Mars B Van't Veer

Publications (18)259.07 Total impact

• Article: Quality of life after successful treatment of early-stage Hodgkin's lymphoma: 10-year follow-up of the EORTC-GELA H8 randomised controlled trial.

  Natacha Heutte, Henning H Flechtner, Nicolas Mounier, Wilhelmina A M Mellink, Jacobus H Meerwaldt, Houchingue Eghbali, Mars B van't Veer, Evert M Noordijk, Johanna C Kluin-Nelemans, Elzbieta Lampka, [......], Oumédaly Reman, Hein P Muller, Jacques Troncy, Michel Blanc, Wilfried Schroyens, Paul J Voogt, Pierre Wijermans, Chantal Rieux, Christophe Fermé, Michel Henry-Amar
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  ABSTRACT: Little is known about the longitudinal course of health-related quality of life (HRQoL) in patients with Hodgkin's lymphoma during their post-treatment follow-up and re-adaptation to normal life. We report on the HRQoL of patients treated in the randomised H8 trial of the European Organisation for Research and Treatment of Cancer (EORTC) Lymphoma Group and the Groupe d'Etudes des Lymphomes de l'Adulte (GELA). We aimed to assess HRQoL and fatigue following treatment, to analyse relations with treatment, and to identify factors that predict persistent fatigue. Patients received HRQoL questionnaires at the end of primary therapy and during follow-up. The EORTC QLQ-C30 was used to assess HRQoL, and the Multidimensional Fatigue Inventory (MFI-20) was used to assess fatigue. Changes of mean HRQoL scores over time were analysed with mixed models. Multiple polytomic nominal logistic regression was done to identify independent baseline predictors of fatigue within MFI-20 dimensions. Analyses were done on an intention-to-treat basis. This study is registered with www.ClinicalTrials.gov, number NCT00379041. 2666 assessments from 935 patients were analysed. Mean follow-up was 90 months (range 52-118). Age affected all functioning and symptom scores except emotional functioning, with younger age associated with higher functioning and lower severity of symptoms; improvement with time showed similar patterns between age groups. Women reported lower HRQoL and higher symptom scores than did men. Overall, 3.2% (14/439 for role functioning) to 9.7% (43/442 for social functioning) and 5.8% (29/498 for reduced motivation) to 9.9% (49/498 for general fatigue) of patients reported impairments of 10 points or more (on a 0-100 scale) in QLQ-C30 and MFI-20 scores, respectively, independent of age and sex. Emotional domains were more affected than physical ones. There was no relation between HRQoL outcome and type of treatment. Fatigue (MFI-20 scores) at the end of treatment was the only predictive variable for persistent fatigue, with odds ratios varying from 2.58 (95% CI 1.00-6.67) to 41.51 (12.02-143.33; p</=0.0001). Sensitivity analyses adjusting for missing data were much the same as the main results. HRQoL data after treatment for early-stage Hodgkin's lymphoma show that patients experience strain and limitations in all subdomains apart from cognitive functioning (QLQ-C30), and also have reduced motivation (MFI-20). Differences in HRQoL improvement with time were linked to age and sex, but not type of treatment. Fatigue status at the end of treatment seems to predict subsequent HRQoL. French Ministry of Health, Programme Hospitalier de Recherche Clinique 1994, and French National League Against Cancer.
  The lancet oncology 10/2009; 10(12):1160-70. · 14.47 Impact Factor
• Article: Breast cancer risk in female survivors of Hodgkin's lymphoma: lower risk after smaller radiation volumes.

  Marie L De Bruin, Judith Sparidans, Mars B van't Veer, Evert M Noordijk, Marieke W J Louwman, Josée M Zijlstra, Hendrik van den Berg, Nicola S Russell, Annegien Broeks, Margreet H A Baaijens, Berthe M P Aleman, Flora E van Leeuwen
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  ABSTRACT: We assessed the long-term risk of breast cancer (BC) after treatment for Hodgkin's lymphoma (HL). We focused on the volume of breast tissue exposed to radiation and the influence of gonadotoxic chemotherapy (CT). We performed a cohort study among 1,122 female 5-year survivors treated for HL before the age of 51 years between 1965 and 1995. We compared the incidence of BC with that in the general population. To assess the risk according to radiation volume and hormone factors, we performed multivariate Cox regression analyses. After a median follow-up of 17.8 years, 120 women developed BC (standardized incidence ratio [SIR], 5.6; 95% CI, 4.6 to 6.8), absolute excess risk 57 per 10,000 patients per year. The overall cumulative incidence 30 years after treatment was 19% (95% CI, 16% to 23%); for those treated before age 21 years, it was 26% (95% CI, 19% to 33%). The relative risk remained high after prolonged follow-up (> 30 years after treatment: SIR, 9.5; 95% CI, 4.9 to 16.6). Mantle field irradiation (involving the axillary, mediastinal, and neck nodes) was associated with a 2.7-fold increased risk (95% CI, 1.1 to 6.9) compared with similarly dosed (36 to 44 Gy) mediastinal irradiation alone. Women with >or= 20 years of intact ovarian function after radiotherapy at young ages (< 31 years) experienced significantly higher risks for BC than those with fewer than 10 years of intact ovarian function. Reduction of radiation volume appears to decrease the risk for BC after HL. In addition, shorter duration of intact ovarian function after irradiation is associated with a significant reduction of the risk for BC.
  Journal of Clinical Oncology 09/2009; 27(26):4239-46. · 18.37 Impact Factor
• Article: Increased risk of stroke and transient ischemic attack in 5-year survivors of Hodgkin lymphoma.

  Marie L De Bruin, Lucille D A Dorresteijn, Mars B van't Veer, Augustinus D G Krol, Helena J van der Pal, Arnoud C Kappelle, Willem Boogerd, Berthe M P Aleman, Flora E van Leeuwen
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  ABSTRACT: Information on clinically verified stroke and transient ischemic attack (TIA) following Hodgkin lymphoma is scarce. We quantified the long-term risk of cerebrovascular disease associated with the use of radiotherapy and chemotherapy in survivors of Hodgkin lymphoma and explored potential pathogenic mechanisms. We performed a retrospective cohort study among 2201 five-year survivors of Hodgkin lymphoma treated before age 51 between 1965 and 1995. We compared incidence rates of clinically verified stroke and TIA with those in the general population. We used multivariable Cox regression techniques to study treatment-related factors and other risk factors. All statistical tests were two-sided. After a median follow-up of 17.5 years, 96 patients developed cerebrovascular disease (55 strokes, 31 TIAs, and 10 with both TIA and stroke; median age = 52 years). Most ischemic events were from large-artery atherosclerosis (36%) or cardioembolisms (24%). The standardized incidence ratio for stroke was 2.2 (95% confidence interval [CI] = 1.7 to 2.8), and for TIA, it was 3.1 (95% CI = 2.2 to 4.2). The risks remained elevated, compared with those in the general population, after prolonged follow-up. The cumulative incidence of ischemic stroke or TIA 30 years after Hodgkin lymphoma treatment was 7% (95% CI = 5% to 8%). Radiation to the neck and mediastinum was an independent risk factor for ischemic cerebrovascular disease (hazard ratio = 2.5, 95% CI = 1.1 to 5.6 vs without radiotherapy). Treatment with chemotherapy was not associated with an increased risk. Hypertension, diabetes mellitus, and hypercholesterolemia were associated with the occurrence of ischemic cerebrovascular disease, whereas smoking and overweight were not. Patients treated for Hodgkin lymphoma experience a substantially increased risk of stroke and TIA, associated with radiation to the neck and mediastinum. Physicians should consider appropriate risk-reducing strategies.
  CancerSpectrum Knowledge Environment 07/2009; 101(13):928-37. · 14.07 Impact Factor
• Article: Survival after Hodgkin lymphoma: causes of death and excess mortality in patients treated in 8 consecutive trials.

  Olav Favier, Natacha Heutte, Aspasia Stamatoullas-Bastard, Patrice Carde, Mars B Van't Veer, Berthe M P Aleman, Evert M Noordijk, José Thomas, Christophe Fermé, Michel Henry-Amar
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  ABSTRACT: The objective of this study was to analyze cause-specific excess mortality in adult patients with Hodgkin lymphoma (HL) with respect to treatment modality. The study population consisted of 4401 Belgian, Dutch, and French patients aged 15 to 69, in all stages of disease, who were treated between 1964 and 2000. Excess mortality was expressed by using a standardized mortality ratio (SMR) and calculating the absolute excess risk (AER). Relative survival was calculated and analyzed using a previously described regression model. At a median follow-up of 7.8 years, 725 of 4401 patients (16.5%) had died, 51% of HL, 10% of treatment-related toxicity, 18% of second cancer, 5% of cardiovascular diseases, 2% of infections, 8% of other causes, and 6% of an unspecified cause. Overall, the SMR was 7.4 (95% confidence limits [CL], 6.9-8.0), and the AER was 182.8 (95% CL, 167.7-198.8). These indicators were 3.8 (95% CL, 3.2-4.5) and 27.9, respectively, for deaths from a second cancer and 4.0 (95% CL, 2.3-6.7) and 3.3, respectively for deaths from infection. After 15 years, the observed survival rate was 75%, and the relative survival rate was 80%. In patients with early-stage disease, the overall excess mortality was associated with age > or =40 years (P = .007), men (P < .001), unfavorable prognosis features (P < .001), and 2 treatments: combined nonstandard nonalkylating chemotherapy plus involved-field radiotherapy (P = .002) and mantle-field irradiation alone (P = .003). With follow-up censored at the first recurrence, no treatment modalities were associated with excess mortality. Progressive disease remained the primary cause of death in patients with HL in the first decades after treatment. Excess mortality in patients with early-stage disease was linked significantly to treatment modalities that were associated with poor treatment failure-free survival.
  Cancer 02/2009; 115(8):1680-91. · 4.77 Impact Factor
• Article: Treatment-related risk factors for premature menopause following Hodgkin lymphoma.

  Marie L De Bruin, Jeannine Huisbrink, Michael Hauptmann, Marianne A Kuenen, Gabey M Ouwens, Mars B van't Veer, Berthe M P Aleman, Flora E van Leeuwen
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  ABSTRACT: We conducted a cohort-study among 518 female 5-year Hodgkin lymphoma (HL) survivors, aged 14 to 40 years (median: 25 years) at treatment (1965-1995). Multivariable Cox regression was used to quantify treatment effects on risk of premature menopause, defined as cessation of menses before age 40 years. After a median follow up of 9.4 years, 97 women had reached menopause before age 40 years. Chemotherapy was associated with a 12.3-fold increased risk of premature menopause compared with radiotherapy alone. Treatment with MOPP (mechlorethamine, vincristine, procarbazine, prednisone)/ABV (doxorubicine, bleomycine, vinblastine) significantly increased the risk of premature menopause (hazard ratio [HR]: 2.9), although to a lesser extent than MOPP treatment (HR: 5.7). Alkylating agents, especially procarbazine (HR: 8.1) and cyclophosphamide (HR: 3.5), showed the strongest associations. Ten years after treatment, the actuarial risk of premature menopause was 64% after high cumulative doses (> 8.4 g/m(2)) and 15% after low doses (<or= 4.2 g/m(2)) of procarbazine. The cumulative risk of menopause at age 40 years did not differ much according to age, but time to premature menopause was much longer in women treated at early ages. As long as alkylating agents will be used for curing HL, premature menopause will remain a frequent adverse treatment effect, with various clinical implications.
  Blood 01/2008; 111(1):101-8. · 9.90 Impact Factor
• Source

  Available from: Pieternella J Lugtenburg

  Article: Chemotherapy plus involved-field radiation in early-stage Hodgkin's disease.

  Christophe Fermé, Houchingue Eghbali, Jacobus H Meerwaldt, Chantal Rieux, Jacques Bosq, Françoise Berger, Théodore Girinsky, Pauline Brice, Mars B van't Veer, Jan A Walewski, [......], José Thomas, Brigitte Vié, Johanna C Kluin-Nelemans, Fernando Viseu, Joke W Baars, Philip Poortmans, Pieternella J Lugtenburg, Christian Carrie, Jérôme Jaubert, Michel Henry-Amar
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  ABSTRACT: Treatment of early-stage Hodgkin's disease is usually tailored in line with prognostic factors that allow for reductions in the amount of chemotherapy and extent of radiotherapy required for a possible cure. From 1993 to 1999, we identified 1538 patients (age, 15 to 70 years) who had untreated stage I or II supradiaphragmatic Hodgkin's disease with favorable prognostic features (the H8-F trial) or unfavorable features (the H8-U trial). In the H8-F trial, we compared three cycles of mechlorethamine, vincristine, procarbazine, and prednisone (MOPP) combined with doxorubicin, bleomycin, and vinblastine (ABV) plus involved-field radiotherapy with subtotal nodal radiotherapy alone (reference group). In the H8-U trial, we compared three regimens: six cycles of MOPP-ABV plus involved-field radiotherapy (reference group), four cycles of MOPP-ABV plus involved-field radiotherapy, and four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The median follow-up was 92 months. In the H8-F trial, the estimated 5-year event-free survival rate was significantly higher after three cycles of MOPP-ABV plus involved-field radiotherapy than after subtotal nodal radiotherapy alone (98% vs. 74%, P<0.001). The 10-year overall survival estimates were 97% and 92%, respectively (P=0.001). In the H8-U trial, the estimated 5-year event-free survival rates were similar in the three treatment groups: 84% after six cycles of MOPP-ABV plus involved-field radiotherapy, 88% after four cycles of MOPP-ABV plus involved-field radiotherapy, and 87% after four cycles of MOPP-ABV plus subtotal nodal radiotherapy. The 10-year overall survival estimates were 88%, 85%, and 84%, respectively. Chemotherapy plus involved-field radiotherapy should be the standard treatment for Hodgkin's disease with favorable prognostic features. In patients with unfavorable features, four courses of chemotherapy plus involved-field radiotherapy should be the standard treatment. (ClinicalTrials.gov number, NCT00379041 [ClinicalTrials.gov].).
  New England Journal of Medicine 11/2007; 357(19):1916-27. · 53.30 Impact Factor
• Source

  Available from: haematologica.com

  Article: The predictive value of lipoprotein lipase for survival in chronic lymphocytic leukemia.

  Mars B van't Veer, Anne M Brooijmans, Anton W Langerak, Brenda Verhaaf, Chantal S Goudswaard, Wilfried J Graveland, Kirsten van Lom, Peter J M Valk
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  ABSTRACT: The mutational status of the immunoglobulin heavy chain variable region genes (IGVH) is a strong indicator of prognosis in B-cell chronic lymphocytic leukaemia (CLL). Since the determination of the IGVH mutation status is very labor-intensive, alternative prognostically relevant markers would facilitate CLL diagnostics. Ten genes were selected from previously published gene expression profiling studies based on their differential expression in IGVH mutated versus unmutated cases of CLL, and tested with real-time quantitative polymerase chain reaction (RQ-PCR) in unpurified samples from 130 CLL patients. To ascertain potential contaminating effects by normal hematopoietic cells, the expression levels of the selected genes were determined in normal monocytes, B cells, T cells, NK cells and granulocytes. The selected genes, i.e., ZAP70, LPL, SPG20, ADAM29, NRIP1, AKAP12, DMD, SEPT10, TPM2 and CLECSF2, showed prognostic significance. In multivariate logistic regression analysis expression levels of LPL, ZAP70, ADAM29 and SEPT10 were the most predictive for IGVH mutational status. In univariate analysis the expression of LPL was the best predictor. For survival, expression of LPL was the strongest prognostic factor. In combination with the three cytogenetic markers associated with a poor prognosis, i.e., deletions 17p13, 11q22 and trisomy 12, expression of LPL and IGVH mutational status performed equally well with regard to their predictive value for survival, both being more predictive than ZAP70. This study demonstrates that LPL expression is a predictor for survival in CLL, and for this purpose is as good as IGVH mutational status and more reliable than ZAP70 expression when tested in unpurified CLL samples.
  Haematologica 02/2006; 91(1):56-63. · 6.42 Impact Factor
• Article: Optimal treatment of premature ovarian failure after treatment for Hodgkin's lymphoma is often withheld.

  Sylvia I Verschuuren, Jiska J Schaap, Mars B Van't Veer, Theo Stijnen, Curt W Burger, Anca C Ansink
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  ABSTRACT: The purpose of this study is to determine: 1. the effect of treatment for Hodgkin's lymphoma on ovarian function, and 2. the interventions to relieve postmenopausal symptoms. Seventy-seven consecutive patients treated between 1989 and 2003 in the Rotterdam region for Hodgkin's lymphoma stages I and II were approached for this study. A questionnaire consisting of 45 questions was carried out to evaluate premature menopausal symptoms, hormonal replacement therapy and use of contraception, menstrual cycle, and subsequent pregnancies. After informed consent 67 patients were willing to participate in the study and 66 patients filled in a questionnaire. After antitumor treatment 13 patients developed treatment-related premature ovarian failure, 35 patients had a spontaneous cycle, and 18 patients could not be classified as they used hormonal contraception. Women who developed treatment-related premature ovarian failure had a significantly higher mean age at the start of treatment for Hodgkin's lymphoma than women who remained premenopausal (p < 0.002). Only 6 of these 13 women (46%) received hormonal substitution. In all, 21 women conceived after antitumor treatment, and 28 children were born. All pregnancies were the result of spontaneous conception. The effect of antitumor treatment for Hodgkin's lymphoma on ovarian function is age dependent (odds ratio of 1.18 per year). There is a striking inconsistency regarding the management of ovarian protection before and during antitumor treatment. Premenopausal women who undergo therapy for Hodgkin's lymphoma should be offered hormonal substitution therapy after loss of ovarian function.
  Acta Obstetricia Et Gynecologica Scandinavica 01/2006; 85(8):997-1002. · 1.77 Impact Factor
• Article: Resolution of EBV(+) CNS lymphoma with appearance of CSF EBV-specific T cells.

  Janet W de Beukelaar, Cornelis van Arkel, Martin J van den Bent, Mars B van't Veer, Gerard J van Doornum, Jan J Cornelissen, Peter A Sillevis Smitt, Jan W Gratama
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  ABSTRACT: Current knowledge of Epstein-Barr virus (EBV)-specific T-cell responses in the cerebrospinal fluid (CSF) of patients with EBV-related lymphoproliferative disease (EBV-LPD) in the central nervous system (CNS) is very limited. Here, we present two recipients of hematopoietic stem cell transplants with EBV-LPD in the CNS. EBV-specific CD8(+) T lymphocytes were detected in CSF and peripheral blood using major histocompatibility complex (MHC) class I multimers loaded with EBV-derived peptides. The appearance of EBV-specific CD8(+) T cells in CSF and blood correlated with neurological improvement and disappearance of EBV-LPD. These observations suggest a role for EBV-specific CD8(+) T cells in the control of EBV-LPD in the CNS.
  Annals of Neurology 12/2005; 58(5):788-92. · 11.09 Impact Factor
• Article: Cumulative absolute breast cancer risk for young women treated for Hodgkin lymphoma.

  Lois B Travis, Deirdre Hill, Graça M Dores, Mary Gospodarowicz, Flora E van Leeuwen, Eric Holowaty, Bengt Glimelius, Michael Andersson, Eero Pukkala, Charles F Lynch, David Pee, Susan A Smith, Mars B Van't Veer, Timo Joensuu, Hans Storm, Marilyn Stovall, John D Boice, Ethel Gilbert, Mitchell H Gail
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  ABSTRACT: Many women develop breast cancer after treatment for Hodgkin lymphoma (HL) at a young age. We estimated this future risk, taking into account age and calendar year of HL diagnosis, HL treatment information, population breast cancer incidence rates, and competing causes of death. Relative risks of breast cancer for categories defined by radiation dose to the chest (0, 20- < 40 Gy, or > or = 40 Gy) and use of alkylating agents (yes or no) were estimated from a case-control study conducted within an international population-based cohort of 3817 female 1-year survivors of HL diagnosed at age 30 years or younger from January 1, 1965, through December 31, 1994. To compute cumulative absolute risks of breast cancer, we used modified standardized incidence ratios to relate cohort breast cancer risks to those in the general population, enabling application of population-based breast cancer rates, and we allowed for competing risks by using population-based mortality rates in female HL survivors. Cumulative absolute risks of breast cancer increased with age at end of follow-up, time since HL diagnosis, and radiation dose. For an HL survivor who was treated at age 25 years with a chest radiation dose of at least 40 Gy without alkylating agents, estimated cumulative absolute risks of breast cancer by age 35, 45, and 55 years were 1.4% (95% confidence interval [CI] = 0.9% to 2.1%), 11.1% (95% CI = 7.4% to 16.3%), and 29.0% (95% CI = 20.2% to 40.1%), respectively. Cumulative absolute risks were lower in women treated with alkylating agents. Breast cancer projections varied considerably by type of HL therapy, time since HL diagnosis, and age at end of follow-up. These estimates are applicable to HL survivors treated with regimens of the past and can be used to counsel such patients and plan management and preventive strategies. Projections should be used with caution, however, in patients treated with more recent approaches, including limited-field radiotherapy and/or ovary-sparing chemotherapy.
  CancerSpectrum Knowledge Environment 10/2005; 97(19):1428-37. · 14.07 Impact Factor
• Article: Impact of three courses of intensified CHOP prior to high-dose sequential therapy followed by autologous stem-cell transplantation as first-line treatment in poor-risk, aggressive non-hodgkin's lymphoma: comparative analysis of Dutch-Belgian Hemato-Oncology Cooperative Group Studies 27 and 40.

  Gustaaf W van Imhoff, Bronno van der Holt, Marius A Mackenzie, Mars B Van't Veer, Pierre W Wijermans, Gerrit J Ossenkoppele, Harry C Schouten, Pieter Sonneveld, Monique M C Steijaert, Philip M Kluin, Hanneke C Kluin-Nelemans, Leo F Verdonck
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  ABSTRACT: Timing, appropriate amount, and composition of treatment before high-dose therapy and autologous stem-cell transplantation (ASCT) in patients with poor-risk, aggressive non-Hodgkin's lymphoma (NHL) are still unknown. We conducted two consecutive multicenter phase II trials with up-front, high-dose, sequential chemotherapy and ASCT in poor-risk, aggressive NHL. Both trials had identical inclusion criteria and only differed in amount and duration of induction treatment before ASCT. Between 1994 and 2001, 147 newly diagnosed, poor-risk, aggressive NHL patients, age < or = 65 years with stage III to IV and lactate dehydrogenase (LDH) more than 1.5x upper limit of normal (ULN), entered the Dutch-Belgian Hemato-Oncology Cooperative Group (HOVON) -27 and HOVON-40 trials. Treatment in HOVON-27 consisted of two up-front, high-dose induction courses followed by carmustine, etoposide, cytarabine, and melphalan plus ASCT in responding patients. In HOVON-40, the same treatment was preceded by three intensified courses of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP). Patient characteristics in both trials were comparable: 80% had diffuse large B-cell lymphoma, 77% had stage IV disease, and median LDH levels were 3.1x ULN. Complete remission (CR) in both trials was 45% to 51%. Before ASCT, CR was 14% in HOVON-27 versus 28% in HOVON-40 (P = .03). Treatment failure was similar (27%). Four-year survival estimates in HOVON-27 compared with HOVON-40 were overall survival, 21% v 50% (P = .007); event-free survival, 15% v 49% (P = .0001); and disease-free survival, 34% v 74% (P = .008). This different outcome favoring HOVON-40 remained highly significant when correcting for competing risk factors in multivariate analysis. In patients with poor-risk, aggressive NHL, addition of intensified CHOP before up-front, high-dose, sequential therapy and ASCT significantly improved the duration of response and survival.
  Journal of Clinical Oncology 06/2005; 23(16):3793-801. · 18.37 Impact Factor
• Article: Intracranial granulocytic sarcoma (chloroma) may mimic a subdural hematoma.

  Martijn H Smidt, Hein G de Bruin, Mars B van't Veer, Martin J van den Bent
  Journal of Neurology 05/2005; 252(4):498-9. · 3.47 Impact Factor
• Article: The value of alloantibody detection in predicting response to HLA-matched platelet transfusions.

  Mark-David Levin, Mies Kappers-Klunne, Kees Sintnicolaas, Bronno van der Holt, Huub H D M van Vliet, Bob Löwenberg, Mars B van't Veer
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  ABSTRACT: Alloantibody tests demonstrate immunological causes of insufficient increments in random platelet transfusions. The value of a positive or negative test result in predicting the outcome of human leucocyte antigen (HLA)-matched transfusions in patients refractory to leucodepleted random platelet transfusions has not been assessed. We retrospectively evaluated the outcome of the first HLA-matched platelet transfusion in 72 patients with haematological diseases in two ways: first, the strategy according to which the patient was selected for HLA-matched platelet transfusions was analysed. The strategies were: (i) results of alloantibody tests were not available, (ii) a positive alloantibody test, (iii) a negative alloantibody test. Secondly, the outcome of the first HLA-matched transfusion was investigated relative to the results of alloantibody tests, irrespective of the decision strategy. No significant association was found between the decision strategy and the outcome of the first HLA-matched platelet transfusion. Positive alloantibody tests, however, predicted a better outcome of the first HLA-matched platelet transfusion (P = 0.04 and P = 0.03 after 1 and 16 h respectively). In patients refractory to random platelet transfusions, positive alloantibody tests predicted a better outcome of HLA-matched platelet transfusions. Patients with negative alloantibody tests, however, may benefit from HLA-matched platelet transfusions.
  British Journal of Haematology 02/2004; 124(2):244-50. · 4.94 Impact Factor
• Article: Long-term cause-specific mortality of patients treated for Hodgkin's disease.

  Berthe M P Aleman, Alexandra W van den Belt-Dusebout, Willem J Klokman, Mars B Van't Veer, Harry Bartelink, Flora E van Leeuwen
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  ABSTRACT: To assess long-term cause-specific mortality of young Hodgkin's disease (HD) patients. The study population consisted of 1,261 patients treated for HD before age 41 between 1965 and 1987. Follow-up was complete until October 2000. For 95% of deaths, the cause was known. Long-term cause-specific mortality was compared with general population rates to assess relative risk (RR) and absolute excess risk (AER) of death. After a median follow-up of 17.8 years, 534 patients had died (55% of HD). The RR of death from all causes other than HD was 6.8 times that of the general population, and still amounted to 5.1 after more than 30 years. RRs of death resulting from solid tumors (STs) and cardiovascular disease (CVD) were increased overall (RR = 6.6 and 6.3, respectively), but especially in patients treated before age 21 (RR = 14.8 and 13.6, respectively). When these patients grew older, this elevated mortality decreased. The overall AER of death from causes other than HD increased throughout follow-up. Patients receiving salvage chemotherapy had a significantly increased RR of death from STs, compared to patients receiving initial therapy only. The main cause of death among HD patients was lymphoma, but after 20 years, HD mortality was negligible. The RRs and AERs of death from second primary cancers (SCs) and CVDs continued to increase after 10 years. Even more than 30 years after diagnosis, HD patients experienced elevated risk of death from all causes other than HD. Increased risk of death from SCs and CVDs was found especially in patients treated before age 21, but these risks seemed to abate with age.
  Journal of Clinical Oncology 10/2003; 21(18):3431-9. · 18.37 Impact Factor
• Article: Roles of radiation dose, chemotherapy, and hormonal factors in breast cancer following Hodgkin's disease.

  Flora E van Leeuwen, Willem J Klokman, Marilyn Stovall, Ellen C Dahler, Mars B van't Veer, Evert M Noordijk, Mariad A Crommelin, Berthe M P Aleman, Annegien Broeks, Mary Gospodarowicz, Lois B Travis, Nicola S Russell
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  ABSTRACT: Female survivors of Hodgkin's disease (HD) have a strongly elevated risk of breast cancer, but factors responsible for the increased risk are not well known. We investigated the effects of radiation dose, chemotherapy (CT), and reproductive factors on breast cancer risk in a nested case-control study in The Netherlands in a cohort of 770 female patients who had been diagnosed with HD before age 41. Detailed treatment information and data on reproductive factors were collected for 48 case patients who developed breast cancer 5 or more years after diagnosis of HD and 175 matched control subjects. The radiation dose was estimated to the area of the breast where the case patient's tumor had developed and to a comparable location in matched control subjects. Relative risks (RRs) of breast cancer were calculated by conditional logistic regression. Statistical tests were two-sided. The risk of breast cancer increased statistically significantly with radiation dose (P(trend) =.01); patients who received 38.5 Gy or more had an RR of 4.5 (95% confidence interval [CI] = 1.3 to 16) times that of patients who received less than 4 Gy. Patients who received both CT and radiotherapy (RT) had a statistically significantly lower risk than those treated with RT alone (RR = 0.45, 95% CI = 0.22 to 0.91). Breast cancer risk increased with increasing radiation dose among patients who received RT only (RR = 12.7, 95% CI = 1.8 to 86, for patients receiving > or =38.5 Gy) but not among patients treated with CT and RT. Sixty-nine percent of control subjects treated with RT and more than six cycles of CT, but only 9% of those who received RT alone, reached menopause before age 41. Reaching menopause before age 36 was associated with a strongly reduced risk of breast cancer (RR = 0.06, 95% CI = 0.01 to 0.45). Breast cancer risk increases with increasing radiation dose up to at least 40 Gy. The substantial risk reduction associated with CT may reflect its effect on menopausal age, suggesting that ovarian hormones promote tumorigenesis after radiation has produced an initiating event.
  CancerSpectrum Knowledge Environment 07/2003; 95(13):971-80. · 14.07 Impact Factor
• Source

  Available from: Eric Holowaty

  Article: Breast cancer following radiotherapy and chemotherapy among young women with Hodgkin disease.

  Lois B Travis, Deirdre A Hill, Graça M Dores, Mary Gospodarowicz, Flora E van Leeuwen, Eric Holowaty, Bengt Glimelius, Michael Andersson, Tom Wiklund, Charles F Lynch, Mars B Van't Veer, Ingrid Glimelius, Hans Storm, Eero Pukkala, Marilyn Stovall, Rochelle Curtis, John D Boice, Ethel Gilbert
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  ABSTRACT: Second cancer is the leading cause of death in long-term survivors of Hodgkin disease (HD), with exceptionally high risks of breast cancer among women treated at a young age. Quantitative associations between radiotherapy dose delivered to the breast and administered chemotherapy have not been reported to date in large series, nor has the influence of ovarian exposures on subsequent risk. To quantify the long-term risk of breast cancer associated with use of radiotherapy and chemotherapy to treat young women with HD. Matched case-control study of breast cancer within a cohort of 3817 female 1-year survivors of HD diagnosed at age 30 years or younger, between January 1, 1965, and December 31, 1994, and within 6 population-based cancer registries. The study was conducted March 1, 1996, through September 30, 1998. Relative risk (RR) of breast cancer associated with radiation dose delivered to site of breast cancer or to ovaries and with cumulative dose of alkylating agents. Breast cancer occurred in 105 patients with HD who were matched to 266 patients with HD but without breast cancer. A radiation dose of 4 Gy or more delivered to the breast was associated with a 3.2-fold (95% confidence interval [CI], 1.4-8.2) increased risk, compared with the risk in patients who received lower doses and no alkylating agents. Risk increased to 8-fold (95% CI, 2.6-26.4) with a dose of more than 40 Gy (P<.001 for trend). Radiation risk did not vary appreciably by age at exposure or reproductive history. Increased risks persisted for 25 or more years following radiotherapy (RR, 2.3; 95% CI, 0.5-16.5; P =.03 for trend with dose). Treatment with alkylating agents alone resulted in a reduced risk (RR, 0.6; 95% CI, 0.2-2.0) of breast cancer, and combined alkylating agents and radiotherapy in a 1.4-fold (95% CI, 0.6-3.5) increased risk. Risk of breast cancer decreased with increasing number of alkylating agent cycles (P =.003 for trend). Risk also was low (RR, 0.4; 95% CI, 0.1-1.1) among women who received 5 Gy or more delivered to ovaries compared with those who received lower doses. Hormonal stimulation appears important for the development of radiation-induced breast cancer, as evidenced by the reduced risk associated with ovarian damage from alkylating agents or radiation. The high radiation-related risk, which did not diminish at the highest doses or the longest follow-up, however, suggests the need for lifetime surveillance and programs of patient and public awareness.
  JAMA The Journal of the American Medical Association 07/2003; 290(4):465-75. · 30.03 Impact Factor
• Article: Screening for alloantibodies in the serum of patients receiving platelet transfusions: a comparison of the ELISA, lymphocytotoxicity, and the indirect immunofluorescence method.

  Mark-David Levin, Jos C de Veld, Bronno van der Holt, Mars B van't Veer
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  ABSTRACT: For screening of alloimmunization in patients repeatedly receiving platelet transfusions, different tests are used, none of which is the standard. Here we describe a comparison of four tests most commonly used for detection of alloimmunization in a group of nonselected patients receiving platelet transfusions. In 99 patients with hematologic malignancies who received platelet transfusions, 192 random serum samples were tested in the ELISA, the lymphocytotoxic test (LCT), the lymphocyte immunofluorescence test (LIFT), and the platelet immunofluorescence test (PIFT). Results of all tests were compared. The results of all tests were significantly correlated with each other (p < 0.005). ELISA and LIFT were more often positive than LCT and PIFT. ELISA and LIFT showed the best correlation (chi-square test = 63.7, p < 0.001). ELISA, the least time-consuming test, detects alloimmunization as often as LIFT and more often than LCT and PIFT.
  Transfusion 01/2003; 43(1):72-7. · 3.22 Impact Factor
• Article: Second malignant neoplasms among long-term survivors of Hodgkin's disease: a population-based evaluation over 25 years.

  Graça M Dores, Catherine Metayer, Rochelle E Curtis, Charles F Lynch, E Aileen Clarke, Bengt Glimelius, Hans Storm, Eero Pukkala, Flora E van Leeuwen, Eric J Holowaty, Michael Andersson, Tom Wiklund, Timo Joensuu, Mars B van't Veer, Marilyn Stovall, Mary Gospodarowicz, Lois B Travis
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  ABSTRACT: To quantify the relative and absolute excess risks (AER) of site-specific second cancers, in particular solid tumors, among long-term survivors of Hodgkin's disease (HD) and to assess risks according to age at HD diagnosis, attained age, and time since initial treatment. Data from 32,591 HD patients (1,111 25-year survivors) reported to 16 population-based cancer registries in North America and Europe (1935 to 1994) were analyzed. Two thousand one hundred fifty-three second cancers (observed-to-expected ratio [O/E] = 2.3; 95% confidence interval [CI] = 2.2 to 2.4), including 1,726 solid tumors (O/E = 2.0; 95% CI, 1.9 to 2.0) were reported. Cancers of the lung (observed [Obs] = 377; O/E = 2.9), digestive tract (Obs = 376; O/E = 1.7), and female breast (Obs = 234; O/E = 2.0) accounted for the largest number of subsequent malignancies. Twenty-five years after HD diagnosis, the actuarial risk of developing a solid tumor was 21.9%. The relative risk of solid neoplasms decreased with increasing age at HD diagnosis, however, patients aged 51 to 60 years at HD diagnosis sustained the highest cancer burden (AER = 79.2/10,000 patients/year). After a progressive rise in relative risk and AER of all solid tumors over time, there was an apparent downturn in risk at 25 years. Temporal trends and treatment group distribution for cancers of the esophagus, stomach, rectum, female breast, bladder, thyroid, and bone/connective tissue were suggestive of a radiogenic effect. Significantly increased risks of second cancers were observed in all HD age groups. Although significantly elevated risks of stomach, female breast, and uterine cervix cancers persisted for 25 years, an apparent decrease in relative risk and AER of solid tumors at other sites is suggested.
  Journal of Clinical Oncology 09/2002; 20(16):3484-94. · 18.37 Impact Factor