Thrombotic Microangiopathy (TMA) Associated With Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) In Adult Patients

Recruiting

• Conditions: Thrombotic Microangiopathy

• Registration Number: NCT07059026
• Lead Sponsor: ITAC (Instituto de Trasplantes y Alta Complejidad)

Brief Summary

Thrombotic Microangiopathy (TMA) Associated with Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) is a serious complication that is associated with increased morbidity, related to multiple organ failure, with increased mortality in transplant patients. The incidence and evolution of TMA, especially in the adult population, is unclear due to the lack of early systematic screening and clear criteria for its diagnosis. For this reason, we designed this protocol to study the incidence and evolution of TMA Associated with allogeneic HSCT in adult patients from Argentina.

Detailed Description

This is a prospective multicenter non-interventional observational study that will include sites that perform routine screening using harmonized definitions and diagnostic criteria during the first 100 days post-HSCT (screening period).

All patients entering the study (HSCT accessible population), regardless of suspicion or diagnosis of TMA, will be followed every 3 months up to 12 months after transplant to evaluate secondary outcomes (follow-up period).

Study Timeline

• Study Start: 2024-12-03
• Status Verified: 2025-07
• Study First Submitted: 2025-07-01
• Study First Submitted QC: 2025-07-01
• Last Update Submitted: 2025-07-09
• Study First Posted: 2025-07-10
• Last Update Posted: 2025-07-14
• Primary Completion: 2027-12
• Study Completion: 2027-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Adult patients (≥ 18 years) undergoing allogeneic HSCT in specialized centers that, as part of their usual follow-up protocol, carry out basic screening (laboratory/clinical) for TMA and in which patients consent (within the general transplant consent), to have their data used in observational studies.
• Patients with ≥ 3/laboratory/clinical diagnostic markers of TMA in two consecutive assessments within 14 days, namely: 1-Elevated Schistocytes in peripheral blood; 2-LDH above the upper normal limit; 3-De novo thrombocytopenia or requirement for platelet transfusion; 4-De novo anemia or requirement for red blood cell transfusion; 5-High blood pressure (≥140/90); 6-Protein/creatinine ratio > 1mg/mg or proteinuria ≥ 30mg/dl in a random sample).
• Patients with suspected/diagnosed TMA who have signed the specific consent for the study.

Exclusion Criteria

• Participation in an interventional treatment study of any therapy for TMA.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Incidence of TMA in adult patients receiving allogeneic HSCT in specialized centers in Argentina	100 days post-HSCT (screening period)	The incidence of TMA will be assessed by the presence of ≥ 4/diagnostic laboratory/clinical markers present in 2 successive assessments within 14 days or if TMA is identified histologically by tissue biopsy up to day 100 post-transplant. Laboratory/clinical diagnostic markers (Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated published by Schoettler et al Transplant Cell Ther. 2023) are: 1-Elevated schistocytes in peripheral blood; 2-LDH above the upper limit of normal; 3-De novo thrombocytopenia or requirement for platelet transfusion; 4-De novo anemia or requirement for red blood cell transfusion; 5-High blood pressure (≥140/90); 6-Protein/creatinine ratio \> 1 mg/mg or proteinuria ≥ 30 mg/dl in a random sample; 7-sC5b-9 above the upper limit of normal.

Secondary Outcome Measures

Name	Time	Method
Overall Survival	3, 6, 9, 12 months (follow-up period)	Proportion of TMA patients alive at each evaluation time frame
Non-relapse Mortality	3, 6, 9, 12 months (follow-up period)	Proportion of TMA patients that have died (death from any cause with exception of death due to progression or recurrence of the underlying disease) at each evaluation time frame
Proportion of patients achieving TMA response	3, 6, 9, 12 months (follow-up period)	TMA response is defined through the presence of response criteria (platelet count ≥ 50,000/mm3, lactate dehydrogenase \< 1.5 upper limit of normal, absence of schistocytes (if present at baseline) and increase in eGFR ≥ 30% from baseline or interruption of dialysis for patients on dialysis treatment at baseline), at each evaluation time frame
Proportion of patients free of transfusion requirement	3, 6, 9, 12 months (follow-up period)	Assessed through the non-requirement of transfusion of red blood cells or platelets indicated for the management of TMA for ≥ 28 days, at each evaluation time frame (Transfusions required for causes other than TMA will not be considered within the evaluation of this endpoint)
Proportion of patients with high-risk TMA,	3, 6, 9, 12 months (follow-up period)	Assessed using the following criteria: LDH \> 2 upper limit of normal; Protein/creatinine ratio \> 1 mg/mg or proteinuria ≥ 30 mg/dl in a random sample; Any multi-organ dysfunction except grade 1 acute kidney injury; sC5b-9 above the upper limit of normal; Grade II-IV acute graft-versus-host disease, systemic viral or bacterial infection, evaluated at any time up to 12 months after HSCT
Proportion of patients with multiple organ dysfunction	3, 6, 9, 12 months (follow-up period)	Assessed through specific definitions (Schoettler et al Transplant Cell Ther. 2023)

Trial Locations

Locations (1)

Instituto de Trasplantes de Alta Complejidad (ITAC); 🇦🇷 Buenos Aires, Argentina