Table II.
Infants with low TRECs and T cell lymphopenia who required immune restoring therapy.
| SCID case # | Sex | Ethnicity | Nurserya | TREC copies | Lymphocyte phenotype | CD3 T cells | CD4 CD45RA T cells | Disease causing gene (mutations)b | Presenting clinical informationc |
|---|---|---|---|---|---|---|---|---|---|
| CA007 | M | Black | NICU | 0/μL | T− B+ NK− | 493/μL | <20/μL | IL2RG (R226C18) | 35 week gestation, prenatal diagnosis (older affected brother). Asymptomatic, infection-free; maternal engraftment present; PHA <10%. |
| CA053 | M | Hispanic | Regular | 0 | T− B+ NK− | <20 | <20 | IL2RG (M270fs) | Asymptomatic, infection-free, XY/XO mosaic; no maternal engraftment, PHA <10%. |
| CA096 | M | Asian | NICU | 0 | T− B+ NK− | 20 | <20 | IL2RG (W177X) | 1 of triplets, 33 week gestation, asymptomatic, infection-free; maternal engraftment present; PHA <10%. |
| CA125 | M | Hispanic | Regular | 0 | T− B+ NK− | 78 | 23 | IL2RG (L132R) | Asymptomatic, infection-free; maternal engraftment present; PHA <10%. |
| CA103 | F | Hispanic | Regular | 4 | T− B+ NK− | 1736 | <20 | JAK3 (L527_G528del) | Rash and cellulitis; maternal engraftment present; PHA not tested. |
| CA004 | F | Hispanic | Regular | 0 | T− B+ NK+ | 60 | 49 | IL7R (F71S, H180P) | Asymptomatic, infection-free; maternal engraftment present; PHA <10%. |
| CA005 | F | Hispanic | Regular | 0 | T− B+ NK+ | <20 | <20 | IL7R (I94fs, H180P) | Asymptomatic, infection-free, but acquired coxsackie virus at home pre-HCT; maternal engraftment present, PHA <10%. |
| CA067 | F | Hispanic | Regular | 0 | T− B+ NK+ | <20 | <20 | IL7R (G215V) | Asymptomatic, infection-free; maternal engraftment present, PHA <10%. |
| CA013 | M | Hispanic | Regular | 0 | T− B− NK+ | <20 | <20 | RAG1 (M661del) | Asymptomatic, infection-free, maternal engraftment not tested; PHA not tested. |
| CA027 | M | Hispanic | Regular | 0 | T− B− NK+ | 28 | <20 | RAG1 (R404Q19 R764P) | Rash coinciding with TREC report, deceased affected brother, infection-free; maternal engraftment present; PHA not tested. |
| CA177 | M | Hispanic | NICU | 0 | T− B+ NK+ | 80 | 3 | unknownd | 37 week gestation, maternal diabetes & hepatitis. Low glucose, respiratory distress, hepatomegaly, feeding difficulties; maternal engraftment present; PHA <10%. |
| CA024 | F | White | Regular | 20 | T− B− NK+ | 1583 | 24 | RAG1 (W522C20, N968K) | Asymptomatic, infection-free; no maternal cells; PHA not done. Omenn syndrome. |
| CA174 | F | Hispanic | Regular | 0 | T− B− NKlow | 51 | 3 | RAG1 (R474C21, I956T22) | Asymptomatic, infection-free, but acquired rhinovirus at home pre-HCT; no maternal cells; PHA 50%. Leaky SCID. |
| CA158 | F | White | Regular | 19 | T− B+ NK+ | 380 | 99 | RMRP I (r.211c>g, 262g>u)23 | Intrauterine growth retardation, short limbs; no maternal cells; PHA 40%. Leaky SCID, cartilage hair hypoplasia. |
| CA019 | F | Hispanic | NICU | 0 | T− B+ NK+ | <20 | <20 | 22q11 deletion | Complete DiGeorge syndrome with congenital heart disease. |
| SCID case # | Treatmente / donor (match) / cell type | Age at HCT(s) | Conditioningf | Graft vs. host disease prophylaxisg | Clinical courseh | Current status (age)i |
|---|---|---|---|---|---|---|
| CA007 | HCT, CD34-selected maternal cryopreserved mobilized peripheral blood | 3 wk | None | None | Acute skin graft vs. host disease (GvHD); T cell engraftment | Alive (28 mo), vitiligo, on IVIG |
| CA053 | HCT, MUD (10/10) bone marrow | 2.5 mo | G-CSF, Plerixafor | CsA | Slow T cell recovery, →boost | Alive (21 mo), on IVIG |
| Boost: 4 mo | None | CsA, MTX, tacrolimus | T cell engraftment | |||
| CA096 | HCT, maternal CD34-selected peripheral blood | 8 wk | None | None | Slow T cell recovery, →boost | Alive (15 mo), on scIG |
| Boost: 4 mo | None | CsA, methylprednisolone | T cell engraftment | |||
| CA125 | Autologous transduced CD34 cell gene therapy (trial #NCT01129544) | 4 mo | None | None | Failed T cell engraftment → unrelated donor cord blood HCT, T cell engraftment | Alive (13 mo), on IVIG, |
| CA103 | HCT, MUD (10/10) bone marrow | 4 mo | Flu, Bu, rATG, KGF | MTX, tacrolimus, methylprednisolone | T cell engraftment | Alive (14 mo), on IVIG |
| CA004 | HCT, maternal CD34-selected peripheral blood | 2 mo | Plerixafor | None | T cell engraftment and B cell function | Alive (28 mo), off IVIG, given live vaccines |
| CA005 | HCT, MUD (10/10) bone marrow | 4.5 mo | Flu, Bu, Cytoxan | Tacrolimus, MTX | T cell engraftment and B cell function | Alive (28 mo), off IVIG |
| CA067 | HCT, maternal CD34-selected peripheral blood | 1.5 mo | None | None | Slow T cell recovery, →boost | Alive (17 mo), on scIG |
| Boost: 5 mo | None | None | T cell engraftment | |||
| CA013 | HCT, matched sibling bone marrow | 3.5 mo | rATG x3 | Tacrolimus | Autologous recovery, →2nd HCT | Alive (27 mo), off IVIG |
| 2nd HCT: 9 mo | Flu, Bu, rATG | Tacrolimus | T cell engraftment | |||
| CA027 | HCT, unrelated (7/10) umbilical cord blood | 4 mo | Flu, Bu, rATG | Tacrolimus, methylprednisolone | Veno-occlusive disease (d+28), pulmonary hemorrhage | Died day +46 (at 5 mo) post transplant |
| CA177 | HCT, MUD (10/10) bone marrow | 4 mo | Flu, Bu, rATG, KGF | Tacrolimus, MTX, methylprednisolone | Acute skin and gut GvHD; T cell engraftment | Alive (7 mo), on IVIG |
| CA024 | HCT, MUD (9/10) T cell-depleted mobilized peripheral blood | 3.5 mo | Flu, Bu, Campath | CsA, MMF | Slow T cell recovery, →boost | Alive (25 mo), on IVIG |
| Boost: 7 mo | Flu, ATG | CsA, MMF | T cell engraftment | |||
| CA174 | HCT, MUD (9/10) bone marrow | 4.5 mo | Flu, Bu, Campath | MTX, CsA | T cell engraftment | Alive (7 mo), on IVIG |
| CA158 | HCT, MUD (10/10) bone marrow | 7 mo | Flu, Bu, Campath | MTX, CsA | T cell engraftment | Alive (9 mo), on IVIG |
| CA019 | Thymus transplant | 12 mo | Bu | None | Immune reconstitution; heart surgery after transplant | Alive (26 mo), off CsA, on IVIG |
a
NICU: neonatal intensive care unit.
b
Single mutation: hemizygous in IL2RG, homozygous for other genes, heterozygous for 22q deletion. Two mutations: compound heterozygotes. Previously reported mutations are referenced with superscript numbers; others not published to date.
c
Proliferative response in vitro to phytohemagglutinin, <10% of healthy control range is a criterion for diagnosis of typical SCID; 10–50% consistent with leaky SCID.
d
No damaging variants found in ADA, AK2, CD3D, CD3E, CD3Z, DCLRE1C, IL2RG, IL7R, JAK3, LIG4, NHEJ1, PNP, PTPRC, RAC2, RAG1, RAG2, RMRP, ZAP70.
e
HCT, hematopoietic cell transplant; MUD, matched unrelated donor.
f
G-CSF, granulocyte colony stimulating factor; Flu, Fludarabine; Bu, Busulfan; rATG, rabbit anti-thymocyte globulin; KGF, keratinocyte growth factor.
g
CsA, cyclosporine A; MTX, methotrexate; MMF, mycophenolate mofetil.
h
No major infectious complications.
i
IVIG, intravenous immunoglobulin; scIG, subcutaneous immunoglobulin.