Assessment of cellular adequacy of fine needle aspiration biopsy for small solid renal tumors.

OBJECTIVE: Our aim was to evaluate the performance of fine needle aspiration (FNA) as a method for obtaining cellular material for the tissue diagnosis of small solid renal tumours. METHODS: Fifty-five patients with a small solid renal tumour (4 cm or smaller) underwent a FNA biopsy under computed tomography guidance. Direct smears and rinse of needle with Cytolyt® were prepared. The cellular adequacy was divided into three groups: satisfactory cellular material, scant cellular material and noncellular material. RESULTS: Postoperative pathological diagnosis showed 35 clear cell carcinomas, 10 papillary carcinomas, four chromophobe carcinomas, four oncocytomas, one adenoma and one metastatic carcinoma. A total of 21 (38.2%) FNA biopsies belonged to noncellular group. For clear cell carcinomas, the cellularity of satisfactory cellular group, scant cellular group and noncellular group was, respectively, seven (20.0%), nine (25.7%) and 19 (54.3%). Of the 10 papillary carcinomas, nine (90%) and all four chromophobe carcinomas (100%) had satisfactory cellular materials. The percentages of noncellular group among clear cell carcinoma, papillary carcinoma and chromophobe carcinoma were significantly different (P = 0.0020). Fifteen tumours were 2 cm or smaller and 40 tumours were larger than 2 cm. No significant difference was found in the percentage of noncellular material for the tumours 2 cm or less (40.0%) and for the tumours larger than 2 cm (37.5%; P > 0.05). CONCLUSIONS: The cellularity of FNA biopsy of small solid renal masses might correlate with the subtype of renal cancers. FNA biopsy was an effective method of tissue sampling for papillary and chromophobe renal carcinomas.

[Internet-based self-management interventions : Quality criteria for their use in prevention and treatment of mental disorders]. / Internetbasierte Selbstmanagementinterventionen : Qualitätskriterien für ihren Einsatz in Prävention und Behandlung psychischer Störungen.

BACKGROUND: Internet-based self-management interventions are effective in the prevention and treatment of mental disorders; however, for those affected as well as treating clinicians and decision makers in the healthcare sector, it is difficult to identify safe and effective interventions. AIM: Development of quality criteria for self-management interventions. METHODS: Based on a non-specific assessment matrix, a task force from two scientific societies formulated specific quality criteria for self-management interventions for mental disorders. Patients and other relevant stakeholders were involved in the process. RESULTS: A total of 8 key criteria with 17 subordinate points were developed. These must be met for the certification of an intervention. The criteria focus on therapeutic quality requirements, patient safety, data protection and security as well as proof of efficacy in at least one randomized study. A further five criteria are only descriptive and are not required for certification. DISCUSSION: These quality criteria serve as a starting point for the establishment of a certification process. This could help to make internet-based self-management interventions for mental disorders part of routine care in the German healthcare system.

Neurocognitive deficits in schizophrenia. Are we making mountains out of molehills?

BACKGROUND: Most original studies and all meta-analyses conducted to date converge on the conclusion that patients with schizophrenia display rather generalized neurocognitive deficits. For the present study, we reopen this seemingly closed chapter and examine whether important influences, such as lack of motivation and negative attitudes towards cognitive assessment, result in poorer secondary neuropsychological performance. METHOD: A sample of 50 patients with an established diagnosis of schizophrenia were tested for routine neurocognitive assessment and compared to 60 nonclinical volunteers. Before and after the assessment, subjective momentary influences were examined (e.g. motivation, concerns about assessment, fear about poor outcome) for their impact on performance using a new questionnaire called the Momentary Influences, Attitudes and Motivation Impact (MIAMI) on Cognitive Performance Scale. RESULTS: As expected, patients performed significantly worse than controls on all neurocognitive domains tested (large effect size, on average). However, patients also displayed more subjective momentary impairment, as well as more fears about the outcome and less motivation than controls. Mediation analyses indicated that these influences contributed to (secondary) poorer neurocognitive performance. Differences in neurocognitive scores shrank to a medium effect size, on average, when MIAMI scores were accounted for. CONCLUSIONS: The data argue that performance on measures of neurocognition in schizophrenia are to a considerable extent due to secondary factors. Poor motivation, fears and momentary impairments distinguished patients from controls and these variables heavily impacted performance. Before concluding that neurocognitive deficits in psychiatric patients are present, clinicians should take these confounding influences into account. Although patients with schizophrenia achieved, on average, worse test scores than controls, a large subgroup displayed spared performance.

[Guideline-adherent inpatient psychiatric psychotherapeutic treatment of obsessive-compulsive disorder : Normative definition of personnel requirements]. / Leitliniengerechte stationäre psychiatrisch-psychotherapeutische Behandlung der Zwangsstörung : Normative Personalbedarfsermittlung.

BACKGROUND: Guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with obsessive-compulsive disorder (OCD) is an important part of the care available for these patients. It may not be adequately reflected in the current personnel resources available according to the German psychiatry personnel regulation (Psych-PV). OBJECTIVES: The goal of this work was to assess the personnel resources necessary for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD and compare the necessary resources with the resources available according to Psych-PV. METHODS: Based on the German national guidelines for OCD and a meta-analysis on treatment intensity, we formulated a normative weekly treatment plan. Based on this plan we calculated the necessary personnel resources and compared these with the resources available according to Psych-PV category A1 (standard care). RESULTS: The weekly treatment time for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD is 23.5 h per week. This corresponds to a weekly personnel requirement of 20.9 h. This requirement is only partly reflected in the Psych-PV (17.3 h, 82.8 %). The coverage of personnel resources by Psych-PV is even lower for psychotherapy provided by psychiatrist and psychologists (38.3 %, i. e. 183 min in the normative plan versus 70 min in Psych-PV). CONCLUSIONS: The current paper shows that the personal resources required for a guideline-oriented inpatient psychiatric and psychotherapeutic treatment of patients with OCD is not adequately reflected in the German psychiatry personnel regulation (Psych-PV). The actual shortage may be underestimated in our paper.

[Internet-based interventions in the treatment of mental disorders : Overview, quality criteria, perspectives]. / Internetbasierte Interventionen in der Behandlung psychischer Störungen : Überblick, Qualitätskriterien, Perspektiven.

BACKGROUND: Mental disorders are frequently not or only insufficiently treated. Internet-based interventions offer the potential of closing the existing gaps in the treatment of mental disorders; however, it is very difficult for patients and providers to choose from the numerous interventions available. OBJECTIVE: The aim of this study was to develop a set of quality criteria that can help patients and care providers to identify recommendable internet-based interventions. METHODS: A selective literature search was carried out and the existing evidence on internet-based interventions in the treatment of mental disorders was collated. A panel of experts then developed quality criteria based on existing models for the systematic assessment of telemedicine applications. RESULTS: Internet-based interventions are effective in the treatment of a broad range of mental disorders. The best evidence is available for depression and anxiety disorders. A set of criteria is proposed for the evaluation of available internet-based interventions using a checklist. These criteria have to be developed further with input from other stakeholders. DISCUSSION: When taking these quality criteria into account, evidence-based interventions available on the internet can make an important contribution to improvement of the care of patients with mental disorders.

[Resource use and financing of guideline-adherent psychotherapeutic inpatient care]. / Aufwand und Finanzierung leitliniengerechter, psychotherapeutischer Behandlung im Krankenhaus.

BACKGROUND: The financing of psychiatric psychotherapeutic care in Germany is determined by the German psychiatric staffing regulations which are unchanged since 1991. Psychotherapy was established after 1991 as an effective and indispensable treatment of mental and behavioral disorders. AIMS AND OBJECTIVES: The aim of this study was to empirically investigate the use of psychiatrists' and psychologists' working time for psychotherapy in guideline-adherent hospital care. A further aim was to compare these results to the resources defined by the German psychiatric staffing regulations and in the new prospective payment system for psychiatry and psychosomatics in Germany. MATERIAL AND METHODS: University hospitals for psychiatry and psychotherapy were asked to retrospectively provide data of patients for which guideline-adherent care was possible. Participating institutions provided both data describing the staff time utilization of psychotherapeutic services provided by psychiatrists and psychologists and patient classifications according to the German psychiatric staffing regulations and the new prospective payment system for psychiatry and psychosomatics. RESULTS: Resources defined by the German psychiatric staffing regulations covered a mean of only 71 min of psychotherapy per patient and week while the actual mean intensity of psychotherapeutic care provided by the participating hospitals was 194 min per patient and week. The associated use of staff time was 102 min per patient and week. Both figures increased during an inpatient episode. The resources defined by the German psychiatric staffing regulations covered only 70 % of medical and psychological personnel. The current configuration of the new prospective payment system for psychiatry and psychosomatics covered only 59 % of staff time. CONCLUSION: The results of this study provide another unambiguous recommendation to adjust the out-dated German psychiatric staffing regulations to the current evidence and S3 guidelines for psychiatric psychotherapeutic hospital care. In particular, more resources are required for the provision of psychotherapeutic care.

A Psychometric Evaluation of the German Version of the Quick Inventory of Depressive Symptomatology (QIDS-SR16) in Outpatients with Depression.

BACKGROUND: The self-rated, 16-item Quick Inventory of Depressive Symptomatology (QIDS-SR16) is a well-established measure of depression severity. This study aimed to evaluate the psychometric properties of the German translation of the QIDS-SR16. METHODS: 332 depressed German adults awaiting psychotherapy were assessed with the German translations of the QIDS-SR16, the Beck Depression Inventory (BDI-II) and the 24-item Hamilton Rating Scale for Depression (HRSD-24). RESULTS: Internal consistency for the QIDS-SR16 was acceptable (Cronbach's alpha = .77). Corrected item-total correlations indicated adequate discriminatory power of all the items. The QIDS-SR16 highly correlated with the BDI-II (r = .810) but only moderately correlated with the HRSD-24 (r = .581). Regarding discriminant validity, the QIDS-SR16 discriminated between patients with and without a depressive episode but not between patients with and without panic disorder. CONCLUSION: The German translation of the QIDS-SR16 has adequate psychometric properties. Our results support the usefulness of the German version of the QIDS-SR16 as a brief depression rating scale in clinical and research settings.

The association between reduced knee joint proprioception and medial meniscal abnormalities using MRI in knee osteoarthritis: results from the Amsterdam osteoarthritis cohort.

BACKGROUND: Osteoarthritis (OA) of the knee is characterized by pain and activity limitations. In knee OA, proprioceptive accuracy is reduced and might be associated with pain and activity limitations. Although causes of reduced proprioceptive accuracy are divergent, medial meniscal abnormalities, which are highly prevalent in knee OA, have been suggested to play an important role. No study has focussed on the association between proprioceptive accuracy and meniscal abnormalities in knee OA. OBJECTIVE: To explore the association between reduced proprioceptive accuracy and medial meniscal abnormalities in a clinical sample of knee OA subjects. METHODS: Cross-sectional study in 105 subjects with knee OA. Knee proprioceptive accuracy was assessed by determining the joint motion detection threshold in the knee extension direction. The knee was imaged with a 3.0 T magnetic resonance (MR) scanner. Number of regions with medial meniscal abnormalities and the extent of abnormality in the anterior and posterior horn and body were scored according to the Boston-Leeds Osteoarthritis Knee Score (BLOKS) method. Multiple regression analyzes were used to examine whether reduced proprioceptive accuracy was associated with medial meniscal abnormalities in knee OA subjects. RESULTS: Mean proprioceptive accuracy was 2.9° ± 1.9°. Magnetic resonance imaging (MRI)-detected medial meniscal abnormalities were found in the anterior horn (78%), body (80%) and posterior horn (90%). Reduced proprioceptive accuracy was associated with both the number of regions with meniscal abnormalities (P < 0.01) and the extent of abnormality (P = 0.02). These associations were not confounded by muscle strength, joint laxity, pain, age, gender, body mass index (BMI) and duration of knee complaints. CONCLUSION: This is the first study showing that reduced proprioceptive accuracy is associated with medial meniscal abnormalities in knee OA. The study highlights the importance of meniscal abnormalities in understanding reduced proprioceptive accuracy in persons with knee OA.

Testicular biodistribution of 450 nm fluorescent latex particles after intramuscular injection in mice.

The significant expansion in the use of nanoparticles and submicron particles during the last 20 years has led to increasing concern about their potential toxicity to humans and particularly their impact on male fertility. Currently, an insufficient number of studies have focused on the testicular biodistribution of particles. The aim of our study was to assess the distribution of 450 nm fluorescent particles in mouse testes after intramuscular injection. To this end, testes were removed from 5 groups of 3 mice each at 1 h (H1), 4 days (D4), 21 days (D21), 45 days (D45) and 90 days (D90) after the injection of 7.28 × 109 particles in the tibialis anterior muscles of each mouse. We examined histological sections from these samples by epifluorescence microscopy and confocal microscopy and identified testicular biodistribution of a small number of particles in groups H1, D4, D21, D45 and D90. Using CD11b immunostaining, we showed that particles were not carried into the testis by macrophages. The intratesticular repartition of particles mainly followed testicular vascularization. Finally, we found some particles in seminiferous tubules but could not determine if the blood-testis barrier was crossed.

[Ocular cicatricial pemphigoid - state of the art in clinic and therapy for a problematic disease]. / Das okuläre vernarbende Pemphigoid - aktuelle Aspekte zu Klinik und Therapie einer problematischen Erkrankung.

The ocular cicatricial pemphigoid (OCP) belongs to a family of chronically progressive autoimmune disorders, predominantly affecting mucous membranes (mucous membrane pemphigoids). It is an immunopathologically heterogeneous group of disorders with variable phenotypes that share the unique feature of a subepidermal blistering, through disruption of the adhesion between epidermis and dermis. A key feature is the chronically active inflammation with consecutive fibrosis, leading to a partial or complete loss of function of the affected organ. The ocular disease as a chronic cicatrising conjunctivitis is a common manifestation of the mucous membrane pemphigoid. The identification of the subtle pathology and the prompt initiation of an appropriate therapy are of pivotal importance. One purpose is to prevent further vision loss due to extensive corneal scarring and life-threatening systemic complications, such as the formation of oesophageal or tracheal strictures. So far there are no prospective, randomised studies, regarding the therapy guidelines with an evidence level more than III. The autoimmune nature of the disease implies that systemic immunosuppression is the only effective treatment option, most notably in extended stages. The aim of our study is to give a guideline for a stage adjusted therapy with conventional immunosuppressants and to give a perspective for alternative therapies, especially for recalcitrant disease.

[Application possibilities of modern thermography--first experience with the new Tomey TG 1000]. / Anwendungsmöglichkeiten der modernen Thermografie--ste Erfahrungen mit dem neuen Tomey TG 1000.

Temperature is one of the fundamental characteristics of tissue metabolism and is certainly of major interest to investigate ocular physiology. Current instrumentation offers the potential to measure the ocular surface temperature (OST) with high accuracy and resolution. Potential applications of OST measurement may include any condition of the ocular surface. The present study gives a survey of the possible applications of thermography and describes our first experience with the new Tomey TG 1000.

Biomechanical implications of the negative heel rocker sole shoe: gait kinematics and kinetics.

Rocker sole shoes are commonly prescribed to diabetic patients with insensate feet. Recent passage of the therapeutic shoe bill has drawn an increased focus to prescription rehabilitative footwear. The purpose of this work is to investigate the dynamics of lower extremity joints (hip, knee and ankle) with the application of a negative heel rocker sole shoe under controlled lab conditions. Forty normal adults volunteered for gait evaluations using controlled baseline and prescription negative heel rocker sole shoes. Three-dimensional motion analysis techniques were used to acquire kinematic and kinetic data using a six-camera Vicon 370 motion system and two AMTI force plates. No significant change in walking speed or stride length was seen with the negative heel rocker shoe, although cadence was increased. The most significant kinematic changes with the application of the negative heel shoe occurred at the ankle in the sagittal plane with increased plantarflexion at terminal stance. Significant hip and knee changes were also noted with increased mid-stance hip extension and knee flexion. The most significant kinetic effects were seen in the transverse plane followed by changes in the sagittal and coronal planes. Changes in power were mostly noted in the sagittal plane. Other statistically significant changes in gait kinematics and kinetics were observed, although the magnitudes and durations were limited and as a result were not considered clinically significant. The study results indicated the negative heel rocker shoe significantly altered proximal joint metrics (hip and knee). The most significant distal joint alterations were seen in sagittal plane ankle kinetics. These kinematic and kinetic changes, along with previously studied effects of pressure relief at the metatarsal heads, should aid medical professionals in prescribing prophylactic footwear.

Intraoperative Near-Infrared Fluorescence Imaging using indocyanine green in colorectal carcinomatosis surgery: Proof of concept.

PURPOSES: This study assesses the value of using Intraoperative Near Infrared Fluorescence Imaging and Indocyanine green to detect colorectal carcinomatosis during oncological surgery. In colorectal carcinomatosis cancer, two of the most important prognostic factors are completeness of staging and completeness of cytoreductive surgery. Presently, intraoperative assessment of tumoral margins relies on palpation and visual inspection. The recent introduction of Near Infrared fluorescence image guidance provides new opportunities for surgical roles, particularly in cancer surgery. METHODS: The study was a non-randomized, monocentric, pilot "ex vivo" blinded clinical trial validated by the ethical committee of University Hospital of Saint Etienne. Ten patients with colorectal carcinomatosis cancer scheduled for cytoreductive surgery were included. Patients received 0.25 mg/kg of Indocyanine green intravenously 24 h before surgery. A Near Infrared camera was used to detect "ex-vivo" fluorescent lesions. RESULTS: There was no surgical mortality. Each analysis was done blindly. In a total of 88 lesions analyzed, 58 were classified by a pathologist as cancerous and 30 as non-cancerous. Among the 58 cancerous lesions, 42 were correctly classified by the Intraoperative Near-Infrared camera (sensitivity of 72.4%). Among the 30 non-cancerous lesions, 18 were correctly classified by the Intraoperative Near-Infrared camera (specificity of 60.0%). CONCLUSIONS: Near Infrared fluorescence imaging is a promising technique for intraoperative tumor identification. It could help the surgeon to determine resection margins and reduce the risk of locoregional recurrence.

Purification and partial characterization of rat macrophage Fc receptor and binding factor for IgA.

By using a biotinylated ligand and Western blotting techniques, a receptor (RFc alpha) and a binding factor (BF) for IgA were detected, respectively, on membrane and in the cell-free culture supernatant of rat peritoneal macrophages. Extraction of the RFc alpha was obtained by solubilization of macrophages with Nonidet P-40, and purification was performed by HPLC affinity chromatography on a column derivatized with IgA. RFc alpha is formed of two subunits, with molecular masses of 56 and 70 kDa, which are both involved in the IgA binding ability of rat peritoneal macrophages. IgABF was recovered from the cell-free supernatant of a short-term culture of rat macrophages and was affinity-purified in the same manner as RFc alpha. Like RFc alpha, IgABF retained its IgA binding activity in its native, as well as denatured form. Since the molecular masses of RFc alpha and IgABF are similar, and IgABF competes with RFc alpha for IgA binding, one can assume that IgABF probably represents a shed RFc alpha.

Radiation-free preparation for allogeneic bone marrow transplantation in adults with acute lymphoblastic leukemia.

PURPOSE: The study was undertaken to investigate the effectiveness of allogeneic bone marrow transplantation from HLA-identical siblings after preparation with busulfan and cyclophosphamide in adults with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Thirty-nine patients aged 15 to 42 years underwent transplantation at three different centers from November 1984 through November 1990. All patients received 16 mg/kg busulfan and 120 mg/kg cyclophosphamide as preparative therapy. Cyclosporine plus methotrexate or cyclosporine plus corticosteroids with or without methotrexate were given for prevention of graft-versus-host disease (GVHD). RESULTS: Twelve patients died of treatment-related complications, 12 patients relapsed, and 15 patients are leukemia-free survivors. For 27 patients in group 1 (first remission, second remission, first relapse), the estimated leukemia-free survival (LFS) rate is 42.3% (95% confidence interval [CI], 22.9% to 71.7%) at 3 years. For 12 patients with more advanced disease (group 2), the 1-year LFS rate is 13.5% (95% CI, 0% to 37.1%). Chronic GVHD occurred at an estimated incidence of 63.3% and developed significantly more frequently among patients who received corticosteroids for prevention of acute GVHD. Chronic GVHD was associated with a significantly lower incidence of relapse and with improved LFS rates. CONCLUSION: LFS rate in this study is comparable to that obtained with radiation-containing regimens; however, the effectiveness of this preparative regimen in ALL requires further study.

Prevention of central venous catheter-related infections and thrombotic events in immunocompromised children by the use of vancomycin/ciprofloxacin/heparin flush solution: A randomized, multicenter, double-blind trial.

PURPOSE: To determine whether an antibiotic flush solution containing vancomycin, heparin, and ciprofloxacin (VHC) can prevent the majority of line infections. PATIENTS AND METHODS: A prospective double-blind study was performed comparing VHC to vancomycin and heparin (VH) to heparin alone in 126 pediatric oncology patients. RESULTS: The 153 assessable lines resulted in 36,944 line days studied. There were 58 blood stream infections (43 gram-positive, 14 gram-negative, and one fungal). Forty were defined as line infections (31 heparin, three VH, six VHC). The time to develop a line infection was significantly increased using either antibiotic flush (VH, P =.011; VHC, P =.036). The rate of total line infections (VH, P =.004; VHC, P =.005), gram-positive line infections (VH, P =. 028; VHC, P =.022), and gram-negative line infections (VH, P =.006; VHC, P =.003) was significantly reduced by either VH or VHC. Sixty-two (41%) of the lines developed 119 occlusion episodes (heparin, 3.99 per 1,000 line days; VHC, 1.75 per 1,000 line days; P =.0005). Neither antibiotic could be detected after flushing, and no adverse events were detected, including increased incidence of vancomycin-resistant Enterococcus colonization or disease. CONCLUSION: The use of either VH or VHC flush solution significantly decreased the complications associated with the use of tunneled central venous lines in immunocompromised children and would save significant health care resources.

Autotransplants for Hodgkin's disease in patients never achieving remission: a report from the Autologous Blood and Marrow Transplant Registry.

PURPOSE: Hodgkin's disease patients who never achieve complete remission with conventional chemotherapy (i.e., those with primary induction failure) have a poor prognosis. Some subjects who receive high-dose therapy with autologous hematopoietic progenitor-cell infusion experience prolonged progression-free survival. PATIENTS AND METHODS: Detailed records from the Autologous Blood and Marrow Transplant Registry (ABMTR) on 122 Hodgkin's disease patients who failed to achieve complete remission after one or more conventional therapy regimens and subsequently received an autotransplant between 1989 and 1995 were reviewed. RESULTS: Median age was 27 years (range, 7 to 57 years). Median time from diagnosis to transplantation was 14 months (range, 5 to 38 months). Most patients received high-dose chemotherapy without radiation for pretransplantation conditioning (n = 107). The regimen most frequently used was cyclophosphamide, carmustine, and etoposide (n = 47). Fifteen patients received total-body irradiation (n = 15). The graft consisted of bone marrow (n = 86), blood stem cells (n = 25), or both (n = 11). The 100-day mortality was 12% (95% confidence interval, 7% to 19%). Sixty patients (50%) were considered to have achieved complete remission after autotransplantation; 37 of these had negative imaging studies, whereas scan abnormalities of unknown significance persisted in 23 patients. Twenty-seven patients (22%) had no response or progressive disease after transplantation. Probabilities of progression-free and overall survival at 3 years were 38% (95% confidence interval, 28% to 48%) and 50% (95% confidence interval, 39% to 60%), respectively. In multivariate analysis, "B" symptoms at diagnosis and poor performance score at transplantation were adverse prognostic factors for outcome. CONCLUSION: Autotransplants should be considered for patients with Hodgkin's disease who do not achieve complete remission with conventional therapy.

Results of allogeneic bone marrow transplants for leukemia using donors other than HLA-identical siblings.

PURPOSE: To compare outcomes of bone marrow transplants for leukemia from HLA-identical siblings, haploidentical HLA-mismatched relatives, and HLA-matched and mismatched unrelated donors. PATIENTS: A total of 2,055 recipients of allogeneic bone marrow transplants for chronic myelogenous leukemia (CML), acute myelogenous leukemia (AML), and acute lymphoblastic leukemia (ALL) were entered onto the study. Transplants were performed between 1985 and 1991 and reported to the International Bone Marrow Transplant Registry (IBMTR). Donors were HLA-identical siblings (n = 1,224); haploidentical relatives mismatched for one (n = 238) or two (n = 102) HLA-A, -B, or -DR antigens; or unrelated persons who were HLA-matched (n = 383) or mismatched for one HLA-A, -B, or -DR antigen (n = 108). HLA typing was performed using serologic techniques. RESULTS: Transplant-related mortality was significantly higher after alternative donor transplants than after HLA-identical sibling transplants. Among patients with early leukemia (CML in chronic phase or acute leukemia in first remission), 3-year transplant-related mortality (+/-SE) was 21% +/- 2% after HLA-identical sibling transplants and greater than 50% after all types of alternative donor transplants studied. Among patients with early leukemia, relative risks of treatment failure (inverse of leukemia-free survival), using HLA-identical sibling transplants as the reference group, were 2.43 (P < .0001) with 1-HLA-antigen-mismatched related donors, 3.79 (P < .0001) with 2-HLA-antigen-mismatched related donors, 2.11 (P < .0001) with HLA-matched unrelated donors, and 3.33 (P < .0001) with 1-HLA-antigen-mismatched unrelated donors. For patients with more advanced leukemia, differences in treatment failure were less striking: 1-HLA-antigen-mismatched relatives, 1.22 (P = not significant [NS]); 2-HLA-antigen-mismatched relatives, 1.81 (P < .0001); HLA-matched unrelated donors, 1.39 (P = .002); and 1-HLA-antigen-mismatched unrelated donors, 1.63 (P = .002). CONCLUSION: Although transplants from alternative donors are effective in some patients with leukemia, treatment failure is higher than after HLA-identical sibling transplants. Outcome depends on leukemia state, donor-recipient relationship, and degree of HLA matching. In early leukemia, alternative donor transplants have a more than twofold increased risk of treatment failure compared with HLA-identical sibling transplants. This difference is less in advanced leukemia.

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.