Use Of High-dose Chemotherapy Research Articles

Impending Challenges in the Hematopoietic Stem Cell Transplantation Physician Workforce

With increasing use of high dose chemotherapy with autologous and allogeneic transplants the need for the transplant physician workforce requires reassessment. The types of transplants and patients are also shifting toward transplants being done in patients with more comorbidities and more commonly these types of patients require more work effort per patient from the transplant physician. Additionally, HSCT survivors often require ongoing care at the transplant center due to the inability of the primary care workforce or the hematology/oncology workforce to absorb caring for post complex post transplant patients. The adult transplant workforce has had very few physicians join under age 40. Nearly 50% of adult transplant physicians are over age 50 whereas only 28% of pediatric transplant physicians are over age 50. By 2020, it is projected that we will need 1,264 new adult transplant physicians and 94 pediatric transplant physicians. Training time for a physician is approximately 15 years. The capping of both medical school slots and residency slots since the early '80s is now having a very big impact on supply, but other factors are also affecting supplies such as generational differences, lifestyle expectations, and the change of the medical workforce from being mostly men. Workforce shortages are being reported for many specialities. Workforce problems are also present for nurses, pharmacists and medical technologists. So increasing use of general internists and mid-level providers may not exist as a solution. Transplant physicians must be actively engaged in the medical education process to show young medical students and residents who are not committed to another sub specialty career the excitement and challenges of a career in bone marrow transplantation, so that our field will have providers for the future.

7183 Outcomes in metastatic (met) germ cell tumours (GCT): 5-year experience from a single institution

Germ cell tumours (GCTs) of the testis are the most common cancer in young men; they are also one of the most curable cancers. Standard treatment of metastatic GCTs has evolved on the basis of randomised trials and prognostic factors.This review summarises the evolving role of chemotherapy in the treatment of previously treated and untreated patients with metastatic GCTs and outlines the current standard treatment.Randomised and nonrandomised trials of first-line, salvage, and palliative therapy were reviewed.Three cycles of standard bleomycin, etoposide, and platinum (BEP) can be considered the gold-standard treatment in good-risk patients, and four cycles of the same combination can result in cure in approximately 80% of intermediate-risk and 50% of poor-risk patients. The routine use of high-dose chemotherapy in patients with intermediate- or poor-prognosis GCT has not improved treatment outcome, but the role of tumour marker decline during the first cycles may provide useful prognostic information. Prognostic variables in patients who experience treatment failure after cisplatin-based chemotherapy can be used to guide salvage strategies, and many new drugs or combinations have shown activity in this setting. Patients and physicians should be aware of the risk of short- and long-term toxicity of treatments, and guidelines for screening and prevention of this risk should be established.A risk-based strategy offers the best chance of cure, even in patients with refractory GCT.

Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989

This study assesses whether new treatment strategies developed in clinical trials translate into improved survival for multiple myeloma (MM) patients in the Netherlands. All patients diagnosed with MM in the Northern part of the Netherlands between 1989 and 2005 were retrieved from two regional population-based cancer registries. Information on study participation was derived from linkage with trial information systems. The effect of period of diagnosis (1989–1992, 1993–1996, 1997–2000, 2001–2005), age (<50, 50–65, 66–74, ⩾75), gender, Salmon–Durie (SD) stage, trial participation and treatment on relative survival were studied. In total 4985 patients were included. When trial participation was analysed for exact periods in which trials were open, 16% of patients aged ⩽65 years with SD-stage I and 38% with SD-stage II or III were enrolled compared to 2% of patients aged >65 years with SD-stage I and 5% with SD-stage II or III. Relative survival decreased with age ( p < .001), with advanced stage ( p < .001) and was better for patients enrolled in trials ( p < .001). Five-year relative survival increased from 34% (95% confidence interval (95% CI) 28–39%) in 1989–1992 to 56% (95% CI 50–61%) in 2001–2005 for patients ⩽65 years. The excess mortality was 37% lower in 2001–2005 than in 1989–1992 for these patients, adjusted for age, stage, trial participation and gender ( p < .001). Survival did not improve for older patients. In conclusion: MM survival improved among younger but not among older patients since the mid-1990s. The improved survival of younger patients coincided with increasing trial participation and increasing use of high-dose chemotherapy and autologous stem-cell transplantation.

High-dose chemotherapy with autologous stem cell transplantation for relapsed Ewing's sarcoma

10545 Background: Nearly 30–40% of patients with newly diagnosed, non-metastatic Ewing's Sarcoma (EWS) relapse. Post-relapse survival (PRS) in EWS is very poor, with less than 15–20% alive 5-years after recurrence. The role of high-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is under investigation in metastatic and high risk localized EWS patients. In order to improve PRS, we employed HDCT with ASCT in EWS patients at 1st relapse. Methods: All non-metastatic EWS patients treated in Italian Sarcoma Group centers who relapsed between 1999 and June 2008 were offered HDCT (busulfan 4 mg/kg × 4 days orally and melphalan 140 mg/m2) with ASCT whenever possible (no previous HDCT; stable or responding disease after standard dose chemotherapy; adequate peripheral blood stem cells harvest). Results: 72 EWS patients experienced disease recurrence. Fifty (62%) were male. Twenty-eight (39%) of patients had previously received HDCT. Median relapse free interval (RFI) was 16 months (2.8–64). Pattern of relapse was: lung metastases in 20 (28%) patients, bone metastases in 12 (16%), local recurrence in 11 (15%) and multiple sites in 29 (40%). Treatment at 1st relapse was: standard dose chemotherapy in 31 (43%) patients; HDCT followed by ASCT in 24 (33%); palliative treatment in 12 (17%) and surgery only in 5 (7%). Three patients died of treatment-related toxicity. With a median follow-up of 24 months (1–64), the 3-year post-relapse survival (PRS) was 21% (95%CI 7–35). 3-year PRS was better for patients with a lung only relapse [48%, (95%CI 21–74)] and a RFI &gt; 2 years [51%, (95%CI 27–76)]. 3-year PRS was 33% (95%CI 13–54) for patients treated with HDCT and 22% (95%CI 6–39) for those receiving standard dose chemotherapy. A significant (P 0.02) advantage was observed in the subgroup of patients with a shorter RFI treated with HDCT [3-year PRS 29% (95%CI 5–52)] compared to those treated with standard dose chemotherapy [3-years PRS 13%, (95%CI 2–29)]. Conclusions: Pattern of recurrence and RFI are the main factors influencing PRS in EWS. The use of HDCT with ASCT in recurrent EWS is investigational. Patients with shorter RFI could more likely benefit from HDCT. No significant financial relationships to disclose.

Therapeutic challenges in primary CNS lymphoma

Optimum treatment for patients with primary CNS lymphoma remains challenging because there have not been any large randomised clinical trials of this rare tumour. Drugs used in treating systemic non-Hodgkin lymphoma have mostly proven ineffective because of difficulties crossing the blood-brain barrier. The recognition of the efficacy of high-dose methotrexate was a substantial therapeutic breakthrough and further advances, such as the development of polychemotherapy regimens, have built on this. Whole-brain radiotherapy can consolidate response to chemotherapy, but the associated toxic effects of chemoradiation can be unacceptable. Other effective approaches include disruption of the blood-brain barrier and the use of high-dose chemotherapy. Recently, there have been attempts to optimise multi-drug chemotherapy regimens by focusing on improving survival and reducing toxic effects. A promising area of research is the incorporation of novel targeted drugs into standard treatment frameworks. In the future, greater cooperation between research groups should hopefully lead to further therapeutic advances.

Prognostic Factors for Long-Term Survival in Metastatic Breast Cancer Patients Treated with High Dose Chemotherapy and Autologous Stem Cell Transplantation

Despite the introduction of modern therapeutics, overall survival (OS) in metastatic breast cancer (MBC) has not changed in 20 ys. In the 1990s a major effort was made to improve the situation through the use of high dose chemotherapy with autologous stem cell transplantation (HD-ASCT). Although OS was not affected in randomized trials, which led to near abandonment of this therapy, some studies suggested that progression-free survival (PFS) can be improved with HD-ASCT. To identify distinct transplant-, disease- and patient-related characteristics predictive of survival in patients with MBC who received HD-ASCT, we reviewed records of all patients in the bone marrow transplant registry at UCSD treated with HD-ASCT for MBC between 1989 and 2000.METHODS: Age, race, stage at diagnosis, histology, estrogen receptor (ER) and menopausal status, body mass index (BMI) in kg/m2, time to transplant and death, site of metastasis, disease status prior to and after transplant, and days in hospital were extracted from medical records. Brookmeyer & Crowley's 95% confidence intervals were used for median survival times, Cox models for predictors of a time-to-event variable and Schoenfeld tests for proportional hazard assumptions, respectively.RESULTS: Of 96 patients with MBC 21, 43, 23, 8 and 1 had stage I, II, III, IV or unknown disease at diagnosis, respectively. Histologies were: infiltrating ductal, lobular, inflammatory or unknown in 79, 10, 6 and 1 of the cases, respectively. ER status was positive in 59.4% of patients and 29.2% of patients were post-menopausal. 84.4%, 4.2% and 11.5 % of patients were of caucasian, black or other ethnicity, respectively. Mean ages at diagnosis and at transplant were 43.7 ys (SD 8.6) and 47.4 ys (SD 8.7), respectively, with a median time to transplant of 29 months (range 3.8–180.8). When progression of disease (PD) was diagnosed, primary sites were visceral (39.6%), bone (29.2%), local (16.7%) or nodal (14.6%). Mean BMI at transplant was 26 (SD 5.9); 24% of patients were obese (BMI ≥ 30). Mean length of hospitalization after transplant was 17 days (SD 9.5 days); 33% of patients were hospitalized ≥ 18 days. Pre-transplant, 30.2% of patients were in complete remission; after HD-ASCT, this percentage increased to 41.7%. Median PFS and OS were 3.9 ys (CI 2.9–5.4) and 5.6 ys (CI 4.1–7.4) after initial diagnosis and 0.6 ys (CI 0.5–0.8) and 1.7 ys (CI 1.36–2.07) after transplant, respectively. As opposed to ER+ patients the rate of death events in ER− patients slowed down substantially after 5 ys from diagnosis. Although not statistically significant, at 12 ys, survival after HD-ASCT was 18.5% in ER− patients and 2.6% in ER+ patients. Stratified by ER status, stage at diagnosis was an independent predictor of length of PFS and OS. At diagnosis, stage I patients were at lowest risk of death when compared to stage II–IV patients with HRs of 2.7 (II vs I CI 1.4–5.2), 4.6 (III vs I CI 2.1–10) and 17 (IV vs I CI 6.1–47.8) disease; lower risk of death persisted for patients with initial stage I after PD was diagnosed with HRs of 2.4 (II vs I CI 1.3–4.6), 2.8 (III vs I CI 1.3–5.7) and 3.9 (IV vs I CI 1.6–9.9). Death risks were increased with infiltrating lobular carcinoma when compared with infiltrating ductal carcinoma (HR 2.5; CI 1.1–5.38) or when BMI was ≥ 30 (HR 3.1; CI 1.8–5.4); PFS in patients with a BMI ≥ 30 was significantly shorter after PD was diagnosed (death HR 3.1 [CI 1.8–5.5] when compared to BMI < 30). Visceral when compared to bone metastasis was a negative predictor of OS (HR 2.3; CI 1.3–4.1). Hospitalization ≥ 18 days after HD-ASCT was the strongest predictor of time to death after transplant (HR 2.2; CI 1.4–3.6).DISCUSSION: The survival rate at 12 ys after HD-ASCT was 8.2% for patients with MBC. Survival was higher for ER- compared to ER+ patients. Negative prognostic factors for OS and PFS were higher stages of disease at initial diagnosis, but also once PD was diagnosed, infiltrating lobular histology and obesity. Since all transplants were carried out prior to routine assessment of Her-2 neu receptor status, this information was not part of our analysis. At PD, visceral metastasis translated into poorer OS and after HD-ASCT, length of hospitalization became the most important outcome predictor. Although HD-ASCT in MBC has lost favor because of no improvement in global OS, our analysis may provide a rationale for selection criteria to determine which patients could benefit from future trials of HD-ASCT.

High-dose chemotherapy followed by stem cell rescue for high-risk germ cell tumors: the Stanford experience

Germ cell tumors carry an excellent prognosis with platinum-based therapy upfront. The patients who either relapse or demonstrate refractoriness to platinum pose a challenge. There exist many reports in the literature on the use of high-dose chemotherapy and stem cell rescue improving the outcome in patients with relapsed germ cell tumors. However, the reports have great variability in the patient selection, prior treatments, the choice of the conditioning regimen and variability of the doses within the same regimen. In this report, we present 37 patients who underwent a uniform protocol of high-dose chemotherapy with stem cell rescue. Stem cell mobilization was performed with high-dose CY (4 g per m(2)) and we were able to collect adequate cells for marrow rescue in all patients. Patients received a high-dose regimen with etoposide (800 mg/m(2) per day) days -6, -5 and -4 as a continuous infusion, carboplatin (667 mg/m(2) per day) on days -6, -5 and -4 as a 1 h infusion, and CY (60 mg/kg per day) on days -3 and -2. In this high-risk group of patients, high-dose chemotherapy with autologous stem cell rescue led to a 3-year overall survival of 57% and a 3-year event-free survival of 49%. The results are reflective of a single procedure. No tandem transplants were performed. The treatment-related mortality was low at 3% in this heavily pretreated group.

Salvage chemotherapy after failure of first-line chemotherapy in patients with metastatic testicular cancer

Because of the small number of relapsed patients, their prognostic variability and the complexity of second-line therapy, randomized studies are largely lacking and treatment recommendations for patients with relapse after first-line chemotherapy are derived from retrospective series or phase II studies. This review summarizes the existing evidence including several recently published larger studies on the use of high-dose chemotherapy in these patients. Patients with unfavorable features such as incomplete response to first-line therapy, cisplatin refractoriness, multiple relapses or advanced stage at initial diagnosis have been shown to benefit from salvage high-dose chemotherapy with autologous stem cell support. Long-term survival rates of up to 60% have been reported after salvage high-dose chemotherapy for these patients. The treatment for patients relapsing after complete remission to first-line therapy, cisplatin-sensitive disease and gonadal primary remains controversial. Excellent long-term event-free survival rates of up to 80% have been reported after both conventional and high-dose chemotherapy. Surgery remains an important part of any salvage strategy. The prognosis of patients relapsing after first-line cisplatin-based chemotherapy has improved with multimodality therapy including conventional and high-dose chemotherapy, surgery and radiation. The treatment of these patients requires a close cooperation of experienced medical oncologists, urologists and radiation oncologists.

High-dose Chemotherapy and Adoptive Immunotherapy in the Treatment of Recurrent Pediatric Brain Tumors

Pediatric patients with recurrent brain tumors have a poor prognosis and limited therapeutic options. We investigated the use of high-dose chemotherapy with adoptive immunotherapy for recurrent brain tumors. Three pediatric patients with recurrent brain tumors received high-dose chemotherapy. This was followed by adoptive transfer of ex-vivo expanded T-cells. The T-cells were generated from peripheral blood after immunization with autologous cancer cells. The objectives of this study included (1) establishing the safety and feasibility of this potential treatment, (2) measuring changes in immune response after high-dose chemotherapy and adoptive immunotherapy, and (3) determining whether adoptive immunotherapy would be able to translate into a clinical response. Immune function was tested in all patients at the time of enrollment into the study. Humoral responses to recall antigens delayed-type hypersensitivity (DTH) were intact in all patients. After immunizing patients with autologous cancer cells, peripheral blood lymphocytes were harvested and activated with anti-CD3, expanded in-vitro, and infused post-autologous transplant. Patients received at least three doses of the vaccine, each consisting of an intradermal administration near a draining lymph node at biweekly intervals. Toxicity was limited and well tolerated in all patients. All three patients showed a tumor-specific immune response by serial imaging. Responses were durable at 16, 23, and 48 months, respectively.

Dose-Intensive Chemotherapy with Growth Factor or Autologous Bone Marrow or Stem-Cell Transplant Support in First-Line Treatment of Advanced or Metastatic Adult Soft Tissue Sarcoma: A Clinical Practice Guideline

In patients with inoperable locally advanced or metastatic soft tissue sarcoma, does first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation improve response rate, time to disease progression, or survival as compared with standard-dose chemotherapy? What are the effects of first-line dose-intensive chemotherapy supported by growth factor or autologous bone marrow or stem-cell transplantation on toxicity and quality of life? Because therapeutic options for adult patients with advanced or metastatic soft tissue sarcoma are scarce and the possibility of cure for these patients is extremely limited, the Sarcoma Disease Site Group (dsg) felt that a review of the available literature on dose-intensive chemotherapy for adult patients with locally advanced or metastatic soft tissue sarcoma and subsequent development of a clinical practice guideline based on the evidence were important. A systematic review was developed and clinical recommendations relevant to patients in Ontario were drafted. The practice guideline report was reviewed and approved by the Sarcoma dsg, which comprises medical oncologists, radiation oncologists, surgeons, a pathologist, a methodologist, and community representatives. External review by Ontario practitioners was obtained through a mailed survey, the results of which were incorporated into the practice guideline. Final review and approval of the practice guideline was obtained from the Report Approval Panel. Based on the systematic review, consensus, and external review, the Sarcoma dsg makes these recommendations: Dose-intensive chemotherapy with growth factor support is not recommended in the first-line treatment of patients with inoperable locally advanced or metastatic soft tissue sarcoma. The data are insufficient to support the use of high-dose chemotherapy with autologous bone marrow or stem-cell transplantation as first-line treatment in this group of patients. Eligible patients should be encouraged to enter clinical trials assessing novel approaches or compounds. High-dose chemotherapy with growth factor or autologous bone marrow or stem-cell transplantation has adverse effects similar to those seen with standard-dose chemotherapy. With high-dose regimens, the incidence of grades 3 and 4 thrombocytopenia is significantly higher, and neutropenic fever and febrile neutropenia occur more frequently. Compared with standard treatment, the rate of treatment-related death is also higher with high-dose regimens.

High‐dose chemotherapy with autologous stem cell transplantation in adults with recurrent embryonal tumors of the central nervous system

Embryonal central nervous system (CNS) tumors (medulloblastoma, cerebral neuroblastoma, pineoblastoma, and primitive neuroectodermal tumors) are rare in adults. Recurrent disease has an extremely poor outcome. The use of high-dose chemotherapy (HDC) with autologous stem cell transplantation (ASCT) has demonstrated promising results in children with recurrent disease, but there are only limited data regarding its role in adults. The purpose of the current study was to evaluate adult patients with embryonal CNS tumors who were treated with HDC with ASCT and compare their outcomes with those of patients who received conventional-dose chemotherapy. The authors reviewed the medical records of 23 adult patients (age >or= 18 years) who were treated at the Mayo Clinic for recurrent embryonal CNS tumors between 1976 and 2004. The authors compared treatment with HDC with ASCT (10 patients) with an historic control of patients treated with conventional-dose chemotherapy (nitrosourea based, cisplatin based, or both) (13 patients). HDC with ASCT was associated with increased survival (P= .044) and a longer time to disease progression (TTP) (P= .028). The conventional-dose chemotherapy group had a median TTP of 0.58 years and a median survival of 2.00 years. The HDC with ASCT group had a median TTP of 1.25 years and a median survival of 3.47 years. When restricted to patients receiving ASCT after first disease recurrence, the median TTP was 2.5 years and the median survival was 4.16 years. Toxicities were similar in both groups. Improvements in the median TTP and survival noted with the administration of HDC with ASCT, as well as the acceptable toxicity of this regimen, supports consideration of its use in adults with recurrent embryonal CNS tumors.

182: Conventional Chemotherapy with Interferon Versus Conventional Chemotherapy followed by High Dose Chemotherapy and Autologous Stem Cell Transplantation in Untreated Patients with Advanced Follicular Lymphoma. A Meta-Analysis of Randomized Clinical Trials

Purpose: High dose chemotherapy (HDT) followed by autologous stem cell transplantation has been used as part of the initial therapy of patients with untreated advanced follicular lymphoma and has been compared with standard dose therapy (SDT) with variable benefit in randomized clinical trials (RCT). Therefore, to address the variability in results, we undertook a systematic review of all RCT that evaluated the outcome of upfront use of HDT versus SDT. Patients and Methods: We performed a wide search in the main computerized databases of interest (MEDLINE, EMBASE, LILACS, CANCERLIT, and Cochrane Library).

High-dose chemotherapy supported by autologous stem cell transplantation in patients with primary central nervous system lymphoma: facts and opinions

The standard approach to primary central nervous system lymphomas (PCNSL), that is high-dose methotrexate (HD-MTX)-based chemotherapy followed by whole-brain irradiation (WBRT), is associated with disappointing outcome. Moreover, this strategy is heavily conditioned by increased risk of disabling neurotoxicity, mostly among elderly patients. Several drugs and strategies have been investigated to improve results and neurotolerability. Among others, some investigators focused on the use of high-dose chemotherapy supported by autologous stem cells transplant (HDC/ASCT) as consolidation after primary chemotherapy. This approach has been used as salvage therapy in patients who experienced progressive disease or relapse after conventional chemo-radiotherapy or as consolidation after primary HD-MTX-based chemotherapy, replacing or preceding WBRT. Evidence supporting the role of HDC/ASCT is growing but several questions are still unanswered. The best conditioning regimen, the role of concomitant intrathecal chemotherapy, the neurotoxicity risk of further WBRT after transplant, the best time for response assessment and late effects both on neurological performance and extraneural organs remain to be characterised. This critical review is focused on the analysis of published experiences on HDC/ASCT in PCNSL in order to provide preliminary answers to the most pressing questions in this field.

Stem cell transplantation for neuroblastoma

High-risk neuroblastoma is a childhood malignancy with a poor prognosis. Gradual improvements in survival have correlated with therapeutic intensity, and the ability to harvest, process and store autologous hematopoietic stem cells has allowed for dose intensification beyond marrow tolerance. The use of high-dose chemotherapy with autologous hematopoietic stem cell rescue in consolidation has resulted in improvements in survival, although further advances are still needed. Newer approaches to SCT and supportive care, most notably the transition to PBSC, have resulted in further improvement in survival and decreases in treatment-related mortality. Research into experimental approaches to hematopoietic SCT is ongoing.

Enhanced Anti-Breast Cancer Cytotoxicity after Autologous Peripheral Blood Stem Cell Transplant (PBSCT) by Boosting with Multiple Infusions of Activated T Cells (ATC) Armed with Anti-CD3 x Anti-Her2 Bispecific Antibody (Her2Bi) Prior to PBSCT.

More aggressive treatment strategies are needed for women with metastatic breast cancer(mBrCa). Although peripheral blood stem cell transplant (PBSCT) permits the use of high-dose chemotherapy (HDC) that could not otherwise be given, results for PBSCT have not been encouraging. In order to boost tumor kill, we combined a protocol that targets Her2 using activated T cells (ATC) armed with anti-CD3 × anti-Her2 bispecific antibody (Her2Bi) with a second protocol that involves infusions of ATC after PBSCT to boost anti-tumor immunity. In our phase I trial using ATC with Her2Bi to treat women with mBrCA who have Her2 positve or negative disease, we found that multiple infusions of armed ATC induced cytotoxicity directed at BrCa cells in the peripheral blood mononuclear cells (PBMC) of the patients that develop in 2 weeks and last up to 4 mos (Clin Canc Res 12:569, 2006). Armed ATC lyse tumors that are Her2 low-expressors (0–1+). Targeting leads to specific cytotoxicity, induces cytokine/chemokine release, and proliferation of the armed ATC. In a second study, ATC were infused after PBSCT into 23 women with mBrCa leading to 70% overall survival and 50% progression free survival at 32 mos after PBSCT. Therefore, the combined strategy involved obtaining T cells by another leukopheresis after the boosting with armed ATC, expanding the immune T cells and infusing the expanded ATC after PBSCT to transfer pre-immune anti-BrCa cytotoxicity to reconstitute cytotoxicity after PBSCT. Two patients (one pt was Her2 3+ ; one pt was Her2 0–1+) underwent treatment with this treatment approach. Both patients were given 8 infusions (20 billion/infusion with a total of 160 billion) of ATC armed with Her2Bi in the first protocol and subsequently leukopheresed and ATC were produced for the second protocol. The expanded ATC at an effector:target ratio (E/T) of 25:1, exhibited cytotoxicity at BrCa tumor cells (SK-BR-3) at 71% and 75% for pts 1 and 2, respectively. The cell product for pt 1 contained 68% CD3+, 32% CD4+, 39% CD8+, 29% CD16+56+, 12% CD4+CD25+, and 15% CD8+CD25+ cells and the cell product for pt 2 contained 35% CD3+, 25% CD4+, 8.5% CD8+, 23.3% CD16+56+, 10.4% CD4+CD25+, and 4.7% CD8+CD25+ cells. The protocol involves infusing 15 doses of ATC after PBSCT with 3 doses of ATC/week for 3 weeks and then ATC once/week for six more weeks. The pt1 and pt 2 received total of 114 and 70 billion ATC, respectively. Pt1 developed anti-BrCA cytotoxicity of 9% 2 weeks after PBSCT. Pt2 exhibited anti-BrCa cytotoxicity at an E:T of 25:1 of 38% and 15% at 3 weeks and 6 months after PBSCT, respectively. Phenotyping of peripheral blood at 6 mos after PBSCT showed 61% CD3+, 36% CD4+, 19.5% CD8+, and 15.5% CD56+ cells. There was no cytotoxicity directed at Daudi cells. These data strongly suggest that transfer of pre-immune cells after PBSCT accelerate immune reconstitution of tumor specific cytotoxicity after PBSCT. The preboost strategy with targeted T cells is being combined in a proof of principle trial to assess whether enhanced cytotoxicity can be consistently enhanced after PBSCT.

The Role of High-Dose Chemotherapy Supported by Hematopoietic Stem Cell Transplantation in Patients With Multiple Myeloma: Implications for Nursing

Multiple myeloma (MM), a neoplastic proliferation of plasma cells originating from the B-cell line, is associated with deleterious complications and poor outcomes. The failure of conventional combination chemotherapies to improve the overall survival of patients with MM has led to the use of high-dose chemotherapy supported by stem cell transplantation (SCT). Although several novel therapies have emerged since the late 1990s, their survival benefits are undetermined. High-dose chemotherapy with SCT provides better response rates compared to conventional chemotherapy and yields a trend toward greater survival benefits, especially with the use of a tandem (two successive) transplantation strategy. This article discusses standard SCT in patients with MM and some of the new transplantation strategies, including tandem autologous SCTs and reduced-intensity nonmyeloablative allogeneic SCT, and their implications for nursing.

Primary central nervous system lymphoma – Biological aspects and controversies in management

Introduction This review was produced from the workshop on primary central nervous system lymphoma (PCNSL) at the European Cancer Conference (ECCO 13) in Paris in 2005. It covers the presentation and biological features of the disease (Professor Khe Hoang-Xuan). The role of chemotherapy, including the management of intraocular lymphoma and the use of high dose chemotherapy followed by autologous stem cell transplantation for PCNSL, is discussed (Dr. Andres Ferreri) as well as controversies in the use of whole brain radiotherapy (WBRT) after chemotherapy (Dr. Michele Reni). The topics covered with discussants at the workshop are also summarised. Conclusion The imaging of the brain and the histopathology including detailed immunohistochemistry is of vital importance in making an accurate diagnosis of the disease and understanding the extent of spread of the disease in the CNS. The importance of high dose methotrexate (HDMTX; dose ⩾1 g/m 2), as the most active drug in the treatment of PCNSL, is stressed. The authors recommend that HDMTX alone or in combination with other active chemotherapy agents should be used to treat PCNSL followed by whole brain radiotherapy (WBRT) unless contraindicated because of the advanced age of the patient and existing cognitive impairment. Only published protocols should be used unless the patient is to be offered a trial that has either national or international support. Baseline neuropsychological tests should be carried out before treatment and repeated during and after treatment. The risks of cognitive impairment associated with the disease, with methotrexate – containing chemotherapy and with whole brain radiotherapy should be explained to patients and relatives when obtaining informed consent. Long-term survival, with current treatment regimes, is possible with PCNSL but this appears limited to patients less than 60 years of age at presentation (mostly patients less than 50 years of age).

High-Dose Chemotherapy Followed by Autologous Hematopoietic Stem-Cell Transplantation for the Treatment of Solid Tumors in Adults: A Critical Review

High-dose chemotherapy (HDCT) plus autologous hematopoietic stem-cell transplantation (HSCT) has been explored in several solid tumors in the attempt to prevent and/or overcome tumor-cell chemo-resistance, based on in vitro evidence of a "dose-response" effect. Preliminary encouraging results from non-randomized trials, led to an increased use of this strategy in the 1990s. Since the end of the nineties, the fraudulent nature of initial reports in breast cancer, the failure of positive prospective randomized trials, HDCT-related toxicities, determined a dramatic decline of interest in this approach. Loss of accrual in ongoing randomized studies was the first consequence, causing the current unavailability of optimal information. From the review of available published data, the use of HDCT with autologous HSCT may improve tumor response rates and/or possibly progression-free survival, especially in some selected patient subgroups. However, this strategy did not demonstrate in almost all cases to produce significantly higher cure rates than standard-dose chemotherapy. Well-designed randomized studies and future strategies integrating HDCT with concomitant and/or subsequent anti-tumor therapies targeted against the residual disease might be suggested in clinically and biologically selected patients.

Advances in Urologic Oncology: Results Progress From Successful Interdisciplinary Research

Despite its relative rarity, GCT in the adult male serves as a model of curability. The appropriate use of surgery, radiation, chemotherapy, and multimodality approaches has been studied in randomized trials that have successfully established many treatment paradigms. de Wit and Fizazi 4 review the controversies and treatment options in the optimal management of clinical stage I seminoma and nonseminomatous GCTs, and provide a detailed overview of the clinical trial results with a discussion of the risks and benefits of surveillance, surgery, radiation therapy (for seminoma), and adjuvant chemotherapy. In the treatment of metastatic disease, the International Germ Cell Cancer Collaborative Group’s risk algorithm established international agreement on the clinical features that constitute good, intermediate, and poor prognosis, 5 each of which has established standards of care. Kondagunta and Motzer 6 update the standards of care for the treatment of patients with both previously untreated and relapsed disease and address controversies such as the use of bleomycin in good-risk disease, the use of high-dose chemotherapy with stem-cell rescue, and postchemotherapy management of advanced seminoma. Oldenberg et al 7 review the risk factors associated with, and the clinical management of, late relapse, defined as disease recurrence 2 or more years after primary therapy. Once thought to be an exceedingly rare event, recent reports suggest that late relapses may be more common. An improved understanding of the genetic molecular events that are observed in GCT has emerged in the last two decades, beginning with the observation that an isochromosome of 12p (i[12p]) was frequently observed in GCT. Houldsworth et al provide an overview of the pathobiology of adult GCT, the role of 12p genes implicated in malignant transformation of germ cells, and insights into chemotherapy sensitivity and resistance. 8

Autologous peripheral blood stem cell transplantation in children with non-Hodgkin’s lymphoma: a report from the Korean society of pediatric hematology-oncology

Recent development of stratified chemotherapeutic regimens has rapidly improved the survival rate of non-Hodgkin's lymphoma (NHL) of childhood. Despite these improvements, the outcome for children with recurrent or refractory NHL remains dismal. We explored the use of high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation (HDC/PBSCT) for children with either refractory or recurrent NHL, and we evaluated various factors influencing outcome of HDC/PBSCT. Thirty-three patients underwent HDC/PBSCT in 11 institutes were enrolled. All patients had refractory or recurrent NHL. Sex, stage at diagnosis, histologic subtype (lymphoblastic, Burkitt's, and large-cell lymphoma), LDH level at diagnosis, disease status at transplantation, and preparative regimens for HDC/PBSCT were explored. In regard to the patients, six had Burkitt's lymphoma, 13 had lymphoblastic lymphoma, and 14 had large-cell lymphoma. The 2-year event-free survival (EFS) was 59.1+/-9.3%. The EFS for Burkitt's, lymphoblastic, and large-cell lymphoma was 66.7+/-27.2, 50.5+/-14.8, and 82.1+/-11.7%, respectively. In comparison with lymphoblastic and non-lymphoblastic lymphoma, the relative risk for lymphoblastic lymphoma was higher than the others (P = 0.037). EFS between anaplastic large-cell and diffuse large-cell lymphoma was 100 and 55.6+/-24.9%, respectively (P = 0.106). Status at transplantation was the most predictive factor for the survival after HDC/PBSCT (EFS for CR 70.8+/-9.5% vs non-CR 20.0+/-17.9%, P = 0.008). Transplantation-related complications were minimal, and infection was the most prevalent complication. HDC/PBSCT is considered applicable to recurrent or refractory pediatric NHL patients safely and it could replace conventional chemotherapy. In this study, children with CR status at the time of HDC/PBSCT showed higher survival rate. However, refractory or recurrent lymphoblastic lymphoma patients showed dismal results. Therefore, new therapeutic modalities may be needed for this group of NHL patients.