SavedAdd your journal

Journals / Turkish Journal of Hematology / 2015 / Cilt: 32 - Sayı: 3

Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions

Erişkin Orak Hücre Hastalığında Hematopoietik Kök Hücre Nakli: Problemler ve Çözüm Önerileri

Hakan ÖZDOĞU
Can BOGA
Pages
195–205
DOI
—
🏛️Bibliographic metadata and full text access for this article are provided via DergiPark.
DergiPark Record ↗
✨

AI Summary & Key Takeaways

AI Insight
⚡ TL;DR(Too Long; Didn't Read)

Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation.

📌 3 Key Takeaways

🎯
Objective & Hypothesis:Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies.
📊
Key Findings & Data:As a consequence, disease-related mortality reaches 14% in adolescents and young adults.
💡
Conclusion & Impact:Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation.
🔬Design:Research Article
📍Scope:Comprehensive Sample
⚙️Variables:Domain Parameters

Abstract

Sickle cell disease-related organ injuries cannot be prevented despite hydroxyurea use, infection prophylaxis, and supportive therapies. As a consequence, disease-related mortality reaches 14% in adolescents and young adults. Hematopoietic stem cell transplantation is a unique curative therapeutic approach for sickle cell disease. Myeloablative allogeneic hematopoietic stem cell transplantation is curative for children with sickle cell disease. Current data indicate that long-term disease-free survival is about 90% and overall survival about 95% after transplantation. However, it is toxic in adults due to organ injuries. In addition, this curative treatment approach has several limitations, such as difficulties to find donors, transplant-related mortality, graft loss, graft-versus-host disease (GVHD), and infertility. Engraftment effectivity and toxicity for transplantations performed with nonmyeloablative reduced-intensity regimens in adults are being investigated in phase 1/2 trials at many centers. Preliminary data indicate that GVHD could be prevented with transplantations performed using reduced-intensity regimens. It is necessary to develop novel regimens to prevent graft loss and reduce the risk of GVHD

Özet

Günümüzde hidroksiüre kullanımı, enfeksiyon proflaksisi ve destek tedavileriyle ilgili gelişmelere rağmen orak hücre hastalığına bağlı organ hasarları engellenememekte, adölesan ve genç yetişkinlerde hastalık ilişkili mortalite %14'lere kadar ulaşmaktadır. Hematopoietik kök hücre transplantasyonu, orak hücre hastalığı tedavisinde tek küratif tedavi yaklaşımıdır. Myeloablatif allojenik hematopietik kök hücre transplantasyonu orak hücre hastalığı olan çocuklar için küratiftir. Güncel veriler çocuklarda transplant sonrası uzun dönem hastalıksız yaşam oranının %90 ve toplam yaşam oranının %95 civarında olduğunu göstermektedir. Erişkinde hazırlama rejimleri organ hasarları nedeniyle fazla toksiktir. Ayrıca bu küratif tedavi yaklaşımının donör bulma güçlüğü, transplant ilişkili mortalite, graft kaybı, graft-versus-host hastalığı (GVHH), infertilite gibi nedenlerle sınırlamaları vardır. Güncel olarak erişkinde toksisitesi azaltılmış hazırlama rejimleri (myeloablatif olmayan indirgenmiş yoğunluklu) ile yapılan transplantların faz 1/2 çalışmalar ile graft yerleşmesi üzerine etkinliği ve toksisitesi birçok merkez tarafından araştırılmaktadır. Ön veriler, toksisitesi azaltılmış rejimler ile yapılan nakillerde başarılı olarak GVHH'nin engellenebildiğini göstermiştir. Bununla birlikte yüksek graft kaybı riski devam etmektedir. Bu yüzden orak hücre hastalarında uygulanabilen, GVHH riski azaltılmış ve graft kaybının engellenebildiği yeni rejimlerin geliştirilmesi gereklidir

🔖

Cite This Article

ÖZDOĞU, H., BOGA, C. (2015). Hematopoietic Stem Cell Transplantation in Adult Sickle Cell Disease: Problems and Solutions. Turkish Journal of Hematology, Cilt: 32 - Sayı: 3, 195–205. https://ajindex.com/articles/412799

📄 Full Text PDF Viewer

📄

PDF görüntüleyici hazırlanıyor...

References (3)

  1. Transplant Regimen Patients (age without GVHD range, years) SCD Acute Chron- ic GVHD (cause) Bolanos- Meade et al. [36], 2012 Cy 14.5 mg/ kg, ATG 4.5 mg/kg, post TX Cy 100 mg/kg, tacrolimus or sirolimus 17 1 limited (skin) 14 haploidentical related donors, in 6 patients graft rejected; 3 matched sibling donors, no grafts rejected Hsieh et al. [28], 2009 alemtuzumab 1 mg/kg, sirolimus 9 At 3 years after HSCT, mixed chimerism in all Hsieh et al. [49], 2014 alemtuzumab 1 mg/kg, sirolimus 26 1 (GVHD) years 15 patients discontinued immunosuppression medication Krishnamurti et al. [48], 2008
  2. PO, FLU 175 mg/kg, ATG, 500 cGy of TLI, CSA, MMF 6 1 (Gr 2, skin) (skin) Mixed chimerism in 4 Jacobsohn et al. [46], 2004
  3. IV, FLU 180 mg/m2, ATG, CSA, MMF (Gr 1) 1 extensive 1 (GVHD) Iannone et al. [47], 2003 m2, CSA or tacrolimus, MMF 1 (Gr 2) 0 Transient engraftment in 5 patients for 97- 441 days ATG: Antithymocyte globulin, cGy: centigray, CSA: cyclosporine A, Cy: cyclophosphamide, FLU: fludarabine, Gr: grade, IV: intravenous, MMF: mycophenolate mofetil, MTX: methotrexate, PO: per os, SCD: sickle cell disease, TBI: total body irradiation, TLI: total lymphoid irradiation, GVHD: graft-versus-host disease, HSCT: hematopoietic stem cell transplantation. In general, small proportions of engrafted donor red cells seem to be sufficient for clinical control of the disease in SCD patients [50]. Hsieh et al. reported that they achieved permanent engraftment in 26/30 patients and that no patients developed acute GVHD (aGVHD) or cGVHD with a nonmyeloablative- conditioning regimen using alemtuzumab (Campath) and low-dose total-body irradiation (TBI). The mean donor T-cell level was 48% and the myeloid chimerism level was 86%. Fifteen engrafted patients discontinued immunosuppression medication with continued stable donor chimerism and no GVHD [49]. In this study, sirolimus (rapamycin) was selected as the immunosuppressive agent instead of cyclosporine. Differently from calcineurin inhibitors, sirolimus does not block T-cell activation, but it inhibits T-cell proliferation. The activated but nonproliferated T cells become anergic, resulting in T-cell tolerance. Sirolimus accelerates the differentiation of regulatory and helper T cells and this plays a key role in immune tolerance development. Additionally, the renal toxicity of sirolimus is less than that of cyclosporine. Luznik et al. showed that high-dose cyclophosphamide given in the early posttransplantation period could lead to im