Immune profiles of carriers and patients with CD40L deficiency and HSCT characteristics
| Patient ID . | Carrier characteristics . | Patient and transplant characteristics . | Transplant outcomes . | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) . | CD40L expressed in CD4 cells (%) . | B cells . | Class-switched memory B cells (%) . | Patient age at diagnosis/transplant . | Clinical features† . | Donor match and type . | Preparative regimen/ busulfan‡ . | CD34 × 106 cells per kilogram . | Myeloid/CD3 chimerism (when last checked) . | Outcome (at last follow-up) . | After HSCT, CD40L at time of evaluation . | Memory B/class-switched memory B cells (%) . | Ig replacement . | IgG/IgA/IgM, mg/dL . | Vaccine response . | Immune function phytohemagglutinin assay . | |
| 1 | 45 | 63.2 | 583 | 5.9 | 3 y/15 y | Neutropenia, Pneumocystis jirovecii pneumonia | 4/8 mismatched related donor, peripheral blood stem cells | busulfan (70)‡/fludarabine/thiotepa/anti-thymocyte globulin-r | 6.15 | 100/100 (49 mo) | Alive (49 mo) | 64.8% at 30 mo | 17/5.4 | No | 1020/158/106 (49 mo) | Protective pneumococcus, tetanus, diphtheria | Normal |
| 2 | 3 | 37 | 693 | 3.2 | 5 mo/8 mo | Neutropenia, Pneumocystis jirovecii pneumonia | 8/8 matched sibling donor, bone marrow | busulfan (64)‡/fludarabine/alemtuzumab | 23.1 | 100/91 (62 mo) | Alive (62 mo) | 34% at 62 mo | 21/3.2 | No | 1060/<7/114 (62 mo) | Protective pneumococcus, tetanus, diphtheria | Normal |
| 3 | 3.2 | 45 | 1596 | 2.6 | 5 mo/1.6 y | Neutropenia, adenovirus, cytomegalovirus, respiratory syncytial virus | 8/8 matched sibling donor, bone marrow | busulfan (64)‡/ fludarabine/anti-thymocyte globulin-r§ | 17.3 | 95/100 (28 mo) | Alive (45 mo) | 45% at 12 mo | 10.6/1.8 (L) | No | 551/75/140 (36 mo) | Protective tetanus, diphtheria, (pneumococcus not tested) | Normal |
| 4 | 9 | 54 | 164 (L) | 5 | 16 mo/3 y | Neutropenia, recurrent lower respiratory tract infections | 8/8 matched sibling donor, bone marrow | busulfan (90)‡/ fludarabine/anti-thymocyte globulin-gǁ | 16.2 | 99/92 (20 mo) | Alive (20 mo) | 35% at 20 mo | 6.3/0.5 (L) | Yes¶ | 400/<5/42# (22 mo) | Not tested | Not tested |
| 5 | 32 | 67 | 265 | Not applicable | |||||||||||||
| 6 | 35 | 78 | 43 (L) | 24.5 | |||||||||||||
| 7 | 37 | 41 | 42 (L) | 13 | |||||||||||||
| Patient ID . | Carrier characteristics . | Patient and transplant characteristics . | Transplant outcomes . | ||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age (y) . | CD40L expressed in CD4 cells (%) . | B cells . | Class-switched memory B cells (%) . | Patient age at diagnosis/transplant . | Clinical features† . | Donor match and type . | Preparative regimen/ busulfan‡ . | CD34 × 106 cells per kilogram . | Myeloid/CD3 chimerism (when last checked) . | Outcome (at last follow-up) . | After HSCT, CD40L at time of evaluation . | Memory B/class-switched memory B cells (%) . | Ig replacement . | IgG/IgA/IgM, mg/dL . | Vaccine response . | Immune function phytohemagglutinin assay . | |
| 1 | 45 | 63.2 | 583 | 5.9 | 3 y/15 y | Neutropenia, Pneumocystis jirovecii pneumonia | 4/8 mismatched related donor, peripheral blood stem cells | busulfan (70)‡/fludarabine/thiotepa/anti-thymocyte globulin-r | 6.15 | 100/100 (49 mo) | Alive (49 mo) | 64.8% at 30 mo | 17/5.4 | No | 1020/158/106 (49 mo) | Protective pneumococcus, tetanus, diphtheria | Normal |
| 2 | 3 | 37 | 693 | 3.2 | 5 mo/8 mo | Neutropenia, Pneumocystis jirovecii pneumonia | 8/8 matched sibling donor, bone marrow | busulfan (64)‡/fludarabine/alemtuzumab | 23.1 | 100/91 (62 mo) | Alive (62 mo) | 34% at 62 mo | 21/3.2 | No | 1060/<7/114 (62 mo) | Protective pneumococcus, tetanus, diphtheria | Normal |
| 3 | 3.2 | 45 | 1596 | 2.6 | 5 mo/1.6 y | Neutropenia, adenovirus, cytomegalovirus, respiratory syncytial virus | 8/8 matched sibling donor, bone marrow | busulfan (64)‡/ fludarabine/anti-thymocyte globulin-r§ | 17.3 | 95/100 (28 mo) | Alive (45 mo) | 45% at 12 mo | 10.6/1.8 (L) | No | 551/75/140 (36 mo) | Protective tetanus, diphtheria, (pneumococcus not tested) | Normal |
| 4 | 9 | 54 | 164 (L) | 5 | 16 mo/3 y | Neutropenia, recurrent lower respiratory tract infections | 8/8 matched sibling donor, bone marrow | busulfan (90)‡/ fludarabine/anti-thymocyte globulin-gǁ | 16.2 | 99/92 (20 mo) | Alive (20 mo) | 35% at 20 mo | 6.3/0.5 (L) | Yes¶ | 400/<5/42# (22 mo) | Not tested | Not tested |
| 5 | 32 | 67 | 265 | Not applicable | |||||||||||||
| 6 | 35 | 78 | 43 (L) | 24.5 | |||||||||||||
| 7 | 37 | 41 | 42 (L) | 13 | |||||||||||||
Patient ID: 1-4 indicates carriers C1-C4 and patients P1-P4; 5-7 indicates carriers C5-C7. Memory B cells are defined as CD27+ B cells; class-switched memory B cells are defined as IgD-CD27+ B cells.
IgG levels were normal in 5 of 7 carriers and borderline low in 2 carriers based on age and laboratory-specific norms.
g, Grafalon; L, low; r, rabbit.
CD40L expression was 0 in all patients, except patient 4 in whom it was 4%; IgG and IgA were undetectable in all patients; IgM was normal in 2 patients and elevated in 2 patients.
Area under the curve for busulfan (mg*h/L).
Genzyme rabbit ATG.
Grafalon rabbit ATG.
Restarted during winter months because of insufficient production.
#Ig profile before re-initiation of Ig replacement.