Purpose Malignancy relapse remains a major obstacle for successful allogeneic hematopoietic cell transplantation (HCT). Chronic graft-versus-host disease (cGVHD) is associated with fewer relapses. However, when studying effects of cGVHD on relapse it is difficult to separate from acute GVHD effects as most cases of cGVHD occur within the first year post-transplant at the time when acute GVHD is still active. Experimental design The current study based on CIBMTR registry data investigated cGVHD and its association with the incidence of late relapse and survival in 7489 patients with acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), chronic myeloid leukemia (CML) and myelodysplastic syndromes (MDS) who were leukemia-free at12 months after myeloablative allogeneic HCT. Results Forty-seven percent of the study population was diagnosed with cGVHD at 12 months after transplant. The protective effect of cGVHD on relapse was present only in patients with CML (RR: 0.47, 95% CI: 0.37-0.59, P <0.0001). cGVHD was significantly associated with higher risk of treatment related mortality, (RR: 2.43, 95% CI: 2.09-2.82, P <0.0001) and inferior overall survival (RR: 1.56, 95% CI: 1.41-1.73, P <0.0001) for all diseases. In patients with CML all organ sites and presentation types of cGVHD were equally associated with lower risk of late relapse. Conclusions These results indicate that clinically relevant anti-leukemia effects of cGVHD on late relapses are present only in CML but not in AML, ALL or MDS. Chronic GVHD in patients who are one year survivors after myeloablative allogeneic HCT is primarily associated with higher TRM and inferior survival.

A cute graft-versus-host disease remains a major threat to a successful outcome after allogeneic hematopoietic cell transplantation. While improvements in treatment and supportive care have occurred, it is unknown whether these advances have resulted in improved outcome specifically among those diagnosed with acute graft-versus-host disease. We examined outcome following diagnosis of grade II-IV acute graft-versus-host disease according to time period, and explored effects according to original graft-versus-host disease prophylaxis regimen and maximum overall grade of acute graft-versus-host disease. Between 1999 and 2012, 2,905 patients with acute myeloid leukemia (56%), acute lymphoblastic leukemia (30%) or myelodysplastic syndromes (14%) received a sibling (24%) or unrelated donor (76%) blood (66%) or marrow (34%) transplant and developed grade II-IV acute graft-versus-host disease (n=497 for 1999–2001, n=962 for 2002–2005, n=1,446 for 2006–2010). The median (range) follow-up was 144 (4–174), 97 (4–147) and 60 (8–99) months for 1999–2001, 2002–2005, and 2006–2010, respectively. Among the cohort with grade II-IV acute graft-versus-host disease, there was a decrease in the proportion of grade III-IV disease over time with 56%, 47%, and 37% for 1999–2001, 2002–2005, and 2006–2012, respectively (P<0.001). Considering the total study population, univariate analysis demonstrated significant improvements in overall survival and treatment-related mortality over time, and deaths from organ failure and infection declined. On multivariate analysis, significant improvements in overall survival (P=0.003) and treatment-related mortality (P=0.008) were only noted among those originally treated with tacrolimus-based graft-versus-host disease prophylaxis, and these effects were most apparent among those with overall grade II acute graft-versus-host disease. In conclusion, survival has improved over time for tacrolimus-treated transplant recipients with acute graft-versus-host disease.

Abstract. We give an exact geometry kernel for conic arcs, algorithms for exact computation with low-degree algebraic numbers, and an algorithm for computing the arrangement of conic arcs that immediately leads to a realization of regularized boolean operations on conic polygons. A conic polygon, or polygon for short, is anything that can be obtained from linear or conic halfspaces (= the set of points where a linear or quadratic function is non-negative) by regularized boolean operations. The algorithm and its implementation are complete (they can handle all cases), exact (they give the mathematically correct result), and efficient (they can handle inputs with several hundred primitives).

In this study, we sought to identify specific individual high-intensity or reduced-intensity conditioning regimens with the best relapse-free survival (RFS) rather than the global high- vs reduced-intensity regimen comparison. Patients (median age, 58 years) with acute myeloid leukemia (AML; n = 1258), who were in first or subsequent remission, or with MDS (n = 951) who had refractory anemia with unilineage or multilineage dysplasia, 5q- syndrome, or refractory anemia with excess blasts received nonirradiation-containing regimens and were transplanted between 2009 and 2014 in the United States. Three-year RFS with high-intensity busulfan/cyclophosphamide (Bu4/Cy; 44%) was comparable to conditioning with high-intensity fludarabine/busulfan (Flu/Bu4; 44%), reduced-intensity fludarabine/melphalan (Flu/Mel; 52%; = .53), and Flu/Mel + anti-thymocyte globulin (ATG; 44%; = .38). RFS was lower with reduced-intensity Flu/Bu2 + ATG (31%; = .0006). RFS was also lower with high-intensity Flu/Bu4 + ATG (38%; = .05) and reduced-intensity Flu/Bu2 (38%; = .02), although the difference did not reach the level of significance set for these analysis. RFS with Flu/Mel was superior to RFS with Flu/Bu2 ( = .01) and Flu/Bu2 + ATG ( = .0006). The 3-year incidence of relapse was 22% with Flu/Mel compared with 46% with Flu/Bu2 and 56% with Flu/Bu2 + ATG. With only a modest reduction in nonrelapse mortality with the Flu/Bu2 regimens, the higher relapse incidence resulted in lower RFS. The data support optimal RFS with Bu4/Cy, Flu/Bu4, and Flu/Mel regimens for AML in remission or MDS. The low relapse rate with reduced-intensity Flu/Mel resulted in RFS comparable to that after the higher-intensity regimens.

No abstract