Central nervous system effects of high-dose cytosine arabinoside.
Explore the source record for details and available documents.
Adult↗
Biomedical subjects
R H Herzig
Publications and source records attributed to R H Herzig.
Reptilase for ANLL with DIC.
Explore the source record for details and available documents.
Batroxobin↗
High-dose chemotherapy, fractionated total-body irradiation, and allogeneic marrow transplantation for malignant lymphoma.
Seventeen patients with malignant lymphoma, including 13 with progressive disease and four in remission following primary chemotherapy, received high-dose chemotherapy, fractionated total-body irradiation (TBI), and allogeneic marrow transplants. Eleven of the 13 (85%) patients in relapse who received transplants achieved remission, and three remain disease free 41, 21, and 17 months later; one patient in second remission who received a transplant is disease free at 11 months. Thirteen patients are dead: four because of progressive lymphoma, seven because of interstitial pneumonitis, and two because of complications of severe acute graft-v-host disease. These results are similar to those noted in marrow transplantation series for advanced acute leukemia; since transplantation during remission has decreased relapse and improved survival in leukemia, earlier transplantation may produce improved results in lymphoma patients as well. However, the effectiveness of conventional therapy regimens for most lymphomas and the high incidence of severe transplant-related complications usually limit allogeneic transplantation to lymphoma patients in situations other than consolidation of first remission. Initial partial remission, early relapse from an initial remission, and perhaps second remission are situations in which conventional therapy is often ineffective, but the adverse features of very advanced lymphoma are not present; marrow transplantation may be considered in eligible patients. Transplant recipients with more advanced disease are anticipated to have poorer survivals.
Adolescent↗
Intensive 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU) monochemotherapy and autologous marrow transplantation for malignant glioma.
Intensive monochemotherapy with carmustine (BCNU) (either 1,050, 1,200, or 1,350 mg/m2) and cryopreserved autologous marrow transplantation was administered to 36 patients with malignant glioma: 27 with progressive disease and nine without progression (adjuvant therapy group). Twelve (44%) of the patients with progressive disease responded; two remain disease free 84 and 60 months after BCNU treatment. In the adjuvant therapy group, three patients remain progression free at 70, 48, and 27 months after BCNU therapy. Tumor progression posttransplantation occurred in 25 patients; six others died of therapy-induced complications. In addition, late neurologic deterioration of unknown cause has developed in two surviving patients. Results from this and other series using intensive BCNU monochemotherapy and autologous marrow transplantation for progressive malignant glioma indicate that prolonged progression-free survival can be produced in an occasional patient, an extremely unusual result with conventional chemotherapy. Although intensive BCNU and autologous marrow transplant regimens are toxic, these results are encouraging. The treatment of patients in an adjuvant fashion with BCNU and other active agents may produce improved results.
Adolescent↗
Bone-marrow transplantation for chronic myelogenous leukaemia.
Explore the source record for details and available documents.
Adolescent↗
Percutaneous silastic catheter insertion in patients with thrombocytopenia.
A retrospective analysis of 33 patients with malignancy and thrombocytopenia of less than 100,000/microliter who underwent percutaneous Silastic (Evermed) catheter insertion is presented. Thirty-seven catheter insertions were performed in these patients during a 2-year period. The insertion technique includes intraoperative platelet transfusion for patients with platelet counts of less than 50,000/microliter, the use of general anesthesia for infants and children, and intravenous sedation with local anesthesia in adults. Minimizing the dissection required for the subcutaneous catheter tunnel is achieved with a modified shunt-tunneling device. The majority of catheters were placed by the subclavian approach. Fifty-nine percent of the procedures took place when the platelet count was less than or equal to 30,000/microliter. There was no mortality related to the procedure. Four complications directly related to the technique (arterial puncture, 3; cervical hematoma, 1) and eight related to the catheter occurred without serious sequelae. With appropriate precautions, percutaneous placement of Silastic catheters can be performed safely in patients with thrombocytopenia. This technique produces less tissue injury than operative venotomy, may be performed more rapidly, obviates sacrifice of the vein that is used and, consequentially, allows for multiple subsequent insertions via the same vein.
Adolescent↗
High-dose cytosine arabinoside in previously treated patients with poor-prognosis non-Hodgkin's lymphoma.
Fourteen previously treated patients with relapsed or refractory poor-prognosis non-Hodgkin's lymphoma were given chemotherapy regimens containing high doses of cytosine arabinoside alone (seven patients) or with an anthracycline or amsacrine (seven patients). Five patients achieved a complete remission and two patients had a partial remission. The durations of remission, however, were short (median, 3 months; range, 2-6 months). Toxicities included conjunctivitis, photophobia, stomatitis, dermatitis, cerebellar dysfunction, diarrhea, nausea, vomiting, liver dysfunction, and severe myelosuppression. Recovery of an absolute granulocyte count greater than 500/microliter and an untransfused platelet count greater than 20,000/microliter required a median of 31 (range, 28-35) and 30 (range, 27-43) days, respectively. Six patients died with recurrent or residual disease before bone marrow recovery. Younger age, good performance status, and a previous complete remission were predictive of a good response. High-dose cytosine arabinoside has major myelotoxicity but significant activity in some patients with poor-prognosis non-Hodgkin's lymphoma.
Adolescent↗
High-dose cytosine arabinoside therapy with and without anthracycline antibiotics for remission reinduction of acute nonlymphoblastic leukemia.
Seventy-eight patients with acute nonlymphoblastic leukemia in relapse were treated with high-dose cytosine arabinoside (3 g/m2 intravenously (IV) every 12 hours for 12 doses) alone, or with three days of anthracycline antibiotics (doxorubicin 20 mg/m2 or daunorubicin 30 mg/m2 IV daily) after completing the course of cytosine arabinoside. Consolidation and maintenance therapy was not given. When anthracyclines were added there was no increase in frequency or severity of nonhematologic toxicity including conjunctivitis, photophobia, dermatitis, cerebellar dysfunction, and gastrointestinal disturbance. All 78 patients achieved aplasia of the bone marrow. Five patients in each group died before bone marrow recovery. The use of anthracyclines did not prolong bone marrow recovery, with both groups demonstrating adequate granulocyte and platelet counts about four weeks after beginning treatment. Forty-one (53%) of the total 78 patients achieved a complete remission. In patients not clinically resistant to conventional-dose cytosine arabinoside, both regimens were equally effective inducing a complete remission (high-dose cytosine arabinoside alone, 12/19 [63%]; with anthracycline, 11/17 [65%], P = .270); in patients clinically resistant, the regimen including anthracycline was superior (15/27 [56%] v 3/15 [20%], P = .022). The duration of unmaintained response was similar (median, five months), but the longest remissions occurred when anthracyclines were used. Thus, high-dose cytosine arabinoside is effective in producing remissions in relapsed patients with acute nonlymphoblastic leukemia, and the addition of an anthracycline enhances this effect.
Acute Disease↗
Treatment of metastatic malignant melanoma with intensive melphalan and autologous bone marrow transplantation.
Twenty patients with metastatic malignant melanoma were treated with melphalan (180-225 mg/m2 iv over 3 days) followed by re-infusion of previously harvested and cryopreserved autologous bone marrow. Granulocyte (greater than 500/microliter) and platelet (greater than 20,000/microliter) count recovery occurred a median of 14 days (range, 12-22) and 19.0 days (range, 12-28) after bone marrow transplantation, respectively. Three patients died due to hemorrhage or infection. One of these patients and another (who ultimately achieved a complete response), both with brain metastases, developed intralesional hemorrhage when the platelet count was only moderately reduced. Complete responses occurred in six patients and ranged from 4 to 14 months, with a median of 5 months. Six patients achieved a partial remission lasting 2-5 months. High-dose melphalan and autologous bone marrow transplantation are a promising therapy for patients with metastatic malignant melanoma.
Adult↗
Bone marrow transplantation for acute leukemia and lymphoma with high-dose cytosine arabinoside and total body irradiation.
Explore the source record for details and available documents.
Acute Disease↗
Central nervous system toxicity with high-dose cytosine arabinoside.
Explore the source record for details and available documents.
Acute Disease↗
High-dose cytosine arabinoside and daunorubicin as consolidation therapy for acute nonlymphocytic leukemia in first remission: a pilot study.
High-dose (HD) cytosine arabinoside (ARA-C) is more effective treatment than conventional-dose ARA-C regimens for patients with relapsed acute nonlymphocytic leukemia (ANLL). We report here that HD ARA-C given during the first remission of ANLL has resulted in long remission durations and a high proportion of patients who survive more than three years free of disease. From August 1979 to September 1983, 36 adult patients with ANLL in first remission received one to three courses of HD ARA-C (3 g/m2 by one-hour infusion every 12 hours for 12 doses on days 1 through 6) alone or with daunorubicin (30 mg/m2 for two or three doses on days 7 through 9). Three patients died of sepsis or hemorrhage during consolidation, and 14 patients have relapsed from five to 48 months after diagnosis. The remaining 19 patients are in continued complete remission (CCR) from 11 to 62 months. Denoting all deaths in remission as relapse, the actuarial probability of CCR is 42% at 62 months, with an apparent plateau in the survival curve. Of the first 22 patients treated, ten remain in CCR from 37 to 62 months with no therapy for at least three years. Due to its heightened anti-leukemic activity, HD ARA-C allows brief but effective consolidation of ANLL in first remission, with long-term disease-free survival comparable to other approaches.
Acute Disease↗
Treatment of resistant malignant lymphoma with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow.
Twenty-seven patients with malignant lymphoma in whom primary chemotherapy had failed and the prognosis was poor were treated with cyclophosphamide, total body irradiation, and transplantation of cryopreserved autologous marrow. The median time to recovery of more than 500 neutrophils per microliter and more than 10,000 platelets per microliter was 18 and 24 days, respectively. Complete remission was achieved in 15 patients (56 per cent), five of whom were in continuous remission at this writing 19 to 71 months after transplantation without further therapy and one of whom was alive in a subsequent remission at 20 months. Fifteen patients died of lymphoma, three of interstitial pneumonitis, two of sepsis, and one of congestive heart failure. This experience shows that intensive therapy and autologous-marrow transplantation can produce prolonged remissions in patients with malignant lymphoma in whom conventional chemotherapy has failed.
Adolescent↗
Allogeneic bone-marrow transplantation for chronic myelogenous leukaemia.
In 117 patients with chronic myelogenous leukaemia (CML) treatment with a combination of high-dose chemoradiotherapy plus transplantation of allogeneic bone-marrow from HLA-identical, mixed-lymphocyte-culture-identical siblings resulted in an actuarial probability of 3-year survival of 63 +/- 16% (95% confidence interval) for 39 patients transplanted in chronic phases; 36 +/- 14% for 56 transplanted in accelerated phase; and 12 +/- 15% for 22 transplanted during blast crisis. Irrespective of disease status at the time of transplantation, and in contrast to chemotherapy, a plateau-effect was observed in the survival curves starting 14 to 19 months after transplantation. The actuarial probability of recurrent or persistent leukaemia at 3 years was 7 +/- 9% for patients transplanted in chronic phase, 41 +/- 19% for accelerated phase, and 41 +/- 39% for blastic phase. All relapses occurred within 18 months of transplantation. This study demonstrates that long-term disease-free survival in CML can be achieved with bone-marrow transplantation. Best results were obtained in patients transplanted during chronic phase of the disease.
Adolescent↗
High-dose melphalan therapy for the treatment of children with refractory neuroblastoma and Ewing's sarcoma.
Neuroblastoma and Ewing's sarcoma are examples of pediatric cancers in which disseminated disease is often present at diagnosis or develops later in spite of combination therapy. The demonstration that marrow-ablative doses of chemotherapy can increase tumor cell kill, and that autologous bone marrow can be cryopreserved and reinfused into the patient to reverse such marrow ablation, has stimulated interest in this approach to refractory childhood cancers. We present results of treating eighteen patients with recurrent neuroblastoma and Ewing's sarcoma resistant to conventional therapy. We used supralethal doses of melphalan, supported by reinfusion of previously cryopreserved autologous bone marrow. Seven of 10 neuroblastoma and six of eight Ewing's sarcoma patients had complete or partial responses, lasting for a median of 6 months (neuroblastoma) and 3 months (Ewing's sarcoma). Prolonged hospitalization, pancytopenia complicated by sepsis, and reversible gastrointestinal toxicity were the major side effects. These results suggest this approach should be tested in therapeutic trials at an earlier disease stage in children who have cancers with a predictably bad prognosis.
Abdominal Neoplasms↗
Incidence of acute graft-versus-host disease with and without methotrexate prophylaxis in allogeneic bone marrow transplant patients.
Methotrexate has been used as the mainstay therapy to prevent or ameliorate graft-versus-host disease (GVHD) in allogeneic bone marrow transplantation. We began a nonrandomized study in which methotrexate was not given routinely. Fifty-five patients underwent transplant for acute leukemia (44 patients), aplastic anemia (6 patients), and other malignancies (5 patients). Methotrexate was given to 34 patients (MTX +) and was withheld in 21 patients (MTX -). Median (range) age of patients was 12 (0.8-43) years in the MTX + group, and 16 (3-45) years in the MTX- group. Mean days (+/- SEM) to engraftment (neutrophils greater than 500/microL, and platelets greater than 20,000/microL untransfused) occurred earlier in the MTX- patients (19.6 +/- 1.4 v 24.9 +/- 1.8 days for granulocytes, and 19.3 +/- 1.5 v 27.4 +/- 2.8 days for platelets, P less than .05). There were no statistically significant differences between the patient groups for the incidence or severity of GVHD (10/34 in the MTX + group had grade O-l GVHD compared to 9/21 in the MTX- group). The interstitial pneumonitis occurred at a significantly increased rate in patients who received methotrexate (15/34) compared to those patients who did not (3/21) (P = .02). However, there was also a significant relationship between the interstitial pneumonitis and the preparative regimen: if the preparative regimen contained 1,000 rad single fraction total body irradiation, 8/14 patients were affected compared to 5/22 patients affected when 1,200 rad fractionated total body irradiation was used (P = .03). Because methotrexate significantly retards hematopoietic reconstitution, randomized trials for GVHD prevention are recommended.
Acute Disease↗
Occlusion and infection in Broviac catheters during intensive cancer therapy.
Before administration of intensive cytotoxic therapy, 90 central venous catheters were inserted into 80 patients with malignancies. Twenty-seven episodes of bacteremia and fungemia occurred during 96 treatment courses. The majority of these infections were due to gram-positive bacteria (45%) or fungi (22%), although gram-negative organisms accounted for 33%. Catheter occlusion occurred in patients receiving intravenous phenytoin, but blood products could be infused without difficulty. An increase in gram-positive bacteremias in patients with these catheters and drug-induced catheter occlusion must now be appreciated.
Adolescent↗
Intensive 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), NSC #4366650 and cryopreserved autologous marrow transplantation for refractory cancer. A phase I-II study.
One hundred forty-three patients with refractory cancer were treated with intensive BCNU (600-2850 mg/m2) and autologous marrow transplantation to determine the maximum tolerated dose and antitumor effects of this regimen. Recovery from severe pancytopenia in less than 4 weeks after transplantation occurred in 92.8% of evaluable patients, suggesting the efficacy of the autologous marrow in limiting the prolonged myelosuppression anticipated with intensive BCNU. Serious extramedullary toxicity was encountered at BCNU 1200 mg/m2, where a 9.5% incidence of fatal interstitial pneumonitis and a 3.0% incidence of fatal hepatic necrosis was observed. Higher BCNU doses, 1500 to 2850 mg/m2, were associated with a 35.3% incidence of fatal hepatotoxicity. Fatal encephalomyelopathy was encountered in two patients given BCNU 2250 and 2850 mg/m2. One patient who received the highest cumulative dose of BCNU (3450 mg/m2 in 2 courses) died of cardiac necrosis. Other serious extramedullary toxicities were not encountered, even in the 14 patients who survived from 1 to nearly 5 years after BCNU therapy. Antitumor responses occurred in 40.0% of evaluable patients; a dose effect could not be evaluated due to patient heterogeneity. The BCNU doses associated with acceptable toxicity, 600 to 1200 mg/m2, produced a 37.5% total and an 11.3% complete response (CR) rate, including five patients with prolonged CRs of 1 to nearly 5 years. Notable among the CRs was the 25.0% CR rate in previously untreated metastatic melanoma, and the production of CRs in malignant disease in the central nervous system (CNS) including melanoma, lung cancer, adenocarcinoma of unknown primary, acute leukemia and glioblastoma multiforme. It is concluded that augmented doses of BCNU can be given when autologous marrow transplantation is used to limit myelosuppression. Lung and liver toxicity prevent the use of BCNU doses greater than 1200 mg/m2; neurotoxicity, and perhaps cardiotoxicity, are manifestations of the highest doses used in this study. The antitumor activity of BCNU 600 to 1200 mg/m2 remains to be determined for most neoplasms; these results suggest improved results in melanoma and CNS malignancy compared to conventional-dose BCNU therapy.
Adolescent↗