Unrelated partially matched lymphocyte infusions in a patient with complete DiGeorge/CHARGE syndrome

Abstract

We present an infant with cDGS overlapping with CHARGE syndrome, who suffered from T-cell deficiency treated with screened healthy DLI from an unrelated donor (8/10 match). The first dose of DLI (1.1 x 10(6) CD3+/kg) was administered at the age of six months, the second one (0.9 x 10(6) CD3+/kg) 36 days later. No conditioning was employed, GvHD prophylaxis consisting of CsA was used only during the second infusion. Since day+10 after the first DLI, split chimerism showing T-cell engraftment has been documented. Proliferative response to PHA was detected on day+145. The treatment was complicated by severe acute GvHD (grade II-III) after the first DLI and prolonged chronic liver cholestatic GvHD developing after the second DLI. Vigorous EBV proliferation four wk after the second DLI was accompanied by peripheral expansion of CD8+ donor cells. The patient, 26-months old, is clinically well and has slowly started to gain his developmental milestones. We believe that infusions of small doses of DLI from an unrelated donor represent a potentially helpful therapeutic option in patients with cDGS/CHARGE phenotype.

CHARGE syndrome: a review of the immunological aspects

“…For 23 of 26 (88%) patients, T-cell lymphopenia was concomitant with T-cell dysfunction. 14,17,18,20,[22][23][24][25][26][27][28][29][30][31]33,[35][36][37] In our collected cohort, B-and/or NK-cell numbers were reported in only 29 of 59 patients, and of these 29 patients, 1 had low B-cell numbers, 1 had high B-cell numbers, 1 had low NK-cells numbers and 3 had high NK-cell numbers. The reported B-and NK-cells numbers of other patients were normal.…”

“…14,[16][17][18][19][20][21][22] Three patients had features resembling Omenn syndrome, a form of severe combined immune deficiency, characterized by autoimmune-like features and macular skin rash due to the formation of abnormal, autoreactive T cells. 18,23 Other severe presentations included a patient with recurrent oral candidiasis, recurrent severe infections, and septic shock due to colonization with multiresistant species of Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Acinobacter (Janda et al, 22 Table 1B); another patient with severe general dermatitis and ulcers of the colon (Boudny et al, 24 Table 1B); and a patient with CHARGE association and T-cell deficiency with a chronic viral infection of the gut (Wood et al, 25 Table 1C). …”

“…T-cell lymphopenia in our collected cohort was associated with thymic aplasia or hypoplasia in 21 of 22 (95%) patients. [18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] T-cell function by response on mitogens was available for 28 of 59 patients and of these 28 patients 24 (86%) had a low or absent response on mitogen. For 23 of 26 (88%) patients, T-cell lymphopenia was concomitant with T-cell dysfunction.…”

“…14,17,[22][23][24][25][26][27][28][29]35,36 Thirteen of 33 (39%) patients with known immunoglobulin levels had IgG deficiency and 2 of these patients had received immunoglobulin replacement therapy. 14,[16][17][18][22][23][24][25][26][27][28][29]38 Of these 13 patients with IgG deficiency, 6 had recurrent or chronic infections and 1 had absent specific antibody responses. 14,[16][17][18]22,24,25 Isolated immunoglobulin deficiencies were rarely reported in CHARGE syndrome.…”

“…14,[16][17][18][22][23][24][25][26][27][28][29]38 Of these 13 patients with IgG deficiency, 6 had recurrent or chronic infections and 1 had absent specific antibody responses. 14,[16][17][18]22,24,25 Isolated immunoglobulin deficiencies were rarely reported in CHARGE syndrome. One patient with an isolated IgG2 subclass deficiency 17 and two patients with an isolated IgA deficiency 14 were reported.…”