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 |
| 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 |
| 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 |
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