Use of adjuvant ICE chemotherapy in the treatment of anaplastic ependymomas

Despite the improved outcome for patients with ependymoma treated by surgery and radiotherapy, their prognosis remains relatively poor. To assess the impact of adjuvant chemotherapy, we reviewed the overall survival of consecutive patients with anaplastic ependymoma treated over a 10-year period with surgery and ICE (ifosfamide+ VP 16+carboplatin) chemotherapy with or without radiation at our institution. There were 11 patients (6 male, 5 female), with a median age of 3.4 years (range 1.2-1 1.1): 4 under 2 years and 7 were over 2 years old. Overall, 5 had gross total resections: 4 are alive, 2 in continuous complete remission and 2 in second complete remission. One patient who was less than 2 years old died. Among the 6 with subtotal resection, 2 achieved a complete remission after chemotherapy. However, 5 of the 6 patients have since died of progressive disease, with a median overall survival of 75 months. Overall survival was 24% and progression-free survival was 39%. In 2 of 6 patients with residual postoperative disease a temporary objective response was noted with adjuvant ICE chemotherapy. This regimen did not confer an overall survival advantage.     

Combined modality therapy in previously untreated patients with advanced Hodgkin's disease: A 24-year follow-up study

PURPOSE: To describe the long-term results of treatment with chemotherapy plus adjuvant low-dose, involved-field radiation therapy (CMT) in patients with advanced Hodgkin's disease. Data on disease-free and failure-free survival, second malignancies, and the results of salvage therapy are presented. PATIENTS AND METHODS: From 1969 to 1989, CMT was administered to 186 patients with previously untreated stage IIB, III, and IV Hodgkin's disease. Chemotherapy included MVVPP (47%), MOPP (25%), MOPP/ABVD (26%) and ABVD (2%). After 6 months of chemotherapy, patients received radiation to all involved sites with the exception of the bone marrow. RESULTS: The failure-free survival for all patients was 63% at 5 years, 56% at 10 years, and 40% at 23.5 years, respectively. Significantly worse results were observed in patients older than 40 years and those with stage IV disease. The overall survival of 45 patients after recurrence was 39% at 10 years, but was only 21% if the initial complete remission lasted less than 1 year. Thus far, 21 of 165 patients (12.7%) who achieved complete remission have developed a second malignancy, and 16 have died. CONCLUSIONS: In comparison with comparable chemotherapy programs, chemotherapy plus radiation therapy may improve disease-free survival; however, the results of treatment in patients older than age 40 or with stage IV disease are still poor. Although patients with initial remissions lasting longer than 1 year can have durable second remissions, the long-term disease-free survival is poor and in the current series the majority of failures were due to recurrent Hodgkin's disease.     

An expression system for the single-step production of recombinant human amidated calcitonin

The authors evaluate 32 patients affected by paranasal sinuses and nasal cavity carcinoma observed at Orl-Rt Department of Oncologic Center at Umberto l(zero) Hospital in Mestre (VE), Italy from 1985 to 1994. Among these: 16 maxillary sinus, 10 ethmoid and 6 nasal cavity carcinomas. Histologic diagnosis showed squamous cell carcinoma in 15 cases, adenocarcinoma in 8 cases, lymphoma in 2 cases, transitional cell carcinoma in 2 cases, undifferentiated carcinoma in 2 cases and adenoidocistic carcinoma in 3 cases. The mean age was 64.5 years (range 46-88 years), and mean performance status was 80 (range 60-90). Four patients had lymphonodal involvement. Eleven patients were operated, eight of them radically. All patients were treated with radiation therapy. Treatment planning was performed using Theraplan V05-B program, on extensive number of CT scans. The minimal tumor dose was 50 Gy for patients operated radically and was 60 Gy with maximum of 73-80 Gy for the others. The follow-up is 39.7 months (range 10-108). Three patients treated with radical surgery developed local relapses, two of them died. Fourteen patients treated with non radical or diagnostic surgery and radiotherapy obtained local complete remission, five of them developed local relapses inside treatment volume. Ten patients died (eight for neoplastic disease). The 3 years, 5-years and 7-years overall survival are respectively 72% and 51%. The 5-years and 7-years disease free survival rate are respectively 48% and 19% with median at 3.7 years. Complication have been minimal. Only one patient affected by glaucoma had a severe and permanent reduction of the virus. The authors conclude that 2D and 3D treatment planning can assure a better accuracy for target definition and a better precision of the treatment with a reduction of complications.     

Curative potential of combined modality therapy for advanced Hodgkin's disease

During the period from 1969 through 1977, 124 patients with advanced Hodgkin's disease underwent treatment with combination chemotherapy and radiotherapy. Sixty-three cases were previously untreated, and 61 were relapses following radical radiotherapy for localized Hodgkin's disease. No patient in this series had received prior chemotherapy. Of 102 patients (84%) who have entered complete remission, 92 remain in complete remission with a median follow up time of five years, 10 patients having relapsed, and acute leukemia having developed in 2. The cumulative survival rate for all 124 patients is 80% at five years; the relapse-free survival rate is 74%. In many, if not most cases, the Hodgkin's disease appears to be cured. We have also identified two subgroups of patients for whom the prognosis is worse than for patients with advanced-stage disease as a whole. Patients over the age of 40 years have a five-year survival rate of only 45%, compared with 89% for all other patients. Those Stage IV patients with multiple extranodal sites of involvement have a five-year survival rate of 48%, compared with 81% for other Stage IV patients with only a single extranodal site involved.     

Long-term outcome of adult-onset minimal-change nephropathy

BACKGROUND: Adult-onset minimal-change nephropathy has been associated with a slower response to corticosteroids and a less benign prognosis when compared to children. However, there are few long-term outcome data reported. METHODS: We have reviewed retrospectively 51 idiopathic adult-onset minimal-change nephropathy patients investigated and treated at a single centre. RESULTS: Male to female ratio was 1:1.4, mean age at diagnosis was 37 years, and average length of follow-up was 14.1 years. Significant comorbidity was identified in 33%. A raised serum creatinine was found in 55% but returned to normal almost invariably upon remission. At presentation, hypertension was found in 47% of patients, microscopic haematuria in 33%, hypercholesterolaemia and hypertriglyceridaemia in 96%, and hyperuricaemia in 42%. Remission (complete or partial) was achieved by 46, 70 and 92% within 4, 8 and 21 weeks respectively, in patients treated with steroids; steroid resistance was encountered in 8%. The time to remission was positively correlated with age (P = 0.002) and initial albumin level (P = 0.005), and negatively correlated to the number of subsequent relapses (P = 0.029); 33% of patients had a spontaneous remission at some time during the disease course. Patients with multiple relapses were treated with cyclophosphamide and 63% of them had remained in remission after 5 years. Hypertension was present in 25% of patients after an average interval of 11 years. At the time of the final follow-up, only three patients had a raised creatinine and all but three patients were in complete remission. CONCLUSIONS: Adult-onset minimal-change nephropathy shares the same good long-term outcome as the childhood counterpart, with sustained remission and preserved renal function.     

Efficacy of two different ProMACE-CytaBOM derived regimens in advanced aggressive non-Hodgkin's lymphoma. Final report of a multicenter trial conducted by GISL

BACKGROUND AND OBJECTIVE: To compare the efficacy of ProME(Epidoxorubicin)CE-CytaBOM (PE-C) and ProMI(Idarubicin)CE-CytaBOM (PI-C) in the treatment of adult patients with aggressive non Hodgkin's lymphoma in a multicenter randomized controlled trial performed by 18 centers of the Italian Lymphoma Study Group (GISL). DESIGN AND METHODS: One hundred and twenty-eight and 122 patients were randomly assigned to receive either 6 courses of PE-C or PI-C, respectively. Some patients achieving complete remission with induction therapy participated in another randomized study comparing no further therapy versus maintenance therapy consisting of four blocks of two drugs. RESULTS: The rate of CRs was 62% and 64% for patients treated with PE-C and PI-C, respectively (p = 0.51). The 5-year relapse-free survival was 60% for PE-C and 53% for PI-C (p = 0.29). The estimated relapse-free disease survival rates at 4 years were 75% for patients in the consolidation group and 57% for those in the observation group (p = 0.11). Patients alive in first complete remission 4 years after study entry were estimated to be 39% in the PE-C arm and 38% in the PI-C arm (p = 0.90). The 3-year and 5-year estimated survival rates were 61% and 55% for the PE-C group and 56% and 47% for the PI-C group (p = 0.26). Fatal toxicities occurred in 7 patients (2.9%) with active disease and in 4 patients (1.7%) in complete remission. Stage (p = 0.04), bulky disease (p = 0.02), serum LDH (p = 0.0006), serum albumin (p = 0.0051), hemoglobin (p = 0.0011), performance status (p = 0.0001), International prognostic index (p < 0.0001) and the index proposed by the French group G.E.L.A. (p < 0.0001) were of prognostic value. In a multivariate analysis (Cox regression model) alternatively IPI alone or G.E.L.A. index plus performance status emerged as independent prognostic factors. INTERPRETATION AND CONCLUSIONS: The present study indicates that epirubicin and idarubicin in a combined chemotherapy regimen, have similar activities. The toxic profile also indicates the safety of both anthracyclines at the dosages employed, suggesting their possible dose escalation in a combined chemotherapy setting. PE-C and PI-C were both effective and feasible regimens in an outpatient setting, with acceptable cardiovascular toxicity. The trend toward a better outcome in patients undergoing consolidation therapy after the achievement of a complete remission, warrants further investigation.     

Respiratory allergy to parietaria pollen in 348 subjects

Present-day chemotherapy warrants complete remissions in 45-70% of patients with acute nonlymphoblastic leukemia. However, therapeutic policy at the stages of remission induction and residual disease remains disputable. The authors studied the role of 3 chemotherapy programs (7 + 3, 7 + 3 + vincristine, C-ROPM) in achievement of remission of acute leukemia and effects of long-term standard regimens of remission maintenance and bone marrow transplantation on long-term relapse-free survival of patients. The addition of vincristine to the program 7 + 3 failed to make remission more frequent and recurrence-free survival longer. C-ROMP program warranted remission in 70% of patients, this proportion being significantly higher than on programs 7 + 3 and 7 + 3 + vincristine. More intensive chemotherapy during remission induction resulted in a rise of 4-year recurrence-free survival from 12 to 44%. Bone marrow transplantation used for treatment intensification in remission increased 4-year recurrence-free survival compared to standard chemotherapy from 44 to 80%.     

Gastric MALT lymphoma and Helicobacter pylori infection

The results of an intensive treatment program for patients 16-60 yr of age with de novo acute myeloid leukemia are presented. The patients were given conventional induction treatment with daunorubicin and cytarabine. Patients not entering complete remission (CR) after 1 course of daunorubicin/cytarabine were given 1 course of amsacrine/etoposide/cytarabine. Those entering complete remission received 3 consolidation courses using mitoxantrone, etoposide, amsacrine and cytarabine. One hundred and eighteen patients were enrolled. Complete remission was attained after 1-2 courses in 90 patients (76%). Another 6 patients reached CR after 3-4 induction courses for a total CR rate of 81%. If feasible, patients were offered either allogeneic or unpurged autologous bone marrow transplantation. Twenty-four patients underwent allogeneic bone marrow transplantation; 15 in first remission, 8 in second remission, 1 in early relapse. Thirty patients below 56 yr of age underwent autologous bone marrow transplantation in first remission. The overall probability of survival at 4 yr was 34%, and for patients below 40 yr of age 50%. Leukemia-free survival was 35% for the whole cohort of patients; 52% for patients below 40 yr of age. Patients undergoing allogeneic or autologous bone marrow transplantation in first remission had an overall survival of 86% and 47%, respectively, while the probability of leukemia-free survival in these groups was 87% vs. 40% at 4 yr. The CR rate and long-term results of this intensive treatment program compare favorably with other recent studies using intensive consolidation with allogeneic or autologous bone marrow transplantation or high dose cytarabine.     

Intensive postremission chemotherapy in adults with acute myeloid leukemia. Cancer and Leukemia Group B

BACKGROUND: About 65 percent of previously untreated adults with primary acute myeloid leukemia (AML) enter complete remission when treated with cytarabine and an anthracycline. However, such responses are rarely durable when conventional postremission therapy is administered. Uncontrolled trials have suggested that intensive postremission therapy may prolong these complete remissions. METHODS: We treated 1088 adults with newly diagnosed AML with three days of daunorubicin and seven days of cytarabine and randomly assigned patients who had a complete remission to receive four courses of cytarabine at one of three doses: 100 mg per square meter of body-surface area per day for five days by continuous infusion, 400 mg per square meter per day for five days by continuous infusion, or 3 g per square meter in a 3-hour infusion every 12 hours (twice daily) on days 1, 3, and 5. All patients then received four courses of monthly maintenance treatment. RESULTS: Of the 693 patients who had a complete remission, 596 were randomly assigned to receive postremission cytarabine. After a median follow-up of 52 months, the disease-free survival rates in the three treatment groups were significantly different (P = 0.003). Relative to the 100-mg group, the hazard ratios were 0.67 for the 3-g group (95 percent confidence interval, 0.53 to 0.86) and 0.75 for the 400-mg group (95 percent confidence interval, 0.60 to 0.94). The probability of remaining in continuous complete remission after four years for patients 60 years of age or younger was 24 percent in the 100-mg group, 29 percent in the 400-mg group, and 44 percent in the 3-g group (P = 0.002). In contrast, for patients older than 60, the probability of remaining disease-free after four years was 16 percent or less in each of the three postremission cytarabine groups. CONCLUSIONS: These data support the concept of a dose-response effect for cytarabine in patients with AML who are 60 years of age or younger. The results with the high-dose schedule in this age group are comparable to those reported in similar patients who have undergone allogeneic bone marrow transplantation during a first remission.     

Autologous bone marrow transplantation for acute myeloid leukemia using busulfan plus etoposide as a preparative regimen

We have studied the use of a new preparative regimen for the treatment of patients in remission of acute myeloid leukemia (AML) with autologous bone marrow transplantation. Chemotherapy consisted of busulfan 1 mg/kg every 6 hours for 4 days (total dose, 16 mg/kg) on days -7 through -4 followed by an intravenous infusion over 6 to 10 hours of etoposide 60 mg/kg on day -3. Autologous bone marrow, treated in vitro with 100 micrograms/mL of 4-hydroperoxycyclophosphamide, was infused on day 0. We have treated 58 patients up to the age of 60 years, 32 in first remission, 21 in second or third remission, and 5 with primary refractory AML unresponsive to high-dose Ara-C, but achieving remission with aggressive salvage regimens. Of the first remission patients, there has been 1 treatment related death and 5 relapses. With median follow-up of 22 months, the actuarial relapse rate is 22% +/- 9% and disease-free survival is 76% +/- 9% at 3 years. Patients with favorable French-American-British (FAB) subtypes (M3 or M4 EO) did especially well, with no relapses seen in 15 patients observed for a median of 30 months. Actuarial relapse rate at 3 years was 48% for first remission patients with less favorable FAB subtypes. Of patients in second or third remission, there were 5 treatment related deaths and 4 relapses. With median follow-up of 22 months, the actuarial relapse rate is 25% +/- 11% and disease-free survival is 56% +/- 11% at 3 years. Four of five primary refractory patients died during treatment and 1 remains in remission with short follow-up. These preliminary data are very encouraging and, if confirmed, support the use of autologous purged bone marrow transplantation using aggressive preparative regimens as one approach to improve the outcome of adults with AML.     

The role of thiotepa in autologous bone marrow transplantation for acute leukemia

Post-transplant leukemic relapse remains the major problem following autologous bone marrow transplantation (ABMT). One possible approach to reducing the relapse rate is to intensify pre-transplant conditioning. Thiotepa (TTP) is an alkylating agent that has been used mainly in breast and ovarian cancer with 20-50% response rates. This report presents our results on 33 patients with acute leukemia (acute myeloblastic leukemia (AML) 27 patients, acute lymphoblastic leukemia (ALL) six patients) who underwent ABMT following conditioning with busulfan (BU), 4 mg/kg x 4 days (days -8 to -5), TTP 5 mg/kg x 2 days (days -4, -3) and cyclophosphamide (CY) 60 mg/kg x 2 days (days -2, -1). Of the 33 patients, 22 were males and 11 females, of median age 24 (1-55) years. Twenty-eight patients were transplanted in complete remission (AML 26; ALL 2) while 5 (AML 1; ALL 4) were in early relapse. Twenty-nine additional AML patients (15 females, 14 males) of median age 22 (2-48) years, who underwent ABMT following a standard BU-CY conditioning regimen (25 in complete remission and four in relapse) served as historical controls. There were no significant differences between the study and control groups with respect to patient age, sex, diagnosis, stage of disease, FAB classification, and prior chemotherapy, at ABMT. Overall survival, disease free survival (DFS), and relapse rate at 72 months were 33, 33 and 61%, respectively, for the study group, and 38, 34.5 and 52%, respectively, for the historical controls. Engraftment and transplant related toxicity also did not differ significantly in the two groups. In conclusion, TTP appears to have made no substantial improvement to the outcome of ABMT for acute leukemia.     

Inflammatory bowel diseases in children]

From an incidence cohort diagnosed during 1962-1987 we identified all patients with onset of IBD before the age of 15 in order to describe the course and to compare course and prognosis with adult onset IBD. The mean incidence of IBD among children below 15 years was 2.2/10(5), 2.0 for ulcerative colitis (UC), and 0.2 for Crohns disease (CD). At diagnosis, UC children had more extensive disease compared to adults (p < 0.05). Abdominal pains were also more frequent. The cumulative colectomy probability was 6% after one year and 29% after 20 years, not different from adults. Regarding disease activity, it was found that 60-70% of UC patients were in remission in the first 10 years of disease, for CD about 50% were in remission. One UC patient developed carcinoma of the sigmoid colon. Time between onset and development of carcinoma was 12 years. For CD no differences in clinical appearance at diagnosis and course between children and adults were found. No deaths occurred among CD patients. Three CD patients were found to have severe growth retardation already at diagnosis. In conclusion, the incidence of IBD is low in childhood. At diagnosis children with UC have more widespread disease than adults. Children with CD do not differ in clinical presentation, course or prognosis compared to adult onset CD. However, growth retardation is a problem among CD patients.     

Chemotherapy of acute myeloblastic leukaemia with DAM regimen

32 patients of denovo-ANLL were treated with Doxorubicin, Ara-C and 6-Mercaptopurine (DAM) regimen. Remission induction was instituted with 1-3 cycles of DAM regimen and maintenance was given by 6-MP continuously with intermittent DA (1,5) regimen. In the remission induction, Doxorubicin 30 mg/m2 for 3 days, Ara-C 150 mg/m2 for 5 days and 6-Mp 100 mg/m2 daily was given. Complete remission (CR) was observed in 60% cases. The probability of 2 years disease-free survival of patients with complete remission is 56.73%.     

2-Chlorodeoxyadenosine (2-CdA) in the treatment of patients with relapsed chronic lymphocytic leukemia

This study attempts to characterize the response of patients with chronic lymphocytic leukemia (CLL) to the purine analog 2-chlorodeoxyadenosine (2-CdA). We have treated 10 patients with 2-CdA, at a dose 0.05-0.1 mg/kg/daily, for 7 days as a 2-hour infusion. Mean age was 54.6 years (range, 34-68 years). Mean time from diagnosis to treatment with 2-CdA was 37.0 months (range, 8-84 months). All the studied patients had received preliminary therapy consisting of other than 2-CdA chemotherapeutic regimens. Eight out of 10 patients had Rai stage III-IV disease. Four patients had Coombs positive hemolytic anemia before 2-CdA treatment. Seven patients responded to 2-CdA. Two complete remission (CR) and 5 partial remission (PR) were achieved. All patients but one with Coombs positive autoimmune positive hemolytic anemia achieve complete resolution of hemolysis. Severe neutropenia was frequent, and serious infections were noted in 20%, 43% and 50% of cases during the first, second and third course of 2-CdA, respectively. We conclude that 2-CdA is an effective agent in relapsed CLL patients, particularly in cases complicated by autoimmune hemolytic anemia.     

Results of the National Protocol for Antineoplastic Drugs in the treatment of adult acute lymphoblastic leukemia. Experience at the Hospital del Salvador, 1990-1997

BACKGROUND: Acute lymphoblastic leukemia has a different evolution in children and adults. Complete remission is achieved in 70-85% of the latter, but only 25 to 35% have a prolonged disease-free survival. AIM: To assess the treatment outcome of adults with acute lymphoblastic leukemia in Chile. PATIENTS AND METHODS: A retrospective review of the medical files of 51 adults with acute lymphoblastic leukemia treated according to the national protocol for antineoplastic drugs, in a public hospital of Santiago. RESULTS: Mean age of patients was 35.9 years old and 53% were younger than 20 years old. Complete remission was achieved in 64%. Early mortality occurred in 22%, mostly due to infections. Treatment failure occurred in 16%. Global survival was 17 months and global survival at 5 years was 24%. Prognostic criteria of the protocol, defined a low risk group that had a complete remission of 100%, no early deaths and 5 year disease-free survival of 53%. The group defined as having high risk had a complete remission of 47%, a 29% early mortality and a 5 years disease-free survival of 6%. CONCLUSIONS: Aiming to improve treatment results in acute lymphoblastic leukemia, efforts should be made to improve the management of febrile neutropenic patients and to intensify chemotherapy.     

Randomized comparison of cisplatin and etoposide and either bleomycin or ifosfamide in treatment of advanced disseminated germ cell tumors: an Eastern Cooperative Oncology Group, Southwest Oncology Group, and Cancer and Leukemia Group B Study

PURPOSE: To compare standard therapy with bleomycin, etoposide, and cisplatin (BEP) to experimental therapy with etoposide, ifosfamide, and cisplatin (VIP) as primary treatment of men with advanced, disseminated germ cell tumors. PATIENTS AND METHODS: A total of 304 men with advanced disseminated germ cell tumors were randomly allocated to receive four courses of BEP or VIP. Two hundred ninety-nine patients were assessable for toxicity and 286 were assessable for response. Complete response rates, favorable response (complete remission, surgical free of disease, continuous partial remission for 2+ years), time to treatment failure, and overall survival were assessed. RESULTS: Overall complete remission rate (VIP, 37%; BEP, 31%), favorable response rate (VIP, 63%; BEP, 60%), failure-free at 2 years (VIP, 64%; BEP, 60%), and 2-year overall survival (VIP, 74%; BEP, 71%) were not significantly different between the two treatments. Grade 3 or worse toxicity, particularly hematologic and genitourinary toxicity, was significantly more common in patients who received VIP. CONCLUSION: BEP and VIP produce comparable favorable response rate and survival in patients with poor-risk germ cell tumors. The substitution of ifosfamide for bleomycin, however, was associated with significantly greater toxicity. Four courses of BEP remain the standard treatment for advanced disseminated germ cell tumors.     

The value of gallium imaging after therapy for Hodgkin's disease

BACKGROUND: Although it is used widely, the value of gallium imaging in managing Hodgkin's disease remains unclear. METHODS: A retrospective review of gallium imaging and treatment outcome in 60 patients with Hodgkin's disease treated between January 1990 and July 1995 was conducted. The minimum follow-up was 1 year. RESULTS: Based on gallium imaging, 46 patients were in complete remission (CR) after initial treatment, 10 were in partial remission (PR), and 4 had persistent or progressive disease (NR). Ten of 29 patients (34%) with gallium CR after chemotherapy subsequently recurred, compared with no recurrences in 17 patients receiving initial radiotherapy or combined chemoradiation. Eight of ten patients received further therapy after gallium PR, and nine patients remained disease free at last follow-up. Survival did not differ in patients achieving a gallium CR or PR. CONCLUSIONS: Gallium-67 imaging may help confirm the presence of active Hodgkin's disease, but was unreliable in defining disease remission after chemotherapy in this study population. Patients with a gallium PR may still have a good prognosis after additional therapy.     

Quality of life in chronic inflammatory bowel diseases. Validation of a questionnaire and first French data]

One hundred and seventy patients with Graves' disease underwent thyroidectomy between 1987 and 1994 (10.5% of all thyroidectomies performed in the same period). Female/male ratio was 9/1; mean age 55.2 years and average period between diagnosis and surgical treatment 5.3 years. The average thyroid weight was 230 g (range 90-950 g). Thyroidectomy was subtotal in 110 and total in 60 patients, 5 of which had been previously treated elsewhere from 5 to 33 years before. Malignancy was incidentally found in 2.35% of patients. The complication rate resulted higher in total thyroidectomies than in subtotal procedures (bleeding 0.9% vs 5.4%, transient hypoparathyroidism 4.5% vs 12.7%, recurrent nerve lesion 0.45% vs 2.72%) however the differences were not statistically significant; this probably because both the procedures were carried out with the same technique for parathyroid gland and recurrent nerve safety. The need of repeated surgery increased the risk. In opposition to total thyroidectomy, subtotal thyroidectomy does not doom to complete and permanent replacement therapy (96.4% of hypothyroidism at 2 months, 72.6% at 4 years), but in this series it failed to achieve remission in 2 patients who maintained a mild hyperthyroidism and in one more patient who developed a relapse 4 years later. Serum TSI meaning is not clear, but preoperative positivity suggests a wider resection and postoperative persistence a closer follow-up by functional assessment. In conclusion surgical procedures for Graves' disease range from subtotal to total thyroidectomy but for a safe outcome the choice depends more on the intraoperative troubles of each single case than on theoretic advantages.     

BEAM chemotherapy and autologous haemopoietic progenitor cell transplantation as front-line therapy for high-risk patients with diffuse large cell lymphoma

In two consecutive and unselected cohorts of diffuse large cell lymphoma (DLCL) patients with advanced stage disease (IIB or bulk or more) and aged < 60 years, we compared a standard (MACOP-B for 12 weeks, 60 patients) versus a high-dose chemotherapy programme (8 weeks of MACOP-B plus one or two cycles of intensification with mitoxanthrone, dexamethasone, high-dose Ara-C, and finally BEAM chemotherapy with autologous haemopoietic progenitor cell transplantation, 61 patients). 41 patients (68%) in the standard group and 51 (84%) in the high-dose chemotherapy group, achieved a complete remission (CR) or an uncertain complete remission (CRu) (P = 0.0491). With a median follow-up time of 28 months for the high-dose group and 63.5 months for the standard group, the actuarial estimate of event-free survival (EFS) at 2 years demonstrates a significant benefit (70% v 50%, P = 0.03) for patients treated with the intensive regimen. The analysis of subgroups of patients showed that only high-risk patients (two or three risk factors) benefitted from the high-dose chemotherapy programme. Nevertheless, the overall survival does not show a significant difference between the two treatment modalities. The treatment-related morbidity was similar and the mortality rate was 8% in the standard (MACOP-B) group and 3% in the high-dose chemotherapy programme. In conclusion, our results show that high-dose chemotherapy and autologous stem cell transplantation is a safe procedure which should be considered for the front-line treatment of non-Hodgkin lymphoma patients with poor prognostic features.     

Successful treatment of non-Hodgkin's lymphoma of the central nervous system with BMPD chemotherapy followed by radiotherapy

The treatment of patients with primary non-Hodgkin's lymphoma of the central nervous system (PCNSL) is still of limited success, as compared with other extranodal sites. The poor results obtained with radiotherapy alone can be improved by adding chemotherapy reaching a median survival up to over 30 months and 5-years-survival rate up to 35%. The optimal management for patients with CNS relapse of systemic lymphoma remains uncertain and their prognosis is even worse. Here, we describe our preliminary data on the treatment of patients with CNS lymphoma with a new regimen composed of CNS-penetrating drugs, namely: carmustine (BCNU) 80 mg/m2 i.v. dl, methotrexate 1500 mg/m2 over 24h i.v. d2, procarbacine 100 mg/m2 p.o. d1-8, and dexamethasone 3 x 8 mg p.o. d1-14. An average of 3 treatment courses were given under response control seen using CT-scan or NMR. Patients with positive CSF cytology received additionally intrathecal therapy with methotrexate. Until now between March 1994 and September 1997, 7 patients with PCNSL and 4 patients with CNS relapse of systemic lymphoma have been treated. The median age of the patients was 56 (range, 39-74); 5 patients were > or =60 years old. Three patients had multifocal disease. Whole brain radiotherapy with 4000 to 5000 cGy was given in 7 patients (cerebrospinal in 1 patient). Complete response at the end of chemotherapy was achieved in 6 patients, and a partial response in two. Most remarkably, 2 elderly patients (70 and 57 years), 1 patient with multifocal disease and 1 with simultaneous CNS and systemic relapse after chemotherapy had a complete remission lasting for 40 months, and a partial remission lasting for 37 months, respectively.