As cord blood (CB) lacks memory T- and B-cells, and recent decreases in herd immunity to vaccine preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five (63%) patients (engrafting units median HLA-allele match 5/8, range 2–7/8) received protein-conjugated vaccines, and 63 (median age 34 years, range 0.9–64) were evaluated for responses. Median vaccination time was 17 months (range 7–45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19f, 23f) were seen in children and adults (60% versus 49%, p = 0.555). Responses to tetanus, diphtheria, pertussis, H. influenzae, and polio were observed in children (86–100%) and adults (53–89%) even if patients had prior GVHD or rituximab. CD4+CD45RA+ and CD19+ cell recovery significantly influenced tetanus and polio responses. In a smaller cohort, responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side-effects were identified and all vaccinated patients survive (median follow-up 57 months). While GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients.

Autoimmune hemolysis (AH) and immune thrombocytopenic purpura (ITP) are recognized complications after cord blood transplantation (CBT). We evaluated the incidence and characteristics of AH/ ITP after double-unit CBT in a day 100 landmark analysis of 152 patients (median age 36 years, range 0.9–70) transplanted for hematologic malignancies with myeloablative or non-myeloablative conditioning and calcineurin-inhibitor (CNI)/ mycophenolate mofetil. With a median 5.2 year (range 1.6–9.7) survivor follow-up, 10 patients developed autoimmune cytopenias (8 AH, 1 ITP, 1 both) at a median of 10.4 months (range 5.8–24.5) post-CBT for a 7% cumulative incidence 3 years after the day 100 landmark. Six patients presented with severe disease (hemoglobin ≤ 6 g/dl and/ or platelets < 20 × 109/L). All AH patients were direct anti-globulin test positive. All 10 cases developed during immunosuppression taper with 8 having prior acute graft-versus-host disease. All 10 patients received rituximab 2–18 days after diagnosis, and corticosteroids combined with rituximab within < 7 days was the most effective. No patient died of AH/ ITP. AH/ ITP occurs infrequently after CBT but may be life-threatening requiring emergency therapy. Rituximab combined with corticosteroids at diagnosis is warranted in patients with severe disease.

Study Design A retrospective chart review of cases with congenital vertebral malformations (CVM) and controls with normal spine morphology. Objective To determine the relative contribution of maternal environmental factors (MEF) during pregnancy including maternal insulin dependent diabetes mellitus, valproic acid, alcohol, smoking, hyperthermia, twin gestation, assisted reproductive technology, in-vitro fertilization and maternal clomiphene usage to CVM development. Summary of Background Data Congenital vertebral malformations (CVM) represent defects in formation and segmentation of somites occurring with an estimated incidence of between 0.13–0.50 per 1000 live births. CVM may be associated with congenital scoliosis, Klippel-Feil syndrome, hemifacial microsomia and VACTERL syndromes, and represent significant morbidity due to pain and cosmetic disfigurement. Methods A multicenter retrospective chart review of 229 cases with CVM and 267 controls with normal spine morphology between the ages of 1–50 years was performed in order to obtain the odds ratio (OR) of MEF related to CVM among cases vs. controls. CVM due to an underlying syndrome associated with a known gene mutation or chromosome etiology were excluded. An imputation based analysis was performed in which subjects with no documentation of MEF history were treated as no maternal exposure.” Univariate and multivariate analysis was conducted to calculate the OR. Results Of the 229 total cases, 104 cases had single or multiple CVM without additional congenital malformations (CM) (Group 1) and 125 cases had single or multiple CVM and additional CM (Group 2). Nineteen percent of total cases had an identified MEF. The OR (95% CI, P-value) for MEF history for Group 1 was 6.0 (2.4–15.1, P<0.001) in the univariate analysis. The OR for MEF history in Group 2 was 9.1 (95%CI, P-value) (3.8–21.6, P<0.001) in the univariate analysis. The results were confirmed in the multivariate analysis, after adjusting for age, gender, and institution. Discussion These results support a hypothesis for an association between the above MEF during pregnancy and CVM and have implications for development of prevention strategies. Further prospective studies are needed to quantify association between CVM and specific MEF.

Introduction: Autoimmune hemolysis (AH) & immune thrombocytopenic purpura (ITP) are recognized complications of CBT. However, the incidence, severity, treatment response, & prognosis of these autoimmune cytopenias are not established. Methods: We evaluated AH/ITP after CBT in a landmark analysis of 152 patients who received double-unit grafts, had sustained donor engraftment, & were disease-free at 100 days post-transplant. This landmark was chosen as no patient has developed AH/ITP prior to day 100. CBT recipients (median 38 years, range 0.9-70) were transplanted for hematologic malignancies with myeloablative (MA) or non-myeloablative (NMA) conditioning and calcineurin-inhibitor (CNI)/mycophenolate mofetil immunosuppression. Results: With a median follow-up of survivors in this cohort of 50.6 months (range 7.6-105.4) post-CBT, 9 patients [median age 42 years (range 2-54), 5 MA & 4 NMA conditioning] have developed autoimmune cytopenias (7 AH, 1 ITP, 1 both). All AH patients were IgG Direct Antiglobulin Test (Coombs) positive and ITP diagnosis was made by standard criteria. The cumulative incidence of AH/ITP is 6% (95%CI:3-11) at 3-years after the day 100 landmark with a median onset of 8.6 months (range 5.8-24.5) post-CBT (Figure). Six patients presented with severe disease (Hb <6 gm/dl &/or plts <20) requiring immediate aggressive supportive care. The lowest counts (Hb 2.6-6.8 & plts 0-4) were observed a median of 1 day (range 0-94) after diagnosis. Six patients had grade II-IV acute GVHD (onset 17-175 days post-CBT, all prior to development of AH/ITP), and all 9 cases developed in the context of immunosuppression taper. No relationship was observed according to age, diagnosis (acute leukemia vs lymphoma), preparative regimen intensity (MA vs NMA), or recipient CMV serostatus. Treatment during the first week included IVIg/corticosteroids/rituximab in 3 patients or a variety of approaches (1 increased CNI dose, 2 IVIg only, 2 rituximab only, 1 corticosteroids/IVIg). Overall, all 9 patients received rituximab starting 2-18 days (4-6 doses) with initial treatment. Early rituximab at <7 days from diagnosis reduced time to complete response (CR, Hb >8 &/or plts >100): median 13 days (7-49 days) in 4 early rituximab patients vs 58 days (19-98 days) in 5 without early rituximab. Moreover, an initial IVIg/corticosteroids/rituximab combination was best (CR 7-13 days). Four patients flared after CR at 28-393 days & all patients achieved CR with further therapy. Three patients underwent splenectomy (2 with initial therapy & 1 with flare). Eight/9 AH/ITP patients are alive & disease-free (one patient died of GVHD in remission from AH). Seven/8 surviving patients are in CR from AH/ITP (median 30 months after AH/ITP diagnosis, range 9-102) & 1 has recurrent AH requiring therapy. Treatment was well tolerated although 4 patients required intermittent IVIg & 4 had transient neutropenia. Conclusions: AH/ITP occurs infrequently after CBT but is associated with sudden onset and may be life-threatening. The onset during immunosuppressant taper suggests the mechanism may be due to transient immune dysregulation at this time-point, and investigation of whether AH/ITP can be predicted from analysis of B-cell immune reconstitution is underway. IVIg/corticosteroid/rituximab combination is appropriate initial therapy in severe disease & our data suggests this is the most effective although the role of IVIg is unclear. Earlier treatment with Rituximab may reduce corticosteroid exposure & avoid early splenectomy. While the optimal treatment regimen is not established, our series suggests rituximab is essential to achieve & maintain CR & has an excellent safety profile. Finally, survival was high in AH/ITP patients with no deaths from this complication although this was likely contingent on aggressive supportive care in these patients. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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donors. Herein we compare outcomes of Haplo-HCT using PT-CY to MRD-HCT. Methods: Included are 987 adult pts who underwent either Haplo-(n¼180) or MRD-HCT (n¼807) following NMA/RIC regimens between 2008-13. The primary end-point was overall survival (OS). Secondary endpoints included incidence of aGVHD, cGVHD, non-relapse mortality (NRM), relapse/progression (R/P) and progression-free survival (PFS). Results: Baseline characteristics are shown in Table 1. Haplo pts received Flu/CY/2Gy TBI conditioning followed by GVHD prophylaxis with PT-CY AE a calcineurin inhibitor (CNI) + mycophenolate. MRD-HCT pts received Flu-based (+ an alkylator and/or 2GyTBI) conditioning and CNI-based GVHD prophylaxis. Day28 neutrophil and platelet recovery rates were 97% vs 95% (p¼.31) and 63% vs 91% (p<.001) after Haplo vs. MRD-HCT respectively. Despite similar grade II-IV aGVHD rates at day 100 (27% vs. 25%), 1-yr cGVHD rates were significantly lower after Haplo-HCT (12% vs. 45%; p<.001). For Haplo vs. MRD-HCT, 3-yr rates of NRM (15 vs 13%; p¼.41), R/P (37 vs 40%; p¼.51), PFS (48% vs 48%; p¼.96) or OS (61 vs 62%; p¼.82) were not significantly different. On multivariate analysis (MVA), risk of cGVHD was lower with Haplo-HCT (RR 0.21, 95%CI 0.14-0.31; p<.001). MVA showed no difference between Halpo-and MRD-HCT in terms of NRM (RR¼1.52; p¼.06), R/P (RR¼0.80; p¼.09), PFS (RR¼0.98; p¼.83) and OS (RR¼1.14; p¼.34). No center effect on OS was seen. Conclusion: Despite significantly lower chronic GVHD, haplo-HCT provides survival outcomes comparable to MRD-HCT. Prospective, randomized data are warranted before wide spread adoption of haploidentical HCT as preferred donor source in lymphomas pts without MRDs.

polymorphism, with the exception of an unexpected finding of significantly higher relapse in association with MICA mismatches in 10/10 patients (HR 1.7, 95% CI 1.2-2.4, p¼ 0.003) but not in 9/10 patients. There was a suggestion that MICA mismatches were associated with a higher risk of aGVHD grades II-IV (HR 1.4, 95% CI 1.1-1.9, p¼ 0.013) but not grades III-IV and with higher risk of cGVHD (HR 1.8, 95% CI: 1.0-3.1, p value 0.04). There were no significant interactions between MICA mismatches and HLA matching (9/10 vs. 10/ 10). There was also a suggestion of an association between donor MICA-129 non-VV genotypes and slower platelet engraftment with HR 1.4 (95% CI 1.109-1.985, p¼ 0.02). Conclusions: In this cohort neither MICA-129 polymorphism nor MICA mismatches were associated with HSCT outcomes at a level that reached the predetermined level of statistical significance. This registry analysis in patients with ALL, AML and MDS was discordant with prior reports of single center studies of patients with mixed diagnoses.

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