Nur SOYER, Ayşe Uysal ORUÇ, MURAT TOMBULOĞLU, FİLİZ VURAL

Ağır aplastik anemili hastalarda allojeneik periferik kök hücre nakli sonuçları: Tek merkez deneyimi

Amaç: Erişkin kök hücre nakil ünitesinde ağır aplastik anemi tanısıyla nakil olan hastaların klinik özelliklerini, nakil sonuçlarını ve sağkalımlarını geriye dönük olarak değerlendirmeyi amaçladık. Gereç ve Yöntem: On bir olguya (6 erkek ve 5 kadın) edinsel aplastik anemi tanısı ile 12 allojeneik kök hücre nakli yapıldı. Nakil öncesinde 2 hasta hariç tüm hastalar immunsupresif tedavi almıştı. Tüm nakillerde HLA tam uyumlu kardeş donörden elde edilen periferik kök hücreler kullanıldı. Hazırlama rejimleri, siklofosfamid, antitimosit globulin, fludarabin ve busulfan kombinasyonlarından oluşuyordu. Bulgular: Ortanca nakil yaşı 22 yıl ve tanıdan nakile kadar geçen süre ortanca 9 ay idi. Ortanca 5.49 x 106/kg (4.9-12.7 x 106/kg) CD34 pozitif kök hücre verildi. Ortanca nötrofil ve trombosit engrafmanları sırasıyla 21.5 (1037) ve 15 günde oldu. On bir hastanın 4'ünde (%36.3) akut graft versus host hastalığı (GVHH) ve 1'inde (%9) kronik GVHH ortaya çıktı. Graft yetmezliği 11 hastanın 2'sinde (%18.1) görüldü. İzlemde 11 hastanın 4'ü (%36.3) (3'ü enfeksiyon ve 1'i karaciğer yetmezliği) kaybedildi. Ortanca izlem süresi 33.5 ay idi. On bir hastanın %63.7'si halen hayattadır. Beş yıllık toplam sağkalım %66.7 ve olaysız sağkalım %58.3 idi. Sonuç: Hasta sayımız az olmakla birlikte tam uyumlu kardeş donörden allojeneik kök hücre naklinin, 40 yaş altındaki ağır aplastik anemili hastalarda ilk tedavi seçeneği olduğunu destekler bulgular elde edilmiştir. Tam uyumlu kardeş donör, tanıdan nakile kadar geçen sürenin kısalığı, uygun hazırlama rejimi ve uygun kök hücre kaynağı seçimi, nakil başarısını ve sağkalımı arttırır görünmektedir.

Allogeneic peripheral stem cell transplantation in patients with severe aplastic anemia: Single center experience

Aim: We retrospectively analyzed the clinical features, transplantation results and survival of patients with severe aplastic anemia (SAA) treated with allogeneic stem cell transplantations (ASCT) in adult transplantation unit. Materials and Methods: Eleven patients (6 male, 5 female) treated with 12 ASCTs were analyzed. All patients except 2 were treated with immunosuppressive treatment before ASCT. Peripheral CD34+ stem cells from HLA matched sibling donors (MSD) were transfused after conditioning regimens including cyclophosphamide, busulphan, antithymocyte globulin and fludarabine. Results: The median age at ASCT and time from diagnosis to ASCT were 22 years and 9 months , respectively. The median 5.49 x 106/kg (4.9-12.7 x 106/kg) CD34+cells were transfused. The median duration of time to neutrophil and platelet engraftments were 21.5 and 15 days, respectively. Acute graft versus host disease (GVHD) and limited chronic GVHD were observed in 4 (36.3%) patients and 1 (9%) patient, respectively. Graft failure was seen in 2 (18.1%) of 11 patients. The median follow-up period was 33.5 months . Four (36.3%) of 11 patients died due to infection (3 patients) and liver failure (1 patient). Approximately 64% of all recipients are alive. The 5-year overall and event-free survival rates were 66.7% and 58.3%, respectively. Conclusion: Although we have few patients, our findings are seems to support that ASCT from a MSD remains the first choice for SAA patients younger than 40 years. Presence of MSD, shorter time from diagnosis to ASCT, using optimal conditioning regimens and choosing optimal stem cell source are seems to increase the success and survival rates of transplantation.

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1. Young NS, Calado RT, Scheinberg P. Current concepts in the pathophysiology and treatment of aplastic anemia. Blood 2006; 108(8):2509-19.
2. Marsh JC, Ball SE, Cavenagh J, et al; British Committee for Standards in Haematology. Guidelines for the diagnosis and management of aplastic anaemia. Br J Haematol 2009;147(1):43-70.
3. Aljurf M, Al-Zahrani H, Van Lint MT, et al. Standard treatment of acquired SAA in adult patients 18-40 years old with an HLAidentical sibling donor. Bone Marrow Transplant 2013;48(2):178-9.
4. Scheinberg P, Young NS. How I treat acquired aplastic anaemia. Blood 2012;120(6):1185-96.
5. Gupta V, Eapen M, Brazauskas R, et al. Impact of age on outcomes after bone marrow transplantation for acquired aplastic anemia using HLA matched sibling donors. Haematologica 2010;95(12):2119-25.
6. Sangiolo D, Storb R, Deeg HJ, et al. Outcome of allogeneic hematopoietic cell transplantation from HLA-identical siblings for severe aplastic anemia in patients over 40 years of age. Biol Blood Marrow Transplant. 2010;16(10):1411-8.
7. Kim H, Lee K, Yoon S, et al. Allogeneic hematopoietic stem cell transplant for adults over 40 years old with acquired aplastic anaemia. Biol Blood Marrow Transplant 2012;18(10):1500-8.
8. Peinemann F, Grouven U, Kroger N, et al. First-line matched related donör hematopoietic stem cell transplantation compared to immunosuppressive therapy in acquired severe aplastic anaemia. PLoSOne 2011;6:e18572.
9. Scheinberg P, Young NS. How I treat acquired aplastic anaemia. Blood 2012;120(6):1185-96.
10. Bacigalupo A, Socie G, Schrezenmeier H, et al. Bone marrow versus peripheral blood as the stem cell source for sibling transplants in acquired aplastic anaemia: survival advantage for bone marrow in all age groups. Haematologica 2012;97(8):1142-8.
11. Eapen M, Le Rademacher J, Antin JH. Effect of stem cell source on outcomes after unrelated donor transplantation in severe aplastic anaemia. Blood 2011;118(9):2618-21.
12. Aksoylar S, Çetingül N, Kansoy S. Ağır edinsel aplastik anemili çocuklarda kök hücre transplantasyonu:15 olgunun değerlendirilmesi. Ege Tıp Dergisi 2012;51(1):31-5.
13. Bacigalupo A, Marsh JC. Unrelated donör search and unrelated donör transplantation in the adult aplastic anaemia patient aged 18-40 years without an HLA-identical sibling and failing immunosuppression. Bone Marrow Transplant 2013;48(2):198-200.
14. Marsh JC, Gupta V, Lim Z, et al. Alemtuzumab with fludarabine and cyclophosphamide reduces chronic graft-versus-host disease after allogeneic stem cell transplantation for acquired aplastic anaemia. Blood 2011;118(8):2351-7.
15. Young ME, Potter V, Kulasekararaj AG, Mufti GJ, Marsh JC. Haematopoietic stem cell transplantation for acquired aplastic anaemia. Curr Opin Hematol 2013;20(6):515-20.
16. Seth T, Kanga U, Sood P, Sharma V, Mishra P, Mahapatra M. Audit of peripheral stem cell transplantation for aplastic anemia in multitransfused infected patients. Transplant Proc 2012;44(4):922-4.
17. Aki SZ, Sucak GT, Ozkurt ZN, Yeğin ZA, Yağci M, Haznedar R. Allogeneic stem cell transplantation for severe aplastic anemia: graft rejection remains a problem. Transfus Apher Sci 2009;40(1):5-11.