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Development and validation of the pediatric nausea assessment tool for use in children receiving antineoplastic agents.

STUDY OBJECTIVE: To develop and validate an instrument to assess nausea intensity in children aged 4-18 years. DESIGN: Prospective, descriptive study. SETTING: Tertiary-quaternary, university-affiliated pediatric hospital. PATIENTS: Four pediatric inpatient groups (177 patients): group 1 (107), those receiving cancer chemotherapy; group 2 (24), those receiving cancer chemotherapy before hematopoietic stem cell transplantation; group 3 (23), those with cancer who were not receiving cancer chemotherapy; and group 4 (23), those without cancer. INTERVENTION: We developed a scale with a standard script for administration, the Pediatric Nausea Assessment Tool (PeNAT). Revisions were made after face validity testing with clinicians and parents, and pilot testing with 15 inpatients undergoing chemotherapy. MEASUREMENTS AND MAIN RESULTS: The PeNAT scores were obtained 4-24 hours after chemotherapy in groups 1 and 2. Dietary intake scores and number of emetic episodes were recorded for the 4 hours before PeNAT administration for all patients in group 2 and 36 patients in group 1. Parents of a subset of patients made an independent assessment of their child's nausea and pain intensities immediately before PeNAT administration. Reliability was evaluated in groups 1 and 2 by correlating the first and second (obtained 1 hr after the first) PeNAT scores. Construct validity was evaluated by comparing PeNAT scores in groups 1-4. Criterion-related validity was evaluated by correlating PeNAT scores with emetic episodes and dietary intake. Convergent and discriminant validity were evaluated by correlating PeNAT scores with parental assessments of nausea and pain. Significant differences in PeNAT scores were noted among the study groups (p=0.035). Moderate correlation was noted between the first and second PeNAT scores (Spearman rho = 0.649). The PeNAT scores correlated modestly with emetic episodes (Spearman rho = 0.322) but not with dietary intake (Spearman rho = -0.217). Children's PeNAT scores correlated moderately with their parents' assessment of nausea (Spearman rho = 0.442), whereas little correlation was seen between children's PeNAT scores and parents' assessment of pain (Spearman rho = 0.167). CONCLUSION: The PeNAT is a new instrument that can be used by children to assess nausea intensity.

Adolescent↗

[Morphology of borderline mucinous ovarian tumors].

The examination of structures of the tumor tissues taken from 47 patients with borderline mucinous tumours of the ovary showed that the tumors belonging to this group, like their serous analogues, were an indistinctly limited nosological entity that characterizes a particular stage in the malignant transformation of the epithelium as evidenced by a wide range of structures that are interchangable from mucinous adenofibroma to mucinous carcinoma. Death may result from pseudomyxoma or dissemination that follows the pattern seen in cancer. The latter generally stems from small-sized areas of occult cancer which are detectable from a retrospective analysis of the material available. Intraoperative laceration of the tumor makes no contribution to the occurrence of peritoneal pseudomyxoma. The results of the histochemical study into the mucosa indicated that the tumor cells were heterogeneous in mucosaccharides. The cells which were completely free from acid fractions in the presence of neutral mucins were identified. Disregarding the features indicated, one can reasonably reject the fact that the neoplasm is of mucinous character as judged from alcian blue-stained specimens.

Adenocarcinoma, Mucinous↗

[Autologous hematopoietic stem cell transplantation for the treatment of breast cancer].

To obtain higher anti-tumor efficacy for breast cancer (BC), high-dose chemotherapy (HDC) with autologous bone marrow transplantation (ABMT) and peripheral blood stem cell transplantation (PBSCT) is believed to be one of most effective strategies. PBSCT shows earlier hematological recovery comparing with ABMT, therefore HDC could be performed more safety to introduce PBSCT in the treatment of BC. Several investigators have reported that higher complete response (CR) rate and continuously CR rate were obtained to employ HDC in the earlier course of treatment for patient with advanced or recurrent BC responding to standard-dose chemotherapy. The efficacy of HDC has been also observed in adjuvant setting for patient with high-risk (> or = 10 axillary lymph nodes) after mastectomy. Phase III studies will clarify the efficacy of HDC with ABMT, PBSCT for the treatment of BC in near future.

Antineoplastic Combined Chemotherapy Protocols↗

High-dose chemotherapy and autologous stem cell transplant in women with de novo chemosensitive metastatic breast cancer.

The prognosis of patients with de novo stage IV breast cancer seems to be similar to that of patients with metastatic disease. Because these patients have not been exposed to prior therapy, the use of high dose chemotherapy (HDCT) may be beneficial. Twenty-four newly diagnosed (median age 42) responding metastatic breast cancer patients underwent HDCT (Stamp V) and stem cell support as their initial treatment. The predominant sites of metastatic disease were bone (12), lung (5), liver (2), lymph nodes (6), marrow (4), and soft-tissue (1). Estrogen/progesterone receptors were positive in 35%, negative in 45%, and unknown in 20%. Before transplantation, 10 patients were in complete remission (CR), 6 were in partial remission (PR), and 8 were inevaluable. Radiotherapy was administered to sites of documented metastatic disease. Tamoxifen was given to patients with receptor positive and unknown tumor status. After a median follow-up of 60 months from diagnosis (range 42 to 96 months), 15 patients have relapsed and 10 died. Mean and median progression free survival from transplant are 53 (SE 6.6, CI 40-66) and 60 (SE 18, CI 25-96) months, respectively. The median survival has not yet been achieved (>6 years). There was no treatment-related mortality. The use of HDCT in patients with chemosensitive, de novo metastatic breast cancer is safe and well tolerated. Overall clinical outcome is good; however, this study cannot determine whether this was due to treatment or selection bias.

Adult↗

[High dose chemotherapy with peripheral blood stem cell transplantation (PBSCT) For advanced testicular cancer].

Five patients with metastatic testicular cancer of advanced extent according to the Indiana University criteria were enrolled into this study. All tumors were non-pretreated non-seminomas. Initially all patients were treated with standard dose etoposide, ifosfamide and cisplatin (VIP) regimen. The response of two cycles of VIP was evaluated by tumor markers and diagnostic imagings. Two of the five patients showed a good response to VIP and subsequently achieved a pathological complete response (pCR) following surgical resection of residual masses after 3 or 5 courses of VIP. However, they suffered from severe myelosuppression and underwent peripheral blood stem cell transplantation (PBSCT) following the final course of VIP. The remaining three patients unlikely to be cured by VIP underwent chemotherapy consisting of high dose ICE:ifosfamide (6-10 g/m2 over 4days) carboplatin (1,500 mg/m2 over 4 days), etoposide (1,600-2,400 mg/m2 over 4 days) combined with PBSCT. This regimen resulted in one partial response (PR) with marker-negative and two PR with marker-positive. Residual masses were removed in all three patients and viable tumor cells were found in two. Of the five patients enrolled, four patients (80%) remain disease-free with minimal follow-up of 20 months, and the remaining one died of cancer 10 months after PBSCT. No serious side effects or complications were encountered. This study shows that standard dose induction therapy of VIP followed by early salvage chemotherapy of high dose ICE with PBSCT is well tolerated and effective in the treatment of advanced poor-risk testicular cancer.

Adult↗

[CBDCA, etoposide and epirubicin high-dose combination chemotherapy supported by peripheral blood stem cell transplantation (PBSCT) in metastatic breast cancer].

Six metastatic breast cancer patients, including one brain metastasis, one lung metastasis, three local recurrences and one bone metastasis, underwent multidrug chemotherapy with CBDCA, Etoposide (ETP) and Epirubicin (EPI). Each patient received two courses of PBSC mobilization chemotherapies and subsequently received high-dose chemotherapies for at least two courses. CBDCA AUC 4, ETP 300 mg/m2 and EPI 40 mg/m2 were administered intravenously as a PBSC mobilization chemotherapy, and high-dose chemotherapies were performed under the regimen of CBDCA AUC 8, ETP 900 mg/m2 and EPI 60 mg/m2. Severe bone marrow suppression due to high-dose chemotherapies was off sct by autologous peripheral blood stem cell transplantation (PBSCT). The PBSC mobilization chemotherapies resulted in one CR, three PR, one NC and one PD in the six patients. The PD patient died before high-dose chemotherapy. Consequently, the remaining five patients received the high-dose chemotherapies, which achieved three CR, one PR and one PD in the five patients. The response rate of high-dose chemotherapy was 80% (4/5 cases). In overall outcome, three patients have continued 16, 12 and 10 months tumor-free survival, and three patients died of cancer progression. High-dose chemotherapy with CBDCA, ETP and EPI has led to increased CR rates in metastatic breast cancer, and such therapy has desirable effect on the patient's prognosis.

Adult↗

Caveolin-1, mammary stem cells, and estrogen-dependent breast cancers.

Estrogen exposure is considered a significant risk factor for breast cancer development. Estrogen receptor (ER) alpha is expressed at low levels in normal epithelia, and its expression is dramatically up-regulated as transformation progresses during mammary hyperplasia and adenocarcinoma development. The mechanism(s) driving ERalpha up-regulation during mammary tumorigenesis remains unclear. Caveolin-1 (Cav-1) is the structural protein of plasmalemmal invaginations, termed caveolae, which functions as a tumor suppressor gene. Interestingly, Cav-1 dominant-negative mutations are exclusively found in ERalpha-positive breast cancer samples. In support of these clinical findings, ERalpha expression is increased in Cav-1 (-/-) null mammary epithelia, and estrogen stimulation further enhances the growth of Cav-1-deficient three-dimensional epithelial structures. These phenotypes correlate with augmented levels of cyclin D1. In addition, Cav-1 gene inactivation induces the accumulation of a cell population with the characteristics of adult mammary stem cells. Primary cultures of Cav-1 (-/-) mammary epithelial cells exhibit premalignant changes, such as abnormal lumen formation, epidermal growth factor-independent growth, defects in cell substrate attachment, and increased cell invasiveness. Thus, Cav-1 gene inactivation promotes premalignant alterations in mammary epithelia and induces increased ERalpha expression levels and the up-regulation of cyclin D1. As tumor formation is a multihit process, Cav-1 mutations that occur during the early stages of mammary transformation may be a critical upstream/initiating event leading to increased ERalpha levels.

Adult Stem Cells↗

Cancer chemopreventive agents, labdane diterpenoids from the stem bark of Thuja standishii (Gord.) Carr.

Seven labdane-type diterpenoids from the stem bark of Thuja standishii (Gord.) Carr. (Cupressaceae) and their analogues showed strong inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among these compounds, 15,16-bisnor-13-oxolabda-8(17), 11E-dien-19-oic acid was revealed to have the strongest inhibitory effect on the EBV-EA activation, being stronger than that of beta-carotene which has been intensively studied in cancer prevention using animal models. 15,16-bisnor-13-Oxolabda-8(17), 11E-dien-19-oic acid was also found to exhibit the excellent anti-tumor promoting activity in two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene and TPA.

9,10-Dimethyl-1,2-benzanthracene↗

High-dose treatment with carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in relapsed or refractory germ cell cancer: a phase I/II study. The German Testicular Cancer Cooperative Study Group.

PURPOSE: This trial evaluated the toxicity and efficacy of high-dose carboplatin, etoposide, and ifosfamide followed by autologous stem-cell transplantation in patients with refractory or relapsed germ cell cancer. PATIENTS AND METHODS: Between August 1989 and September 1992, 74 patients with refractory or recurrent germ-cell tumors received one cycle of escalating doses of carboplatin (1,500 to 2,000 mg/m2), etoposide (1,200 to 2,400 mg/m2), and ifosfamide (0 to 10 g/m2). Before high-dose therapy, two cycles of conventional-dose cisplatin, etoposide, and ifosfamide were administered to assess tumor responsiveness. Seventy-four patients were assessable for toxicity and 68 for response. RESULTS: The doses of carboplatin 1,500 mg/m2, etoposide 2,400 mg/m2, and ifosfamide 10 g/m2 appeared to be safe. At this dosage, we treated 20 patients and observed World Health Organization (WHO) grade 3 and 4 hematotoxicity (100%), nausea (100%), diarrhea (30%), and hepatotoxicity (10%). All patients developed granulocytopenic fever. At carboplatin doses of 1,500 mg/m2, kidney toxicity was mild, with a median maximum creatinine level of 1.4 mg/dL (range, 1.1 to 3.0 mg/dL). However, at carboplatin doses of 1,750 and 2,000 mg/m2, we observed nonacceptable nephrotoxicity and neurotoxicity. Two (3%) patients died of treatment-related complications. Six patients required hemodialysis, which was temporary in five patients and permanent in one. Objective responses were obtained in 43 of 68 (63%) patients, including 21 (31%) complete remissions (CRs) and 14 (20%) inoperable partial remissions (PRs) with marker normalization. The median observation time of surviving patients was 12 months (range, 2 to 32). The probabilities of overall survival, event-free survival, and the relapse-free survival at 2 years were 44% (SD 8%), 35% (SD 6%), and 67% (SD 9%), respectively. Patients with disease refractory to conventional-dose pretreatment had a poor prognosis, with only one of 23 patients surviving event-free at 7 months after high-dose chemotherapy (HDT). In contrast, 24 of 45 (53.3%) patients with sensitive disease survive event-free with a probability of event-free survival at 2 years of 50% (SD 8%). CONCLUSION: High-dose carboplatin, etoposide, and ifosfamide plus autologous stem-cell transplantation can be used in refractory and relapsed germ cell cancer with acceptable toxicity, and represents an effective, potentially curative salvage treatment.

Adult↗

Expression of stem cell factor and c-kit in human neuroblastoma. The Children's Cancer Group.

During development, mice with mutations of stem cell factor (SCF) or its receptor c-kit exhibit defects in melanogenesis, as well as hematopoiesis and gonadogenesis. Because melanocytes derive from neural crest cells, the role of SCF and c-kit was investigated in the neural crest-derived childhood tumor neuroblastoma. Using reverse transcription-polymerase chain reaction analysis, simultaneous expression of steady-state mRNA for the SCF ligand and its receptor c-kit was found in 14 of 14 (100%) human neuroblastoma cell lines and clones and in 8 of 18 (45%) human neuroblastoma tumor samples. Functional blockade of c-kit receptors in the cell lines SK-N-BE(2) and SH-SY5Y using the mouse monoclonal anti-c-kit antibody SR-1 resulted in a significant decrease in cellular growth rate when measured by either 3H-thymidine incorporation or clonogenicity. In addition, higher levels of c-kit mRNA expression were associated with parental neuroblastoma cell lines and subclones with a neuronal (N) differentiation phenotype, whereas lower levels of c-kit mRNA were associated with neuroblastoma cell line subclones having a schwannian/glial/melanocytic pattern of differentiation. However, the differentiation phenotype of neuroblastoma cell lines was not directly altered when c-kit expression was blocked using the SR-1 antibody. In summary, these data indicate that c-kit receptor expression may play a significant role in the growth regulation of the two neuroblastoma cell lines examined and suggest that c-kit may also play a similar role in neuroblastoma growth regulation in vivo. Simultaneous expression of SCF and c-kit mRNA in both neuroblastoma cell lines and tumors implies that c-kit may act as part of an autocrine growth loop in conjunction with endogenous production of SCF in this disease.

Animals↗

Prognostic significance of the detection of tumour cells in peripheral blood stem cell collections in stage II and III breast cancer patients treated with high-dose therapy.

The purpose of this study was to evaluate the incidence and extent of tumour cell contamination in bone marrow specimens and stem cell collections from 34 breast cancer patients undergoing high-dose therapy as adjuvant treatment, and to determine the prognostic significance for the clinical outcome. Tumour cell contamination was evaluated by flow cytometry using a double-colour test and an anti- Pan cytokeratin (CK) antibody. Two out of 34 (6%) baseline bone marrow specimens, none of seven marrow harvests and nine out of 32 aphereses (28%) mobilised from seven out of 27 patients (26%) contained CK+ cells. Tumour contamination was more frequent in patients with 10 or more involved lymph nodes and in those who received a shorter course of adjuvant chemotherapy before mobilisation. At a median follow-up of 43 months, 24 patients are in complete remission, whereas 10 patients experienced recurrence. Out of the 10 patients who relapsed, five (50%) had CK+ peripheral blood stem cell (PBSC) collections, whereas disease recurrence was seen in only two out of 24 (8%) patients who received CK- products (P=0.02). Moreover, CK+ PBSC collections were associated with a significantly shorter event-free survival and overall survival. CK+ collection is an unfavourable prognostic factor for patients treated with high-dose therapy. Whether the negative impact on clinical outcome depends on reinfusion of tumour cells or whether it simply indicates a larger disease extension is still unclear.

Adult↗

Cell cycle control as a basis for cancer drug development (Review).

Normal cell cycle progression relies on the cell's ability to translate extracellular signals such as mitogenic stimuli and intact extracellular matrices in order to efficiently replicate DNA and divide. Cyclin dependent kinases (cdks) respond to these signals and are largely responsible for positively pushing cells through the cell cycle. Due to their pivotal role in cell division, nature has evolved elaborate mechanisms to regulate the kinase activity of cdks. Cyclins are cdk binding partners which are required for kinase activity and their protein levels are intimately linked to the cell cycle stage. A variety of other cdk regulators such as phosphorylation events, natural inhibitors and complex stability are discussed. Phosphorylation of various cdk substrates results in diverse outcomes such as changes in gene expression, formation of prereplicative complexes and breakdown of the nuclear envelope. Cancer cells evolve in part by over-riding normal cell cycle regulation. Abnormal cdk activity is accomplished by cyclin amplification, cdk or substrate mutation as well as inactivation of inhibitors. The selective growth advantage of cancer cells also stems from amplification of positive growth signals, mutation of checkpoint and surveillance genes as well as deregulation of programmed cell death or apoptosis. The full potential of cancer therapies, such as small molecule inhibitors and gene therapy among others, focusing on our knowledge of cell cycle regulation has yet to be reached.

Antineoplastic Agents↗

Phase I/II trial of cyclophosphamide, mitoxantrone, and escalated doses of carboplatin supported by peripheral-blood stem cells in women with metastatic breast cancer.

PURPOSE: To intensify a regimen of high-dose cyclophosphamide, mitoxantrone, and carboplatin that had previously produced high complete and overall response rates in metastatic breast cancer (MBC). PATIENTS AND METHODS: Forty-four patients with a median age of 43 years (range, 25 to 57 years) and previously untreated MBC who were responding to anthracycline-based or single-agent taxane chemotherapy received cyclophosphamide 1.5 g/m(2)/d and mitoxantrone 16 mg/m(2)/d combined with escalating doses of carboplatin 200 to 500 mg/m(2)/d, each given daily from days -6 to -3. Hematopoiesis was supported by mobilized peripheral-blood stem cells infused on day 0 and by use of granulocyte-macrophage colony-stimulating factor 300 microg/d subcutaneously starting on day 1. RESULTS: A total of six dose levels of carboplatin were examined. Grades 3 and 4 toxicity occurred in 10 patients and one patient, respectively, with grade 3 toxicity occurring in only five of 31 patients treated with < or = 400 mg/m(2) of carboplatin. Major dose-limiting toxicities were cardiac, pulmonary, and renal. Four patients developed congestive heart failure: two had persistently low ejection fraction 11 and 36 months after peripheral-blood stem-cell transplantation (PBSCT), and two recovered. Hematologic recovery to an absolute neutrophil count of greater than 0.5 x 10(9)/L occurred at a median of 11 days (range, 8 to 25 days) and to a platelet count of greater than 20 x 10(9)/L at a median of 10.5 days (range, 6 to 60 days). There were two toxic deaths from sepsis: one on day 27 (level 5) and one from cardiac arrest on day 42 (level 6). CONCLUSION: The maximum-tolerated dose of carboplatin was 400 mg/m(2)/d in combination with mitoxantrone 16 mg/m(2)/d and cyclophosphamide 1,500 mg/m(2), all drugs given over 4 days. This regimen is being tested in a phase III trial of high-dose chemotherapy and PBSCT versus standard treatment.

Adolescent↗

Five-year results of cyclic semi-high dose neoadjuvant chemotherapy supported by autologous peripheral blood stem-cell transplantation in patients with advanced ovarian cancer.

BACKGROUND: To achieve anti-ovarian tumor responses similar to those obtained with high-dose chemotherapy but with milder side effects, we developed a treatment protocol in which semi-high dose multi-cycle neoadjuvant chemotherapy was supported by autologous peripheral blood stem-cell transplantation (auto-PBSCT). METHODS: Seventeen patients with advanced ovarian cancer were enrolled in this study. Two cycles of semi-high dose neoadjuvant chemotherapy, using carboplatin (AUC, 8.75; average dose, 621 mg/m(2)) and etoposide (average dose, 960 mg/m(2)) were supported by auto-PBSCT and followed by cytoreductive surgery and further chemotherapy. Each patient was followed for at least 5 years. RESULTS: This treatment schedule achieved an overall response rate of 70.6% in 17 patients with stage III or stage IV ovarian cancer. The 5-year disease-free survival rate was 52.9% (95% confidence interval, 29.2%-76.6%) and the median survival time was 63 months (95% confidence interval, 16-79 months). Thus, we obtained superior treatment outcomes in these 17 patients in comparison with published conventional protocols. CONCLUSION: Cyclic semi-high dose neoadjuvant chemotherapy supported by auto-PBSCT may be tolerable and favorable for patients with advanced ovarian cancer. To achieve anti-ovarian tumor responses similar to those obtained with high-dose chemotherapy but with milder side effects, we developed a treatment protocol in which semi-high dose multi-cycle neoadjuvant chemotherapy was supported by autologous peripheral blood stem-cell transplantation (auto-PBSCT).

Antineoplastic Combined Chemotherapy Protocols↗

Single-agent paclitaxel in patients with metastatic breast cancer receiving high-dose chemotherapy with peripheral blood stem cell support.

The purpose of this trial was to determine the effects of paclitaxel in patients with newly diagnosed metastatic breast cancer scheduled to receive high-dose chemotherapy with peripheral blood stem cell support. Eighty-four patients received anthracycline-based induction and two doses of paclitaxel at 170 mg/m2 (n = 52) or 250 mg/m2 (n = 32). Eighty-two (98%) received cyclophosphamide and etoposide (n = 50) or paclitaxel and cyclophosphamide (n = 32) with granulocyte colony-stimulating factor for mobilization of peripheral blood stem cells, and 79 (94%) received cyclophosphamide, thiotepa, and carboplatin with peripheral blood stem cell support. One patient (1%) died of infection and 56 (67%) died of progressive disease. For patients with measurable disease, the complete response rate was 21% after induction and 29% after paclitaxel (p = 0.54). Results were compared with those of 125 patients who received the same sequence of therapy without paclitaxel. The complete response rate after high-dose chemotherapy was 54% for patients receiving paclitaxel and 62% for those not receiving paclitaxel (p = 0.60). The probabilities of overall survival and event-free survival at 3 years for patients receiving paclitaxel were 46% and 24%, respectively, compared with 54% and 22%, respectively, for patients not receiving paclitaxel (p = 0.62). Further trials evaluating this dose and schedule of paclitaxel in patients with metastatic breast cancer receiving high-dose chemotherapy are not warranted.

Adult↗

Palifermin for oral mucositis in the high-dose chemotherapy and stem cell transplant setting: the Royal Adelaide Hospital Cancer Centre experience.

GOALS OF WORK: the aim of this paper was to review the initial use of Palifermin(rHu-KGF1) in a single institution, for the prevention of oral mucositis in high-dose chemotherapy and stem cell transplantation. METHODS: the case records of the first five patients treated with Palifermin at the Royal Adelaide Hospital Cancer Centre were reviewed, and incidence,severity and duration of the oral mucositis were recorded, as well as demographics and toxicities. RESULTS: two of the five patients developed grade 4 mucositis, and the remaining three patients developed grade 2 mucositis. Palifemin was well tolerated with only one patient developing a rash. CONCLUSIONS: the severity of oral mucositis was less than would be expected in these patients without anti-mucositis therapy. Palifermin was well tolerated. Obviously this single institution report is from a very small cohort of patients, but it is encouraging for the ease of use of this drug in the future.

Adult↗

Is bone marrow purging proving to be of value?

Although the role of hematopoietic stem-cell transplantation (HSCT) in cancer treatment is rapidly expanding, decreasing the side effects of stem-cell infusion is a major challenge. Cancer cells present in the stem-cell collection can cause relapse after autologous transplantation. In allogeneic transplantation. T lymphocytes contribute to graft-versus-host disease. Various methods of purging have been used to remove these unwanted cells, and there is some evidence that such manipulations are clinically useful. Nevertheless, the inability to detect minimal disease makes it difficult to determine whether relapse is caused by incomplete disease eradication in the patient or by the infused cells. This makes it hard to justify the clinical benefit of ex vivo purging. Researchers can focus on this issue by designing studies with minimal variation in other factors that affect the success of stem-cell transplantation.

Bone Marrow Purging↗