Background Combined immunodeficiencies (CIDs) form a heterogeneous group of inherited conditions that affect the development, function, or both of T cells. The treatment of CIDs with allogeneic ...hematopoietic stem cell transplantation (HSCT) is complicated by a high incidence of life-threatening infections and an increased risk of graft-versus-host disease (GVHD). Objective In view of the growing evidence that alloreactivity is mainly derived from human naive T cells, the selective depletion of naive T cells from allografts might constitute a way of reducing alloreactivity while maintaining memory T-cell responsiveness to pathogens. Methods Five consecutive patients with CIDs and chronic viral infections underwent an allogeneic, HLA-mismatched HSCT. Given the patients' infection status and the potential risk of severe GVHD in the mismatched setting, the CD34− fraction of the allograft was depleted of naive T cells by using magnetic CD45RA beads. Results Engraftment occurred in 4 of the 5 patients. No severe GVHD occurred. In the 4 engrafted patients viral infections were cleared within 2 months of the HSCT, and both cellular and humoral immunity were re-established within a year of the HSCT. An early T-cell response against viral pathogens was documented in 2 patients. Conclusion The present pilot study shows that clinical-grade depletion of naive T cells from an allograft through the use of magnetic CD45RA beads seems to be a feasible and efficacious option for the treatment of patients with CIDs at high risk of GVHD, infection, or both in an HLA-mismatched setting.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
The CEC count was persistently higher at day 30 in patients with VE (median = 98/mL; range: 1-548) as compared to patients without VE (median = 4/mL; range: 2-52; P = .002) (Fig 1, A). ...the ...increase of CEC counts was significantly higher in patients with VE during the first month post-transplant (median δD0-D30 = 92; range: 16.5-547; P = .007) as compared to patients without (Fig 1, B).  No vascular event (n = 23) Vascular event (n = 11) Total patients (n = 34) Sex ratio female/male 9/14 3/8 12/22 Age: median (range) 3 y (0.5-14 y) 0.9 y (0.25-9 y) 3 and 5 y (0.25-14 y) Diagnosis    SCID 6 2 8 CID 8 5 13 HLH 5 3 8 Neutrophil disorders 3 1 5 Donor    Matched sibling donor 7 0 7 MUD 7 5 12 MMUD 4 2 6 Haploidentical donor 5 4 9 Defibrotide conditioning regimen 8 9 17 Bu/Flu/ATG 16 6 22 Bu/Flu/ThioTEPA/ATG 6 5 11 Mel/Flu/Alemtuzumab 1 0 1 Graft characteristics    In vitro T-depletion 5 6 11 No in vitro T-depletion 18 5 23 CD34 cell dose (106/kg) 8.2 (1.4-24.2) 13 (5-24.2) 10.5 (1.4-24.2) Engraftment day 19 (9-49) 18.5 (13-31) 19 (9-49) Rejection 2 1 3 GVHD 8 3 11 Grade 1-2 6 1 7 Grade 3-4 2 2 4 Time onset (days) 16.5 (2-60) 27 (10-47) 17 (2-60) CMV systemic replication 4 3 7 Severe sepsis 2 1 3 Duration of hospitalization post-HSCT (days) 78 (38-212) 92 (56-155) 83 (38-212) Death 3 5 8 Table I Hematopoietic transplantation characteristics For CD34 number, engraftment, time of onset of GVHD, and duration of post-HSCT hospitalization, median time is indicated with range in brackets.ATG, Antithymocyte globulin; Bu, busulfan; CID, combined immunodeficiency; CMV, cytomegalovirus; Flu, fludarabine; HLH, hemophagocytic lymphohistiocytosis; Mel, Melphalan; MMUD, mismatched unrelated donor; MUD, matched unrelated donor; SCID, severe combined immunodeficiency.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
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