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

Completed
Conditions
Hematopoietic Stem Cell Transplantation
Interventions
Other: Lower lymphocyte/ATG ratio
Other: Higher lymphocyte/ATG ratio
Registration Number
NCT04869254
Lead Sponsor
IRCCS Burlo Garofolo
Brief Summary

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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
102
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 & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
Hematopoietic stem cells transplantationHigher lymphocyte/ATG ratiopatients undergone allogeneic or autologous bone marrow transplant who received immunomodulatory therapy with Thymoglobulin
Hematopoietic stem cells transplantationLower lymphocyte/ATG ratiopatients undergone allogeneic or autologous bone marrow transplant who received immunomodulatory therapy with Thymoglobulin
Primary Outcome Measures
NameTimeMethod
Development of GVHD according to lymphocyte/ATG ratio24 months after transplant

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

Secondary Outcome Measures
NameTimeMethod
Number of episodes of sepsis during the post-transplant period according to lymphocyte/ATG ratio24 months after transplant

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)

Entity of GVHD according to lymphocyte/ATG ratio24 months after transplant

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)

Number of episodes of fungal infections during the post transplant period according to lymphocyte/ATG ratio24 months after transplant

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)

Transplant related mortality according to lymphocyte/ATG ratio24 months after transplant

Comparison of transplant related mortality 24 months after HSCT in the two exposure's groups (lymphocyte/ATG ratio \<0.01 vs \>0.01)

Incidence of Graft Failure according to lymphocyte/ATG ratio24 months after transplant

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)

Number of episodes of viral reactivations during the post transplant period according to lymphocyte/ATG ratio24 months after transplant

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)

Trial Locations

Locations (1)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"

🇮🇹

Trieste, Italy

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