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)

SCN is an inherited hematological disorder with severe neutropenia and recurrent infections. Although there are some reports that recombinant rhG-CSF improves clinical outcome, allogeneic HSCT appears to be the only curative treatment for these patients. We report here two children with SCN successfully treated by CBT from unrelated donors. They were refractory to rhG-CSF treatment and have no identical family donor. Bu + CY were given as conditioning. Case 1 and Case 2 received 6/6 and 5/6 HLA-matched unrelated umbilical cord blood, respectively. The number of infused nucleated cells was 6, 18 x 10(7)/kg and CD34(+) cell number was 3, 74 x 10(5)/kg in Case 1. Those cell numbers were 8, 8 x 10(7)/kg and 5, 34 x 10(5)/kg for Case 2, respectively. Neutrophil/platelet engraftments were 45/49 days in Case 1 and 24/36 days in Case 2. Grade II cutaneous acute GVHD was seen in Case 2 that was treated successfully with prednisolone. Both patients are well with normal hematological findings and full donor chimerism for post-transplant 20 and 24 months, respectively. We conclude that UCB can be considered as a safe source of stem cell in patients with SCN who need urgent HSCT.
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PMID:Unrelated cord blood transplantation in children with severe congenital neutropenia. 1899 63

Pegfilgrastim (PEGFIL) has been found to be comparable to daily filgrastim (FIL) in managing chemotherapy-induced neutropenia. In the present study, we evaluated the ability of PEGFIL to mobilize stem cells in 38 consecutive patients with lymphoproliferative diseases (multiple myeloma, n = 18; lymphomas, n = 15; chronic lymphocytic leukemia, n = 5). Patients were mobilized using PEGFIL (6-18 mg as a single dose) during 2005-2006; 32 then received high-dose chemotherapy followed by autologous stem cell transplantation. PEGFIL-mobilized patients were matched by age, disease, and treatment line at a ratio of 1:2 to historical FIL-mobilized controls. The primary study endpoint was the blood CD34(+) concentration at onset of leukapheresis. Leukapheresis began a median of 10 days from the beginning of mobilization chemotherapy in both groups. At the onset of leukapheresis, median blood CD34(+) cell counts did not differ significantly in the FIL group compared with the PEGFIL group (79 x 10(6)/L vs 64 x 10(6)/L, respectively; p = 0.44). In the different disease categories, the respective CD34(+) cell counts after FIL and PEGFIL mobilization were 72 x 10(6)/L vs 123 x 10(6)/L (p = 0.08) in myeloma, 51 x 10(6)/L vs 62 x 10(6)/L (p = 0.6) in lymphomas, and 27 x 10(6)/L vs 30 x 10(6)/L (p = 0.62) in CLL, respectively. The target CD34(+) cell yield was harvested with one leukapheresis in 53% of PEGFIL-mobilized patients. Engraftment after autografting did not differ significantly in the two groups. Stem cell mobilization with a single dose of PEGFIL was, therefore, comparable to that achieved using daily FIL in patients with lymphoproliferative diseases. PEGFIL is a more practical way to mobilize stem cells than daily FIL.
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PMID:Single-dose pegfilgrastim is comparable to daily filgrastim in mobilizing peripheral blood stem cells: a case-matched study in patients with lymphoproliferative malignancies. 1913 94

We identified nicotinamide phosphoribosyltransferase (NAMPT), also known as pre-B cell colony enhancing factor (PBEF), as an essential enzyme mediating granulocyte colony-stimulating factor (G-CSF)-triggered granulopoiesis in healthy individuals and in individuals with severe congenital neutropenia. Intracellular NAMPT and NAD(+) amounts in myeloid cells, as well as plasma NAMPT and NAD(+) levels, were increased by G-CSF treatment of both healthy volunteers and individuals with congenital neutropenia. NAMPT administered both extracellularly and intracellularly induced granulocytic differentiation of CD34(+) hematopoietic progenitor cells and of the promyelocytic leukemia cell line HL-60. Treatment of healthy individuals with high doses of vitamin B3 (nicotinamide), a substrate of NAMPT, induced neutrophilic granulocyte differentiation. The molecular events triggered by NAMPT include NAD(+)-dependent sirtuin-1 activation, subsequent induction of CCAAT/enhancer binding protein-alpha and CCAAT/enhancer binding protein-beta, and, ultimately, upregulation of G-CSF synthesis and G-CSF receptor expression. G-CSF, in turn, further increases NAMPT levels. These results reveal a decisive role of the NAD(+) metabolic pathway in G-CSF-triggered myelopoiesis.
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PMID:NAMPT is essential for the G-CSF-induced myeloid differentiation via a NAD(+)-sirtuin-1-dependent pathway. 2005 15

The practice of hematopoietic stem cell transplantation (HSCT) has undergone many changes that affect the likelihood that a given patient would develop an invasive fungal infection (IFI). The risks for IFI and the types of IFI that may occur are not continuous over the time course after transplantation. IFIs vary with the events that occur during the pre-engraftment neutropenic period, the early post-engraftment period until approximately day 100 post-transplant, and those in the late post-engraftment period after day 100. A number of well-recognized transplant recipient-, transplant procedure-, and transplant complication-related factors play a role in the likelihood of IFI. Important recipient-related factors include age, state of the underlying disease for which the HSCT is being done, and treatment-related history. Transplant procedure-related factors include the type of transplant (autologous or allogeneic), the use of and timing of anti-fungal prevention strategies including whether or not the transplant was conducted in a protected environment to minimize environmental exposure to mould conidia, the choice of conditioning (myeloablative or non-myeloablative), human leucocyte antigen-relatedness [autologous, matched related, mismatched related (including haploidentical pairings), unrelated (matched or mismatched)], stem cell source (bone marrow, peripheral, or cord blood), stem cell dosing, and stem cell product processing (red cell, plasma, or T-lymphocyte depletions, or CD34 selections). Transplant-related complications include duration of pre-engraftment period of neutropenia, graft failure or rejection, the degree of cytotoxic conditioning therapy-related intestinal mucosal damage, acute and chronic graft-versus-host disease (GvHD), the use of corticosteroids for the prevention or management of GvHD, the presence of cytomegalovirus infection and disease. The interaction of these factors over a given patient's journey through HSCT conspires to promote or reduce the overall IFI risk and set the conditions for the development of any given IFI. The following discussion attempts to look at this from the perspective of the transplant physician struggling to account for these interactions and their attendant risks for IFI.
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PMID:Invasive fungal infection in haematopoietic stem cell transplant recipients: epidemiology from the transplant physician's viewpoint. 1934 34

Lymphoid enhancer-binding factor 1 (LEF1) is a neutrophilic granulopoiesis regulator whose absence is critical in congenital neutropenia. We have shown LEF1 downregulation in the CD34(+) cells of the majority of myelodysplastic syndromes (MDS) patients. LEF1 was the most significant differentially expressed gene between early and advanced MDS. Marked LEF1 downregulation was found in 27/32 patients with advanced MDS and in 6/35 patients with early MDS, and was associated with neutropenia. Downregulation of LEF1 mRNA was reflected at the protein level. Immunostaining for CD34/LEF1 may represent a marker of advanced MDS. LEF1 may play a role in the defective maturation of myeloid progenitors in MDS.
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PMID:Marked downregulation of the granulopoiesis regulator LEF1 is associated with disease progression in the myelodysplastic syndromes. 1943 82

The optimal timing for recombinant human (rh)G-CSF administration after chemotherapy for PBSC mobilization has not yet been determined. In this study, we compared two different time schedules of rhG-CSF; 4th (early) vs 7th day (late), in 48 consecutive patients with multiple myeloma and lymphoma undergoing PBSC mobilization with CE (CY 4 g/m(2) on day 1 and etoposide 200 mg/m(2) on days 1-3). The rhG-CSF dose was 10 microg/kg/day for all patients. Both groups were comparable in terms of sex, age and number of previously given different chemotherapy regimens. Duration of neutropenia, CD34(+) cell count on the first day of apheresis and numbers of aphereses were not statistically different between the two arms. However, the number of doses of rhG-CSF up to the first cycle of apheresis procedures was significantly lower in the late group than in the early group (P=0.005). The median number of total CD34(+) cells collected was 10.54 x 10(6)/kg (range 0.11-37.27) in the early group and 10.81 x 10(6)/kg (range 0.17-49.83) in the late group of rhG-CSF (P=0.781). We conclude that PBSC mobilization after late use of rhG-CSF is an effective approach and therefore, in routine clinical practice, late rhG-CSF may be used for PBSC collections after chemotherapy-based mobilization regimens in this cost-conscious era.
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PMID:Mobilization of PBSCs with chemotherapy and recombinant human G-CSF: a randomized evaluation of early vs late administration of recombinant human G-CSF. 1959 20

To describe utilization of a biosimilar product containing filgrastim (Neutromax), data of 414 myeloma or lymphoma patients subjected to autologous SCT between 1998 and 2007 were analyzed. Filgrastim was used for mobilization of progenitors (5 days at 300 microg/day) and for the recovery of neutropenia after transplantation (100 microg/day, since day +5). In 2003, the excipient mannitol was replaced by sorbitol. A mean dose of 9.47 x 10(6)CD34(+)cells/kg was infused; 100 neutrophils/mm(3) required 5-day treatment; 500 neutrophils/mm(3), 6 days and 1000 neutrophils/mm(3), 7 days. Neutromax effect in SCT is similar to reports with other brands. No difference was found between formulations.
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PMID:Utilization study of filgrastim (Neutromax) during autologous haematopoietic precursor transplantation for myeloma and lymphoma patients. 1969 52

The purpose of this study was to evaluate the efficacy and safety of short-course bortezomib, melphalan, prednisone (VMP) in previously untreated multiple myeloma as frontline therapy for transplant-ineligible patients and induction prior to autologous stem cell transplantation (ASCT). Patients received up to 6 28-day cycles of bortezomib 1.3 mg/m(2), days 1, 4, 8, and 11, plus melphalan 6 mg/m(2) and prednisone 60 mg/m(2), days 1-7. After 2-6 cycles, eligible and consenting patients could proceed to ASCT. Responses were assessed by International Uniform Response Criteria. The primary endpoint was complete response (CR) rate with VMP. Forty-five patients were enrolled. Among 44 evaluable patients, response rate was 95%, including 18% >or=CR (9% stringent CR), 27% very good partial responses (VGPR), and 50% partial responses (PR). Twenty patients proceeded to ASCT. Stem cell collection was successful in all; median yield was 5.6 x 10(6) CD34(+) cells/kg. Posttransplant response rates were 30% >or=CR (10% stringent CR), 65% VGPR, and 5% PR. After median follow-up of 14.0/14.6 months, median time to progression and progression-free survival were both 19.8/27.9 months in non-ASCT/ASCT patients. Seven patients have died; 1-year survival rates were 82%/95% in non-ASCT/ASCT patients. The most common grade 3/4 toxicities were thrombocytopenia (20%), neutropenia (28%), and infection (9%). Peripheral neuropathy grade 2-4 was the most common nonhematopoietic side effect occurring 17 patients (38%), although it was typically reversible, and only 5 patients (11%) discontinued therapy as a result of it. Short-course VMP is highly effective and generally well tolerated, both as initial treatment in non-ASCT patients and induction prior to ASCT. VMP did not negatively affect stem cell collection. Longer follow-up and prospective phase III trials are required to validate these initial observations.
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PMID:"Short course" bortezomib plus melphalan and prednisone as induction prior to transplant or as frontline therapy for nontransplant candidates in patients with previously untreated multiple myeloma. 1973 51

Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used for treatment of neutropenia. Filgrastim, Nartograstim, and Lenograstim are clinically available in Japan. However, the differences in potential benefit for radiation-induced disorder between these types of rhG-CSFs remain unknown. Therefore, the effects of three different types of rhG-CSFs on granulocyte progenitor cells and expansion of neutrophils from nonirradiated or 2 Gy X-irradiated human CD34+ hematopoietic progenitor cells were examined. For analysis of granulocyte colony-forming units (CFU-G) and a surviving fraction of CFU-G, nonirradiated or X-irradiated CD34+ cells were cultured in methylcellulose containing rhG-CSF. These cells were cultured in serum-free medium supplemented with rhG-CSF, and the expansion and characteristics of neutrophils were analyzed. All three types of rhG-CSFs increased the number of CFU-G in a dose-dependent manner; however, Lenograstim is superior to others because of CFU-G-derived colony formation at relatively low doses. The surviving fraction of CFU-G was independent of the types of rhG-CSFs. Expansion of neutrophils by rhG-CSF was largely attenuated by X-irradiation, though no significant difference in neutrophil number was observed between the three types of rhG-CSFs under both nonirradiation and X-irradiation conditions. In terms of functional characteristics of neutrophils, Lenograstim-induced neutrophils produced high levels of reactive oxygen species compared to Filgrastim, when rhG-CSF was applied to nonirradiated CD34(+) cells. In conclusion, different types of rhG-CSFs lead to different effects when rhG-CSF is applied to nonirradiated CD34+ cells, though Filgrastim, Nartograstim, and Lenograstim show equal effects on X-irradiated CD34+ cells.
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PMID:Inductive potential of recombinant human granulocyte colony-stimulating factor to mature neutrophils from x-irradiated human peripheral blood hematopoietic progenitor cells. 1988 Dec 96

This study was aimed to investigate the characteristics of immunophenotypes in the patients with myelodysplastic syndrome (MDS) without an increase of marrow blasts, and to confirm their diagnostic significance. Marrow cells from 222 patients with pancytopenia, dysplastic changes in one or more hematopoietic lineages and blast cells less than 5% were analyzed by multiparametric flow cytometry(FCM). The abnormal immunophenotypes were evaluated in asynchronous antigen expression (CD34 or CD117 in mature granulocytes or mature monocytes, HLA-DR in mature granulocytes), in cross-lineage antigen expression (CD7 or CD56 in granulocytes or monocytes), in aberrant light-scatter (CD45/SSC in mature granulocyte or monocyte) and in abnormal expression of differentiation antigen (CD13/CD16 pattern in granulocytes and HLA-DR under-expression in monocytes). The sensitivity and specificity of abnormal immunophenotypes were determined on diagnosis. Among 222 cases, 127 cases were diagnosed as MDS by traditional diagnostic method and 95 cases were non-MDS (drug-related neutropenia, autoimmune cytopenia and idiopathic thrombocytopenia). In mature granulocyte gate, the sensitivity of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC and abnormal expression of differentiation antigen were 31.5%, 30.7%, 49.6% and 60.6% respectively, and the specificity were 100%, 100%, 88.4% and 52.6% respectively. In monocyte gate, the sensitivity of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC and abnormal expression of differentiation antigen were 2.3%, 11%, 37% and 12.6% respectively. The specificity was 100% in all of them. Among 8 above mentioned items, sensitivity of more than 2 abnormalities was 77.9%, and specificity was 95.8%. The positive predictive value was 96.1%. It is concluded that the abnormal expression of asynchronous, cross-lineage antigen expression, aberrant light-scatter of CD45/SSC have a high specificity and a low sensitivity for diagnosis of MDS. The abnormal expressions of differentiation antigens have a high sensitivity and a low specificity; however, the detection of multiple expression abnormalities possesses the high sensitivity and specificity for diagnosis of MDS.
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PMID:[Diagnostic significance of immunophenotyping of bone marrow cells in myelodysplastic syndrome without an increase of marrow blasts]. 2003 Sep 30


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