Optimized peripheral blood progenitor cell mobilization for autologous hematopoietic cell transplantation in children with high‐risk and refractory malignancies

2019 ◽  
Vol 24 (1) ◽  
Author(s):  
Eliska Furlong ◽  
Jesper Jensen ◽  
Mark Woodard ◽  
Katherine Griffiths ◽  
Geoff Knight ◽  
...  
Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1132-1132
Author(s):  
Melhem M. Solh ◽  
Rathmann Kristin ◽  
Sauvi chang-Fong ◽  
Jeremiah Oyer ◽  
Wesam B. Ahmed ◽  
...  

Abstract Method of Mobilization: Implication on Cell Subsets in The Graft and Immune Reconstitution post Autologous Hematopoietic Cell Transplantation (AHCT) The optimal mobilization method for either myeloma or lymphoma patients undergoing AHCT is still debatable and strategies for graft collection vary between different institutions. Plerixafor, a CXCR4 antagonist is used for peripheral blood stem cell mobilization in multiple myeloma and non-Hodgkins lymphoma patients requiring AHCT. The effect of plerixafor on graft composition has scarce data that are based mostly on cryopreserved samples. Moreover; the effect of plerixafor on immune reconstitution and hematologic recovery post AHCT has not been well evaluated. The goal of our study was to compare graft composition, hematologic and immune reconstitution recovery among patients mobilized with plerixafor plus G-CSF to those mobilized with G-CSF alone. Methods: 49 patients eligible for AHCT were enrolled on a single arm prospective trial at a single transplant center. All patients were mobilized with G-CSF 10µg/kg/day for 4 consecutive days. A peripheral blood CD34 level of <20/µl on day 4 was used as a cutoff to use plerixafor 0.24mg/kg in addition to G-CSf on 9pm of the fourth day. Peripheral blood collection was started on day 5 and was continued till the target dose is achieved or a minimum CD 34+ cell dose of >2x106 cells/Kg was obtained after 3 collection days. Samples from the freshly collected graft and patients' peripheral blood on days +30 and +60 were analyzed by flow cytometry (BD FACSCanto II) . A single platform assay was used (Beckman-Coulter Stem kit) via a ISHAGE protocol. The antibody cocktail contained the following pre-conjugated monoclonal antibodies: CD56-PE (Miltenyi Biotech, Auburn, CA), CD3-APC, CD16-FITC, (Beckman Coulter, Brea, CA), CD19-PE-CY7 (BD Biosciences, San Jose, CA). Data were acquired using BD FACSCanto II (BD Biosciences) and analyzed with the FACSDiva software (BD Biosciences) to quantify CD3+ T cells, CD3+ CD56+ NK-like T cells, CD56+ CD16+ and CD56+ CD16- NK cells as well as CD19+ B cells. Results: 49 patients with a median age of 58 years (range 21-75) were mobilized with either G-CSF alone (N=16) or plerixafor +G-CSF (G+P)(N=33).The median number of collection days was 1.42 and 1.81 (p=0.2) and the median collected CD34+ dose was 8.28x106/kg and 5.24x106 /kg (p=022) in the G+P and G-CSF alone groups respectively. Both groups had similar times to neutrophil and platelet engraftment. The graft analysis showed a white blood count of 309x109/l and 262x109/l (p=0.38), median percentage of CD34+ cells of 0.75% and 0.73% (p=0.81), percentage of CD3+ T cells of 25.6% and 22% (p=0.6) in the G+P and G-CSF alone groups resepectively. Both groups had similar proportions of CD3+, CD4+,CD8+, NK, NKT and iNKT cells in the mobilized grafts. Peripheral blood samples at day +30 and day +60 were analyzed for T cell markers and hematologic recovery (table 1). There was no significant difference between absolute lymphocyte counts, NK cell counts, T cells and absolute neutrophil count. Conclusion: Plerixafor when combined with G-CSF helps in achieving mobilization goals in patients predicted to be poor mobilizers based on peripheral CD34 levels. The addition of plerixafor doesn't not seem to affect T cell composition of the graft and yields similar hematologic and immune recovery when compared to mobilization with G-CSF alone. Table 1: Immune Reconstitution at Day 30 and Day 60 post Autologous Transplantation Treatment Group G-CSF (N=16) Plerixafor + G-CSF (N=33) P-value G-CSF (N=16) Plerixafor + G-CSF (N=33) P-value Day 30 Day 60 WBC 5.08 5.41 0.873 4.94 5.38 0.654 HGB 10.86 11.19 0.353 11.22 11.17 0.757 HCT 32.35 33.66 0.321 33.36 33.53 0.565 PLT 119.88 161.42 0.068 166.94 173.73 0.949 Abs Lymph 1.09 1.44 0.296 1.41 1.50 0.974 % NK 26.14 30.38 0.277 11.53 20.09 0.095 Abs NK 0.31 0.35 0.186 0.17 0.21 0.470 % T cell 67 60 0.183 76.15 67.39 0.340 Abs T cell 0.72 0.96 0.717 1.35 .82 0.095 NKT%* 5.28 3.33 8.25 3.38 B cell % 2.38 1.52 0.922 2.63 5.58 0.424 Abs. Neut count 2.99 2.64 0.488 2.85 3.01 0.848 Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5823-5823
Author(s):  
Elsa Sleiman ◽  
Alexandra Gomez ◽  
Julio C. Chavez ◽  
Mohamed A Kharfan-Dabaja ◽  
Ernesto Ayala

Abstract Background: High dose therapy (HDT) followed by autologous hematopoietic cell transplantation (autoHCT) has been shown to be safe and effective in patients with HIV-related lymphoma (HRL). Data is limited to small case series, transplant registries and a single prospective multicenter observational study. Here we report our institutional experience with auto-HCT in patients with HRL. Patients and methods: Twenty patients with HRL [non-Hodgkin=14 (70%), Hodgkin=6 (30%)] and treatable HIV infection underwent HDT consisting of carmustine, etoposide, cytarabine and melphalan (BEAM) followed by peripheral blood auto-HCT from 04/2006 to 07/2015. In 2 cases rituximab was administered as part of the preparative regimen. Patient-, disease-, and transplant-related characteristics are summarized in Table 1. Results: Median age was 48 years (range 35-61). The median follow-up for surviving patients was 42 months (range 6-110). At transplant, median peripheral blood CD4 count was 226 cells/µl (range 41-761). HIV viral load was undetectable in 14 out of 20 patients and lower than 4 logs in all of them. The median time to neutrophil and platelet engraftment were 11 days (range 10-13) and 14 days (range 13-176), respectively. Response rates at day +100 post-autografting in 17 evaluable patients were as follows: complete remission (CR)=11/17 (65%), partial response (PR)=2/17 (12%), and relapse/progression=4/17 (24%). Median event-free survival (EFS) was 58.4 months. Median overall survival (OS) was 74.3 months. At 5-years post-transplantation, EFS and OS were 68% and 53%, respectively. Non-hematologic toxicities consisted of mucositis in 8 (grade 1=3, grade 2=5), and enteritis in 13 patients (grade 1=2, grade 2=3, and grade 3=8). There were 13 documented infections in 11 patients (bacterial=9, viral=2, fungal=2). Six patients died from disease relapse/progression (n=5) and infection (n=1). Non-relapse mortality was 0% at day 100 and 5% at 5 years. Conclusion: Patients with HRL and treatable HIV infection should be offered autoHCT if indicated. HIV infection is no longer a contraindication for autoHCT in this population. Disclosures Chavez: Janssen: Speakers Bureau. Kharfan-Dabaja:Seattle Genetics: Speakers Bureau; Incyte: Speakers Bureau.


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