8 research outputs found
Expression of some ATP-binding cassette transporters in Acute Myeloid Leukemia.
Hematopoietic cells express ATP binding
cassette (ABC) transporters in relation
to different degrees of differentiation. One
of the known multidrug resistance mechanisms
in acute myeloid leukemia (AML) is
the overexpression of efflux pumps belonging
to the superfamily of ABC transporters
such as ABCB1, ABCG2 and ABCC1.
Although several studies were carried out to
correlate ABC transporters expression with
drug resistance, little is known about their
role as markers of diagnosis and progression
of the disease. For this purpose we
investigated the expression, by real-time
PCR, of some ABC genes in bone marrow
samples of AML patients at diagnosis and
after induction therapy. At diagnosis,
ABCG2 was always down-regulated, while
an up regulated trend for ABCC1 was
observed. After therapy the examined genes
showed a different expression trend and
approached the values of healthy subjects
suggesting that this event could be considered
as a marker of AML regression. The
expression levels of some ABC transporters
such as ABCC6, seems to be related to gender,
age and to the presence of FLT3/ITD
gene mutation
Plerixafor Added to Chemotherapy Plus G-CSF Is Safe and Allows Adequate PBSC Collection in Predicted Poor Mobilizer Patients with Multiple Myeloma or Lymphoma
We evaluated the safety and efficacy of plerixafor, subsequent to disease-specific chemotherapy followed by granulocyte-colony stimulating factor (G-CSF), in 37 multiple myeloma (MM) or lymphoma patients, who were candidates for autologous stem cell transplantation (ASCT) predicted as poor mobilizers (PMs). Patients were identified as predicted PMs according to the history of a previously failed mobilization attempt or the presence of ≥1 factors predicting an unsuccessful harvest, such as advanced disease, prior extensive radiotherapy, or prolonged treatment, with stem cell poisons, advanced age, or extensive bone marrow involvement. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to 3 consecutive days while continuing G-CSF for 9 to 11 hours before the planned apheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a median 4-fold increase (range: 1.4-32) in the number of circulating CD34+ cells following plerixafor compared with baseline CD34+ cell concentration (from a median of 5 cells/μL, range: 1-32, to a median of 32 cells/μL, range: 6-201). Twenty-seven of the 37 patients (14 of 17 with MM and 13 of 20 with lymphoma) had ≥2×106 CD34+ cells/kg collected in 1-3 apheretic procedures. Of the 27 patients rescued with plerixafor, 24 (13 MM, 11 lymphoma) have been transplanted with plerixafor-mobilized peripheral blood stem cells, showing a rapid and durable hematologic recovery. Our results suggest that the addition of plerixafor to G-CSF after disease-oriented chemotherapy is safe and allows for a satisfactory harvest in order to perform a safe ASCT, in a relevant proportion of lymphoma and MM patients considered to be PMs
Predicting failure of hematopoietic stem cell mobilization before it starts: the predicted poor mobilizer (pPM) score
Predicting mobilization failure before it starts may enable patient-tailored strategies. Although consensus criteria for predicted PM (pPM) are available, their predictive performance has never been measured on real data. We retrospectively collected and analyzed 1318 mobilization procedures performed for MM and lymphoma patients in the plerixafor era. In our sample, 180/1318 (13.7%) were PM. The score resulting from published pPM criteria had sufficient performance for predicting PM, as measured by AUC (0.67, 95%CI: 0.63â\u80\u930.72). We developed a new prediction model from multivariate analysis whose score (pPM-score) resulted in better AUC (0.80, 95%CI: 0.76â\u80\u930.84, p < 0001). pPM-score included as risk factors: increasing age, diagnosis of NHL, positive bone marrow biopsy or cytopenias before mobilization, previous mobilization failure, priming strategy with G-CSF alone, or without upfront plerixafor. A simplified version of pPM-score was categorized using a cut-off to maximize positive likelihood ratio (15.7, 95%CI: 9.9â\u80\u9324.8); specificity was 98% (95%CI: 97â\u80\u9398.7%), sensitivity 31.7% (95%CI: 24.9â\u80\u9339%); positive predictive value in our sample was 71.3% (95%CI: 60â\u80\u9380.8%). Simplified pPM-score can â\u80\u9crule inâ\u80\u9d patients at very high risk for PM before starting mobilization, allowing changes in clinical management, such as choice of alternative priming strategies, to avoid highly likely mobilization failure