Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders,Journal of Allergy and Clinical Immunology

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Comparison of hematopoietic cell transplant conditioning regimens for hemophagocytic lymphohistiocytosis disorders
Journal of Allergy and Clinical Immunology ( IF 11.4 ) Pub Date : 2021-08-08 , DOI: 10.1016/j.jaci.2021.07.031
Rebecca A Marsh ₁ , Kyle Hebert ₂ , Soyoung Kim ₂ , Christopher C Dvorak ₃ , Victor M Aquino ₄ , K Scott Baker ₅ , Deepak Chellapandian ₆ , Blachy Dávila Saldaña ₇ , Christine N Duncan ₈ , Michael J Eckrich ₉ , George E Georges ₅ , Timothy S Olson ₁₀ , Michael A Pulsipher ₁₁ , Shalini Shenoy ₁₂ , Elizabeth Stenger ₁₃ , Mark Vander Lugt ₁₄ , Lolie C Yu ₁₅ , Andrew R Gennery ₁₆ , Mary Eapen ₂

Affiliation

University of Cincinnati and Division of Bone Marrow Transplantation and Immune Deficiency, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio.
Center for International Blood and Marrow Transplant Research, Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisc.
Division of Pediatric Allergy, Immunology, and Bone Marrow Transplantation, University of California San Francisco, Benioff Children's Hospital, San Francisco, Calif.
UT Southwestern Medical Center, Dallas, Tex.
Fred Hutchinson Cancer Research Center, Seattle, Wash.
Center for Cell and Gene Therapy for Non-Malignant Conditions, Johns Hopkins All Children's Hospital, St Petersburg, Fla.
Division of Bone Marrow Transplant, Children's National Hospital, Washington, DC.
Dana-Farber Cancer Institute, Boston, Mass.
Sarah Cannon Pediatric Transplant and Cellular Therapy Program, Methodist Children's Hospital, San Antonio, Tex.
Department of Pediatrics, Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pa.
Children's Hospital Los Angeles, Los Angeles, Calif.
Department of Pediatrics, Washington University School of Medicine, St Louis, Mo.
Children's Hospital of Pittsburgh, Pittsburgh, Pa.
The University of Michigan, Ann Arbor, Mich.
Children's Hospital, New Orleans, La.
Newcastle University, Newcastle Upon Tyne, United Kingdom.

Background

Allogeneic hematopoietic cell transplantation for hemophagocytic lymphohistiocytosis (HLH) disorders is associated with substantial morbidity and mortality.

Objective

The effect of conditioning regimen groups of varying intensity on outcomes after transplantation was examined to identify an optimal regimen or regimens for HLH disorders.

Methods

We studied 261 patients with HLH disorders transplanted between 2005 and 2018. Risk factors for transplantation outcomes by conditioning regimen groups were studied by Cox regression models.

Results

Four regimen groups were studied: (1) fludarabine (Flu) and melphalan (Mel) in 123 subjects; (2) Flu, Mel, and thiotepa (TT) in 28 subjects; (3) Flu and busulfan (Bu) in 14 subjects; and (4) Bu and cyclophosphamide (Cy) in 96 subjects. The day 100 incidence of veno-occlusive disease was lower with Flu/Mel (4%) and Flu/Mel/TT (0%) compared to Flu/Bu (14%) and Bu/Cy (22%) (P < .001). The 6-month incidence of viral infections was highest after Flu/Mel (72%) and Flu/Mel/TT (64%) compared to Flu/Bu (39%) and Bu/Cy (38%) (P < .001). Five-year event-free survival (alive and engrafted without additional cell product administration) was lower with Flu/Mel (44%) compared to Flu/Mel/TT (70%), Flu/Bu (79%), and Bu/Cy (61%) (P = .002). The corresponding 5-year overall survival values were 68%, 75%, 86%, and 64%, and did not differ by conditioning regimen (P = .19). Low event-free survival with Flu/Mel is attributed to high graft failure (42%) compared to Flu/Mel/TT (15%), Flu/Bu (7%), and Bu/Cy (18%) (P < .001).

Conclusions

Given the high rate of graft failure with Flu/Mel and the high rate of veno-occlusive disease with Bu/Cy and Flu/Bu, Flu/Mel/TT may be preferred for HLH disorders. Prospective studies are warranted.

中文翻译：

噬血细胞性淋巴组织细胞增生症造血细胞移植预处理方案的比较

背景

用于治疗噬血细胞性淋巴组织细胞增生症 (HLH) 疾病的同种异体造血细胞移植与高发病率和死亡率相关。

客观的

检查了不同强度的预处理方案组对移植后结果的影响，以确定 HLH 疾病的最佳方案或方案。

方法

我们研究了 261 名在 2005 年至 2018 年间移植的 HLH 疾病患者。通过 Cox 回归模型研究了预处理方案组移植结果的危险因素。

结果

研究了四个方案组：(1) 123 名受试者中的氟达拉滨 (Flu) 和美法仑 (Mel)；(2) 28 名受试者的流感、梅尔和噻替哌 (TT)；(3) 14 名受试者的流感和白消安 (Bu)；(4) 96 名受试者的 Bu 和环磷酰胺 (Cy)。与 Flu/Bu (14%) 和 Bu/Cy (22%) 相比，Flu/Mel (4%) 和 Flu/Mel/TT (0%) 的第 100 天静脉闭塞性疾病发生率较低（P < . 001). 与 Flu/Bu (39%) 和 Bu/Cy (38%) 相比，Flu/Mel (72%) 和 Flu/Mel/TT (64%) 后 6 个月的病毒感染发生率最高（P < .001 ). 与 Flu/Mel/TT (70%)、Flu/Bu (79%) 和 Bu/ Cy (61%) ( P =.002）。相应的 5 年总生存率为 68%、75%、86% 和 64%，并且没有因预处理方案而不同 ( P = .19)。与 Flu/Mel/TT (15%)、Flu/Bu (7%) 和 Bu/Cy (18%) 相比，Flu/Mel 的低无事件生存率归因于高移植失败率 (42%)（P < .001）。