Dataset Information

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

ABSTRACT: We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 ?g/kg daily for 6 days starting on day -9) plus plerixafor (doses of 0, 80, 160 or 240 ?g/kg daily for 4 days starting on day -7) along with the busulfan-fludarabine (Bu-Flu) conditioning regimen. In the phase 1 part, we determined that G-CSF plus plerixafor is safe in this setting. We compared the clinical effects and outcomes of AML/MDS study patients (n=40) with 164 patients from a historical data set who received Bu-Flu alone before allo-SCT by stratifying on cytogenetics and disease status to correct for bias. Study patients had increased myeloid chimerism and lower rates of GvHD. There was no significant difference in relapse-free survival or overall survival. The G-CSF plus plerixafor combination increased circulating WBCs, CD34+ cells and CXCR4+ cells, and preferentially mobilized FISH+ leukemic cells.

SUBMITTER: Konopleva M

PROVIDER: S-EPMC4490031 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

Konopleva Marina M Benton Christopher B CB Thall Peter F PF Zeng Zhihong Z Shpall Elizabeth E Ciurea Stefan S Kebriaei Partow P Alousi Amin A Popat Uday U Anderlini Paolo P Nieto Yago Y Parmar Simrit S Qiao Wei W Chen Julianne J Rondon Gabriela G McMullin Becky B Wang Rui-Yu RY Lu Hongbo H Schober Wendy W Woodworth Glenda G Gulbis Alison A Cool Rita R Andreeff Michael M Champlin Richard R

Bone marrow transplantation 20150413 7

We hypothesized that during conditioning chemotherapy for allogeneic stem cell transplant (allo-SCT), the disruption of stromal-leukemia interactions using G-CSF in combination with the CXCR4-specific inhibitor, plerixafor, may promote the release of leukemic cells from the niche and increase tumor elimination. In a phase 1/2 investigation, we treated 45 AML/myelodysplastic syndrome (MDS)/CML patients (34 AML, 7 MDS and 4 CML) with G-CSF (10 μg/kg daily for 6 days starting on day -9) plus plerix ...[more]

PMID: 25867648

Similar Datasets

Project description:Large, multicenter studies comparing commonly used reduced-intensity conditioning (RIC) approaches in follicular lymphoma (FL) have not been performed. Using the Center for International Blood and Marrow Transplant Research database, we report the outcomes of the 2 most commonly used RIC approaches, fludarabine and busulfan (Flu/Bu) versus fludarabine, cyclophosphamide, and rituximab (FCR) in FL patients. We evaluated 200 FL patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) who received RIC with either Flu/Bu (n = 98) or FCR (n = 102) during 2008 to 2014. All patients received peripheral blood grafts, and graft-versus-host disease (GVHD) prophylaxis was limited to calcineurin inhibitor-based approaches. Median follow-up of survivors in the Flu/Bu and FCR groups was 48 months and 46 months, respectively. On univariate analysis in the Flu/Bu and FCR groups, the 3-year rates of nonrelapse mortality (11% versus 11%, P = .94), relapse/progression (18% versus 15%, P = .54), progression-free survival (PFS) (71% versus 74%, P = .65), and overall survival (OS) (73% versus 81%, P = .18) were not significantly different. On multivariate analysis no difference was seen between the FCR and Flu/Bu cohorts in terms of grades II to IV (relative risk [RR], 1.06; 95% confidence interval [CI], .59 to 1.93; P = .84) or grades III to IV (RR, 1.18; 95% CI, .47 to 2.99; P = .72) acute GVHD, nonrelapse mortality (RR, .83; 95% CI, .38 to 1.82; P = .64), relapse/progression (RR, .99; 95% CI, .49 to 1.98; P = .97), PFS (RR, .92; 95% CI, .55 to 1.54; P = .76), or OS (RR, .70; 95% CI, .40 to 1.23; P = .21) risk. However, RIC with FCR was associated with a significantly reduced chronic GVHD risk (RR, .52; 95% CI, .36 to .77; P = .001). RIC with either Flu/Bu or FCR in patients with FL undergoing allo-HCT provides excellent 3-year OS, with acceptable rates of nonrelapse mortality. FCR-based conditioning was associated with a lower risk of chronic GVHD.

Project description:To improve the outcome of allogeneic stem cell transplantation in refractory acute myeloid leukemia (AML), we conducted a single-arm phase II clinical trial to evaluate the efficacy and feasibility of conditioning regimen following cytoreduction chemotherapy with 7-day interval. Adult patients with refractory AML were enrolled in the study and received fludarabine, cytarabine, and idarubicin (FLAG-IDA) as cytoreductive chemotherapy followed by busulfan and fludarabine (Flu-BU) conditioning regimen and transfusion of mobilized peripheral stem cells from human leukocyte antigen-matched sibling or unrelated donor. The primary endpoint of the study was 2-year leukemia-free survival (LFS) and secondary endpoints included complete-remission rate, 2-year overall survival (OS), nonrelapse mortality (NRM), and relapse rate. A total of 16 patients were enrolled with median age of 36 (16-60), which included 9 primary induction failure, 2 early relapse, and 5 with relapse/refractory disease. The median cycles of previous chemotherapy were 4 (3-10) with a median of 55% (1%-90%) blasts in bone marrow. Six patients received transplantation from matched sibling and 10 from matched unrelated donors. After transplantation, 15 patients achieved bone marrow remission (11 complete remissions [CRs] and 4 bone marrow remissions without platelet recovery) at day +28. A total of 8 patients remained alive in CR with median LFS of 29.5 months (9.5-40.5 months). Four patients relapsed and 3 of them died of disease and another 4 patients died because of transplantation-related toxicity. The 2-year NRM and relapse rates were 25.0% ± 10.8% and 33.4% ± 13.8%, respectively with 2-year OS at 53.5% ± 13.1% and LFS at 50.0% ± 12.5%. Based on the Simon 2-stage design, 5 out of first eligible 14 patients remained leukemia-free for more than 2 years after allogeneic hematopoietic stem cell transplantation; thus, the null hypothesis of the study will be rejected and the study protocol is accepted as being warranted for further study. Based on the above data, our phase II study demonstrated that the sequential FLAG-IDA cytoreduction chemotherapy followed by Flu-BU conditioning regimen given at the hematological nadir was feasible and has sufficient activity to warrant further investigation prospectively with a larger patient sample (clinicaltrials.gov identifier: NCT01496547).

Dataset Information

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

Publications

Leukemia cell mobilization with G-CSF plus plerixafor during busulfan-fludarabine conditioning for allogeneic stem cell transplantation.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets