Chemosensitivity of nonleukemic clonogenic precursors in AML patients in complete remission: Association with CD34+ mobilization and with disease-free survival

Milone, Giuseppe; Avola, Giuseppe; Leotta, Salvatore; Strano, Aurora; Camuglia, Maria Grazia; Pinto, Valeria; Mercurio, S; Poidomani, Massimo; Coppoletta, Stefania; Marco, Anna Lia Di; Consoli, Carla; Triolo, Anna; Spadaro, André Gasparini; Privitera, Agata; Ragusa, Angela; Tibullo, Daniele; Mercurio, Sandra Di

doi:10.1016/j.exphem.2011.10.002

Cited by 5 publications

(6 citation statements)

References 25 publications

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“…This hypothesis has been put forward recently by our group [26] on the basis of experimental work in marrow cell of AML patients in complete remission. In these experiments, we found that a chemo-sensitivity of normal non-leukemic cells in complete remission is heterogeneous and that this heterogeneity correlated with LFS [27].…”

Section: Discussionmentioning

confidence: 75%

Autologous Transplantation in 1st Cr Aml Patients with Purged or Unpurged Bone Marrow: Good Clinical Results in Favorable Cytogenetic Group and in those Infused with a Low Number of Marrow Cells

Leotta¹

2014

J Bone Marrow Res

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In a single institution, 31 patients affected with Acute Myeloid Leukaemia (AML) in 1st Complete Remission (CR) received autologous bone marrow transplantation (ABMT). Mafosfamide was employed in a non-randomized fashion to purge marrows, in 15 cases bone marrow cells were purged, while in 16 they were left unpurged. Dose of infused Total Nucleated Cells (TNC) was an important factor for myeloid engraftment (P=0.02). LFS was 58% in purged and 40% in unpurged groups (P=0.26). Patients having a good prognosis cariotype had a LFS of 100% while the group of all other patients had a LFS of 37.5%. Patients receiving a dose of TNC below to median had a LFS of 65% and those receiving a dose of TNC>median had a LFS of 28% (P=0.017). Purging significantly improved LFS in patients "not harbouring good cytogenetic abnormalities" (53% LFS in purged group versus 18% in unpurged group, P=0.05). In conclusion, ABMT is associated with excellent results in "good prognosis cytogenetic". Purging may improve results in patients belonging to "intermediate cytogenetic group". A high number of infused TNC produces a fast myeloid engraftment but a poor LFS.

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Section: Discussionmentioning

confidence: 75%

Autologous Transplantation in 1st Cr Aml Patients with Purged or Unpurged Bone Marrow: Good Clinical Results in Favorable Cytogenetic Group and in those Infused with a Low Number of Marrow Cells

Leotta¹

2014

J Bone Marrow Res

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“…In super mobilizing patients we observed an increase in the chemoresistance of the marrow hematopoietic clonogenic precursors obtained from CR patients. 26 Interestingly, this increase in in vitro chemoresistance of the clonogenic precursors found in some AML patients correlated not only to a high mobilization of CD34 þ cells but also with decreased DFS. Our findings suggest that abnormal behavior of normal non-leukemic marrow precursors cells causes CD34 þ super mobilization.…”

Section: Discussionmentioning

confidence: 96%

“…This hypothesis could also explain the fact that super mobilizing patients have shorter aplastic phases after consolidation cycles. 2,26 It can also be expected that this function of some leukemia cells will be associated and dependent on other known molecular malignancy markers.…”

Section: Discussionmentioning

confidence: 99%

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation

Milone

Poidomani

Leotta

et al. 2011

Bone Marrow Transplant

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Ninety-six AML patients in 1st CR were evaluated for peak CD34 þ cell levels in peripheral blood (PB) during PBSC mobilization and harvest. Distribution of CD34 þ cell peaks was determined and cases were grouped on the basis of 50th and 75th percentile: group A, those having a CD34 þ cell peak p70 Â 10 9 /L (n ¼ 48); group B, those having a CD34 þ cell peak between 70 and 183 Â 10 9 /L (n ¼ 24); group C, those having a CD34 þ cell peak 4183 Â 10 9 /L (n ¼ 24). Irrespective of post-remission treatment received, group A had a disease free survival (DFS) of 73%, group B a DFS of 51% and group C of 30% (P ¼ 0.0003). In intermediate cytogenetic risk patients, those treated by autologous transplantation had a DFS of 68, 33 and 14% in the groups A, B and C, respectively, (P ¼ 0.01) whereas after allogeneic transplantation DFS was 87% in group A þ B vs 50% in group C (P ¼ 0.009). The peak of CD34 þ cells in PB, was an independent predictor for DFS in multivariate analysis.

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“…12,13 In AML patients, chemosensitivity of colony-forming units of granulocytes and monocytes derived from BM cells were described to correlate inversely with the peripheral maximum CD34 + cells peak during SC mobilization. 14…”

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confidence: 99%

“…Whereas available data suggest that ASCT with PBSC can be recommended to distinct subgroups of AML patients, there is little information on the mobilization failure rate and on rescue strategies for AML patients with a failed attempt of autologous PBSC collection 12,13 . In AML patients, chemosensitivity of colony‐forming units of granulocytes and monocytes derived from BM cells were described to correlate inversely with the peripheral maximum CD34 + cells peak during SC mobilization 14 …”

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confidence: 99%

Hematopoietic Stem Cell Mobilization With Plerixafor Is Safe and Effective in Poorly Mobilizing Acute Myeloid Leukemia Patients

et al. 2019

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Autologous stem cell transplantation (ASCT) can be applied to consolidate first remission (CR1) in favorable/intermediate-risk acute myeloid leukemia (AML) patients. [1][2] However, up to 20% of AML patients in CR1 fail to mobilize a sufficient number of peripheral blood stem cells (PBSC). 3 We evaluated safety and effectiveness of adding plerixafor to continued G-CSF stimulation in 5 AML patients in CR1, who had failed to mobilize at least 10 CD34 + cells/mL in the peripheral blood. The patients received a single dose of 24 mg plerixafor intravenously 4 hours before apheresis. Subsequent PBSC collection was successful in all patients enabling them to proceed to ASCT, and all autografts were molecularly minimal residual disease (MRD)-negative. These data suggest that plerixafor added to G-CSF stimulation is effective in AML patients with otherwise failing stem cell PBSC mobilization.In AML patients in CR1, high CD34 + cell counts harvested in a single apheresis or high percentages of CD34 + cells in the autografts are associated with adverse outcome. 4 We and others demonstrated that high numbers of peripheral circulating CD34 + cells at PBSC collection predicted higher relapse risk, whereas delayed hematologic recovery after ASCT was associated with better survival rates. [5][6][7][8] Accordingly, a decreased mobilization potential after induction chemotherapy can indicate a favorable course in AML patients, in contrast to, for example, myeloma patients undergoing high-dose chemotherapy (HDCT)/ASCT. [5][6][7]9 Mobilization failure in AML patients in CR1 is so far poorly studied, and subsequent alternative strategies are limited to bone marrow (BM) harvesting with all its inconveniences. Moreover, physicians are reluctant to use the rescue CXCR4 antagonist plerixafor in AML patients given the possible mobilization of residual leukemic stem cells and the possibility to harvest mobilized leukemic cells. 10 However, this conclusion is not based on clinical data in this situation. Accordingly, we investigated in this study the safety and effectiveness of adding rescue plerixafor in AML patients, which otherwise would have failed stem cell mobilization.We studied 5 patients with therapy-naïve de novo AML, who received 2 cycles of induction chemotherapy at the University Hospital of Bern. All patients had achieved CR after the first induction cycle and were planned for consolidation with HDCT/ ASCT based on their genetic risk profiles (Table 1). The second induction cycle comprised cytarabine and daunorubicin in all patients, and when BM assessment on day 18 confirmed remission, G-CSF was started on the first day of neutrophils rising >0.5 G/L. Stem cell collection was planned on the first day of peripheral circulating CD34 + cells exceeding 20/mL. However, all 5 patients failed to achieve at least 10/mL despite continued G-CSF stimulation and were considered mobilization failure.According to European Leukemia Net criteria, 4 patients had favorable and 1 patient had intermediate risk. 11 Four patients showed mutations ...

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Chemosensitivity of nonleukemic clonogenic precursors in AML patients in complete remission: Association with CD34+ mobilization and with disease-free survival

Cited by 5 publications

References 25 publications

Autologous Transplantation in 1st Cr Aml Patients with Purged or Unpurged Bone Marrow: Good Clinical Results in Favorable Cytogenetic Group and in those Infused with a Low Number of Marrow Cells

Autologous Transplantation in 1st Cr Aml Patients with Purged or Unpurged Bone Marrow: Good Clinical Results in Favorable Cytogenetic Group and in those Infused with a Low Number of Marrow Cells

Prognostic value of CD34+ peak in peripheral blood during mobilization in intermediate-risk AML patients treated in first CR by autologous or allogeneic transplantation

Hematopoietic Stem Cell Mobilization With Plerixafor Is Safe and Effective in Poorly Mobilizing Acute Myeloid Leukemia Patients

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