were in complete (CCR) or major (MCR) cytogenetic response. Complete success was considered a sufficient harvest (> 1 x 10(6)/kg CD34(+) cells/kg) without Philadelphia (Ph)+ metaphases in at least one apheresis; a partial success was a sufficient harvest with 1-35% Ph(+) cells. RESULTS: A total of 78 aphereses were performed. No patient had major side-effects. The median number (range) of mononuclear and CD34(+) cells obtained was, respectively, 8.6 x 10(8)/kg (0.9-22.6) and 3.3 x 10(6)/kg (0.4-26.3) per patient. A sufficient cell yield was collected in all but three patients. A complete/partial success was achieved in seven CCR/MCR patients (63%) and in three (33%) with other responses. Four patients underwent successful autografting using the stem cells obtained after rHuG-CSF mobilization. INTERPRETATION AND CONCLUSIONS: Mobilization of IFN-treated patients using rHuG-CSF is safe and provides a significant proportion of Ph-negative progenitors in CML patients in complete or major cytogenetic response.

Adolescent↗

Effect of G-CSF on peripheral blood progenitor cell mobilization and collection from healthy donors.

We studied granulocyte colony-stimulating factor (G-CSF) mediated peripheral blood progenitor cells (PBPC), which were mobilized and collected from healthy donors for allogeneic transplantation. A total of 26 donors, age ranged from 21-41 years were mobilized with G-CSF at a dose of 7.5 microg/kg/day subcutaneously for 5 days and the collection was started on day 5. The CD34 cell counts reached a maximum on day 5 and subsequently declined despite continually given G-CSF. White blood cells (WBC), absolute neutrophil counts (ANC), absolute lymphocytes (AL) and their subsets, absolute mononuclear cells (AMNC), colony-forming unit-granulocyte, macrophage (CFU-GM) and CD34+ cells were increased about 6, 9, 2, 3, 34 and 40-fold, respectively, but red blood cells (RBC), hematocrit (Hct) and platelets (Pit) decreased on day 5 when compared to day 0. All parameters decreased after stem cell collection. For stem cell collection by Cobe Spectra, we used a blood volume of 19.27 +/- 4.65 liters, flow rate of 60.53 +/- 10.03 ml/minute, acid citrate dextrose solution (ACD)/blood ratio of 1:13.31, the final product volume was 314.14 +/- 72.24 ml, collection time was 325.40 +/- 73.36 minutes and one or two procedures were sufficient. The correlation between the number of CD34+ cells/kg, CFU-GM/kg and MNC/kg found in the harvested product and CD34 cells can be used for determining the necessary amount of progenitor cells for transplantation.

Adult↗

[Experience with fludarabine treatment and review of the literature].

INTRODUCTION: Fludarabine is the most commonly used purine analog, its mechanism of action is complex. Fludarabine inhibits DNA synthesis, acts on non-dividing (G0 phase) cells influencing apoptosis. PATIENTS, RESULTS, CONCLUSIONS: In our institute 47 patients were treated with fludarabine or fludarabine based combination chemotherapy. Fludarabine was given in 19 patients with chronic lymphocytic leukaemia (CLL), complete remission (CR) was achieved in one case, partial remission (PR) was obtained in 10 patients. Fludarabine was more effective in patients who received less intensive chemotherapy prior to fludarabine therapy and in those patients who had less advanced diseases. Elderly patients (over sixty years of age) also responded to fludarabine therapy. Fludarabine and cyclophosphamide combination (FCy) were used in three lymphocytic lymphoma patients, two of them obtained PR, in the third case the disease progressed. Fludarabine + mitoxantrone (Novantrone) + dexamethasone (FND) regimen was administered in nine patients who were previously heavily treated (one patient with B-CLL, one with T-CLL, one with peripheral T-cell lymphoma and six with indolent B-cell lymphoma). More patients and longer follow up is needed to determine the efficacy of FCy and FND protocol. FLAG-IDA (fludarabine, high dose Ara-C, granulocyte colony-stimulating factor, idarubicin) was applied in 16 acute leukaemia patients with poor prognosis including therapy refractory and relapsing cases. Three CR and two PR, one CR and three PR was achieved in nine patients with acute myeloid leukaemia and in seven patients with acute lymphoid leukaemia, respectively. For this reason, despite the short period of remission, this regimen can be recommended to patients who are candidate for stem cell transplantation.

Adult↗

[Mobilization of peripheral blood cells for auto- and allogenic transplantations of hemopoietic cells].

AIM: To study mobilisation of peripheral blood stem cells (PBSC) via single and split subcutaneous injection of granulocytic colony-stimulating factor (G-CSF) and isolation of PBSC concentrates for their transplantation with leukapheresis (LA) and large volume leukapheresis (LVL) in patients with solid tumors and hematological diseases as well as in the group of relative donors. MATERIAL AND METHODS: LA procedures were made on cell blood fractionator COBE Spectra. In groups 1 and 2 LVL was made with apparatus perfusion of circulating blood of the patient or donor (15-33 l) vs 7-12 l in LA by standard technique in group 3. To reduce the volume of sodium citrate solution used in LVL, to prevent citrate intoxication and hypervolemia, a sharp rise of anticoagulant/blood ration was applied. RESULTS: PBSC-mobilisation with split doses of G-CSF and large volume leukapheresis in 23 patients and 11 relative donors vs mobilisation in 26 patients with single-daily dose of G-CSF and leukapheresis of 3 TBV has revealed that split administration of G-CSF increased the number of leukocytes and CD34+ cells more considerably. CONCLUSION: LVL provides PBSC dose sufficient for transplantation during one procedure in the majority of donors and relative donors. This makes the method more comfortable and cost-effective.

Adolescent↗

[Common variable immunodeficiency. Report of 2 cases].

We report two cases with common variable immunodeficiency. Both of them had gammaglobulin concentration lower than 300 mg/dL and evolved differently. The first one had three pneumonic episodes that responded satisfactorily to antibiotics. Today, this patient presents only two or three sinusitis clinical schemes per year, and has a good response to treatment. The second one has a bad evolution and presents hematological problems like thrombocytopenia and neutropenia. She also suffers lymphoid nodular hyperplasia in the intestinal tract and atrophy in the intestinal. These cases illustrate the wide clinical, immunological and genetic variety of the syndrome.

Anti-Bacterial Agents↗