Clinical Edge Journal Scan

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.

Key clinical point: Outcomes remain poor for patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome who suffer relapse after allogeneic hematopoietic cell transplantation; factors associated with mortality included acute graft vs. host disease grade II-IV.

Major finding: The cumulative incidence of morphologic relapse in patients with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome after allogeneic hematopoietic cell transplantation was 19%, 24%, and 26%, respectively at 12 months; the estimated median survival after relapse across all diseases was 2.9 months.

Study details: The data come from 420 adults with acute lymphocytic leukemia, acute myeloid leukemia, and myelodysplastic syndrome.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Hong S et al. Hematol Oncol Stem Cell Ther. 2020 Dec 5. doi: 10.1016/j.hemonc.2020.11.006.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Use of the Eastern Cooperative Oncology Group Performance Status (ECOG PS) added to the International Prognostic Scoring System, revised (IPSS-R) could identify low, intermediate, and high-risk groups of patients with patients with higher-risk myelodysplastic syndromes and oligoblastic acute myeloid leukemia.

Major finding: Serum ferritin levels < 520 ng/mL, ECOG PS scores of 0 or 1, and IPSS-R independently predicted stronger response to 5-AZA in patients with myelodysplastic syndromes and oligoblastic acute myeloid leukemia. 

Study details: The data come from a retrospective study of 687 consecutive patients with myelodysplastic syndrome and oligoblastic acute myeloid leukemia who were treated with 5-azacytidine (5-AZA).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Papageorgiou SG et al. Ther Adv Hematol. 2020 Dec 8. doi: 10.1177/2040620720966121.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: Myelodysplastic syndrome patients who responded to treatment with azacytidine showed significantly reduced peripheral blood levels of Wilms’ tumour 1 mRNA (WT-1) compared to nonresponders.

Major finding: A total of 20 patients (63%) showed a response to azacytidine; 7 patients (22%) achieved complete response and 19 patients (59%) achieved hematologic improvement. Responders had an average peripheral blood WT-A mRNA of 2,050 copies per micrograms of RNA vs. 7,550 copies per micrograms of RNA for nonresponders (P = 0.03).

Study details: The data come from 32 adult patients aged 31 to 85 years with myelodysplastic syndrome who were treated with azacytidine for an average of five cycles.

Disclosures: The study was supported in part by the Practical Research for Innovative Cancer Control Program from the Japan Agency for Medical Research and Development, AMED. Lead author Dr. Maeda disclosed relationships with Nippon Shinyaku and Janssen; several coauthors also disclosed relationships with multiple companies.

Source: Maeda T et al. Leukemia Res Rep. 2020 Dec 8. doi: 10.1016/j.lrr.2020.100231.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: A simplified system based on four clinical parameters of the flow cytometric score (MFCM-Score) was positively correlated with the Revised International Prognostic Scoring System (IPSS-R) for myelodysplastic syndrome.

Major finding: No significant difference appeared between the MFCM-score and FCM-score in diagnosing myelodysplastic syndrome (P > 0.05).

Study details: The data come from 118 adults with suspected myelodysplastic syndrome. Patients were compared using the FCM and MFCM. Four parameters were used in the standard FCM scoring: myeloblast-related cluster size (myeloblast-related cells/all nucleated cell), B-progenitor-related cluster size (B-progenitor-related cells/all CD34⁺ cells), CD45 mean fluorescence intensity (MFI) ratio (lymphocytes/myeloid blast cells), and SSC peak channel ratio (granulocyte/lymphocyte). The MFCM simplified the scoring further by using CD19 and CD33 to separate B lymphocyte progenitor cells and myeloblasts within the CD34⁺CD45^dimm population.

Disclosures: The study was funded by the National Natural Science Foundation of China and the Natural Science Research Project of Anhui Medical University. The researchers had no financial conflicts to disclose.

Source: Guo J et al. Am J Transl Res. 2020 Nov 15. 12(11):7449–7458.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Overall survival improved by more than 20% in older adults with myelodysplastic syndrome who received allogeneic stem cell transplantation.

Major finding: Overall survival at 3 years was 47.9% for patients who received allogeneic hematopoietic cell transplantation compared to those who did not.

Study details: The data come from myelodysplastic syndrome patients with a median age of 66 years who were part of the prospective Blood and Marrow Transplant Clinical Trials Network (BMT CTN) Study 1102 (NCT02016781) presented at the American Society of Hematology (ASH) 2020 virtual meeting.

Disclosures: Lead author Dr. Cutler disclosed serving as a consultant for Mesoblast, Generon, Medsenic, Jazz, Kadmon, and Incyte.

Source: Cutler C et al. ASH 2020.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: Incidence of graft vs. host disease was significantly lower in patients undergoing matched sibling donor stem cell transplants who received low-dose rabbit antitymoctye globulin (rATG).

Major finding: The 2-year cumulative incidences of chronic GVHD (cGVHD) were 35.4% and 60.4%, respectively, for patients in the rATG and non-rATG groups (P=0.039).

Study details: The data come from a retrospective study of 79 patients aged 16 years and older with hematologic malignancies who were treated with matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT); all received standard prophylaxis and 38 received 5 mg/kg of rATG in addition.

Disclosures: The study was supported in part by the Scientific Research Seed Fund of Peking University First Hospital. The researchers had no financial conflicts to disclose.

Source: Song ZY et al. Cancer Manag Res. 2020 Nov 30. doi: 10.2147/CMAR.S283855.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: The compound APR‐246 (PRIMA‐1Met/Eprenetapopt) caused synergistic tumor death in myelodysplastic syndrome with combined with inhibitors of efflux pump MRP1/ABCC1.

Major finding: A combination of combination of APR‐246 with the MRP1 inhibitor MK‐571 significantly reduced IC₅₀ values in 21 cell lines (P < 0.0001).

Study details: The data come from a combination of in vitro, ex vivo, and in vivo models, using combined treatment of APR‐246 and inhibitors of efflux pump MRP1/ABCC1. 

Disclosures: The study was funded by multiple organizations including Vetenskapsrådet, Cancerfonden (Swedish Cancer Society), Barncancerfonden (Swedish Childhood Cancer Foundation), Radiumhemmets Forskningsfonder (Cancer Research Foundations of Radiumhemmet, Knut och Alice Wallenbergs Stiftelse (Knut and Alice Wallenberg Foundation), Aprea Therapeutics, Karolinska Institutet (KI), Department of Health, Australian Government/National Health and Medical Research Council (NHMRC), Department of Health and Human Services, State Government of Victoria (DHHS), Tour de Cure Foundation, UKRI/Medical Research Council (MRC), Australian Cancer Research Foundation (ACRF), Australian Government’s National Collaborative Research Infrastructure Strategy (NCRIS) program, Peter MacCallum Cancer Centre Foundation, University of Melbourne Research Collaborative Infrastructure Program (MCRIP), and Cancer Research UK.

Source: Ceder S et al. EMBO Mol Med. 2020 Dec 14. doi: 10.15252/emmm.201910852.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.

Key clinical point: Researchers developed a flow score based on three variables: developed a “flow score” with the three variables percentage of myeloid CD34⁺ cells > 2%; percentage of B-cell progenitors < 0.05%; and CD16⁺ monocytes/TNCs > 1.0%.

Major finding: Of the 95 patients in the study, 23 remained alive after the end of the study period. A high percentage of CD16⁺ monocytes/TNCs > 1.0% (in the highest quartile) was associated with significantly worse survival.

Study details: The data come from 95 adult patients with newly diagnosed myelodysplastic syndrome seen at a single center and followed for an average of 42 months.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Vido-Marques JR et al. Sci Rep. 2020 Nov 20. doi: 10.1038/s41598-020-77158-z.

Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.

Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.

Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.

Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.

Higher expression of Wilms’ tumor 1 (WT-1) has been associated with poor survival in MDS. To further characterize the prognostic value of WT-1 expression level, peripheral WT-1 mRNA expression level at baseline was measured in MDS patients undergoing treatment with azacitidine. Lower WT-1 mRNA level was associated with higher overall response, as defined by CR, marrow CR, partial response, or HI (p=0.03), although WT-1 mRNA level did not show difference in overall survival. This was a small retrospective, single center study; role of WT-1 mRNA level as a biomarker for response to azacitidine should be further investigated.

Results of a multi-center trial comparing reduced intensity allogeneic stem cell transplant (SCT) to hypomethylating agents or best supportive care in higher risk MDS patients aged 50-75 was reported in the annual meeting of the American Society of Hematology in 2020. Patients with intermediate-2 or higher risk by IPSS were assigned based on SCT or no SCT arm based on donor status, and patients who had donor proceeded to reduced intensity SCT within 6 months of enrolment. In an intent-to-treat analysis, the study showed different in 3-year overall survival, which was the primary endpoint between SCT vs non-SCT arms (47.9% vs 26.6%, p=0.0001). Leukemia-free survival at 3 years was also greater for the SCT arm (35.8% vs 20.6%, p=0.003). Allogenic stem cell transplant is currently offered to patients with higher risk MDS given this is the only potential curable approach for MDS patients. This study further supports allogeneic stem cell transplant for older patients with higher risk MDS.

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School

Bariatric surgery rates continue to climb in the setting of increasing obesity throughout the world. While effective at promoting weight loss, a growing body of literature has clearly demonstrated that bone loss and increased fracture risk occurs following bariatric surgery. However, major important questions remain regarding the impact of specific types of bariatric surgery on bone metabolism. Notably, most previous studies were not performed in a randomized manner with respect to the type of weight loss surgery. As such, indication bias exists with respect to current knowledge regarding how specific weight loss surgeries impact bone. Here, a randomized, triple-blind single center study in Norway assessed skeletal endpoints in patients with severe obesity and type 2 diabetes who were randomized to receive either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy weight loss surgery. The primary focus of this study, reported elsewhere, was to assess rates of diabetes remission. Areal bone mineral density in the hip and spine decreased significantly more one year after RYGB than after sleeve gastrectomy. The authors investigated serum bone turnover markers over time in these subjects. Both forms of bariatric surgery led to increases in bone formation and resorption markers, with higher levels of both markers seen after RYGB than sleeve gastrectomy. Importantly, these effects were independently associated with surgical procedure and not resultant weight change. Findings here strongly support the emerging notion that RYGB in particular is linked to high bone turnover and bone loss. While many hypotheses exist as to the underlying mechanism linking RYBG and bone loss, this remains an active and open area of investigation.

Denosumab, a neutralizing antibody against RANKL, is a potent antiresorptive agent that increases bone density and reduces fracture risk. In addition to its major role in osteoclast development, the paracrine-acting cytokine RANKL plays an important role in development and maintenance of the adaptive immune system. As such, a concern has been raised that denosumab treatment may increase risk of malignancies kept at bay by lymphoid surveillance. In this systematic review and meta-analysis of randomized controlled trials, the authors assessed risk of malignancy of denosumab versus comparator in 25 prospective randomized controlled trials. In these trials, >21,000 patients were analyzed who were treated for osteoporosis with either denosumab or control. The risk of malignancy was similar between osteoporosis denosumab dosing (60 mg every 6 months) and control. Drug exposure in these studies was up to 48 months. As such, additional post-marketing surveillance safety data are needed to address longer-term risks of malignancy. Nonetheless, these data are largely reassuring and provide additional evidence of the safety of denosumab therapy for osteoporosis.

Marc Wein, M.D., Ph.D
Assistant Professor of Medicine
Massachusetts General Hospital Endocrine Unit, Harvard Medical School