Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The aim of our study was to determine the effectiveness and toxicity of combined chemotherapy consisting of cladribine (2-chloro-deoxyadenosine, 2-CdA), mitoxantrone and cyclophosphamide (CMC regimen) in the treatment of refractory or relapsed indolent lymphoproliferative disorders. The treatment course consisted of 2-CdA given at a dose of 0.12 mg/kg/24 h in a 2-h intravenous infusion for 5 (CMC5) or 3 (CMC3) consecutive days, mitoxantrone 10 mg/m2 on day 1 and cyclophosphamide 650 mg/m2/iv on day 1. Thirty-three patients (19 with B-CLL and 14 with LG-NHL) entered the study and all of them were eligible. Twenty patients (60.6%) were recurrent after prior therapy and 13 (39.4%) had refractory disease. All patients received 5 or more cycles of chemotherapy before CMC treatment. Twenty-one patients were treated with CMC5 regimen and 12 with CMC3 regimen. The overall response rate, including CR and PR, was 48.6% (95% CI 32-66). There were no differences in the frequency of responses between the CMC3 and CMC5 treated groups (p>0.05). One patient with B-CLL and three patients with lymphocytic lymphoma achieved CR (12.1%). Among 12 patients (36.4%) who achieved PR there were 6 CLL patients, and 6 lymphoma patients. The major toxicity was myelosuppression. Severe neutropenia was seen in 11/33 (33.3%) patients, more frequently in patients who received CMC5 than in the patients who received CMC3, both in the CLL (50.0% and 28.5%, respectively) and in the LG-NHL group (22.2% and 0%, respectively). The rate of thrombocytopenia was similar in both groups. Infections and fever of unknown origin complicated the treatment with CMC5 more often than with CMC3: five episodes were seen in 3 patients treated with CMC3 when compared to 15 episodes in 12 patients treated with CMC5. In conclusion, the CMC programme is an active combined regimen in heavily pre-treated CLL and LG-NHL patients. However, its toxicity is significant and we suggest a shortening of 2-CdA infusion from 5 to 3 d in further studies. Whether a combination of 2-CdA with cyclophosphamide and mitoxantrone would result in improved outcome as compared to 2-CdA alone, is being investigated in a prospective, randomised trial.
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PMID:Cladribine in combination with mitoxantrone and cyclophosphamide(CMC) in the treatment of heavily pre-treated patients with advanced indolent lymphoid malignancies. 1135 Apr 87

We treated 33 patients with a variant of the standard 3 weekly CHOP regime, replacing doxorubicin with liposomal daunorubicin (DaunoXome, NeXstar Pharmaceuticals) 120 mg/m2 (COP-X). Eighteen subjects had relapsed/refractory aggressive NHL and 15 had indolent NHL/CLL. Median number of courses received was 4 (1-8). Thirty-two patients were evaluable for efficacy and 26 (81%) responded. 88% of patients with aggressive NHL responded; three (18%) patients achieved complete remission (CR), 12 (70%) achieved partial remission (PR), 1 (6%) patient had stable disease (SD) and 1 (6%) patient progressed through treatment. Median duration of response for patients with aggressive NHL was 3 months. The response rate in indolent NHL/CLL was 73%. Four (27%) patients achieved CR, 7 (46%) PR and 4 (27%) SD. At two years post treatment, 55% of the patients with indolent NHL/CLL remain progression-free, although 4 patients have proceeded to consolidation therapy. Twenty-seven out of 28 (96%) patients developed neutropenia of short duration following one or more of their treatments. Twenty-three patients developed an infection at some stage during therapy (all associated with neutropenia) and required hospitalisation. There were two toxic deaths (infection) both of which occurred in patients who were neutropenic before starting COP-X. Platelet toxicity was mild in patients with normal platelet counts at the commencement of therapy. Alopecia and mucositis were mild. No clinical evidence of myocardial failure was observed. We conclude that the substitution of DaunoXome for doxorubicin in the CHOP regimen to form COP-X provides excellent efficacy against non-Hodgkin's lymphoma. Response durations were short but comparable to those reported with other regimens. COP-X was well tolerated with some suggestion of reduced non-haematological toxicity. The regimen should be considered as an alternative to CHOP with potentially less non-haematological toxicity, particularly cardiac; further studies are required to evaluate the regimen in this context.
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PMID:Liposomal daunorubicin (DaunoXome) in combination with cyclophosphamide, vincristine and prednisolone (COP-X) as salvage therapy in poor-prognosis non-Hodgkins lymphoma. 1169 26

This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL). Injections were administered subcutaneously 3 times per week, from week 2 to 3 onward. An overall response rate (OR) of 87% (95% CI, 76%-98%; complete remission [CR], 19%; partial remission [PR], 68%) was achieved in 38 evaluable patients (81% of intent-to-treat population). CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes. The median time to treatment failure has not yet been reached (18+ months; range, 8-44+ months). Transient injection site skin reactions were seen in 90% of patients. Rigor, rash, nausea, dyspnea, and hypotension were rare or absent. Transient grade IV neutropenia developed in 21% of the patients. Infections were rare, but 10% patients developed cytomegalovirus (CMV) reactivation. These patients rapidly responded to intravenous ganciclovir. One patient, allergic to cotrimoxazole prophylaxis, developed Pneumocystis carinii pneumonia. Alemtuzumab is highly effective as first-line treatment in patients with B-CLL. Prolonged treatment is important for maximal bone marrow response. Subcutaneous administration induced very few "first-dose" flulike symptoms and may reduce health care costs in comparison with the intravenous infusions.
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PMID:Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). 1213 Apr 84

The aim of the study was to evaluate the activity and toxicity of cladribine (2-CdA) in combination with cyclophosphamide (CY), the CC schedule, in patients with previously untreated B-cell chronic lymphocytic leukemia (B-CLL). From November 1998 to May 2002 82 patients with advanced or progressive B-CLL received treatment with 2-CdA at a dose of 0.12 mg/kg for three consecutive days and CY at a dose of 650 mg/m(2) on day 1. The cycles were repeated at four week intervals or longer if severe myelosuppression occurred. Guidelines for the evaluation of response and toxicity were those developed by the National Cancer Institute sponsored Working Group. Minimal residual disease (MRD) was detected by immunophenotyping only in patients with CR by standard criteria. In the analysed group an overall response (OR) rate (CR+PR) of 87.8% (95% CI 80.7-94.9%) was achieved, including complete response (CR) in 29.3% patients (95% CI 19.4-39.1%). Twenty-two of 24 patients with CR and 39 of 48 patients with PR are still in remission. Median duration of follow-up in these patients is 11.8 months (range 3-25.4). MRD was only detected in six out of 24 (25%) patients with CR. Grade III/IV thrombocytopenia was seen in four patients (4.9%) and neutropenia in 10 (12.2%). Severe infections were noted in 21 (25.6%) patients. Thirteen patients died, including seven with treatment related toxicity, one because of CLL progression and five because of reasons not related to CLL. In conclusion, the CC schedule is a highly active regimen in previously untreated B-CLL, with acceptable toxicity. The efficacy of the regimen seems to be higher than observed earlier after treatment with 2-CdA alone. A randomized clinical trial is in progress in our institutions.
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PMID:Cladribine combined with cyclophosphamide is highly effective in the treatment of chronic lymphocytic leukemia. 1239 42

Combined treatment of fludarabine (FLU) with cyclophosphamide (CY) may increase the complete remission (CR) rate, decreased minimal residual disease (MRD) and, possibly, prolong survival in B-chronic lymphocytic leukemia patient's (B-CLL). The aim of study was to evaluate the activity and toxicity of FLU in combination with CY, the FLU-CY schedule, in patients with previously untreated B-CLL. From May 1999 to December 2002, 57 patients with advanced or progressive B-CLL received treatment with FLU at a dose of 30 mg/m2 for three consecutive days and CY at a dose of 300 mg/m2 for three days. The cycles were repeated at four week intervals or longer if severe myelosupression occurred. Guidelines for the evalution of response and toxicity were those developed by the National Cancer Institute Sponsored Working Group. Minimal residual disease (MRD) was detected by immunophenotyping only in patients with CR by standard criteria. In the analyzed group an overall response (OR) rate (CR+PR) of 89.5% (95% CI 80.6-94.7%) was achieved, including complete response in 29.8%. At the time of analysis 15 of 17 patients with CR are still in remission. Median duration of follow up in these is 12 (range 4-29.2) months. MRD was detected only in five out of 17(29.4%) patients with CR. Grade III/IV thrombocytopenia was seen in 3 (5.2%) patients and grade III/IV neutropenia in 6 (10.5%). Severe infections were noted in 14 (24%) patients. Two (3.5%) patients died, one due to sepsis, one as a result of disease progression. The FLU-CY regimen is highly effective combination in previously untreated CLL patients with acceptable toxicity. The efficacy of the regimen seems to be higher than that observed earlier after treatment with FLU alone.
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PMID:Fludarabine combined with cyclophosphamid is highly effective in the treatment of chronic lymphocytic leukemia. 1468 65

A regimen combining fludarabine, cyclophosphamide and mitoxantrone (FCM) was used to treat 29 patients with relapsed or refractory chronic lymphocytic leukemia (CLL, N = 24) and low-grade non-Hodgkin's lymphoma (NHL, N = 5) based on evidence suggesting synergism between the 3 drugs. Patients were treated with mitoxantrone 5mg/m2 i.v. day 1 only, fludarabine 25 mg/m2 i.v. for 3 days or 24 mg/m2 orally for 5 days, cyclophosphamide 250 mg/m2 i.v. for 3 days or 150 mg/m2 orally for 5 days inclusive. Eighteen patients had previously received fludarabine and most were heavily pretreated with 40% having >2 prior treatments. A median number of 4 FCM courses (range of 1-9) were given. The response rate was 78.5%: 32% complete remission, 25% nodular partial remission, 21.5%, partial remission. Median duration of response was 19 months and median survival was 42 months. Sixteen patients (57%) developed neutropenia to < 0.5 x 10(9)/l and 12 (43%) infectious complications. Four patients developed large cell lymphoma (Richter's syndrome) and 2 acute myeloid leukemia. FCM is a useful combination for relapsed or refractory CLL and low grade NHL with high response rates and long duration of response. The role of FCM as first line therapy deserves study as well as its combination with the monoclonal antibody Rituximab.
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PMID:Fludarabine, cyclophosphamide and mitoxantrone in relapsed or refractory chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma. 1529 53

T-Large Granular Lymphocyte (T-LGL) leukaemia is a rare clonal disease characterized by neutropenia and/or anaemia. Because of its strong association with rheumatoid arthritis (RA), T-LGL leukaemia is an important differential diagnosis to Felty's syndrome. This differentiation might be especially difficult since, in severe RA with extraarticular manifestations, there is often an expanded memory effector T-cell population which can hardly be separated from T-LGL leukaemia cells by means of immunophenotyping. The main criterion for T-LGL leukaemia is the detection of a clonal T-cell-receptor rearrangement by PCR. First-line therapy consists of weekly low-dose methotrexate. Alternatively, other immunosuppressives or cytotoxic agents can be useful. There are very limited data from therapy studies. The German CLL study group has initiated a protocol using parenteral low-dose methotrexate as first-line therapy and fludarabine as second-line medication.
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PMID:[T-large granular lymphocyte leukaemia. An important differential diagnosis to Felty's syndrome]. 1645 Jan 50

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

Traditionally, classification of leukaemia in dogs has relied on morphological examination and cytochemical staining patterns, but aberrant cellular morphology and stain uptake often curtails accurate categorization, and historical data based on this classification may be unreliable. Immunophenotyping is now the gold standard for classification of leukaemias. The purpose of this prospective study was to assess the clinical pathological and epidemiological features of a population of dogs with morphologically and immunologically confirmed leukaemia and to compare them within categories: acute and chronic lymphoid leukaemia (ALL and CLL), and acute and chronic myeloid leukaemia (AML and CML). There were 64 cases of morphologically and immunologically confirmed leukaemia: 25 cases of ALL, 17 cases of CLL and 22 cases of AML. Prevalence of B and T immunophenotypes in ALL and CLL was not statistically different. Dogs with AML were significantly younger than those with ALL at presentation (P = 0.04). Golden Retriever dogs in the study population were overrepresented in comparison with a control population of dogs (6/25 ALL cases, 8/64 leukaemia cases). No sex was overrepresented. Dogs with ALL had significantly more severe neutropenia (P = 0.001) and thrombocytopenia (P = 0.002) than those with CLL and had significantly more cytopenias. The severity and numbers of cytopenias seen in ALL and AML were not significantly different. Twenty-one of the leukaemia cases showed one cytopenia, fourteen had two cytopenias and twenty-one cases had pancytopenia. Anaemia was the most common cytopenia seen in isolation (17/21). No dogs had neutropenia without anaemia and/or thrombocytopenia. Total white blood cell counts were not different between the groups. The atypical cell counts within the peripheral blood were significantly higher in ALL than AML; both in isolation and as a percentage of the total white blood cell count (P = 0.03). This study strengthens the hypothesis that acute leukaemias give rise to more profound cytopenias, affecting more cell lines, than chronic leukaemias.
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PMID:Clinical pathological and epidemiological assessment of morphologically and immunologically confirmed canine leukaemia. 1969 47

Certain malignant B cells rely on B-cell receptor (BCR)-mediated survival signals. Spleen tyrosine kinase (Syk) initiates and amplifies the BCR signal. In in vivo analyses of B-cell lymphoma cell lines and primary tumors, Syk inhibition induces apoptosis. These data prompted a phase 1/2 clinical trial of fostamatinib disodium, the first clinically available oral Syk inhibitor, in patients with recurrent B-cell non-Hodgkin lymphoma (B-NHL). Dose-limiting toxicity in the phase 1 portion was neutropenia, diarrhea, and thrombocytopenia, and 200 mg twice daily was chosen for phase 2 testing. Sixty-eight patients with recurrent B-NHL were then enrolled in 3 cohorts: (1) diffuse large B-cell lymphoma (DLBCL), (2) follicular lymphoma (FL), and (3) other NHL, including mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), mucosa-associated lymphoid tissue lymphoma, lymphoplasmacytic lymphomas, and small lymphocytic leukemia/chronic lymphocytic leukemia (SLL/CLL). Common toxicities included diarrhea, fatigue, cytopenias, hypertension, and nausea. Objective response rates were 22% (5 of 23) for DLBCL, 10% (2 of 21) for FL, 55% (6 of 11) for SLL/CLL, and 11% (1/9) for MCL. Median progression-free survival was 4.2 months. Disrupting BCR-induced signaling by inhibiting Syk represents a novel and active therapeutic approach for NHL and SLL/CLL. This trial was registered at www.clinicaltrials.gov as #NCT00446095.
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PMID:Inhibition of Syk with fostamatinib disodium has significant clinical activity in non-Hodgkin lymphoma and chronic lymphocytic leukemia. 2036 Apr 72


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