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)

Hairy cell leukemia (HCL) is an indolent B-cell neoplasm, strongly expressing CD20. Despite initial very high response rates following cladribine, many patients (pts) ultimately relapse. Having relapsed after prior treatment with cladribine, 24 HCL pts (21 male, 3 female) with a median age of 53.5 years were treated with rituximab at 375 mg/m2 intravenously weekly for 4 weeks. Of the pts, 3 (13%) achieved complete remissions and 3 (13%), partial responses. Thus, 6 (25%) of 24 pts achieved a response following rituximab. At a median follow-up of 14.6 months, 2 responders have relapsed; median time to relapse was not yet reached. The only grade III or IV toxicities demonstrated were culture-negative febrile neutropenia, transient and reversible disseminated intravascular coagulation related to rituximab administration, and a diverticular abscess, each in single patients. Of 18 nonresponders, 9 pts subsequently received other treatments; 5 pts were retreated with cladribine, 3 underwent splenectomy, and 1 received pentostatin. Follow-up data are available on 7 of these 9 patients; all 7 patients achieved improvements in hematologic parameters. Rituximab, administered at this dose and schedule, has only modest single-agent activity in cladribine-failed HCL patients when compared with other agents active in this disease.
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PMID:Phase 2 study of rituximab in the treatment of cladribine-failed patients with hairy cell leukemia. 1266 46

Hairy cell leukemia is an indolent, chronic B-cell lymphoproliferative disorder comprising approximately 2 to 3% of all adult leukemias in the United States. Hairy cells are clonal expansions of mature, activated B-cells. They co-express CD11c, CD19, CD20, CD22, CD25, and CD103. Hairy cells possess clonal immunoglobulin gene rearrangements and express monoclonal surface immunoglobulin of either IgG or multiple heavy-chain isotypes. Treatment of hairy cell leukemia should be considered for symptomatic patients. It is indicated in patients with significant neutropenia, anemia, thrombocytopenia, symptomatic splenomegaly, constitutional symptoms due to hairy cell leukemia, or recurrent serious infections. Many treatments exist, including cladribine, pentostatin, interferon-alpha, splenectomy, rituximab (mabthera), and BL-22 immunotoxin.
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PMID:Hairy cell leukemia: an update. 1279 30

Rituximab, an anti-CD20 monoclonal antibody, is increasingly used in the treatment of B-cell non-Hodgkin's lymphoma. Late-onset neutropenia in relation to rituximab has been recently described. In this report, we present six cases occurring after stem cell transplantation and discuss the potential impact of this complication.
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PMID:Rituximab-related late-onset neutropenia after autologous stem cell transplantation for aggressive non-Hodgkin's lymphoma. 1503 44

We report a patient with B-cell prolymphocytic leukemia (PLL) who was treated successfully with the monoclonal anti-CD20 antibody (rituximab). The patient had recurrent infections due to relative neutropenia, secondary to bone marrow infiltration. After treatment with monoclonal anti-CD20 antibodies (rituximab) 375 mg/m(2) weekly for 4 weeks, complete remission was obtained. It was documented by normalization of peripheral blood counts, disappearance of organomegaly, and by molecular cytogenetics-fluorescent in situ hybridization (FISH) on bone marrow cells. She remains in complete remission 8 months following the discontinuation of treatment. This is the second reported case of successful treatment of B-cell PLL with rituximab.
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PMID:Successful treatment of B-cell prolymphocytic leukemia with monoclonal anti-CD20 antibody. 1506 Jul 51

The purpose of this study was to determine the efficacy and toxicity of combined therapy consisting of rituximab (RIT), an anti-CD20 monoclonal antibody, and cladribine (2-chlorodeoxyadenosine, 2-CdA) (RC regimen) in patients with refractory or relapsed indolent lymphoproliferative disorders. Twenty six CD20 antigen positive patients, 15 with B-cell chronic lymphocytic leukemia (B-CLL) and 11 with low grade non-Hodgin's lymphoma (LG-NHL) were enrolled to the study. Fourteen patients (53.8%) had refractory disease, the other 12 (46.2%) were recurrent after prior chemotherapy. RC regimen consisted of RIT at a dose of 375 mg/m2 in 6 h infusion on day 1 and 2-CdA at a dose of 0.12 mg/kg, in 2 h infusion, given on days 2-6. The RC courses were repeated at 4 week intervals or longer if severe myelosuppression occurred. Seventy eight cycles of RC with median of 3 cycles per patient were administered (range 1-5 cycles). Four patients (15.4%) (95% CI 1.5-29.3%), 1 with B-CLL and 3 with LG-NHL, achieved a complete response (CR). Fourteen patients (53,8%) (95%CI 34.6-72.9%), including 10 with B-CLL and 4 with LG-NHL, had a partial response (PR). Overall response rate (OR) was 69.2% (95%CI 51.4-86.9%) in the whole group, from 63.6% (95% CI 35.2 92.0%) in LG-NHL to 73.3% (95%CI 50.1-95.7%) in B-CLL patients. Twelve of 18 patients with CR/PR are still in remission, with the median follow up 10 (7-28 months). The median failure-free survival (FFS) of responders was 6.5 months. Hypersensitivity to RIT was the major toxicity of RC regimen, and occurred in 9 patients (34.6%), mostly only during the first infusion of RIT. Severe neutropenia (grade III) was seen in 3 patients (11.5%). Anemia and thrombocytopenia associated with RC treatment were observed in 5 (19.2%) and 2 patients (7.7%), respectively. Four episodes (15.4%) of grade III-IV infections were observed. There was no treatment related mortality. During the follow-up six patients (23.1%) died from the disease progression. In conclusion, the combination of RIT and 2-CdA is an effective and well tolerated treatment, even for heavily pre-treated patients, and the results seem to be better than in patients previously treated in our institution with 2-CdA alone. This regimen can be considered as an alternative treatment of CD-20 positive indolent lymphoproliferative disorders.
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PMID:Rituximab followed by cladribine in the treatment of heavily pretreated patients with indolent lymphoid malignancies. 1529 52

The median survival for patients with advanced indolent non-Hodgkin's lymphoma (NHL) has remained at 7 to 8 years since the 1960s. Targeted treatment using radioimmunotherapy (RIT), radiolabeled monoclonal antibodies directed against tumor-specific antigens, is an attractive option for this patient population, combining the advantages of an active biologic therapy with low dose-rate irradiation of an inherently radiosensitive tumor. Two anti-CD20 RIT agents have now been approved for the treatment of refractory NHL: 90Y-ibritumomab tiuxetan (Zevalin; Biogen Idec Inc, San Diego, CA, and Schering AG, Berlin, Germany) is approved in both the United States and Europe, and 131I-tositumomab (Bexxar; Corixa Corp, Seattle, WA) is approved only in the United States. This article discusses the development of 131I-tositumomab. Because 131I-labeled antibody clearance varies significantly among patients, prescription of 131I-tositumomab activity must be based on a calculated total-body dose derived from quantitative whole-body imaging. The maximum tolerated total-body dose has been established at 75 cGy in patients with adequate bone marrow reserves and less than 25% bone marrow involvement by lymphoma (65 cGy in patients with mild thrombocytopenia; 45 cGy in patients who have received stem cell transplantation). In a phase III trial, overall response rate (ORR) and complete response (CR) rate were significantly higher following 131I-tositumomab than following the patient's last qualifying chemotherapy (ORR, 65% v 28%; P <.001; CR, 20% v 3%; P <.001). 131I-tositumomab has also been shown to be effective in patients who are refractory to rituximab (ORR, 70%; CR, 32%) and as first-line therapy in patients with NHL (ORR, 97%; CR, 63%). The major side effects of 131I-tositumomab are hematologic. In the phase III study, 20% of patients experienced grade 4 neutropenia and 22% experienced grade 4 thrombocytopenia. Myelodysplastic syndromes or secondary acute myeloid leukemia have been reported in 8.4% of patients with chemotherapy-refractory disease treated with 131I-tositumomab, but have not been observed to date in patients receiving 131I-tositumomab as first-line therapy. Future progress in NHL management is likely to include RIT as part of a multi-modality approach; trials are planned or currently underway to investigate the combination of RIT with chemotherapy regimens.
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PMID:Development of 131I-tositumomab. 1578 26

Idiopathic thrombocytopenic purpura is an autoimmune disease which involves opsonization of platelets by autoantibodies directed against different surface glycoproteins, leading to their premature destruction by the reticuloendothelial system. Management of patients with refractory ITP is difficult. Recent studies have shown that rituximab, a chimeric anti-CD20 monoclonal antibody, is useful in the treatment of these patients, with overall response rates of about 50%. Most published reports have included a small number patients including case reports. The present study reports the results of a retrospective Danish multicenter study of rituximab in the treatment of adult patients with refractory ITP. Thirty-five patients (median age 52 years, range 17-82 years, 17 males) were included. One patient had immune thrombocytopenia and neutropenia. All patients had received prednisolone (Pred). Next to Pred, 25 patients had been treated with high-dose IgG, and in 16 patients a splenectomy had been performed. Sixteen patients had been treated with azathioprine. Other treatments included, e.g., cyclosporine, danazol, cyclophosphamide, vincristine, interferon, and dexamethasone. The patients were treated with a dose regimen of 375 mg/m2 i.v. approximately once weekly for 4 consecutive weeks. Six patients received a fixed dose of 500 mg disregarding their weight supplemented by 100 mg of methylprednisone i.v. or 50-100 mg of Pred given as premedication together with an antihistamine just before infusion of rituximab. The large majority of patients also received Pred and, in some cases, other concomitant immunosuppressive treatment during part of their rituximab treatment. A complete response (CR) was defined as a rise in the platelet count > 100 x 10(9)/L, a partial response (PR) as a rise in the platelet count > 50 x 10(9)/L, and a minor response (MR) as a rise in the platelet count < 50 x 10(9)/L. No response (NR) was defined as no increase in the platelet count. Because 4 patients were treated twice, a total of 39 outcomes of rituximab treatment were evaluated. Rituximab proved to be effective in 17 of 39 treatments [overall response 44% with 7 CR (18%) (1 patient showed a CR twice), 6 PR (15%), and 4 MR (10%)]. In 9/13 cases of CR or PR, the response (platelet level > 50 x 10(9)/L) was prompt, 1-2 weeks after the first infusion. The remaining patients responded 3-8 weeks later. Patients with CR and PR have been in remission for a median of 47 weeks. In general the side effects were few. In 2 cases, the treatment was stopped because of side effects either during or after the first infusion. Two fatal outcomes were recorded. A 71-year-old female with severe lung disease died 6 days after the first infusion of respiratory failure. The other patient, a 73-year-old man also with severe chronic obstructive lung disease, died of pneumonia approximately 13 weeks following the last rituximab treatment. It is concluded that rituximab may be a useful alternative therapy in patients with severe and symptomatic ITP refractory to conventional treatment.
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PMID:Rituximab chimeric anti-CD20 monoclonal antibody treatment for adult refractory idiopathic thrombocytopenic purpura. 1579 20

This report is the first to describe the successful treatment of a 14-year-old boy with aggressive recurrent, CD20-positive, B-cell large cell non-Hodgkin's lymphoma. The patient responded to three 4-week courses of rituximab (MabThera) given every 6 months and six cycles of CHOP given every 3 weeks in addition to a modified BFM 86 protocol. Transient neutropenia and lymphopenia occurred but with no clinical significance. The boy has been disease-free for the last 48 months (after 64 months of follow-up); his organ functions are normal. Rituximab and CHOP in addition to chemotherapy may be an alternative treatment for aggressive recurrent, pediatric CD20-positive B-cell large cell non-Hodgkin's lymphoma if highly intensive chemotherapy and stem cell transplantation are not available.
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PMID:Rituximab combined with CHOP for successful treatment of aggressive recurrent, pediatric B-cell large cell non-Hodgkin's lymphoma. 1583 96

From 1999 to 2002, 20 patients with aggressive non-Hodgkin lymphoma, among 28 who failed autologous peripheral blood progenitor cell transplantation, were rescued with cyclophosphamide, hydroxydaunomycin, Oncovin (vincristine), and prednisone (CHOP)/rituximab (RTX) and granulocyte-macrophage colony-stimulating factor (GM-CSF). RTX was administered twice during each course of chemotherapy, before CHOP and after GM-CSF. This cytokine was given to increase the antibody-dependent cell-mediated cytotoxicity and to reduce the leukopenia on the basis of our preliminary data, which suggested that this cytokine can upregulate CD20 expression. The relevant (World Health Organization grade 3-4) toxicity mainly consisted of myelosuppression (neutropenia in 60% of patients). Fifteen patients achieved complete remission (CR) or had a partial response, with an overall response rate of 75% (60% CR and 15% partial response). Six of the 12 patients who achieved CR relapsed: 2 died of progressive disease, 1 died of infectious complications after allogeneic transplantation, and 3 are alive in second CR. Eight patients showed progressive disease: 5 died of progressive disease, 1 of secondary acute leukemia, and 1 of infectious complications after allogeneic transplantation, whereas 1 is alive in second CR. At last follow-up, 10 patients are alive, 6 of whom are in complete continuous remission, with a median follow-up of 31 months (range, 3-51 months). The projected 4-year progression-free survival is 31.4%, and the 4-year overall survival is 50%. This new association (RTX, CHOP, and GM-CSF) was feasible in approximately 70% of patients; the overall toxicity was manageable. The good response rate and the promising outcome observed in this subset of patients could be explained by the possible increased synergy between chemotherapy, RTX, and GM-CSF, which should be explored in further studies.
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PMID:A new schedule of CHOP/rituximab plus granulocyte-macrophage colony-stimulating factor is an effective rescue for patients with aggressive lymphoma failing autologous stem cell transplantation. 1604 13

Rituximab, a human/mouse chimeric anti-CD20 antibody, has become part of standard therapy for patients with CD20-expressing B-cell lymphoma, and is currently under investigation for other indications including autoimmune diseases, in particular rheumatoid arthritis (RA). Its characteristic tolerability profile was established soon after clinical testing began and compares favourably with chemotherapy. The majority of patients experience mild to moderate infusion-related reactions (IRRs) during the first administration of rituximab, but the incidence decreases markedly with subsequent infusions. Current data suggest that the type of adverse events in patients with RA are similar to those in lymphoma, but that adverse events related to the rituximab infusions are less severe and less frequent. Rituximab induces a rapid depletion of normal CD20-expressing B-cells in the peripheral blood, and levels remain low or undetectable for 2-6 months before returning to pretreatment levels, generally within 12 months. Serum immunoglobulin levels remain largely stable, although a reduction in IgM has been described. T-cells are unaffected by rituximab and consequently opportunistic infections rarely occur in association with rituximab therapy. When used in combination with a variety of chemotherapeutic regimens, rituximab does not add to the toxicity of chemotherapy, with the exception of a higher rate of neutropenia. However, this does not translate into a higher infection rate. Over 540,000 patients worldwide have now received rituximab and serious adverse reactions have occurred in a small minority of patients, but for the great majority of patients, rituximab is safe and well tolerated.
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PMID:Tolerability and safety of rituximab (MabThera). 1605 60


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