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Detecting hereditary MDS/AML
Unexplained cytopenias or failure to mobilize stem cells in related donors of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) – important clues for the detection of a hereditary MDS/AML syndrome – should prompt efforts to obtain germ line tissue sources for collaborative research, Jane E. Churpek, MD, of the Hereditary Hematologic Malignancies Program at The University of Chicago Medicine, wrote.
Partnering with families to obtain germ line tissue sources uncontaminated by tumor cells from large numbers of patients with MDS/AML, and international collaboration to determine the mechanisms and multi-step processes from the carrier state to overt disease, have enormous potential to improve the outcomes of patients with both familial and sporadic forms of MDS/AML. Incorporating collection of ideal germ line tissue along with family histories to the already robust international MDS/AML registries and data sharing are all essential to future progress in this field, she wrote in a recent article published onlne in Best Practice & Research Clinical Haematology.
Prophylactic granulocyte transfusions
Giving prophylactic granulocyte transfusions to AML patients during the induction phase of therapy is feasible and safe, but assuring an adequate donor pool and patient continuation of the transfusions are another matter.
In a phase 2 trial of 45 neutropenic patients with AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy, non-irradiated allogeneic granulocyte transfusions were to be given every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. But logistical problems limited the success of the protocol: 5 patients never received a granulocyte transfusion due to donor screening failure or donor unavailability and the other 40 received a median of 3 (range 1-9) granulocyte transfusions.
“We anticipated approximately 8 GTs per patient ... only 11 received 6 or more GTs,” Fleur M. Aung, MD, and colleagues at The MD Anderson Cancer Center, Houston, wrote in the Journal of Blood Disorders and Transfusion (DOI 10.4172/2155-9864.1000376).
The authors concluded that while the process is feasible, ex vivo expanded neutrophils, produced from multiple donors and cryopreserved to provide an “off the shelf” myeloid progenitor product, will likely prove more reliable for treating patients with prolonged neutropenia.
From ONC201 to ONC212
Oncoceutics has expanded its research collaboration agreement with The University of Texas MD Anderson Cancer Center, Houston, to include the clinical development of a second novel imipridone called ONC212.
Oncoceutics and MD Anderson are already collaborating on the clinical development of another imipridone, ONC201. Both drugs have the same chemical core that interacts with G-Protein Coupled Receptors (GPCRs). ONC212 targets GPR132, which influences the growth of acute leukemias and has not previously been successfully targeted by a small molecule.
This alliance between MD Anderson and Oncoceutics will support Phase I and Phase II clinical trials of ONC212 in patients with refractory acute myeloid leukemia (AML), according to Oncoceutics. The alliance provides for a sharing of risk and rewards from potential commercialization of ONC212.
Top risk factor miRNA
The miRNA hsa-mir-425 was identified as the top risk factor miRNA of AML survival and CD44 was identified as one of the top three risk factor target-genes associated with AML survival, based on a miRNA-mRNA interaction network.
Chunmei Zhang, MD, of the department of hematology at Taian City Central Hospital, Taian, Shandong, China, and colleagues used The Cancer Genome Atlas database to obtain miRNA and mRNA expression profiles from AML patients. Of 14 miRNAs associated with AML survival, 3 were associated with risk – hsa-mir-425, hsa-mir-1201, and hsa-mir-1978. GTSF1, RTN4R, and CD44 were the top risk factor target-genes associated with AML survival. Med Sci Monit 2017; 23:4705-14 (DOI: 10.12659/MSM.903989)
Detecting hereditary MDS/AML
Unexplained cytopenias or failure to mobilize stem cells in related donors of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) – important clues for the detection of a hereditary MDS/AML syndrome – should prompt efforts to obtain germ line tissue sources for collaborative research, Jane E. Churpek, MD, of the Hereditary Hematologic Malignancies Program at The University of Chicago Medicine, wrote.
Partnering with families to obtain germ line tissue sources uncontaminated by tumor cells from large numbers of patients with MDS/AML, and international collaboration to determine the mechanisms and multi-step processes from the carrier state to overt disease, have enormous potential to improve the outcomes of patients with both familial and sporadic forms of MDS/AML. Incorporating collection of ideal germ line tissue along with family histories to the already robust international MDS/AML registries and data sharing are all essential to future progress in this field, she wrote in a recent article published onlne in Best Practice & Research Clinical Haematology.
Prophylactic granulocyte transfusions
Giving prophylactic granulocyte transfusions to AML patients during the induction phase of therapy is feasible and safe, but assuring an adequate donor pool and patient continuation of the transfusions are another matter.
In a phase 2 trial of 45 neutropenic patients with AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy, non-irradiated allogeneic granulocyte transfusions were to be given every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. But logistical problems limited the success of the protocol: 5 patients never received a granulocyte transfusion due to donor screening failure or donor unavailability and the other 40 received a median of 3 (range 1-9) granulocyte transfusions.
“We anticipated approximately 8 GTs per patient ... only 11 received 6 or more GTs,” Fleur M. Aung, MD, and colleagues at The MD Anderson Cancer Center, Houston, wrote in the Journal of Blood Disorders and Transfusion (DOI 10.4172/2155-9864.1000376).
The authors concluded that while the process is feasible, ex vivo expanded neutrophils, produced from multiple donors and cryopreserved to provide an “off the shelf” myeloid progenitor product, will likely prove more reliable for treating patients with prolonged neutropenia.
From ONC201 to ONC212
Oncoceutics has expanded its research collaboration agreement with The University of Texas MD Anderson Cancer Center, Houston, to include the clinical development of a second novel imipridone called ONC212.
Oncoceutics and MD Anderson are already collaborating on the clinical development of another imipridone, ONC201. Both drugs have the same chemical core that interacts with G-Protein Coupled Receptors (GPCRs). ONC212 targets GPR132, which influences the growth of acute leukemias and has not previously been successfully targeted by a small molecule.
This alliance between MD Anderson and Oncoceutics will support Phase I and Phase II clinical trials of ONC212 in patients with refractory acute myeloid leukemia (AML), according to Oncoceutics. The alliance provides for a sharing of risk and rewards from potential commercialization of ONC212.
Top risk factor miRNA
The miRNA hsa-mir-425 was identified as the top risk factor miRNA of AML survival and CD44 was identified as one of the top three risk factor target-genes associated with AML survival, based on a miRNA-mRNA interaction network.
Chunmei Zhang, MD, of the department of hematology at Taian City Central Hospital, Taian, Shandong, China, and colleagues used The Cancer Genome Atlas database to obtain miRNA and mRNA expression profiles from AML patients. Of 14 miRNAs associated with AML survival, 3 were associated with risk – hsa-mir-425, hsa-mir-1201, and hsa-mir-1978. GTSF1, RTN4R, and CD44 were the top risk factor target-genes associated with AML survival. Med Sci Monit 2017; 23:4705-14 (DOI: 10.12659/MSM.903989)
Detecting hereditary MDS/AML
Unexplained cytopenias or failure to mobilize stem cells in related donors of patients with myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) – important clues for the detection of a hereditary MDS/AML syndrome – should prompt efforts to obtain germ line tissue sources for collaborative research, Jane E. Churpek, MD, of the Hereditary Hematologic Malignancies Program at The University of Chicago Medicine, wrote.
Partnering with families to obtain germ line tissue sources uncontaminated by tumor cells from large numbers of patients with MDS/AML, and international collaboration to determine the mechanisms and multi-step processes from the carrier state to overt disease, have enormous potential to improve the outcomes of patients with both familial and sporadic forms of MDS/AML. Incorporating collection of ideal germ line tissue along with family histories to the already robust international MDS/AML registries and data sharing are all essential to future progress in this field, she wrote in a recent article published onlne in Best Practice & Research Clinical Haematology.
Prophylactic granulocyte transfusions
Giving prophylactic granulocyte transfusions to AML patients during the induction phase of therapy is feasible and safe, but assuring an adequate donor pool and patient continuation of the transfusions are another matter.
In a phase 2 trial of 45 neutropenic patients with AML or high-risk myelodysplastic syndrome undergoing induction or first-salvage therapy, non-irradiated allogeneic granulocyte transfusions were to be given every 3-4 days until sustained ANC recovery, initiation of new therapy, or completion of 6 weeks on study. But logistical problems limited the success of the protocol: 5 patients never received a granulocyte transfusion due to donor screening failure or donor unavailability and the other 40 received a median of 3 (range 1-9) granulocyte transfusions.
“We anticipated approximately 8 GTs per patient ... only 11 received 6 or more GTs,” Fleur M. Aung, MD, and colleagues at The MD Anderson Cancer Center, Houston, wrote in the Journal of Blood Disorders and Transfusion (DOI 10.4172/2155-9864.1000376).
The authors concluded that while the process is feasible, ex vivo expanded neutrophils, produced from multiple donors and cryopreserved to provide an “off the shelf” myeloid progenitor product, will likely prove more reliable for treating patients with prolonged neutropenia.
From ONC201 to ONC212
Oncoceutics has expanded its research collaboration agreement with The University of Texas MD Anderson Cancer Center, Houston, to include the clinical development of a second novel imipridone called ONC212.
Oncoceutics and MD Anderson are already collaborating on the clinical development of another imipridone, ONC201. Both drugs have the same chemical core that interacts with G-Protein Coupled Receptors (GPCRs). ONC212 targets GPR132, which influences the growth of acute leukemias and has not previously been successfully targeted by a small molecule.
This alliance between MD Anderson and Oncoceutics will support Phase I and Phase II clinical trials of ONC212 in patients with refractory acute myeloid leukemia (AML), according to Oncoceutics. The alliance provides for a sharing of risk and rewards from potential commercialization of ONC212.
Top risk factor miRNA
The miRNA hsa-mir-425 was identified as the top risk factor miRNA of AML survival and CD44 was identified as one of the top three risk factor target-genes associated with AML survival, based on a miRNA-mRNA interaction network.
Chunmei Zhang, MD, of the department of hematology at Taian City Central Hospital, Taian, Shandong, China, and colleagues used The Cancer Genome Atlas database to obtain miRNA and mRNA expression profiles from AML patients. Of 14 miRNAs associated with AML survival, 3 were associated with risk – hsa-mir-425, hsa-mir-1201, and hsa-mir-1978. GTSF1, RTN4R, and CD44 were the top risk factor target-genes associated with AML survival. Med Sci Monit 2017; 23:4705-14 (DOI: 10.12659/MSM.903989)