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      Prognostic Factors and a New Prognostic Index Model for Children and Adolescents with Hodgkin’s Lymphoma Who Underwent Autologous Hematopoietic Stem Cell Transplantation: A Multicenter Study of the Turkish Pediatric Bone Marrow Transplantation Study Group Translated title: Otolog Hematopoetik Kök Hücre Nakli Uygulanmış Hodgkin Lenfomalı Çocuk ve Adölesanlarda Prognostik Faktörler ve Yeni Bir Prognostik İndeks Modeli: Türk Pediatrik Kemik İliği Nakli Çalışma Grubundan Çok Merkezli Çalışma

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          Abstract

          Objective:

          The prognostic factors and a new childhood prognostic index after autologous hematopoietic stem cell transplantation (AHSCT) in patients with relapsed/refractory Hodgkin’s lymphoma (HL) were evaluated.

          Materials and Methods:

          The prognostic factors of 61 patients who underwent AHSCT between January 1990 and December 2014 were evaluated. In addition, the Age-Adjusted International Prognostic Index and the Childhood International Prognostic Index (CIPI) were evaluated for their impact on prognosis.

          Results:

          The median age of the 61 patients was 14.8 years (minimum-maximum: 5-20 years) at the time of AHSCT. There were single relapses in 28 patients, ≥2 relapses in eight patients, and refractory disease in 25 patients. The chemosensitivity/chemorefractory ratio was 36/25. No pretransplant radiotherapy, no remission at the time of transplantation, posttransplant white blood cell count over 10x10 3/µL, posttransplant positron emission tomography positivity at day 100, and serum albumin of <2.5 g/dL at diagnosis were correlated with progression-free survival. No remission at the time of transplantation, bone marrow positivity at diagnosis, and relapse after AHSCT were significant parameters for overall survival.

          Conclusion:

          The major factors affecting the progression-free and overall survival were clearly demonstrated. A CIPI that uses a lactate dehydrogenase level of 500 IU/L worked well for estimating the prognosis. We recommend AHSCT at first complete remission for relapsed cases, and it should also be taken into consideration for patients with high prognostic scores at diagnosis.

          Translated abstract

          Amaç:

          Relaps/refrakter Hodgkin lenfomanın (HL) otolog hematopoetik kök hücre nakli (OHKHN) sonrasındaki prognozunu gösterecek belirteçler ve çocukluk çağında yeni bir prognostik skorlama araştırıldı.

          Gereç ve Yöntemler:

          Bu çalışmada, Ocak 1990-Aralık 2014 tarihleri arasında OHKHN uygulanan 61 hastanın OHKHN sonrası prognozunu etkileyen faktörlerin sağkalım üzerine etkisi araştırıldı. Aynı zamanda Yaşa Göre Düzeltilmiş Uluslararası Prognostik İndeks ve Çocukluk Dönemi Uluslararası Prognostik İndeks’lerinin (ÇDUPİ) prognoz üzerindeki etkisi değerlendirildi.

          Bulgular:

          Altmış bir hastanın ortanca yaşı OHKHN sırasında 14,8 yıl (5-20 yıl) idi. Hastalardan, 28 olguda bir relaps, 8 olguda ≥2 relaps ve 25 olguda refrakter hastalık vardı. Kemosensitivite/kemoterapiye dirençlilik oranı 36/25 idi. Nakil öncesi radyoterapi almamak, nakil öncesi remisyonda olmamak, nakil sonrası beyaz kan hücresi sayısının 10x10 3/µL üzerinde olması, nakil sonrası 100. gün pozitron emisyon tomografisi pozitifliği, tanıda 2,5 g/dL’den düşük serum albümin düzeyi progresyonsuz sağkalım üzerinde etkili belirteçler iken transplantasyon zamanı remisyonda olmamak, tanıda kemik iliği pozitifliği ve OHKHN sonrası relaps ise genel sağkalım üzerinde etkili parametreler olarak bulundu.

          Sonuç:

          Relaps/refrakter HL’li çocuklarda progresyonsuz ve genel sağkalımı etkileyen faktörler açıkça gösterildi. Serum laktat dehidrogenaz üst sınırını 500 IU/L olarak kullanan ÇDUPİ prognozu göstermede etkili bulundu. Relaps hastalarda ilk tam remisyonda OHKHN yapılmasını ve tanı anında yüksek prognostik skoru olan olguların da OHKHN açısından değerlendirmeye alınmasını önermekteyiz.

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          Most cited references25

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          • Abstract: found
          • Article: not found

          A prognostic score for advanced Hodgkin's disease. International Prognostic Factors Project on Advanced Hodgkin's Disease.

          Two thirds of patients with advanced Hodgkin's disease are cured with current approaches to treatment. Prediction of the outcome is important to avoid overtreating some patients and to identify others in whom standard treatment is likely to fail. Data were collected from 25 centers and study groups on a total of 5141 patients treated with combination chemotherapy for advanced Hodgkin's disease, with or without radiotherapy. The data included the outcome and 19 demographic and clinical characteristics at diagnosis. The end point was freedom from progression of disease. Complete data were available for 1618 patients; the final Cox model was fitted to these data. Data from an additional 2643 patients were used for partial validation. The prognostic score was defined as the number of adverse prognostic factors present at diagnosis. Seven factors had similar independent prognostic effects: a serum albumin level of less than 4 g per deciliter, a hemoglobin level of less than 10.5 g per deciliter, male sex, an age of 45 years or older, stage IV disease (according to the Ann Arbor classification), leukocytosis (a white-cell count of at least 15,000 per cubic millimeter), and lymphocytopenia (a lymphocyte count of less than 600 per cubic millimeter, a count that was less than 8 percent of the white-cell count, or both). The score predicted the rate of freedom from progression of disease as follows: 0, or no factors (7 percent of the patients), 84 percent; 1 (22 percent of the patients), 77 percent; 2 (29 percent of the patients), 67 percent; 3 (23 percent of the patients), 60 percent; 4 (12 percent of the patients), 51 percent; and 5 or higher (7 percent of the patients), 42 percent. The prognostic score we developed may be useful in designing clinical trials for the treatment of advanced Hodgkin's disease and in making individual therapeutic decisions, but a distinct group of patients at very high risk could not be identified on the basis of routinely documented demographic and clinical characteristics.
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            • Article: not found

            Report of a committee convened to discuss the evaluation and staging of patients with Hodgkin's disease: Cotswolds meeting.

            The Ann Arbor classification for describing the stage of Hodgkin's disease at initial presentation has formed the basis upon which treatment is selected and has allowed comparison of results achieved by different investigators for almost two decades. A meeting was convened to review the classification and modify it in the light of experience gained in its use and new techniques for evaluating disease. It was concluded that the structure of the classification be maintained. It was particularly recommended: (1) that computed tomography (CT) be included as a technique for evaluating intrathoracic and infradiaphragmatic lymph nodes; (2) that the criteria for clinical involvement of the spleen and liver be modified to include evidence of focal defects with two imaging techniques and that abnormalities of liver function be ignored; (3) that the suffix 'X' to designate bulky disease (greater than 10 cm maximum dimension) be introduced; and (4) that a new category of response to therapy, unconfirmed/uncertain complete remission (CR[u]), be introduced to accommodate the difficulty of persistent radiological abnormalities of uncertain significance.
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              • Article: not found

              Randomized comparison of low-dose involved-field radiotherapy and no radiotherapy for children with Hodgkin's disease who achieve a complete response to chemotherapy.

              Current standard therapy for children and adolescents with Hodgkin's disease includes combination chemotherapy and low-dose involved-field radiation (LD-IFRT). Because radiation may be associated with adverse late effects, the Children's Cancer Group (CCG) investigated whether radiation could be omitted in patients achieving a complete response to initial chemotherapy without jeopardizing the excellent outcome obtained with combined-modality therapy. Between January 1995 and December 1998, 829 eligible patients were enrolled onto CCG 5942. A total of 501 patients who achieved an initial complete response after risk-adapted combination chemotherapy were randomized to receive LD-IFRT or no further treatment. Event-free survival (EFS) and overall survival were assessed from the date of study entry or the date of randomization, as appropriate. The projected 3-year EFS from study entry for the entire cohort was 87% +/- 1.2%. Among patients who achieved a complete response to initial chemotherapy, 92% +/- 1.9% of those randomized to receive LD-IFRT were alive and disease free 3 years after randomization, versus 87% +/- 2.2% for patients randomized to receive no further therapy (stratified log-rank test; P =.057). With an "as-treated" analysis, 3-year EFS after randomization for the radiation cohort was 93% +/- 1.7% versus 85% +/- 2.3% for patients receiving no further therapy (stratified log-rank test; P =.0024). Three-year survival estimates for patients treated with and without LD-IFRT were 98% +/- 1.1% for patients who received radiation and 99% +/- 0.5% for patients who did not receive radiation. LD-IFRT after an initial complete response to risk-adapted chemotherapy improved EFS. At this time, there is no survival advantage for LD-IFRT, but follow-up remains short.
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                Author and article information

                Journal
                Turk J Haematol
                Turk J Haematol
                TJH
                Turkish Journal of Hematology
                Galenos Publishing
                1300-7777
                1308-5263
                December 2016
                1 December 2016
                : 33
                : 4
                : 265-272
                Affiliations
                [1 ] Gülhane Training and Research Hospital Clinic of Pediatric Oncology, Ankara, Turkey
                [2 ] Erciyes University Faculty of Medicine, Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation Unit, Kayseri, Turkey
                [3 ] Ege University Faculty of Medicine, Department of Pediatric Oncology and Bone Marrow Transplantation Unit, İzmir, Turkey
                [4 ] Medical Park Bahçelievler Hospital, Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
                [5 ] Ankara University Faculty of Medicine, Department of Pediatric Oncology and Bone Marrow Transplantation Unit, Ankara, Turkey
                [6 ] Akdeniz University Faculty of Medicine, Department of Pediatric Hematology-Oncology and Bone Marrow Transplantation Unit, Antalya, Turkey
                [7 ] Tepecik Training and Research Hospital, Clinic of Pediatric Oncology and Bone Marrow Transplantation Unit, İzmir, Turkey
                [8 ] Ondokuz Mayıs University Faculty of Medicine, Department of Pediatric Oncology and Bone Marrow Transplantation Unit, Samsun, Turkey
                [9 ] Gazi University Faculty of Medicine, Department of Pediatric Hematology and Bone Marrow Transplantation Unit, Ankara, Turkey
                [10 ] Dokuz Eylül University Faculty of Medicine, Department of Pediatric Hematology and Bone Marrow Transplantation Unit, İzmir, Turkey
                [11 ] Medical Park Göztepe Hospital, Pediatric Bone Marrow Transplantation Unit, İstanbul, Turkey
                Author notes
                * Address for Correspondence: Gülhane Training and Research Hospital Clinic of Pediatric Oncology, Ankara, Turkey Phone: +90 312 304 43 94 E-mail: vural73@ 123456yahoo.com
                Article
                1841
                10.4274/tjh.2015.0280
                5204179
                27094103
                a67aa91a-73b1-4948-8941-0c76d576a14a
                © Turkish Journal of Hematology, Published by Galenos Publishing.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 July 2015
                : 2 November 2015
                Categories
                Research Article

                childhood hodgkin’s lymphoma,prognosis,autologous hematopoietic stem cell transplantation,prognostic index

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