This is somewhat similar to the situation seen when multiple cord blood units are given to one recipient, in which case chimerism from one particular unit becomes dominant.29 Even though factors that determine dominance of one donor over another have not been clarified, immune-mediated mechanisms are suspected. syndrome caused by mutations in at least 13 different genes. It is characterized by the absence of T-cells. Immune reconstitution can be achieved through non-ablative related donor bone marrow transplantation. However, the first transplant may not provide sufficient immunity. In these cases, booster transplants may be helpful. A prospective/retrospective study was conducted of 49 SCID patients (28.7 percent of 171 SCIDs transplanted over 30 years) who had received booster transplants to define the long term outcome, factors contributing to a need for a booster and factors that predicted success. Of the 49 patients, 31 (63 percent) are alive for up ADL5747 to 28 years. Age at initial transplantation was found to have a significant effect on end result (mean of 194 days old for patients currently alive, versus a mean of 273 days aged for those now deceased, p=0.0401). Prolonged viral contamination was present in most deceased booster patients. In several patients, the use of two parents as sequential donors resulted in striking T and B cell immune reconstitution. A majority of the patients alive today have normal or adequate T-cell function and are healthy. Non-ablative booster bone marrow transplantation can be life-saving for SCID. pneumonia and oral moniliasis were found to be most common at presentation and resolved with appropriate therapy. All but 4 deceased patients experienced a clinically documented chronic viral contamination, whereas 93.33% of living patients have never experienced a clinically documented chronic viral infection. This difference was highly significant (X2=24.85, N=47 P 0.0000). Current Clinical Statuses The 31 living patients current clinical statuses were evaluated in 6 groups and a score was calculated with 6 being the most unhealthy. Patients were included in this evaluation if they had been seen within the last 2 years or had responded to a recent questionnaire (N=28).18 The categories were regular antibiotic use, ADHD, neurological issues, ADL5747 gastrointestinal issues, receiving Cs or lower in school, and being in the 5th percentile or below in height or weight. The average clinical total score was 1.8 (S.D. 1.6). Immune Reconstitution Lymphocyte Enumeration and T-Cell Function All infants lacked T-cells prior to initial transplantation. As expected, transplants that resulted in improved immune function were more often found in patients who are now alive. Shown in Table 2 are the latest results of SELPLG immune evaluations in all patients. The absolute numbers of CD3 (z=3.609, p=0.0003) and CD4 (z=4.096, P 0.0001) positive T cells were significantly higher in the surviving patients, but the percentage of CD45RA positive T cells was not significantly different when compared to that of the deceased (z=1.535, p=0.1247). Improved T-cell function, measured by lymphocyte proliferation assays, was used to assess immune reconstitution. If a patient experienced one response greater than 50,000 CPM to any of the mitogens tested, the transplant was considered to have improved T-cell function. Seventy-five of 130 transplants given to these patients resulted in improved T-cell function; 62 (78%) of these transplants were in patients who are currently living, while only 13 were in patients who are deceased. This difference was found to be highly significant (p 0.0000 X2=32.4369, N=129). Mean responses to PHA (cpm) at the latest evaluations were also significantly higher in the living patients (z= 4.210, p 0.0001) (Table 2). Table 2 Latest Immune Function in Boosted Patients thead th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Pat. No. /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ SCID Type /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Age (da) 1st Trans* /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ # Boosts /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ DR Sex** /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Days to 1st Boost /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Days to Last Boost /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Donor B cells /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ mg/dl IgA /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ mg/dl IgM /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ IG RX*** /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Donor T Cells /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ #/cmm CD3 /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ #/cmm CD4 /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ #/cmm CD8 /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ % CD3+ CD45RA+ /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ % CD3+ CD45RO+ /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ TREC g/ml /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Medium CPM /th th valign=”top” ADL5747 align=”center” rowspan=”1″ colspan=”1″ PHA CPM /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Yrs Post Trans* /th /thead Alive1ADADef1121F-FM2908NAYes78440Yes514297152NDNDN.D.4,46040,44723.682ADADef1822F-F-MM145702No67631No10761367.067.011219124,25715.223ADADef1351F-FM4074NANo52241Yes45726614211.869.4N.D.1,73824,84612.594AutoRec1472F-M-FM168154No001ND50947831NDNDN.D.14924,05614.405AutoRec1702F-F-MF12511374No001ND5826328.056.0 1001087,29612.526AutoRec3031F-MF215NANo7101Yes50635214241.237.0N.D.190137,6153.297CartHair2071F-FM4515NANo001Yes1925834117032.845.6N.D.1942,44322.458CD3Def1712M-F-MF1831027No1081210Yes5514409413.857.91,130691255,03823.569RAG2Def1192F-F-FM13812198No001Yes241971272.376.2 10016623,45724.1010RAG2Def3953F-F-F-FM586699No001Yes5593012476.864.2 1008616,05811.6511RAG2Def332F-F-FM3291430No1201Yes272611.691.6N.D.1,62018,0896.5812RAG2Def1621F-FM616NANo041Yes3141541542.071.8 10020362,6026.1013RAG1Def252F-F-MM189483No001Yes11973785829.877.9 100226226,2908.2214IL7RDef1641F-MM174NANo2591130Yes90350942653.123.6906327242,17822.715IL7RDef3941M-MF614NANo1031970Yes53022125513.054.4119151184,90611.9616IL7RDef3221F-FF210NANo01780Yes109573633652.420.66,010293177,1387.5517IL7RDef122F-F-MM254154No29761Yes64628332060.522.3 100128142,3423.6818Jak3Def2381F-FM3129NANo0831Yes92633949022.940.7126785260,86027.219Jak3Def3342M-M-CF317195Yes1392770Yes74665097206377.69.82,740847203,59516.920Jak3Def1652M-M-FF203196Yes97640Yes144676557561.114.114,000247160,3288.221X-linked452F-F-FM4869532No0161Yes413693733723.886.08748429,11827.122X-linked2171F-FM6941NANo38461Yes158862092014.756.2 1009860,07624.823X-linked1752M-M-MM1314823No0131Yes1851433136810.665.0 1009787,13919.424X-linked2893F-M-F-MM146796Yes121760Yes82453223135.528.6 100292157,80519.025X-linked3672F-F-FM13041827No081Yes2901871013.882.3 10017528,44817.226X-linked3511F-FM1641NANo12491Yes83957325930.350 100876212,32016.827X-linked101M-MM238NANo0251Yes1827387128919.440.5 10031885,51916.728X-linked1631F-CM141NAYes761620Yes174969186254.223.9N.D.179181,49716.029X-linked2241F-FM182NANo01051Yes2047114679855.011.374102,658112,4109.8230X-linked1101F-FM1750NANo0191Yes114044760435.536.4352128212,6328.8831X-linked2603F-F-M-MM322700No17661Yes5947115.379.3 10028255,4547.09Medians1712322701546824387259155490620387,13915Means19421,2621,0815/31346922/3128/311,17257055526503,071580111,49215Deceased32ADADef2551F-FM276NANo388421Yes1150129254NDNDND2583213.5633ADADef2501M-MF340NANo14994103759727722.567.915146745,44518.2734ADADef1401F-FM196NANo001012763ND1.772.9ND2,62110,8330.5835AutoRec1983M-F-F-CF138252No001Yes810250.010.0ND10841,1791.7236AutoRec1811F-FF1271NANo001Yes290235525.180.4369956,79512.3637AutoRec4471F-MF159NANo218107546230.074.7ND2358,1230.8838Cd3Def3953F-F-M-MF105651No627010910219225.514.8ND872,2646.9539RAG2Def1092F-F-FM161751No00101865816910.692.3ND4,56511,5113.1640IL7RaDef1991F-FM117NANo01810111048NDNDND1,2311,2820.341IL7RaDef5593F-F-M-FM91266No54318105551021.088.507662,8732.042IL7RaDef1622F-F-MM15491No83210531825.89.7ND2231,8530.843Jak3Def4482F-F-G-M161119No0481042240.830.802504941.944X-linked5972F-F-FM208558No02101511711NDNDND106115572.445X-linked1942F-F-CM54351No671861Yes34181837.150.4ND7710138,6082.046X-linked2221F-FM987NANo04151Yes13412129735.850.6039127,0054.647X-linked1471F-FM357NAYes15615701Yes8406156242500.188.4ND46626,5641.248Unknown2201F-FM483NANo110103524287.584.6ND594351844.249Unknown1904F-M-F-M-CM124323No172510182NDND11.744.7ND9868,7142.2Medians210217926652965585011685318,4192Means27323263401/1851158186/1868415840116571,28321,1454p=0.04p=0.02p= 0.03p=0.0003p 0.0001p=0.02p=0.13p 0.0001p 0.0001 Open in a separate window *Trans=first transplant **F=female, M=male, C=unrelated cord, G=gene therapy ***IG RX=immunoglobulin treatment, 1=Yes B-cell Function B-cell function has proven difficult to reconstitute in SCID patients.3,19C21 Two patients reported here (#s 9 and 18, Table 2) were given boosters solely to gain B-cell function, and both failed. Currently, only 9 (29%).