Low Nonrelapse Mortality after HLA-Matched Related 2-Step Hematopoietic Stem Cell Transplantation Using Cyclophosphamide for Graft-versus-Host Disease Prophylaxis and the Potential Impact of Non- Cyclophosphamide-Exposed T Cells on Outcomes

Dolores Grosso , Matthew Carabasi , Joanne Filicko-O'Hara , John L. Wagner , William O'Hara , Michael Sun , Beth Colombe , W. Shi , Maria Werner-Wasik , Shannon Rudolph , Onder Alpdogan , Adam Binder , Margaret Kasner , Thomas Klumpp , Ubaldo Martinez-Outschoorn , Neil Palmisiano , Lindsay Wilde , Pierluigi Porcu , Usama Gergis , Neal Flomenberg
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引用次数: 1

Abstract

The use of cyclophosphamide (CY) for bidirectional tolerization of recipient and donor T cells is associated with reduced rates of graft-versus-host disease (GVHD) and nonrelapse mortality (NRM) after HLA-matched hematopoietic stem cell transplantation (HSCT). However, recurrent disease remains the primary barrier to long-term survival. We extended our 2-step approach to HLA-matched related HSCT using a radiation-based myeloablative conditioning regimen combined with a high dose of T cells in an attempt to reduce relapse rates while maintaining the beneficial effects of CY tolerization. After conditioning, patients received their grafts in 2 components: (1) a fixed dose of 2 × 108/kg T cells, followed 2 days later by CY, and (2) a CD34-selected graft containing a small residual amount of non-CY-exposed T cells, at a median dose of 2.98 × 103/kg. Forty-six patients with hematologic malignancies were treated. Despite the myeloablative conditioning regimen and use of high T cell doses, the cumulative incidences of grade II-IV acute GVHD, chronic GVHD, and NRM at 1 year and 5 years were very low, at 13%, 9%, and 4.3%, respectively. This contributed to a high overall survival of 89.1% at 1 year and 65.8% at 5 years. Relapse was the primary cause of mortality, with a cumulative incidence of 23.9% at 1 year and 45.7% at 5 years. In a post hoc analysis, relapse rates were significantly lower in patients receiving greater than versus those receiving less than the group median of non-CY-exposed residual T cells in the CD34 product (19.3% versus 58.1%; P = .009), without a concomitant increase in NRM. In its current form, this 2-step regimen was highly tolerable, but strategies to reduce relapse, potentially the addition of T cells not exposed to CY, are needed.

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使用环磷酰胺进行hla匹配相关2步造血干细胞移植预防移植物抗宿主病后的低非复发死亡率和非环磷酰胺暴露的T细胞对结果的潜在影响
环磷酰胺(CY)用于受体和供体T细胞的双向耐受与hla匹配的造血干细胞移植(HSCT)后移植物抗宿主病(GVHD)和非复发死亡率(NRM)的降低有关。然而,复发性疾病仍然是长期生存的主要障碍。我们将两步方法扩展到hla匹配的相关HSCT,使用基于放射的清髓调节方案结合高剂量T细胞,试图降低复发率,同时保持CY耐受性的有益效果。经调节后,患者接受2组移植物:(1)固定剂量2 × 108/kg T细胞,2天后接受CY, (2) cd34选择的移植物含有少量未CY暴露的T细胞,中位剂量为2.98 × 103/kg。对46例恶性血液病患者进行了治疗。尽管采用了清髓调节方案和使用高剂量的T细胞,但1年和5年II-IV级急性GVHD、慢性GVHD和NRM的累积发病率非常低,分别为13%、9%和4.3%。这使得1年和5年的总生存率分别达到89.1%和65.8%。复发是死亡的主要原因,1年和5年的累计发病率分别为23.9%和45.7%。在一项事后分析中,接受CD34产品中非cy暴露残余T细胞大于或小于组中位数的患者的复发率显著低于接受CD34产品中位数的患者(19.3%对58.1%;P = 0.009), NRM未同时升高。在目前的形式下,这种两步治疗方案是高度耐受的,但需要减少复发的策略,可能需要添加未暴露于CY的T细胞。
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来源期刊
CiteScore
6.60
自引率
0.00%
发文量
1061
审稿时长
3-6 weeks
期刊介绍: Biology of Blood and Marrow Transplantation publishes original research reports, reviews, editorials, commentaries, letters to the editor, and hypotheses and is the official publication of the American Society for Transplantation and Cellular Therapy. The journal focuses on current technology and knowledge in the interdisciplinary field of hematopoetic stem cell transplantation.
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