Table 1.
HCT outcomes for CNS-HLH patients
| Patient | 1 | 2 | 3 | 4 (first SCT) | 4 (second SCT) |
|---|---|---|---|---|---|
| Bone marrow donor source | HLA-B, HLA-C mismatched unrelated | HLA-matched unrelated | HLA-matched unrelated | HLA-matched sibling | HLA-matched unrelated |
| Conditioning* | Reduced-intensity alemtuzumab (−14), fludarabine (5 d), melphalan | Reduced-intensity alemtuzumab (−14), fludarabine (5 d), melphalan | Reduced-intensity alemtuzumab (−14), fludarabine (5 d), melphalan | Reduced-intensity alemtuzumab (−14), fludarabine (5 d), melphalan | Reduced-intensity alemtuzumab (−8), fludarabine (6 d), busulfan |
| Total marrow cell, dose/kg | 3.32e+08 | 2.82e+08 | 5.29e+08 | 5.93e+08 | 5.30e+08 |
| Duration to myeloid engraftment, d† | 14 | 13 | 13 | 13 | 16 |
| Duration to platelet engraftment, d† | 12 | 19 | 17 | 144 | 14 |
| Patient-specific toxicities | Pericardial effusion, posttransplant microangiopathy (not requiring eculizumab) | Disseminated adenovirus infection, parainfluenza virus respiratory infection, Clostridium difficile colitis | C difficile colitis | Adenovirus viremia cytomegalovirus viremia, Staphylococcus aureus and α-hemolytic Streptococcus bacteremia, recurrent C difficile colitis | CMV reactivation, coagulase negative Staphylococcal bacteremia |
| Day +100 chimerism | CD3 and WB >97% donor | CD3 13%, WB 95% donor | CD3 26%, WB 52% donor | CD3 33%, WB 79% donor | CD3 69%, WB >97% donor |
| Most recent chimerism | 37 mo: CD3, WB, CD33/66 >97% | 27 mo: CD3 91%, WB 91%, CD33/66, CD56 >97% | 23 mo: CD3 23%, WB 20%, CD33/66 9%, CD56 22% | At relapse: CD3 46%, WB 47%, CD33/66 51%, CD56 50% | 14 mo: CD3 91%, WB >97%, CD33/66, CD56 >97%, |
| NK-cell perforin positivity (normal, 73%-91%) | 37 mo: 93% | NP | NP | At relapse: 52% | 3 mo: 87% |
| CD107a expression (normal, 11%-35%) | NP | 20 mo: 11% | 17 mo: 11% | At relapse: 11% | NP |
| CD107a MCF (normal, 206-678 MCF) | NP | 20 mo: 413 | 17 mo: 212 | At relapse: 209 | NP |
| Most recent MRI monitoring, mo | 30 | 23 | 17 | 13 | 9 |
| Duration of follow-up post-BMT, mo | 39 | 32 | 28 | Relapse: 13 | 15 |
*
Parentheses indicate number of days before HCT for start of alemtuzumab administration or total number of days of fludarabine administration.
†
Myeloid engraftment defined as absolute neutrophil count stably >0.5 × 109/L; platelet engraftment defined as platelet count stably >50 × 109/L.
CD3, T-cell donor chimerism; CD33/66, myeloid donor chimerism; CD56, NK-cell donor chimerism; MCF, mean channel fluorescence; NP, not performed; SCT, stem cell transplantation; WB, whole blood donor chimerism.