Clinical and prognostic importance of XIAP and USP8 in advanced stages of non-small cell lung cancer.

PURPOSE: To investigate the relationship of the apoptosis regulators X-linked inhibitor of apoptosis (XIAP) and ubiquitin specific protease 8 (USP8) with clinical parameters, survival and response to chemotherapy in patients with advanced stages of non-small cell lung cancer (NSCLC). METHODS: The study included 34 NSCLC patients (28 females, 6 males) and 44 healthy individuals (17 males, 27 females) as a control group. XIAP and USP8 levels were determined by ELISA. RESULTS: The median serum XIAP level of the patients and the control group showed no significant difference. USP8 level was higher in patients than in controls (p<0.0001). In univariate analysis, there was no significant relationship between XIAP and USP8 serum levels and age, sex, performance status, weight loss, stage of disease, histopatological type and response to chemotherapy. Response to chemotherapy did not differ between the high and low XIAP and USP8 groups . There was no significant difference in progression- free survival (PFS) (p=0.432 and p=0.50, respectively) and overall survival (OS) (p=0.989 and p=0.90, respectively) between the low and high XIAP and USP8 groups. CONCLUSION: No relationship was found in serum XIAP and USP8 levels with clinical parameters, response to chemotherapy, PFS and OS in patients with advanced stages of NSCLC.

Sequential adjuvant docetaxel and anthracycline chemotherapy for node positive breast cancers: a retrospective study.

PURPOSE: Anthracyclines and taxanes are the most active agents in the adjuvant treatment of breast cancer (BC). They can be used simultaneously or sequentially. The optimal schedule and duration for their administration is unknown. We analyzed the efficacy of sequential adjuvant anthracycline and docetaxel administration in node positive BC patients. METHODS: Node positive BC patients (N=539) from 6 medical oncology centers in Turkey who received sequential adjuvant anthracycline-based regimens and taxane chemotherapy were included in this study between 2006 - 2010. One-hundred and thirty-eight (25%) patients received 3 cycles of anthracycline-based chemotherapy followed by 3 cycles of docetaxel (3+3) and 401 (75%) patients received 4 cycles of anthracycline-based chemotherapy followed by 4 cycles of docetaxel (4+4). Prognostic factors analyzed were estrogen receptor (ER), progesterone receptor (PR), HER2, tumor grade, and nodal status in relation to disease free survival (DFS) and HER2 status in relation to overall survival (OS). RESULTS: The patient median age was 48 years (range 18-79). Most common grade 3-4 toxicities were neutropenia, mucositis and arthralgia. No treatment-related toxic deaths were seen. With a median follow up of 26 months (range 1-115) 61 (11.3%) recurrences and 11 (2%) deaths were registered. Three-year DFS was 81% and OS 96% for all patients. There was no statistically significant difference between 3+3 and 4+4 groups in terms of survival (3-year DFS 88% and 79% [p=0.28] and OS 97% and 95% [p=0.60), respectively). CONCLUSION: Sequential chemotherapy with 4+4 cycles of anthracycline and docetaxel every 3 weeks is an acceptable regimen for adjuvant treatment of node positive BC patients. Duration of chemotherapy should be planned depending on prognostic factors. In this study there was no difference between 3+3 and 4+4 groups in DFS and OS despite the presence of good prognostic factors in the 3+3 group.

Endocrine therapy alone vs. chemotherapy plus endocrine therapies for the treatment of elderly patients with endocrine-responsive and node positive breast cancer: a retrospective analysis of a multicenter study (Anatolian Society of Medical Oncology).

PURPOSE: The extra benefit of adding chemotherapy to effective endocrine therapy (ET) has not been clearly or consistently identified in patients older than 70 years with estrogen receptor (ER) positive and node positive breast cancer. The aim of this study was to evaluate the efficacy of adjuvant ET vs. chemotherapy plus endocrine therapies (Chemo/ET) in such patients. METHODS: In this retrospective multicenter study 191 patients ≥ 70 years with operated hormone receptor breast cancer, who were administered adjuvant ET or Chemo/ET were assessed. RESULTS: The median patient follow-up time was 29.0 months (range 1-252). Therefore disease free survival (DFS) and overall survival (OS) analysis was limited, due to the rather short median follow-up, and only 30-month cumulative percentages are reported herein. The 30-month DFS rates were 50.0% in the ET arm and 49.0% in the Chemo/ET arm (p=0.79). The 30-month OS rates were 86% in the ET arm and 96.0% in the Chemo/ET arm (p=0.08). Cox proportional hazard model showed that only surgery was independent prognostic factor for survival (p=0.047), while tumor size showed a strong trend for statistical significance (p=0.051). CONCLUSION: The addition of chemotherapy to endocrine therapy in older patients has no significant impact on DFS and OS.

Prognostic analysis of patients with operable gastric cancer and tolerability to adjuvant radio-chemo-therapy.

The aim of this study is to evaluate the tolerability and toxicity of adjuvant chemoradiotherapy (CRT) and to analyze the prognosis in patients with operable gastric cancer. The retrospective analysis included 723 patients with operable gastric cancer; stage IB-IV (M0), received adjuvant CRT from 8 Medical Centers in Turkey between 2003 and 2010. The patients' age, sex, tumor localization, Lauren classification, grade and stage of the disease, type of dissection, the toxicity and tolerability status and survival rate were analyzed. All patients were divided into two groups as tolerable group to adjuvant CRT and intolerable group to adjuvant CRT .Among the patient, 73.9% had stage III-IVM0 disease; 61.0% had the intestinal type of gastric cancer, 51.1% had the distal type, and 61.4% had undergone D2 dissections. The number of patients who completed the entire course of the adjuvant CRT was 545 (75.4%).The median follow-up period was 20.8 months (range: 1.5-107 months). Overall Survival (OS) rates were 80% and 52%, while the relapse free survival (RFS) rates were 75% and 48% at 1 and 3 years, respectively.In the univariate analysis of the groups based on the the age defined as <65 or ≥ 65 (p=0.16 / p=0.003), Lauren classification (p=0.004 / p<0.001), localization of tumor (p=0.02 / p=0.04), tumor grade (p=0.06 / p=0.003), disease stage (p<0.001 / p<0.001), type of dissection (p=0.445 / p=0.043), presence or absence of toxicity (p=0.062 / p=0.077) and tolerability of the therapy (p=0.002 / p=0.001). In the cox regression analysis, tumor stage (Hazard Ratio (HR): 0.332; 95% confidence interval (CI): 0.195-0.566; p<0.001), and tolerability (HR: 0.516; 95% CI: 0.305-0.872; p=0.014), were found to be related with the OS. Tumor stage (HR: 0.318; 95% CI: 0.190-0.533; p=<0.001) and tolerability (HR: 0.604; 95% CI: 0.367-0.995; p=0.048) were observed to be statistically significant in terms of the RFS.We have observed that whether a patient can or cannot tolerate adjuvant CRT due to its toxicity is an independent prognostic factor besides the known prognostic factors like tumor stage and Lauren classification. We are of the opinion that the treatment of patients who cannot tolerate adjuvant CRT should be replaced with less toxic adjuvant therapies.

Trabectedin in advanced soft tissue sarcoma: case series.

The prognosis of advanced soft tissue sarcomas (STS) is poor. The median overall survival (OS) is 6 months in unresectable and metastatic STS that progress after treatment with anthracyclines and ifosfamide. Trabectedin is an alkylating agent, effective in advanced STS, especially in leiomyosarcoma and liposarcoma. In the present study, the effectiveness and safety of trabectedin was retrospectively evaluated in 8 unresectable and metastatic STS patients. Their median age was 47 years. The median progression free survival (PFS) was 3.75 months and the median OS 15 months in relapse or progression after anthracyclines and/or ifosfamide. Toxicities were mainly hematologic. In the present study, trabectedin showed efficacy in different histological subtypes of sarcomas like liposarcoma and leiomyosarcoma.

Long term experience in high grade glial tumors with temozolomide.

PURPOSE: Temozolomide is used concurrently with radiotherapy (RT) and as consolidation therapy in high grade gliomas (HGGs). In the present study we present our experience of long-term efficacy and toxicity of temozolomide in HGGs. METHODS: After surgery, temozolomide was administered at 75 mg/m(2) daily concurrently with RT, followed by 6 courses of consolidation therapy (150-200 mg/m(2) for 5 days every 28 days). RESULTS: A total of 172 patients with either glioblastoma multiforme (GBM) (n= 142; 82.6%) or anaplastic astrocytoma (AA) (n= 30; 17.4%) were studied. The objective response rate (ORR) was 42.5%, including 12 (7%) complete responses (CRs) and 61 (35.5%) partial responses (PRs). In the GBM group, median progression free survival (PFS) and overall survival (OS) were 9 and 16 months, respectively. In the AA group, median PFS and OS were 16 and 24 months, respectively. Three-year OS was 18.2% for GBM, and 39.4% for AA. In elderly patients (14.5%), median PFS and OS were 8 and 11 months respectively for both HGGs. Serious toxicities were mainly hematologic. CONCLUSION: Temozolomide is an effective agent in HGGs with favorable outcome and low toxicity profile even in advanced age.

Prognostic factors in patients with advanced pancreatic cancer treated with gemcitabine alone or gemcitabine plus cisplatin: retrospective analysis of a multicenter study.

PURPOSE: The majority of patients with pancreatic cancer present with advanced disease. Systemic chemotherapy for patients with pancreatic cancer has limited impact on overall survival (OS). Patients eligible for chemotherapy should be selected carefully. The aim of this study was to analyse prognostic factors for OS in advanced pancreatic cancer patients treated with first-line palliative chemotherapy with gemcitabine alone or gemcitabine plus cisplatin. METHODS: We retrospectively reviewed 343 locally advanced or metastatic pancreatic cancer patients who were treated with gemcitabine or gemcitabine plus cisplatin as first-line chemotherapy between December 2000 and June 2011. Fifteen potential prognostic variables were chosen for analysis. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS. Univariate and multivariate statistical methods were used to determine prognostic factors. RESULTS: Among the 15 variables of univariate analysis, 6 were identified to have prognostic significance: stage (p<0.001), cholestasis (p=0.02), weight loss, prior pancreatectomy, serum CEA level (p<0.001) and serum CA19-9 level (p>0.001). In addition, age, chemotherapy and liver metastasis were of borderline significance (p=0.06). Multivariate analysis (Cox proportional hazard model) included the 6 significant prognostic factors of univariate analysis and showed that stage was independent prognostic factor for OS, as were weight loss, and serum CEA level. CONCLUSION: Stage, weight loss, and serum CEA level were identified as important prognostic factors for OS in advanced pancreatic cancer patients. These findings may also facilitate pretreatment prediction of OS and can be used for selecting patients for treatment.

Gemcitabine alone versus combination of gemcitabine and cisplatin for the treatment of patients with locally advanced and/or metastatic pancreatic carcinoma: a retrospective analysis of multicenter study.

The majority of patients with pancreatic cancer is of advanced disease. Several randomized Phase II and III trials suggest that the combination of gemcitabine and cisplatin (GemCis) response rates were higher than Gemcitabine (Gem) alone, however the trials were not enough powered to indicate a statistically significant prolongation of survival in patients with advanced pancreatic adenocarcinoma. The aim of this retrospective multicenter study is to evaluated the efficiency of Gem alone versus GemCis in patients with locally advanced and/or metastatic pancreatic adenocarcinoma .A total of 406 patients, from fourteen centers were evaluated retrospectively. All patients received Gem or GemCis as first-line treatment between September 2005 to March 2011. Primary end of this study were to evaluate the toxicity, clinical response rate, progression-free survival (PFS) and overall survival (OS) between the arms. There were 156 patients (M: 98, F: 58) in Gem arm and 250 patients (M: 175, F: 75) in the combination arm. Gemcitabin arm patients older than the combination arm ( median 63 vs 57.5, p=0.001). In patients with the combination arm had a higher dose reduction (25.2% vs 11.3%, p=0.001) and dose delay (34% vs 16.8%, p=0.001). Among patients with the combination and Gemcitabin arm gender, diabetes mellitus, performance status, cholestasis, grade, stage did not have a statistically difference (p>0.05). Clinical response rate to the combination arm was higher than the Gem arm (69.0% vs 49.7%, p=0.001). PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance (8.9 vs 6.0, p=0.08). OS was not significantly superior in the GemCis arm (12.0 vs 10.2, p>0.05). Grade III-IV hematologic and nonhematologic toxicity were higher in the combination arm. PFS was more favorable in the GemCis arm than Gem alone, but the difference did not attain statistical significance. OS was not significantly superior in the GemCis arm.

Hypoxia inducible factor-1 alpha and carbonic anhydrase IX overexpression are associated with poor survival in breast cancer patients.

PURPOSE: Hypoxia is common in many solid tumors such as breast, head-neck, and soft tissue malignancies. Hypoxia causes overexpression of hypoxia inducible factor-1 alpha (HIF-1α) and carbonic anhydrase IX (CA IX) which are associated with unfavorable prognosis in breast cancer. In our study, we evaluated HIF-1α and CA IX expression in patients with breast cancer. METHODS: Between June 1996 and June 2008, 111 women with breast cancer were evaluated. Estrogen receptor (ER) and progesterone receptor (PR) status and Her2/ neu expression were evaluated by immunohistochemical methods. Her-2/neu expression was also assessed by FISH method when needed. Two groups were created: ER and PR positive, Her-2/neu negative (group 1, n=56); and ER and PR negative, Her-2/neu positive (group 2, n=55). HIF-1α and CA IX expressions were investigated in both groups and results were compared. In addition, we investigated the association between HIF-1α and CA IX expressions with stage, grade, lymph node metastasis, tumor size, menopause status and survival. RESULTS: Median patient age in group 1 was 52 years (range 34-77), and in group 2 47 years (range 27-83). HIF-1α expression was detected in 26 (46.4%) of group 1 and in 46 (83.6%) of group 2 patients (p=0.0001). CA IX expression was detected in 25 (46.4%) of group 1 and in 37 (67.3%) of group 2 patients (p7equals;0.0137rpar;. In group 1, median disease free survival (DFS) was 97 months and in group 2 46 months (p=0.0308). In group 1, median overall survival (OS) was 108 months and in group 2 75 months (p=0.0339). CONCLUSION: HIF-1α and CA IX overexpressions are observed more often in ER and PR negative, Her-2/neu positive breast cancer and are associated with poor survival.

Multiple primary malignant neoplasms: multi-center results from Turkey.

PURPOSE: Multiple primary malignant neoplasms (MPMNs) are defined as a diagnosis of two or more indepen-dent primary malignancies of different histologies/origins in an individual. The frequency of MPMN is being increasing. In this study we aimed to determine the frequency and clinical features of second primary cancers (SPCs). METHODS: From January 1990 to December 2010, patients with MPMNs were screened in 5 centers. Data were obtained retrospectively from hospital charts. RESULTS: Three hundred seventy-seven patients with MPMNs were evaluated. The median age at initial cancer diagnosis was 61 years (range 18-88). The median age at second cancer was 64 years (range 20-89). The median time between two cancer diagnoses was 15 months (range 0-504). Male to female ratio was 1.44 (M/F 223/154). The most frequent initial cancer types were head and neck (54 patients, 14.3%), breast (54 patients, 14.3%), and colorectal (43 patients, 11.4%). The most frequent second cancer types were lung (76 patients, 20.2%), colorectal (39 patients, 10.3%) and breast (33 patients, 8.8%). The most common cancer pairs in females were breast-gynecologic cancers (15 patients, 9.7%), colorectal-breast cancers (9 patients, 5.8%) and breast-colorectal cancers (7 patients, 4.5%). The most common cancer pairs in males were head and neck-lung cancers (29 patients, 13%), bladder-lung cancers (9 patients, 4%), and bladder-prostate cancers (7 patients, 3%). The median follow up was 36 months (range 17horbar;595). CONCLUSION: Physicians should be aware of SPCs probabilities. Newly developed suspicious lesions should be evaluated rigorously. Histopathologic evaluations of suspicious lesions for second tumors should be used extensively if needed. In our series, the most common pairs were breast-gynecologic cancers in females and head and neck-lung cancers in males.

Serum granulocyte colony-stimulating factor levels in gliomas.

PURPOSE: Apart from its known effects on granulopoiesis, granulocyte-colony stimulating factor (G-CSF) is also involved in growth and progression of malignant cells. In this study we report the serum G-CSF levels and their relationship with survival in patients with glial cell tumors. METHODS: Serum G-CSF levels of 17 patients (10 male, 7 female, median age 55 years, range 19-75), with histologically proven glial cell tumors and of 17 sex- and age-matched healthy controls were assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: All patients were treated with radiotherapy and concomitant temozolomide, followed by temozolomide alone. Eight patients were treated with carboplatin plus cyclophosphamide combination as second-line chemotherapy. The median follow-up was 21 months (4-42). The median OS was 36 months (95% CI, 15.7-56.4). Serum G-CSF levels in glioma patients and healthy controls were 44.14 ± 18.89 pg/ ml and 28.84±15.65 pg/ml, respectively (p=0.027). There was no significant correlation between survival time and serum G-CSF levels (r=0.384; p=0.217). CONCLUSION: Serum G-CSF levels were high in glioma patients compared with healthy controls and they may be involved in tumor progression, but the G-CSF role in prognosis was not clarified. Further studies with larger numbers of patients must be conducted to elucidate the role of G-CSF in glial cell tumors.

Efficacy and toxicity of preoperative chemotherapy with docetaxel and epirubicin in locally advanced invasive breast cancer.

PURPOSE: To investigate the efficacy and safety of neoadjuvant chemotherapy with docetaxel plus epirubicin with granulocyte colony-stimulating factor (G-CSF) support in locally advanced breast cancer patients. METHODS: We retrospectively evaluated the records of 39 patients with locally advanced breast cancer. All of them received neoadjuvant epirubicin 75 mg/m(2) plus docetaxel 75 mg/m(2) every 3 weeks with G-CSF support. Responding patients were subjected to breast-conserving or modified radical mastectomy. RESULTS: Four (10.3%) patients achieved clinical complete response (cCR) and 25 (64.1%) clinical partial response (cPR). Pathologic complete response (pCR) was observed in 4 patients with cCR. Ten (25.6%) patients achieved stable disease (SD), while no patient had progressive disease (PD). Grade 3 and 4 neutropenia was observed in 6 (15.3%) and 4 cases (10.3%), respectively. Febrile neutropenia was observed in 2 (5.1%) cases and anemia in 7 (17.9%) cases. Grade 1/2 mucositis was observed in 12 (30.7%) patients and grade 1/2 peripheral neuropathy in 7 (17.9%) patients. Dose reduction was necessary in 4 patients with grade 4 neutropenia. The median disease-free survival was 60 months (95% CI: 41-79 months). Median overall survival was not reached. Five-year overall survival was 64.2%. CONCLUSION: The combination of docetaxel plus epirubicin was active and tolerable in neoadjuvant treatment of locally advanced breast cancer.

Intrasellar plasmacytoma: an unusual presentation of multiple myeloma.

INTRODUCTION: Plasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities. LITERATURE REVIEW: We reviewed the pertinent literature and discuss here in the light of an illustrative case of our own. DISCUSSION: A 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain. Further studies confirmed the diagnosis of multiple myeloma. The patient was successfully treated with radiotherapy followed by systemic chemotherapy. Because they have different therapeutic implications, extramedullary plasmacytomas involving pituitary gland should be considered in the differential diagnosis of a nonfunctioning pituitary mass.

Xelox (capecitabine plus oxaliplatin) as neoadjuvant chemotherapy of unresectable liver metastases in colorectal cancer patients.

Complete resection of liver metastasis may provide long term survival in patients with colorectal cancer. Increased number of studies on successful resection after neoadjuvant chemotherapy with initially unresectable liver metastasis has been reported. We evaluated retrospectively the results of 35 patients with unresectable liver only metastases from colorectal cancer treated with capecitabine plus oxaliplatin combination (XELOX). Treatment consisted of IV oxaliplatin 130 mg/m2 day 1 and oral capecitabine 1000 mg/m2 day twice daily on days 1 to 14 followed by 7 days of rest repeated every 3 weeks. After chemotherapy, 13 (37, 2 %) patients showed partial clinical response. Among them, 7 patients were considered suitable for surgery but 2 patients refused the surgery. While one of 5 patients had unresectable disease at surgery, the remaining 4 patients (11, 4 %) had a complete resection. There was one postoperative mortality due to sepsis within 2 months after surgery. Our data suggests that XELOX regimen seems to be useful in unresectable liver only metastases from colorectal cancer because of its activity, feasibility and tolerability. Further studies of XELOX in combination with bevacizumab and/ or cetuximab are warranted in this setting.

Adrenomedullin expression does not correlate with survival in lung cancer.

It is suggested that adrenomedullin (AM) plays a role in lung carcinogenesis although, to confirm this suggestion, further clinical studies are needed to determine its relationship with prognosis in lung cancer. Archived 50 paraffin-embedded tumor samples of the lung were retrospectively evaluated for AM expression by immunohistochemistry and analyzed for a possible correlation with patient characteristics and survival. Quantitation of immunoreactivity was accomplished using an immunohistochemical scoring system. The pulmonary resection specimens contained 22 squamous cell carcinomas, 15 adenocarcinomas, and 13 small cell carcinomas. Non-small cell carcinomas of the lung were more likely to express AM than small cell carcinomas of the lung. Ninety-one percent of squamous cell carcinomas and 87% of adenocarcinomas expressed AM at a moderate to strong level and grade2-4 (30-100%), which were significantly higher from the non-neo-plastic lung tissue. Twenty-three percent of small cell carcinomas of lung expressed AM. Interestingly, AM immunoreactivity was essentially weak and grade 1 (<%30) in this group. AM expression is upregulated in non-small cell carcinomas of the lung, whereas it is downregulated in small cell carcinomas and non-neo-plastic lung tissues. AM expression did not show any correlation with the differentiation of the tumor, the stage of cancer, and the overall survival of patients. These results did not support the role of adrenomedullin as an independent survival factor for lung cancer. However, AM inhibition in conjunction with other anti-angiogenic agents may be useful in the prevention and treatment of malignancies.

A case representing coexistence of acute myeloblastic leukemia and dedifferentiated liposarcoma: the possible role of chemotherapy in triggering dedifferentiation.

Acute myelogenous leukemia (AML) is a hematological disorder that is characterized by an abnormal proliferation of immature myeloid cells. Dedifferentiated and well-differentiated liposarcomas are the two pathological subtypes of liposarcoma, based on the WHO classification. Transition from well-differentiated to dedifferentiated liposarcoma is a well-recognized phenomenon. Well-differentiated tumors are known to have low malignancy grade. However, when dedifferentiation occurs, the tumor acquires the aggressive features of a fully malignant lesion. This process largely is believed to progress in a time-dependant manner; however, time is not the only factor of importance. The potential roles of other factors in this transition are still unclear. To date, the coexistence of AML and liposarcoma has not been reported in the literature. In this paper, we report on a case of coexistence of AML and liposarcoma, and on the unusual behavior of a well-differentiated tumor after dedifferentiation occurs.

High-dose thiotepa, melphalan and carboplatin (TMCb) followed by autologous peripheral blood stem cell transplantation in patients with lymphoma -- a retrospective evaluation.

The purpose of this evaluation was to investigate the efficacy of high-dose chemotherapy with thiotepa, melphalan, and carboplatin (TMCb), and of autologous peripheral blood stem cell (PBSC) infusion in patients with aggressive non-Hodgkin's lymphoma (NHL) or Hodgkin's disease (HD). A total of 42 patients, 23 with intermediate-grade NHL and 19 with HD, received thiotepa (500 mg/m2), melphalan (100 mg/m2), and carboplatin (1050-1350 mg/m2) followed by autologous PBSC infusion. Of 21 patients with more advanced disease, four had primary refractory disease, one was in complete remission (CR)-2, 11 were in first refractory relapse, and five were beyond first relapse. Of 21 patients with less advanced disease, two were in CR-1, four were in CR-2, and 15 were in first responding relapse. In all, 14 patients (33%) had received prior radiotherapy prohibiting a total-body irradiation (TBI)-based conditioning regimen. The projected 2-year probabilities of survival, event-free survival (EFS), and relapse for all patients were 0.65, 0.60, and 0.21 (0.85, 0.80, and 0.10 for patients with less advanced disease and 0.47, 0.42, and 0.33 for patients with more advanced disease). The probability of nonrelapse mortality in the first 100 days was 0.12. Grade 3-4 regimen-related toxicities (RRT) occurred in five of 42 (12%) patients and death due to grade-4 RRT occurred in only one (2.5%) patient. These preliminary data suggest that 0.42% EFS in this study for advanced disease patients is highly encouraging and high-dose TMCb followed by autologous PBSC transplantation is well tolerated as well as an effective regimen in patients with intermediate-grade NHL or HD, and may be comparable to some previously used regimens including TBI-based regimens.