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)

Although the CHOP regimen remains a standard first line chemotherapy for diffuse large cell lymphoma (DLCL) in adults, a majority of these patients will still experience disease progression after the completion of this treatment. The LMB protocol is an intensive chemotherapy regimen which yields high survival rates in Burkitt's lymphoma (BL) and diffuse large cell lymphoma (DLCL) in children, as well as in primary cerebral DLCL (PCL) of adults. Here, we report the long term results of this regimen in a prospective series of 22 adult patients with DLCL excluding PCL. Fifteen male and 7 female patients with a median age of 30 years (range: 20-55) were treated prospectively between 1988 and 1993. 16 (72%) patients had an age adjusted International Pronostic Index (IPI) > or = 1. The median duration of the treatment was 15 weeks (range 13-19). Nineteen of the 22 patients (87%) experienced an objective response (14 complete, and 5 partial responses) at the end of the protocol. The predominant toxicity was myelosuppression: 89% of the COPADEM courses were followed by grade IV neutropenia and 5% with grade IV infection. One patient died (4%) of treatment related toxicity. With a median follow-up of 94 months and a minimum follow-up of 65 months, 8-year overall and progression-free survival are 73% and 67% respectively. The 8 year overall survival were 100%, 78% and 42% in patients with an IPI 0, 1, and 2-3 respectively. This short intensive regimen yields promising long term survival rates in this monocentric prospective study and may deserve to be tested in a larger multicentric prospective study comparing it to the CHOP regimen.
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PMID:A prospective study of the LMB regimen for diffuse large cell non Hodgkin's lymphoma in adults. 1078 97

Advanced age is an adverse prognostic factor in patients with DLCL. CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) has frequent dose-limiting toxicities, including myelosuppression. We retrospectively reviewed 50 consecutive patients > 60 years of age (median age 72) with B-cell DLCL who received CHOP with G-CSF. Patients received CHOP (median 6 cycles) at three-week intervals. G-CSF was given following all cycles of chemotherapy ("prophylactic G-CSF") in 28 of 50 patients, and following an episode of febrile neutropenia and thereafter in 19 patients, according to ASCO guidelines. Dose intensity, treatment delays, episodes of febrile neutropenia, complete response (CR) rate, disease-free survival, time-to-treatment failure, and overall survival were all analyzed according to the age-adjusted International Prognostic Index (aaIPI). The actual dose intensity for cyclophosphamide was 225.9 mg/m2/week and 0.90, respectively and for doxorubicin was 14.9 mg/m2/week (90% of ideal CHOP dosing for both drugs). Median followup was 4 years for the patients still living. Treatment delays and episodes of febrile neutropenia were less frequent among patients receiving G-CSF with all cycles of CHOP. The CR rates were 100%, 81%, 85%, and 36% for the low, low-intermediate, high-intermediate, and high aalPI risk groups, respectively. The 5-year actuarial relapse-free and overall survival for our patients were comparable to that of the cohort < or = 60 years of age and superior to the > 60 years of age cohort used to establish the aaIPI. With optimization of CHOP dosing, advanced age may not be an adverse prognostic factor for patients with DLCL. The routine use of G-CSF in elderly patients with DLCL should be further investigated.
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PMID:Granulocyte-colony stimulating factor (G-CSF) may improve disease outcome in elderly patients with diffuse large cell lymphoma (DLCL) treated with CHOP chemotherapy. 1097 85

This prospective study was undertaken to evaluate the efficacy and toxicity of combination chemotherapy with alternating cycles of vincristine, doxorubicin and dexamethasone (VAD) and cyclophophamide, doxorubicin, etoposide and prednisone (CHEP) in patients over 60 years old with previously untreated and advanced non-Hodgkin's lymphoma (NHL) of intermediate- and high-grade malignancy. Eighty one consecutive, patients with NHL referred from April 1992 to October 1997 to GOELAMS centers were enrolled in this study and their outcome updated to June 1, 1999. Of 81 enrolled patients, 77 were eligible and assessable for response. The median age was 70 years (61 to 78), 85.7% were stage III or IV, 39% were of performance status > or = 2, 27.3% > or = 2 involved extra-nodal sites and 57.3% had higher LDH levels than normal. The immunophenotype was B in 87% and T in 13%. Fifty-one (66.2%) patients received the scheduled eight cycles of therapy and treatment was withdrawn in only 6 patients (7.8%) because of toxicity. Neutropenia grade 3-4 occurred in 11.1% after VAD courses vs 40.6% after CHEP courses. The mean cumulative dose of doxorubicin was 269 mg/m2 and the relative dose intensity was 84%. The overall response and complete response rates were 66.2% and 51.9% respectively, and after a median follow-up of 52 months the 3 year overall survival (OS) and event-free survival rates (EFS) were 43.5% and 33.0% respectively. In multivariate analysis, OS and EFS were statistically influenced by IPI (p = 3 x 10(-3); p < 1 x 10(-4)) and phenotype (p = 2 x 10(-3); p < 1 x 10(-4)). Our findings support the alternation of 4 courses of VAD and CHEP as it is well tolerated in patients over 60 years old with advanced intermediate- or high-grade NHL and provides response and survival rates comparable to 6 courses of CHOP.
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PMID:Continuous infusion of vincristine-doxorubicin with bolus of dexamethasone(VAD) alternated with CHEP in the treatment of patients over 60 years old with aggressive non-Hodgkin's lymphoma. 1142 26

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

Records from 653 patients treated between 1991 and 1998 in the Oncology Practice Patterns Study (OPPS) were analyzed to determine contemporary chemotherapy delivery patterns in patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Of the 653 patient records reviewed, 90 (14%) omitted an anthracycline or mitoxantrone (Novantrone) from primary therapy. Among patients receiving CHOP (cyclophosphamide [Cytoxan, Neosar], doxorubicin HCl, vincristine [Oncovin], prednisone) or CNOP (cyclophosphamide, mitoxantrone, vincristine, prednisone), 134 (27%) of 492 received an average relative dose intensity of less than 80% of the literature-referenced dose, due either to an inadequate planned or delivered dose. Of 181 advanced-stage patients with responsive disease, 28 (15%) failed to receive at least six treatment cycles. Overall, 283 (43%) of 653 patients potentially received suboptimal chemotherapy due either to choice of regimen or chemotherapy delivered. Patient age > or = 65 years and cardiac comorbidity appeared to have the greatest influence on a physician's decision regarding chemotherapy administration. Among the 492 patients who received CHOP or CNOP, 235 (48%) experienced a delay or reduction in chemotherapy dose (usually neutropenia-related), 100 (20%) developed mucositis, and 116 (24%) were hospitalized for febrile neutropenia. Growth factor was administered to 261 patients (53%), and its primary prophylactic use was associated with a significant reduction in the incidence of hospitalizations for febrile neutropenia in all patient subgroups receiving appropriate chemotherapeutic dose intensity (P = .02). This assessment of chemotherapy delivery to patients with intermediate-grade NHL showed significant variation from current standards. Further analysis of factors influencing chemotherapy delivery might improve therapeutic outcomes.
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PMID:Patterns of chemotherapy administration in patients with intermediate-grade non-Hodgkin's lymphoma. 1170 59

The purpose of this historical case series study was to evaluate the association of age on delivered dose intensity of initial CHOP (cyclophosphamide/doxorubicin/ vincristine/prednisone) chemotherapy and the occurrence of hospitalizations for febrile neutropenia for patients with intermediate-grade non-Hodgkin's lymphoma (NHL). Findings are reported for 12 managed community and academic practices. Medical records of 930 NHL patients not enrolled on clinical trial protocols were reviewed. We reported on 577 of the study patients (62%) who received initial CHOP chemotherapy. Median age of the patients was 65.1 years. Older patients (age > or = 65 years) had more hospitalizations for febrile neutropenia (28% vs. 16%; P < 0.05) than younger patients (age, 18-64 years). In patients with advanced-stage NHL (stage III/IV), older patients received fewer cycles of CHOP (< 6 cycles, 35% vs. 22%; P < 0.05) than younger patients. Older patients were planned for lower average relative dose intensity (ARDI < or = 80%; P < 0.05) and had more heart disease and comorbid conditions (P < 0.05) than younger patients. Multiple logistic regression models showed that older patients were more likely to receive a lower dose intensity (ARDI < or = 80%; odds ratio = 2.46, 95% confidence interval [CI]: 1.62-3.72) during their first 3 cycles of therapy and to experience more hospitalizations for febrile neutropenia (odds ratio = 2.17, 95% CI: 1.43-3.30). We found the dose intensity of delivered CHOP chemotherapy for elderly patients to be less than standard CHOP therapy and the risk of hospitalizations for febrile neutropenia to be greater than in younger patients. Prospective clinical trials examining supportive care measures, such as colony-stimulating factor, for elderly NHL patients are recommended.
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PMID:The impact of age on delivered dose intensity and hospitalizations for febrile neutropenia in patients with intermediate-grade non-Hodgkin's lymphoma receiving initial CHOP chemotherapy: a risk factor analysis. 1170 70

A late phase II clinical trial of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, was conducted at 14 institutions nationwide, in patients with non-Hodgkin's lymphoma. In this multi-center collaborative study, doxorubicin hydrochloride was replaced by amrubicin hydrochloride in CHOP therapy, a standard regimen for non-Hodgkin's lymphoma consisting of cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisolone. A total of 39 patients were enrolled in this study between January 1996 and March 1998. Among them, 37 patients were eligible for this study. The study drugs were administered to patients with non-Hodgkin's lymphoma according to the following schedule: amrubicin hydrochloride (100 mg/m2, body surface area), cyclophosphamide (750 mg/m2) and vincristine sulfate (1.4 mg/m2, a maximal dose of 2.0 mg/body) were administered intravenously on day one, while prednisolone (60 mg/m2/day) was administered orally on days 1 to 5. This cycle of treatment was repeated every three weeks in principle. The efficacy and safety were assessed for 37 eligible patients. The combined rate for CR + CRu was 70.3% (26/37) and the overall response rate (CR + CRu + PR) was 86.5% (32/37). demonstrating that amrubicin hydrochloride was very effective in the treatment of non-Hodgkin's lymphoma. The most frequent adverse reactions that occurred during the study were myelosuppressions: leukopenia and neutropenia, 100% (37/37); and decreases in hemoglobin levels, 81.1% (30/37). Thrombocytopenia, elevations of serum GOT and GPT levels, anorexia, nausea/vomitting, fever, stomatitis and alopecia were also observed. Although leukopenia and neutropenia of grade 3 or higher were noted in 89.2% (33/37) and 94.6% (35/37), respectively, they were controllable by administrations of G-CSF or solely by follow-up observations. One patient developed intestinal paralysis (grade 4) and another developed hematemesis. In conclusion, these results indicate that amrubicin hydrochloride is an effective agent as a component of combination chemotherapy for non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of amrubicin hydrochloride, a novel synthetic anthracycline derivative anticancer agent, for malignant lymphoma]. 1172 79

We describe a case of T-cell large granular lymphocyte (LGL) leukaemia that transformed into a large-cell T-cell lymphoma 11 years from diagnosis. A 29-year-old asymptomatic female presented in 1989 with lymphocytosis, neutropenia and mild bone marrow infiltration. The circulating cells were LGL with a CD2+, CD3+, CD8+, CD4-, CD16+, CD56+, CD57- phenotype. In August 2000, she developed fever, a large submandibular mass and hepatosplenomegaly. Biochemistry showed abnormal liver function tests and raised lactate dehydrogenase (LDH) levels. A serological screen for Epstein-Barr virus, cytomegalovirus, human T-lymphotropic virus-I, human herpes virus (HHV)-6 and HHV-7 was negative. Histology of the mass was consistent with the diagnosis of peripheral T-cell lymphoma composed of large cells, and immunohistochemistry showed that the lymphoma cells had a phenotype identical to the mature LGL. Molecular analysis with the polymerase chain reaction (PCR) demonstrated rearrangement of the T-cell receptor (TCR) gamma-chain gene with a band of identical size in both bone marrow mature LGL and lymph node cells. The patient was treated with CHOP (cyclophosphamide, vincristine, doxorubicin and prednisolone), resulting in the disappearance of the mass and improvement of the hepatosplenomegaly, LDH and liver abnormalities. She underwent splenectomy, and spleen histology showed involvement by T-cell LGL leukaemia with no evidence of transformation. This case illustrates that transformation or Richter syndrome may occur in a minority of patients with T-cell LGL leukaemia, a disease that has a benign clinical course in most cases. This is the first case documented by molecular methods of the transformation of the pre-existing clone.
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PMID:Transformation of T-cell large granular lymphocyte leukaemia into a high-grade large T-cell lymphoma. 1184 12

Myelosuppression is a common side effect in elderly patients undergoing chemotherapy. Neutropenia and anemia cause considerable morbidity, may increase mortality, and can result in a worse outcome of treatment in elderly patients compared to younger patients with comparable type and stage of disease. The availability and proven efficacy of hematopoietic growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte-macrophage colony-stimulating factor (GM-CSF) and erythropoietin (EPO) have had a considerable impact on supportive care in cancer patients: Several randomized trials have demonstrated a reduction of neutropenia and the frequency of severe infections in elderly patients treated with G-CSF following myelotoxic chemotherapy compared with patients without growth factor support. Both for G-CSF and for recombinant human erythropoietin (rHu-EPO) several studies have demonstrated the safety and effectiveness of these molecules in elderly patients with regard to increasing hemoglobin concentrations, improving quality of life (rHu-EPO), and neutrophil recovery. Although a positive effect of the use of growth factors on overall survival in elderly cancer patients is not yet proven, a reduction of chemotherapy-induced side effects could clearly be shown. The National Comprehensive Cancer Network (NCCN) of cancer centers has recommended that all patients aged 70 years and older treated with CHOP or cytotoxic chemotherapy of comparable intensity should receive prophylactic G-CSF administration, and that the hemoglobin concentration be maintained at >or=12 g/dl in elderly patients undergoing chemotherapy.
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PMID:Use of hematopoietic growth factors in elderly patients receiving cytotoxic chemotherapy. 1189 81

A 65-year old man, a known case of non-Hodgkin's lymphoma of base of the tongue and epiglottis presented with complaints of pneumaturia and faecaluria. He had received the first cycle of cytotoxic therapy (CHOP-regimen). At the end of the cycle he developed febrile neutropenia (circulating granulocyte count <1500/mm3). Cystogram showed air in the bladder area and a fistulous communication to a cavity behind the bladder. CT-scan showed air in the bladder, a fistulous communication between the sigmoid colon and bladder along with an intervening small abscess cavity. On exploration a fistulous communication between the sigmoid and bladder along with an intervening small abscess cavity was found. Resection of involved portion of sigmoid and end to end anastomosis along with a diverting colostomy was done. The bladder was closed in two layers with an omental interposition between it and the sigmoid along with a suprapubic cystostomy. The histopathology demonstrated only inflammatory response without any evidence of malignancy or diverticular disease.
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PMID:Colovesical fistula an unusual complication of cytotoxic therapy in a case of non-Hodgkin's lymphoma. 1209 59


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