Efficacy of iptacopan in treatment of transplant-associated thrombotic microangiopathy (TA-TMA) post-allogeneic hematopoietic stem cell transplantation: A case series analysis

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is pivotal for treating blood disorders but is complicated by graft-versus-host disease (GVHD), infections, and transplant-associated thrombotic microangiopathy (TA-TMA). This case series evaluates the clinical utility of novel agents (Iptacopan, Vedolizumab, Ruxolitinib) in managing these complications. Case Summaries Methods -Interventions: Novel agents combined with standard therapies (immunosuppressants, antivirals). -Monitoring: Serial blood counts, liver/kidney function, viral load (CMV/EBV DNA), and coagulation profiles. Results Symptom Improvement: GVHD: Reduced diarrhea frequency (Case 2) and abdominal pain severity (Case 3) with vedolizumab.TA-TMA: Stabilized blood pressure and improved renal function using Iptacopan. Lab Trends: Blood Counts: Platelet recovery in Case 2 (19→44×10⁹/L).Liver Function: Declined ALT/AST (Case 3: ALT 35→25 U/L).Viral Load: EBV DNA turned negative in Cases 2 and 3. Safety: Infections: EBV/Enterococcus faecium reactivation (Case 3).Organ Toxicity: Transient liver enzyme elevation (Case 1). Discussion - Efficacy: Novel agents demonstrated targeted efficacy in GVHD/TA-TMA with improved lab parameters.Safety: Increased infection risk and transient organ toxicity necessitate vigilant monitoring.Personalization: Tailored dosing based on genetic/clinical factors may optimize outcomes. Conclusion: Iptacopan, Vedolizumab and Ruxolitinib show promise in managing post-allo-HSCT complications. Balancing efficacy with safety through personalized regimens and long-term follow-up is critical. Keywords: Allo-HSCT, GVHD, TA-TMA, Novel agents, Iptacopan, Vedolizumab, Ruxolitinib Table: Baseline Characteristics vs. Post-Treatment Lab Trends Case Diagnosis Complications Key Novel Agents Used 1 Severe Aplastic Anemia (SAA) Intestinal GVHD, TA-TMA, Cytomegalovirus (CMV) viremia Iptacopan, Vedolizumab 2 Myelodysplastic Syndrome (MDS)-EB-2 Intestinal GVHD, TA-TMA, Epstein-Barr Virus (EBV) infection Iptacopan 3 MDS-LB Liver/Intestinal GVHD, TA-TMA, EBV viremia Iptacopan, Vedolizumab, Ruxolitinib Parameter Case I (41F, SAA) Case II (53F, MDS-EB-2) Case III (28M, MDS-LB) Baseline Characteristics Diagnosis Severe Aplastic Anemia (SAA) Myelodysplastic Syndrome with Excess Blasts-2 (MDS-EB-2) Myelodysplastic Syndrome-Low Blast (MDS-LB) Pre-Treatment Labs - WBC: ↓ (2.13×10⁹/L)- HGB: 65g/L↓- PLT: 4×10⁹/L↓↓- ALT/AST: ↑ (44.56/50.96 U/L) - WBC: ↓ (3.73×10⁹/L)- HGB: 44g/L↓↓- PLT: 19×10⁹/L↓- PT/INR: ↑ (24.8s/2.17) - WBC: ↑ (15.42×10⁹/L)- HGB: 105g/L↓- ALT/AST: ↑ (35.49/47.32 U/L)- D-dimer: 3.56 mg/L↑ Complications CMV viremia, TA-TMA, intestinal GVHD, heart failure EBV infection, TA-TMA, intestinal GVHD EBV viremia, liver GVHD, intestinal GVHD, TA-TMA New Drugs Used Iptacopan, Vedolizumab Iptacopan Iptacopan, Vedolizumab, Ruxolitinib Post-Treatment Trends Blood Routine - WBC/HGB/PLT: Continued fluctuations (no stabilization) - PLT: ↑ (improvement)- WBC/HGB: Partial stabilization - WBC: Stabilized- HGB/PLT: Gradual improvement Liver Function - ALT/AST: Persistent fluctuations (disease/drug-related) - Bilirubin: Improved with supportive care - ALT/AST: ↓ (improved with ruxolitinib)- Bilirubin: Stabilized Kidney Function - Creatinine: Fluctuations - Urea/Creatinine: Partial improvement - Creatinine: Stabilized Coagulation - PT/INR/D-dimer: Persistent abnormalities - PT/INR: Partial improvement - D-dimer: ↓ (3.56 → lower)- Fibrinogen: Remained low Viral Load - CMV DNA: Controlled (↓ with ganciclovir/foscarnet) - EBV DNA: Turned negative - EBV DNA: Significant ↓ Other - Heart failure: Improved with cardiac drugs - Brain lesions: Stabilized with adjusted treatment -Hypokalemia/Hyponatremia: Corrected