Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation
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Biol. Blood Marrow Transplant. · Jan 2016
Multicenter Study Clinical TrialDNMT3A R882 Mutation with FLT3-ITD Positivity Is an Extremely Poor Prognostic Factor in Patients with Normal-Karyotype Acute Myeloid Leukemia after Allogeneic Hematopoietic Cell Transplantation.
The prognostic relevance of epigenetic modifying genes (DNMT3A, TET2, and IDH1/2) in patients with acute myeloid leukemia (AML) has been investigated extensively. However, the prognostic implications of these mutations after allogeneic hematopoietic cell transplantation (HCT) have not been evaluated comprehensively in patients with normal-karyotype (NK)-AML. A total of 115 patients who received allogeneic HCT for NK-AML were retrospectively evaluated for the FLT3-ITD, NPM1, CEBPA, DNMT3A, TET2, IDH1/2, WT1, NRAS, ASXL2, FAT1, DNAH11, and GATA2 mutations in diagnostic samples and analyzed for long-term outcomes after allogeneic HCT. ⋯ In addition, both mutations were significant risk factors for EFS and relapse. People with DNMT3A R882(mut) accompanied by FLT3-ITD(pos) had worse OS and EFS, and higher relapse rates than those with the other mutations, which were confirmed in a propensity score 1:2 matching analysis. These results suggest that DNMT3A R882(mut), particularly when accompanied by FLT3-ITD(pos), is a significant prognostic factor for inferior transplantation survival outcome by increasing relapse risk, even after allogeneic HCT.
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Biol. Blood Marrow Transplant. · Jan 2016
Multicenter Study Clinical TrialParent Outlook: How Parents View the Road Ahead as They Embark on Hematopoietic Stem Cell Transplantation for Their Child.
Pediatric hematopoietic stem cell transplantation (HSCT) offers cure for high-risk malignancies and other conditions, but carries a risk of complications. Parental outlook regarding their child's transplantation course and future health has been largely unexplored. This report presents the Parent Outlook Scale, describes its properties, and examines the outlook of parents embarking on their child's transplantation course and the associated variables. ⋯ Clinical factors (solid tumor diagnosis and unrelated donor transplant) and a parent factor (worse emotional functioning) were associated with higher scale and subscale scores. Our findings show that the outlook of parents embarking on their child's HSCT course is varied and not solely a product of clinical factors readily apparent to clinicians. Referring and transplantation clinicians should create opportunities to explore with parents their perspectives and concerns before and during the course of HSCT.
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Biol. Blood Marrow Transplant. · Jan 2016
Multicenter StudyPhase II Trial of Reduced-Intensity Busulfan/Clofarabine Conditioning with Allogeneic Hematopoietic Stem Cell Transplantation for Patients with Acute Myeloid Leukemia, Myelodysplastic Syndromes, and Acute Lymphoid Leukemia.
Clofarabine has potent antileukemia activity and its inclusion in reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (HSCT) for acute leukemia could potentially improve outcomes. We conducted a phase II study of busulfan (.8 mg/kg i.v. twice daily on days -5, -4, -3, and -2) with clofarabine (40 mg/m(2) i.v. daily on days -5, -4, -3, and -2) conditioning before allogeneic 8/8 HLA-matched related or unrelated HSCT. The primary endpoint was donor neutrophil engraftment by day +40. ⋯ The 2-year PFS was 50% (95% CI, 32 to 65) and OS was 56% (95% CI, 38 to 71). For patients with AML in first complete remission, 2-year PFS and OS were both 82% (95% CI, 55 to 94). RIC with busulfan and clofarabine leads to successful engraftment with acceptable rates of NRM and GVHD.
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Biol. Blood Marrow Transplant. · Jan 2016
Comparative StudyRisk Factors for Acute and Chronic Graft-versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation with Umbilical Cord Blood and Matched Sibling Donors.
Allogeneic hematopoietic cell transplantation is often complicated by graft-versus-host disease (GVHD). We analyzed the incidences and risk factors for acute (aGVHD) and chronic GVHD (cGVHD), and their impact on disease relapse and survival, among recipients of single umbilical cord blood (sUCB, n = 295), double umbilical cord blood (dUCB, n = 416), and matched sibling donor (MSD, n = 469) allografts. The incidences of grades II to IV aGVHD and chronic GVHD among dUCB, sUCB, and MSD were 56% and 26%, 26% and 7%, 37% and 40%, respectively. ⋯ This large contemporary analysis suggests distiinct risks and consequences of GVHD for UCB and MSD recipients. Limiting the severity of aGVHD remains important in all groups. Increasing the cord blood inventory or developing strategies that reduce the cell-dose threshold and thereby increase the chance of identifying an adequately dosed, better HLA-matched sUCB unit may further limit risks of aGVHD after UCB transplantation.
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Biol. Blood Marrow Transplant. · Jan 2016
Clinical TrialDynamic Detection of Anti-Human Leukocyte Antigen (HLA) Antibodies but not HLA-DP Loci Mismatches Can Predict Acute Graft-versus-Host Disease and Overall Survival in HLA 12/12-Matched Unrelated Donor Allogeneic Hematopoietic Stem Cell Transplantation for Hematological Malignancies.
The National Marrow Donor Program and Center for International Blood and Marrow Transplant Research provided guidelines for the use of anti-HLA antibodies and HLA-DP-mismatched loci in unrelated donor hematopoietic stem cell transplantation (HSCT). However, a deeper understanding of other potentially useful biomarkers for predicting clinical outcomes in HLA-A, -B, -C, -DRB1, -DQB1, and -DQA1 (12/12)-matched unrelated donor HSCT is needed to further improve clinical outcomes. We tested HLA genotyping for 123 pairs of patients and donors. ⋯ Furthermore, HLA-DP loci-matched subgroup showed a trend towards a lower rate of acute GVHD and a higher OS in the anti-HLA Abs-negative group. Our results suggest that dynamic changes of anti-HLA antibodies independently predict for a negative outcome of HSCT, independent of HLA-DP loci mismatches. Routine monitoring for anti-HLA antibody dynamics should be conducted before and after HSCT.