Table 2 –
Hematopoietic Stem Cell Transplantation in Patients with Pathogenic PAX1 Variants
| Patient | P1 | P2 | P3 | P4 |
|---|---|---|---|---|
| Age at Transplantation | 12 months | 4.5 months | 3.5 months | 4 months |
| Transplant Characteristics | ||||
| Donor Type, HLA-matching | URD, 9/10 | Mother, 4/8 | Mother, 4/8 | URD, 4/6 |
| Source of Stem Cells | Bone Marrow | T-cell-depleted Bone Marrow | PBSC | Cord Blood |
| Conditioning Regimen | Alemtuzumab 1 mg/kg Fludarabine 150 mg/m2 Melphalan 140 mg/m2 |
Busulfan 8 mg/kg Cyclophosphamide 200 mg/kg |
First HSCT: Treosulfan 30 g/m2 Fludarabine 120 mg/m2 ATG 4 mg/kg Second HSCT (7 months): Thiotepa 10 mg/kg Cyclophosphamide 150 mg/kg ATG 25 mg/kg |
Busulfan 16 mg/kg Fludarabine 160 mg/m2 ATG 20 mg/kg |
| Engraftment and Immune Reconstitution | ||||
| Time post-transplant | 9 months | 2 months | 11.5 months after 2nd HSCT | 4 years |
| Chimerism (source) | 100% Donor, Whole Blood | Autologous | 78% Recipient; 22% Donor | 100% Donor |
| ANC (×10−3/μL) | 1.96 | 4.5 | 3.27 | 2.99 |
| ALC (×10−3/μL) | 0.71 | 0.45 | 2.7 | 0.44 |
| CD3+ cells/μL | 247 | 9 | 54 | 24 |
| CD4+ cells/μL | 76 | 4 | 13 | 21 |
| CD8+ cells/μL | 128 | 13 | 0 | 4 |
| CD19+ cells/μL | 189 | 36 | 2265 | 0* |
| CD16/56+ cells/μL | 91 | n.d. | 323 | 86 |
| Outcome, Age, Cause of Death | Alive, 6y 4m, waiting for thymic transplantation | Deceased, 9.5 m, Respiratory distress | Deceased, 4y 7m, septic shock | Alive, 4y 4m |
*
Post-rituximab for severe autoimmune hemolytic anemia.
ATG, Anti-Thymocyte Globulin; HCT, Hematopoietic Cell Transplantation; PBSC, Peripheral Blood Stem Cells; URD, Unrelated Donor