Effect of Priming with Granulocyte Colony-Stimulating Factor on the Outcome of Chemotherapy for Acute Myeloid Leukemia

Löwenberg, Bob; Putten, Wim van; Theobald, Matthias; Gmür, J; Verdonck, Leo F.; Sonneveld, Pieter; Fey, Martin F.; Schouten, Harry C.; Greef, Georgine de; Ferrant, Augustin; Kovacsovics, Tibor; Gratwohl, Aloïs; Daenen, Simon; Huijgens, Peter C.; Boogaerts, Marc

doi:10.1056/nejmoa025406

Cited by 355 publications

(252 citation statements)

References 29 publications

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“…Recent studies have shown that sensitization of leukemic cells with G-CSF or GM-CSF may enhance the cytotoxicity of chemotherapy in younger adults with newly diagnosed AML, 5,15 while other published studies, especially in elderly AML patients, have failed to show enhanced therapeutic efficacy of priming. 16 The reasons for these Figure 3.…”

Section: Discussionmentioning

confidence: 99%

“…The type of growth factor may also influence the results of priming. Although priming with other hematopoietic growth factors such as G-CSF have shown efficacy, 15 this may not be identical in terms of efficacy to priming with GM-CSF that is, at least theoretically, more efficient by recruiting earlier leukemia progenitors and potentially stem cells instead of only bulk leukemic cells. 19 Although G-CSF stimulates the development of granulocyte colonies, GM-CSF stimulates the proliferation and differentiation of neutrophils and eosinophils and, at higher doses, some megakaryocyte colonies.…”

Section: Discussionmentioning

confidence: 99%

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Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Thomas

Raffoux

Renneville

et al. 2010

Cancer

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BACKGROUND:Priming with granulocytic hematopoietic growth factors may modulate cell cycle kinetics of leukemic cells and render them more susceptible to phase‐specific chemotherapeutic agents. In a first report, we have shown that priming with granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) may enhance complete remission (CR) rate and event‐free survival (EFS) in younger adults with acute myeloid leukemia (AML).METHODS:In this randomized trial, 259 patients with AML were randomized at baseline to receive or not receive GM‐CSF concurrently with all cycles of chemotherapy. The effects of GM‐CSF on survival were reported herein with a long‐term follow‐up and studied according to distinct biological subgroups defined on cytogenetics and molecular markers.RESULTS:The EFS rate was better in the GM‐CSF group (43% vs 34%; P = .04). GM‐CSF did not improve the outcome in patients from good risk subgroups, while patients from poor risk subgroups benefited from GM‐CSF therapy. In this population, the difference in terms of EFS probability was mainly observed in patients with high initial white blood cell count and in those with FLT3‐ITD or MLL rearrangement. When combining these 2 molecular abnormalities for comparison of the effect of GM‐CSF priming, the difference in terms of EFS was highly significant (5‐year EFS, 39% with GM‐CSF vs 8% without GM‐CSF; P = .007).CONCLUSIONS:Sensitization of leukemic cells and their progenitors by GM‐CSF appears as a plausible strategy for improving the outcome of patients with newly diagnosed AML. Patients with poor‐prognosis FLT3‐ITD or MLL rearrangement might be a good target population to further investigate priming strategies. Cancer 2010. © 2010 American Cancer Society.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Thomas

Raffoux

Renneville

et al. 2010

Cancer

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“…The safety and efficacy of this regimen for the treatment of AML were evaluated previously, 5,6 and the administration of G-CSF enhanced the efficacy of chemotherapy in patients with AML. 7 After the conditioning chemotherapy, peripheral blood stem cells were reinfused. Neutrophil engraftment was achieved on day 24 after transplantation without G-CSF administration.…”

Section: B Cmentioning

confidence: 99%

Successful Treatment of Bulky Granulocytic Sarcoma of the Retroperitoneum with High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

Matsui

Hidaka

Kiyokawa

et al. 2013

J Clin Exp Hematopathol

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Granulocytic sarcoma is a rare disease that is rarely curable with conventional chemotherapy. This report describes a case of a patient with bulky granulocytic sarcoma of the retroperitoneum who was treated with high-dose chemotherapy and autologous peripheral blood stem cell transplantation without administering granulocyte colony-stimulating factor before stem cell collection. According to bone marrow assessment and imaging studies, the patient remained in complete remission at 5 years after transplantation. This case suggests that high-dose chemotherapy followed by autologous peripheral blood stem cell transplantation is a therapeutic option for granulocytic sarcoma. 〔J Clin Exp Hematop 53(3) : 235-239, 2013〕

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“…Löwenberg. [35], [36], [37] Patient data represent log2 expression levels and were normalized to the expression levels of the two house keeping genes HMBS and ABL. For better readability we multiplied the results by (-1) and excluded Ct values higher than 40 (ΔCt = 40-Ct GENE-1 -(Mean Ct HMBS and Ct ABL1 ) * (-1)).…”

Section: Introductionmentioning

confidence: 99%

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation

et al. 2016

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The RNA binding proteins RBM binding motif protein 38 (RBM38) and DEAD END 1 (DND1) selectively stabilize mRNAs by attenuating RNAse activity or protecting them from micro(mi)RNA-mediated cleavage. Furthermore, both proteins can efficiently stabilize the mRNA of the cell cycle inhibitor p21 CIP1 . Since acute myeloid leukemia (AML) differentiation requires cell cycle arrest and RBM38 as well as DND1 have antiproliferative functions, we hypothesized that decreased RBM38 and DND1 expression may contribute to the differentiation block seen in this disease. We first quantified RBM38 and DND1 mRNA expression in clinical AML patient samples and CD34 + progenitor cells and mature granulocytes from healthy donors. We found significantly lower RBM38 and DND1 mRNA levels in AML blasts and CD34 + progenitor cells as compared to mature neutrophils from healthy donors. Furthermore, the lowest expression of both RBM38 and DND1 mRNA correlated with t(8;21). In addition, neutrophil differentiation of CD34 + cells in vitro with G-CSF (granulocyte colony stimulating factor) resulted in a significant increase of RBM38 and DND1 mRNA levels. Similarly, neutrophil differentiation of NB4 acute promyelocytic leukemia (APL) cells was associated with a significant induction of RBM38 and DND1 expression. To address the function of RBM38 and DND1 in neutrophil differentiation, we generated two independent NB4_RBM38 as well as DND1 knockdown cell lines. Inhibition of both RBM38 and DND1 mRNA significantly attenuated NB4 differentiation and resulted in decreased p21 CIP1 mRNA expression. Our results clearly indicate that expression of the RNA binding proteins RBM38 and DND1 is repressed in primary AML patients, that neutrophil differentiation is dependent on increased expression of both proteins, and that these proteins have a critical role in regulating p21 CIP1 expression during APL differentiation. Highlights RBM38 and DND1 expression is attenuated in primary AML patients  Normal and leukemic neutrophil differentiation induces RBM38 and DND1 expression  New function for the RNA binding proteins RBM38 and DND1 in APL differentiation Keywords: RBM38, DND1, acute myeloid leukemia, acute promyelocytic leukemia, neutrophil differentiation

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Effect of Priming with Granulocyte Colony-Stimulating Factor on the Outcome of Chemotherapy for Acute Myeloid Leukemia

Cited by 355 publications

References 29 publications

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Which AML subsets benefit from leukemic cell priming during chemotherapy? Long‐term analysis of the ALFA‐9802 GM‐CSF study

Successful Treatment of Bulky Granulocytic Sarcoma of the Retroperitoneum with High-Dose Chemotherapy and Autologous Peripheral Blood Stem Cell Transplantation

The RNA binding proteins RBM38 and DND1 are repressed in AML and have a novel function in APL differentiation

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