Patient and transplantation characteristics and outcome after HCT in children with MHC class II expression deficiency (N = 25)
Variables . | Results . |
---|---|
Patient characteristics | |
Year of transplant | |
1998-2007 | 6 (24) |
2008-2018 | 19 (76) |
Male | 15 (60) |
Age at diagnosis, median (range), mo | 6.5 (birth-89.6) |
Age at transplant, median (range), mo | 21.4 (0.9-93.3) |
Interval between diagnosis and HCT, median (range), mo | 9.2 (0.9-71.5) |
Newborn MHC class II expression deficiency | 4 (16) |
Positive family history | 12 (48) |
Consanguineous parents | 22 (88) |
BCG vaccination | 21 (84) |
History of PCP | 10 (40) |
Pretransplant chronic diarrhea | 13 (52) |
Growth failure at HCT (<9th centile) | 14 (56) |
Pretransplant autoimmune disease | 2 (8) |
Donor characteristics | |
Type of donor | |
MFD | 6 (24) |
MUD | 6 (24) |
MMUD* | 6 (24) |
Parental HID† | 7 (28) |
Stem cell source | |
Marrow | 7 (28) |
Unmanipulated PB | 10 (40) |
TCRαβ/CD19-depleted PBSCs | 7 (28) |
CB | 1 (4) |
Graft details, median (range) | |
Marrow | |
TNC, ×108/kg | 4.1 (2.5-11.5) |
CD34, ×106/kg | 3.4 (3.1-5.9) |
CD3, ×108/kg | 0.61 (0.37-1.0) |
CD19, ×107/kg | 3.85 (1.6-6.1) |
Unmanipulated PB | |
TNC, ×108/kg | 16.8 (13.4-42.7) |
CD34, ×106/kg | 12.5 (6.3-28.6) |
CD3, ×108/kg | 4.95 (3.4-9.6) |
CD19, ×107/kg | 9.6 (1.6-22.0) |
TCRαβ/CD19-depleted PBSCs | |
TNC, ×108/kg | 12.7 (7.6-28.0) |
CD34, ×106/kg | 26.1 (6.9-56.6) |
CD3, ×107/kg | 4.2 (1.4-45) |
CD19, ×105/kg | 6.0 (3.6-12.0) |
TCRαβ, ×104/kg | 5.0 (2.7-7.0) |
NK cells, ×107/kg | 5.5 (1.8-11.0) |
Transplant characteristics | |
Conditioning regimen | |
Myeloablative conditioning | |
Busulfan-cyclophosphamide | 3 (12) |
Treosulfan-cyclophosphamide | 2 (8) |
Fludarabine-treosulfan-thiotepa | 7 (28) |
RTC | |
Treosulfan-fludarabine | 12 (48) |
Fludarabine-melphalan | 1 (4) |
Serotherapy | |
None | 4 (12) |
ATG‡ | 8 (32) |
Alemtuzumab | 14 (56) |
GvHD prophylaxis | |
None | 5 (20) |
CSA alone | 3 (12) |
CSA + MTX | 2 (8) |
CSA + MMF | 14 (56) |
CSA + steroid (for CB) | 1 (4) |
Hematopoietic recovery | |
Days to neutrophil recovery, median (range) | 15 (8-22) |
Days to platelet recovery, median (range) | 16 (11-42) |
Transplant-related complications | |
Acute GvHD | 13 (52) |
Grade II-IV | 4 (16) |
Grade III-IV | 0 |
Chronic GvHD | 0 |
Veno-occlusive disease | 0 |
CMV viremia | 7 (28) |
Adenoviremia | 9 (36) |
HHV6 viremia | 7 (28) |
EBV viremia | 1 (4) |
Patients who required parenteral nutrition | 17 (68) |
Patients with graft failure | 3 (12) |
Secondary autologous reconstitution | 2 (8) |
Secondary aplasia | 1 (4) |
Cause of death (n = 6) | |
Pneumonitis | 4 (16) |
Cerebral hemorrhage | 1 (4) |
Infection | 1 (4) |
Variables . | Results . |
---|---|
Patient characteristics | |
Year of transplant | |
1998-2007 | 6 (24) |
2008-2018 | 19 (76) |
Male | 15 (60) |
Age at diagnosis, median (range), mo | 6.5 (birth-89.6) |
Age at transplant, median (range), mo | 21.4 (0.9-93.3) |
Interval between diagnosis and HCT, median (range), mo | 9.2 (0.9-71.5) |
Newborn MHC class II expression deficiency | 4 (16) |
Positive family history | 12 (48) |
Consanguineous parents | 22 (88) |
BCG vaccination | 21 (84) |
History of PCP | 10 (40) |
Pretransplant chronic diarrhea | 13 (52) |
Growth failure at HCT (<9th centile) | 14 (56) |
Pretransplant autoimmune disease | 2 (8) |
Donor characteristics | |
Type of donor | |
MFD | 6 (24) |
MUD | 6 (24) |
MMUD* | 6 (24) |
Parental HID† | 7 (28) |
Stem cell source | |
Marrow | 7 (28) |
Unmanipulated PB | 10 (40) |
TCRαβ/CD19-depleted PBSCs | 7 (28) |
CB | 1 (4) |
Graft details, median (range) | |
Marrow | |
TNC, ×108/kg | 4.1 (2.5-11.5) |
CD34, ×106/kg | 3.4 (3.1-5.9) |
CD3, ×108/kg | 0.61 (0.37-1.0) |
CD19, ×107/kg | 3.85 (1.6-6.1) |
Unmanipulated PB | |
TNC, ×108/kg | 16.8 (13.4-42.7) |
CD34, ×106/kg | 12.5 (6.3-28.6) |
CD3, ×108/kg | 4.95 (3.4-9.6) |
CD19, ×107/kg | 9.6 (1.6-22.0) |
TCRαβ/CD19-depleted PBSCs | |
TNC, ×108/kg | 12.7 (7.6-28.0) |
CD34, ×106/kg | 26.1 (6.9-56.6) |
CD3, ×107/kg | 4.2 (1.4-45) |
CD19, ×105/kg | 6.0 (3.6-12.0) |
TCRαβ, ×104/kg | 5.0 (2.7-7.0) |
NK cells, ×107/kg | 5.5 (1.8-11.0) |
Transplant characteristics | |
Conditioning regimen | |
Myeloablative conditioning | |
Busulfan-cyclophosphamide | 3 (12) |
Treosulfan-cyclophosphamide | 2 (8) |
Fludarabine-treosulfan-thiotepa | 7 (28) |
RTC | |
Treosulfan-fludarabine | 12 (48) |
Fludarabine-melphalan | 1 (4) |
Serotherapy | |
None | 4 (12) |
ATG‡ | 8 (32) |
Alemtuzumab | 14 (56) |
GvHD prophylaxis | |
None | 5 (20) |
CSA alone | 3 (12) |
CSA + MTX | 2 (8) |
CSA + MMF | 14 (56) |
CSA + steroid (for CB) | 1 (4) |
Hematopoietic recovery | |
Days to neutrophil recovery, median (range) | 15 (8-22) |
Days to platelet recovery, median (range) | 16 (11-42) |
Transplant-related complications | |
Acute GvHD | 13 (52) |
Grade II-IV | 4 (16) |
Grade III-IV | 0 |
Chronic GvHD | 0 |
Veno-occlusive disease | 0 |
CMV viremia | 7 (28) |
Adenoviremia | 9 (36) |
HHV6 viremia | 7 (28) |
EBV viremia | 1 (4) |
Patients who required parenteral nutrition | 17 (68) |
Patients with graft failure | 3 (12) |
Secondary autologous reconstitution | 2 (8) |
Secondary aplasia | 1 (4) |
Cause of death (n = 6) | |
Pneumonitis | 4 (16) |
Cerebral hemorrhage | 1 (4) |
Infection | 1 (4) |
Unless otherwise indicated, data are n (%).
BCG, bacille Calmette-Guérin; CB, cord blood; PB, peripheral blood; TNC, total nucleated cell dose.
Six patients had a 9/10 MMUD transplant.
Three patients received add-back T cells.
Six patients received ATG (Grafalon) and 1 patient received thymoglobulin.