Correspondence n engl j med 375;11 nejm.org September 15, 2016 excluded for right-sided pulmonary-vein diameters greater than 26 mm. In the trial, 98.9% of all pulmonary veins were isolated at the index procedure in the cryoballoon group, as compared with 97.9% in the radiofrequency group. In the cryoballoon group, 100% of the left common pulmonary veins (28 of 28) and 92% of the right middle pulmonary veins (12 of 13) were isolated at the index procedure. In the radiofrequency group, 77% of the left common pulmonary veins (30 of 39) and 48% of the right middle pulmonary veins (11 of 23) were isolated at the index ablation.Currently, prescreening of pulmonary-vein anatomical features is not required. More important, the cryoballoon group has shown significantly fewer reinterventions and rehospitalizations than the radiofrequency group, 3 and these patient-relevant disease-burden characteristics should be considered when making the decision about what type of catheter ablation should be performed.

The best antithymocyte globulin preparation for first-line immune suppression in patients with severe aplastic anemia is still not clear. The aim of this study was to compare hematological response and overall survival in patients submitted to horse or rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia. We retrospectively compared 71 consecutive patients with severe aplastic anemia, classified according to the antithymocyte globulin preparation. Analyses included variables related to patients and to immune suppression. Forty two patients (59.1%) received horse and 29 (40.9%) rabbit antithymocyte globulin. Response rates were higher at 6 months in patients submitted to horse in comparison to rabbit antithymocyte globulin (59.5% versus 34.5% respectively, p = 0.05). Median time to response was similar between the two groups (99 versus 88.5 days, respectively, for horse and rabbit antithymocyte globulin; p = 0.98). Overall survival at 2 years was significantly higher in patients submitted to horse in comparison to rabbit antithymocyte globulin (78.4% versus 55.4%, p = 0.03). Post-treatment response was strongly associated with survival at 2 years (97% in responders versus 41.2% in non-responders, p < 0.001). Use of rabbit antithymocyte globulin was an independent predictor of death (odds ratio 2.5; 95% confidence interval 1.03-6.04; p = 0.04). Rabbit antithymocyte globulin was associated with a significant and prolonged lymphopenia in comparison with horse antithymocyte globulin. Our data suggest the superiority of horse over rabbit antithymocyte globulin as first-line treatment for severe aplastic anemia, both regarding hematological response and survival.

For treatment of severe aplastic anemia, immunosuppressive therapy with horse antithymocyte globulin results in superior response and survival compared with rabbit antithymocyte globulin. This relative benefit may be different in the setting of transplantation as rabbit antithymocyte globulin results in more profound immunosuppression. We analyzed 833 severe aplastic anemia transplants between 2008 and 2013 using human leukocyte antigen (HLA)-matched siblings (n=546) or unrelated donors (n=287) who received antithymocyte globulin as part of their conditioning regimen and bone marrow graft. There were no differences in hematopoietic recovery by type of antithymocyte globulin. Among recipients of HLA-matched sibling transplants, day 100 incidence of acute (17% versus 6%, P<0.001) and chronic (20% versus 9%, P<0.001) graft-versus-host disease were higher with horse compared to rabbit antithymocyte globulin. There were no differences in 3-year overall survival, 87% and 92%, P=0.76, respectively. Among recipients of unrelated donor transplants, acute graft-versus-host disease was also higher with horse compared to rabbit antithymocyte globulin (42% versus 23%, P<0.001) but not chronic graft-versus-host disease (38% versus 32%, P=0.35). Survival was lower with horse antithymocyte globulin after unrelated donor transplantation, 75% versus 83%, P=0.02. These data support the use of rabbit antithymocyte globulin for bone marrow transplant conditioning for severe aplastic anemia.

Hematologic malignancy and healthcare-associated infection were significantly associated with MDR-GNB infection in this sample of pediatric oncology patients.

Early lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non-hematological cancers. Sixty-five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre-collection absolute lymphocyte count (ALC). The CD81 lymphocyte dose in the autograft and the pre-mobilization ALC were independently associated with ELR (P < 0.001 and P 5 0.008, respectively). CD81 lymphocyte doses higher than 0.1 3 10 9 /kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98-127.69] and this cutoff may be used to predict ELR (P 5 0.001, area under the curve 0.75, 95% CI 0.62-0.88). Mobilization with granulocyte colony-stimulating factor (G-CSF) alone, the pre-collection ALC and the number of apheresis sessions were independently associated with the CD81 lymphocyte dose (P 5 0.04, P 5 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD81 lymphocyte dose (r s 5 0.68, P < 0.001). Median pre-mobilization ALC was higher than pre-collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G-CSF (1090 vs. 758 lymphocytes/lL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G-CSF (1920 vs. 1539/lL, respectively; P 5 0.23). These results suggest that the CD81 lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G-CSF significantly decreases the pre-collection ALC, especially in patients with low pre-mobilization ALC. Am. J. Hematol. 84:21-28, 2009. V

The standard regimen for HLA-identical sibling bone marrow transplant (BMT) in severe aplastic anemia (SAA) is cyclophosphamide (Cy) and horse antithymocyte globulin (ATG). Horse ATG has been replaced by rabbit ATG in many countries due to the unavailability of the former product. This study was designed to assess if these ATG preparations are interchangeable in the preparative regimen for matched related BMT in SAA. Forty consecutive BMTs were retrospectively analyzed: 20 received Cy plus horse ATG and 20 received Cy plus rabbit ATG as the preparative regimen. Conditioning with rabbit ATG was protective against acute graft-versus-host disease (aGVHD) grades II-IV and moderate-severe chronic GVHD (cGVHD), with incidence rates of 0% versus 35.2% (P 5 .009) and 0% versus 34.0% (P 5 .04), respectively. On day 1100, the probability of proven/probable invasive fungal disease (IFD) was higher in patients conditioned with rabbit ATG, 31.2% versus 5.5%, respectively (P 5 .04). Earlier cytomegalovirus (CMV) reactivation (40 versus 50 days; P 5.02) was observed with rabbit ATG. An inferior lymphocyte count on days 130 (0.360 versus 0.814 Â 10 9 /L; P 5 .01) and 190 (0.744 versus 1.330 Â 10 9 /L; P 5 .006) was noticed in recipients of rabbit ATG. The incidence of stable mixed chimerism was higher in recipients of rabbit ATG (18.2% versus 80%, respectively; P 5 .004). These results suggest that horse and rabbit ATG preparations have different biological and clinical properties and should not be used interchangeably in the preparative regimen for related BMT in SAA.

Despite being recommended as first-line immunosuppressive therapy in severe aplastic anemia (SAA), horse antithymocyte globulin (ATG) is still unavailable in many countries outside the USA. Rabbit ATG is more lymphocytoxic than horse ATG, and this might result in a higher incidence of severe infections and early mortality. This study was designed to identify the risk factors for early mortality and overall survival (OS) after rabbit ATG in patients with SAA. We retrospectively reviewed 185 patients with SAA who underwent rabbit ATG and cyclosporine. The incidence of death in 3 months following rabbit ATG therapy was 15.1% (28/185). Early mortality was mainly related to infectious complications, despite adequate antibiotic and/or antifungal treatment. Age > 35 years (odds ratio [OR] 5.06, P = 0.001) and baseline absolute neutrophil count (ANC) ≤ 0.1 × 10/L (OR 7.64, P < 0.001) were independent risk factors for early mortality after immunosuppressive therapy with this agent. Hematological response at 6 months was observed in only 29.7% of all patients. OS at 1 year after rabbit ATG was 75.3%; and age > 35 years (OR 1.88, P = 0.03), baseline ANC ≤ 0.1 × 10/L (OR 2.65, P < 0.001), and lack of response to rabbit ATG (OR 11.40, P < 0.001) were independently associated with mortality. Alternative strategies are needed for the treatment of SAA patients in countries were horse ATG is unavailable, particularly for those at high risk for early mortality after rabbit ATG due to a higher age and very low pre-treatment neutrophil count.

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