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At least 433 records · Page 24Linked to original sources
PubMed2006

Ototoxicity of cisplatin plus standard radiation therapy vs. accelerated radiation therapy in glioblastoma patients.

PURPOSE: To assess the effect of cisplatin (CDDP) plus concurrent radiation therapy on hearing loss. METHODS: 451 patients with glioblastoma multiforme (GBM) were randomly assigned after surgery to: Arm A: Carmustine (BCNU) + standard radiation therapy (SRT); Arm B: BCNU + accelerated radiation therapy (ART: 160 cGy twice daily for 15 days); Arm C: CDDP + BCNU + SRT; or Arm D: CDDP + BCNU + ART. Patients on arms C and D received audiograms at baseline, and prior to the start of RT, and prior to cycles 3 and 6. Otologic toxicities were recorded at each visit. RESULTS: 56% of patients had hearing loss at baseline. 13% and 50% of patients experienced worsening ototoxicity after 1 year of treatment in arms A and B vs. C and D, respectively, with 13% of those on arms C and D experiencing significant ototoxicity (>or= grade 3) at 6 months. Increasing age was associated with an increased risk of ototoxicity. CONCLUSIONS: Increased exposure to CDDP increases the risk of ototoxicity over time. Older patients are more susceptible to hearing loss with CDDP. The low proportion of patients with clinically significant ototoxicity suggests that baseline screening is unnecessary in GBM patients.

Adult↗
PubMed2006

Monitoring the effects of BCNU chemotherapy Wafers (Gliadel) in glioblastoma multiforme with proton magnetic resonance spectroscopic imaging at 3.0 Tesla.

Carmustine wafers (Gliadel Wafer) are implanted at resection in some patients with high-grade gliomas. Studies suggest that proton magnetic resonance spectroscopic imaging ((1)H MRSI) demonstrates early changes predictive of future failure or response to systemic chemotherapy. This study explores (1)H MRSI as a means to assess peri-tumoral tissue response post-resection and Gliadel((R)) implantation in patients with high-grade gliomas. Pilot (1)H MRSI data are presented that demonstrate noninvasive, serial monitoring of metabolic changes at the tumor site following Gliadel implantation. Three patients with newly diagnosed glioblastoma multiforme (GBM) underwent MRI and (1)H MRSI at 3.0 Tesla prior to resection and at 3-5 and > or =12 weeks post-operatively. Baseline MRS spectra of tumor tissue from all patients were characterized by marked increases of choline (CHO) and lactate (LAC), and a decrease of N-acetylaspartate (NAA), typical of GBM compared with normal contra-lateral brain tissue. Post-operatively, spectra were analyzed from the resection cavity and peri-tumoral regions and compared with normal tissue from the contra-lateral brain at baseline. In 2 of 3 patients, peri-tumoral NAA/CRE increased and CHO/NAA decreased compared to contra-lateral brain at 3-5 weeks compared with baseline following Gliadel therapy and surgery but prior to radiotherapy. This study indicates that (1)H MRSI has the ability to localize regions of heterogeneous response following Gliadel treatment. Although data are limited, these results suggest that metabolic indicators of outcome can be successfully monitored pre- and post-surgical resection and Gliadel implantation with (1)H MRSI. Additional study of patients receiving Gliadel Wafers using (1)H MRSI may serve to aid clinicians in assessing tumor regression and gauging efficacy of this chemotherapy treatment.

Aged↗
PubMed1985

Age and the treatment of multiple myeloma. Southeastern Cancer Study Group experience.

To determine the impact of age upon the response to treatment, survival, and toxicity of chemotherapy for multiple myeloma, the results of a large cooperative group trial were examined. Patients were randomly assigned to induction therapy with either carmustine, cyclophosphamide, and prednisone or melphalan and prednisone; patients with response received two years of treatment. The age distribution of patients in this trial compared with the incidence figures from the Surveillance Epidemiology and End Results (SEER) study shows a degree of under-representation of the oldest patient groups. Prognostic factors were evenly distributed over the age range and treatment groups. Older patients had responses and survival rates equivalent to younger patients and with both treatment regimens regardless of prognostic factor characteristics. Hematologic toxicity was no greater for the older group in either regimen despite the presence of a nitrosourea in one. Gastrointestinal toxicity was increased in the older patients who received the regimen of melphalan and prednisone. The study suggests that in myeloma and perhaps other such chemotherapy-responsive malignancies treated with moderately intense chemotherapy, without bone marrow ablation, elderly and younger patients have similar outcomes.

Adult↗
PubMed1996

Retrovirus-mediated transfer of the human O6-methylguanine-DNA methyltransferase gene into a murine hematopoietic stem cell line and resistance to the toxic effects of certain alkylating agents.

O6-Methylguanine-DNA methyltransferase (MGMT) is an important DNA repair protein that plays a key role in cancer chemotherapy by alkylating agents such as carmustine (BCNU) and Dacarbazine (DTIC). Therapy by BCNU and DTIC is reduced by dose-limiting hematological toxicity as a result of low MGMT repair activity in bone marrow cells. In this study, we have constructed a Moloney murine leukemia virus retroviral vector containing the human mgmt gene. High-titer retrovirus producer cells lines have been generated. Retroviral-mediated transfer of the human mgmt gene into murine multi-potent hematopoietic stem cells, FDCP-1, resulted in the expression of a high level of MGMT activity. In comparison with the control cells that were transduced with the parent vector, the MGMT-expressing clones were considerably more resistant to the cytotoxicity of the methylating agents, such as N-methyl-N'-nitro-N-nitrosoguanidine, N-nitroso-N-methyl-urea, and temozolomide, as well as the chloroethylating agents 1-(2-chloroethyl)-1-nitrosourea and BCNU. The protection provided by MGMT could be eliminated by the MGMT inactivator O6-benzylguanine. Thus, the principal lethal lesions produced by these alkylating agents in the murine hematopoietic stem cells and the MGMT deficiency in these cells can be complemented by retroviral-mediated gene transduction.

3T3 Cells↗
PubMed1991

GM-CSF instead of autologous bone-marrow transplantation after the BEAM regimen.

Five patients with resistant non-Hodgkin lymphoma (NHL) were given granulocyte-macrophage colony-stimulating factor (GM-CSF, 250 micrograms/m2 daily) after the BEAM pretransplant chemotherapy regimen (carmustine 300 mg/m2, etoposide 1.2 g/m2, cytarabine 800 mg/m2, melphalan 140 mg/m2) because persistent lymphoma cell infiltration of the bone marrow precluded autologous bone-marrow transplantation (BMT). In three patients full haemopoietic reconstitution occurred, with similar kinetics to that seen after autologous BMT. The other two patients died without sustained haemopoietic recovery. GM-CSF may replace autologous BMT in highly selected cases of NHL with progressive disease and bone-marrow involvement.

Adolescent↗
PubMed1993

Dose intensification with autologous bone-marrow transplantation in relapsed and resistant Hodgkin's disease: results of a BNLI randomised trial.

High-dose chemotherapy and radiotherapy with autologous bone-marrow transplantation (ABMT) are increasingly used for the treatment of relapsed and resistant Hodgkin's disease, although there has been no randomised trial of this treatment. The British National Lymphoma Investigation therefore undertook a randomised comparison of high-dose chemotherapy (BEAM = carmustine, etoposide, cytarabine, and melphalan) plus ABMT with the same drugs at lower doses not requiring bone-marrow rescue (mini-BEAM) in patients with active Hodgkin's disease, for whom conventional therapy had failed. 20 patients were assigned treatment with BEAM plus ABMT and 20 mini-BEAM. All have been followed up for at least 12 months (median 34 months). 5 BEAM recipients have died (2 from causes related to ABMT and 3 from disease progression) compared with 9 mini-BEAM recipients (all disease progression). This difference was not significant (p = 0.318). However, both event-free survival and progression-free survival showed significant differences in favour of BEAM plus ABMT (p = 0.025 and p = 0.005, respectively). Recruitment to the trial became increasingly difficult because patients refused randomisation and requested ABMT. It was therefore closed early (40 patients rather than 66 intended). Nevertheless, we found a dose-response effect in these patients with relapsed and resistant Hodgkin's disease. High doses facilitated by ABMT can lead to better disease-free survival.

Adolescent↗
PubMed1988

Preliminary experimental results with the nitrosourea derivative ACNU in the treatment of malignant gliomas.

Comparative studies were carried out to evaluate the cytotoxic effectiveness of the nitrosureas ACNU (Nimustine) and BCNU (Carmustine) at equitoxic dose levels in xenografts from two astrocytomas grades III/IV (Li, Re) and one oligodendroglioma grade III (Oe) on nude mice. Growth delay was measured as the endpoint. All tumours were characterized initially and at regular intervals in later passages as to their histomorphologic pattern, expression of glial fibrillary acid protein and DNA-content by means of flow cytometry. These characteristics were shown to be unchanged in our xenografts over more than 27 passages. Growth delays of 18.7 days (ACNU) and 2.4 days (BCNU) for the Li-xenograft (p less than 0.01) were observed at an LD10 for both drugs. For the Re- and Oe-xenografts, growth delays of 18.0 vs. 14.0 days (p less than 0.001) and greater than 27.0 vs. 14.2 days (p less than 0.02) were observed at an equitoxic dose of 33 mg/kg ACNU or BCNU i.p., respectively. These preclinical data suggest a therapeutic advantage with ACNU for these high grade gliomas and should encourage further experimental and clinical investigations.

Animals↗
PubMed1990

Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report.

Data from Northern California Oncology Group protocol 6G61, which was closed in February 1983, were reanalyzed in December 1988. The protocol called for a randomized trial that compared the effects of following 60 Gy radiation/oral hydroxyurea treatment with either carmustine (BCNU) or the combination of procarbazine, lomustine (CCNU), and vincristine (PCV) for two histologic strata: glioblastoma multiforme and other anaplastic gliomas. PCV produced longer survival and time to tumor progression than BCNU for both histologic groups, although the difference was statistically significant only for the anaplastic gliomas. With PCV treatment, time to progression and survival doubled for anaplastic glioma patients in the 50th and 25th percentiles.

Adult↗
PubMed1992

Enhancement of alkylating agent activity in vitro by PD 128763, a potent poly(ADP-ribose) synthetase inhibitor.

The ability of DNA repair inhibitors to potentiate alkylating agent cytotoxicity was explored with PD 128763, a dihydroisoquinolinone known to effectively inhibit poly(ADP-ribose) synthetase. The cytotoxic activity of streptozotocin in L1210 leukemia cells was maximally potentiated (7-fold decrease in IC50) under conditions of 24 hr exposure to PD 128763 following treatment with the alkylating agent for 1 hr. Similar treatment conditions resulted in a much greater effect (36-fold enhancement in activity) for the 2-nitroimidazole RSU 1069. In contrast, 3-aminobenzamide was only weakly effective at enhancing activity of either streptozotocin or RSU 1069 (2-3 fold potentiation). However, PD 128763 was ineffective at potentiating the cytotoxicity of the bifunctional alkylating agents carmustine (BCNU) and lomustine (CCNU). Our results are consistent with a role for (poly-ADP) ribosylation in the repair of monofunctional alkylating agent damage. This study supports further exploration of the combination of PD 128763 and RSU 1069 as a potentially useful chemotherapeutic regimen.

Alkylating Agents↗
PubMed1992

Post-mastectomy radiotherapy following adjuvant chemotherapy and autologous bone marrow transplantation for breast cancer patients with greater than or equal to 10 positive axillary lymph nodes. Cancer and Leukemia Group B.

Between 2/87 and 2/91, 49 women with operable breast cancer involving greater than or equal to 10 axillary nodes were treated following mastectomy, with four cycles of Cyclophosphamide, Adriamycin, 5FU, followed by high doses of Cyclophosphamide, Cisplatin, Carmustine (HDCT) with autologous bone marrow transplant support. Forty patients received local-regional radiotherapy (generally to the chest wall, internal mammary, supraclavicular, +/- axillary nodal areas; minimum 44-50 Gy, 1.8-2 Gy/fraction, +/- 10-15 Gy scar boost; standard radiation techniques). The first nine patients did not receive local-regional radiotherapy. Three developed a local-regional failure (6-12 months after HDCT); six are without evidence of disease. Local-regional radiotherapy (LR XRT) was delivered to the subsequent 40 patients following HDCT+autologous bone marrow transplant. Six received less than 44 Gy of the planned local-regional radiotherapy due to significant toxicity and one of these failed locally. Only one local failure was observed among the 34 patients who received greater than or equal to 44 Gy. Two additional patients developed distant metastases. None of these 40 patients have failed in the axilla despite the fact that the axilla was irradiated in only 18 cases. Overall, 36/40 (90%) of these patients are without evidence of disease 4-30 months following HDCT (approximately 10-36 months after mastectomy, median 22 months). Radiotherapy was interrupted or discontinued because of progressive dyspnea, thrombocytopenia, or neutropenia in nine patients. Further studies to determine the roles of local-regional radiotherapy and HDCT in the development of these toxicities are underway. These encouraging results suggest that HDCT + autologous bone marrow transplant+local-regional radiotherapy may improve the survival rate in these high risk patients. A national randomized study to test the efficacy of this HDCT regimen is currently underway (Cancer and Leukemia Group B#9082 and Southwest Oncology Group #9114).

Adenocarcinoma↗
PubMed1992

Induction of resistance to 6-thioguanine and cytarabine by a range of anticancer drugs in Chinese hamster AA8 cells.

A mutagenicity assay using AA8 Chinese hamster cells has been used to explore the potential of some currently used clinical anticancer drugs to induce cells resistant to 6-thioguanine and cytarabine. Preliminary experiments gave evidence of a "low dose" and "high dose" resistance to cytarabine, and subsequent work considered only the latter of these events. When ethyl methane sulphonate was used as a reference mutagen, induced resistance to cytarabine developed substantially later and at a lower frequency than resistance to 6-thioguanine. Of the clinical drugs tested, carmustine showed the highest ability to induce either 6-thioguanine or cytarabine resistant cells. Bleomycin, daunomycin and amsacrine showed moderate ability, while vincristine was essentially inactive in these assays. Such information could potentially be used in selecting new drug combinations or timing of drug administration in cancer chemotherapy.

Amsacrine↗
PubMed1992

High-dose chemotherapy and autologous bone marrow transplantation for relapsed and refractory Hodgkin's disease.

The results of high-dose chemotherapy with melphalan or melphalan (carmustine) etoposide for 66 consecutive patients with relapsed or resistant Hodgkin's disease are described. 55 patients were evaluable for response and 22% of these achieved complete remission and 59% partial remission. The actuarial survival at 2 years was 45% and the principal factors determining survival were the sensitivity of the disease to therapy given before high-dose chemotherapy and the type of treatment received. Intensive chemotherapy with autologous bone marrow transplantation can produce long-term survivors among patients for whom long-term survival would otherwise be improbable. However, this treatment remains toxic with an uncertain place in management.

Adolescent↗
PubMed1992

Treatment of melphalan-resistant multiple myeloma with vincristine, BCNU, doxorubicin, and high-dose dexamethasone (VBAD).

A total of 65 patients (35 male/30 female) with multiple myeloma primarily (33) or secondarily (32) resistant to melphalan and prednisone were treated with vincristine, carmustine (BCNU), doxorubicin, and high-dose dexamethasone (VBAD) at 4-week intervals. Among 60 evaluable patients the overall response was 36.6% (21.6% objective response plus 15% improvements). The response rate was significantly higher in primarily resistant patients than in those becoming resistant after a prior response (48.4 vs. 24.1%, P < 0.05). The median duration of response was 17.5 months. When survival of responders and non-responders were compared by the conventional method, a highly significant difference was observed (P < 0.001). However, using the Mantel and Byar procedure and the landmark method, only a trend for longer survival in the responders was registered. These results indicate that although VBAD is effective in at least one third of patients with advanced multiple myeloma resistant to melphalan, its impact on survival is limited.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

A phase Ib clinical trial of PV701, a milk-derived protein extract, for the prevention and treatment of oral mucositis in patients undergoing high-dose BEAM chemotherapy.

Despite the best available agents to prevent mucositis, most patients receiving high-dose chemoradiotherapy regimens experience severe mucositis, and new therapies are needed. In this study, we evaluated the safety and tolerability of a milk-derived growth factor extract (PV701 mouthwash) intended to prevent oral mucositis (OM) after carmustine, etoposide, cytosine arabinoside, and melphalan (BEAM) chemotherapy. PV701 mouthwash (15 mL x 13.5 mg/mL) was administered 6 times a day for 12 days, from day--6 to day +5, to patients with lymphoma, who were given BEAM on day--6 to day--2, with autologous stem cells infused on day 0. Dose de-escalation of PV701 was planned if dose-limiting toxicities occurred. The severity and duration of OM, the duration of enteral/parenteral feeding, the requirement for intravenous opiates, and admission to intensive care were recorded. Outcomes were also compared with those of historical control patients. Nine patients received PV701 13.5 mg/mL. PV701 was well tolerated, and no dose-limiting toxicities were observed. Compared with 89 historical controls, the 9 PV701-treated patients had significantly less frequent grade 2 or 3 OM ( P=.0006) and had grade>or=3 OM for an estimated 5 fewer days ( P=.0003). There was a reduction in the need for enteral/parenteral feeding ( P=.012), its duration ( P=.010), and its frequency ( P=.022) and in the duration of intravenous opiates ( P=.0006). We conclude that PV701 mouthwash is readily administered with minimal side effects at a dose of 1215 mg/d, and further investigation of this agent is warranted.

Adult↗
PubMed2005

Differential inhibition of cellular glutathione reductase activity by isocyanates generated from the antitumor prodrugs Cloretazine and BCNU.

The antitumor, DNA-alkylating agent 1,3-bis[2-chloroethyl]-2-nitrosourea (BCNU; Carmustine), which generates 2-chloroethyl isocyanate upon decomposition in situ, inhibits cellular glutathione reductase (GR; EC 1.8.1.7) activity by up to 90% at pharmacological doses. GR is susceptible to attack from exogenous electrophiles, particularly carbamoylation from alkyl isocyanates, rendering the enzyme unable to catalyze the reduction of oxidized glutathione. Evidence implicates inhibition of GR as a cause of the pulmonary toxicity often seen in high-dose BCNU-treated animals and human cancer patients. Herein we demonstrate that the prodrug Cloretazine (1,2-bis[methylsulfonyl]-1-[2-chloroethyl]-2-[(methylamino)carbonyl]hydrazine; VNP40101M), which yields methyl isocyanate and chloroethylating species upon activation, did not produce similar inhibition of cellular GR activity, despite BCNU and Cloretazine being equally potent inhibitors of purified human GR (IC(50) values of 55.5 microM and 54.6 microM, respectively). Human erythrocytes, following exposure to 50 microM BCNU for 1h at 37 degrees C, had an 84% decrease in GR activity, whereas 50 microM Cloretazine caused less than 1% inhibition under the same conditions. Similar results were found using L1210 murine leukemia cells. The disparity between these compounds remained when cells were lysed prior to drug exposure and were partially recapitulated using purified enzyme when 1mM reduced glutathione was included during the drug exposure. The superior antineoplastic potential of Cloretazine compared to BCNU in animal models could be attributed in part to the contribution of the methyl isocyanate, which is synergistic with the co-generated cytotoxic alkylating species, while at the same time unable to significantly inhibit cellular GR.

Animals↗
PubMed2005

Chemistry and biology of dihydroisoxazole derivatives: selective inhibitors of human transglutaminase 2.

3-halo-4,5-dihydroisoxazoles are attractive warheads for the selective inhibition of nucleophilic active sites in biological systems. A series of 3-bromo-4,5-dihydroisoxazole compounds were prepared and tested for their ability to irreversibly inhibit human transglutaminase 2 (TG2), an enzyme that plays an important role in the pathogenesis of diverse disorders including Celiac Sprue and certain types of cancers. Several compounds showed high specificity for human TG2 (k(inh)/K(I) > 2000 min(-1)M(-1)) but essentially no reactivity (k < 1 min(-1)M(-1)) toward physiological thiols such as glutathione. The pharmacokinetic and pharmacodynamic properties of a prototype dihydroisoxazole inhibitor, 1b, were evaluated; in mice the compound showed good oral bioavailability, short serum half-life and efficient TG2 inhibition in small intestinal tissue, and low toxicity. It also showed excellent synergism with N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU, carmustine) against refractory glioblastoma tumors in mice. A fluorescent dihydroisoxazole inhibitor 5 facilitated microscopic visualization of TG2 endocytosis from the extracellular surface of HCT-116 cells. Together, these findings demonstrate the promise of dihydroisoxazole compounds as probes for the biology of TG2 and its role in human disease.

Animals↗
PubMed2004

Phase I study of involved-field radiotherapy preceding autologous stem cell transplantation for patients with high-risk lymphoma or Hodgkin's disease.

PURPOSE: This Phase I study was designed to evaluate the tolerability of involved-field radiotherapy (IFRT) to areas of persistent disease in patients with high-risk Hodgkin's disease and non-Hodgkin's lymphomas before autologous stem cell transplantation (ASCT). METHODS AND MATERIALS: Thirty-one patients with primary refractory or relapsed Hodgkin's disease (n = 13) and non-Hodgkin's lymphoma (n = 18) were treated with IFRT followed by high-dose chemotherapy and ASCT. All patients had bulky disease (> or =5 cm) and/or an inadequate response to salvage chemotherapy. The IFRT dose was escalated to a maximum of 36 Gy. Dose-limiting toxicity was defined as Grade 3-4 Bearman toxicity (life-threatening/fatal toxicity occurring within 28 days of ASCT). The chemotherapy regimen consisted of cyclophosphamide, etoposide, and carmustine. RESULTS: The delivered dose of IFRT was 20 Gy in 9 patients, 28-30 Gy in 20, and 32-36 Gy in 2 patients to mediastinal (n = 19) and nonmediastinal (n = 12) sites. The median interval between IFRT completion and ASCT was 19 days. One patient developed Bearman Grade 3 hepatic toxicity. No other Grade 3 or 4 Bearman toxicity was observed. An increased requirement for i.v. narcotics was observed in patients treated with mediastinal IFRT vs. nonmediastinal IFRT (p = 0.02). A trend toward increased mucositis severity was seen in patients previously treated with a larger number of chemotherapy agents (p = 0.09) and in those with a shorter interval between IFRT and ASCT (p = 0.12). Pulmonary toxicity was more common in patients treated with mediastinal IFRT than in those treated with nonmediastinal IFRT (21% vs. 0%, p = 0.13). The 2-year overall and progression-free survival rate was 70% and 49% for all patients, 84% and 50% for patients with Hodgkin's disease, and 59% and 47% for patients with non-Hodgkin's lymphoma, respectively. CONCLUSION: The maximal tolerated dose of IFRT was not reached when Grade 3-4 Bearman toxicity was dose limiting. Increased pulmonary toxicity and mucositis severity was seen after mediastinal IFRT compared with nonmediastinal IFRT. Because local control was excellent, higher doses of IFRT are not recommended. The absolute benefit of IFRT in this patient population needs investigation in future studies.

Adult↗
PubMed2004

Primary non-Hodgkin's lymphoma of the CNS treated with CHOD/BVAM or BVAM chemotherapy before radiotherapy: long-term survival and prognostic factors.

PURPOSE: To assess the long-term survival and prognostic factors associated with the cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/carmustine, vincristine, methotrexate, and cytarabine (BVAM) and BVAM chemotherapy regimens followed by cranial radiotherapy in the treatment of primary central nervous system (CNS) non-Hodgkin lymphoma. METHODS AND MATERIALS: Since 1986, high-dose methotrexate (1.5 g/m(2)), cytarabine, vincristine, and carmustine have been used in the BVAM chemotherapy regimen for primary CNS non-Hodgkin's lymphoma, with one cycle of CHOD given before BVAM in patients or=60 years, performance status >or=2, and multifocal and/or meningeal disease [advanced stage]), a score of 0 (8 patients) was associated with a median survival of 55 months, a score of 1 (29 patients) of 41 months, a score of 2 (28 patients) of 32 months, and a score of 3 (12 patients) a median survival of 1 month (p <0.001). The actuarial overall survival for the 35 patients aged <60 years was 32.4% (95% confidence interval, 14.1-50.8%) at 10 years. CONCLUSION: The Nottingham/Barcelona prediction score, which is similar to the International Prognostic Index, may be useful in comparing survival with different regimens studied in Phase II trials. Patients with primary CNS non-Hodgkin's lymphoma aged <60 years treated with CHOD/BVAM or BVAM followed by radiotherapy have a similar long-term survival to that of patients with large B cell non-Hodgkin's lymphoma at other extranodal sites.

Adult↗