Lymphocyte Count, ATG Dose and Incidence and Severity of GVHD in Pediatric Recipients of HSCT

Correlation Between the Pre-transplantation Lymphocyte Count, Administered Dose of Thymoglobulin and Graft Versus Host Disease (GVHD) in Pediatric Recipients of Hematopoietic Stem Cells Transplantation: a Retrospective Study

Despite increasing success rate in hematopoietic stem cell transplantation (HSCT) control of graft versus host disease (GVHD) remains a significative burden in mortality and morbidity. A lot of strategies could lower the incidence and gravity of the disease and immunosuppressive treatment as GVHD prophylaxis still represent the main method.

Although immunosuppressive treatment showed a good effect on GVHD mortality a lot of studies also highlight an increase of relapse and infection related mortality that jeopardize the effect on overall survival of HSCT recipient. Using anti thymocyte globulin (ATG) as GVHD prophylaxis shares the same double-edge effect as other immunosuppressive treatment although is still unclear how manage dose and timing of the infusion to minimize promoting effect on infections and maximize protective effect on GVHD. Biological effect of ATG lead to a dose- related delay in all class of T-cell reconstitution but our data are mostly from adult studies with high doses between 30 and 60 mg/kg due to the more important burden of GVHD in HSCT adult population. As for other treatment in HSCT conditioning we would like to study a personalized approach for ATG treatment: some studies focus on tuning of ATG dose for kilos but previous evidence showed that the same dose could made too little or too much immunosuppressive effect for different patients, even though same age and same stem cell source.

Study Overview

• Status: Completed
• Conditions: Hematopoietic Stem Cell Transplantation
• Intervention / Treatment: Other: Lower lymphocyte/ATG ratio; Other: Higher lymphocyte/ATG ratio

• Study Type: Observational
• Enrollment (Actual): 102

Contacts and Locations

Study Locations

• Italy
  • Trieste, Italy, 34137
    • Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Pediatric recipients of hematopoietic stem cells transplantation

Description

Inclusion Criteria:

1. Age of the patients between 0 and 17
2. Diagnosis of hematological or oncological disease undergoing allogeneic bone marrow transplantation
3. Patients undergoing myeloablative conditioning
4. Patients that received ATG as GVHD prophylaxis
5. Patients whose consent has already been acquired for the processing of data for research purposes
6. Minimum follow-up of 12 months

Exclusion Criteria:

1. Bacterial and / or fungal infection present at the time of bone marrow transplantation
2. Use of Thymoglobulin in the 3 months prior to transplantation
3. Allergy and / or intolerance to the active substances or excipients contained in Thymoglobulin

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Hematopoietic stem cells transplantation; patients undergone allogeneic or autologous bone marrow transplant who received immunomodulatory therapy with Thymoglobulin	Other: Lower lymphocyte/ATG ratio; Other Names: Lymphocyte/ATG ratio <0.01; Other: Higher lymphocyte/ATG ratio; Other Names: Lymphocyte/ATG ratio >0.01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Development of GVHD according to lymphocyte/ATG ratio	Differences in the frequency of GVHD according to the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01). Adjustment for potentially associated variables (e.g., dose of drug actually received by patients, age of patients, type of conditioning, underlying disease, type of donor) will be carried out	24 months after transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplant related mortality according to lymphocyte/ATG ratio	Comparison of transplant related mortality 24 months after HSCT in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant
Incidence of Graft Failure according to lymphocyte/ATG ratio	Frequency of engraftment failure and hematological reconstitution time (defined as the first post-transplant day of at least three consecutive days with the presence of at least 500 neutrophils / mmc for myeloid engraftment and the first appearance of lymphoid cell subpopulations) in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant
Number of episodes of sepsis during the post-transplant period according to lymphocyte/ATG ratio	Number of episodes of sepsis after HSCT and correlated mortality and morbidity in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant
Number of episodes of fungal infections during the post transplant period according to lymphocyte/ATG ratio	Number of episodes of fungal infections after HSCT and correlated mortality and morbidity in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant
Number of episodes of viral reactivations during the post transplant period according to lymphocyte/ATG ratio	Number of episodes of viral reactivations after HSCT and correlated mortality and morbidity in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant
Entity of GVHD according to lymphocyte/ATG ratio	Severity and organ involvement of acute and chronic GVHD defined by the Glucksberg classification by degrees of severity in the two exposure's groups (lymphocyte/ATG ratio <0.01 vs >0.01)	24 months after transplant

Collaborators and Investigators

• Sponsor: IRCCS Burlo Garofolo
• Investigators: Study Chair: Natalia Maximova, MD, IRCCS Burlo Garofolo; Study Director: Alessandra Maestro, PharmD PhD, IRCCS Burlo Garofolo

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2000
• Primary Completion (Actual): December 31, 2018
• Study Completion (Actual): December 31, 2020

Study Registration Dates

• First Submitted: April 28, 2021
• First Submitted That Met QC Criteria: April 28, 2021
• First Posted (Actual): May 3, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2021
• Last Update Submitted That Met QC Criteria: April 28, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: pediatric patients; hematopoietic cell transplantation; Gvhd prophylaxis
• Other Study ID Numbers: RC 08/2019

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No