ATG in Haploidentical HSCT for Acute Graft-versus-host Disease Prophylaxis

Conditions

Antithymocyte Globulin, Hematopoietic Stem Cell Transplantation, Viral Infection

Keywords

haploidentical hematopoietic Stem Cell Transplantation, Antithymocyte globulin, viral infection

Brief summary

The purpose of this study is to compare the incidences of GVHD and viral infections in haploidentical hematopoietic stem cell transplant recipients receiving different dose of antithymocyte globulin (ATG) for acute graft-versus-host disease(aGVHD) prophylaxis. Our first objective was to investigate the optimal dose of ATG for aGVHD and second object was to evaluate the effect of different dose of ATG on post-transplant viral infection.

Detailed description

Allogeneic hematopoietic stem cell transplantation (allo-HSCT)is the only therapeutic option for many hematological malignancies. Unfortunately, about 75% of patients who require allo-HSCT lack human leukocyte antigen (HLA)-matched donors. The alternative is hematopoietic stem cells from an HLA-mismatched family donor. However, this strategy, which is called haploidentical HSCT, may be associated with high risk of early death and severe GVHD. Opportunistic infections are common complications after allo-HSCT. Due to the absence of effective preventive and therapeutic drugs for most viruses, viral infections has become one of the most important causes of death. The immunosuppression regimen including ATG has been shown effective to prevent severe GVHD in haploidentical HSCT. But this strategy delays immune reconstitution, and therefore increase the risk of viral infection. The optimal dose of the different ATG preparations with respect to prevention of GvHD is not fully understood today. The total doses between 6 mg/kg to 15 mg/kg are effective for prevention of GVHD, but the dose above 10 mg/kg may increase the development of viral infection. In this trial, we will focus on the incidence of aGVHD and viral infections in patients treated with 7.5mg/kg or 10mg/kg of ATG. The incidence of GVHD and viral infections will be compared between different dose arms.

Menglin Fan, Yu Wang, Ren Lin, Tong Lin, Fen Huang et al. (18 authors)

Chinese Medical Journal2021-11-309 citations

10.1097/cm9.0000000000001852

Long-Term Follow-up of a Randomized Trial of Two Dose Levels of Antithymocyte Globulin in Haploidentical Hematopoietic Stem Cell Transplantation

Yu Wang, Ren Lin, Lan‐Ping Xu, Kai‐Yan Liu, Xiaohui Zhang et al. (7 authors)

Blood2020-11-0510 citations

10.1182/blood-2020-139063

Haploidentical versus HLA-matched sibling transplantation for refractory acute leukemia undergoing sequential intensified conditioning followed by DLI: an analysis from two prospective data.

Yu S, Huang F, Fan Z, Xuan L, Nie D, Xu Y, Yang T, Wang S, Jiang Z, Xu N, Lin R, Ye J, Lin D, Sun J, Huang X, Wang Y, Liu Q.

2020-03-1244 citations

10.1186/s13045-020-00859-5

Preemptive Therapy Based on the Load and Time of EBV-Emia for Preventing EBV Related PTLD after Haploidentical Hematopoietic Stem Cell Transplantation: A Prospective Multicenter Study

Can Liu, Ren Lin, Yu Wang, Fen Huang, Zhiping Fan et al. (14 authors)

Blood2019-11-13

10.1182/blood-2019-132106

Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study.

Lin R, Wang Y, Huang F, Fan Z, Zhang S, Yang T, Xu Y, Xu N, Xuan L, Ye J, Sun J, Huang X, Liu Q.

2019-08-1268 citations

10.1186/s12916-019-1393-7

Interventions

DRUGATG

ATG will be intravenously infused via a central venous catheter in 3 or 4 days, from day -4 or -3 until day -1. The other conditioning drugs administered before transplantation include cytosine arabinoside (Ara-C), busulfan (Bu),cyclophosphamide (Cy), Semustine(Me-CCNU), and ATG. All transplant recipients will receive cyclosporine A (CsA), mycophenolate mofetil(MMF), and short-term methotrexate for aGVHD prevention.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

14 Years to 65 Years

Healthy volunteers

No

Inclusion criteria

* A patient age of 14-65 years * Haploidentical hematopoietic stem cell transplant recipient * Subjects (or their legally acceptable representatives) must have signed an informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study

Exclusion criteria

* Any abnormality in a vital sign (e.g., heart rate, respiratory rate, or blood pressure) * Patients with any conditions not suitable for the trial (investigators' decision)

Design outcomes

Primary

Measure	Time frame	Description
Incidence of Epstein-Barr virus(EBV) viremia	1 year	Incidence of EBV viremia within 1 year

Secondary

Measure	Time frame	Description
Incidence of EBV-associated diseases	2 years	the Incidence of EBV-associated end-organ diseases
Immune reconstitution	1 year	Immune reconstitution is performed every 3 months after transplantation.
Survival	3 years	Survival includes overall and disease-free survival within 2 years after transplantation.
Incidence of acute GVHD	100 days	Acute GVHD was graded according to standard criteria.
Incidence of cytomegalovirus(CMV) viremia	1 year	Incidence of CMV viremia within 1 year
Incidence of CMV-associated diseases	2 years	the Incidence of CMV-associated end-organ diseases
Incidence of chronic GVHD	2 years	Chronic GVHD was assessed in patients alive after day 100.

Countries

China

Outcome results

None listed