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1.
Bone Marrow Transplant ; 57(12): 1827-1832, 2022 12.
Article in English | MEDLINE | ID: mdl-36163427

ABSTRACT

Plerixafor, a CXCR4 receptor antagonist, reduces the binding and chemotaxis of hematopoietic stem cells to the bone marrow stroma, resulting in predictable peak of cluster of differentiation 34+ (CD34+) cells in the peripheral blood (PB) approximately 10 h after its administration. We developed a model that could predict the CD34+ harvest volume on the first day of apheresis (AP-CD34+) based on PB-CD34+ counts immediately prior to commencing apheresis in pediatric population. In all, data from 45 pediatric patients from the MOZAIC study who received either granulocyte colony-stimulating factor (G-CSF) alone or G-CSF plus plerixafor were included. The modeling of the data exhibited a strong and highly predictive linear relationship between the counts of PB-CD34+ cells on the first day of apheresis and AP-CD34+ cells collected on the same day. It is predicted that there are approximately 13 new collected CD34+ cells for 100 new circulating CD34+ cells before apheresis. Our predictive algorithm can be used to quantify the minimal count of PB-CD34+ cells that enables to collect at least 2 × 106 or 5 × 106 AP-CD34+ cells/kg with sufficient assurance (probability = 0.90) and can guide the use of plerixafor in patients at higher perceived risk for mobilization failure. Trial registration of MOZAIC study: ClinicalTrials.gov, NCT01288573; EudraCT, 2010-019340-40.


Subject(s)
Cyclams , Heterocyclic Compounds , Multiple Myeloma , Humans , Child , Hematopoietic Stem Cell Mobilization/methods , Heterocyclic Compounds/pharmacology , Heterocyclic Compounds/therapeutic use , Multiple Myeloma/therapy , Benzylamines , Granulocyte Colony-Stimulating Factor , Antigens, CD34/metabolism
2.
Am J Transplant ; 19(8): 2252-2261, 2019 08.
Article in English | MEDLINE | ID: mdl-30838775

ABSTRACT

This report describes the results of 2 international randomized trials (total of 508 kidney transplant recipients). The primary objective was to assess the noninferiority of rabbit anti-thymocyte globulin (rATG, Thymoglobulin® ) versus interleukin-2 receptor antagonists (IL2RAs) for the quadruple endpoint (treatment failure defined as biopsy-proven acute rejection, graft loss, death, or loss to follow-up) to serve as the pivotal data for United States (US) regulatory approval of rATG. The pooled analysis provided an incidence of treatment failure of 25.1% in the rATG and 36.0% in the IL2RA treatment groups, an absolute difference of -10.9% (95% confidence interval [CI] -18.8% to -2.9%) supporting noninferiority (noninferiority margin was 10%) and superiority of rATG to IL2RA. In a meta-analysis of 7 trials comparing rATG with an IL2RA, the difference in the proportion of patients with BPAR at 12 months was -4.8% (95% CI -8.6% to -0.9%) in favor of rATG. In conclusion, a rigorous reanalysis of patient-level data from 2 prior randomized, controlled trials comparing rATG versus IL-2R monoclonal antibodies provided support for regulatory approval for rATG for induction therapy in renal transplant, making it the first T cell-depleting therapy approved for the prophylaxis of acute rejection in patients receiving a kidney transplant in the United States.


Subject(s)
Antilymphocyte Serum/therapeutic use , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Animals , Basiliximab/therapeutic use , Glomerular Filtration Rate , Graft Rejection/etiology , Graft Rejection/pathology , Graft Survival , Humans , Kidney Function Tests , Prognosis , Rabbits , Randomized Controlled Trials as Topic , Receptors, Interleukin-2/antagonists & inhibitors , Risk Factors
3.
J Clin Oncol ; 30(28): 3499-506, 2012 Oct 01.
Article in English | MEDLINE | ID: mdl-22949147

ABSTRACT

PURPOSE: Treatment for metastatic colorectal cancer (mCRC) commonly involves a fluoropyrimidine-based chemotherapy regimen such as infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) or fluorouracil, leucovorin, and oxaliplatin, often combined with bevacizumab or an epidermal growth factor receptor monoclonal antibody. We studied the effect of adding the novel antiangiogenic agent aflibercept (also known as ziv-aflibercept in the United States) to FOLFIRI in patients with mCRC previously treated with oxaliplatin, including patients who received prior bevacizumab. PATIENTS AND METHODS: Patients were randomly assigned to receive aflibercept (4 mg/kg intravenously; 612 patients) or placebo (614 patients) every 2 weeks in combination with FOLFIRI. Treatment was administered until disease progression or unacceptable toxicity. The primary end point was overall survival. RESULTS: Adding aflibercept to FOLFIRI significantly improved overall survival relative to placebo plus FOLFIRI (hazard ratio [HR], 0.817; 95.34% CI, 0.713 to 0.937; P = .0032) with median survival times of 13.50 versus 12.06 months, respectively. Aflibercept also significantly improved progression-free survival (PFS; HR, 0.758; 95% CI, 0.661 to 0.869; P < .0001), with median PFS times of 6.90 versus 4.67 months, respectively. The effects on overall survival and PFS exhibited a consistent trend across prespecified subgroup analyses, including bevacizumab pretreated patients. Response rate was 19.8% (95% CI, 16.4% to 23.2%) with aflibercept plus FOLFIRI compared with 11.1% (95% CI, 8.5% to 13.8%) with placebo plus FOLFIRI (P = .0001). Adverse effects reported with aflibercept combined with FOLFIRI included the characteristic anti-vascular endothelial growth factor effects and also reflected an increased incidence of some chemotherapy-related toxicities. CONCLUSION: Aflibercept in combination with FOLFIRI conferred a statistically significant survival benefit over FOLFIRI combined with placebo in patients with mCRC previously treated with oxaliplatin.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Colorectal Neoplasms/drug therapy , Recombinant Fusion Proteins/administration & dosage , Adult , Aged , Aged, 80 and over , Camptothecin/analogs & derivatives , Camptothecin/therapeutic use , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease-Free Survival , Double-Blind Method , Female , Fluorouracil/therapeutic use , Humans , Leucovorin/therapeutic use , Male , Middle Aged , Organoplatinum Compounds/administration & dosage , Oxaliplatin , Receptors, Vascular Endothelial Growth Factor , Survival Rate , Young Adult
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