Table 2.
Hematopoietic stem cell transplant outcomes for IKBKB immune deficiency.
| Patient: |
3 |
4 |
6 |
8 |
10 |
12 |
15 |
16 |
|---|---|---|---|---|---|---|---|---|
| Decade of Diagnosis | 1980s | 2000s | 2000s | 2000s | 2010s | 2010s | 2010s | 2010s |
| Identified by IKBKB NBS | No | No | No | No | No | No | Yes | Yes |
| Major Infections Present at Start of HCT | HSV | Disseminated BCG, Adenovirus, CMV | Disseminated Adenovirus, CMV | Pneumonia Syndrome ND (Likely Viral) | Parainfluenza Pneumonia | RSV Pneumonia and Serratia Marcescens Abscesses | None | None |
| Age at First HCT | 19 months | 4 months | 4.5 months | 5 months | 7 months | 8 months | 2 months | 1 month |
| Donor | Father | Half-Sibling | Mother | Unrelated | Brother | Unrelated | Unrelated | Unrelated |
| HLA Match | 6/6 antigen match (HLA-A, B, HLA—C) and non-reactive in mixed leukocyte culture | 10/10 | 10/10 | 6/6 | 10/10 | 5/6 | 5/6 | 5/6 |
| Graft Source | Marrow | Marrow | Marrow | Cord Blood | Marrow | Cord Blood | Cord Blood | Cord Blood |
| Conditioning | MAC - Bu/Cy/ATG | None | None | RIC - Flu/Mel/Campath | MAC - Bu/Cy/ATG | MAC – Bu/Cy/ATG | MAC – Bu/Flu/ATG | MAC – Bu/Flu/ATG |
| GVHD Prophylaxis | None | None | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate | Tacrolimus / Methotrexate |
| Time to ANC >0.5 × 109/L | N/A | Never Achieved | Primary Graft Failure | +14 | +23 | +15 | +15 | + 14 |
| Time to Platelets >50 × 109/L | N/A | Never Achieved | Primary Graft Failure | N/A | +31 | +54 | +44 | +35 |
| Second Transplant or Boost | No | No | Yes. Mother, Bone Marrow, Myeloablative (Bu/Flu/ATG) with neutrophil engraftment day +12. | No | No | No | No | No |
| Donor Chimerism at Last Follow-Up (Time Post-HCT) | Secondary graft-rejection of paternal marrow determined by karyotype by 3-years. | N/A. Uncertain engraftment of half-sibling marrow | 97% donor at day +12 after second transplant | Mixed Donor:Recipient with declining donor chimerism to <10% over 2-years. No myeloid donor chimerism. | T-cell: 67% | T-cell: 98% | T-cell: 95% | T-cell: 82% |
| B-cell: 96% | B-cell: 98% | B-Cell: 98% | B-Cell: 100% | |||||
| Myeloid: 80% (7-years) | Myeloid: 98% (2-years) | Myeloid: 100% (7-months) | Myeloid: 94% (5-months) | |||||
| CD3 T-Cell Count Post-HCT (x109/L) | N/A | N/A | N/A | 6.55 | 3.51 | 5.78 | 6.55 | 3.04 |
| CD4 T-Cell Count Post-HCT (x109/L) | N/A | N/A | N/A | 3.84 | 1.51 | 4.36 | 5.27 | 1.91 |
| CD8 T-Cell Count Post-HCT (x109/L) | N/A | N/A | N/A | 2.71 | 1.73 | 1.27 | 0.9 | 0.11 |
| CD56 NK cell Count Post-HCT (x109/L) | N/A | N/A | N/A | 0.61 | 0.22 | 0.13 | 0.9 | 0.11 |
| CD19 B-Cell Count Post-HCT (x109/L) | N/A | N/A | N/A | 1.57 | 1.62 | 3.26 | 5.27 | 7.98 |
| IgG (g/L) off IVIg | N/A | N/A | N/A | 19.2 | 14.2 | 6.53 | 2.06 | N/A (on IVIg) |
| IgA (g/L) | N/A | N/A | N/A | 1.62 | 2.04 | 0.65 | <0.07 | <0.07 |
| Response to Post HCT Vaccinations | N/A | N/A | N/A | No response to tetanus, diphtheria (3 vaccinations). No pneumococcal titres despite Streptococcus pneumoniae infections and conjugate and PV23 vaccination. | No response to tetanus, diphtheria (4 vaccinations). Negative anti-HBs (6 hepatitis B vaccinations). No pneumococcal titres (2 PV23 vaccinations) | Not tested. | No Post-HCT vaccinations | Too early post-HCT |
| PHA Response Post-HCT | N/A | N/A | N/A | Normal | Normal | Normal | Normal | N/A |
| Major Infections in First 6-Months Post-HCT | HSV (stomatitis, perianal, ocular) Thrush |
Disseminated BCG, Adenovirus, CMV* Streptococcus pneumoniae bacteremia |
Disseminated Adenovirus, CMV* Enterobacter cloacae bacteremia |
Streptococcus pneumoniae bacteremia | Varicella Zoster Recurrent Pneumonias |
Disseminated Adenovirus Pseudomonas aeruginosa bacteremia |
Candida Diaper Dermatitis |
Streptococcus pneumoniae bacteremia Candida Diaper Dermatitis Methicillin-Resistant Staphylococcus aureus bacteremia |
| Major Infections After 6-Months Post-HCT |
Salmonella bacteremia / gastroenteritis Disseminated Mycobacterium avium-intracellulaire* |
N/A | N/A |
Streptococcus pneumoniae bacteremia / osteomyelitis. Disseminated Mycobacterium avium-intracellulaire* |
Mycobacterium tuberculosis pulmonary disease. Staphylococcus aureus bacteremia / osteomyelitis / cellulitis HPV-70 Warts Norwegian Scabies |
Streptococcus pneumoniae bacteremia / septic arthritis Bordetella pertussis pneumonia Scabies Varicella Zoster |
Parainfluenza pneumonia Influenza A pneumonia Candida Diaper Dermatitis Streptococcus pneumoniae bacteremia / meningitis* |
N/A |
| Graft Versus Host Disease | “Mild” Acute GVHD (skin) | None | None | Grade III acute GVHD (gastrointestinal) | None | None | None | None |
| Died After HCT | Yes | Yes | Yes | Yes | No | No | Yes | No |
| Time of Death Post-HCT | 5-years | Day +9 | Day +122 | 2-years | N/A | N/A | 8-months | N/A |
| Time of Last Follow Up Post-HCT if Alive | N/A | N/A | N/A | N/A | 7-years | 6-years | N/A | 6-months |
Abbreviations: ANC: Absolute Neutrophil Count; ATG: Antithymocyte globulin; BCG: bacillus Calmette-Guerin; Bu: Busulfan; CMV: Cytomegalovirus; Cy: Cyclophosphamide; Flu: Fludarabine; GVHD: Graft-versus-host disease; HCT: Hematopoietic Cell Transplant; HPV: Human papilloma virus. HSV: Herpes simplex virus; IVIg: Intravenous immunoglobulin; MAC: Myeloablative conditioning; Mel: Melphalan; N/A: Not available; NBS: Newborn screening; ND: Not determined; RIC: Reduced intensity conditioning; RSV: Respiratory syncytial virus;
*Asterisks refer to infections that ultimately resulted in death due to multi-organ failure and/or severe neurological injury. Involvement of organs was confirmed at the time of autopsy.