Browsing by Subject "Platelet Count"
Now showing 1 - 4 of 4
- Results Per Page
- Sort Options
Item Open Access A multicenter phase I/II study of obatoclax mesylate administered as a 3- or 24-hour infusion in older patients with previously untreated acute myeloid leukemia.(PloS one, 2014-01) Schimmer, Aaron D; Raza, Azra; Carter, Thomas H; Claxton, David; Erba, Harry; DeAngelo, Daniel J; Tallman, Martin S; Goard, Carolyn; Borthakur, GautamAn open-label phase I/II study of single-agent obatoclax determined a maximum tolerated dose (MTD) and schedule, safety, and efficacy in older patients (≥ 70 yr) with untreated acute myeloid leukemia (AML).Phase I evaluated the safety of obatoclax infused for 3 hours on 3 consecutive days (3 h × 3 d) in 2-week cycles. Initial obatoclax dose was 30 mg/day (3 h × 3 d; n = 3). Obatoclax was increased to 45 mg/day (3 h × 3 d) if ≤ 1 patient had a dose-limiting toxicity (DLT) and decreased to 20 mg/day (3 h × 3 d) if DLT occurred in ≥ 2 patients. In the phase II study, 12 patients were randomized to receive obatoclax at the dose identified during phase I (3 h × 3 d) or 60 mg/day administered by continuous infusion over 24 hours for 3 days (24 h × 3 d) to determine the morphologic complete response rate.In phase I, two of three patients receiving obatoclax 30 mg/day (3 h × 3 d) experienced grade 3 neurologic DLTs (confusion, ataxia, and somnolence). Obatoclax was decreased to 20 mg/day (3 h × 3 d). In phase II, no clinically relevant safety differences were observed between the 20 mg/day (3 h × 3 d; n = 7) and 60 mg/day (24 h × 3 d; n = 5) arms. Neurologic and psychiatric adverse events were most common and were generally transient and reversible. Complete response was not achieved in any patient.Obatoclax 20 mg/day was the MTD (3 h × 3 d) in older patients with AML. In the schedules tested, single-agent obatoclax was not associated with an objective response. Evaluation in additional subgroups or in combination with other chemotherapy modalities may be considered for future study.ClinicalTrials.gov NCT00684918.Item Open Access Influence of nucleated cell dose on overall survival of unrelated cord blood transplantation for patients with severe acquired aplastic anemia: a study by eurocord and the aplastic anemia working party of the European group for blood and marrow transplantation.(Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation, 2011-01) Peffault de Latour, Regis; Purtill, Duncan; Ruggeri, Annalisa; Sanz, Guillermo; Michel, Gerard; Gandemer, Virginie; Maury, Sebastien; Kurtzberg, Joanne; Bonfim, Carmen; Aljurf, Mahmoud; Gluckman, Eliane; Socié, Gerard; Passweg, Jakob; Rocha, VandersonInformation is scarce on outcomes after unrelated cord blood transplantation (UCBT) for patients with severe aplastic anemia (SAA). We retrospectively analyzed 71 patients (median age, 13 years; 28 adults) with SAA (9 with paroxysmal nocturnal hemoglobinuria [PNH]) who received a single-unit (n = 57; 79%) or double-unit UCBT (n = 14; 19%) in 32 centers between 1996 and 2009. A reduced-intensity conditioning regimen was provided in 68% of the patients. The cumulative incidence (CI) of neutrophil recovery was 51% ± 6% at day 60, with significantly better engraftment seen in recipients of higher prefreezing total nucleated cell (TNC) dose (>3.9 10(7)/kg; hazard ratio [HR], 1.5; P = .05). The CI of platelet engraftment at day 180 posttransplantation was 37% ± 7%, that of grade II-IV acute GVHD was 20% ± 5%, and that of chronic GVHD at 3 years was 18% ± 5%. At a median follow-up of 35 months (range, 3-83 months), the estimated probability of 3-year overall survival (OS) was 38% ± 6%. Significantly improved OS was seen in recipients of >3.9 10(7) TNCs/kg prefreezing (45%, compared with 18% for recipients of ≤ 3.9 10(7) TNC/kg; HR, 0.4; P = .007). These results highlight the fundamental role of cell dose for both engraftment and OS in patients with SAA undergoing UCBT.Item Open Access Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery.(Anesthesiology, 2016-02) Kertai, Miklos D; Zhou, Shan; Karhausen, Jörn A; Cooter, Mary; Jooste, Edmund; Li, Yi-Ju; White, William D; Aronson, Solomon; Podgoreanu, Mihai V; Gaca, Jeffrey; Welsby, Ian J; Levy, Jerrold H; Stafford-Smith, Mark; Mathew, Joseph P; Fontes, Manuel LBACKGROUND: Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. METHODS: The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. RESULTS: The median postoperative nadir platelet count was 121 × 10/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 10/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). CONCLUSION: The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.Item Open Access Plerixafor (a CXCR4 antagonist) following myeloablative allogeneic hematopoietic stem cell transplantation enhances hematopoietic recovery.(J Hematol Oncol, 2018-03-04) Green, Michael MB; Chao, Nelson; Chhabra, Saurabh; Corbet, Kelly; Gasparetto, Cristina; Horwitz, Ari; Li, Zhiguo; Venkata, Jagadish Kummetha; Long, Gwynn; Mims, Alice; Rizzieri, David; Sarantopoulos, Stefanie; Stuart, Robert; Sung, Anthony D; Sullivan, Keith M; Costa, Luciano; Horwitz, Mitchell; Kang, YubinBACKGROUND: The binding of CXCR4 with its ligand (stromal-derived factor-1) maintains hematopoietic stem/progenitor cells (HSPCs) in a quiescent state. We hypothesized that blocking CXCR4/SDF-1 interaction after hematopoietic stem cell transplantation (HSCT) promotes hematopoiesis by inducing HSC proliferation. METHODS: We conducted a phase I/II trial of plerixafor on hematopoietic cell recovery following myeloablative allogeneic HSCT. Patients with hematologic malignancies receiving myeloablative conditioning were enrolled. Plerixafor 240 μg/kg was administered subcutaneously every other day beginning day +2 until day +21 or until neutrophil recovery. The primary efficacy endpoints of the study were time to absolute neutrophil count >500/μl and platelet count >20,000/μl. The cumulative incidence of neutrophil and platelet engraftment of the study cohort was compared to that of a cohort of 95 allogeneic peripheral blood stem cell transplant recipients treated during the same period of time and who received similar conditioning and graft-versus-host disease prophylaxis. RESULTS: Thirty patients received plerixafor following peripheral blood stem cell (n = 28) (PBSC) or bone marrow (n = 2) transplantation. Adverse events attributable to plerixafor were mild and indistinguishable from effects of conditioning. The kinetics of neutrophil and platelet engraftment, as demonstrated by cumulative incidence, from the 28 study subjects receiving PBSC showed faster neutrophil (p = 0.04) and platelet recovery >20 K (p = 0.04) compared to the controls. CONCLUSIONS: Our study demonstrated that plerixafor can be given safely following myeloablative HSCT. It provides proof of principle that blocking CXCR4 after HSCT enhances hematopoietic recovery. Larger, confirmatory studies in other settings are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01280955.