VACOP-B versus VACOP-B plus autologous bone marrow transplantation for advanced diffuse non-Hodgkin's lymphoma: results of a prospective randomized trial by the non-Hodgkin's Lymphoma Cooperative Study Group

PURPOSE: The aim of this multicenter randomized study was to compare conventional therapy with conventional plus high-dose therapy (HDT) and autologous bone marrow transplantation (ABMT) as front-line treatment for poor-prognosis non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS: Between October 1991 and June 1995, 124 patients, aged 15 to 60 years, with diffuse intermediate- to high-grade NHL (Working Formulation criteria), stages II bulky (> or = 10 cm), III, or IV were enrolled. Sixty-one patients were randomized to receive etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin (VACOP-B) for 12 weeks and cisplatin, cytarabine, and dexamethasone (DHAP) as a salvage regimen (arm A), and 63 to receive VACOP-B for 12 weeks plus HDT and ABMT (Arm B). RESULTS: There was no significant difference in terms of complete remissions (CRS) in the two groups: 75% in arm A, and 73% in arm B. The median follow-up observation time was 42 months. The 6-year survival probability was 65% in both arms. There was no difference in disease-free survival (DFS) or progression-free survival (PFS) between the two groups. DFS was 60% and 80% (P = .1) and PFS was 48% and 60% (P = .4) for arms A and B, respectively. Procedure feasibility was the major problem. In arm B, 29% of enrolled patients did not undergo HDT and ABMT. A statistical improvement in terms of DFS (P = .008) and a favorable trend in terms of PFS (P = .08) for intermediate-/high- plus high-risk group patients assigned to HDT and ABMT was observed. CONCLUSION: In this study, conventional chemotherapy followed by HDT and ABMT as front-line therapy seems no more successful than conventional treatment in terms of overall results. However, our results suggest that controlled studies of HDT plus ABMT should be proposed for higher risk patients.     

Adjuvant cyclophosphamide, doxorubicin, vincristine, and prednisone chemotherapy after radiation therapy in stage I low-grade and intermediate-grade non-Hodgkin lymphoma. Results of a prospective randomized study

BACKGROUND: In a prospective randomized manner, this study evaluated the effect of adjuvant chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; CHOP) in patients with Stage I non-Hodgkin lymphoma (NHL) who have achieved a complete response (CR) after radiation therapy (RT). METHODS: Forty-four patients with clinical or pathologic Stage I intermediate-grade or low-grade NHL were randomized to receive regional RT alone (median dose, 40 Gy) or regional RT followed by six cycles of CHOP chemotherapy. There were no differences in clinical and pathologic characteristics between the two treatment groups. RESULTS: The median follow-up was 7 years (range, 2-10 years). The actuarial relapse-free survival (RFS) rate for the RT plus CHOP group at 7 years was 83% compared with 47% (P < 0.03) for the RT-alone group. The overall survival (OS) for the two groups was 88% and 66%, respectively (P = 0.2). In patients with intermediate-grade NHL, the 7-year actuarial RFS for RT and CHOP was 86% compared with 20% for RT alone (P = 0.004). The corresponding actuarial survival rates were 92% and 47%, respectively (P = 0.08). In patients with low-grade histologic findings, the addition of adjuvant CHOP did not improve RFS (P = 0.6) or OS. All relapses in this study were at sites remote from the initially involved areas, and in 5 of 11 patients (45%), there were recurrences 5 years or longer after initial treatment. CONCLUSIONS: This study showed that adjuvant CHOP chemotherapy significantly improves RFS in patients with Stage I intermediate-grade NHL who achieve a CR after regional-field RT. The chemotherapeutic regimen favorably affected their probability of survival.     

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.     

Autologous bone marrow transplantation in poor-prognosis intermediate-grade and high-grade B-cell non-Hodgkin's lymphoma in first remission: a pilot study

PURPOSE: Using high-dose therapy and autologous bone marrow transplantation (ABMT) to overcome cellular resistance and eradicate minimal disease, we initiated a pilot study during first remission in patients with non-Hodgkin's lymphoma (NHL) to examine whether the long-term disease-free survival (DFS) rate can be improved for patients with poor-prognosis intermediate/high-grade NHL. PATIENTS AND METHODS: Twenty-six patients with advanced-stage diffuse intermediate/high-grade B-cell NHL (including 16 patients with diffuse small cleaved-cell [DSC]) were selected at presentation by histologic and clinical characteristics to have less than a 25% probability of long-term DFS with conventional treatment. After induction chemotherapy, 16 patients were in complete remission (CR) and 10 were in a minimal disease state. Patients were then treated with high-dose cyclophosphamide, total-body irradiation (TBI), and anti-B-cell monoclonal antibody-purged ABMT. RESULTS: Following ABMT, no acute in-hospital treatment deaths occurred, and engraftment of granulocytes and platelets was significantly faster than for patients undergoing ABMT who were in second or subsequent remission. Of 26 patients, 21 remain in CR maintained without continued therapy, three relapsed in sites of prior nodal disease (4.8, 5.4, and 28 months post-ABMT), and two died in remission. The DFS rate is estimated to be 85% at 28 months and thereafter. The median follow-up period for the 21 patients who are alive and disease-free is 32 months. CONCLUSION: This pilot study suggests that consolidation of first remission with ABMT may improve the long-term DFS rate for diffuse intermediate/high-grade NHL patients at high risk for relapse.     

BEAM chemotherapy followed by autologous stem cell support in lymphoma patients: analysis of efficacy, toxicity and prognostic factors

In the present paper, we evaluate tolerability, outcome and prognostic factors in patients with poor prognosis non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) when uniformly treated with BCNU, etoposide, cytarabine and melphalan (BEAM) and autologous stem cell transplant (ASCT). On hundred and forty-eight patients with NHL (n = 112) or HD (n = 36) received BEAM followed by infusion of bone marrow (n = 55), peripheral blood stem cells (n = 79) or both (n = 14). Twenty-eight patients had low-grade lymphoma (LGL), 68 intermediate- and 16 high-grade lymphoma (IGL). Within the NHL group, 21 patients were in 2nd or subsequent complete remission (CR) at transplant, 34 had sensitive disease and 11 resistant disease; 46 patients were transplanted in 1st CR due to the presence of > or = 2 adverse prognostic features at diagnosis or to a slow CR. Of the HD patients at transplant 17 had active disease, 16 were in > or = 2 CR and three in 1st CR. The overall percentage of toxic deaths was 5.4%, while in the group of patients transplanted with PBSC it was only 1.3%. NHL patients: 78% were in CR following ASCT, including 25 out of 45 patients (56%) who were transplanted with active disease. Only two of the 11 patients transplanted with resistant disease achieved CR. Incidence of overall survival (OS) and disease-free survival (DFS) at 3 years was 65 and 75%, respectively. As far as histology was concerned, OS was significantly better for patients with LGL in comparison with IGL (88 vs 56%) (P = 0.002). DFS was significantly higher for patients transplanted in first CR or first partial remission (PR) than it was for those transplanted in a later CR or PR (86 vs 53%) (P = 0.02). Multivariate analysis for OS showed that histology, bulky disease, poor performance status at transplant and achievement of CR were independent prognostic factors. In addition, a high number of infused MNC was associated with poor DFS. HD patients: 30 (83%) were in CR after transplantation, with 25 maintaining CR at the end of the study. Only one of the four patients transplanted with resistant disease reached CR. Incidence of OS and DFS at 3 years was 78 and 81%. DFS was similar for patients transplanted with early or late relapse (95 and 93%). With multivariate analysis, the only independent variable for OS was CR after transplant. In conclusion, the present results demonstrate the efficacy and low toxicity of the BEAM regimen in high-risk lymphoma patients with sensitive disease. Other strategies should be investigated for patients with refractory lymphoma.     

Clinical analysis of elderly patients with malignant lymphoma

An epidemiological study on 173 consecutive elderly malignant lymphoma patients age 65 years or over was performed and the clinical outcome of chemotherapy is reported. Of there, 131 patients (75.7%) had non-Hodgkin's lymphoma (NHL) and 21 patients had Hodgkin's disease (HD). As for clinical staging, 58.9% of patients were in stage 3 or 4. The initial sites were nodal in 61.8% of the patients the most common sites of involvement in superficial lymph nodes being cervical, inguinal and axillar. The most frequent site of extranodal involvement was the gastrointestinal tract. The cases were treated with CHOP/COPP, BACOP or COP-BLAM combination chemotherapy. The clinical efficacy of these modalities was similar, with complete remission rates being about 50%. However, the total response rate (CR+partial remission) by the COP-BLAM regimen were 88.1%. The median survival time of cases achieving CR, was longer than 47 months. The most frequent cause of death was infection, especially pneumonia and septicemia. Many elderly ML patients were found and diagnosed when the disease developed to an advanced stage. Therefore it is necessary to make efforts to find early ML patients by screening apparently healthy elderly people. Improvement of the complete remission rate should be obtained if vigorous and intensive chemotherapy is carried out with careful supportive therapy concerning the general condition and complications in patients.     

Comparison of autologous bone marrow transplantation with sequential chemotherapy for intermediate-grade and high-grade non-Hodgkin's lymphoma in first complete remission: a study of 464 patients. Groupe d'Etude des Lymphomes de l'Adulte

PURPOSE: Intensive chemotherapy followed by autotransplantation has given promising results in partially responding or sensitive relapsed patients with aggressive non-Hodgkin's lymphoma. In 1987, we designed a randomized study to evaluate the potential benefit of a high-dose regimen containing cyclophosphamide, carmustine, and etoposide (CBV) followed by autotransplantation over a consolidative sequential chemotherapy (ifosfamide, etoposide, asparaginase, and cytarabine) in patients in first complete remission with intermediate- and high-grade non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were younger than 55 years and had at least one adverse prognostic factor. Induction treatment was that of the LNH84 protocol with an open randomization on the anthracycline. Patients in complete remission were further randomly assigned to receive either consolidation procedure. RESULTS: After induction treatment, 464 patients were assessable for the consolidation phase. With a median follow-up duration of 28 months, the 3-year disease-free survival rate was 52% (95% confidence interval, 45% to 59%) in the sequential chemotherapy arm and 59% (95% confidence interval, 52% to 66%) in the autologous transplant arm (P = .46, relative risk = 0.90). The 3-year survival rate did not differ between sequential chemotherapy and autotransplantation, at 71% (95% confidence interval, 64% to 78%) and 69% (95% confidence interval, 62% to 76%), respectively (P = .60, relative risk = 1.11). CONCLUSION: For such a subset of patients, consolidation with the CBV regimen followed by autologous bone marrow transplantation is not superior to sequential chemotherapy.     

Epipodophyllotoxin-related acute myeloid leukemia: a study of 35 cases

To define better the risk of epipodophyllotoxin-related acute myeloid leukemia (AML) after extended follow-up and to assess responses to intensive salvage therapy, all patients who developed this complication after treatment for acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) in consecutive clinical trials at St Jude Children's Research Hospital from 1979 to 1994 were studied. Cases with 'lineage switch' or 'clonal selection' were excluded. Epipodophyllotoxin-related AML developed in 32 of 1140 patients treated for ALL and in three of 332 treated for NHL; it was a first adverse event in 25 and two cases, respectively. The complication was diagnosed at 12-130 months (median 34 months) after the initiation of treatment with epipodophyllotoxins; all but one of the cases occurred within 73 months, indicating that the risk is negligible after 6 years. The predominant karyotypic feature was 11q23 translocations (71% of cases); 21q22 rearrangements were rare. In a stepwise Cox regression analysis, two factors increased the risk of this complication: weekly or twice weekly administration of epipodophyllotoxins (P < 0.001); and the administration of asparaginase immediately before epipodophyllotoxin therapy (P < 0.001). Initial responses to salvage therapy were comparable to those reported for de novo AML: 92% of the evaluable patients entered complete remission after combination treatment. Single-agent therapy with 2-chlorodeoxyadenosine induced complete or partial remissions in one-half of the patients treated. The long-term survival rate was dismal. Of the 17 evaluable patients treated exclusively with chemotherapy, only one is alive at 84 months, compared to three of 16 patients who underwent bone marrow transplantation (alive at 10, 23 and 73 months). Cases of epipodophyllotoxin-related AML constitute a unique clinical syndrome that will require innovative strategies for cure.     

Autologous stem-cell transplantation for non-Hodgkin's lymphomas: the role of graft purging and radiotherapy posttransplantation--results of a retrospective analysis on 120 patients autografted in a single institution

PURPOSE: To analyze retrospectively survival and prognostic factors of patients with non-Hodgkin's lymphoma (NHL) autografted from 1979 to 1995 in a single institution. PATIENTS AND METHODS: A total of 120 patients, 64 with aggressive and 56 with low-grade NHL, were autografted. The carmustine (BCNU), etoposide, cytarabine, and melphalan (BEAM) regimen was used in 104. The autograft was marrow in 101 patients. Marrow was purged in vitro by mafosfamide for 63 patients (adjusted dose [AD] in 32; unique dose [UD] in 31); 27 patients received a CD34+-selected graft. Following intensification, 45 patients received additional radiotherapy on previous sites of involvement. RESULTS: Outcome at 5 years for patients transplanted with low-grade NHL in first complete remission (CR1), in first partial remission (PR1), and in second complete remission (CR2) or beyond showed an event-free survival (EFS) of 75% +/- 12%, 46% +/- 18%, and 57% +/- 24%, a relapse incidence (RI) of 21% +/- 12%, 49% +/- 19%, and 43% +/- 25%, and a transplant-related mortality (TRM) of 5% +/- 5%, 10% +/- 7%, and 0%, respectively. For patients with aggressive NHL transplanted in CR1, in PR1, in CR2 or beyond, and in resistant relapse or in primary refractory disease, the EFS was of 73% +/- 9%, 58% +/- 19%, 29% +/- 16%, and 10% +/- 9%, the RI 22% +/- 9%, 14% +/- 9%, 77% +/- 18%, and 66% +/- 20%, and the TRM 6% +/- 6%, 32% +/- 21%, 11% +/- 10%, and 71% +/- 22%, respectively. In patients autografted upfront in first remission, additional radiotherapy was associated with a higher EFS, in univariate (P = .03) and multivariate analysis (P = .02, relative risk [RR] = .021). The role of graft purging with mafosfamide on the outcome reflected by the dose of colony-forming unit-granulocyte-macrophage (CFU-GM) per kilogram infused postpurging was assessed by univariate analysis: patients in first remission who received lower doses of CFU-GM had a lower RI and a higher EFS. CONCLUSION: This retrospective analysis suggests that marrow purging and posttransplant radiotherapy improve the outcome of patients with NHL autografted in first remission.     

Characterization of anticapsular monoclonal antibodies that regulate activation of the complement system by the Cryptococcus neoformans capsule

PURPOSE: To evaluate the effectiveness of adding interferon (IFN) alfa-2b to chemotherapy in the induction treatment of low-grade non-Hodgkin's lymphoma (NHL), and to assess the role of maintenance IFN. PATIENTS AND METHODS: A multicenter, two-phase controlled trial with double randomization was conducted in 155 patients with low-grade NHL. In the first randomization, 78 patients received cyclophosphamide, vincristine, and prednisone (CVP) and IFN, 3 MU/m2 three times a week for 3 months, and 77 patients received CVP alone. Responding patients were randomized to receive IFN for 1 year versus observation. RESULTS: Of 144 assessable patients, 73 received CVP + IFN and 71 received CVP. Responses were similar: CVP + IFN 79% versus CVP 76% (P = .62). The number of patients who did not complete the treatment was higher in the CVP + IFN group than in the CVP group (18% v 4%; P = .009), although the received dose-intensity of chemotherapy was comparable. Duration of response and progression-free survival (PFS) were significantly higher in the CVP + IFN group than in the CVP group (P = .0004). However, we observed no differences in overall survival (OS) (P = .30), with a median follow-up for the surviving patients of 3 years. Grade 3/4 granulocytopenia was the most frequent toxicity and was similar in both groups (33% v32%). Eighty-three (74%) of the 112 responding patients were randomized to maintenance IFN or observation. The duration of response was similar between 42 patients that received IFN compared with 41 control patients (P = .83), independently of treatment previously administered. CONCLUSION: Adding IFN alfa-2b to induction CVP in low-grade NHL did not induce a higher response rate, but it significantly increased the duration of the responses. We found significant differences in PFS that favored the patients who received CVP + IFN, but not in OS. To date, no additional benefit has been seen from the administration of IFN for maintenance.     

Non-Hodgkin's lymphomas of the salivary gland: analysis of prognostic factors in 28 cases

Primary malignant lymphomas of the major salivary glands are rare and usually arise in the parotid gland (2% of all neoplastic disorders). In this report clinical records of 28 cases of NHL of salivary glands (27 in the parotid gland and one in the submandibular gland) are reviewed and problems related to diagnosis and management strategies are discussed. The 5-year overall survival rate was 72% and did non differ from the survival of other NHL of the head and neck. Statistical evaluation of prognostic factors (age, histology, clinical stage, grading, bulky and surgical approach--biopsy versus parotidectomy), are presented. Analysis of these factors showed that prognosis was not influenced by age, histology, clinical stage and grading of disease. Poor survival was significantly correlated to bulky lesions (tumor size greater than 6 cm). In our experience surgical treatment did not significantly affect survival rate. It is concluded that diagnostic surgical procedures in case of suspected NHL of the parotid gland are fine needle aspiration biopsy. (FNAB) or incisional biopsy. The treatment of choice is radiotherapy associated with chemiotherapy in cases of localized-bulky or disseminated disease.     

The MACOP-B and VACOP-B combination chemotherapy for young patients with intermediate-grade non-Hodgkin's lymphoma

Since the early 1970s, three generations of combination chemotherapy for intermediate-grade non-Hodgkin's lymphomas (NHL) have been developed. One of the third-generation regimens is MACOP-B (methotrexate, doxorubicin, cyclophosphamide, vincristine, prednisone, and bleomycin). The VACOP-B regimen is a modification of MACOP-B in which methotrexate is omitted and etoposide is added. This study assesses treatment outcome using the MACOP-B and VACOP-B combination chemotherapy in a population of young patients with intermediate-grade NHL treated in a single tertiary hematological center. The files of 45 patients aged 18-55 who were diagnosed as having intermediate-grade NHL (working formulation types F-H) and treated between January 1986 and March 1994 were reviewed. Treatment response, overall survival, disease-free survival and treatment toxicity were determined. The predictive value of the age-adjusted international prognostic index was also assessed. Median follow-up was 80 months in the MACOP-B group and 29 months in the VACOP-B group. The complete response rate was 71% (95% confidence interval CI: 58-84), 4-year overall survival was 74 +/- 7% and 4-year disease-free survival was 79 +/- 8%. No toxicity-related deaths were observed. The main adverse effects were WHO grade 3 or 4 neutropenia (51%), anemia (24%) and mucositis (20%). Only the CR rate was correlated with the Age-Adjusted International Prognostic Index. Mean relative dose intensity was high (95.7%, 95%) CI: 91.7-99.7) and had no correlation with treatment outcome. The MACOP-B and VACOP-B combination chemotherapy regimens were found to be effective and minimally toxic for young patients up to 55 years old with intermediate-grade NHL.     

Identification and partial characterization of two steroid 5 alpha-reductase isozymes in the canine prostate

BACKGROUND AND OBJECTIVE: Intensive induction and post-remission therapies have improved the prognosis in adult acute lymphoblastic leukemia (ALL). However, different from children, the impact of late intensification therapy in the overall results of treatment has not been consistently evaluated. The objective of this study was to analyze the results of a multicenter prospective protocol, PETHEMA ALL-89, in which, after intensive induction and consolidation therapy, randomization to receive delayed intensification treatment was performed. DESIGN AND METHODS: One hundred and eight adults (age > or = 15 years) diagnosed with ALL (ALL L3 excluded) in 22 Spanish hospitals from 1989 to 1994 were treated with a five-drug induction therapy, followed by four cycles of early post-remission treatment during four months, and maintenance therapy for two years. Patients in remission at the end of the first year were randomized to receive one six-week cycle of late intensification therapy. Uni- and multivariate analyses of early response to treatment, complete remission (CR), leukemia-free survival (LFS) and overall survival (OS) were performed. RESULTS: The median (range) age of the series was 28 (15-74) years and leukocyte count 26 x 10(9)/L (1-600). ALL L1/L2 was present in 38/70 patients, early pre-B in 13, common in 53, pre-B in 12 and T in 30 cases. The CR rate was 86%, and refractory disease 9%. Median LFS was 34 months, with a 5-yr probability of 41% (95% CI, 29-53), whereas median OS was 51 months and 5-year probability 47% (34-59%). There were no differences in either LFS and OS between patients who did or did not receive delayed intensification therapy. Prognostic factors for CR attainment were advanced age and slow response to therapy. These two features were, in addition to high leukocyte counts, the parameters with negative influence in both LFS and OS. INTERPRETATION AND CONCLUSIONS: The results of PETHEMA ALL-89 are similar to those referred in other chemotherapy-based protocols in adult ALL. Delayed intensification has not improved the length of remission and survival. Efforts to improve the prognosis of adult ALL patients must be mainly focused in early intensification treatment.     

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.     

Phase II study of carboplatin in blast crisis of chronic myeloid leukemia: Eastern Cooperative Oncology Group Study E1992

This study was a phase II evaluation of the activity of carboplatin in patients with Philadelphia chromosome positive accelerated or blastic phase of CML. Carboplatin, 250 mg/m2/day as an intravenous continuous infusion was given for 5 days, for a total dose of 1250 mg/m2 per course. If necessary, a second induction course could be given, and patients achieving complete remission were to receive an additional consolidation cycle at the same dose. Thirty-six patients were eligible and evaluable. There were five complete and three partial remissions for an overall response rate of 22% (95% CI 10.1-39.1%). The complete remission rate was 13.9% (95% CI 4.7-29.9%). The median remission duration was 3 months (range 1.4-8.94 months) and the median survival on study for all patients was 3.5 months (95% CI, 2.4-11.4 months). The median survival of responders was 12.8 months (95% CI, 3.6-17.2 months). Three eligible patients survived 2.0, 2.5 and 3.5 years following carboplatin therapy. Carboplatin has activity in blast crisis of CML, but responses are brief. Response did allow one patient to proceed to bone marrow transplantation and two other patients to continue therapy for chronic phase disease before returning to blast crisis. Activity in combination regimens should be explored.     

Comparison between four and eight cycles of intensive chemotherapy in adult acute myeloid leukemia: a randomized trial of the Finnish Leukemia Group

In acute myelogenous leukemia (AML) intensive postremission treatment is needed for an optimal result. However, it is not known how long the treatment should last and how many courses are necessary. The object of this prospective study was to compare four and eight intensive chemotherapy cycles in the treatment of adult de novo AML. In a multicenter study, 248 consecutive patients, aged from 16 to 65 years, were treated with intensive induction treatment. The patients in remission after two courses were randomized to receive either two (short arm) or six (long arm) additional intensive cycles of chemotherapy. The median follow-up time of the living patients is 68 months. Of the patients, 77% achieved complete remission, and 36% of all patients survived for 5 years. Seventy-three patients were randomized to the short arm and 66 to the long arm. There was no significant difference in the relapse-free survival (median 21 months vs 17 months) or overall survival (43 months vs 39 months) between the short and long arms, respectively. Treatment-related deaths occurred in 31 patients (13%), 11 of them in first remission. More than one-third of the patients survived for 5 years. It seems probable that the first few months after diagnosis are decisive for the prognosis if the chemotherapy is intensive, and further treatment cannot markedly influence the outcome.     

Maintenance therapy with interferon alfa 2b in Hodgkin's disease

We performed a randomized clinical trial to assess the efficacy and toxicity of interferon alfa 2b (IFN) as maintenance therapy in patients with advanced Hodgkin's disease in complete remission (CR) after conventional chemotherapy. One hundred and thirty-five patients (stage IIIB-IV B) were initially treated with EBVD (epirubicin, bleomycin, vinblastine, dacarbazine). IF CR was achieved they were randomly assigned to receive either maintenance therapy with IFN 5.0 MU three times a week for one year or no further treatment (control group). Clinical and laboratory characteristics at diagnosis were quite similar in both groups. After a median follow-up of 74.3 months (range 49 to 108), 61 out of 68 patients (91%; 95% confidence interval (CI): 76% to 97%) remain in first complete remission in the IFN-treated group compared to 38 out of 67 (58%; 95% CI: 49% to 71%) in the control group (p<.01). Overall survival was also better in the IFN treated group: 62 patients (92%; 95% CI: 82% to 97%) are alive free of disease at 7-years compared to 40 patients (67%, 95%: 55% to 76%) in the control group (p<.01). Toxicity secondary to IFN administration was mild and no dose modification was necessary during treatment. All patients received the planned dose of IFN. This was not an intent-to treat analysis. IFN administration as maintenance therapy was appears to be the only cause of improvement in outcome in these patients. We feel that IFN should be considered as maintenance therapy in patients with advanced Hodgkin's disease because this treatment improves the final outcome without the excessive toxicities of more aggressive therapeutic approaches such as bone marrow transplantation during first CR. We hope that IFN will be considered in future randomized clinical trials in order to define it's role in the treatment of Hodgkin's disease.     

Long term follow-up and late complications of 2-chlorodeoxyadenosine in previously treated, advanced, indolent non-Hodgkin's lymphoma

BACKGROUND: The aim of this study was to determine the long term outcome and toxicities after the administration of 2-chlorodeoxyadenosine (2-CdA) to patients with previously treated, advanced, indolent non-Hodgkin's lymphoma (NHL). METHODS: Twenty-two patients (median age, 55 years) with relapsed or refractory low grade NHL (median disease duration, 2.8 years) were treated with 2-CdA by continuous infusion at 0.1 mg/kg/day over 5 or 7 days every 28 days, for a maximum of 6 cycles. RESULTS: The overall response rate was 45%. Two patients (9%) achieved a complete response (CR), 8 patients (36%) achieved a partial response, and 12 patients (55%) had no response. The two patients achieving CR have remained in CR for 46 and 38 months, respectively. Freedom from treatment failure at 24 months was 32%. Overall survival at 24 months was 59%. Three patients developed second malignancies: acute myelogenous leukemia (AML), myelodysplastic syndrome, and a cutaneous lymphoproliferative disorder. Fourteen patients have died after a median follow-up of 28 months (range, 3.9-49.2 months) due to progressive NHL (11 patients), infection (2 patients), and AML (1 patient). CONCLUSIONS: 2-CdA is an active agent for patients with previously treated, advanced, indolent NHL and may result in lasting remissions. Late complications following treatment may include delayed bacterial, fungal, or viral infection. Determination of whether the second malignancies that occurred in three patients reported herein were related to treatment with 2-CdA will require further study.     

Bulky centroblastic non-Hodgkin's lymphoma of the cranium vault mimicking brain involvement managed with chemotherapy: a case report

BACKGROUND: Patients with central nervous system (CNS) involvement by high grade non-Hodgkin's lymphoma (NHL) have a poor prognosis. The roles of computed tomography, radiotherapy, and intrathecal and systemic chemotherapy still need to be defined. METHODS: A patient with bulky cranial lymphoma mimicking brain involvement is reported. A 62-year-old man was admitted with a huge scalp lump, headache, fatigue, and focal and generalized neurologic symptoms. Computed tomography showed an abnormal mass in the frontoparietal region involving the subcutaneous scalp, osteolytic destruction of the cranial vault, and a bulky mass that was interpreted to be intracranial. A systemic survey also revealed bulky retroperitoneal involvement and focal involvement of the spleen. Biopsy revealed a B-cell NHL of centroblastic type according to the Kiel classification. RESULTS: The patient was treated with a modified combination of cyclophosphamide plus mitoxantrone plus vincristine plus prednisone (CNOP) and intrathecal methotrexate. The patient responded with complete remission, including partial bone restoration of the cranium. At the time of this writing, his relapse free survival lasted 5 years. CONCLUSIONS: The initial interpretation of this case indicated that systemic chemotherapy with modified CNOP plus intrathecal methotrexate would be useful in the management of NHL with CNS involvement. The clinical outcome with rapid neurologic repair and also bone restoration of the cranial vault within 5 years suggests that the lymphoma probably never penetrated the dura and a successful treatment was achieved with combination chemotherapy only.     

序贯诱导法治疗高危急性非淋巴细胞白血病

目的 探讨小剂量HA(LD-HA)方案及标准方案序贯诱导法治疗高危急性非淋巴细胞白血病(ANLL)的疗效.方法 对50例不适合常规诱导的高危ANLL患者(LD-HA组)进行了序贯诱导.第1个周期诱导方案为LD-HA,首次诱导仍未缓解者,更换为标准方案(DA或HA)诱导.选择同期以DA或HA方案诱导治疗的23例ANLL患者(DA/HA组)作为对照,最多诱导2个周期.结果 LD-HA组患者完全缓解率为80.0%(40/50),诱导过程死亡2例;中位无瘤生存时间为19.6个月,中位生存时间为12.2个月;1、3、5年生存率分别为57.0%、24.1%、18.8%.DA/HA组共17例完全缓解,缓解率为73.9%;中位无瘤生存时间为19.8个月,中位生存时间为12.1个月;1、3、5年生存率分别为56.58%、27.1%、27.1%,两组相比,1、3、5年生存率差异无统计学意义(x2值分别为0.009、0.237、1.807,P值均＞0.05).结论 以LD-HA及标准方案序贯诱导高危ANLL患者,可获得较高的完全缓解率及长期生存率.