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Objective: The objective of this prospective multicenter study was to obtain insight into the severity and burden of hair loss among cancer patients treated with chemotherapy. In addition, we described the effectiveness and burden of scalp cooling and the satisfaction with wigs, with hair regrowth, and with body image.Materials and Methods: Breast cancer patients treated with (n = 98) and without (n = 168) scalp cooling completed questionnaires before chemotherapy and 3 weeks and 6 months after completion of chemotherapy.Results: Scalp cooling was effective in preventing chemotherapy-induced hair loss in 32 of 62 available patients (52%). Even though patients knew hair loss was temporary, it was a burden to 54% of them (n = 100). Scalp cooling was a burden for only 17 out of 51 patients (33%). Most patients who used a wig or head cover were satisfied with it (82%, n = 126). Patients were moderately satisfied with the regrowth of their hair after chemotherapy (mean 11.6; SD 2.53; range 0-20). Successfully cooled patients rated their hair as less important for their body image compared to patients who did experience hair loss (p = 0.014).Discussion: Chemotherapy-induced hair loss is perceived as burdensome. It may be prevented by offering scalp cooling which is often an effective method to prevent this form of hair loss and is tolerated well by patients. However, if possible, scalp-cooling techniques should be improved and their effectiveness should be increased because if scalp cooling is unsuccessful, patients' rate their hair loss as more burdensome compared to noncooled patients. [ABSTRACT FROM AUTHOR]

Purpose: For patients, chemotherapy-induced alopecia (CIA) is one of the most distressing side effects of treatment. Scalp cooling can prevent or minimise CIA; the results may depend on the duration of cooling. Since a previous study on post-infusion cooling time in patients treated with docetaxel chemotherapy found no difference between 90 and 45 min, we investigated whether hair-preserving results could be maintained with a shorter post-infusion cooling time., Methods: In this prospective, multi-centre randomised study, 134 patients who started treatment with docetaxel 75-100 mg/m(2) in a 3-weekly schedule were randomly assigned in a 1:1 ratio to a post-infusion cooling time of 45 or 20 min. The primary end point was the need for a wig or other head covering as assessed by the patient. A visual analogue scale (VAS) with a range from 0 (not tolerable) to 10 (very tolerable) was used to measure tolerance., Results: Scalp cooling results were similar for 45- and 20-min post-infusion cooling times. Thirty-three out of 45 patients (73 %) treated with 20 min of post-infusion cooling did not need a form of head covering, compared with 41 out of 52 patients (79 %) treated with 45 min of post-infusion cooling (p = 0.5). The procedure was well tolerated (mean visual analogue score 8.3). Six patients stopped due to intolerance during the first treatment cycle., Conclusions: A 20-min post-infusion cooling time is effective and tolerable for patients treated with scalp cooling to prevent docetaxel-induced alopecia., Trial Registration: Trialregister.nl Identifier, NTR 1856.

Background: The efficacy of hair loss prevention by scalp cooling to prevent chemotherapy induced hair loss has been shown to be related to scalp skin temperature. Scalp skin temperature, however, is dependent not only on local cooling but also on the thermal status of the body., Objectives: This study was conducted to investigate the effect of body temperature on scalp skin temperature., Methods: We conducted experiments in which 13 healthy subjects consumed ice slurry to lower body temperature for 15 minutes after the start of scalp cooling and then performed two 12-minute cycle exercise sessions to increase body core temperature. Esophageal temperature (Tes ), rectal temperature (Tre ), mean skin temperature (eight locations, Tskin ), and mean scalp temperature (five locations, Tscalp ) were recorded., Results: During the initial 10 minutes of scalp cooling, Tscalp decreased by >15 °C, whereas Tes decreased by 0.2 °C. After ice slurry ingestion, Tes , Tre , and Tskin were 35.8, 36.5, and 31.3 °C, respectively, and increased after exercise to 36.3, 37.3, and 33.0 °C, respectively. Tscalp was significantly correlated to Tes (r = 0.39, P < 0.01): an increase of 1 °C in Tes corresponded to an increase of 1.6 °C in Tscalp ., Conclusions: Slight cooling of patients with an elevated body temperature during scalp cooling contributes to the decrease in scalp temperature and may improve the prevention of hair loss. This may be useful if the desired decrease of scalp temperature cannot be obtained by scalp cooling systems., (© 2015 The International Society of Dermatology.)

Objective: Scalp cooling (SC) is applied to reduce chemotherapy-induced alopecia (CIA). The aim of this study was to investigate patients' familiarity and opinions and oncological professionals' attitude and knowledge about SC in the Netherlands., Methods: Ex breast cancer patients, nurses and medical oncologists (MDs) from SC and non-SC hospitals filled out questionnaires., Results: The majority of MDs and nurses were satisfied with the results of SC, as were SC patients. Over 33% of MDs and nurses perceived their knowledge level insufficient to inform patients about effectiveness, which was over 43% for information about safety. MDs main reason to not apply SC was doubt about effectiveness and safety. Nurses generally offered SC to a minority of eligible patients. Patients were frequently unfamiliar with SC before diagnosis. Seventy percent of SC patients with insufficient results (20/52) reported to mind it very much. With expected success rates of 35% and 50%, respectively, 36% and 54% of patients would use SC again., Conclusion: Room for improvement has been shown for both patients' familiarity and oncological professionals' knowledge about SC. Sharing knowledge about results, safety and patients' experiences will improve patient counseling and SC availability. The results of this survey led to the development of a national standard on CIA and SC., Competing Interests: Conflicts of Interest: None declared.

Background: Alopecia is a frequently occurring side effect of chemotherapy that often can be prevented by cooling the scalp during the infusion. This study compared effects and costs of scalp cooling with usual general oncological care, i.e. purchasing a wig or head cover., Material and Methods: Scalp-cooled patients (n = 160) were compared with non-scalp-cooled patients (n = 86) at 15 Dutch hospitals. Patients were enrolled prior to anthracycline and/or taxane-based chemotherapy for several types of cancer between 2007 and 2008. Cost-effectiveness of scalp cooling compared with that of usual care was determined by the ratio of costs to quality adjusted life years (QALYs). Costs for scalp cooling (machines and nursing time), hair dressers, wigs and head covers were estimated from a societal perspective. QALYs were measured using the Short Form-36., Results: Scalp cooling reduced the use of a wig or head cover by 40%, but wigs were still purchased unnecessarily by 38% of scalp-cooled patients. Average societal costs decreased therefore only by €269 per patient due to scalp cooling (p = 0.02). Given the eligibility for scalp cooling at the time, the insignificant difference in QALYs resulted from a balance of the benefits for those patients with successful scalp cooling and those without success. For the Dutch, given the generally accepted threshold of willingness to pay for a QALY (between €20 000 and €40 000), scalp cooling was cost-effective, therefore justifying the choice of scalp cooling or purchasing a wig or head cover., Conclusion: Given the right indication, cost-effectiveness might be improved further by postponing wig and head cover purchases, by improving scalp cooling efficacy, as well as using the scalp cooling capacity more intensively.

Introduction: Cytotoxic therapy for patients with cancer frequently induces reversible, but long-lasting alopecia which might be prevented by scalp cooling. This study evaluates the effectiveness of scalp cooling with respect to the severity of chemotherapy-induced alopecia (CIA) and the purchase and use of wigs and head covers., Materials and Methods: In this observational study, scalp-cooled patients (n = 160) were compared with non scalp-cooled patients (n = 86) with several types of cancer. Patients were enrolled in 15, mostly general hospitals prior to taxane and/or anthracycline-based chemotherapy. Patients completed four questionnaires between the start and one year after the last chemotherapy., Results: Severity of CIA, and purchasing and actually wearing wigs and head covers were significantly lower among scalp-cooled than non scalp-cooled patients. Overall, scalp cooling reduced the use of wigs and head covers by 40%. Among 84 scalp-cooled patients who purchased a wig (53%), only 52 patients actually wore it (62%), and they just wore it intensively (86% daily) for less than six months (80%). Especially young patients camouflaged CIA with a head cover instead of a wig., Discussion: The relatively long duration of CIA, the wish of many patients to camouflage or rather prevent it and the 40% reduction for head covering by scalp cooling, makes it a worthwhile supportive intervention. However, (cost-) effectiveness can be improved. Many scalp-cooled patients purchased a wig unnecessarily., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

With modern scalp cooling equipment cytotoxic damage of hair root cells can be prevented in half of the patients with cancer at high risk of alopecia. However, traditionally doubt has existed whether scalp cooling might facilitate hiding and disseminating scalp skin metastases and thus decrease survival. We discuss this risk using frequency data on metastases in breast cancer from observational and autopsy studies and the Munich cancer registry. They showed the incidence of scalp skin metastases to be very low and not differ between scalp-cooled (0.04-1%) and non scalp-cooled (0.03-3%) patients with breast cancer and in need of chemotherapy. We found it rather unlikely that the incidence of scalp skin metastases might increase at all after scalp cooling, whereas a very small proportion of patients receiving chemotherapy are at risk to develop metastases at this site. Scalp cooling can thus safely be offered to patients treated with alopecia-inducing chemotherapy., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Purpose: In order to evaluate the efficacy of scalp cooling for the prevention of chemotherapy-induced alopecia (CIA), it is essential to precisely quantify the amount of hair mass that is present. We wanted to determine if the hair mass index (HMI), obtained by cross-section trichometry (CST), was a suitable parameter for hair mass measurement, and whether or not marking the measurement site on the scalp was necessary., Methods: Ten patients receiving chemotherapy were sequentially measured using CST during their treatment. At the same time, they were asked to report severity of hair loss via three subjective parameters: World Health Organization (WHO) grade, visual analog scale (VAS) score, and patients' need to wear wig or head cover. To investigate the need of marking of the measurement area, differences in HMI between a random 2 × 2-cm site (HMI-C) and four surrounding areas (HMI-S4) on the scalp of eight volunteers and eight chemotherapy patients were calculated and compared., Results: Using CTS, hair loss due to CIA was quite measurable and ranged from 13 to 82 %. Reported VAS scores and WHO grades showed an increase in patients in time; 50 % of patients reported the need to wear a wig or head cover. The difference between HMI-S4 and the HMI-C values in all subjects of the marking group was homogeneously distributed between -11 and +10 and was not statistically different between the volunteer and the patient groups (p = 0.465)., Conclusions: CST for HMI measurement is a useful mechanical modality for assessing hair loss in CIA patients. It is quantitatively more precise than existing non-mechanical measuring methods. It is recommended when detection of minor changes in hair quantity is required. Marking a fixed sampling area to ensure return to the exact same site is only required when a minor change in pre- and posttreatment HMI values is anticipated and the mid-line locating device is not/cannot be used.

Purpose: The patient impact of chemotherapy-induced alopecia (CIA) is high. Scalp cooling is applied to reduce CIA. The potential optimum post-infusion cooling times (PICTs) are currently unknown., Methods: Scalp cooling was applied in 53 patients receiving docetaxel chemotherapy with 90-min PICT (observational part). Also 15 non-scalp-cooled patients were included. If hair preservation was observed in >80 % of the patients, randomisation between 45 and 90-min PICT was planned. Patients reported tolerance of scalp cooling and use of head covering., Results: Observational study: 81 % of scalp-cooled patients did not require head covering versus 27 % of non-scalp-cooled patients. Randomised study: 79 % of 38 patients with 90-min PICT did not need head covering versus 95 % of 38 patients with 45-min PICT (p = 0.04). Scalp cooling was very well tolerated (visual analogue scale = 79)., Conclusion: A 45-min PICT can be recommended in 3-weekly docetaxel regimens with a dose of 75 or 100 mg/m(2), administered in 60 min. The shorter PICT is a major advantage in time investment for patients. Patients (women and men) who receive docetaxel, except combined with doxorubicin and cyclophosphamide (taxotere, adriamycin and cyclophosphamide (TAC)) should be informed about the protective effect and high tolerability of scalp cooling in avoiding CIA.

Background: Until now, there has been no reliable, simple method available for measuring hair quantity that is suitable in clinical practice. Recently, the cross-section trichometer by Cohen has been introduced. This study was designed to test its clinical utility., Methods: The hair mass index (HMI) is ratio of the cross-sectional area of an isolated bundle of hair and the premeasured area of skin from which it was taken using the trichometer device. The intra- and interobserver reproducibility of measurements at the same location and after relocation were evaluated., Results: For intraobserver reproducibility, the HMI ranged from 3 to 120 (mean difference .2, 95% confidence interval [CI] = -4.7-5.1, correlation coefficient [r] = .99. For interobserver reproducibility, the HMI ranged from 18 to 119 (mean difference -.4, 95% CI = -8,0-7,2, r = .98). With relocation, the HMI ranged from 2 to 113 (mean difference -1.0, 95% CI = -10.1-8.1, r = .97). Measurements took 5-10 minutes per area., Conclusion: Measurements were simple to perform, and the data showed high reproducibility. The trichometer is a promising technology for hair quantity measurements and has multiple clinical and research applications., (© 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.)

Background: Chemotherapy-induced alopecia is a frequently occurring side effect of cancer treatment with a high psychological impact which can be prevented by scalp cooling. With this multi-centre patient series we estimated the results of scalp cooling for currently used chemotherapies to provide patient information and we identified characteristics associated with the results., Material and Methods: The Dutch Scalp Cooling Registry collected data on scalp-cooled patients in 28 Dutch hospitals. Nurses and patients completed questionnaires on patients, chemotherapy and scalp cooling characteristics. Logistic regression analysis was used to examine associated characteristics of the scalp cooling result., Results: Overall, 50% of the 1411 scalp-cooled patients did not wear a head cover during their last chemotherapy session. Patients were satisfied with the results in 8% of cases after TAC chemotherapy and up to 95% after paclitaxel treatment. Besides type of chemotherapy, higher dose and shorter infusion time, older age, female gender and non-West-European type of hair significantly increased the proportion head cover use. Hair length, quantity, chemical manipulation (dyeing, waving, colouring), wetting hair before scalp cooling, and treatment with chemotherapy ever before did not influence the degree of head covering among patients., Conclusions: Scalp cooling results as recorded in this open patient registry were positive for most regimens, justifying it's use by all eligible patients, except for those needing TAC. Lengthening infusion time may improve the results.

Little is known about time trends in metastases in the patients treated in routine health care facilities without metastases at diagnosis (M0) and about survival after these metastases. Data on 33,771 M0 patients with primary breast cancer diagnosed between 1978 and 2003 were obtained from the Munich Cancer Registry. Survival analyses were restricted to the patients with metastases within 5 years of the initial diagnosis. The incident number of the patients approximately doubled each period and 5-year overall survival increased from 77% in the first to 82% percent in the last period. 5490 (16%) M0 patients developed metastases within 5 years after the initial diagnosis. The hazard of developing metastases was lowest in the most recent period compared to the first period (HR = 0.50, P < 0.001). The hazard of dying after metastases was equal for patients diagnosed between 1978-1984 and 1995-2003 (HR 1.08, P = 0.3). The percentage of the patients that developed bone metastases decreased each time period, but the percentage primary liver and CNS metastases increased. Exclusion of site of metastases in the multivariate analysis led to a 20% (P = 0.02) higher hazard of dying following metastases in the last versus the first period. In the period 1978-2008, unfavourable changes in the pattern of metastases were exhibited and no improvement was observed in survival of the patients after occurrence of metastases. An explanation might be the increased use of adjuvant systemic treatment, which has less effect on the highly lethal liver and CNS metastases than on bone metastases. The increased use also appeared to contribute to the overall prevention of metastases in breast cancer and therefore to improve overall survival.

Objective: Chemotherapy-induced alopecia, a common and distressing side effect of chemotherapy, may be prevented by scalp cooling, which reduces toxicity of cytostatics in hair root cells. This is the first study designed to assess the effect of scalp cooling on well-being., Methods: A prospective multi-centre study was performed in 13 hospitals. Breast cancer patients treated with (N=98) and without (N=168) scalp cooling completed questionnaires (EORTC QLQ-C30 and EORTC-QLQ-BR23, BIS, MBA, HADS) before chemotherapy, and three weeks and six months after the last chemotherapy cycle., Results: Scalp cooling was effective in 52% of the cases. Alopecia was considered among the most distressing problems at all three moments of measurement. A trend towards higher well-being was found in successfully scalp-cooled patients, as indicated by a general better health-related quality of life and better body image, whereas unsuccessfully scalp-cooled patients reported lowest well-being., Conclusions: Scalp cooling contributes not only to the well-being of successfully scalp-cooled patients but also seems to cause additional distress when patients lose their hair despite scalp cooling. This might be related to disappointment due to alopecia despite scalp cooling or possibly to a general higher biological availability of cytostatics. We recommend additional support for patients when scalp cooling is not successful and to spend more effort to maximise the effectiveness of scalp cooling., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Background: The effect of interferon-alpha 2b (IFN-alpha-2b) on progression-free and overall survival as well as quality of life (QoL) was studied in mainly elderly patients with multiple myeloma (MM), who reached a plateau phase after melphalan/prednisone induction., Patients and Methods: In an open phase III trial, 262 patients, median age 69 years (range 34-91), received at least 10 monthly courses of melphalan/prednisone followed by response evaluation. Plateau phase was reached by 128 patients. Next, 90 patients were randomized between IFN-alpha-2b and no maintenance therapy. Reasons for non-randomization were: refusal (18), concomitant disease (nine), protocol violation (six), WHO performance status >2 (four) and allogeneic transplantation (one), Results: At a median follow-up from diagnosis of 97 months (0-140) for those patients alive, IFN-alpha-2b therapy was associated with improved progression-free survival (median 13.5 versus 8.4 months from randomization), although this did not translate in a better overall survival (41 versus 38.4 months). One-third of patients discontinued IFN-alpha due to toxicity. No differences were observed between patient groups in QoL., Conclusions: IFN maintenance therapy in MM prolongs progression-free survival and, provided that the burden of toxicity is not too high, does not adversely affect QoL.

Background: Chemotherapy-induced temporary hair loss is one of the most common and distressing side-effects of cancer therapy. Scalp cooling to reduce this hair loss is a controversial issue for many doctors and nurses. This may be due to inadequate knowledge., Methods: This review from 53 publications and three personal communications focuses on the efficacy of the treatment, side-effects, possible disadvantages and the controversies in these areas., Results: Scalp cooling has become an increasingly effective method to prevent hair loss, especially when anthracyclines or taxanes are used. Unfortunately, many studies were small and badly designed and are therefore difficult to compare. There is a considerable variation in the success rates in the various studies. This remains unexplained, but the cooling time, the chemotherapy used and the temperature seem to be influential. Scalp cooling should not be used if chemotherapy is given with a curative intent in patients with generalised haematogenic metastases. The majority of patients tolerate cooling very well., Conclusion: Scalp cooling is effective but not for all chemotherapy patients. Further psychological, clinical and biophysical research is needed to determine exact indications for cooling and to improve the effect, tolerance, side-effects and the cooling procedure. Multicentre trials should be carried out to gather this information.

Since about 1970 scalp cooling has been used to prevent chemotherapy-induced hair loss, one of the most common and emotionally distressing side effects of cancer therapy. Generally accepted opinions, uncertainty and controversy, topics to study and recommendations for improving the results of scalp cooling are the subjects of this article which was also presented at the MASCC Symposium, June 2003, Berlin.

A population-based series of patients with cancer is likely to comprise more patients with serious co-morbidity than clinical trials because of restrictive eligibility criteria for the latter. Since co-morbidity may influence decision-making, we studied the age-specific prevalence of co-morbidity and its relationship to applied treatment. Data on all 194 patients with Hodgkin's disease (HD) and on 904 patients with non-Hodgkin's lymphoma (NHL) diagnosed between 1993 and 1996 were derived from the Eindhoven Cancer Registry. In the age-group below 60 years, 87% of patients with HD and 80% with NHL did not have a co-morbid condition. The prevalence of serious co-morbidity was 56% for patients with Hodgkin's disease who were 60 years and over and 43% and 61% for non Hodgkin patients who were 60-69 years and 70 years and over, respectively. The most common co-morbid conditions were cardiovascular disease (18%), hypertension (13%), chronic obstructive pulmonary disease (COPD; 13%), and diabetes mellitus (10%) for elderly Hodgkin's patients. For non-Hodgkin's patients of 60-69 years and 70 years and over, cardiovascular disease (15 and 22%, respectively), hypertension (14 and 14%, respectively), COPD (6 and 10% respectively), and diabetes mellitus (8 and 10%, respectively) were the most prevalent co-morbid conditions. The presence of co-morbidity was not related to stage or grade of disease at diagnosis. In the presence of co-morbidity, 50% less chemotherapy was administered to elderly patients with Hodgkin's disease and 10-15% less to elderly patients with non-Hodgkin's lymphoma. The presence of co-morbidity was associated with a decreased overall survival within the first 4 months after diagnosis in both Hodgkin's disease and non-Hodgkin's lymphoma for all age-groups. In conclusion, serious co-morbidity was found for more than half of all lymphoma patients who were 60 years and older. Elderly patients with serious co-morbidity received chemotherapy less often, which is likely to affect survival adversely, as was indicated by a decreased survival within the first 4 months after diagnosis.

This randomised controlled multicentre trial evaluated the effectiveness of recombinant human erythropoietin (rhEPO) in preventing anaemia and reducing the need for blood or erythrocyte transfusion in 122 ovarian cancer patients receiving platinum-based chemotherapy. The patients were randomly allocated to receive rhEPO 150 U/kg or 300 U/kg subcutaneously, three times a week, or open control. Patients also received up to 6 cycles of carboplatin or cisplatin, alone or in combination with other cytotoxic agents. Intention-to-treat analysis showed that 39.4% of patients in the control group received at least one blood transfusion, compared with 9.2% of patients treated with rhEPO. Patients treated with rhEPO experienced a significantly longer time to first erythrocyte transfusion than the control group and were less likely to experience nadir haemoglobin levels < 10 g/dl (P < 0.001 and < 0.05, respectively). A haemoglobin decrease < 1 g/dl during the first chemotherapy cycle, as well as a low baseline serum erythropoietin concentration, predicted a low transfusion need in rhEPO-treated patients but not in controls. During the study, 103 patients suffered at least one adverse event, but no serious, and only nine non-serious adverse events were considered possibly related to rhEPO therapy. These results indicate that treatment with rhEPO prevents anaemia, it reduces the need for blood or rhEPO erythrocyte transfusion in patients with ovarian cancer receiving platinum-based chemotherapy, and it is well tolerated. A starting dose of 150 U/kg of rhEPO, three times a week, may be recommended.

Since prolonged remission can be induced in the majority of patients with Hodgkin's disease (HD), treatment-related mortality and morbidity have emerged. We investigated whether awareness of toxicity diminished treatment-related mortality for unselected patients treated between 1972 and 1993 in general hospitals in the southeastern Netherlands. We also estimated the prevalence of treatment-related morbidity among patients treated in the 1980s. Data were collected on all 345 HD patients registered in the Eindhoven Cancer Registry between 1972 and 1993. Medical records and histology were reviewed; follow-up ended in 1994. Administration of MOPP chemotherapy decreased, and there was a shift from total nodal irradiation to less extended low-dose radiotherapy. For cured patients the 10-year relative survival improved from 84% in the 1970s to 90% in the 1980s, which is reflected by a decline in excess mortality from 16% to 10%. The 10-year relative mortality risk due to secondary malignancies decreased from 4.3 (95% CI, 1.2-7.4) to 3.0 (CI 0.2-5.8), which is also reflected by a decline in the 10-year cumulative incidence for all cancers from 10% to 5%. However, the relative risk of late cardiovascular death, which is closely related to previous irradiation, barely changed, as shown by a decrease from 2.4 (CI 0.4-4.5) to 2.2 (CI.0-4.7). HD survivors profited less from the sharp decline in cardiovascular mortality observed for the general population. Among patients, the prevalence of serious treatment-related morbidity 5 years or more after initial diagnosis was 34%. In conclusion, modest decline in excess mortality among cured HD patients was observed in the 1980s, as reflected by a decrease in mortality due to second malignancies. However, late mortality, especially due to radiation-related cardiovascular disease, is still substantial. About one third of HD survivors suffer radiation-induced sequelae. Clinical trials to find ways to minimize iatrogenic complications are important.

An 81-year-old man known to have a stable cold agglutinin syndrome presented with a progressive cerebral hemorrhage. Coagulation tests revealed prolonged APTT and prothrombin time and severely decreased factor V activity, which could not be normalized by mixing with normal plasma. The patient appeared refractory to substitution with fresh-frozen plasma, suggesting the presence of a circulating inhibitor specific for factor V. To our knowledge, this is the first case of a lymphoproliferative disease leading to a cold agglutinin syndrome and a putative inhibitor of factor V. In patients with paraproteinemia presenting with bleeding diathesis, the presence of a circulating inhibitor of a specific coagulation factor must be considered.

In the past 30 years, staging and treatment of Hodgkin's disease have changed dramatically, and prolonged remission can now be induced in the majority of patients. Our purpose was to assess improvement in long-term survival, previously reported for specific patient groups, among unselected patients diagnosed and treated between 1972 and 1993 in general hospitals in South-East Netherlands. Data on all 345 Hodgkin's patients were derived from the population-based Eindhoven Cancer Registry; histopathology and clinical records were reviewed. Follow-up was attained up to 1994. Relative survival rates, i.e. the ratio of observed to expected rates, were 80% after 5, 70% after 10 and 67% after 15 years. Independent prognostic factors for lower overall survival were (in decreasing order of significance): advanced age, histology (lymphocyte depletion), advanced stage and earlier period of diagnosis. Distribution of age and stage did not change over the study period, but there was a modest increase in the incidence of the nodular sclerosis histological subtype. Crude 5-year survival rates improved from 60% in the period 1972-1976 to 81% in the period of 1987-1992 (P < 0.005). The largest improvement occurred in the 1970s and was most prominent among those aged over 50 years. As previously reported, cured Hodgkin's patients exhibit a higher mortality rate, which can be explained by treatment-related long-term complications such as second malignancies and cardiovascular diseases. The relatively high survival rates compared to other population-based studies may be attributable to the existence of a regional network within the framework of a comprehensive cancer centre. Better staging, new combinations of chemotherapy, improved radiation technology, advances in supportive care as well as more frequent intensive treatment of the elderly could explain the improvement in prognosis.

The importance of the subclassification of nodular sclerosing Hodgkin's disease (NSHD) according to the British National Lymphoma Investigation Group (BNLI) criteria, which had an independent prognostic value for 90 unselected patients diagnosed in our region in the period 1972-83, is still equivocal. Because survival of patients with Hodgkin's disease improved in our region during the period 1972-92 and because treatment may modify prognostic factors, we re-evaluated the prognostic value of NSHD subclassification up to 1993. A registry-based study was performed with data on all 345 Hodgkin patients diagnosed in the period 1972-92. Available histology was reviewed. The prognostic value of nodular sclerosis (NS) grading was evaluated for two periods, 1972-80 and 1981-92, designated as the seventies and the eighties, respectively. NSHD was diagnosed in 57% (n = 195) of all registered cases of Hodgkin's disease, 17 of which could not be evaluated. NS stage I (NSI; 73%) and NS stage II (NSII; 27%) patients exhibited the same distribution of stage during both periods; NSII patients were older than NSI patients in the seventies. NSII patients presented with an elevated ESR and B symptoms more frequently during the eighties and subsequently received combined modality therapy more often. The crude 5-year survival rate for grade I v grade II NSHD was 85% v 38% (P < 0.05) for the seventies and 84% v 83% for the eighties. Subclassification of NSHD was not an independent prognostic factor after adjustment for age, stage, gender, B symptoms and ESR, though it remained of independent prognostic value when ESR was left out of the Cox model. The most important factors adversely influencing survival were advanced age, advanced stage and male gender. The independent prognostic value of the subclassification of NSHD has disappeared, as reflected by the clearly improved survival of NSII patients, probably due to more intensive treatment in the eighties, whereas survival of NSI patients did not changes.

In Hodgkin's disease DNA aneuploidy is not a prognostic factor. However, the prognostic significance of DNA content in Hodgkin's disease may be missed by either intratumor DNA heterogeneity or DNA analysis of limited samples. For flow cytometry usually one section of 40-60 microns is used for the analysis. In breast cancer this proved to be insufficient. In Hodgkin's disease no data are available. Therefore, we examined if analysis of more sections does increase the yield of aneuploidy. Archival, formalin-fixed, parafin embedded tissues were used. From 13 patients four sections of 50 microns could be analysed for DNA content. In 12 of 13 patients the results were consistent in all four sections of one patient case; seven diploid, four aneuploid and one multiploid. In one case ploidy status changed: two sections were diploid and two were aneuploid. The DNA-index of the aneuploid samples ranged from 0.75 to 1.38 and varied from 0.02 to 0.14 within one case. The S-phase fraction remained constant within all evaluable cases (sd: 0.5-1.5%), except for one (sd: 4.7%). In conclusion, in Hodgkin's disease the ploidy status of the first section can be regarded to represent the whole tissue sample. Therefore, the absence of prognostic value of ploidy status is not explained by sampling errors in tissues analysed.

We describe a patient with severe symptomatic thrombocytopenia and haemolytic anaemia caused by cytomegalovirus (CMV) infection. As far as we know, this is the second case in the literature. Treatment with ganciclovir seemed to be more effective for thrombocytopenia than treatment with corticosteroids. The hypothetical mechanisms leading to thrombocytopenia and haemolysis in CMV infection are briefly discussed. In cases of acute thrombocytopenia and clinical manifestations of an infectious disease, with or without haemolysis, testing for CMV may be useful in connection with therapeutic consequences.

Purpose: We report a prospective randomized study comparing the relative efficacy of alternating chemotherapy mechlorethamine, vincristine, procarbazine, and prednisone/doxorubicin, bleomycin, vinblastine, and dacarbazine (MOPP/ABVD) with the standard MOPP chemotherapy in patients with stage IIIB and IV Hodgkin's disease (HD). The purpose is to study the influence of time of remission on clinical outcome., Patients and Methods: After two courses of MOPP, patients were randomized to receive six further courses of MOPP, or two courses of ABVD followed by two courses of MOPP and two courses of ABVD. Radiotherapy was given to areas presenting with masses > or = 5 cm and to residual masses after course no. 4. Evaluation of response (complete remission [CR]) took place after two courses (CR2), after four courses (CR4), at the end of chemotherapy (CR8), and after additional radiotherapy (CR(CT + RT)). Logistic regression analysis was used to study prognostic factors for response at the end of chemotherapy. Cox analysis was used to study prognostic factors for survival. Two hundred seven patients were registered, 192 (93%) of whom were randomized., Results: The CR rate at the end of chemotherapy (CR8) was similar in both arms (57% v 59%). However, there were more progressions in the MOPP arm compared with the MOPP/ABVD arm (23% v 8%, P = .014). A significantly higher failure-free survival (FFS) rate was found in the MOPP/ABVD arm (60% v 43% at 6 years, P = .025). There was no difference in the relapse-free survival (RFS) or survival rate. Of patients not in CR4, only 28% still reached a CR8. RFS at 6 years of patients with CR4 (69%) was not different from that of patients with CR8 (68%); patients with a CR(CT + RT)) had a lower RFS rate (48%). CR4 (P < .001) predicted strongly for final remission at the end of chemotherapy. Cox analysis showed that age more than 50 years, six or more involved lymph node areas, no CR by the fourth cycle, chemotherapy with MOPP alone, and no radiotherapy were unfavorable factors for survival., Conclusion: MOPP/ABVD chemotherapy significantly improved response and FFS rates, but had no influence on RFS and survival rates. Early CR (CR4) is an important factor for final remission and might be used to select a group of patients with a good prognosis.

To assess the reliability of DNA estimation using image cytometry, deparaffinized lymph nodes from 70 patients with Hodgkin's disease were examined and the results obtained were compared with those from flow cytometry. Image analysis without discriminating between the various cell types, as found in Hodgkin's disease, revealed no separate aneuploid peak. Selecting on morphologically defined nuclear types DNA aneuploidy was detected in 20% of the cases (14/70). The aneuploid populations were limited to the population of nuclei defined as Reed-Sternberg (RS)-like or medium-sized lymphocytes. Benign lymph nodes DNA aneuploidy was not found in any of the controls. Comparison of DNA histograms obtained by image and flow cytometry showed aneuploid peaks using image cytometry in 4 of 30 diploid and 10 of 40 aneuploid flow histograms. In conclusion, image analysis using the CAS 200 system as compared to flow cytometry is more time-consuming and less sensitive to assess ploidy status, although it may provide extra information in some selected cases. Evidence is obtained that DNA aneuploidy in Hodgkin's disease is preferentially expressed by cells with the RS/H-like and medium-sized lymphocyte morphology.

Background: The p53 gene has a tumor-suppressor function. The mutated gene encodes for a protein which has a longer half-life than the normal p53 protein. This enables the detection of the mutated p53 protein by immunohistochemistry., Materials and Methods: In this study we examined 53 lymph nodes of patients with Hodgkin's disease for the presence of p53. The lymph nodes were stained with DO-1 and CM-1, two antibodies directed against the p53 protein., Results: DO-1 weakly stained 2/14 samples positively, and CM-1 10/25. When preincubated with Target Unmasking Fluid, CM-1 stained 51/53 samples positively. Although, only Hodgkin and Reed-Sternberg cells stained positively, p53-negative Hodgkin and Reed-Sternberg cells were also seen in the same sample., Conclusion: Based on these results, we conclude that the p53 mutated protein is present in a high number of cases with Hodgkin's disease, which is suggestive for an important event in the pathophysiology of the disease. In addition, because of the absence of positive staining in the surrounding lymphocytes, these cells are unlikely to be part of the malignant clone.

Paraffin-embedded lymph nodes from patients with Hodgkin's disease were examined for flow cytometric DNA content. In order to increase the sensitivity of the assay we tried to enrich for the neoplastic cells by bivariate analysis using a polyclonal anti-nucleolar antibody (AN-AB) and the forward scatter (FSC). DNA aneuploidy was found to be present in 67 of all 137 cases (49%), in 24 cases only demonstrable by dual-parameter analysis. The DNA index varied from 0.69 to 1.89 with a total of 22 hypo-diploid cases. The number of aneuploid nuclei exceeded the expected frequency of Reed-Sternberg (RS) and Hodgkin (H) cells in most of the analysed specimens. In conclusion, flow cytometry in Hodgkin's disease appears to give useful information regarding the ploidy status and evidence has been provided that the malignant cell population in Hodgkin's disease is not limited to the classical RS/H cells.

Over the years several methods for evaluating mediastinal involvement in Hodgkin's disease have been applied to chest radiographs and conflicting results have been reported. In a retrospective study of 104 patients we evaluated interobserver variability in assessing mediastinal involvement and investigated various cut-off points for mediastinal size as to their ability to identify patients with high- and low-risk for recurrence. For mediastinal involvement the concordance rate for two reviewing radiologists was 94% (98/104) and compared with prior assessment by outside radiologists the concordance rates were 90% (94/104) and 88% (92/104), respectively. A good correlation between the reviewing radiologists was found for the quantitative evaluation of mediastinal diameter and thoracic ratios. ROC curves and relative risk figures were used to investigate the various cut-off points for mediastinal width and for the ratios of the maximal mediastinal diameter to the chest diameter at Th 5-6 (M1) and to the chest diameter at the widest thoracic level (M2). Neither the ROC curve analysis nor the use of relative risk figures revealed a cut-off point clearly more accurate in predicting recurrence. In conclusion, our results do not suggest that interobserver variability in mediastinal assessment, differences in the method of mediastinal measurement, or the cut-off points applied to mediastinal width can explain the discrepancies in the reported data on the prognostic value of mediastinal width in Hodgkin's disease, but rather factors such as patient selection and differences in treatment given may be responsible.

Background: Aneuploidy and S-phase fraction are well recognized prognostic features of solid tumors and non-Hodgkin's lymphoma. However, only limited data on Hodgkin's disease are available., Patients and Methods: In this study flow cytometric data on ploidy status and S-phase fraction are analyzed in relation to clinical characteristics and prognosis in 137 patients with Hodgkin's disease., Results: The presence of DNA aneuploidy was not associated with other clinical characteristics. When the histologic subtypes were clustered according to a higher number of Reed-Sternberg/Hodgkin cells into two classes (LP + NSI and the histologic NSII + MC + LD), it appeared that cases with an SPF > or = 7.5% had the histologic subtypes NSII + MC + LD significantly more frequently than those with an SPF < 7.5% (P = 0.001). There was no significant difference in complete remission rates, relapse-free or overall survivals between the patients with diploid and those with aneuploid lymph nodes. The complete remission rate for patients with and SPF < 7.5% was higher than for those with an SPF > or = 7.5%, 95% (56/59) and 76% (50/66), respectively (P = 0.006). The 10-year survival rate was 78% for patients with an SPF < 7.5% and 48% for those with an SPF > or = 7.5% (P = 0.04). However, by multivariate analysis only the ESR, age and clinical stage proved to be of independent prognostic importance., Conclusion: DNA aneuploidy did not correlate with known prognostic factors or survival, but the SPF might turn out to be an indicator of patients who will have less favourable outcomes.

Limited data regarding the cause of the age-related decrease in survival times in patients with Hodgkin disease are available. In a retrospective study of a nonselected population of patients with Hodgkin disease, the authors evaluated which factors contributed to the age-related prognostic effect in this disease. The survival curves of 182 patients were compared, and survival time was found to decrease markedly after the age of 50 years. Differences in disease characteristics between older and younger patients were small and not statistically significant. Significantly fewer older patients received adequate treatment (34% versus 2%), and they were less likely to have complete disease remission (61% versus 90%). However, the relapse-free survival time of patients with complete disease remission was not significantly different from that of younger patients, 50% of all patients being free of disease after 10 years. Intercurrent disease did not appear to be responsible for decreased survival times in the elderly (32% versus 26%). The authors conclude that the inability to give adequate treatment seems to be the major determinant of the poorer overall survival time of older patients with Hodgkin disease.

The usefulness of the pre-incubated acidified glycerol lysis test (AGLT), a laboratory test for spherocytosis, has been investigated in a selected hospital population of 348 patients with haemolytic and non-haemolytic anaemia. The AGLT was positive in 58 out of 59 patients with hereditary spherocytosis. In all 32 patients with other types of hereditary haemolytic anaemia the AGLT was normal or equivocal, but clearly different from spherocytosis. Adults with a positive AGLT, but without hereditary spherocytosis, had auto-immune haemolytic anaemia, myelodysplastic syndrome or were pregnant women. In newborn infants the AGLT was positive, in the first week of life, in those babies having hereditary spherocytosis or immune haemolysis due to blood group incompatibility; no positive AGLT results were seen if no haematological explanation for neonatal hyperbilirubinaemia could be found. At the optimal cut-off point the sensitivity of the AGLT for hereditary spherocytosis was 98.3% and the specificity 91.1%, under the most unfavourable conditions. The AGLT is a very useful and simple test for the diagnosis of hereditary spherocytosis.

The EORTC Lymphoma Cooperative Group and the Pierre and Marie Curie Group conducted a multicentre randomised trial on clinical stages IIIB-IV Hodgkin's disease from 1981-1986. Two hundred seven patients were registered and 192 randomised. Actuarial survival at five years for the whole group was 68%. Induction chemotherapy with eight cycles of MOPP resulted in more patients with progressive disease and fewer partial responders than a combination of MOPP and ABVD, for an equal complete remission rate. Half of the partial responders went into complete remission after radiotherapy. At five years there was no significant survival difference between the arms. Progression was recorded in 39 patients of whom only 4 survived. Relapses were most frequent in previously involved unirradiated areas. For 46 relapsed patients, including 21 early relapses within 18 months of start of treatment, the four-year survival rate was 53%. When complete remission was reached, whether early or late with combination chemotherapy or after additional radiotherapy, prognosis was independent of the way in which it was achieved. All efforts should be taken to reach a complete remission for initially progressing patients and for partial responders.

A new system is described for cooling the scalp with cold air in order to prevent chemotherapy-induced alopecia. Compressed air was cooled by means of a vortex tube built into a hair-drier cap. This system reduced the blood flow in the scalp to 35%, the surface temperature to 14.2 degrees C and the intradermal temperature at hair follicle level to 29.2 degrees C. The low temperature could be kept constant for at least one hour of cooling. By means of comparison, with cryogel packs the lowest epidermal temperature attained was 17.9 degrees C; moreover, once this was reached after 10 min, it rapidly rose again to 20.6 degrees C after 40 min. Forty-eight patients receiving cytostatic treatment for breast cancer were subjected to scalp cooling with the cold air system, starting 15 min before chemotherapy and lasting for 90 min. With the system set at an air temperature of -12 degrees C, the treatment was well tolerated. Of the 13 patients treated with 40 mg/m2 doxorubicin in combination with other cytostatics, 6 had hair loss less than WHO grade 3, in contrast to 1 of 4 patients given cryogel packs. However, patients treated with epirubicin at 75 mg/m2 all showed grade 3 hair loss in spite of air cooling. In view of the possibility of achieving and maintaining low scalp temperatures, the cold air system is to be preferred to cryogel packs. Whether better clinical results may be obtained with cooling for longer periods and/or to lower temperatures remains to be determined.

Chromosomal studies of the bone marrow and cultured peripheral blood cells in a 42-year-old female with the clinical and laboratory features typical for CML revealed a previously undescribed variant translocation involving chromosomes 12 and 22.

In this study we compared the results of the acidified glycerol lysis test, the Pink test and the osmotic fragility test in 38 patients with hereditary spherocytosis and in healthy controls. The sensitivity of the acidified glycerol lysis test was 81.6% when performed within 3 h after blood collection. After incubating for 24 h, the sensitivity increased to 100% whereas the specificity remained maximal. Similar incubation did not improve the diagnostic utility of the Pink test. All patients, but none of the controls, showed a positive osmotic fragility test. It is concluded, because of sensitivity and specificity in this study, that the acidified glycerol lysis test after incubation and the osmotic fragility test are superior to the Pink test in detecting spherocytosis.

A detailed classification of plasma cells stained for acid phosphatase activity is introduced. With this method, patients with multiple myeloma, non-myeloma gammopathies, reactive plasmacytosis and other diseases in which plasma cells are involved, were investigated. The results show that our method can discriminate between multiple myeloma and reactive plasmacytosis. The overlap between multiple myeloma and other monoclonal gammopathies is much smaller than observed in other studies. Surprisingly low levels of acid phosphatase activity were found in the cells from patients with lymphoplasmacytoid immunocytoma. It is concluded that the acid phosphatase score can be of value for studying disorders in which plasma cells are involved.

Subclassification of the nodular sclerosis (NS) type of Hodgkin's disease in Grade 1 and 2 was reported for the first time by the British National Lymphoma Investigation (BNLI). Three groups, the BNLI, Gärtner et al. and the current authors, found clearly different survival rates between Grade 1 and 2 NS patients. The authors studied retrospectively if this NS grading has an independent prognostic value in 90 NS patients, diagnosed in ten hospitals in the southeastern part of the Netherlands (1972-1983). In this study there is no significant difference in sex, age, B-symptoms, erythrocyte sedimentation rate (ESR), stage, positive laparotomy, involvement of mediastinum or spleen, lymphocyte count, and percentage of complete remissions between the NS subgroups. Multivariate analysis suggests that the subclassification of NS in Grades 1 and 2 is a prognostic factor in survival independent of age, stage and ESR. This finding and the high relative frequency of NS makes application of this NS subdivision probably clinically useful to identify patients for a risk-adapted therapy.

The results of a European Organization for Research and Treatment of Cancer (EORTC) retrospective study on non-Hodgkin's lymphoma (NHL) in elderly patients (greater than or equal to 70 years of age) seen in Europe in 1984 are reported. A precodified form was sent to 55 European institutes in order to evaluate the incidence of NHL in the elderly with regard to natural history, treatment-related toxicity, response, and survival. Thirteen institutes participated in the study. One hundred thirty-seven cases of NHL were observed in the elderly during 1984, making up 28% of the total number of NHL seen in those institutes. The median age was 77 years; 21% of the patients had favorable (low-grade) and 73% unfavorable (intermediate- and high-grade) histology, according to the Working Formulation. Stage at presentation was localized (I and II) in 60% and advanced in 37% of the patients. Most of the physicians used standard therapy regimens at reduced doses, from the beginning of the treatment. Sixty patients (44%) underwent a "conservative" treatment (one or two antineoplastic drugs or local field radiotherapy) and 77 (56%) an "aggressive" treatment (polychemotherapy regimens or extended field radiotherapy). Response was similar between the two treatment groups, but severe and lethal toxicity was significantly higher among patients treated with aggressive therapy. Prospective randomized studies are clearly needed to define the optimal treatment in elderly patients with advanced unfavorable NHL.

Retrospectively we observed an early-onset transient decrease in platelet counts in a group of patients treated with cisplatin, vinblastine and bleomycin. Though less pronounced, the decrease was also found in a prospectively studied group of patients treated with bleomycin, etoposide and cisplatin, but was absent after treatment with etoposide ad cisplatin. In a randomized cross-over study acetylsalicylic acid (ASA) appeared not to prevent the drop in platelet counts. Bleomycin appears to induce an early-onset transient decrease in platelet numbers, possibly by direct or indirect platelet lysis. Vinblastine may have a synergistic effect to this phenomenon.