Search

Several studies have reported an impact of adult hematopoietic stem cell donor cytomegalovirus (CMV) serostatus on allogeneic hematopoietic cell transplantation outcomes. Limited data, however, are available on the impact of cord blood unit (CBU) CMV serostatus on allogeneic umbilical cord blood transplantation (UCBT) outcomes. We analyzed, retrospectively, the impact of CBU CMV serostatus on relapse incidence (RI) and 2-year nonrelapse mortality (NRM) of single-unit CBU transplantation for acute leukemia. Data from 1177 de novo acute leukemia pediatric and adult patients transplanted within European Group for Blood and Marrow Transplantation centers between 2000 and 2012 were analyzed. CBUs were provided by the European Cord Blood Banks. The median follow-up time for live patients was 59.9 months. The recipients of CMV-seropositive and -seronegative CBUs showed a comparable RI (33% versus 35%, respectively, P = .6) and 2-year cumulative incidence of NRM (31% versus 32%, respectively, P = .5). We conclude that CBU CMV serostatus did not influence RI and NRM in de novo acute leukemia patients after allo-UCBT and should not be included as a criteria for cord blood choice.

Adenosine deaminase (ADA) deficiency is a systemic disorder of purine metabolism. Deficiency of the purine salvage enzyme ADA leads to the build-up of the toxic metabolites, deoxyadenosine triphosphate and deoxyadenosine. ADA is ubiquitously expressed in all tissues of the body but most profoundly affects lymphocyte development and function leading to severe combined immunodeficiency (SCID). Unlike most other forms of SCID, ADA deficiency also results in non-immunologic manifestations. Associations between ADA deficiency and sensorineural hearing loss, behavioural abnormalities, non-infectious pulmonary disease and skeletal dysplasia are all recognised, and affect the long term outcome for these patients. Identification of new non-immunological manifestations and clinical presentations of ADA deficiency is essential to allow early optimisation of supportive care.Here we report four patients with ADA deficiency whose presenting feature was haemolytic uremic syndrome (HUS). 3 of 4 patients were diagnosed with ADA deficiency only after developing HUS, and one diagnosis was made post mortem, after a sibling was diagnosed with SCID. Shiga-toxigenic organisms were not isolated from any of the patients. 2 patients made a good recovery from their HUS with supportive treatment and initiation of PEG-ADA. Both remain well on enzyme replacement with mild or no residual renal impairment.Clinicians should be aware of this previously unreported non-immunologic manifestation of ADA deficiency.

In vivo T-cell depletion might contribute to the delayed immune reconstitution observed after unrelated umbilical cord blood transplantation (UCBT). We studied the impact of early, late, and no antithymocyte globulin (ATG) on immune reconstitution and outcome. One hundred twenty seven children receiving UCBT in London or Utrecht were divided into 3 groups: early ATG (days -9 to -5; n = 33), late ATG (days -5 to 0; n = 48), and no ATG (n = 46). The no-ATG group received mycophenolate mofetile + cyclosporin A as graft-versus-host disease (GVHD) prophylaxis, while the ATG groups received cyclosporin A + prednisone. End points studied were survival, immune recovery, infections, and GVHD. The probability of survival was similar in all groups: no ATG, 71% ± 8%; early ATG, 68% ± 9%; and late ATG, 61% ± 7%. CD3(+), CD4(+), and CD4(+)-naive T-cell counts were significantly higher (P < .001) in the no-ATG group at 1, 2, 3, 6, and 12 months post-UCBT. In the no-ATG group, significantly fewer viral reactivations (P = .021) were noted. A higher probability of severe acute GVHD (aGVHD; 31%) was found in the no-ATG group compared with 18% (P = .018) for early-ATG and 5% (P < .001) for late-ATG groups. This was not associated with more chronic GVHD (cGVHD).

To the editor: Marsh et al[1][1] summarize the international experience of stem cell transplantation for X-linked inhibitor of apoptosis protein (XIAP) deficiency. They demonstrate a poor outcome for patients with active hemophagocytic lymphohistiocytosis (HLH) entering transplant (no survivors)

Haemophagocytic lymphohistiocytosis (HLH) is a severe condition in which there is extreme uncontrolled inflammation, and may progress rapidly to multi-organ failure and death. HLH may be genetic (primary HLH), or secondary to infection or autoimmune/ autoinflammatory conditions; if the latter, it is also referred to as macrophage activation syndrome (MAS). Distinguishing between primary HLH and MAS is challenging but important since the former requires different therapeutic approaches including allogeneic haematopoietic stem cell transplantation (HSCT) for long-term survival. HLH screening tests are now being used in patients presenting with suspected MAS. In systemic Juvenile Idiopathic Arthritis (sJIA), some patients demonstrate temporary perforin expression abnormalities that resolve with disease control. The utility of other screening tests in a rheumatology context is unknown.

Introduction In vivo T-cell-depletion generated by the use of Thymoglobulin (ATG) within the conditioning regimen might contribute to the delayed immune-reconstitution observed after unrelated umbilical cord blood transplantation (UCBT). We studied the impact of early, late and no ATG on immune reconstitution and clinical outcome. Methods 127 Children receiving an unrelated UCBT in London or Utrecht between 2006 and 2011 were included and divided in 3 groups: late ATG (day -5 to 0, n=48), early ATG (day -9 to -5, n= 33) and no ATG(n=46). The no ATG group received MMF and CsA as GVHD prophylaxis, while the ATG groups both received CSA and prednison as prohylaxis, Endpoints studied were survival, early and late immune-recovery, infections and GvHD. Subset analysis CD3+, CD4+ and CD4+naïve, B and NK cell numbers were prospectively measured during post-transplant follow-up at 1, 2, 3, 6 and 12 months post-UCBT. Results The probability of survival was not significantly different between the groups: 71% +/- 8% (no ATG), 68% +/- 9% (early ATG) and 61% +/- 7% (late ATG). There were no significant differences in engraftment and primary or secondary graft failure. Immune reconstitution as defined by CD3+, CD4+ and CD4+ naïve T-cell counts were significantly higher (p Conclusion Cord blood transplantation without Thymoglobulin (ATG), in the context of MMF and CsA post-transplant prophylaxis, is associated with higher GVHD risk but with a surprisingly good immune reconstitution and with an engraftment and survival similar to the groups with ATG. The findings of improved immune-reconstitution, associated with lower viral reactivations, albeit at the cost of increased rates of acute GvHD (but not chronic GvHD), suggest that omitting ATG in cord blood transplantation may be important to prevent viral reactivations, especially in those at high risk for these. Disclosures: No relevant conflicts of interest to declare.