long term outcomes of pediatric patients with malignant and non malignant disorders receiving α β t cell depleted hla haploidentical hematopoietic stem cell transplantation hsct followed by infusion of bpx 501 t cells donor t cells transduced with ic9

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Conditioning with Treosulfan and Fludarabine followed by Allogeneic Hematopoietic Cell Transplantation for High-Risk Hematologic Malignancies

In this prospective study 60 patients of median age 46 (range: 5-60 years), with acute myelogenous leukemia (AML; n = 44), acute lymphoblastic leukemia (ALL; n = 3), or myelodysplastic syndrome (MDS; n = 13) were conditioned for allogeneic hematopoietic cell transplantation with a treosulfan/fludarabine (Flu) combination. Most patients were considered at high risk for relapse or nonrelapse mortality (NRM). Patients received intravenous treosulfan, 12 g/m2/day (n = 5) or 14 g/m2/day (n = 55) on days −6 to −4, and Flu (30 mg/m2/day) on days −6 to −2, followed by infusion of marrow (n = 7) or peripheral blood stem cells (n = 53) from HLA-identical siblings (n = 30) or unrelated donors (n = 30). All patients engrafted. NRM was 5% at day 100, and 8% at 2 years. With a median follow-up of 22 months, the 2-year relapse-free survival (RFS) for all patients was 58% and 88% for patients without high-risk cytogenetics. The 2-year cumulative incidence of relapse was 33% (15% for patients with MDS, 34% for AML in first remission, 50% for AML or ALL beyond first remission and 63% for AML in refractory relapse). Thus, a treosulfan/Flu regimen was well tolerated and yielded encouraging survival and disease control with minimal NRM. Further trials are warranted to compare treosulfan/Flu to other widely used regimens, and to study the impact of using this regimen in more narrowly defined groups of patients

Lack of viral control and development of combination antiretroviral therapy escape mutations in macaques after bone marrow transplantation

We have previously demonstrated robust control of simian/human immunodeficiency virus (SHIV1157-ipd3N4) viremia following administration of combination antiretroviral therapy (cART) in pigtailed macaques. Here, we sought to determine the safety of hematopoietic stem cell transplantation (HSCT) in cART-suppressed and unsuppressed animals

Does FLT3 mutation impact survival after hematopoietic stem cell transplantation for acute myeloid leukemia? A Center for International Blood and Marrow Transplant Research (CIBMTR) analysis: Impact of FLT3 on OS Post-HCT for AML

BACKGROUND: Patients with FMS like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) have a poor prognosis and are referred for early allogeneic hematopoietic stem cell transplantation (HCT). METHODS: Data from the Center for International Blood and Marrow Transplant Research (CIBMTR) were used to evaluate 511 adult patients with de novo AML who underwent HCT during 2008 through 2011 to determine whether FLT3 mutations had an impact on HCT outcomes. RESULTS: In total, 158 patients (31%) had FLT3 mutations. Univariate and multivariate analyses revealed an increased risk of relapse at 3 years in the FLT3 mutated group compared with the wild-type (WT) group (38% [95% confidence interval (CI), 30%-45%] vs 28% [95% CI, 24%-33%]; P = .04; relative risk, 1.60 [95% CI, 1.15-2.22]; P = .0048). However, FLT3 mutation status was not significantly associated with nonrelapse mortality, leukemia-free survival, or overall survival. Although more patients in the FLT3 mutated group died from relapsed primary disease compared with those in the WT group (60% vs 46%), the 3-year overall survival rate was comparable for the 2 groups (mutated group: 49%; 95% CI, 40%-57%; WT group: 55%, 95% CI, 50%-60%; P = .20). CONCLUSIONS: The current data indicate that FLT3 mutation status did not adversely impact overall survival after HCT, and about 50% of patients with this mutation who underwent HCT were long-term survivors. Cancer 2016;122:3005-3014. © 2016 American Cancer Society

Outcome of Pediatric Hematopoietic Stem Cell Transplant Recipients Requiring Mechanical Ventilation

Purpose: To assess the risk factors for intensive care unit admission among children receiving hematopoietic stem cell trans-plantation (HSCT) and to test the hypothesis that multiple organ failure (MOF) increases the odds of death among HSCT patients who receive mechanical ventilation (MV). Methods: The chart of all consecutive HSCTs at Seattle Children’s Hospital and pediatric HSCT patients admitted to the pediatric critical care unit of a tertiary care pediatric hospital from January 2000 to September 2006 were reviewed retrospectively. Results: Charts of 266 HSCT patients were reviewed. Nonmalignant disease compared to hematologic malignancy, acute graft versus host disease grades III and IV, and second transplant increased the odds of pediatric intensive care unit admission. Among patients receiving MV for>24 hours, 9 (25%) survived for 6 months, while 8 patients (22%) were long-term survivors with a median follow-up time of 3.6 years, a significant improvement compared to a long-term survival of 7 % (odds ratio 0.25, 95 % confidence intervals: 0.09-0.72, P .01) reported in a previously published cohort of pediatric HSCT patients at the same institution from 1983 to 1996. Cardiovascular failure, duration of MV for greater than 1 week, and prolonged receipt of continuous renal replacement therapy (CRRT) increased the risk of mortality. Conclusions: Six-month survival of pediatric HSCT patients was 25 % and the odds of death were increased by cardiovascular failure but not by MOF. Receipt of mechanical support (ventilation, CRRT) or cardiovascular support (inotropic agents) decreased the likelihood of long-term survival

Donor and recipient sex in allogeneic stem cell transplantation: what really matters Donor and recipient sex in allogeneic stem cell transplantation: what really matters

Publisher's Disclaimer. E-publishing ahead of print is increasingly important for the rapid dissemination of science. Haematologica is, therefore, E-publishing PDF files of an early version of manuscripts that AUTHOR CONTRIBUTIONS H. T. K. designed the research, analyzed the data and wrote the paper. M-J.Z. analyzed the data, and reviewed the paper. A. E. W. reviewed the paper. A. S. reviewed the paper J. C. reviewed the paper W. S. reviewed the paper M. A. P. reviewed the paper P. A. designed the research, analyzed the data, and wrote the paper. M. E. designed the research, reviewed the paper. CONFLICT OF INTEREST DISCLOSURES The authors have no relevant conflicts of interest to disclose. relative increase compared with female recipients with male donors (p=0.0003). In addition, male recipients with female donors showed a 21% relative increase in the subdistribution hazard of chronic GVHD (p<0.0001) compared with female recipients with male donors. Donor sex had no effect on outcomes for female recipients. Transplantation of grafts from male and female donors was associated with inferior overall survival and progression-free survival in male recipients with differing patterns of failure. Recipient sex is an important prognostic factor independent of donor sex

Allogeneic hematopoietic cell transplantation for infants with acute lymphoblastic leukemia

The role of transplantation in infants with acute lymphoblastic leukemia (ALL) is not defined. We analyzed results of 40 infants diagnosed before age 12 months who received a hematopoietic cell transplant (HCT) between July 1982 and February 2003 in first complete remission (CR1; n = 17), CR2/3 (n = 7), or relapse (n = 16). Patients were conditioned with cyclophosphamide with total body irradiation (n = 39) or busulfan (n = 1). Donors were matched related (n = 8), mismatched related (n = 16), or unrelated (n = 16). Graft-versus-host disease (GVHD) prophylaxis was methotrexate or cyclosporine (n = 7) or methotrexate plus cyclosporine (n = 33). Thirty-nine patients engrafted, 20 developed acute GVHD, and 7 developed chronic GVHD. Sixteen patients relapsed and 7 died of other causes. Patients in CR1 had disease-free survival (DFS) of 76% compared with 45% for CR2/CR3 and 8% for relapse (P < .001). Of 33 patients with cytogenetic data, 26 (79%) had MLL gene rearrangement. Fourteen of these 26 were in CR1 and 11 survive in remission. Outcome was associated with phase of disease, but having the MLL gene was not a factor predictive of outcome. Late effects included growth and other hormone deficiencies. These data demonstrate that infants with ALL and MLL gene have excellent DFS when they received transplants in CR1, and consideration for transplantation in CR1 is warranted