0000000000611562
AUTHOR
David Valcárcel
Analysis of relapse after transplantation in acute leukemia: A comparative on second allogeneic hematopoietic cell transplantation and donor lymphocyte infusions.
Relapse of acute leukemia (AL) after allogeneic hematopoietic cell transplantation (Allo-HCT) entails a dismal prognosis. In this scenario, donor lymphocyte infusions (DLIs) and second Allo-HCT are two major approaches. We compared outcomes of AL patients treated for relapse with DLI or second Allo-HCT after receiving debulking therapy. In total, 46 patients were included in the study; 30 (65%) had acute myeloid leukemia and 16 (35%) had acute lymphoblastic leukemia. The median age was 38 years (range 4-66). Twenty-seven patients received a second Allo-HCT and 19 patients received DLI. The median follow-up of the cohort was 273 days (range 9-7013). Overall survival (OS), disease-free surviv…
CD34+ Cell Selection versus Reduced-Intensity Conditioning and Unmodified Grafts for Allogeneic Hematopoietic Cell Transplantation in Patients Age >50 Years with Acute Myelogenous Leukemia and Myelodysplastic Syndrome .
Reduced-intensity conditioning (RIC) and T cell depletion (TCD) through CD34+ cell selection without the use of post-transplantation immunosuppression are 2 strategies used to reduce nonrelapse mortality (NRM) in older patients after allogeneic hematopoietic cell transplantation (allo-HCT). To compare the efficacy of the RIC and TCD approaches, we evaluated the outcomes of patients age >50 years with acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) who underwent allo-HCT from an HLA-matched donor with one of these strategies. Baseline characteristics were comparable in the patients receiving TCD (n = 204) and those receiving RIC (n = 151), except for a higher proportion o…
Thrombopoietin Receptor Agonists for Severe Thrombocytopenia after Allogeneic Stem Cell Transplantation: Experience of a Multicenter Study from the Grupo Español De Trasplante Hematopoyético (GETH)
Abstract Introduction Thrombocytopenia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-SCT). Underlying mechanisms are poorly known and usually multifactorial. Its treatment is not well defined, mostly based in platelet transfusion. Thus, is important to identify new strategies to manage this important post-SCT complication. Romiplostim and Eltrombopag are currently available thrombopoietin receptor agonists (TPO-RAs) that stimulate platelet production. Some studies with very small number of cases have reported their potential efficacy in the allo-SCT setting. For this reason, the aim of our study is to analyze the efficacy and safety of TPO-RAs for s…
Effect of Sirolimus Exposure on the Need for Preemptive Antiviral Therapy for Cytomeglovirus Infection after Allogeneic Hematopoietic Stem Cell Transplantation
The current study evaluates the clinical effect of sirolimus exposure on the occurrence of cytomegalovirus (CMV) DNAemia necessitating preemptive antiviral therapy. A total of 167 consecutive recipients of reduced-intensity conditioning (RIC) allogeneic hematopoietic stem cell transplantation (allo-HSCT) who received sirolimus- and tacrolimus-based graft-versus-host disease (GVHD) prophylaxis and whose CMV serostatus was positive for donors and/or recipients were included in this multicenter retrospective study. A parametric model with consecutive sirolimus blood levels describing the time to CMV DNAemia-RAT was developed using NONMEM version 7.4. Overall, 122 of 167 patients (73%) were all…
A Time-to-Event Model for Acute Kidney Injury after Reduced-Intensity Conditioning Stem Cell Transplantation Using a Tacrolimus- and Sirolimus-based Graft-versus-Host Disease Prophylaxis.
There is a paucity of data evaluating acute kidney injury (AKI) incidence and its relationship with the tacrolimus-sirolimus (Tac-Sir) concentrations in the setting of reduced-intensity conditioning (RIC) after allogeneic stem cell transplantation (allo-HSCT). This multicenter retrospective study evaluated risk factors of AKI defined by 2 classification systems, Kidney Disease Improving Global Outcome (KDIGO) score and "Grade 0-3 staging," in 186 consecutive RIC allo-HSCT recipients with Tac-Sir as graft-versus-host disease prophylaxis. Conditioning regimens consisted of fludarabine and busulfan (n = 53); melphalan (n = 83); or a combination of thiotepa, fludarabine, and busulfan (n = 50). …
Phase IV open-label study of the efficacy and safety of deferasirox after allogeneic stem cell transplantation
This is the first prospective study of deferasirox in adult allogeneic hematopoietic stem cell transplant recipients with transfusional iron overload in hematologic malignancies. Patients at least six months post transplant were treated with deferasirox at a starting dose of 10 mg/kg/day for 52 weeks or until serum ferritin was less than 400 ng/mL on two consecutive occasions. Thirty patients were enrolled and 22 completed the study. A significant reduction from baseline in median serum ferritin and in liver iron concentration at 52 weeks was observed in the overall population: from 1440 to 755.5 ng/mL (P=0.002) and from 14.5 to 4.6 mg Fe/g dw (P=0.0007), respectively. Reduction in serum fe…
Prospective Randomized Study Comparing Myeloablative Unrelated Umbilical Cord Blood Transplantation versus HLA-Haploidentical Related Stem Cell Transplantation for Adults with Hematologic Malignancies
In this prospective randomized study, we compared the outcomes of single-unit umbilical cord blood transplantation (UCBT) and unmanipulated haploidentical stem cell transplantation (haplo-SCT) with post-transplantation cyclophosphamide (PTCy) in adults with hematologic malignancies. All patients received a myeloablative conditioning (MAC) regimen consisting of thiotepa, busulfan, and fludarabine, with antithymocyte globulin (ATG) added for UCBT recipients. Nineteen patients were randomized to UCBT and the other 26 to haplo-HSCT. Four patients (15%) allocated to the haplo-HSCT arm lacked a suitable donor and were crossed over to the UCBT arm. Finally, 23 underwent UCBT and 22 underwent haplo…
Feasibility of thiotepa addition to the fludarabine-busulfan conditioning with tacrolimus/sirolimus as graft vs host disease prophylaxis.
In classical reduced-intensity conditioning (RIC) regimens, including the fludarabine and busulphan (BF) combination, sirolimus and tacrolimus (SIR-TAC) as graft vs host disease (GVHD) prophylaxis has shown acceptable results. The outcomes of SIR-TAC in a more intense RIC regimen as Thiotepa-fludarabine-busulfan (TBF) have been hardly investigated. This retrospective study included all consecutive patients receiving an allogeneic hematopoietic stem cell transplantation for myeloid malignancies (January 2009-2017) conditioned with either TBF or BF and receiving SIR-TAC. Patients receiving TBF presented higher non-relapse mortality (31.6 vs 12.3%,p = .01), along with shorter overall survival …
Ex vivo T-cell depletion vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil as graft-vs-host disease prophylaxis for allogeneic hematopoietic stem cell transplantation.
Objective To compare the efficacy and safety of CD34+ selected ex vivo T-cell depletion (TCD) vs post-transplant cyclophosphamide, sirolimus, and mycophenolate mofetil (PTCy-Sir-MMF) as graft-vs-host disease (GVHD) prophylaxis. Methods We retrospectively included patients who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) with either TCD (n = 38) or PTCy-Sir-MMF (n = 91). Results Cumulative incidence of neutrophil and platelet recovery was 92% vs 99% (P = .06) and 89% vs 97% (P = .3) in TCD and PTCy-Sir-MMF, respectively. Cumulative incidences of aGHVD grade II-IV, III-IV, and moderate to severe cGVHD were 11% vs 19% (P = .2), 3% vs 2% (P = .9), and 3% vs 36% (P < …
Pevonedistat (PEV) + Azacitidine (AZA) Versus AZA Alone As First-Line Treatment for Patients with Higher-Risk Myelodysplastic Syndromes (MDS)/Chronic Myelomonocytic Leukemia (CMML) or Acute Myeloid Leukemia (AML) with 20-30% Marrow Blasts: The Randomized Phase 3 PANTHER Trial (NCT03268954)
Abstract Background: Older patients with higher-risk MDS/CMML or AML with 20-30% marrow blasts typically receive single-agent hypomethylating agent (HMA) therapy. Median response duration and survival for these patients is poor, and many patients with MDS transform to secondary AML, which is associated with a particularly dismal prognosis. Novel HMA-based combination therapies that improve survival, delay transformation to AML, and increase depth and duration of response vs single-agent HMA therapy without additional toxicity or myelosuppression are needed. In a randomized, proof-of-concept phase 2 study PEV - a first-in-class, selective inhibitor of NEDD8-activating enzyme - in combination…