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)

Forty-seven previously untreated patients with intermediate- or high-grade non-Hodgkin's lymphoma were treated with four courses of a regimen that consisted of high-dose (120 mg/m2) Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH), vincristine (2 mg), cytarabine (3 gm/m2), and dexamethasone (50 mg intravenously [IV] on day 1 and 20 mg/day orally on days 2 to 5) (AVAD), which was administered every 3 to 4 weeks. The median age of the patients was 58 years; 72% were Ann Arbor stage IV, 49% had "B" symptoms, 62% had masses larger than 7 cm, 40% had masses at least 10 cm in diameter, and 49% had serum lactate dehydrogenase (LDH) greater than 250 U/L. Overall, 72% of the patients (89% of diffuse large-cell lymphoma [DLCL] patients) attained complete (CR) or probable complete responses (PCR), and relapses occurred in 32%. There were no episodes of clinical congestive heart failure, but one patient developed recurrent ventricular arrhythmias. Fever during neutropenia occurred with 65% of treatment courses. Three deaths were attributed primarily to complications of therapy. The lymphoma-free survival of all entered patients is 51% (24 of 47), with a follow-up of 30 to 67 months (median, 58 months). These results confirm that high CR/PCR and long-term survival rates can be achieved in patients with aggressive histologies of non-Hodgkin's lymphomas, even in groups with poor prognostic factors, using high-dose anthracycline-containing chemotherapy regimens delivered over a short period of time. However, the apparently higher relapse rate in comparison to our previous study leads us to speculate that consolidation with noncross-resistant agents may be helpful in increasing even further the cure rate in this group of patients.
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PMID:Chemotherapy of intermediate- and high-grade non-Hodgkin's lymphomas with a high-dose doxorubicin-containing regimen. 229 68

Cytosine arabinoside (ara-C) is an S-phase active antineoplastic agent used in the treatment of several hematologic malignancies. We did a retrospective analysis on 48 patients with relapsed or refractory non-Hodgkin's lymphoma (NHL) who were treated with high-dose ara-C between 1982 and 1987. All patients received between 9 and 24 g/m2/course of treatment with 90% receiving 12g/m2/treatment. Fifteen patients (25%) achieved a complete or partial remission. Of these, five (10%) were complete responders. Long-term disease-free survival was maintained only in those responders who were consolidated with autologous bone marrow transplantation. Toxicity was primarily myelosuppression. Seventy-five percent of patients developed fever and neutropenia with an equivalent percent having severe thrombocytopenia sufficient to require platelet transfusion. Five patients (10%) had significant neurotoxicity. There were seven treatment-related deaths (15%). Patients in whom tumors contained a small cell component responded better than patients with purely large cell or undifferentiated lymphomas (50% versus 15%, P = 0.024). We conclude that high-dose ara-C given as 3g/m2 every 12 hours for four doses has a limited role when used as a single agent in the treatment of relapsed or refractory non-Hodgkin's lymphoma. However, there are subsets of patients who may respond favorably to this therapy.
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PMID:High-dose cytosine arabinoside in relapsed and refractory non-Hodgkin's lymphoma. Limited role as a single agent. 255 38

In a series of 320 patients with lymphoid neoplasms treated with polychemotherapy, three patients with non-Hodgkin's lymphoma and one with myeloma were diagnosed as having neutropenic enterocolitis (NEC). All patients were adult, all had received multiple chemotherapeutic drugs and, during neutropenia, they had clinically presented with fever and abdominal pain, generally in the right lower quadrant. The diagnosis was clinical in all cases, and the imaging techniques provided only the suspicion of retro-cecal abscess in one of them. Two patients were operated on because of the development of features of peritoneal involvement, another because of septic shock and another because of retro-cecal abscess. Surgery and pathological study confirmed the diagnosis. The fundamental findings were ileocecal wall edema, mucosa ulceration, local necrosis, hemorrhage and thrombosis, and clusters of bacterial colonies without evidence of granulocytic or tumoral infiltration. NEC can develop with varying types of morphological involvement resulting in a highly variable clinical severity spectrum ranging from nonspecific abdominal symptoms to acute abdomen. Thus, diagnosis is very difficult and is only possible with a high suspicion index. It should rely on clinical data, which are unique, to assess the evolution and to indicate medical or surgical therapy. These therapeutic modalities should be individualized in each patient. All physicians treating neutropenic patients should be familiar with this condition and consider it in the differential diagnosis of abdominal pain.
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PMID:[Neutropenic enterocolitis during treatment of lymphoproliferative neoplasms]. 261 46

Primary lymphoma of bone (PLB) occurs infrequently in children. Between January 1962 and November 1988, 395 children with non-Hodgkin's lymphoma (NHL) were treated at St. Jude Children's Research Hospital. Eleven of these patients (2.8%) presented with a bone primary, usually in the femur (eight of 11 patients). The median age of these seven boys and four girls at presentation was 13 years (range, 5.5 to 19 years). Seven patients had one or more additional bones involved. All patients had high-grade lymphomas based on the National Institutes of Health (NIH) Working Formulation. The histologic subtypes included six large-cell lymphomas, three lymphoblastic lymphomas, one small-noncleaved, non-Burkitt's lymphoma, and one unclassifiable lymphoma. Treatment consisted of multiagent chemotherapy combined with local radiation therapy in seven of 11 patients. Six of 10 children who received chemotherapy as a component of their initial therapy, including all who presented with localized tumor, are alive with no evidence of disease 2+ to 85+ months (median, 42.5 months) after cessation of treatment; one patient has just completed chemotherapy. Each of the four patients who died showed leukemic conversion 5 to 11 months after diagnosis, and three died of progressive disease. One patient died of sepsis during chemotherapy-induced neutropenia with no evidence of disease at necropsy. We conclude that optimal therapy for PLB, as with all other forms of NHL, should focus on the histologic subtype and stage of disease.
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PMID:Primary lymphoma of bone in children. 276 28

Mitoxantrone (Novantrone, NO) and high-dose cytarabine (Ara-C, AC) have each been shown in monotherapy trials to be active in non-Hodgkin's lymphoma (NHL). In the current study, a combination of the two drugs (NOAC) was administered to 31 patients with advanced NHL refractory to modern sequential chemotherapy regimens. Ara-C was administered at 3 g/m2 as a 3 hour infusion every 12 hours on day 1 (2 doses) and mitoxantrone at 10 mg/m2/day on days 2 and 3. Of the 18 patients with high-grade malignant NHL, six have attained a complete remission (CR) and two, a partial remission (PR). One CR and 5 PRs were achieved among the other 13 patients with intermediate or low-grade NHL. The median time to relapse (TTR) of patients achieving CR was 7 months with a range from 4 to 17 months. Myelosuppression with subsequent infections was the major toxicity of this regimen. The median duration of severe neutropenia (less than 0.5/nl) was 9 days with a range of 0 to 27 days and the median duration of severe thrombocytopenia (less than 20/nl), 5 days with a range of 0 to 35 days. Infectious complications during cytopenia was seen in 45.3% of the courses administered and fever of unidentified origin was seen in 42.3%. About 63% of the patients were hospitalized for intravenous antibiotic or antimycotic treatment. Other side effects were mild and included nausea, stomatitis, and transient tachycardia of greater than 100/min. Thus, this regimen was active in refractory NHL with poor prognosis, and the toxic side effects were not excessive. Evaluation of the activity of this regimen at higher dose levels of Ara-C is warranted.
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PMID:Mitoxantrone and high-dose cytarabine as salvage therapy for refractory non-Hodgkin's lymphoma. 277 3

Treatment results remain very poor for some clinical and histopathologic subsets of patients with aggressive non-Hodgkin's lymphoma. We treated 21 such patients with a high-dose combination chemotherapy regimen [Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) + CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)] in an attempt to improve disease-free survival. Neoplasms were classified using the Lukes-Collins system. Eight patients had T-cell lymphomas (convoluted lymphocytic lymphoma, four patients; T-cell lymphoma/leukemia, one; and peripheral T-cell lymphoma, three), eight had B-cell lymphomas (immunoblastic sarcoma, five patients; small noncleaved follicular center cell, one; and large noncleaved follicular center cell, two), and five had nontypable large noncleaved cell lymphomas. All patients were previously untreated; 18 of 21 patients had clinical stage III or IV disease. Following induction therapy (4-8 weeks' duration), 16 patients (76%) achieved complete remission, while three had partial remission. Two patients died of sepsis during induction therapy. Eleven of 16 complete responders (69%) remain in complete remission after a median follow-up of 35 months. The actuarial 3-year survival rate is 51% for the entire group. Myelosuppression with this regimen was severe and prolonged, with a median duration of neutropenia (less than 500 cells/microliter) of 14 days. Seven patients (33%) developed severe neuropathy following induction treatment. High-dose induction therapy with this regimen resulted in a high complete remission rate with manageable toxicity. Survival results are encouraging when compared retrospectively to our patients with similar poor-prognosis histologies treated with standard combination chemotherapy. However, the value of this intensive therapy, relative to newer ("third-generation") regimens, can only be established by prospective randomized studies.
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PMID:Effects of Mega-COMLA (cyclophosphamide, cytarabine, vincristine, and methotrexate followed by leucovorin and prednisone) plus CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) in the treatment of lymphoid neoplasms with very poor prognosis. 301 6

A total of 110 patients with high-grade non-Hodgkin's lymphoma (NHL) not previously treated by chemotherapy or by radiotherapy at more than one site of disease underwent a regimen comprising an intensive 6-week initial, induction phase using vincristine, adriamycin, methotrexate, and prednisolone (VAMP) followed by the non-cross-resistant combination cyclophosphamide, etoposide, and vindesine (EEE). The median age of patients was 54 years, the majority having stage IV disease. The median follow-up was 34 months and all patients have completed treatment. The overall complete remission (CR) rate for all patients was 68%. The initial phase of treatment produced a CR rate of 49%. The full regimen was completed by 87 patients, and of these, 66 (76%) achieved CR. Of those achieving CR, 72% were relapse-free, on an actuarial basis, at 2 years. Overall 2-year survival was 53%, with a median survival of 31 months. The survival of older patients and those with lymphoblastic histology was comparable to that of other groups. The survival prospects of patients with stage IV disease was not as good as that of other patients, with a significant trend to shorter survival in patients with more advanced disease. Toxicity was predictable and manageable for both phases of the regimen, although it was more severe for the initial phase. Dose-limiting toxicities were neutropenia and mucositis. This regimen is active in the treatment of advanced high-grade NHL with acceptable toxicity. These results have encouraged us to continue the study of weekly chemotherapy, which we will compare with standard cyclical chemotherapy in a prospective, randomized trial.
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PMID:A new approach to the treatment of advanced high-grade non-Hodgkin's lymphoma--intensive two-phase chemotherapy. 340 45

To address the problem of historically poor results in the treatment of children with advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia (ALL), an intensive chemotherapy regimen was devised using the most effective single agents in high-dose short courses. Treatment commenced with a fractionated schedule of intravenous (IV) cyclophosphamide (300 mg/m2 every 12 hours for six doses) followed immediately by Adriamycin (50 mg/m2) and vincristine (1.5 mg/m2) with combined intrathecal (IT) methotrexate and cytarabine. Predictably, this treatment produced virtually complete disappearance of all tumor and profound myelosuppression. Immediately on hematologic recovery, IV high-dose methotrexate (1,000 mg/m2 over 24 hours) followed by IV cytarabine (400 mg/m2 over the next 48 hours) was administered with leucovorin rescue and repeated IT treatments. The treatment sequence described above is repeated four times, with the dose of cytarabine doubled in succeeding courses, up to 3,200 mg/m2. The entire planned therapy required approximately 24 weeks. Since 1981, we treated a total of 29 children with this approach, 19 of whom had massive unresectable intraabdominal tumor. According to initial extent of disease, 17 were classified as stage III, four as stage IV non-Hodgkin's lymphoma (NHL), and eight as B cell ALL. Eight of the 12 patients with stage IV NHL or B cell ALL had initial involvement of the CNS. Twenty-seven of 29 patients (93%) attained a complete remission. Fourteen of 17 stage III NHL patients remain disease free, for periods ranging from 3+ months to 4 1/2+ years. The actuarial estimate of the proportion of stage III patients remaining disease free at 2 years is 81%. Results in patients with initial involvement of the CNS and/or marrow are much less favorable, with only two of ten patients who attained remission apparently being cured. In addition to stage, the initial serum lactic dehydrogenase (LDH) level emerged as a prognostic indicator, higher levels (over 1,000 IU/L) being associated with the worst prognosis (P less than .05). Major toxicity consisted of severe hematopoietic suppression and febrile episodes associated with neutropenia. We conclude that this treatment is highly effective for advanced-stage Burkitt's tumors in children free of initial CNS involvement.
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PMID:Results of treatment of advanced-stage Burkitt's lymphoma and B cell (SIg+) acute lymphoblastic leukemia with high-dose fractionated cyclophosphamide and coordinated high-dose methotrexate and cytarabine. 349 Nov 84

Suramin sodium is a reverse transcriptase inhibitor with in vitro activity against the human immunodeficiency virus (HIV), the causative agent of acquired immunodeficiency syndrome (AIDS). Ninety-eight patients with AIDS manifest as opportunistic infections (n = 38), AIDS with Kaposi's sarcoma (n = 38), AIDS-related complex (n = 20), or AIDS-associated non-Hodgkin's lymphoma (NHL) (n = 2) were treated with suramin sodium at 0.5, 1.0, or 1.5 g/wk for six weeks followed by maintenance therapy with 0.5 or 1.0 g/wk. Of 72 patients who were HIV culture positive before therapy and were assessable for subsequent HIV culture 40% became culture negative during treatment, with no apparent correlation between virus recovery and serum suramin concentration. No immunologic improvement was noted. One complete clinical remission was noted in a patient with Kaposi's sarcoma and stage IV NHL. Seven minor clinical responses were also noted. Toxic reactions were generally reversible, and included fever (78%), rash (48%), malaise (43%), nausea (34%), neurologic symptoms (33%), and vomiting (20%). Suramin-induced neutropenia was noted in 26%, thrombocytopenia in 12%, a serum creatinine level of 180 mumol/L or higher (greater than or equal to 2.1 mg/dL) in 12%, liver dysfunction in 14%, and clinical and/or laboratory evidence of adrenal insufficiency in 23%. Sixteen patients died while receiving suramin or within three weeks of discontinuation of drug therapy due to infection (n = 6), hepatic failure (n = 3), pulmonary Kaposi's sarcoma (n = 2), AIDS encephalitis (n = 2), AIDS-associated NHL (n = 1), iatrogenic hemo-pneumothorax (n = 1), or pulmonary disease of uncertain etiology. Suramin as currently administered cannot be recommended as effective therapy for AIDS.
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PMID:Suramin therapy in AIDS and related disorders. Report of the US Suramin Working Group. 365 Mar 39

Ninety-three stage III and IV patients with non-Hodgkin's lymphoma were randomized to either high dose CVP (cyclophosphamide 1500 mg/m2 i.v. day 1, vincristine 1.4 mg/m2 day 1, and prednisone 40 mg/m2 orally days 1-10) or high dose CAVP (cyclophosphamide 1000 mg/m2 i.v. day 1, doxorubicin 45 mg/m2 i.v. day 1, vincristine and prednisone as above). Overall, the complete response (CR) rates were similar (CVP 51%, CAVP 51%). Patients with the International Working Formulation diffuse large cell lymphoma had significantly higher CR with CAVP. No difference in CR duration was detected between the two regimens. CRs were durable with 68% of diffuse and 86% of diffuse large cell complete responders alive and disease free at 7 years. Survival was similar with both regimens except for patients with diffuse large cell lymphoma who survived longer with CAVP. Both regimens were equitoxic with neutropenia less than 1.0 x 10(9)/liter in 36% of courses, infections in 15% of courses, and fatal infections in three patients. These intermittent high dose cyclophosphamide equitoxic regimens produced durable responses. However, the doxorubicin-containing regimen is superior in diffuse large cell lymphoma.
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PMID:A randomized trial of high dose cyclophosphamide, vincristine, and prednisone plus or minus doxorubicin (CVP versus CAVP) with long-term follow-up in advanced non-Hodgkin's lymphoma. 366 68


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