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  • 1
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 5485-5485
    Abstract: INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) is an effective treatment for malignant and nonmalignant diseases. Improved long-term survival after HSCT translates into coming across secondary neoplasms. Contributory factors include primary disease, male sex, young age, prior therapies, conditioning regimens. The secondary neoplasms are particularly solid tumors, as well as lymphoproliferative disorders. Chronic graft-versus-host disease (GvHD) and immunosupressive therapy have also been reported to contribute to neoplasia risk. OBJECTIVE: The purpose of this study was to evaluate the frequency and distribution of the posttransplant secondary neoplasms in our center, to determine the possible contributory factors and relative effect of GvHD. METHODS: From 457 patients who received a HSCT between 1994-2014 clinical records of 312 patients were available to review retrospectively. 21 patients diagnosed with a secondary neoplasia in the posttransplant period are included in the study. Age, sex, primary diagnosis and treatment, time of HSCT, GvHD and immunosupressive treatments, localisation of neoplasms and outcomes were reported. RESULTS: Twenty-one cases of secondary neoplasms were observed (%6,7). The median age at diagnosis and transplantation were 44 and 47, respectively. The median follow-up time was 122 months (32-304). The most common primary diagnosis was Hodgkin's disease (HD). The most commonly used pretransplant conditioning regimen was BEAM. There were no cases of acute GvHD, chronic GvHD was observed in 3 cases. The most common secondary neoplasm was skin cancer followed by urogenital system cancers. The secondary malignancies seen in cases with chronic GvHD are concordant with GvHD sites. Three patients had benign neoplasms comprising fibroadenoma, mol hydatiforme and hibernoma; 2 patients developed preinvasive lesions of vulva (VIN 3) and oral cavity (squamous papilloma). For 20 patients the median time interval between the date of HSCT and diagnosis of a secondary neoplasia is 62 months (5-118); data is missing for 1 case. Two deaths were observed, 1 due to disease progression, 1 due to secondary colorectal malignancy. %90,4 of the study group are alive and in remission. Details are listed in Table 1 and 2. CONCLUSION: Patients undergoing HSCT have an increased risk of secondary cancers later in life. Known risk factors are primary disease, age at transplantation, pretransplant therapies, pretransplant conditioning regimens like total body irradiation, chronic GvHD and immunosuppressive therapies. Our study group is small to comment on these risk factors. Coherent with the literature skin cancer was the most common secondary cancer in our cohort as well. Interestingly we observed a trend towards increased urogenital cancers in comparison to reported data. This finding can be incidental because of the small number of study population or needs to be clarified yet. The increased risk of secondary neoplasms over time after transplantation and the greater risk among younger patients indicate the need for lifelong surveillance. Table 1 Characteristics of patients with secondary neoplasms after HSCT Characteristic n (%) Sex Female 10 (%47) Male 11 (%53) Primary diagnosis Acute myeloid leukemia 1 (%4,7) Acute lymphoblastic leukemia 3 (%14,3) Chronic myelogeneous leukemia 3 (%14,3) Multiple Myeloma 5 (%23,8) Hodgkin’s disease 6 (%28,6) Non-Hodgkin’s lymphoma 3 (%14,3) Prior therapy Chemotherapy 9 (%42,7) Chemoimmunotherapy 3 (%14,3) Chemoradiotherapy 5 (%23,7) Combination treatment* 3 (%14,3) Type of HSCT Allogeneic 5 (%23,8) Related 5 Unrelated 1 Autologous 15(%71,5) Both 1(%4,7) Conditioning regimens TBI+Cy 3 (%14,3) BEAM 8 (% 38,1) MEL 6 (% 28,6) BU+Cy 2 (% 9,5) Unknown 2 (%9,5) Acute GvHD 0 Chronic GvHD 3 (%14,3) Skin 3 Oral cavity 2 Eye 2 Pulmonary 1 Hepatic 1 Acute GvHD prophylaxis 7 (%33,3)  CsA 1 MTX+CsA 6 Chronic GvHD treatment 3 (14,3) Steroid+CsA 2 CsA 1 Table 2 Characteristics and risk factors of patients who had secondary malignancy undergoing HSCT Breast Skin GIS Urogenital Lung Lymphoma Risk factors (n:2) (n:6) (n:2) (n:3) (n:2) (n:1) Prior therapy Chemotherapy 0 4 0 2 1 0 Chemoimmunotherapy 1 1 1 1 0 0 Chemoradiotherapy 1 0 0 0 1 1 Combination 0 1 1 0 0 0 Allogeneic Related 1 3 0 1 0 0 Unrelated 0 1 0 0 0 0 Autologous 1 3 2 2 2 1 TBI+Cy 0 1 0 0 0 0 BEAM 1 2 1 0 1 1 MEL 0 1 1 2 1 0 BU+Cy 0 1 0 1 0 0 Unknown 1 1 0 0 0 0 Chronic GvHD 0 2 0 0 0 0 Sex Female 2 2 2 1 0 0 Male 0 4 0 2 2 1 Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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  • 2
    In: Blood, American Society of Hematology, Vol. 126, No. 23 ( 2015-12-03), p. 4685-4685
    Abstract: Introduction: Recent studies indicate an increased risk for developing low bone mineral density (BMD) in patients with haemophilia. This has been suggested to result from less physical activity, and impaired vitamin D metabolism due to viral liver disease. Here we present the preliminary results of an ongoing study aiming to identify the risk factors for impaired bone health in adult haemophilia patients. Material and Method: Twenty-nine severe and 7 moderate haemophilia A and B patients were included in the study. Patient characteristics were given in Table-1. All patients had haemophilic arthropathy in ≥1 joints and were on prophylactic factor replacement therapy except 2 on demand patients. None of the patients had decompensated chronic liver disease. Eleven patients had a history of joint intervention (RAS or joint replacement). None of the patients had received on vitamin D supplementation. DEXA scans to screen BMD, blood chemical analysis including liver and kidney function tests, vit. D (25 hydroxy vitamin D) calcium, parathormone, alkaline phosphatase were obtained from all patients at study entry. Results: Osteoporosis and/or osteopenia according to WHO criteria were detected by DEXA scans in 2/3 of the patients. Twenty-six patients (72%) had vit. D levels below 20ng/mL, with half of them having levels less than 10ng/mL. Median lumbar and femur T scores were in the osteopenia range, being -1.2 and -2.2, respectively. Osteoporosis/penia rates and vit. D levels did not significantly differ between patients with severe and moderate haemophilia. However, patients with severe haemophilia had lower lumbar T scores (p=0.048) and seemed to acquire low BMD 2 times more likely than moderate haemophiliacs. Patients with a history of joint intervention had significantly lower vit. D levels (p=0.005) and 1.4 times more risk for low BMD. Conclusion: Preliminary results of our study are in line with the recent literature indicating an increased frequency for osteopenia and osteoporosis in patients with haemophilia. Despite their young age our cohort of patients had lower BMD and vitamin D levels than the age-matched healthy population. This is an interesting finding in a country like Turkey where the average yearly total number of hours of bright sunshine is over 3000. Data at hand suggest increased risk for reduced BMD especially in severe haemophiliacs with impaired joint mobility. The most probable underlying cause for reduced BMD seems to be haemophilic arthropathy related inactivity. Furthermore, impaired bone health seems to be partially associated with less sunlight exposure, which is probably a result of increased home confinement of patients with haemophilia due to joint disease. The study is still recruiting. We hope to clarify other questions regarding factors influencing bone health in haemophiliacs when the study is completed and additional data on radiological and physical examination as well as on quality of life are obtained. Table. Patient Characteristics (n=36) Age, years (median [range]) 35 [20 - 55] Type of haemophilia ( A/B), n 32/4 Genotype (severe/moderate), n 29/7 Factor activity level, % (median [range]) 0.4 [0.1 - 4.2] Type of treatment (prophylaxis/on demand) 34/2 Annual bleeding rate (median [range]) 4 [1 - 12] Joint replacement, number of patients (%) 7 (19) Radioactive synoviectomy, number of patients (%) 7 (19) Any joint intervention, number of patients (%) 11 (30.5) Lumbar T scores (median [range]) -1.2 [-5.2 - 1] Femur T scores (median [range]) -2.2 [-3.9 - 0.6] Vit. D, ng/mL (median [range]) 10.5 [1.3 - 45] Calcium, mg/dL (median [range]) 9.6 [8.9 - 10.2] Alkaline phosphatase, U/L (median [range]) 91.5 [53 - 177] Parathormon, pg/mL (median [range]) 39 [20 - 179] Haemoglobin, g/dL (median [range]) 14.75 [8.9 - 16] Osteopenia, number of patients (%) 12 (33) Osteoporosis, number of patients (%) 12 (33) HBV/HCV/HIV, n 1/11/0 Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2015
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    detail.hit.zdb_id: 80069-7
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  • 3
    In: Blood, American Society of Hematology, Vol. 134, No. Supplement_1 ( 2019-11-13), p. 4933-4933
    Abstract: Background: Management of surgical procedures in people with hemophilia (PwH) has always been a major concern. Insufficient hemostatic control might be an important cause of morbidity and mortality. However, the success of surgical procedures does not only depend on appropriate replacement of the missing factor. Pre- and post-operative interventions, laboratory monitoring, care and rehabilitation of the patient are important. Therefore, surgical procedures in hemophilia patients should be performed in full-fledged hospitals capable of providing a multidisciplinary approach as a "Comprehensive Hemophilia Treatment Center". The aim of our study is to evaluate the outcomes of major surgical procedures (MSPs) among PwH who were followed at Cerrahpasa Medical Faculty. Methods: All MSPs performed on PwH between 2004 and 2017 were included. Baseline activated partial thromboplastin time (aPTT)and factor levels prior to MSP, inhibitor screening and (if any) the inhibitor titration results together with complete blood count, blood group and liver function tests were retrospectively obtained from patient files. The type of MSP, amount of factor concentrates given prior to, during and after the operation, the factor levels and aPTT results following factor replacement; complications developing during or after surgery, and information on the type of treatment modality prior to surgery (on demand vs. prophylaxis) were noted. The amount of factor concentrates administered to patients was determined in units per kilogram. Results: Of the 39 patients included in the study (37 hemophilia A and two hemophilia B) 20 were severe, 7 were moderate and 12 were mild hemophilia (Table 1). The median age at the time of MSP was 37 (20-61) years. A total of 49 MSPs were performed, two patients had 3 surgeries, six patients had 2 surgeries, and 30 patients had one surgery. Fifteen surgical procedures were performed in two, one surgical procedure was performed in three, and 33 operation procedures were performed in one operation area. There were no significant differences in complication rates between hemophilia types (A vs. B), severities (severe vs. moderate vs. mild) and number of operated regions (1 vs. 〉 1). In our study, general surgery (n=15) and orthopedic (n=10) operations were the most frequently performed MSPs (Table 2). There was no significant difference in complication rates among surgical branches. Complications were observed in a total of 6 (12%) MSPs, and one patient was deceased due to sepsis. Complication rates were 16% and 11% for MSPs done in PwH with and without inhibitors, respectively (p=non-significant). Factor consumption (U/kg) was highest in patients undergoing orthopedic surgery, followed by cardiovascular and neurosurgical operations. Factor utilization was significantly less for operations done in general surgery, urology and ear, nose and throat departments (p 〈 0.001). There was a significant positive correlation between factor consumption and duration of hospitalization (r = 0,690; p 〈 0.001). The data on the type of factor were available in 36 MSPs. Surgical procedures were carried out using plasma-derived and recombinant factor concentrates only in 26 and 5 patients, respectively. In the remaining 5, plasma-derived and recombinant factor concentrations were alternately applied. No statistically significant difference was noted with regard to the type of the factor used (plasma-derived, recombinant and plasma-derived/recombinant) and the duration of hospitalization or the complication rate. Number of days spent in the hospital were significantly higher in patients with complications than those without (16 vs. 9.5 days; p=0.003). Conclusion: The results of our retrospective study, being consistent with the current literature, clearly demonstrates that, in experienced comprehensive care centers MSPs can effectively and successfully be performed in PwH, even in those with inhibitors. Disclosures No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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