Assessing the Incidence of Transplant Associated Thrombotic Microangiopathy (TA-TMA) in Adult Patients Undergoing Allogeneic Stem Cell Transplant (SCT)

Manuel Ricardo Espinoza-Gutarra

Status: Begins enrollment this month

Conditions: Transplant Complication; Transplant Associated Microangiopathy TAM

Study type: Observational

Funder types: Other

Identifiers

NCT07381205

UAB2537

Details and patient eligibility

About

The goal of this observational study is to learn about the incidence of Transplant Associated Thrombotich Microangiopathy (TA-TMA), which is a known but underreported complication of Allogeneic Stem Cell Transplant (SCT). The main question it aims to answer is:

What is the incidence of TA-TMA in adults undergoing SCT? How does TA-TMA diagnosis impact survival and other outcomes? Patients undergoing SCT will be eligible for this study, which will consist of collection of biological samples and standard clinical follow up.

Full description

This will be a prospective non-interventional study that will include patients undergoing allogeneic stem cell transplant (SCT) deemed to be at high risk for developing Transplant Associated Thrombotic Microangiopathy (TA-TMA). All patients will have prospective biospecimens collected per study schedule starting prior to SCT. Biospecimens will be collected for use in translational testing and sent to Viracor for commercial testing. Results of commercial testing will be made available to treating physicians. Diagnosis of TA-TMA will be made based on clinical and laboratory values according to existing consensus guidelines, however, therapeutic decisions will be left up to the treating clinical team. Patients will be followed up for clinical outcomes.

Enrollment: 85 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Inclusion Criteria

  1. Adult male or female, age ≥18

  2. Undergoing allogeneic SCT at UAB for any indication and any donor source.

  3. For patients in cohort 1: Patients deemed high-risk for developing high-risk TA-TMA as stated by any of the following criteria*:

     1. BMI > 35[42]

     2. Mismatched donor (either Haploidentical or Mismatched Unrelated donor)[18, 29]

     3. Non-Malignant Transplant Indication (Severe Aplastic Anemia or Sickle Cell Disease)[18, 43]

     4. Acute Lymphoblastic Leukemia (any kind)[18, 31]

     5. African American, Hispanic, Asian or Native American Ethnicity [44]

     6. Myeloablative Conditioning Regimen[18]

     7. Pre-Existing Renal Disease** (defined as any of the following: 24 Hr Creatinine Clearance <60, baseline serum creatinine > 1.2, 24 hr proteinuria >150mg or random spot urine Protein Creatinine ratio > 150mg/g)[20, 45]

     8. TBI-containing conditioning regimen >400cGy [46]

     9. Prior Autologous or Allogeneic SCT[45]

        • *Some of these criteria have been adapted from pediatric literature due to a higher number of publications in that setting and in cases where the adult data is lacking or contradictory.
        • **Proteinuria thresholds are obtained from KDIGO guidelines and include moderate and severe levels of proteinuria[47].

  4. Females of childbearing potential must have a negative urine or serum pregnancy test prior to enrollment.

  5. For patients in cohort 2: Patients who develop GVHD with any of the following characteristics and were not included in cohort 1

     1. Grade III-IV aGVHD, or SR-aGVHD of any grade, whichever occurs first
     2. Moderate to Severe cGVHD or SR-cGVHD of any grade, whichever occurs first

  6. For patients in cohort 3: Patients included in either cohort 1 or 2 who are diagnosed with TA-TMA and receive eculizumab

Exclusion criteria

• Exclusion Criteria

  1. Any other active malignancy requiring treatment or with expected survival ≤1 year.
  2. Patients with psychiatric illness or social situations that would limit compliance with the study requirements.

Trial design

85 participants in 3 patient groups

Cohort 1

Description:

Main Cohort of patients who fulfill Inclusion Criteria

Cohort 2

Description:

Patients who develop GVHD with any of the following characteristics and were not included in cohort 1 1. Grade III-IV aGVHD, or SR-aGVHD of any grade, whichever occurs first 2. Moderate to Severe cGVHD or SR-cGVHD of any grade, whichever occurs first

Cohort 3

Description:

Patients included in either cohort 1 or 2 who are diagnosed with TA-TMA and receive eculizumab