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PubMed2001

Pharmacodynamics of high-dose chemotherapy.

There is usually considerable variability in anticancer drug plasma levels when delivered at high doses requiringstem-cell support. Given their narrow therapeuticwindows and wide interpatient pharmacokinetic variability, drug monitoring and pharmacokinetic-directed dosing representan attractive strategy in this setting. A major previous requirement to successful application of therapeuticdrug monitoringis identificationof a significant and clinically meaningful pharmacodynamic correlation between a pharmacokinetic parameter and a toxic or therapeutic outcome, or preferably, both. In this review, we will analyze the current knowledge of identified pharmacodynamic correlations in high-dose chemotherapy. We will summarize the observations from other authors and our own, on drugs employed at high doses, such as cyclophosphamide, melphalan, busulfan, carmustine, paclitaxel, or docetaxel.

Animals↗
PubMed1994

O6-methylguanine-DNA methyltransferase in normal and malignant tissue of the breast.

An important component of high-dose chemotherapy/autologous bone marrow support regimens for adjuvant treatment of breast cancer is carmustine. Preclinical studies have shown that the level of the DNA repair protein O6-methylguanine-DNA methyltransferase is correlated with the resistance of cultured human tumor cells to this drug, but little is known about transferase levels of breast tissue in vivo. We measured the DNA repair activity in 80 tissue samples from 65 patients, including normal, abnormal, benign, and malignant specimens. Wide interindividual variations was observed and average transferase levels were similar in normal and benign tissue. However, transferase levels were significantly elevated in stage I-IV disease. In addition, the frequency of samples with no detectable transferase was greatly reduced in this malignant group, and transferase was positively correlated with the presence of positive nodes, a marker for disease progression. In contrast, transferase levels were not correlated with age or estrogen receptor status, and the levels in normal tissue did not vary between patients with benign or malignant disease. These results suggest that this DNA repair activity may be increased in breast cancer relative to normal tissue and encourage further study of the predictive value of transferase measurements in high-dose chemotherapy/autologous bone marrow transplant for breast cancer.

Adult↗
PubMed1994

Role of upper endoscopy in evaluation of upper gastrointestinal symptoms in patients undergoing bone marrow transplantation.

We reviewed our upper endoscopy (esophagogastroduodenoscopy, EGD) experience in a group of 65 consecutive patients receiving carmustine (BCNU) 600 mg/m2, cisplatin 200 mg/m2, VP-16 2400 mg/m2, and autologous bone marrow transplantation (BMT) for relapsed or refractory non-Hodgkin's lymphoma or Hodgkin's disease. Forty-one patients (33 with chest irradiation) underwent 48 EGDs for the following symptoms: upper gastrointestinal bleeding (melena and/or hematemesis) (12/48); persistent nausea and vomiting (7/48); odynophagia (25/48); and dysphagia (14/48). All patients who had dysphagia or odynophagia had endoscopic evidence of severe esophagitis, with confluent erosions or ulcerations. Gastrointestinal bleeding, which presented as melena or hematemesis, was caused by severe esophagitis in 11 of 12 patients. Yeasts were detected in 11/42 histological, or cytological specimens and were isolated in 4/26 cultures. No bleeding or infectious complications occurred in any patient as a result of the EGD procedure. We conclude that severe esophagitis documented by EGD is common in lymphoma patients receiving autologous BMT. Use of EGD, however, did not affect the decision to initiate empirical therapy with amphotericin B for persistent fever.

Adolescent↗
PubMed2001

Amifostine does not protect malignant lymphoma cell lines from the cytotoxic effects of various chemotherapeutics in vitro.

The effect of amifostine on the cytotoxicity of melphalan, BCNU, doxorubicin and etoposide in lymphoma cell lines; HTB-61 (Burkitt), HTB-142 (nonspesified neck lymphoma), HTB-146 (Hodgkin's) and HTB 176 (Sezarýs syndrome) and a normal human fibroblast cell line was studied in vitro. Amifostine decreased etoposide induced cell kill in the fibroblast cell line. Pretreatment with the same amifostine concentration did not decrease the cytotoxic effects of etoposide, doxorubicin, melphalan and carmustine in lymphoma cell lines. Moreover, it even enhanced the cell killing effects of chemotherapeutics in especially HTB61 cell line. Our results indicate that amifostine does not decrease cytotoxicity of the chemotherapeutics and favor the testing of this drug in accordance with lymphoma treatments in clinical trials.

Amifostine↗
PubMed2006

Chemotherapy for primary central nervous system lymphoma.

Chemotherapy, with or without radiotherapy, is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, and it is used in doses of 1 to 8 g/m(2), either as a single agent or in combination with other drugs such as corticosteroid agents, cytarabine, procarbazine, vincristine, carmustine, lomustine, thiotepa, cyclophosphamide, temozolomide, and rituximab. To date, an overwhelming number of different regimens in which high-dose MTX is used have been reported. Given the lack of randomized trials, however, the optimal treatment remains controversial. Varying methodology makes the comparison of available studies extremely difficult, yet some common themes can be found throughout the literature. Treatment paradigms vary considerably according to the patient's age. Most studies support the use of chemotherapy-only treatments for elderly patients (> 60 years), given the high risks of neurotoxicity associated with radiotherapy. Nevertheless, the prognosis remains poor regardless of the chemotherapy chosen, and less toxic regimens might be preferable for such elderly patients. Conversely, in younger patients (< 60 years), there is growing evidence that commonly used chemotherapy-only regimens are associated with increased relapse rates that may not justify deferral of radiotherapy. Thus, a significant focus of research has been the development of intensified chemotherapy regimens that could replace radiotherapy. In this article, the authors discuss the principles guiding the use of chemotherapy for PCNSL, and critically review the available literature, including the most recent trials.

Antineoplastic Agents↗
PubMed1992

Isolation and preliminary characterization of ACNU-resistant sublines of rat brain tumors in vivo.

Two variant cells lines resistant to the nitrosourea derivative ACNU ((1-4-amino-2-methyl-5-pyrimidinyl)-methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride), namely C6/ACNU and 9L/ACNU, were selected in vivo from rat brain tumors. Stable resistance to ACNU proved to be a characteristic of these cell lines, whether they were grown in vivo or in vitro. These cell lines exhibited a different pattern of cross-resistance to a wide range of chemotherapeutic agents with dissimilar chemical structures and mechanisms of action as compared with that of other ACNU-resistant cell lines established in vitro. Distinct cross-resistance was observed in both the C6/ACNU and 9L/ACNU cell lines to chloroethyl-nitrosoureas such as BCNU (carmustine), CCNU (lomustine), and methyl CCNU and, additionally, to vincristine, vinblastine, Adriamycin (doxorubicin), and arabinosylcytosine, but not to bleomycin, methotrexate, cis-platinum, and 5-fluorouracil. This might point to a multifactorial mechanism of drug resistance in ACNU-resistant cell lines derived from rat C6 and 9L brain tumor cells.

Animals↗
PubMed1996

Salvage chemotherapy for oligodendroglioma.

The authors present their experience with salvage chemotherapy for oligodendroglioma, an uncommon brain tumor that responds predictably to PCV (procarbazine, lomustine (CCNU), and vincristine) when given as initial therapy. The authors reviewed the records of patients with oligodendrogliomas who received a second, third, or fourth cytotoxic regimen prescribed to combat tumor recurrence documented by computerized tomography or magnetic resonance imaging following an initial chemotherapy program. Initial regimens were prescribed at various time points: as neoadjuvant therapy prior to radiotherapy, as adjuvant therapy in conjunction with radiotherapy, or at recurrence following radiotherapy. Response criteria were based on measurable changes in tumor size following published guidelines. Twenty-three patients (14 men and nine women) aged 25 to 58 years (median 36 years) received 33 salvage regimens. When non-PCV chemotherapy had been the prior regimen, seven (88%) of eight patients responded to salvage chemotherapy, all seven (100%) responding to PCV. Administration of PCV was effective after regimens of carmustine and CCNU but was ineffective after prior administration of PCV. When PCV had been given any time previously, only four (19%) of 21 patients responded to salvage chemotherapy; however, four (40%) of 10 patients who received etoposide (VP-16)/cisplatin (CDDP) responded. Despite the small number of patients, two noteworthy trends emerge from these data: first, PCV is a highly effective salvage treatment when used at tumor recurrence following non-PCV chemotherapy regimens, and second, the synergistic combination of VP-16 and CDDP may exert substantial anti-oligodendroglioma activity, and it warrants further evaluation.

Adult↗
PubMed1992

High dose chemotherapy and autologous bone marrow transplantation in advanced Hodgkin's disease.

OBJECTIVE: To present the use of high dose chemotherapy with autologous bone marrow transplantation as salvage therapy for advanced Hodgkin's disease in Australia. DESIGN: A prospective open study for patients whose disease was resistant to conventional treatment. SETTING: The bone marrow transplantation units of four Australian tertiary hospitals. PATIENTS: Seventeen patients (median age 30 years) entered and completed the study. The stage of the disease at initial diagnosis was I or II (seven patients), III (seven patients) and IV (three patients). Histological types were lymphocyte predominant (one), nodular sclerosis (12), mixed cellularity (three) and unknown (one). Therapy before consideration for transplantation included radiotherapy (13), mustine, vincristine, procarbazine and prednisone (MOPP--17 patients) or doxorubicin, bleomycin, vinblastine and dacarbazine (ABVD--13 patients) and other chemotherapy regimens (five). The median interval from diagnosis to transplantation was 29 months (range, 9-178 months). The patient's disease was classified as sensitive (nine) or resistant (eight) to treatment, depending on the response to the most recent course of chemotherapy. INTERVENTIONS: Morphologically normal autologous bone marrow was harvested and cryopreserved. The conditioning regimen given was cyclophosphamide, carmustine and etoposide (14) or busulphan and cyclophosphamide (three). The marrow was then infused. MAIN OUTCOME MEASURES: Remission (complete or partial), disease-free survival and overall survival. RESULTS: Over all, 10 of 17 patients (59%) entered or remained in complete remission and four of 17 (24%) achieved partial remission. The overall actuarial survival at 30 months was 70%. Eight of the nine patients with treatment-sensitive disease (89%) remain disease-free at a median of 22 months (range, 18-29 months) after transplantation. Two of the eight patients with resistant disease (25%) are disease-free at 20 and 28 months. There was one procedure-related death from haemorrhage and four disease-related deaths at six, seven, eight and 13 months after transplantation. CONCLUSION: Autologous bone marrow transplantation may provide an effective salvage therapy in advanced Hodgkin's disease, particularly for patients with treatment-sensitive disease and a low tumour burden.

Adult↗
PubMed1999

Incidence of tumor-cell contamination in leukapheresis products of breast cancer patients mobilized with stem cell factor and granulocyte colony-stimulating factor (G-CSF) or with G-CSF alone.

We have assessed tumor contamination of peripheral blood progenitor cells (PBPC) in 203 high-risk breast cancer patients who were prospectively randomized to mobilization with stem cell factor (SCF) plus granulocyte colony-stimulating factor (G-CSF) versus G-CSF alone. The patients then received high-dose cyclophosphamide, cisplatin, and carmustine (BCNU) with PBPC support. One bone marrow aspirate obtained before treatment, one whole blood specimen obtained before cytokine infusion, and one to five leukapheresis products were tested for the presence of tumor cells by an alkaline phosphatase immunocytochemical technique with a targeted sensitivity of 1.7 tumor cells per 10(6) hematopoietic cells. Tumor cells were detected in the bone marrow, peripheral blood, and/or PBPC of 21 patients (10%). In 14 patients, bone marrow specimens were tumor-positive; in seven patients, premobilization whole blood specimens were tumor-positive, and in eight patients, leukapheresis products were tumor-positive. In five patients, repetitive or multiple specimens were tumor-positive, and in three cases, marrow, peripheral blood, and PBPC products were all tumor-positive. Nine of the patients in whom tumor cells were found in marrow or peripheral blood were clinical stage II to III and 12 were clinical stage IV. Nine of the tumor-positive patients were in the SCF + G-CSF arm and 12 were in the G-CSF arm. Tumor cells were detected in leukapheresis products of eight patients: three in the G-CSF + SCF arm and five in the G-CSF arm. We conclude that detectable tumor-cell contamination of bone marrow, peripheral blood, and/or PBPC occurred in approximately 10% of patients in this trial and was observed in stage II to III patients, as well as in stage IV patients. No significant difference could be found in the rate of PBPC tumor-cell contamination between patients who received SCF + G-CSF compared with those who received G-CSF alone. Neither mobilization regimen was found to increase the rate of tumor-cell contamination when control premobilization blood samples were compared with leukapheresis products.

Breast Neoplasms↗
PubMedDate not supplied

[Long-term follow-up of 2 therapeutic programs for the treatment of high-risk childhood acute lymphoblastic leukemia. Experience at the 20 de Noviembre National Medical Center].

This paper reports the long-term, disease-free survival of children with high-risk (HR) acute lymphoblastic leukemia (ALL) treated with two different chemotherapy regimens. HR was defined in children with ALL, younger than 2 or older than 10 years, with or without initial extrahematopoietic disease, with a leukocyte count higher than 25 x 10(9)L, or with L3 FAB type. The first group, LAL1, included 67 patients; they received induction with vincristine (VCR) and prednisone (PDN), early consolidation with 3 cycles of 6-mercaptopurine (6MP), citarabine (ARA) and VCR: central nervous system (CNS) prophylaxis (PFX) consisted of both chemotherapy in induction, consolidation and maintenance, radiotherapy (RT) in consolidation. Maintenance was given with 6MP, methotrexate (MTX), VCR adriamycin (ADR), ARA, cyclophosphamide (CFA) and PDN. The second group, LAL2, with 45 patients, received induction with VCR, PDN, CFA, epirrubicin (EPI), L-Asparaginase (L-ASP); early and late consolidation with 6MP, ARA, VCR, carmustine (BCNU), CFA, EPI, MTX and teniposide 8VM26): CNS PFX consisted of both chemotherapy in induction, consolidation and maintenance, RT in consolidation, maintenance with 6MP, MTX, EPI, CFA, ARA VM26 and BCNU. At the time of diagnosis, both groups were comparable. Disease-free survival probability, for LAL1 group was 0.41 at 14 years and for LAL2 group 0.34 at 8 years (p = 0.45). In the LAL1 group there were three failures and 20 relapses, and in the LAL2 group, there were two failures and 22 relapses. CNS relapses were one and seven in LAL1 and LAL2 groups respectively (p = 0.04). In the LAL2, group relapses were more frequent in patients with dose reduction or difered dose due to marrow toxicity (p = 0.02). We believe that the increase in CNS relapse in the LAL2 group was caused by the late administration of CNS PFX. We also believe that although intensive chemotherapy can increase long-term survival, dose adjustments due to marrow toxicity have a negative effect on long-term, relapse-free survival.

Adolescent↗
PubMedDate not supplied

Multidrug resistant malignant melanoma with intracranial metastasis responding to immunotherapy.

Metastatic malignant melanoma (MM) is well known for its poor response to chemotherapy, radiotherapy, and its remarkable susceptibility to interleukin-2 (IL-2) based immunotherapies. MM with brain metastatis in particular, has 4-5 months life expectancy from metastasis to death. Drug efflux pumps such as P-glycoprotein (P-gp), or drug detoxifying mechanisms e.g. glutathion epsilon S-transferase-pi (GST) are some of the possible multidrug resistance (MDR) mechanisms in MM. Here we report the first P-gp+ MDR MM with brain metastasis in the literature, demonstrating a remarkable response to IL-2, interferon-alpha (IFN), 5-fluorouracil (5FU) regimen. A 41-year old man was admitted with multiple inoperable brain lesions. Biopsies from intracranial and dermal lesions revealed MM. Cisplatin, carmustine, dacarbazine, tamoxifen (CCDT) together with external cranial radiotherapy were administered, and partial response in lesions and symptoms was achieved. However, after the third course of CCDT treatment, he was admitted to the emergency ward with dramatically increased intracranial lesions, and recurring dermal lesions. A biopsy from the recurred lesions revealed that MM cells were P-gp+, but GST. Administration of a IL-2, IFN and 5FU regimen achieved a remarkable decline in the brain lesions with almost total disappearance of symptoms. He was well and capable of doing work for 18 months. Dermal lesions had not recurred since the beginning of immunotherapy. In contrast, another 34-year old man who developed brain metastases after CCDT for MM, was negative for P-gp and GST. Cranial radiotherapy was started and the above mentioned IL-2 based regimen was administered. However, no response was observed. These two cases together with previous studies demonstrating the susceptibility of P-gp+ MDR cancer cell lines to IL-2 activated killer (LAK) cells in this report suggest that P-gp+ MDR MM is probably a good candidate for IL-2 based treatments.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2000

Immunobiologic, cytogenetic and drug response features of a newly established cell line (SCRC-1) from renal small cell carcinoma.

PURPOSE: We describe the establishment and preliminary characterization of a cell line designated SCRC-1, which was derived from a primary renal small cell carcinoma. MATERIALS AND METHODS: Continuous cultures of a primary stage IVa renal small cell carcinoma and a xenograft in nude mice derived therefrom were characterized by immunohistology, electron microscopy, immunofluorescence/flow cytometry, cytogenetic analysis, and an in vitro drug resistance assay. RESULTS: SCRC-1 cells were reactive with antibodies to NSE, chromogranin-A, bombesin, Bcl-2, CD44s, CD44v6, CD44v7 to 8, vimentin and S100 protein (predominantly beta-subunit), and were unreactive with antibodies to EMA, CD54, EGFR(R1), URO-5, URO-7, URO-8 and URO-10. A similar immunoprofile was also found in both the primary tumor and the xenograft. Cytogenetic analysis revealed the following common clonal aberrations in all 50 metaphases analyzed: 45, XX, t (X;10;18) (p11;p11;q11), -der(18)t(X;10;18), indicating the clonal nature of this neoplasm. SCRC-1 cells showed low drug resistance to cyclophosphamide, doxorubicin, gemcitabine and fluorouracil, intermediate resistance to carmustine and mitomycin-C, and extreme resistance to cisplatin. CONCLUSION: We have documented the initial characterization of SCRC-1, which may be the first cell line reported to be derived from a primary small cell carcinoma of the kidney. This cell line can be used for further studies uncovering the biology and histogenesis of this rare cancer and delineating differences among small cell carcinomas of the kidney and other histological types.

Adult↗
PubMed2000

Macrophage inflammatory protein 1alpha attenuates the toxic effects of temozolomide in human bone marrow granulocyte-macrophage colony-forming cells.

Macrophage inflammatory protein 1alpha (MIP-1alpha) is a chemokine that may act principally by preventing hemopoietic cells from entering G1, thereby attenuating the cytotoxic effects of cell cycle-specific chemotherapeutic agents. Here we examine the effect of MIP-1alpha on the sensitivity of human granulocyte-macrophage hemopoietic progenitor cells (granulocyte-macrophage colony-forming cells; GM-CFCs) with the cytotoxic effects of antitumor agents that act mainly via alkylation at the O6 position of guanine in DNA. Mononuclear cell preparations from human bone marrow were used in an in vitro GM-CFC colony-forming assay. The GM-CFC survival from individual patients displayed a range of sensitivities to the methylating agent temozolomide [(Tz) 20-55% survival at 10 microg/ml Tz]. However, in all 16 cases, MIP-1alpha (50 ng/ml) protected against GM-CFC killing: survival in the presence of MIP-1alpha ranged from 65-97% at 10 microg/ml Tz, with GM-CFCs being 1.5-4.5-fold more resistant than control cells from the same patient. The highest levels of protection were seen in the GM-CFCs with the highest sensitivity in the absence of MIP-1alpha. Similar degrees of protection were seen for the methylating agent streptozotocin, but no protection was detected for the chloroethylating agents carmustine or mitozolomide in the samples for which there was protection against the toxic effects of Tz. Whereas the mechanism of this effect remains to be established, the results may have potential immediate clinical application in the attenuation of hematological toxicity after administration of methylating antitumor agents.

Antineoplastic Agents, Alkylating↗
PubMed2000

Autologous bone marrow transplantation for patients with acute myeloid leukaemia: prospective follow-up study.

OBJECTIVE: To study the use of autologous bone marrow transplantation to treat acute myeloid leukaemia when complete remission had been achieved and when no human leukocyte antigen matched related donor was available. DESIGN: Prospective follow-up study. SETTING: Government hospital, Hong Kong. PATIENTS: Eight patients (median age, 34 years [range, 16-45 years]) with acute myeloid leukaemia in whom complete remission had been achieved. INTERVENTION: Conditioning regimen of carmustine, amsacrine, etoposide VP-16, cytarabine, and infusion of unpurged marrow. MAIN OUTCOME MEASURES: Median time taken to reach neutrophil and platelet counts of > or =0.5 x 10(9) /L and > or = x 10(9) /L, respectively; mortality and relapse rates; and follow-up regimens used. RESULTS: Engraftment was successfully achieved in all patients and there were no early procedure-related mortalities. The median times required to reach a neutrophil count of > or =0.5 x 10(9) /L and a platelet count of > or =20 x 10(9) /L were 30 days (range, 18-36 days) and 38 days (range, 15-53 days), respectively. The median duration of hospital stay was 37 days (range, 25-43 days). Two patients died of a relapse of leukaemia at 6 and 9 months post-transplantation. Two patients experienced relapses: one at 8 months post-transplantation, for which conventional chemotherapy was restarted, and one at 18 months; treatment with all-trans-retinoic acid and conventional chemotherapy achieved a third complete remission in the latter patient, who had acute promyelocytic leukaemia. Continuous remission has been achieved in four of the eight patients after a median follow-up duration of 26 months (range, 6-43 months). CONCLUSION: Autologous bone marrow transplantation is an acceptable treatment for patients with acute myeloid leukaemia who lack a human leukocyte antigen-matched related donor.

Acute Disease↗
PubMed2000

Induction of apoptosis in human prostatic cancer cells with beta-glucan (Maitake mushroom polysaccharide).

PURPOSE: To explore more effective treatment for hormone-refractory prostate cancer, we investigated the potential antitumor effect of beta-glucan, a polysaccharide of the Maitake mushroom, on prostatic cancer cells in vitro. MATERIALS AND METHODS: Human prostate cancer PC-3 cells were treated with various concentrations of the highly purified beta-glucan preparation Grifron-D(R) (GD), and viability was determined at 24 h. Lipid peroxidation (LPO) assay and in situ hybridization (ISH) were performed to unravel the antitumor mechanism of GD. RESULTS: A dose-response study showed that almost complete (>95%) cell death was attained in 24 h with GD > or = 480 microg/mL. Combinations of GD in a concentration as low as 30 to 60 microg/mL with 200 microM vitamin C were as effective as GD alone at 480 microg/mL, inducing >90% cytotoxic cell death. Simultaneous use with various anticancer drugs showed little potentiation of their efficacy except for the carmustine/GD combination (approximately 90% reduction in cell viability). The significantly (twofold) elevated LPO level and positive ISH staining of GD-treated cells indicated oxidative membrane damage resulting in apoptotic cell death. CONCLUSION: A bioactive beta-glucan from the Maitake mushroom has a cytotoxic effect, presumably through oxidative stress, on prostatic cancer cells in vitro, leading to apoptosis. Potentiation of GD action by vitamin C and the chemosensitizing effect of GD on carmustine may also have clinical implications. Therefore, this unique mushroom polysaccharide may have great a potential as an alternative therapeutic modality for prostate cancer.

Agaricales↗
PubMed2000

High dose therapy and autologous stem cell transplantation for human immunodeficiency virus-associated non-Hodgkin lymphoma in the era of highly active antiretroviral therapy.

BACKGROUND: The advent of highly active antiretroviral therapy (HAART) has allowed the exploration of more dose-intensive therapy such as autologous stem cell transplantation (ASCT) in selected patients with human immunodeficiency virus (HIV)-associated non-Hodgkin lymphoma (NHL). METHODS: The authors report on the use of myeloablative chemotherapy with ASCT in two HIV positive patients with NHL. The first patient underwent ASCT at the time of first disease remission for poor risk, diffuse, large cell NHL and the second patient had multiply recurrent, chemosensitive Burkitt lymphoma. ASCT was performed in both patients using a transplant conditioning regimen of high dose cyclophosphamide, carmustine, and etoposide (CBV). RESULTS: The target dose of >/= 5 x 10(6)/kg CD34 positive peripheral blood stem cells (PBSC) utilized for ASCT was collected using granulocyte-colony stimulating factor (G-CSF) after chemotherapy for mobilization while both patients were receiving concomitant HAART for HIV infection. HAART was continued during CBV conditioning. Prompt hematopoietic recovery was observed after ASCT. Both patients remained in clinical disease remission from their lymphoma at 28 months and 20 months after transplant, respectively. CONCLUSIONS: ASCT is feasible in patients with HIV-associated NHL. Adequate numbers of CD34 positive PBSC can be procured from patients receiving HAART and chemotherapy for NHL. Selected patients with HIV-related lymphoma can tolerate the high dose CBV myeloablative chemotherapy regimen without increased acute regimen-related toxicity. Reinfusion of G-CSF-mobilized PBSC can lead to rapid recovery of hematologic function and sustained engraftment after ASCT. Given the poor prognosis of patients with HIV-associated NHL treated with conventional chemotherapy, further investigation of this approach should be considered.

Adult↗
PubMed2000

[Anti-tumor drugs in the therapy of brain tumors].

In order to improve the quality of life and its duration, beside surgical operation with a patient with brain cancer, chemotherapy alone or in combination with radiotherapy may be applied in some cases. There are different protocols of chemotherapeutics (anticarcinomatous drugs) which are applied in treatment of some sorts carcinoma. The success of the therapy depends on the type and stage of the carcinoma, condition of patient well as of anticarcinomatous characteristics of the drug. Performed studies indicated that the life of the patients with glioblastom and astrocitom was prolonged through the application of carmustine or lomustine protocol of chemotherapy after x-rays. New anticarcinomatous drugs and new ways of application are investigated.

Antineoplastic Agents↗
PubMed2000

[High-dose chemotherapy in the treatment of children with malignant lymphoma].

BACKGROUND: Children with primary refractory or recurrent malignant lymphoma have usually poor prognosis. Less than 10% of those, who were treated with conventional-dose regimens had survived for 2 years. In an attempt to improve the outcome for these patients, we explored the role of consolidation high-dose chemotherapy with autografting. METHODS AND RESULTS: Forty-five patients with poor-prognosis lymphoma, of whom 27 were males, underwent megatherapy between January 1992 and December 1999. High-dose chemotherapy was indicated in patients with poor initial response to first-line chemotherapy (14 cases) or in the relapse (31 cases). The group consisted of 27 patients with Hodgkin's disease and 18 patients with non-Hodgkin's lymphoma. The median age was 14.7 years. The conditioning for Hodgkin's disease patients contained cyclophosphamide, etoposide and busulfan or carmustine. Patients with non-Hodgkin's lymphomas received cyclophosphamide, etoposide and busulfan or total body irradiation. Bone marrow was used as the source of haemopoietic stem cells in ten patients, peripheral blood in twenty-eight, and both sources were used in seven patients. After the median follow-up of 47 months, the final survival was 61%. Eleven patients died of the disease progression, four of the infectious complications, one at a car accident. Median time to relapse after the transplantation was 7.5 months. CONCLUSIONS: Further improvement of these results will require earlier transplantation, improved preparative regiments or early posttransplant immunotherapy.

Adolescent↗