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)

Patients with recurrent lymphoma of any grade were treated with mitoxantrone (12 mg/m2 given intravenously (IV) over 15-30 minutes on day 1) followed by fludarabine at a dose of (25 mg/m 2 given IV over 30 minutes on days 1-3) every 28 days fludarabine at a dose of (25 mg/m2 given IV over 30 minutes on days 1-3) every 28 days. All patients had failed one prior chemotherapy regimen that contained either doxorubicin or mitoxantrone, total dose not exceeding 350 mg/m2 doxorubicin or 80 mg/m2 mitoxantrone. mitoxantrone. Thirty one patients (22 with intermediate- or high-grade and 9 with low-grade NHL) were enrolled. Median age was 63 years (range: 21 to 87). The objective response rate for patients with intermediate/high-grade NHL was 55% (27% with CR) and 89% (56% with CR) for patients with low-grade NHL. Median time to disease progression was 5.1 months for patients with intermediate/high-grade NHL and 10.8 months for patients with low-grade NHL. Median time to death for patients with intermediate/high-grade disease was 11.4 months. Median time to death for patients with low-grade NHL was not calculable as only one death (due to respiratory failure) occurred in this group 6.5 months after study start. The regimen was well tolerated. Grade 3/4 neutropenia was reported in 80% (24 of 30) of patients and Grade 3/4 thrombocytopenia in 19% (6 of 31) of patients. Nine hospitalizations for adverse events (primarily fever and neutropenia) occurred among eight patients, all with intermediate/high-grade NHL, during a total of 118 cycles of therapy. Further studies of this combination regimen in patients with intermediate/high-grade NHL and studies combined with monoclonal antibodies in low-grade NHL are warranted.
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PMID:Mitoxantrone and fludarabine in the treatment of patients with non-Hodgkin's lymphoma failing primary therapy with a doxorubicinor mitoxantrone-containing regimen. 1142 53

Hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures to reduce infectious complications associated with congenital or acquired neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the corpus of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors. To prevent serious infection, the use of G-CSF or GM-CSF is recommended in a subset of pediatric cancer patients shortly after having received chemotherapy or a form of a marrow transplant. Children with highly intensive chemotherapy (e.g., children with high risk ALL or NHL) seem to benefit from hematopoietic growth factors whereas this is still unclear for children undergoing therapy for solid tumors. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells for autologous or allogeneic transplantation. In pediatric patients with hematological diseases, there are only few data on the use of hematopoietic growth factors in children with myelodysplastic syndrome. Experts recommend the early administration of G-CSF in children with very severe aplastic anemia. The use of G-CSF is also recommended in children with severe chronic neutropenia, but these patients have to be monitored regularly for cytogenetic abnormalities. No larger study has shown a clinical benefit of hematopoietic growth factor in preterm or term infants. Future studies in pediatric patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups of patients. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.
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PMID:[Hematopoietic growth factors in prophylaxis and therapy of infections complications in children with neutropenia]. 1152 56

The hematopoietic colony-stimulating factors have been introduced into clinical practice as additional supportive measures that can reduce, but not eliminate infectious complications associated with therapy-induced neutropenia. Over the past decade, we have begun to appreciate the subtler aspects of the proper use of G-CSF and GM-CSF, identifying appropriate indications and contraindications. In the course of evaluating the multitude of studies, a set of formal recommendations have been propagated for the judicious use of these expensive growth factors. To prevent serious infection, the use of G- or GM-CSF is recommended in a subset of pediatric cancer patients shortly after receiving chemotherapy or a marrow transplant. Children with intensive chemotherapy (e.g., children with high risk ALL, NHL or metastatic neuroblastoma) seem to benefit from hematopoietic growth factors whereas it is not clear that this applies to children undergoing therapy for solid tumors such as rhabdomyosarcoma or Ewing's sarcoma. An exciting development is the use of G-CSF and GM-CSF to mobilize peripheral-blood progenitor cells. Future studies in pediatric cancer patients are clearly warranted to address several issues. Prospective clinical trials are still needed to define specific treatment groups who can benefit from growth factor support. In this regard, efforts must be directed at better defining the endpoints and in particular, assigning value to reduction in treatment of possible infectious complications, such as days in hospital, antibiotic usage and costs. In addition, randomized studies are required to evaluate the proper dosage and duration of therapy, which most likely will vary between groups, depending upon underlying malignancy and therapy given. In addition, combinations of different growth factors have to be tested, particularly if ex vivo expansion and the storage of hematopoietic stem cells are to be utilized in a wider spectrum of patients.
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PMID:[Hematopoietic growth factors in the prevention of infections complications in children with hematologic-oncologic diseases]. 1157 68

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

No effective salvage regimen has been defined for patients with AIDS-related non-Hodgkin's lymphoma (AIDS-NHL) who do not respond to first-line chemotherapy that contains anthracycline. Combined dexamethasone, cytosine arabinoside, and cisplatin (DHAP) and etoposide, methylprednisolone, cytosine arabinoside, and cisplatin (ESHAP) have shown good response rates in HIV-negative patients with relapsed lymphomas. We retrospectively analyzed patients with refractory or relapsed AIDS-NHL who had been treated with either DHAP or ESHAP to evaluate the feasibility and efficacy of these regimens. Twenty-six patients with refractory or relapsed AIDS-NHL were treated between 1990 and 1999 either with DHAP ( n = 13) or with ESHAP ( n = 13). Only 1 patient from each group (8%) had achieved complete remission with any previous therapy, and most had progressive disease after the regimen immediately preceding DHAP or ESHAP. In the ESHAP group, 4 patients (31%) achieved complete remission (CR) and 3 patients (23%) attained partial remission (PR) for an overall response rate of 54%. The median survival was 7.1 months (range, 1-58.9+ months) from the time ESHAP was begun. Among the 3 patients with primary refractory lymphoma, there was 1 CR, 1 PR, and one patient with stable disease. In contrast, only 1 PR (7%) was observed with DHAP; the median survival was 3 months. Myelosuppression was the most significant toxicity with grade 4 neutropenia occurring in all who received ESHAP and in 54% of patients treated with DHAP. Neutropenic fever occurred in 8 (62%) ESHAP-treated and 6 (46%) DHAP-treated patients. Although hematologic toxicity is profound, ESHAP appears to be an active salvage regimen for patients with relapsed or refractory AIDS-NHL.
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PMID:High-dose cytosine-arabinoside and cisplatin regimens as salvage therapy for refractory or relapsed AIDS-related non-Hodgkin's lymphoma. 1174 28

It is yet undetermined whether patients with different hematological malignancies have different propensities to infectious complications after high-dose chemotherapy (HDC) and autologous hematopoietic stem cell transplantation (HSCT). We retrospectively analyzed 136 cycles of HDC and autologous HSCT in 114 patients with acute myeloid leukemia (AML, 24 cycles), non-Hodgkin's lymphoma/Hodgkin's disease (NHL/HD, 55 cycles), and multiple myeloma (MM, 57 cycles) with respect to early infectious complications. Median duration of neutropenia was longer in patients with AML and NHL/HD than in patients with MM (11 days vs 8 days) and after conditioning including total body irradiation (TBI) compared with chemotherapy only preparative regimens (11 days vs 7 days). Fever requiring antimicrobial therapy was observed in 88 percent of cycles, with fever of unknown origin (FUO) accounting for 60 percent of febrile episodes. There was no proven fungal infection, but one case of probable invasive pulmonary aspergillosis. Microbiologically documented infections were seen in 29 percent and clinically documented infections in 11 percent. Response to first-line empirical antibiotic therapy was better for FUO than for documented infections (70 percent vs 40 percent). Patients with TBI as part of their conditioning regimen had more overall infections than patients without TBI (96 percent vs 82 percent). There were no differences with respect to the type or incidence of infections between patients with AML, NHL/HD, and MM. Patients with different hematological malignancies have similar rates of early infectious complications after HDC and autologous HSCT. TBI may be associated with an increased risk for infections in the early post-transplant period.
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PMID:Infectious complications after autologous hematopoietic stem cell transplantation: comparison of patients with acute myeloid leukemia, malignant lymphoma, and multiple myeloma. 1218 6

The major cause of treatment failure following high-dose therapy with autologous hematopoietic cell transplantation (AHCT) for low-grade lymphomas (non-Hodgkin's lymphoma [NHL]) is persistent disease or recurrence. Most patients whose disease progresses following AHCT have resistant disease and limited bone marrow reserve. In this setting, treatment options are limited and responses to conventional chemotherapy are generally poor. Rituximab is a chimeric immunoglobulin G1 kappa monoclonal antibody that recognizes the CD20 antigen on B-cells. Published data on the use of rituximab for the treatment of recurrent NHL after autologous transplantation are limited. We present a detailed report of anti-CD20 antibody treatment for 8 patients with recurrent follicular low-grade NHL after high-dose therapy and autologous transplantation. Rituximab was administered at 375 mg/m2 intravenously once weekly for a total of 4 infusions. Median follow-up for this study was 23.4 months. Six (75%) of 8 patients responded to rituximab (2 complete response, 4 partial response). The Kaplan-Meier estimated median time to progression was 17.8 months. Rituximab was generally well tolerated. One patient developed delayed neutropenia. Other side effects were infusion related and transient. Two patients were re-treated with rituximab for progressive disease and achieved partial response. In summary, this retrospective study suggests that anti-CD20 antibody treatment is feasible in the treatment of patients who relapse or progress with low-grade NHL after autologous transplantation. There appears to be a high proportion of patients who benefit and have durable responses. Anti-CD20 antibody should be considered as a first-line salvage treatment for patients with CD20+ recurrent low-grade NBL in whom high-dose therapy has failed.
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PMID:Efficacy and safety of monoclonal anti-CD20 antibody (rituximab) for the treatment of patients with recurrent low-grade non-Hodgkin's lymphoma after high-dose chemotherapy and autologous hematopoietic cell transplantation. 1243 49

Elimination of tumor cells from hematopoietic stem cell products is a major goal of bone marow-suported high-dose cancer chemotherapy. In patients (pts) with low-grade lymphoma Gianni et al (2000) assessed the ability of Rituximab, given in combination with high-dose chemotherapy, to eradicate PCR-detectable disease and enable the harvesting of large amounts of uncontaminated circulating progenitor cells. Our study was conducted in 27 consecutive pts with untreated bcl2 positive NHL (follicular lymphoma--7, chronic lymphocytic leukemia--13 and NHL in leukemic phase--7), 14 pts received Rituximab. Patients received 4 courses of standard-dose chemotherapy (CHOP or FLU-CY), followed by one course of high-dose cyclophosphamid plus G-CSF. Patients allocated to Rituximab received i.v. infusions of 375 mg/m2 48 hours before stem cell collection and in 3 weekly doses after transplantation (R-CHT). Clinical response after transplantation was evaluated in 26 pts who completed the treatment. The complete response rate was in 100% in the Rituximab group (PCR negative in 79%) versus 50% of controls (p<0.01). Yield of purged CD34+ cells was with median 5.23x10(6)/kg in CHT and 8.76x10(6)/kg in R-CHT pts. Toxicity in the both arms was acceptated (no difference). No significant difference was observed between CHT and R-CHT group in the mean number of days spent with neutropenia and trombocytopenia. After a follow-up of 31 months, no patient relapsed. Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical (100%) and molecular remission in 79% of evaluable pts. We showed that Rituximab in combination with effective high-dose anti- lymphoma chemotherapy, allowed the harvesting of large amounts of tumor free progenitor cells in evaluable pts.
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PMID:Efficiency of in vivo purging with autologous stem cell transplantation and monoclonal antibody in B-cell lymphomas. 1268 74

High dose chlorambucil has been shown to be an effective single-agent treatment in chronic lymphocytic leukemia (CLL), and to be useful as part of combination chemotherapy in low-grade non-Hodgkin's (NHL) and Hodgkin's disease (HD). In general, it is well tolerated and can be used in an outpatient setting. The optimum dose of chlorambucil has not been defined and there are numerous different dosing schedules available. Pharmacokinetic studies suggest decreased bioavailability with successive cycles, probably due to accelerated metabolism. There is good evidence that regimens which use higher doses of chlorambucil have a better outcome than standard dose therapy. Most of the trials which have compared chlorambucil with fludarabine have not used a higher dose regimen of chlorambucil and cannot truly be described as comparative. There is an increase in the incidence of grade 3 and 4 neutropenia and also of sepsis with fludarabine treatment, compared to chlorambucil. Fludarabine produces a higher initial response rate in CLL but no statistical difference has been shown in long term survival between fludarabine and high dose chlorambucil. In the treatment of lymphoma, single agent chlorambucil does not confer a durable remission. There have been good results with combination chemotherapy regimens such as CID and PECC. The oral route of administration of these combinations makes them particularly useful as part of palliative chemotherapy. A further point to consider is that chlorambucil is very much cheaper than fludarabine and other newer agents. Chlorambucil should not automatically be overlooked in favor of more recently developed drugs such as fludarabine. There is good evidence that the drug is an effective treatment at a suitable dose, and there is a need for randomized trials to compare it fully with other current treatments.
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PMID:High dose chlorambucil in the treatment of lymphoid malignancies. 1510 11

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


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