Methotrexate, uracil and tegafur, and leucovorin chemotherapy for patients with breast cancer in progression after high-dose chemotherapy with peripheral blood progenitor cell transplant: a phase II study

Thirty-four patients with metastatic breast cancer (MBC) who had progression of disease after high-dose chemotherapy (HDCT) with peripheral blood progenitor cell support (PBPC) had methotrexate, uracil and tegafur (UFT), and leucovorin (MUL) therapy administered: methotrexate administered intramuscularly in combination with UFT given orally and leucovorin given orally. All patients had received extensive prior chemotherapy including a high-dose regimen with PBPC support. Two complete responses (CR) and 11 partial responses (PR) were observed (objective response rate: 13/34 or 38%, 95% confidence interval 22-56%). Seven additional patients had stable disease (SD), 4 of whom (12% of the total population) of 6 months or longer duration, with the clinical benefit rate (CR + PR + SD of at least 6-month duration) reaching 50%. Median follow-up was 38 months, and the median time to progression and the median overall survival time from the start of MUL were 5.5 and 11 months, respectively. Toxicity was mainly gastrointestinal. Eight patients (24%) had World Health Organization grade II or greater diarrhea and/or enteritis and, consequently, the UFT dose was reduced. Emesis was mild and easily manageable with thiethylperazine given orally. The regimen did not produce significant myelosuppression or alopecia. In conclusion, patients with MBC retain chemosensitivity even when they progress after HDCT/PBPC and can be treated again with chemotherapy. MUL is active and well tolerated in patients with MBC progressing after HDCT. Further studies with this regimen, as salvage chemotherapy or as maintenance chemotherapy after HDCT/PBPC, would appear to be warranted.     

Treatment of primary progressive Hodgkin's and aggressive non-Hodgkin's lymphoma: is there a chance for cure?

PURPOSE: To determine differences in prognosis between primary progressive Hodgkin's disease (HD) and aggressive non-Hodgkin's lymphoma (NHL), we retrospectively analyzed patients with progressive lymphoma who were treated with different salvage chemotherapy regimens including high-dose chemotherapy (HDCT) followed by autologous stem-cell support (ASCT). PATIENTS AND METHODS: One hundred thirty-one patients with primary progressive lymphoma (HD, n = 67; NHL, n = 64) were enrolled. Primary progressive disease was defined as disease progression during first-line chemotherapy or only transient response (complete or partial response lasting 相似文献   

Single high-dose etoposide and melphalan with non-cryopreserved autologous marrow rescue as primary therapy for relapsed, refractory and poor-prognosis Hodgkin's disease.

A simplified schedule of high-dose chemotherapy (HDC) consisting of melphalan (140 mg m-2) plus VP16 (2.5 g m-2) given over 12-18 h together with autologous non-cryopreserved autologous bone marrow transplant (ABMT) was used for treatment of relapsed (37 patients) and refractory (seven patients) patients and as first-line treatment (four patients) for poor-prognosis Hodgkin''s disease. Two patients had a second HDC-ABMT after relapse following prior HDC-ABMT, giving a total of 50 procedures among 48 patients. The haematological recovery rate was 98% with a complete response rate of the Hodgkin''s disease of > 90%. Factors significantly influencing response rate were performance status and the presence of liver involvement. Thirty-nine patients are alive, with 37 in continuous complete remission. The median duration of survival and median duration of remission have not been reached at a median follow-up time of 45 months. Adverse prognostic factors for survival were disease status at the time of HDC-ABMT (refractory versus relapse, with primarily refractory patients showing significantly poor survival) and the presence of liver involvement. High-dose chemotherapy with short-duration chemotherapy and non-cryopreserved bone marrow is an effective and safe treatment modality for patients with relapsed and poor-prognosis Hodgkin''s disease.     

High-dose chemotherapy and autologous bone marrow transplant in relapsed Hodgkin's disease--a pragmatic prognostic index.

High-dose chemotherapy with autologous bone marrow transplantation is used in the treatment of relapsed or high-risk Hodgkin''s disease. As prospective randomised studies have proved difficult to accrue to, current recommendations are based on the reports of large series of prospectively collected data. We have looked at the outcome of 89 patients treated in this way at a single institution and have developed an index to predict outcome. Of 89 patients, with a median age of 29 years (range 15-51 years), eight patients were in first complete remission/partial remission (CR/PR), 17 in second or later CR, 37 were responding relapses, 13 resistant relapses, 11 primary refractory and three untested relapses. Combinations of melphalan, BCNU and etoposide were given in all cases except in ten patients who received melphalan alone. The median follow-up was 43 months (range 6-77 months). A total of 24 patients were in CR at the time of autologous bone marrow transplantation (ABMT), 33 achieved CR with ABMT, 16 PR, to give a response rate to ABMT of 49/65 = 74% (95% CI 60-83%) with a CR rate of 51% (CI 36-62%). In a Cox''s multivariate analysis the most important factors in predicting outcome after ABMT were response to treatment before entry, number of previous treatments and previous chemosensitivity. Using these factors we devised a prognostic index which reliably selects a group of patients (65%) with at least a 70% chance of being progression free from 1 year onwards. Patients who have never achieved a CR and have received three or more chemotherapy regimens do not benefit from high-dose chemotherapy as used in this study.     

Salvage Therapy in Hodgkin's Lymphoma

Hodgkin's lymphoma (HL) is a commonly cured malignancy. Unfortunately, patients who are refractory to or relapse after first‐line treatment pose a significant therapeutic challenge. There is evidence that these patients are best treated with an approach involving salvage chemotherapy followed by high‐dose chemotherapy and autologous stem cell transplant (HDCT/ASCT). This approach may result in cure, with better results in patients with low‐risk relapse. In patients with high‐risk relapse and refractory disease, HDCT/ASCT is rarely curative. More aggressive transplant approaches have shown promising results in this group and are currently under active investigation. For those relapsing after HDCT/ASCT, there exists a range of therapeutic options, including further salvage chemotherapy, reduced‐intensity allogeneic transplantation, monoclonal antibody therapy, and novel agents. All patients in this category should be considered for enrollment in clinical trials. This review discusses the evidence behind the current practice in patients with relapsed or refractory HL. Specifically, the efficacy of various salvage chemotherapy regimens, the risk factors influencing outcome with HDCT/ASCT, and the results with alternative transplant approaches, monoclonal antibody therapies, and novel agents are addressed. We conclude by providing our approach to these patients, with the hope that this will serve as a framework for the practicing oncologist.     

Salvage high-dose chemotherapy in patients with germ cell tumors: an Italian experience with 84 patients

BACKGROUND: High-dose chemotherapy (HDCT) followed by hematopoietic stem cell support (HSCS) potentially may be curative in patients with germ cell tumor (GCT) who develop recurrent tumors or who have an inadequate response after receiving standard-dose chemotherapy. The authors report their experience with HDCT as salvage therapy for patients with GCT. METHODS: Between 1986 and 2000, 84 patients with GCT, with a median age 29 years (range, 15-50 years), were treated with 105 courses of HDCT with HSCS. Patients were stratified into good, intermediate, and poor risk categories according to a validated prognostic index. RESULTS: Overall, 28 patients (33%) have been continuously disease free. In the good risk group, 24 patients (69%) have been continuously disease free compared with 4 patients (13%) in the intermediate risk group (P < 0.001) and 0 patients in the poor risk group (P < 0.001). Treatment-related mortality occurred only among patients in the poor risk (n = 6 patients) and the intermediate risk groups (n = 4 patients). CONCLUSIONS: In the authors' experience, HDCT induced impressive long-term remissions as salvage treatment among patients in the good risk group. Moreover, the use of validated prognostic classifications may contribute to a better definition of the role of HDCT other than improving the outcome of patients with GCT. The definitive statement on the possible role of HDCT in patients with GCT will derive from the ongoing Phase III randomized studies.     

The value of routine computed tomography scanning of the chest in patients presenting with supradiaphragmatic Hodgkin's disease

Six patients presenting with supradiaphragmatic Hodgkin's disease are presented to demonstrate the potential benefits of chest computed tomography (CT) scanning as a routine staging procedure. These cases show that CT scanning can detect mediastinal and lung involvement not readily detected by other investigations, and that such findings can influence the radiotherapy plan, the need for extended radiotherapy fields or the use of chemotherapy. Following treatment, CT scanning can be useful to assess treatment response and may permit earlier detection of relapse. The use of chest CT scanning as a routine staging procedure in all patients with supradiaphragmatic Hodgkin's disease is advocated.     

Bone involvement in Hodgkin's disease

Bone involvement in Hodgkin's disease is uncommon and seldom encountered at initial diagnosis. Seven cases with osseous involvement were identified from a series of 147 patients with Hodgkin's disease treated at Auckland Hospital from 1980 to 1988. Only one patient was found to have bone lesions at the time of initial presentation. Two patients had multiple lesions and 5 had a solitary lesion. Sites of involvement included the spine, pelvis, femur, humerus, ribs, sternum, scapula and base of skull. Six patients had nodular sclerosing histology and one had mixed cellularity disease. All 7 patients were treated with systemic chemotherapy for their advanced disease, and 5 patients needed local radiotherapy to sites of bone involvement. The radiation dosage schedules were individualized, ranging from 30 Gy to 40 Gy, using either a 6 MeV linear accelerator or cobalt machine. At the time of analysis of this study, 4 patients were in complete remission, 2 patients completed chemotherapy with good response and only 1 patient died of disseminated disease. The current review has demonstrated an encouraging response to treatment and good long term control. We believe that combined-modality therapy is effective in the treatment of osseous involvement in Hodgkin's disease.     

Elevation of serum polyamines in malignant lymphomas and acute myeloid leukemia

In a study of 89 cases of hematological cancers including 55 cases of Hodgkin's disease, 21 of non-Hodgkin lymphoma and 13 of acute myeloid leukemia, the serum total polyamines were considerably elevated (1.2–5.7 nmol/ml) as compared to observations on control values for eight healthy individuals (0.62–0.87 nmol/ml). The assay procedure was based on enzymes oxidizing polyamines isolated from Russell's viper venom. Serial determination of polyamines in the sera of eight cases of Hodgkin's disease done before and after chemotherapy or radiotherapy showed positive correlation with clinical status of the disease. Analysis of individual polyamines in four patients with Hodgkin's disease indicated that putrescine may be a more sensitive marker of the diseased state. By the present method it was undetected in the control sera but rose significantly in the sera of patients with Hodgkin's disease. Overall data suggest that serum polyamines may be useful as indicators of onset of relapse in patients with Hodgkin's disease and could thus be helpful in early start of treatment.     

Ten-year nodular sclerosis Hodgkin's disease and second malignancies

Hodgkin's disease is one of the most curable cancers thanks to progress in radiotherapy and multi-drug chemotherapy regimens such as mechloretamine-vincristine-procarbazine-prednisone, best known as MOPP. However, long-term side-effects and treatment-induced second malignancies are of great concern. In our institution, 69 patients with nodular sclerosis Hodgkin's disease were treated over 10 years. Twenty-two per cent were stage I, 49% stage II, 23% stage III and 6% stage IV. Actuarial 10-year survival was 83% and actuarial relapse-free survival 61%. Six patients developed a second malignancy with a 10-year actuarial risk of 18%. All six cases occurred in the group treated with MOPP and extensive radiotherapy. Acute non-lymphoblastic leukemia occurred in three patients, preleukemia in two and non Hodgkin's lymphoma in one. In all of these patients, the results were quite poor. Overall survival was equally affected by Hodgkin's disease and by second malignancies. Since new multiple-drug chemotherapy regimens such as adriamycin-bleomycin-vinblastine-dacarbazine, known as ABVD, are equally effective and seem less likely to induce second hematologic malignancies, we suggest that MOPP should no longer be used as a first choice for the treatment of Hodgkin's disease, especially when in combination with radiation therapy.     

Follicular Lymphoma: Refining Prognostic Models and Impact of Pod-24 in Clinical Outcomes

Follicular lymphoma (FL) is the most common indolent lymphoma, accounting for 20%-25% of all non–Hodgkin's lymphomas (NHLs). It is a malignancy with variable biologic presentation and heterogeneous clinical outcomes. Several models incorporating clinical laboratory variables and molecular biomarkers are able to predict its prognosis, allowing to stratify patients into different risk groups. However, these prognostic scores should not be used to indicate first-line treatment or risk-adapted therapeutic recommendations. Over the past 5 years, progression of disease within 24 months (POD-24) of first-line chemo-immunotherapy has emerged as a robust adverse prognostic factor, capable of assessing overall survival and identifying high-risk patients with indication for more aggressive therapeutic approaches, such as consolidation based in autologous stem cell transplantation. It should be reinforced that POD-24 is not a baseline measurement, it is based on a post-treatment strategy, and is usually applied to patients with a high tumor burden. The identification of newly diagnosed patients at high risk for disease progression, particularly those with low tumor volume is still a challenge in the context of FL. Therefore, the primary purpose of this review is to provide an overview of the main prognostic models validated to date for FL. Moreover, using these scores, which incorporate clinical and genetic variables, we aim to identify individuals with newly diagnosed FL, advanced disease, and low tumor burden with a high probability of progression or relapse within 24 months of first treatment. Thus, a decision regarding risk-adapted induction therapy could be better stablished for these subset of patients.     

Association between chemotherapy response and rate of disease progression in disseminated melanoma

Fifty-five evaluable patients with disseminated malignant melanoma were treated with the combination of dacarbazine (DTIC) 400 mg i.v. on days 1 to 3 and lomustine (CCNU) 50 to 80 mg m-2 orally on day 1 with intervals of 6 weeks as the first line chemotherapy. Three (5%) patients had complete and 6 (11%) partial response, and 7 (13%) patients had stable disease at least for 3 months. The patients with an objective response (n = 9) survived longer than the rest of the patients if the length of survival was calculated from the start of chemotherapy (P = 0.0006). However, the responding patients also had longer time interval from the diagnosis to the detection of distant metastases (P = 0.05), and survival time from disease progression following DTIC and CCNU therapy (P = 0.005). These findings suggest that patients with an objective response to DTIC-CCNU therapy have melanoma with a slow progression rate, and prolonged survival in such patients may in part result from the less aggressive biological nature of their tumours.     

Immunity in Hodgkin's disease: status after 5 years' remission.

Immunological indices have been reassessed in 27 patients in remission from Hodgkin''s disease for 5 years after treatment and the findings correlated with initial treatment and splenectomy status. Neutrophil counts were lower and lymphocyte and monocyte counts higher at 5 years'' remission than at presentation; the increases in lymphocyte count were mainly a feature of the splenectomized patients. Neutrophil function (nitro-blue tetrazolium) was unchanged in remission but cellular immunity (leucocyte migration inhibition and lymphocyte transformation) was depressed at 5 years and progressive falls in serum immunoglobulins were noted. Low values of IgG and IgM were particularly found in patients who had splenectomy and chemotherapy; there was however no excess of infections in this small group.     

Risk factors in germ cell tumour patients with relapse or progressive disease after first-line chemotherapy: evaluation of a prognostic score for survival after high-dose chemotherapy

PurposeTo retrospectively re-evaluate a published prognostic score for response to salvage treatment in patients with germ-cell tumours relapsing or progressing after cisplatin-based first-line chemotherapy.Patients and methodsFrom a database of 257 germ cell tumour (GCT) patients treated with salvage high-dose chemotherapy (HDCT) we identified 176 patients (67%) with relapse or progression after first-line conventional-dose chemotherapy (CDCT). Patients were retrospectively grouped according to a published prognostic score defined by Fossa and colleagues [Fossa SD, Stenning SP, Gerl A, et al. Prognostic factors in patients progressing after cisplatin-based chemotherapy for malignant non-seminomatous germ cell tumors. Br J Cancer 1999; 80:1392–9]. Overall survival (OS) and event free survival (EFS) after HDCT were retrospectively evaluated in each prognostic group.ResultsAfter a median follow-up of 9 years the OS probability for all 176 patients was 38% and the EFS probability was 35%. The respective survival probability at 5 years in 100/176 (57%) good prognosis patients and 76/176 (43%) poor prognosis patients were 47% versus 28% for OS (p < 0.001) and 41% versus 26% for EFS (p < 0.005). Whereas survival probabilities did not differ in good prognosis patients, OS and EFS in poor prognosis patients were substantially better in the current series of patients treated with HDCT compared to the ones reported by Fossa treated with CDCT.ConclusionThis retrospective analysis confirms the impact of prognostic factors on the results of salvage treatment in patients with GCT and suggests a clinical benefit for patients with poor prognosis features receiving a single course of HDCT.     

High-dose chemotherapy in the treatment of relapsed osteosarcoma: an Italian sarcoma group study.

PURPOSE: To study the feasibility and activity of two courses of high-dose chemotherapy (HDCT) in patients with osteosarcoma in metastatic relapse. PATIENTS AND METHODS: Patients with high-grade osteosarcoma in metastatic relapse (multiple metastases or solitary metastasis at intervals of less than 30 months) were eligible for study. High-dose chemotherapy consisted of carboplatin and etoposide followed by stem-cell rescue. A second course was planned 4 to 6 weeks after the first. Surgery was performed before or after HDCT. RESULTS: Thirty-two patients were enrolled onto the study. At the end of the treatment, 25 patients were in complete remission (CR), six were alive with disease progression, and one died of toxicity. At present, 14 patients are alive with a median survival time of 23 months from study entry: four are in first CR, three are in second CR, and one is in fourth CR. Six patients are alive with disease. Eighteen patients (56%) died: 17 of disease and one of toxicity. Transplantation-related mortality was 3.1%. The relapse or progression disease rate was 84.4%. The 3-year overall survival rate is 20% and the 3-year disease-free survival rate is 12%. CONCLUSION: HDCT combined with surgery is feasible and can induce CR in a large portion of patients. Two points, however, need to be considered: only patients who are chemosensitive to induction treatment can obtain CR after HDCT, and the length of remission is short, because most patients relapse. Thus novel strategies are needed to maintain the remission status or to treat patients who do not respond to induction treatment.     

Intensive salvage therapy with high-dose chemotherapy for patients with advanced Hodgkin's disease in relapse or failure after initial chemotherapy: results of the Groupe d'Etudes des Lymphomes de l'Adulte H89 Trial.

PURPOSE: To evaluate prospectively the feasibility and efficacy of early intensive therapy, including intensified cytoreductive chemotherapy (CT) and high-dose CT (HDCT) followed by autologous stem-cell transplantation (ASCT), in patients with advanced Hodgkin's disease (HD) who failed to respond completely or relapsed after initial treatment. PATIENTS AND METHODS: Among 533 eligible patients with newly diagnosed stage IIIB-IV HD enrolled in the H89 trial, all 157 patients with induction failure (IF) (n = 67), partial response (PR) of less than 75% (n = 22), or relapse (n = 68) were included in this study. Planned salvage therapy included mitoguazone, ifosfamide, vinorelbine, and etoposide monthly for two to three cycles followed by high-dose carmustine, etoposide, cytarabine, and melphalan with ASCT. RESULTS: With a median follow-up of 50 months, the 5-year survival estimates were 30%, 72%, and 76% for the IF, PR, and relapse groups, respectively (P =.0001), 71% for the 101 patients given HDCT, and 32% for the 48 patients treated without HDCT (P =.0001). Multivariate analysis using time-dependent Cox model indicated that B symptoms at progression, salvage without HDCT, and chemoresistant disease before HDCT were significantly associated with shorter overall survival. CONCLUSION: Early intensive therapy improves the outcomes of patients with advanced HD who failed to respond completely to initial treatment and those who relapsed with adverse prognostic factors. However, for patients with IF and chemoresistant disease, this approach remains unsatisfactory.     

Up-front tandem high-dose chemotherapy compared with standard chemotherapy with doxorubicin and paclitaxel in metastatic breast cancer: results of a randomized trial.

PURPOSE: The role of high-dose chemotherapy (HDCT) in metastatic breast cancer remains controversial. Trials with late intensification HDCT have failed to show an advantage in overall survival. This study was initiated to compare up-front tandem HDCT and standard combination therapy in patients with metastatic breast cancer. PATIENTS AND METHODS: Patients without prior chemotherapy for metastatic disease were randomly assigned to standard combination therapy with doxorubicin and paclitaxel (AT) or double HDCT with cyclophosphamide, mitoxantrone, and etoposide followed by peripheral-blood stem-cell transplantation. HDCT was repeated after 6 weeks. Patients were stratified by menopausal and hormone-receptor status. The primary objective was to compare complete response (CR) rates. RESULTS: A total of 93 patients were enrolled onto the trial. Intent-to-treat CR rates for patients randomized to HDCT and AT were 12.5% and 11.1%, respectively (P = .84). Objective response rates were 66.7% for patients in the high-dose group and 64.4% for patients in the AT arm (P = .82). In an intent-to-treat analysis, there were no significant differences between the two treatments in median time to progression (HDCT, 11.1 months; AT, 10.6 months; P = .67), duration of response (HDCT, 13.9 months; AT, 14.3 months; P = .98), and overall survival (HDCT, 26.9 months; AT, 23.4 months; P = .60). HDCT was associated with significantly more myelosuppression, infection, diarrhea, stomatitis, and nausea and vomiting, whereas patients treated with AT developed more neurotoxicity. CONCLUSION: This trial failed to show a benefit for up-front tandem HDCT compared with standard combination therapy. HDCT was associated with more acute adverse effects.     

Safety of treatment of metastatic breast cancer with trastuzumab beyond disease progression.

PURPOSE: In a pivotal phase III trial, the addition of trastuzumab to chemotherapy significantly improved response rate, time to disease progression, and overall survival in women with HER2 overexpressing metastatic breast cancer. We conducted an extension study to this trial to obtain additional safety information and to provide trastuzumab following disease progression. PATIENTS AND METHODS: A total of 247 patients with documented disease progression received weekly intravenous trastuzumab in the extension study. Concurrent therapies were administered at the discretion of the treating physician. Patient groups were based on initial study treatment: chemotherapy alone (group 1, n=154) or chemotherapy plus trastuzumab (group 2, n=93). RESULTS: Sixty-eight percent of group 1 and 76% of group 2 received chemotherapy plus trastuzumab in the extension trial; the remainder received trastuzumab alone or combined with palliative radiotherapy or hormonal therapy. Seventy-six percent of group 1 and 55% of group 2 experienced at least one adverse event, similar to effects observed in the pivotal trial. Symptomatic or asymptomatic cardiac dysfunction occurred in 9% of group 1 and 2% of group 2 patients. Overall objective response rates were 14% in group 1 and 11% in group 2; median durations of response exceeded 6 months in both groups. CONCLUSION: Our results suggest that prolonged use of trastuzumab therapy is safe and well tolerated. Longer durations of therapy did not appear to increase the risk of cardiac dysfunction. Patients progressing on trastuzumab-containing therapy demonstrate some response to a second trastuzumab-containing regimen. The independent contribution of trastuzumab in this setting merits further study.     

A phase II trial of high-dose chemotherapy (HDCT) supported by hematopoietic stem-cell transplantation (HSCT) in germ-cell tumors (GCTs) patients failing cisplatin-based chemotherapy: the Multicentric TAXIF II study

BackgroundHigh-dose chemotherapy (HDCT) is an effective salvage treatment of germ-cell tumors (GCTs) patients. In the first salvage setting, 30%–70% of patients may achieve durable remissions. Even when HDCT is administered as subsequent salvage treatment, up to 20% of patients may still be definitively cured. However, patients with refractory/relapsed disease still have a very poor long-term prognosis, requiring earlier intervention of HDCT.Patients and methodsThis phase II trial was addressed to nonrefractory patients failing Cisplatin-based chemotherapy. Inclusion criteria included seminomatous GCT in relapse after two lines of chemotherapy, nonseminomatous GCT in relapse after first or second lines, partial remission after first line, primary mediastinal GCT in first relapse. Patients received two cycles combining Epirubicin and Paclitaxel (Epi-Tax), followed by three consecutive HDCT, one using a Paclitaxel/Thiotepa (Thio-Tax) association and two using the 5-day Ifosfamide–Carboplatin–Etoposide regimen. The main objective was to determine the complete response rate.ResultsForty-five patients were included between September 2004 and December 2007: 44 received the first HDCT cycle, 39 two HDCT cycles, 29 could receive the whole protocol. Sixteen patients did not receive the entire protocol, including eight (17.7%) for toxic side-effects. Two patients (4.4%) died of toxicities, and 17 (37.7%) of disease progression. With a median follow-up time of 26 months (range, 4–51), the final overall response rate was 48.8% (including a complete response rate of 15.5% and a partial response/negative serum markers rate of 26.6%) in an intent-to-treat analysis. The median progression-free survival (PFS) and overall survival (OS) times were 22 months [95% confidence interval (CI) 2–not reached] and 32 months (95% CI 4–49), respectively. The 2-year PFS was a plateau setup at 50% (95% CI 32–67) and the 2-year OS was 66% (95% CI 44–81).ConclusionThe TAXIF II protocol was effective in nonrefractory GCT patients failing Cisplatin-based chemotherapy. The toxic death rate remained acceptable in the field of HDCT regimens.Trial registration numberNCT00231582.     

Follow-up studies on the immune status of patients with Hodgkin's disease after splenectomy and treatment, in relapse and remission.

Sixty-two patients with Hodgkin''s disease have been followed for one year from the start of treatment. Immunological assessments were repeated after intensive treatment, in patients relapsing and in those in remission at one year. In patients achieving remission, overall cellular immunity, after deteriorating with therapy, particularly cytotoxic chemotherapy, returned to pre-treatment levels in remission when there was little evidence of cellular immune disturbance. Serum IgG and IgM levels fell with intensive chemotherapy in splenectomized patients. IgA and IgM levels were lower (irrespective of splenectomy or therapy status) in remission than at presentation or after treatment. Relapse or non-response was usually associated with deteriorating cellular immunity. Herpes zoster/varicella and candida infections (seen in 6 patients) were preceded by, or associated with, deterioration of cellular immunity.