• Active infection pretransplant adversely impacts survival (81% in patients with active infection vs 95% in infectionfree patients; P 5 .009).• Preparative chemotherapy improved 1-year post-HCT median CD4 counts (P 5 .02) and freedom from IV immunoglobulin (P , .001).The Primary Immune Deficiency Treatment Consortium (PIDTC) is enrolling children with severe combined immunodeficiency (SCID) to a prospective natural history study. We analyzed patients treated with allogeneic hematopoietic cell transplantation (HCT) from 2010 to 2014, including 68 patients with typical SCID and 32 with leaky SCID, Omenn syndrome, or reticular dysgenesis. Most (59%) patients were diagnosed by newborn screening or family history. The 2-year overall survival was 90%, but was 95% for those who were infection-free at HCT vs 81% for those with active infection (P 5 .009). Other factors, including the diagnosis of typical vs leaky SCID/Omenn syndrome, diagnosis via family history or newborn screening, use of preparative chemotherapy, or the type of donor used, did not impact survival. Although 1-year post-HCT median CD4 counts and freedom from IV immunoglobulin were improved after the use of preparative chemotherapy, other immunologic reconstitution parameters were not affected, and the potential for late sequelae in extremely young infants requires additional evaluation. After a T-cell-replete graft, landmark analysis at day 1100 post-HCT revealed that CD3 < 300 cells/mL, CD8 < 50 cells/mL, CD45RA < 10%, or a restricted Vb T-cell receptor repertoire (<13 of 24 families) were associated with the need for a second HCT or death. In the modern era, active infection continues to pose the greatest threat to survival for SCID patients. Although newborn screening has been effective in diagnosing SCID patients early in life, there is an urgent need to identify validated approaches through prospective trials to ensure that patients proceed to HCT infection free. The trial was registered at www.clinicaltrials.gov as #NCT01186913. (Blood. 2017;130(25):2718-2727

Peripheral-blood mononuclear cells (PBMCs) mobilized with AMD3100, a CXCR4 antagonist, combined with granulocyte colony-stimulating factor (G-CSF) have reconstituted autologous hematopoiesis in cancer patients following myeloablative conditioning. The engraftment potential of PBMCs mobilized with AMD3100 alone, however, has remained unproven. We therefore studied AMD3100-mobilized PBMCs in a canine model. Four dogs received 920 cGy total body irradiation (TBI) before infusion of autologous AMD3100-mobilized PBMCs (median CD34 cell count, 3.9 ؋ 10 6 /kg). Neutrophil (> 0.5 ؋ 10 9 /L [500/L]) and platelet (> 20 ؋/10 9 /L [> 20 000/L]) recoveries occurred at medians of 9 (range, 7-10) days and 25 (range, 23-38) days, respectively, after TBI, and all dogs had normal marrow function at 1 year after transplantation. To evaluate the long-term engraftment potential of AMD3100-mobilized PBMCs, 5 dogs were given 920 cGy TBI followed by infusion of AMD3100-mobilized PBMCs (median CD34 cell dose, 4.7 ؋ 10 6 /kg) from their dog leukocyte antigen (DLA)-identical littermates. Neutrophil and platelet recoveries occurred at medians of 8 (range, 8-10) days and 26 (range, 26-37) days, respectively, after TBI. With a median follow-up of 53 (range, 33-61) weeks, recipients' marrow function was normal, and blood-donor chimerism levels were 97% to 100%. In summary, both autologous and allogeneic AMD3100- IntroductionUnder steady-state conditions, CD34 ϩ hematopoietic progenitor and stem cells circulate in the blood of animals and humans at frequencies too low to allow for efficient collection of numbers sufficient to ensure timely hematopoietic reconstitution after myeloablative therapy. The frequencies of CD34 ϩ cells in the blood are considerably increased both in response to various growth factors and during the recovery phase following myelosuppressive chemotherapy. Granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral-blood mononuclear cells (PBMCs) are routinely used as a source of hematopoietic stem cells for transplantation and, owing to the earlier neutrophil and platelet engraftments and shortened hospital stay associated with the use of this product, are often preferred over bone marrow. [1][2][3][4][5][6][7][8] In the setting of autologous hematopoietic cell transplantation (HCT), difficulties in mobilizing and harvesting sufficiently large numbers of hematopoietic stem cells may occur, particularly in patients who have been exposed to repetitive cycles of myelotoxic chemo-and/or radiation therapy. 9 Alternative strategies aimed at improving CD34 ϩ cell mobilization including use of novel growth factors or growth factor combinations have been explored in clinical studies. [10][11][12][13][14][15] With respect to efficacy and/or safety of the mobilization procedure, however, none of these strategies has proven superior to G-CSF used alone or in combination with chemotherapy.Recently, several studies have demonstrated the importance of the interaction between stromal-cell-derived factor-1␣ (SDF-1␣) and its rece...

UL97 drug-resistant mutations occur in pediatric transplant recipients with CMV viremia and can cause serious disease. Screening for mutations conferring resistance to CMV antivirals should be considered for patients with persistent viremia during therapy and the sequences of UL97 mutations evaluated.