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.     

原发结内外周T细胞淋巴瘤19例临床特征及预后分析

目的 分析原发结内外周T细胞淋巴瘤(PTCL)的临床特点、治疗和预后.方法 回顾性分析19例原发结内PTCL患者的临床资料、治疗反应以及预后因素.结果 19例患者中位发病年龄54岁,男女比例2.17∶1,其中94.7%(18/19)为Ⅲ～Ⅳ期,84.2%(16/19)有B症状,84.2%(16/19)有结外器官受累,57.9%(11/19)有骨髓浸润.化疗完全缓解(CR)率36.8%(7/19),2年总生存(OS)率47.4%,2年无进展生存(PFS)率25%.预后分析显示,结外侵犯数量(EN)≥2个、美国东部肿瘤协作组(ECOG)体能状态评分≥2分、国际预后指数(IPI)评分＞2分以及β2-微球蛋白(βrMG)升高为不良预后因素.结论 原发结内PTCL是一类高度侵袭的异质性T细胞淋巴瘤,化疗效果差,多项因素提示不良预后.     

Bleomycin, adriamycin, cyclophosphamide, vincristine, deacadron, etoposide (BACOD-E) chemotherapy for the treatment of non-Hodgkin's lymphoma: long-term survival rate and complications

This study was performed to analyze the effect of Bleomycin, Adriamycin, Cyclophosphamide, Vincristine, Deacadron, Etoposide (BACOD-E) chemotherapy for patients with non-Hodgkin's lymphoma. Seventy patients with non-Hodgkin's lymphoma (stage I: 15, stage II: 23, stage III: 20, and stage IV: 12) were treated at the Department of Radiology, Chiba University Hospital, between 1987 and 1995. The response rates for treatment were CR: 63%, PR: 35%, and PD: 2%. The overall disease-free 5-year survival rate was 54%, and those for each stage were as follows: stage I: 78%, stage II: 55%, stage III: 51%, and stage IV: 28%. There were no significant differences between patients with and without B symptoms, or those with and without elevated LDH levels. Treatment associated deaths occurred in six patients. Two patients died due to side effects of chemotherapy during treatment, and one patient due to leukemia 2 years and 5 months after treatment. One patient died due to radiation pneumonitis, one patient due to heart failure, and one patient due to an unknown reason one month after treatment. This chemotherapy may be useful for patients with advanced disease or unfavorable prognostic factors such as B symptoms or elevated LDH. Moreover, the addition of radiation therapy may prolong survival.     

Prognostic factors for survival of non-Hodgkin's lymphoma patients treated with high-dose chemotherapy and autologous bone marrow transplantation

Prognostic factors to identify patients with high-risk non-Hodgkin's lymphoma (NHL) have recently been developed. We retrospectively investigated the relation between prognostic factors and treatment outcome after autologous bone marrow transplantation (ABMT). From 1984 to 1994, 80 consecutive patients with NHL responding slowly to or relapsing after front-line therapy were treated with high-dose chemotherapy and ABMT. Prognostic factors at the time of diagnosis and of ABMT were related to clinical outcome after ABMT. The cumulative 5-year overall survival (OS) was 51%, progression-free survival (PFS) 41%, and relapse-free survival (RFS) 53%. Absence of B symptoms and intermediate-grade malignancy at first presentation of disease were independently related to prolonged OS (P = 0.02 and P < 0.01, respectively) and prolonged PFS (P = 0.005 and P = 0.01, respectively). At the time of ABMT, first PR or CR, normal LDH levels and tumour stage I + II were associated with prolonged OS (P = 0.0005, P = 0.03 and P = 0.004, respectively). A Coiffier index of 0 or 1, first PR or CR and no extranodal disease involvement were related to prolonged PFS (P = 0.0002, P = 0.005 and P = 0.07, respectively). Treatment-related deaths occurred in 10% of patients. Assessment of disease status, LDH level, tumour stage, extranodal disease involvement and Coiffier index at the time of ABMT is respectively efficient in predicting treatment outcome after ABMT.     

Prognostic factors affecting long term outcome after liver resection for hepatocellular carcinoma: results in a series of 100 Italian patients

BACKGROUND: Long term results after liver resection for hepatocellular carcinoma (HCC) are disappointing because the disease tends to recur. In this study, the authors assessed prognostic factors affecting long term outcome, in the hope that these factors might be used in selecting HCC patients for surgery. METHODS: During the period 1977-1995, 100 consecutive patients underwent curative liver resection; 78 of 100 had HCC arising on preexisting cirrhosis (53 Child's Class A and 25 Child's Class B). Thirty-five prognostic factors were evaluated for their association with overall survival (OS) and disease free survival (DFS) in univariate and multivariate analysis (Cox proportional hazards model). RESULTS: There were four postoperative deaths. Seven patients died in hospital of hepatorenal failure: six had Child's Class B cirrhosis and had undergone preoperative chemoembolization. Of the remaining 89 patients, 50 developed recurrence. All surviving Child's Class B patients had recurrence. Five-year OS, postoperative deaths included, was 38% (median, 36 months). Five-year DFS, postoperative deaths excluded, was 26% (median, 21 months). Independent prognostic factors for DFS were Child's class, glutamic-oxaloacetic transaminase, gamma-glutamyltransferase, alpha-fetoprotein, number of tumor nodules, width of resection margins, preoperative chemoembolization, and experience of the team that performed the surgery. Factors with an independent effect on OS were Child's class and width of resection margins. CONCLUSIONS: Liver resection can provide long term DFS in HCC patients with normal liver function. In patients with liver function impairment or an inadequate resection margin, recurrences are almost certain to occur. Preoperative chemoembolization significantly prolongs DFS but may increase the risk of postoperative liver failure in patients with liver function impairment.     

Multimodality treatment of 128 patients with locally advanced breast carcinoma in the era of mammography screening using standard polychemotherapy with 5-fluorouracil, epirubicin, and cyclophosphamide: prognostic and therapeutic implications

BACKGROUND: Locally advanced breast carcinoma is associated with a poor prognosis. With single treatment modalities, i.e., surgery and/or radiation therapy, results have been consistently dismal. However, several earlier reports have indicated improvement in survival with a combined modality approach, i.e., the utilization of systemic therapy. METHODS: Between 1991 and 1994, 128 patients with locally advanced noninflammatory or inflammatory breast carcinoma (LABC) were treated with a combined modality strategy consisting of 4-6 courses of preoperative 5-fluorouracil (600 mg/m2), epirubicin (60 mg/m2), and cyclophosphamide (600 mg/m2) (FEC) every 3 weeks, followed by modified radical mastectomy or sector resection with axillary dissection in combination with postoperative radiotherapy and concomitant cyclophosphamide (850 mg/m2). Postoperatively, 3-5 adjuvant courses of FEC therapy were given. Nine percent of the patients received preoperative radiotherapy because the FEC therapy was not sufficiently effective. One-third of the patients were given tamoxifen (20 or 40 mg daily) at the end of the multimodal therapy. RESULTS: Clinical responses were observed in 60% of the patients; 5% had complete responses (CR) and 55% had partial responses (PR). Stable disease (SD) was observed in 40%. No patient had progressive disease (PD) preoperatively. With a median follow-up of 37 months, the median disease free survival (DFS) and median overall survival (OS) were 29 and 54 months, respectively. The actuarial 5-year DFS and OS were 36% and 49%, respectively. The locoregional recurrence rate was 20%, and 53% of the patients experienced systemic relapse. Univariate analysis revealed a significant prognostic difference according to clinical stage of LABC in favor of less advanced stages. Clinical and biologic parameters linked to a significantly worse prognosis were the presence of inflammatory breast carcinoma and peau d'orange. There was a significant trend of worse prognosis for patients receiving below 60% and 75% of the intended dose intensity with reference to DFS and OS, respectively. CONCLUSIONS: Standard dose preoperative and postoperative FEC therapy combined with surgery and radiotherapy in the era of mammography screening seem to yield results comparable to those achieved with other conventional strategies in the treatment of unscreened populations.     

The GIMEMA ALL 0183 trial: analysis of 10-year follow-up. GIMEMA Cooperative Group, Italy

We report the 10-year follow-up of the GIMEMA ALL 0183 trial. From 1983 to 1987, 358 adults with acute lymphoblastic leukaemia (ALL) were entered into this trial, which included a mild induction, an early intensive consolidation, a post-consolidation phase randomized in conventional maintenance (arm A) and in more intensive regimen (arm B). CNS prophylaxis did not include CNS irradiation. The overall complete remission (CR) rate was 79.3% (284/358); 212 patient were randomized (110 in arm A and 102 in arm B). The median overall CR duration was 20 months and the median overall survival (OS) 21 months; both curves reach a plateau after 6 years; at 10 years 25% of patients were projected to be in long-term remission and survivors. The median disease-free survival (DFS) was 17 months, at 10 years 27% and 28% of patients were DFSs in arm A and in arm B respectively. In multivariate analysis age, WBC count and L2 FAB subtype were found to significantly influence OS and DFS. With regard to our previous report OS appears to linearly correlate with initial WBC count and age (P = 0.0002 and P = 0.042 respectively). 195 (68.7%) patients relapsed (only 25 had isolated CNS). The overall second CR rate was 56.5%; 23 patients underwent transplantation (12 BMT and 11 ABMT). Post-relapse survival was found to be influenced by the duration of first CR.     

Burkitt's lymphoma in adults with and without human immunodeficiency virus infection: a single-institution clinicopathologic study of 75 patients

BACKGROUND: Burkitt's lymphoma (BL) accounts for 1-2% of all cases of non-Hodgkin's lymphoma (NHL) in the general population and for 35-40% in the setting of human immunodeficiency virus (HIV) infection. The authors report a 9-year single-institution experience with 75 adult BL patients (46 with and 29 without HIV infection) and compare the clinical and pathologic features of the disease in the two groups of patients. METHODS: Between May 1987 and June 1995, 131 patients with HIV infection and systemic NHL were diagnosed and treated at the National Cancer Institute in Aviano, Italy. In 46 cases (35%), the diagnosis was BL. During the same period, 29 of 1004 HIV negative NHL patients (2.8%) were diagnosed with BL and treated at the same institution. RESULTS: No statistical differences were found in the general characteristics of the two groups at the time that BL was diagnosed. Complete response rate was significantly lower for patients with HIV infection than for those without HIV infection (40% vs. 65%, P = 0.03). The median overall survival was significantly shorter for patients with HIV infection (7 months vs. not yet reached, P = 0.0001). However, the disease free survival (DFS) at 4 years was identical for the two groups of patients (74% for HIV positive patients vs. 73% for HIV negative patients, P = 0.70). CONCLUSIONS: The data from this study show that patients with BL with and without HIV infection share similar clinicopathologic characteristics at presentation. Although the median overall survival is significantly shorter for patients with HIV infection, the DFS is identical for both groups.     

Clinical relevance of BCL2, BCL6, and MYC rearrangements in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLCL) is characterized by a marked degree of morphologic and clinical heterogeneity. We studied 156 patients with de novo DLCL for rearrangements of the BCL2, BCL6, and MYC oncogenes by Southern blot analysis and BCL2 protein expression. We related these data to the primary site of presentation, disease stage, and other clinical risk factors. Structural alterations of BCL2, BCL6, and MYC were detected in 25 of 156, 36 of 116, and 10 of 151 patients, respectively. Three cases showed a combination of BCL2 and BCL6 rearrangements, and two cases had a combination of BCL6 and MYC rearrangements. BCL2 rearrangement was found more often in extensive (39%) and primary nodal (17%) lymphomas than in extranodal cases (4%) (P = .003). BCL2 rearrangement was present in none of 40 patients with stage I disease, but in 22% of patients with stage II to IV (P = .006). The presence of BCL2 rearrangements did not significantly affect overall survival (OS) or disease-free survival (DFS). In contrast, high BCL2 protein expression adversely affected both OS (P = .008) and DFS (P = .01). BCL2 protein expression was poorly correlated with BCL2 rearrangement: only 52% of BCL2-rearranged lymphomas and 37% of BCL2-unrearranged cases had high BCL2 protein expression. Rearrangement of BCL6 was found more often in patients with extranodal (36%) and extensive (39%) presentation versus primary nodal disease (28%). No significant correlation was found with disease stage, lymphadenopathy, or bone marrow involvement. DFS and OS were not influenced by BCL6 rearrangements. MYC rearrangements were found in 16% of primary extranodal lymphomas, versus 2% of primary nodal cases (P = .02). In particular, gastrointestinal (GI) lymphomas (5 of 18 cases, 28%) were affected by MYC rearrangements. The distinct biologic behavior of these extranodal lymphomas was reflected by a high complete remission (CR) rate: 7 of 10 patients with MYC rearrangement attained complete remission and 6 responders remained alive for more than 4 years, resulting in a trend for better DFS (P = .07). These data show the complex nature of molecular events in DLCL, which is a reflection of the morphologic and clinical heterogeneity of these lymphomas. However, thus far, these genetic rearrangements fail as prognostic markers.     

Prognostic significance of bcl-2 protein expression in aggressive non-Hodgkin's lymphoma. Groupe d'Etude des Lymphomes de l'Adulte (GELA)

Little is known about the expression of bcl-2 protein in intermediate and high grade non-Hodgkin's lymphoma (NHL) and its clinical and prognostic significance. We performed immunohistochemical analysis of bcl-2 expression in tumoral tissue sections of 348 patients with high or intermediate grade NHL. These patients were uniformly treated with adriamycin, cyclophosphamide, vindesine, bleomycin, and prednisone (ACVBP) in the induction phase of the LNH87 protocol. Fifty eight cases were excluded due to inadequate staining. Of the 290 remaining patients, 131 (45%) disclosed homogeneous positivity (high bcl-2 expression) in virtually all tumor cells, whereas 65 (23%) were negative and 94 (32%) exhibited intermediate staining. High bcl-2 expression was more frequent in B-cell NHL (109 of 214, 51%) than in T-cell NHL (6 of 35, 17%) (P = .0004), and was heterogeneously distributed among the different histological subtypes. Further analysis was performed on the 151 patients with diffuse large B-cell lymphoma (centroblastic and immunoblastic) to assess the clinical significance and potential prognostic value of bcl-2 expression in the most frequent and homogeneous immunohistological subgroup. High bcl-2 expression, found in 44% of these patients (67 of 151), was more frequently associated with III-IV stage disease (P = .002). Reduced disease-free survival (DFS) (P < .01) and overall survival (P < .05) were demonstrated in the patients with high bcl-2 expression. Indeed, the 3-year estimates of DFS and overall survival were 60% and 61%, respectively (high bcl-2 expression) versus 82% and 78%, respectively (negative/intermediate bcl-2 expression). A multivariate regression analysis confirmed the independent effect of bcl-2 protein expression on DFS. Thus bcl-2 protein expression, as demonstrated in routinely paraffin-embedded tissue, appears to be predictive of poor DFS, in agreement with the role of bcl-2 in chemotherapy-induced apoptosis. It might be considered as a new independent biologic prognostic parameter, which, especially in diffuse large B-cell NHL, could aid in the identification of patient risk groups.     

MTAP、CDKN2A和CDKN2B在弥漫大B细胞淋巴瘤中的表达及其临床意义

目的 研究弥漫大B细胞淋巴瘤(DLBCL)MTAP、CDKN2A和CDKN2B基因的表达及其临床意义.方法 以实时定量聚合酶链反应(PCR)方法检测40例DLBCL及19例淋巴结反应性增生组织中MTAP、CDKN2A和CDKN2B基因的表达情况,结合临床特征进行分析,并进行随访.结果 DLBCL组MTAP、CDKN2A和CDKN2B基因表达水平较淋巴结反应性增生组降低,差异有统计学意义(P值分别为0.024、0.044和0.047);三者表达均与Ann Arbor临床分期相关(P值分别为0.004、0.001和0.027);与患者的性别、年龄、淋巴结外病变累及、ECOG体力评分、骨髓累及、血清乳酸脱氢酶水平均无明显相关(均P＞0.05).其中MTAP与CDKN2A基因表达情况还与B症状(P值分别为0.003和0.028)和国际预后指数(IPI)相关(P值分别为0.001和0.011).此外,生存分析结果显示,MTAP、CDKN2A和CDKN2B基因表达水平与患者总生存期相关(P值分别为0.022、0.019和0.042).结论 MTAP、CDKN2A和CDKN2B基因在DLBCL中呈低水平表达,与疾病进展和患者预后有关,可作为反映其生物学行为和评估患者临床疗效的分子标志物.     

三阴性乳腺癌5年随访

Objective: The aim of the study was to investigate the long-term therapeutic effects of triple negative breast cancers (TNBCs) and find a standardized treatment. Methods: The clinical data and survival status of 69 patients with TNBC were collected, who were treated from 2003 to 2007 at Chongqing Cancer Institute, China. Results: Median observation for 61 months showed the local recurrence rate was 13.0% (9/69), the overall survival (OS) rate was 76.8% (53/69) and the disease free survival (DFS) rate was 59.4% (41/69). Log-rank univariate survival analysis showed the OS and DFS rates of TNBCs with axillary lymph node metastasis were 38.1% and 23.8%, respectively, and the OS and DFS rates of triple negative breast cancer with axillary lymph node non-metastasis were 93.8% and 75.0%, respectively. There were significant differences comparing with two groups. Indictor analysis of age, menstruation status, tumor size, TNM stage, histological type,neoadjuvant chemotherapy and p53 did not show any prognostic influence. Conclusion: The axillary nodes metastasis is associated with DFS and OS in triple negative breast cancers. Cisplatin-based chemotherapy may be good choice for triple negative breast cancers with metastasis or local recurrence, who received Anthracyciine and Taxane-based chemotherapy.Targeted therapies strategies such as EGFR-targeted therapy may be necessary.     

Comparison of autologous bone marrow transplantation and intensive chemotherapy as postremission therapy in adult acute myeloid leukemia. The Groupe Ouest Est Leucémies Aigu?s Myéloblastiques (GOELAM)

Three intensive consolidation strategies are currently proposed to younger adults with acute myeloid leukemia (AML) in first complete remission (CR): allogeneic or autologous bone marrow transplantation (BMT) and intensive consolidation chemotherapy (ICC). Patients aged 15 to 50 years with de novo AML received an induction treatment with 7 days of cytarabine and either idarubicin or rubidazone. After achievement of a CR, patients up to the age of 40 and having an HLA-identical sibling were assigned to undergo an allogeneic BMT. All the other patients received a first course of ICC with high-dose cytarabine and the same anthracycline as for induction. They were then randomly assigned to either receive a second course of ICC with amsacrine and etoposide or a combination of busulfan and cyclosphosphamide followed by an unpurged autologous BMT. Of 517 eligible patients, 367 had a CR, but only 219 (59.5%) actually received the planned intensive postremission treatment (73 allogeneic BMT, 75 autologous BMT, and 71 ICC). With a median follow-up of 62 months, the 4-year disease-free survival (DFS) of the 367 patients in CR was 39.5%. The 4-year overall survival (OS) of the 517 eligible patients was 40.5%. In multivariate analysis, DFS and OS were influenced only by the initial white blood cell count and by the French-American-British classification. The type of postremission therapy had no significant impact on the outcome. There was no difference in the 4-year DFS and OS between 88 patients for whom an allogeneic BMT was scheduled (respectively, 44% and 53%) and 134 patients of the same age category and without an HLA-identical sibling (respectively, 38% and 53%). Similarly, there was no difference in the outcome between autologous BMT and ICC. The 4-year DFS was 44% for the 86 patients randomly assigned to autologous BMT and 40% for the 78 patients assigned to ICC (P = .41). The 4-year OS was similar in the two groups (50% v 54.5%, P = .72). The median duration of hospitalization and thrombocytopenia were longer after autologous BMT (39 v 32 days, P = .006, and 109.5 v 18.5 days, P = .0001, respectively). After a first course of ICC, a second course of chemotherapy is less myelotoxic than an unpurged autologous BMT but yields comparable DFS and OS rates.     

Prognostic significance of Bcl-2 protein expression and Bcl-2 gene rearrangement in diffuse aggressive non-Hodgkin's lymphoma

The prognostic significance of Bcl-2 protein expression and bcl-2 gene rearrangement in diffuse large cell lymphomas (DLCL) is controversial. Bcl-2 protein expression prevents apoptosis and may have an important role in clinical drug resistance. The presence of a bcl-2 gene rearrangement in de novo DLCL suggests a possible follicle center cell origin and perhaps a distinct clinical behavior more akin to low-grade non-Hodgkin's lymphoma (NHL). The purpose of this study was to determine the impact of Bcl-2 protein expression and bcl-2 gene rearrangement (mbr and mcr) on survival of a cohort of patients with DLCL who were uniformly evaluated and treated with effective chemotherapy. Patients included the original MACOP-B cohort (n = 121) and the initial 18 patients treated with the VACOP-B regimen (total = 139). All patients had advanced-stage disease, were 16 to 70 years old, and corresponded to Working Formulation categories F, G, or H. No patients had prior treatment, discordant lymphoma, or human immunodeficiency virus seropositivity. Paraffin sections from diagnostic biopsies were analyzed for bcl-2 gene rearrangement including mbr and mcr breakpoints by polymerase chain reaction and Bcl-2 protein expression by immunohistochemistry. With a median follow-up of 81 months, overall (OS), disease-free (DFS), and relapse-free survival (RFS) were measured to determine the prognostic significance of these parameters. Analyzable DNA was present in 118 of 139 (85%) cases, with 14 demonstrating a bcl-2 rearrangement (11 mbr, 3 mcr). All 14 of these bcl-2 gene rearrangement-positive cases were found in the 102 patients with a B-cell immunophenotype, but the presence of this rearrangement had no significant influence on survival. Bcl-2 protein expression was interpretable in 116 of 139 (83%) cases, with immunopositivity detected in 54 of 116 (47%). Using a cut-off of greater than 10% Bcl-2 immunopositive tumor cells for analysis, positive Bcl-2 protein expression was seen in 28 of 116 (24%) patients and the presence of this expression correlated with decreased 8-year OS (34% v 60%, P < .01), DFS (32% v 66%, P < .001), and RFS (25% v 59%, P < .001). Bcl-2 protein expression remained significant in multivariate analysis that included the clinical international prognostic index factors and immunophenotype (P < .02). In conclusion, although bcl-2 gene rearrangement status could not be shown to have an impact on outcome, Bcl-2 protein expression is a strong significant predictor of OS, DFS, and RFS in DLCLs.     

Allogeneic bone marrow transplantation in Korea: 1983-92

Between March 1983 and December 1992, we performed 178 allogeneic BMTs for patients with hematopoietic stem cell disorders: 48 acute myelogenous leukemia (AML), 27 acute lymphoblastic leukemia (ALL), 40 chronic myelogenous leukemia (CML), 55 severe aplastic anemia (SAA), 6 myelodysplastic syndrome (MDS), 1 non-Hodgkin's lymphoma and 1 hybrid leukemia. Twenty-five of 48 AML are in disease-free survival (DFS). Fifteen of 27 ALL are in unmaintained remission. Twenty-four of 40 CML are in DFS. Forty-four out of 55 SAA patients are alive and well. Comparing the survival between standard (< or = CR1: 21 of 31 (68%)) and high risk (> or = CR2: 4 of 17 (24%)) AML, our data suggest that the preparative regimen for high risk AML was not potent enough to eradicate the residual disease in advanced AML. Although our cases are limited and the follow-up period is short, the result of ALL (overall: 56%, standard risk (adult < or = CR1, children < or = CR2: 10 of 14 (71%) and high risk (adult > or = CR2, children > CR2): 5 of 13 (38%)) and CML (overall: 60%; CP: 19 of 27 (70%), AP or BC: 5 of 13 (38%)) are promising. The probability of 5 year survival of SAA was 80 +/- 4 years.(ABSTRACT TRUNCATED AT 250 WORDS)     

High-dose busulfan, melphalan and thiotepa followed by autologous peripheral blood stem cell (PBSC) rescue in patients with advanced stage III/IV ovarian cancer

The purpose of this study was to evaluate the efficacy of high-dose chemotherapy (HDC) with busulfan, melphalan and thiotepa (BUMELTT) followed by autologous PBSC infusion in treating patients with advanced ovarian cancer. Thirty-one patients, 18 with stage III/IIIc and 13 with stage IV ovarian cancer, were treated with BU (12 mg/kg), MEL (100 mg/m2) and TT (500 mg/m2) and autologous PBSC rescue. Fifteen patients were in clinical complete remission (CR) at treatment; 11 had platinum-sensitive disease. Sixteen patients were not in CR; two had platinum-sensitive disease. The probabilities of overall survival (OS), event-free survival (EFS) and relapse (R) for all patients at 18 months were 0.57, 0.30 and 0.63; for patients in CR, the rates were 0.87, 0.44 and 0.49 and for patients not in CR, 0.38, 0.13 and 0.81. Two patients (6.5%) died of treatment-related causes. Among the 13 patients with platinum-sensitive disease, all are still alive, with seven having relapsed 129-1021 days after PBSC infusion. OS, EFS and R were 1.00, 0.52 and 0.48. Of the 18 patients with platinum-resistant disease, four remain alive (two in remission). Six patients did not respond and eight relapsed from days 104-429. The OS, EFS and R were 0.33, 0.11 and 0.78. We conclude that BUMELTT is well tolerated in patients with advanced ovarian cancer and results are equivalent to other published HDC regimens.     

Adjuvant cyclophosphamide, methotrexate and fluorouracil for node-positive breast cancer: a lifetime cost-utility analysis based on a modified Q-TWIST method

The Q-TWIST (time spent without symptoms and toxicity) method [1-4] and the Gompertz extrapolation method [5-11] are two techniques that have been proposed for evaluating survival in cancer patients. The mathematical basis of the Q-TWIST method relies on estimating the area under the survival curve and partitioning its value into three components with different levels of quality of life (presence of toxicity, presence of symptoms, absence of symptoms and toxicity). The Gompertz approach utilises a curve-fitting procedure to extrapolate the survival curves to infinity. A recent report [12] has described a combined application of the Q-TWIST method and the Gompertz approach ("extrapolated Q-TWIST" method), which allows one to conduct a cost-utility analysis with the calculation of the cost per QALY (quality-adjusted life year) gained. In this paper, we describe a reappraisal of an earlier cost-effectiveness study [7] by application of this extrapolated Q-TWIST method [12]. Our cost-effectiveness study [7] evaluated the pharmacoeconomic profile of adjuvant cyclophosphamide, methotrexate and fluorouracil (CMF) in patients with node-positive breast cancer [13] and utilised a Gompertz analysis to estimate lifetime overall survival (OS), which was 862 and 756 discounted years per 100 patients in the CMF and the control groups, respectively. In applying the extrapolated Q-TWIST method to this data set, a second Gompertz analysis is carried out on the disease-free survival (DFS) curve of the two patient groups. Lifetime DFS of Bonadonna's patients can thus be estimated as 741 years in the CMF group and 572 years in the controls (discounted values normalised to 100 patients). Figure 1 shows the two curves of OS and DFS for the CMF group and the partition of the area under the OS curve into its three components. To introduce an assessment of quality of life into these data, the Q-TWIST method partitions the value of OS into the three components called TWIST (absence of symptoms and toxicity), TOX (time spent with toxicity) and REL (survival after relapse). Hence, OS = TWIST + REL + TOX, where REL = OS - DFS. In the control group, TOX = O and TWIST = DFS because no treatment-related toxicity is present.     

Petrous bone approach for the surgery of petroclival meningiomas

Adult patients with acute lymphoblastic leukemia (ALL) were treated according to the ALL90 study, the second prospective study for ALL of the Japan Adult Leukemia Study Group (JALSG). Its characteristics included response-oriented individualized induction therapy with six drugs (doxorubicin, mitoxantrone, vincristine, prednisolone, [corrected] cyclophosphamide and L-asparaginase), and a prospective comparison between allogeneic bone marrow transplantation (allo-BMT) and chemotherapy alone in patients below 45 years of age. The protocol consisted of one or two courses of induction, four courses of consolidation, and three courses of intensification including 12 month maintenance and six times of central nervous system (CNS) prophylaxis. Of 180 evaluable patients (median age, 43), 125 (69%) achieved complete remission (CR). Predicted overall survival (OAS), event-free survival and disease-free survival (DFS) were 15, 10 and 14%, respectively at the median follow-up period of 62 months. No specific toxicities were observed. Leukocytes < 30,000/microliter, normal karyotype, and blasts < 10% in bone marrow at day 15 of induction therapy were significantly favorable prognostic factors for the achievement of CR, DFS and OAS by univariate analysis. Multivariate analysis showed leukocytes < 30,000/microliter and blasts < 10% on day 15 was a significant factor for the achievement of CR, DFS and OAS. Ph-chromosome was found in 28% (36/130) of patients examined and was one of the worst prognostic factors. All Ph positive patients were predicted to die within 600 days. Allo-BMT was not significantly superior to chemotherapy with respect to DFS (P = 0.226). The overall results were inferior to those of the former ALL87 protocol. As reasons, the older median age of 43 years old (vs. 38 years old) and lower dose intensity, especially of l-asparaginase, etc. were suggested. However, patients with good prognostic factors (leukocyte < 30,000/microliter and age < 30 years old) showed better survival than others (P < 0.0001), and the result was similar to that of older children, the high risk group of childhood ALL, suggesting that ALL could be a disease of single entity, showing higher resistance to chemotherapy as patients become older.     

Time to relapse has prognostic value in patients with aggressive lymphoma enrolled onto the Parma trial

PURPOSE: The purpose of this study was to investigate the prognostic value of time to relapse in 188 adult patients with intermediate- or high-grade non-Hodgkin's lymphoma (NHL) included on the Parma trial at the time of their first relapse. PATIENTS AND METHODS: The median follow-up of these patients is 102 months after registration onto the Parma study. Time to relapse was calculated from initial diagnosis, and a cutoff of 12 months was used to separate 77 patients defined as early relapse from 111 patients defined as late relapse. RESULTS: Patients with early and late relapses had significantly different overall response rates to salvage therapy with two courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP; 40% v 69%; P=.00007) and different 8-year survival rates (13% v 29%; P=.00001). Features at relapse with a negative prognostic value in univariate analysis were higher than normal lactic dehydrogenase (LDH) levels, tumor size greater than 5 cm, Ann Arbor stages III to IV, and Karnofsky score less than 80%. Therefore, multivariate analyses were performed. Time to relapse (P=.001) and LDH levels at relapse (P=.003) had independent prognostic value, whereas tumor size did not reach statistical significance in the logistic model that predicted overall response after two courses of DHAP. The study of prognostic factors for overall survival (OS) and progression-free survival (PFS) confirmed the prognostic value of time to relapse (P < .0001 for OS and P=.005 for PFS) independent of response or treatment after two courses of DHAP. CONCLUSION: Time to relapse may be used to stratify patients at time of first relapse of intermediate to high-grade non-Hodgkin's lymphoma.