Allogeneic bone marrow transplant for multiple myeloma.
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Adult↗
Biomedical subjects
E M Bessell
Publications and source records attributed to E M Bessell.
Hodgkin's disease in patients older than 70 years of age: a registry-based analysis.
Between 1973 and 1993, 529 patients aged 15 years and over with Hodgkin's disease (HD) were entered into a lymphoma registry. Twenty-eight cases (1 only diagnosed at autopsy) of histologically proven HD in patients aged 70 years or older were identified. The distribution of sex, 'B' symptoms, histology and stage was not significantly different from that of younger patients, except for the fact that there were no patients aged 70 years or older with lymphocyte predominant HD. Nineteen patients were treated radically, 5 patients palliatively and 4 patients received no radiotherapy or chemotherapy. Three of the 14 patients treated with chemotherapy achieved the planned dose intensity. The cause-specific 5-year survival was 75% for patients aged 15-69 years and 28% for patients aged 70 years and over (logrank chi(2) = 43.7, P < 0.00001). The younger and older groups treated with radical intent had complete response rates of 97% and 74%, respectively (logrank chi(2) = 17.91, P < 0.00001) and relapse rates at 5 years of 27% and 56%, respectively (logrank chi(2) = 4.86, P = 0.0275). The main reason for the poorer prognosis of patients aged 70 years and over was the increasing difficulty of chemotherapy delivery associated with advancing age.
Age Factors↗
Engraftment and molecular monitoring of CD34+ peripheral-blood stem-cell transplants for follicular lymphoma: a pilot study.
PURPOSE: A pilot study to validate the use of CD34+ selection (Ceprate SC) of blood stem-cell collection in patients with advanced follicular lymphoma receiving myeloablative chemoradiotherapy. PATIENTS AND METHODS: Seventeen patients were entered onto the protocol. Thirteen of 17 patients have undergone transplantation; the median age is 42.5 years (range, 33 to 51), seven of 13 are stage IVB, two stage IVA, three stage IIIB, and one stage IIB. All except two patients were treated after first or subsequent relapses after receiving cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy to achieve a good partial (six of 13) or complete (seven of 13) response before stem-cell mobilization with cyclophosphamide 3 g/m2 and filgrastim 300 microg once daily. RESULTS: Eleven of 13 patients had a detectable t(14;18) by nested polymerase chain reaction (PCR). Median CD34+ count before selection was 2.9 x 10(6)/kg (range, 1.17 to 11.3) and after CD34+ selection was 1.54 x 10(6)/kg (range, 0.88 to 7.6) with a median CD34+ yield of 62.4% (range, 17% to 95%) and purity of 60% (range, 39.3% to 73%). Of the 11 patients known to have t(14;18), 10 had PCR-detectable contamination of stem-cell harvests that became PCR negative in six of the 10 after CD34+ selection. Engraftment was rapid with a median day to absolute neutrophil count (ANC) greater than 0.5 x 10(9)/L of 13 days (range, 11 to 21) and platelet count greater than 20 x 10(9)/L of 14 days (range, 10 to 44). With a median follow-up duration of 15 months, three patients have remained persistently PCR-positive, two of whom received PCR-positive stem cells. Two have relapsed. Of the seven patients who received PCR-negative stem cells, five have had no PCR-detectable disease in posttransplant bone marrow samples. CONCLUSION: Longer follow-up duration is required to determine the significance of these findings, but we have confirmed the feasibility of CD34+ selected cells to deplete peripheral-blood stem cells of tumor cells from patients undergoing high-dose therapy for follicular lymphoma.
Adult↗
Non-Hodgkin's lymphoma of the thyroid: a retrospective review of all patients diagnosed in Nottinghamshire from 1973 to 1992.
The pathological and clinical features were reviewed of all primary non-Hodgkin's lymphomas (NHL) of the thyroid gland diagnosed between 1973 and 1992 in the population (1.1 million) served by the Nottingham and North Nottinghamshire Health Authorities. Of the 43 patients with histologically proven NHL, three had low grade mucosa associated lymphoid tissue (MALT) lymphomas (Stage IEA, 2; Stage IIEA, 1), 35 had intermediate or high grade lymphomas, Stage IEA or IIEA (intermediate MALT, 2; high grade MALT, 14; B-cell diffuse centroblastic, 17; anaplastic large cell (Ki-1) of null cell type, 1; high grade unclassifiable, 1), and one had unclassifiable NHL Stage IIEA. One patient had Stage IIIEA disease (high grade MALT) and three had stage IVA disease (high grade MALT, 2; B-cell diffuse centroblastic, 1). The median age was 68 years (range 45-86) with a female: male ratio of 6:1. For the 35 patients with intermediate or high grade thyroid NHL (Stages IEA and IIEA) the 5- and 10-year cause specific survival was 60%. The 21 patients treated between 1985 and 1992 initially with chemotherapy (except stage IEA (< 5 cm diameter) had a 5-year cause specific survival of 69% (95% CI 48-90) compared with 46% (95% CI 19-73) for the 14 patients treated between 1973 and 1984 with initial radiotherapy (Chi 2 = 1.62). The survival of those patients with intermediate or high grade MALT lymphomas was not significantly greater than of those patients with B-cell diffuse centroblastic NHL.
Aged↗
Primary non-Hodgkin's lymphoma of the CNS treated with BVAM or CHOD/BVAM chemotherapy before radiotherapy.
PURPOSE: To assess whether chemotherapy that includes drugs that cross the blood-brain barrier improves survival in primary CNS non-Hodgkin's lymphoma (PCNSL) when combined with radiotherapy. PATIENTS AND METHODS: Thirty-four patients, with no evidence of human immunodeficiency virus type 1 (HIV-1) infection, were treated with the related chemotherapy regimens of carmustine (BCNU), vincristine, cytarabine, and methotrexate (BVAM; 12 patients), cyclophosphamide, doxorubicin, vincristine, and dexamethasone (CHOD)/BVAM (17 patients) and intensified CHOD/BVAM (five patients) between 1986 and 1994. The median age was 60 years (range, 16 to 73) and 47% had a performance status of 3 or 4 (Eastern Cooperative Oncology Group [ECOG]/World Health Organization [WHO]). Ten patients were treated with BVAM chemotherapy between 1986 and 1989, and subsequently 17 patients were treated with CHOD/BVAM (cytarabine 3 g/m2). Twenty of these 27 patients received whole-brain radiotherapy (craniospinal in four). RESULTS: The complete response (CR) rate at the completion of chemotherapy was 63% for BVAM and 67% for CHOD/BVAM; more neutropenia occurred with CHOD/BVAM. The 5-year actuarial probability of survival of all 34 patients was 33% (95% confidence interval [CI], 14% to 52%), with so far only one recurrence after 2 years. Using multivariate analysis, age (P = .0005) and number of tumors at diagnosis (P = .0358) were prognostic factors. All five patients aged > or = 70 years died during or shortly after chemotherapy. Performance status was not an independent variable. CONCLUSION: The BVAM or CHOD/BVAM regimens can be delivered despite neutropenia without significant treatment delay or dose reduction in patients less than 70 years of age. Further intensification of this type of chemotherapy is probably not possible with patients of this age, many of whom have a poor performance status.
Adolescent↗
Primary gastric lymphoma in clinical practice 1973-1992.
This study assessed the presentation, treatment, and prognosis of primary gastric lymphoma in general hospital practice and its relation to infection with Helicobacter pylori. The number of patients that would on the current recommendations have been suitable for H pylori eradication therapy was also examined. All lymphomas were graded according to a standard classification of gut lymphoma into high and low grade disease. Forty five patients (mean age 65 years) were identified. The overall five year survival was 40% with a trend in favour of an improved prognosis for low grade and stage I disease. H pylori was present in 80%. Only one of 18 patients with a low grade mucosa associated lymphoid tissue tumour had mucosal disease alone, which responded to omeprazole and amoxycillin. All other patients had bulk disease. These patients were treated by surgery, chemotherapy or radiotherapy or a combination of these treatments. In district hospital practice, most cases of primary gastric lymphoma have bulk disease at presentation. Even in patients with low grade gastric lymphoma on histological examination, many on the current evidence would not be suitable for anti-H pylori therapy alone.
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Non-Hodgkin's lymphoma in elderly patients: a phase II study of MCOP chemotherapy in patients aged 70 years or over with intermediate- or high-grade histology.
During the period 1 January 1988 to 31 July 1991, 74 patients were seen with intermediate- or high-grade non-Hodgkin's lymphoma who were aged 70 years or over. Of these 74 patients, 20 were treated with radiotherapy alone, and 46 were judged as suitable for treatment with the chemotherapy regime MCOP (mitoxantrone, cyclophosphamide, vincristine and prednisolone). Involved field radiotherapy (35-40 Gy in 20 fractions over 4 weeks) was given to 14 of the 21 patients with stage IA and IIA disease, and 6 of the 25 patients with stage III and IV disease after completion of chemotherapy. The complete response rate was 63% at the completion of all treatment (6 months), and 39% at 12 months. There were no treatment-related deaths, and the 3-year cause-specific survival was 26% (overall survival 21%). For patients aged 70-75 years, the 3-year cause-specific survival was 34% in comparison to 17% for those patients aged 76-93 years. The chemotherapy was well tolerated by those patients aged 70 years and over, 70% of the patients did not vomit and no patients had significant vincristine neuropathy. There were only four infections associated with neutropenia. All patients completing six cycles had moderate, patchy alopecia. This MCOP regime is suitable for patients aged 70 years and over with intermediate- and high-grade non-Hodgkin's lymphoma. The survival of patients is comparable to that obtained with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisolone) with less apparent toxicity.
Aged↗
The effect of prophylactic trimethoprim on aerobic urinary tract infection during pelvic radiotherapy and the incidence of infections due to fastidious or anaerobic organisms.
A total of 210 patients receiving pelvic radiotherapy were prescribed trimethoprim 200 mg p.o. daily for the duration of radiotherapy. It was prescribed after two mid-stream urine specimens were obtained. Two patients refused to take trimethoprim. The incidence of urinary tract infection prior to starting radiotherapy and trimethoprim was 24% (50 patients). Of these 50 initial infections, eight (16%) were resistant to trimethoprim, necessitating a change to an antibiotic to which the organism was sensitive. Persistent infection occurred in 21 of these 50 patients; 14 (67%) of these infections were resistant to trimethoprim. Of the 160 patients with no initial infection, 25 subsequently developed a urinary tract infection, in spite of prophylactic trimethoprim. Seven of these 25 infections (28%) were resistant to trimethoprim. Prophylactic trimethoprim is not worthwhile for preventing urinary tract infection during pelvic radiotherapy. Eight patients (4%) developed a rash while on trimethoprim, necessitating stopping the drug. Fastidious or anaerobic organisms were isolated in only 15 patients prior to radiotherapy and in seven patients during radiotherapy. Twenty of these 22 patients were female. The organism most commonly isolated was Streptococcus sp. The bacteriuria occurring with these organisms may have resulted from contamination from the vagina.
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The effectiveness of radiotherapy for localized relapse in patients with Hodgkin's disease (IIB-IVB) who obtained a complete response with chemotherapy alone as initial treatment.
Eleven patients with Hodgkin's disease (Stages IIB-IVB), diagnosed between 1977 and 1988, were identified from the Nottingham Lymphoma Registry as having been treated with radiotherapy for relapse at a localized site after a complete response (CR) with chemotherapy alone as initial treatment. The age range was 19-56 years (median 29), and the patients were all male. The median time to relapse from the date of CR was 20 months (range 5-50). All 11 patients achieved a CR with radiotherapy. Five patients have had no further relapse of Hodgkin's disease after radiotherapy. The actuarial disease free survival was 44% at 5 and 10 years. The overall survival was 100% at 5 years, and 90% at 10 years, with a median follow-up from relapse of 57 months. Longer follow-up on these patients will be needed to establish whether cure is possible with radiotherapy for localized relapse, or whether the disease behaves in a more indolent manner after chemotherapy with the possibility of further late relapses occurring. However, so far all the relapses have occurred within 4 years of radiotherapy.
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Second-line treatment with ifosfamide and carboplatin in patients with ovarian carcinoma relapsing after treatment with carboplatin.
20 patients with ovarian carcinoma whose disease had relapsed (1-42 months, median 4 months) after showing either response or stable disease to carboplatin, were treated with ifosfamide (5 g/m2 intravenously over 24 h, day 1) and carboplatin (200 mg/m2 intravenously day 2) as second-line treatment. The mean number of treatment cycles was 3.5 (range 1-6). The major toxicities were thrombocytopenia (WHO grade 3/4, 25%), neutropenia (WHO grade 3/4, 40%) and encephalopathy (WHO grade 3/4, 15%). Overall response rate was 15% [complete response, 0; partial response, 3 (15%); no change, 5 (25%) and progressive disease, 12 (60%)]. The median survival from the date of second-line treatment was 7 months. This combination offers no advantage over either agent used alone.
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Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis.
Two hundred and seventy-eight adult chemonaive patients, receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eight-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.
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Efficacy and toxicity of vinblastine, bleomycin, and methotrexate with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease: a British National Lymphoma Investigation pilot study.
PURPOSE: To assess the efficacy and toxicity of vinblastine, bleomycin, and methotrexate (VBM) chemotherapy with involved-field radiotherapy in clinical stage IA and IIA Hodgkin's disease. PATIENTS AND METHODS: Thirty eligible patients with clinical stage IA or IIA Hodgkin's disease, at intermediate risk of relapse, were enrolled into a prospective multicenter pilot study. They received two cycles of VBM chemotherapy, followed by involved-field radiotherapy and then four further cycles of VBM. The median follow-up duration from the start of treatment is 30 months. RESULTS: All 26 patients with assessable disease showed an objective response after two cycles of VBM (nine complete responses, 17 partial responses). By the completion of treatment, 27 patients were in complete remission; two had stable residual masses, which have not progressed at 26 and 34 months of follow-up; and one patient who died of treatment-related sepsis was in complete remission at that time. Two relapses have occurred, 19 and 28 months after starting VBM. Cough and dyspnea developed in 14 of 30 patients, and were associated with impairment of pulmonary function tests. Three episodes of neutropenic sepsis were recorded. CONCLUSION: VBM with involved-field radiotherapy is an effective treatment for early Hodgkin's disease. However, the associated toxicity, both pulmonary and hematologic, is severe, making the regimen unsuitable for routine use.
Adolescent↗
Radiation dose to the lens and cataract formation.
PURPOSE: To determine the radiation tolerance of the lens of the eye and the incidence of radiation-induced lens changes in patients treated by fractionated supervoltage radiation therapy for orbital tumors. METHODS: Forty patients treated for orbital lymphoma and pseudotumour with tumour doses of 20-40 Gy were studied. The lens was partly shielded using lead cylinders in most cases. The dose to the germinative zone of the lens was estimated by measurements in a tissue equivalent phantom using both film densitometry and thermoluminescent dosimetry. Ophthalmological examination was performed at 6 monthly intervals after treatment. RESULTS: The lead shield was found to reduce the dose to the germinative zone of the lens to between 36-50% of the tumor dose for Cobalt beam therapy, and to between 11-18% for 5 MeV x-rays. Consequently, the len doses were in the range 4.5-30 Gy in 10-20 fractions. Lens opacities first appeared from between 3 and 9 years after irradiation. Impairment of visual acuity ensued in 74% of the patients who developed lens opacities. The incidence of lens changes was strongly dose-related. None was seen after doses of 5 Gy or lower, whereas doses of 16.5 Gy or higher were all followed by lens opacities which impaired visual acuity. The largest number of patients received a maximum lens dose of 15 Gy; in this group the actuarial incidence of lens opacities at 8 years was 57% with visual impairment in 38%. CONCLUSION: The adult lens can tolerate a total dose of 5 Gy during a fractionated course of supervoltage radiation therapy without showing any changes. Doses of 16.5 Gy or higher will almost invariably lead to visual impairment. The dose which causes a 50% probability of visual impairment is approximately 15 Gy.
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Regression of transitional cell carcinoma of the bladder with radiotherapy: progression-free control in the bladder at 5 years.
The five-year survival and the local control in the bladder at 5 years were determined for 67 patients with transitional cell carcinoma of the bladder. These 67 patients had been included in a previous study of the regression of carcinoma of the bladder with radical radiotherapy. For these 67 patients treated with radiotherapy alone after transurethral biopsy or excision, the cause-specific 5-year survival was 38.4% (95% confidence interval (CI), 26.5-50.3%), with an overall survival of 31.1% (95% CI, 20-42.2%). The local control in the bladder was 42.6% (95% CI, 29.2-56.0%) at 5 years.
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Intracranial ependymoma: long-term results of a policy of surgery and radiotherapy.
Ninety-three patients with primary intracranial ependymoma were treated at the Royal Marsden Hospital, between 1952 and 1988, with postoperative radiotherapy. The survival probability at 5, 10, and 15 years was 51%, 42% and 31%, respectively, and the corresponding progression free survival (PFS) probability, 41%, 38%, and 30%. Tumor grade was the single most important prognostic factor for survival and PFS with gender of lesser prognostic significance. Treatment parameters were stratified for grade. In patients with low grade tumors survival and PFS were better following complete macroscopic excision compared to incomplete surgery. The extent of resection had no significant influence on survival or PFS in patients with high grade tumors. Extent of irradiation did not influence PFS, irrespective of tumor grade, while patients with high grade tumors had marginally better survival following extensive irradiation compared to more limited radiotherapy. The main problem in the treatment of ependymoma remains local progression which was the cause of death in all but two patients. New treatment strategies should focus on improvement of local control, especially in incompletely resected low grade tumors and all high grade tumors. The use of spinal irradiation is unlikely to significantly improve treatment results.
Adolescent↗
Effective prevention of acute GVHD following allogeneic BMT with low leukaemic relapse using methotrexate and therapeutically monitored levels of cyclosporin A.
Although the combination of cyclosporin A (CYA) and methotrexate has been reported to reduce the incidence of acute GVHD in patients undergoing allogeneic BMT for leukaemia, it has been associated with a higher risk of leukaemic relapse. Since 1987 we have used the combination of CYA and methotrexate for GVHD prophylaxis in 24 patients undergoing allogeneic BMT for leukaemia or myelodysplasia. Over the first 50 days post-transplantation, CYA dosage was adjusted to keep within a therapeutic range of 95-205 ng/ml. This resulted in a 60% reduction in CYA dosage by day 50 post-transplant compared to the original Seattle protocol. Despite the low dosage of CYA administered, the incidence of acute GVHD was only 25% with no patient having greater than grade I GVHD. There have been no leukaemic relapses in low risk patients. The results indicate that decreasing CYA dosage does not increase the incidence of GVHD but may reduce the risk of leukaemic relapse following allogeneic BMT.
Acute Disease↗
Suprahyoid Hodgkin's disease stage IA.
From 1973 to 1987, 71 patients (age greater than or equal to 16 years) with stage IA supradiaphragmatic Hodgkin's disease were treated with radiotherapy alone. 23 patients (20, clinical stage; 3, pathological stage) had disease localised to the suprahyoid region of the neck (upper deep cervical, 11; submandibular, 6; submandibular and upper deep cervical, 5; submental, 1). The age range was 17 to 64 (median 33). The male to female ratio was 2.8:1. The histological types were: lymphocyte predominant, 11; nodular sclerosis grade I, 8; mixed cellularity, 4. The 5 and 10 year cause-specific survival was 100% with a disease-free survival of 90% at 5 and 10 years. The proportion of patients with suprahyoid Hodgkin's disease IA was constant over the 15-year period. This only became apparent when the histology of patients with suprahyoid non-Hodgkin's lymphoma stage IA was reviewed.
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