Allogeneic hematopoietic cell transplantation for metastatic breast cancer.

We reviewed 66 women with poor-risk metastatic breast cancer from 15 centers to describe the efficacy of allogeneic hematopoietic cell transplantation (HCT). Median follow-up for survivors was 40 months (range, 3-64). A total of 39 patients (59%) received myeloablative and 27 (41%) reduced-intensity conditioning (RIC) regimens. More patients in the RIC group had poor pretransplant performance status (63 vs 26%, P=0.002). RIC group developed less chronic GVHD (8 vs 36% at 1 year, P=0.003). Treatment-related mortality rates were lower with RIC (7 vs 29% at 100 days, P=0.03). A total of 9 of 33 patients (27%) who underwent immune manipulation for persistent or progressive disease had disease control, suggesting a graft-vs-tumor (GVT) effect. Progression-free survival (PFS) at 1 year was 23% with myeloablative conditioning and 8% with RIC (P=0.09). Women who developed acute GVHD after an RIC regimen had lower risks of relapse or progression than those who did not (relative risk, 3.05: P=0.03), consistent with a GVT effect, but this did not affect PFS. These findings support the need for preclinical and clinical studies that facilitate targeted adoptive immunotherapy for breast cancer to explore the benefit of a GVT effect in breast cancer.

Valganciclovir is safe and effective as pre-emptive therapy for CMV infection in allogeneic hematopoietic stem cell transplantation.

Despite significant advances in prevention and therapy, cytomegalovirus (CMV) infection continues to be an important cause of morbidity and mortality in the hematopoietic stem cell transplant (HSCT) recipient. The standard drug for pre-emptive therapy is intravenous ganciclovir (GCV). Valganciclovir (VGC), the oral pro-drug of GCV, has excellent bioavailability and is ideal for oral therapy. Since March 2002, VGC was adopted in our center for outpatient pre-emptive therapy in all patients undergoing allogeneic HSCT. Fifty-two allogeneic HSCT recipients were followed weekly via Digene hybrid capture assay. Patients with a positive assay were treated with VGC 900 mg p.o. b.i.d. x 14 days followed by 900 mg p.o. QD until at least 7 days after a negative test. Eighteen patients (14 sib, four MUD) had 30 episodes of CMV DNA detection treated with oral VGC. Median duration of therapy was 21 days (range 10-21 days). The rate of response was 93% (28/30) as confirmed by a negative assay within 14 days. No significant toxicity was encountered. Two patients failed oral VGC. One case of CMV enteritis was diagnosed in a patient with acute GVHD. Pre-emptive therapy of CMV infection with oral VGC is safe and effective in allogeneic HSCT recipients.

Pilot study of a home-based aerobic exercise program for sedentary cancer survivors treated with hematopoietic stem cell transplantation.

We report a pilot study of a home-based aerobic exercise program in a group of 17 adult hematopoietic stem cell transplant (HSCT) recipients. Participants had received no cancer treatment for at least 6 months and reported leisure time physical activity less than 20 min per day and fewer than three times a week during the previous month. Following baseline assessments of aerobic fitness, fatigue symptoms, and quality of life, participants were placed on home-based aerobic exercise programs consisting of 20-40 min of activity in the target heart rate zone (40-60% predicted heart rate reserve) delivered in three to five sessions per week for 12 weeks. Subjects were supplied with electronic heart rate monitors and we encouraged program adherence using weekly telephone contacts and exercise diaries. In all, 32 of the 42 qualified candidates consented (acceptance=76%). Of these, 17 kept appointments for baseline assessments, four did not complete the study (attrition=46%), and no exercise-related adverse events were reported. Scores on measures of aerobic fitness, fatigue severity, and physical well-being improved (signed ranks test; P<0.05) during program participation. Our findings suggest that individually prescribed, home-based aerobic exercise is an acceptable, safe, and potentially effective intervention for improving physical functioning and fatigue in sedentary HSCT recipients.

Syngeneic hematopoietic stem cell transplantation for women with metastatic breast cancer.

Metastatic breast cancer has been a common indication for autologous hematopoietic stem cell transplantation (HSCT). Previous reports indicate 3-year survival and progression-free survival (PFS) rates after autotransplant to be about 30 and 15%, respectively. Most deaths are from recurrent disease. One potential cause for high relapse rates is graft contamination with tumor. We describe 14 women with metastatic breast cancer transplanted between 1991 and 1998 with hematopoietic cells from identical twins. Median age was 41 y (range 34-50). Most women (12 of 14) were treated with mastectomy, and all received anthracycline-based regimens in their pretransplant course; nine women also received a taxane, seven radiotherapy and three hormonal therapy. Four women were in complete remission (one CR, three CRU) at transplant, five were in partial remission, two had stable disease and two had progressive disease. Eight women have died, one of treatment-related causes and seven of progressive breast cancer. Three-year survival was 48% (21-71%) and 3-year PFS was 21% (5-45%). Although the number of patients is small, outcomes for women transplanted with syngeneic grafts are similar to those of women receiving autologous grafts. This suggests that residual cancer in the patient is the major contributor to relapse after transplantation for breast cancer.

Use of PEG-rHuMGDF in platelet engraftment after autologous stem cell transplantation.

This paper summarizes a pilot, sequential dose-escalation study of PEG-rHuMGDF in patients with advanced malignancies who had delayed platelet recovery after autologous stem cell transplantation (ASCT). Patients were randomized to receive either placebo (n = 11) or PEG-rHuMGDF at 5 (n = 9), 10 (n = 6), or 25 (n = 7) microg/kg/day by subcutaneous injection for 14 days and were monitored for 5 weeks. Across all treatment groups, eight patients had platelet recovery to > or = 20 x 10(9)/l by day 21. The proportion of patients achieving platelet recovery, the median number of days and units of platelet transfusions were similar for the placebo and the PEG-rHuMGDF groups. PEG-rHuMGDF was well tolerated at all dosages. The incidence rates of adverse events in all groups were similar. No deaths on study, no drug-related serious adverse events, and no development of neutralizing antibodies to MGDF occurred.

The uncertainty principle and industry-sponsored research.

BACKGROUND: Reporting of pharmaceutical-industry-sponsored randomised clinical trials often result in biased findings, either due to selective reporting of studies with non-equivalent arms or publication of low-quality papers, wherein unfavourable results are incompletely described. A randomised trial should be conducted only if there is substantial uncertainty about the relative value of one treatment versus another. Studies in which intervention and control are thought to be non-equivalent violates the uncertainty principle. METHODS: We examined the quality of 136 published randomised trials that focused on one disease category (multiple myeloma) and adherence to the uncertainty principle. To evaluate whether the uncertainty principle was upheld, we compared the number of studies favouring experimental treatments over standard ones. We analysed data according to the source of funding. FINDINGS: Trials funded solely or in part by 35 profit-making organisations had a trend toward higher quality scores (mean 2.94 [SD 1.3]; median 3) than randomised trials supported by 95 governmental or other non-profit organisations (2.4 [0.8]; 2; p=0.06). Overall, the uncertainty principle was upheld, with 44% of randomised trials favouring standard treatments and 56% innovative treatments (p=0.17); mean and median preference evaluation scores were 3.7 (1.0) and 4. However, when the analysis was done according to the source of funding, studies funded by non-profit organisations maintained equipoise favouring new therapies over standard ones (47% vs 53%; p=0.608) to a greater extent than randomised trials supported solely or in part by profit-making organisations (74% vs 26%; p=0.004). INTERPRETATION: The reported bias in research sponsored by the pharmaceutical industry may be a consequence of violations of the uncertainty principle. Sponsors of clinical trials should be encouraged to report all results and to choose appropriate comparative controls.

Relation of psychological vulnerability factors to posttraumatic stress disorder symptomatology in bone marrow transplant recipients.

OBJECTIVE: Prior research suggests that the diagnosis and treatment of cancer can result in the development of symptoms of posttraumatic stress disorder (PTSD). Based on Lazarus and Folkman's model of stress, the current study examined whether trauma appraisals, coping, social support, and social constraint were associated with the severity of PTSD symptoms in cancer patients who had undergone bone marrow transplantation (BMT). METHODS: Participants were 23 males and 79 females treated with BMT an average of 20 months previously (range = 3-62 months). Past and current psychiatric diagnoses were assessed through a structured clinical interview. PTSD symptomatology and other psychological variables were assessed using standardized self-report measures. RESULTS: Results indicated that 5% of participants met diagnostic criteria for current PTSD. Participants reported an average of three to four symptoms of PTSD (range = 0-16). Univariate analyses confirmed predictions that increased PTSD symptomatology would be associated with more negative appraisals of the BMT experience, greater use of avoidance-based coping strategies, lower levels of social support, and greater social constraint (p < .05). Regression analyses indicated that each of these variables accounted for significant (p < .05) variability in PTSD symptomatology above and beyond relevant demographic and medical variables. CONCLUSIONS: Results of the present study confirm and extend prior research regarding the prevalence of PTSD and PTSD symptoms among patients treated for cancer. In addition, the study identified a set of theoretically derived psychological characteristics that seem to place patients at risk for greater PTSD symptomatology after BMT.

Simultaneous administration of G-CSF and GM-CSF for re-mobilization in patients with inadequate initial progenitor cell collections for autologous transplantation.

BACKGROUND: A proportion of candidates for high-dose chemotherapy with autologous PBPC support (HDC-PBPCS) will not provide an adequate PBPC yield from their first mobilization. The value of re-mobilization and the best regimen for re-mobilization in these patients is unclear. METHODS: In 23 patients who failed to provide > or = 3 x 10(6) CD34+ cells/kg after their first mobilization, PBPC were re-mobilized using a regimen of simultaneous administration of G-CSF and GM-CSF (10 microg/kg/day each) with leukaphereses (LP) starting Day 4 or 5 of CSF administration. Yields of WBC/kg, MNC/kg and CD34+ cells/kg/L of processed blood were compared between the first and second mobilization in each patient. The ability of the combined yield from the two mobilizations to achieve the desired threshold PBPC yield and the tolerability of the re-mobilization were determined. RESULTS: The re-mobilization regimen was well-tolerated and no patient discontinued the regimen because of toxicity. Median collected WBC/kg/L (1.37 x 10(7) versus 2.62 x 10(7), p = 0.0065), MNC/kg/L (0.77 x 10(7) versus 1.97 x 10(7), p = 0.0003), CD34+ cells/kg/L (1.64 x 10(7) versus 4.18 x 10(7), p = 0.001) were significantly higher after the second mobilization (G-CSF/GM-CSF combination). Percentage of CD34+ cells in the leukapheresis was also significantly higher after the second mobilization (median 0.104% versus 0.195%, p = 0.036). Twelve of 22 patients achieved the target PBPC dose (> 3 x 10(6)/CD34+ cells/kg) after two mobilizations (six patients achieved the target from the second mobilization alone). A further eight underwent HDC-PBPCS without achieving the target PBPC dose. These patients experienced a significant delay in neutrophil and platelet engraftment when compared with those patients achieving the target dose. DISCUSSION: This study demonstrates that the combination of G-CSF and GM-CSF is an effective and tolerable method for re-mobilization of PBPC in patients who fail to provide an adequate yield from their first mobilization.

Patients' psychosocial concerns following stem cell transplantation.

Information regarding the nature, frequency, correlates and temporal trajectory of concerns of stem cell transplantation (SCT) recipients is critical to the development of interventions to enhance quality of life (QOL) in these individuals. This study examined psychosocial concerns in 110 SCT (87% autologous) recipients drawn from two SCT centers. Participants were a mean of 46 years of age and 17 months post-SCT (range 3-62 months). Information regarding current and past SCT-related concerns, performance status, and demographic characteristics was collected by telephone interview or questionnaire. Recipients reported a wide variety of psychosocial concerns following SCT. Recipients who were younger, female and evidenced a poorer performance status reported a larger number of post-SCT concerns. Examination of the temporal trajectory of concerns suggests that some concerns are salient throughout the course of post-SCT recovery (eg disease recurrence, energy level, 'returning to normal'), some are salient early in the course of recovery (eg quality of medical care, overprotectiveness by others), and others emerge later in the course of recovery (eg feeling tense or anxious, sexual life, sleep, relationship with spouse/partner, ability to be affectionate). Implications for the development of interventions to enhance post-SCT QOL are identified.

Factors correlated with progression-free survival after high-dose chemotherapy and hematopoietic stem cell transplantation for metastatic breast cancer.

CONTEXT: Women with breast cancer are the most frequent recipients of high-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (autotransplants) in North America. Despite widespread use, controversy exists about the benefits of and appropriate patients for this therapy. OBJECTIVE: To determine factors associated with disease progression or death after autotransplantation in women with metastatic breast cancer. DESIGN: Analysis of data collected retrospectively (January 1989 to 1992) and prospectively (1992 through January 1995) for the Autologous Blood and Marrow Transplant Registry. SETTING: Sixty-three hospitals in North America, Brazil, and Russia. PARTICIPANTS: A total of 1188 consecutive women aged 18 to 70 years receiving autotransplants for metastatic or locally recurrent breast cancer, with a median follow-up of 291/2 months. MAIN OUTCOME MEASURE: Time to treatment failure (disease progression, disease recurrence, or death) after autotransplantation. RESULTS: Factors associated with significantly (P<.05) increased risk of treatment failure in a Cox multivariate analysis included age older than 45 years (relative hazard, 1.17; 95% confidence interval [CI], 1.02-1.33), Karnofsky performance score less than 90% (1.27; 95% CI, 1.07-1.51), absence of hormone receptors (1.31; 95% CI, 1.15-1.51), prior use of adjuvant chemotherapy (1.31; 95% CI, 1.10-1.56), initial disease-free survival interval after adjuvant treatment of no more than 18 months (1.99; 95% CI, 1.62-2.43), metastases in the liver (1.47; 95% CI, 1.20-1.80) or central nervous system (1.56; 95% CI, 0.99-2.46 [approaches significance]) vs soft tissue, bone, or lung, 3 or more sites of metastatic disease (1.32; 95% CI, 1.13-1.54), and incomplete response vs complete response to standard-dose chemotherapy (1.65; 95% CI, 1.36-1.99). Receiving tamoxifen posttransplantation was associated with a reduced risk of treatment failure in women with hormone receptor-positive tumors (relative hazard, 0.60; 95% CI, 0.47-0.87). Women with no risk factors (n = 38) had a 3-year probability of progression-free survival of 43% (95% CI, 27%-61 %) vs 4% (95% CI, 2%-8%) for women with more than 3 risk factors (n = 343). CONCLUSION: These data indicate that some women are unlikely to benefit from autotransplantation and should receive this treatment only after being provided with prognostic information and in the context of clinical trials attempting to improve outcome.

Fatigue and quality of life in breast cancer patients undergoing autologous stem cell transplantation: a longitudinal comparative study.

As more individuals are being treated for cancer with high-dose therapy and autologous stem cell rescue (ASCR), there is growing interest in treatment side effects and their impact on quality of life. The primary aim of this study was to determine if the severity of fatigue and its impact on quality of life is significantly greater in women undergoing ASCR for breast cancer than in women of similar age with no history of cancer. A group of women being treated with ASCR for breast cancer (n = 31) and a group of women of similar age with no history of cancer (n = 49) participated in this study. Patients completed measures of fatigue and psychosocial functioning prior to treatment, midway through treatment, and toward the end of treatment. Healthy comparison subjects completed the same measures three separate times. Breast cancer patients undergoing ASCR reported significantly more frequent fatigue and more severe fatigue than women with no cancer history. In addition, fatigue had a significantly greater impact on daily functioning and quality of life in patients than in women with no cancer history. Fatigue during ASCR for breast cancer was related to both medical factors (i.e., time since transplant) and psychosocial factors. During ASCR for breast cancer, women experience fatigue which is worse than what is "normally" experienced and which interferes with daily functioning and quality of life. Future research should focus on identifying the biological correlates of fatigue, psychological and physiological mechanisms by which fatigue is produced, and interventions to alleviate fatigue.

Borderline personality disorder and bone marrow transplantation: ethical considerations and review.

Bone marrow transplantation (BMT) is rapidly becoming a part of conventional cancer treatment. However, it remains a 'last-ditch' treatment option for patients who have exhausted other treatment modalities. Patients experience a significant amount of emotional distress during all stages of the BMT process. Patients with personality disorders experience even more emotional distress than average and their behavior is often detrimental to effective patient-staff interactions. A case of a borderline patient is presented with a discussion of the ethical issues involved in the evaluation of these patients and the determination of their appropriateness for transplant.

Measurement of fatigue in cancer patients: development and validation of the Fatigue Symptom Inventory.

Although fatigue is one of the most common and debilitating symptoms experienced by cancer patients, it has received little systematic attention. This situation is due in large part to the lack of adequate instruments to measure fatigue. The primary aim of this study was to validate a newly developed measure of fatigue for use with cancer patients: the Fatigue Symptom Inventory (FSI). This 13 item self-report measure was designed to measure the intensity and duration of fatigue and its impact on quality of life. The psychometric properties of the FSI were assessed in women undergoing treatment for breast cancer, women who had completed treatment for breast cancer and women with no history of cancer. A seven-item interference subscale was found to have good internal consistency, with alpha coefficients above 0.90 in all three groups. The complete FSI was found to have rather weak to moderate test-retest reliability among patients in active treatment and healthy comparison subjects assessed on three separate occasions. Convergent validity was demonstrated using comparisons with existing measures of fatigue. Construct validity was demonstrated using comparisons between and within groups as well as comparisons with measures of anxiety and depression. Overall, the FSI was established as a valid and reliable measure of fatigue in cancer patients and healthy individuals. Suggestions are made for the potential application of the measure in clinical research.

Posttraumatic stress disorder symptoms after bone marrow transplantation for breast cancer.

OBJECTIVE: On the basis of revisions of DSM criteria, questions have been raised concerning the occurrence of posttraumatic stress disorder (PTSD) symptoms among adults who have been diagnosed and treated for life-threatening illnesses. The present study examined the prevalence and correlates of PTSD symptoms among women who had undergone autologous bone marrow transplantation (ABMT) for breast cancer. METHODS: Participants were 43 women who had undergone ABMT for breast cancer an average of 19 months previously (range = 2 to 62 months) and had no clinical evidence of disease at their most recent follow-up visit. PTSD symptoms and quality of life were assessed using standardized self-report instruments. RESULTS: Between 12% and 19% of participants were likely to meet DSM-IV criteria for the current diagnosis of PTSD. Women who were less well educated, had more advanced disease at the time of the transplantation and had longer hospital stays for the transplantation reported more symptoms of PTSD. Greater PTSD symptomatology was associated with reports of poorer physical health, mental health, and sleep quality. CONCLUSION: Comparisons with previous research suggest that rates of PTSD are higher among women who undergo ABMT as opposed to less intensive forms of breast cancer treatment. These findings are consistent with the view that development of PTSD symptoms is associated with the degree of life threat. The clinical significance of PTSD in this patient population is underscored by findings indicating that greater PTSD symptoms are associated with poorer health-related quality of life.

Defining the role of novel high-dose chemotherapy regimens for the treatment of high-risk breast cancer.

We have explored several novel high-dose combinations in an attempt to increase antitumor activity while decreasing treatment-related toxicity. From October 1989 through June 1997, we performed phase I/II dose-escalation trials exploring novel high-dose regimens including ifosfamide/carboplatin/etoposide, mitoxantrone/thiotepa, and paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ)/mitoxantrone/thiotepa. We have also evaluated busulfan/cyclophosphamide and cyclophosphamide/thiotepa/carboplatin in phase II trials. Three hundred ninety-three patients have been treated in these trials and followed for a minimum of 3 months. Event-free survival (including relapses and treatment-related mortality; +/-SE) at 3 years by stage and chemosensitivity is as follows: stage II, four to nine positive nodes (n=16), 52%+/-17%; stage II, greater than nine nodes (n=30), 46%+/-11%; stage III (n=59), 50%+/-8%; inflammatory stage III (n=15), 27%+/-17%; stage IV, anthracycline responsive (n=69), 19%+/-5%; stage IV, anthracycline refractory but responsive to salvage therapy with ifosfamide, carboplatin, and etoposide or paclitaxel (n=53), 12%+/-6%; stage IV, refractory (n=128), 5%+/-2%; and stage IV, not evaluable for response (n=23), 10%+/-8%. Treatment-related mortality was 4% for both phase I and II studies involving stage II breast cancer patients, 5% for stage III breast cancer, 15% for inflammatory breast cancer, and 18% for all stage IV breast cancers, responsive and refractory. We conclude that high-dose therapy for the treatment of high-risk early stage breast cancer or metastatic breast cancer results in durable remissions. Chemosensitivity to induction regimens remains the most important prognostic indicator, although long-term survival has been seen even in patients with highly refractory disease. Further studies are necessary to define optimal high-dose strategies based on stage and chemosensitivity of disease.

Nephrotoxicity of high-dose ifosfamide/carboplatin/etoposide in adults undergoing autologous stem cell transplantation.

The objective of this study was to evaluate nephrotoxicity in adult patients treated with high-dose ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation. We conducted a retrospective analysis of clinical and laboratory data from 131 patients with various malignancies who received treatment with escalating doses of ifosfamide, carboplatin, and etoposide followed by autologous stem cell transplantation as part of a phase I/II therapeutic trial. Abnormalities in glomerular filtration were evaluated by measuring peak creatinine levels and tubular dysfunction by the lowest recorded serum levels of potassium, magnesium, and bicarbonate, at different time periods after administration of ifosfamide, carboplatin, and etoposide, and after autologous stem cell transplantation. For the entire group of 131 patients, peak creatinine levels were > 1.5 mg/dL but < 3.0 mg/dL in 37% and levels were > 3.0 mg/dL in 11% at some time during their hospital stay. At the time of discharge, creatinine levels were 1.6 mg/dL to 3.0 mg/dL in 25% of patients and were > 3 mg/dL in 5%. Immediately after high-dose therapy, peak creatinine levels were significantly higher in patients receiving higher doses of ifosfamide compared to those receiving lower doses (P < 0.00001) and those receiving intermediate doses (P < 0.005). There was a dramatic decrease in serum bicarbonate, potassium, and magnesium levels immediately after chemotherapy, and they remained significantly decreased throughout the patient's hospital stay, despite massive replacement efforts (P ranging between < 0.008 and < 0.001). This is the largest adult population study documenting the incidence and severity of ifosfamide/carboplatin/etoposide-associated acute nephrotoxicity. Renal dysfunction was dose related and reversible in the majority of patients.

High-dose chemotherapy with autologous hematopoietic stem-cell support for breast cancer in North America.

PURPOSE: To identify trends in high-dose therapy with autologous hematopoietic stem-cell support (autotransplants) for breast cancer (1989 to 1995). PATIENTS AND METHODS: Analysis of patients who received autotransplants and were reported to the Autologous Blood and Marrow Transplant Registry. Between January 1, 1989 and June 30, 1995, 19,291 autotransplants were reviewed; 5,886 were for breast cancer. Main outcomes were progression-free survival (PFS) and survival. RESULTS: Between 1989 and 1995, autotransplants for breast cancer increased sixfold. After 1992, breast cancer was the most common indication for autotransplant. Significant trends included increasing use for locally advanced rather than metastatic disease (P < .00001) and use of blood-derived rather than marrow-derived stem cells (P < .00001). One-hundred-day mortality decreased from 22% to 5% (P < .0001). Three-year PFS probabilities were 65% (95% confidence intervals [Cls], 59 to 71) for stage 2 disease, and 60% (95% Cl, 53 to 67) for stage 3 disease. In metastatic breast cancer, 3-year probabilities of PFS were 7% (95% Cl, 4 to 10) for women with no response to conventional dose chemotherapy; 13% (95% Cl, 9 to 17) for those with partial response; and 32% (95% Cl, 27 to 37) for those with complete response. Eleven percent of women with stage 2/3 disease and less than 1% of those with stage 4 disease participated in national cooperative group randomized trials. CONCLUSION: Autotransplants increasingly are used to treat breast cancer. One-hundred-day mortality has decreased substantially. Three-year survival is better in women with earlier stage disease and in those who respond to pretransplant chemotherapy.

Dexamethasone, cyclophosphamide, idarubicin and etoposide (DC-IE): a novel, intensive induction chemotherapy regimen for patients with high-risk multiple myeloma.

We evaluated toxicities and responses to a novel, dose intensive and time sequenced, chemotherapy programme (DC-IE) in 45 patients with high-risk myeloma. DC-IE consisted of: dexamethasone (days 1-4); cyclophosphamide (day 5); idarubicin and etoposide (days 8-10). Complete response (CR) was achieved in four patients, six patients achieved near complete responses (nCR) and 21 patients achieved a partial remission (PR). Overall response rate was 76% (CI 56-94%) for newly diagnosed patients (n = 21) and 62% (CI 36-81%) for relapsed/refractory patients (n = 24). Toxicities were limited to myelosuppression; two patients died of sepsis during neutropenia (4%). DC-IE is active and tolerable for high-risk multiple myeloma, including patients with relapsed or refractory disease to anthracycline containing regimens.

Quality of life following bone marrow transplantation for breast cancer: a comparative study.

As more women are treated with bone marrow transplantation (BMT) for breast cancer, there is growing interest in quality of life (QOL) following treatment. Although there have been some clinical studies of QOL following BMT, this area has received little systematic attention. In particular, it is unclear how QOL for women treated with BMT for breast cancer differs from that which might be expected for 'healthy' women of about the same age. To address this issue, we compared QOL reported by women treated with autologous BMT for breast cancer with that of a group of women of similar age with no history of cancer. In addition, we examined the relationship of demographic factors, medical factors, and self-reported symptom prevalence, severity, and distress to QOL in post-BMT patients. All participants completed the SF-36 Health Survey developed from the Medical Outcomes Study (SF-36). Post-BMT patients also completed the ECOG Performance Status Rating Scale (PSR) and the Memorial Symptom Assessment Scale (MSAS). Results indicated that, compared to the women with no cancer history, post-BMT patients reported significantly impaired physical functioning, physical role functioning, general health, vitality, social functioning, and emotional role functioning. Impaired QOL following BMT was significantly associated with lower income, a longer time to engraftment, longer hospital stay, poor performance status, and greater symptom prevalence, severity, and distress. The problems identified in this study may be important targets for intervention when trying to improve QOL following BMT.

Fatigue in women treated with bone marrow transplantation for breast cancer: a comparison with women with no history of cancer.

As more individuals undergo autologous bone marrow transplantation (BMT), there is growing interest in the impact of treatment side effects on quality of life. Fatigue is a potentially disruptive treatment side effect that has not been systematically assessed following BMT. The primary aim of this study was to determine whether the severity of fatigue and its impact on quality of life is significantly greater in women who had undergone BMT for breast cancer than in women of similar age with no history of cancer. Another aim was to identify the medical and psychosocial correlates of fatigue in women who had completed BMT. A group of women treated with autologous BMT for breast cancer (n = 43; mean age = 44; mean time since BMT = 20 months) and a group of women of similar age with no history of cancer (n = 43; mean age = 46) participated in this study. Subjects completed measures of fatigue, anxiety, depression, and sleep habits. Medical data were obtained from computerized patient records. Women who had completed BMT for breast cancer reported significantly more frequent and severe fatigue than women with no cancer history. In addition, fatigue had a significantly greater impact on daily functioning and quality of life in BMT recipients than in women with no cancer history. Fatigue following BMT for breast cancer was related to both medical factors (i.e., time since BMT) and psychosocial factors (i.e., anxiety, depressive symptoms and sleep difficulties). Following BMT for breast cancer, women may experience fatigue that is worse than might "normally" be expected and can interfere with daily functioning and quality of life. Future research should focus on identifying the biological correlates of fatigue, psychological and physiological mechanisms by which fatigue is produced, and interventions to alleviate fatigue.