Myelodysplastic Syndrome

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Adolescent and young adult (AYA) patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT) generally exhibit better survival than their non-AYA counterparts.

Major finding: The 3-year overall survival (OS) in AYA patients was 71.2% (95% confidence interval, 67.4%-74.6%). Predictors of poor 3-year OS were active disease status (adjusted hazard ratio [aHR], 1.54; P = .016), poor cytogenetic risk (aHR, 1.62; P = .011), poor performance status (aHR, 2.01; P = .016), human leukocyte antigen (HLA)-matched unrelated donors (aHR, 2.23; P less than .001), HLA-mismatched unrelated donors (aHR, 2.16; P = .027), and cord blood transplantation (aHR, 2.44; P = 0.001).

Study details: The study included 645 AYA patients with MDS, aged 16-39 years, who received first allo-HSCT.

Disclosures: No funding source was identified. The authors declared no conflicts of interest.

Source: Shimomura Y et al. Bone Marrow Transplant. 2021 May 15. doi: 10.1038/s41409-021-01324-8.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Lenalidomide had no relevant effect on DNA methylation status in patients with myelodysplastic syndrome with isolated deletion of chromosome 5q (MDS del5q).

Major finding: Lenalidomide treatment did not have a relevant impact on genome-wide DNA methylation in patients with MDS del5q. However, methylation analysis before treatment could identify a distinct subgroup of patients (27%) with a trend toward inferior overall survival but not inferior progression-free survival.

Study details: DNA methylation analysis was performed on 51 MDS del5q patients treated with lenalidomide. Direct effects of lenalidomide on DNA methylation were studied using 17 paired samples pre- and posttreatment.

Disclosures: Open access funding by Projekt DEAL. This study was supported by funds from the Deutsche Forschungsgemeinschaft, “Deutsche Krebshilfe,” Gutermuth Foundation, H.W. & J. Hector fund, Baden Wuerttemberg, and Dr Rolf M Schwiete Fund. Mannheim DN is an endowed Professor of the German José-Carreras-Stiftung. The study was partly funded by a research grant from Celgene Inc.

Source: Hecht A et al. Ann Hematol. 2021 April 27. doi: 10.1007/s00277-021-04492-1.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Key clinical point: Pretransplant cytoreductive therapy is not associated with improved outcomes in patients with myelodysplastic syndromes (MDS) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Five-year overall survival after diagnosis was 73.6% (95% confidence interval [CI], 70.3%-76.9%), 43.4% (95% CI, 39.2%-47.6%), and 46.9% (95% CI, 44.7%-49.1%) in the upfront transplantation (upfront), induction chemotherapy (CT), and hypomethylating agents alone (HMA) groups, respectively (P = .033). Treatment-related mortality was 13.0% (95% CI, 11.4%-15.1%), 32.4% (95% CI, 30.1%-35.3%), and 28.4% (95% CI, 26.2%-30.3%) in the 3 groups, respectively (P = .028).

Study details: A total of 157 MDS patients were categorized into 3 groups based on the pretransplantation therapy: upfront (n=54), CT (n=66), and HMA (n=37). In addition, 124 patients underwent allo-HSCT.

Disclosures: This study was supported by the National Natural Science Foundation of China, Research and Development Program in Key Areas of Guangdong Province, Science and Technology Program of Guangzhou, and Clinical Research Start-up Project of Southern Medical University. The authors declared no conflicts of interest.

Source: Chen Y et al. Int J Cancer. 2021 Apr 25. doi: 10.1002/ijc.33608.

Key clinical point: In patients with very high-risk TP53-mutated myelodysplastic syndromes (MDS), addition of eprenetapopt to azacitidine (AZA) was safe and led to better clinical outcomes than AZA alone.

Major finding: The overall response rate in MDS patients was 62% including 47% complete remission. The median duration of response in MDS patients was 10.4 months. At a median follow-up of 9.7 months, the median overall survival in MDS patients was 12.1 months. Eprenetapopt plus AZA was generally well tolerated.

Study details: Phase 2 study of eprenetapopt plus AZA vs. AZA alone in 34 very high-risk TP53-mutated MDS patients.

Disclosures: The study was supported by Groupe Francophone des Myelodysplasies. The authors reported relationships with various pharmaceutical companies.

Source: Cluzeau T et al. J Clin Oncol. 2021 Feb 18. doi: 10.1200/JCO.20.02342.

Key clinical point: In patients with very high-risk TP53-mutated myelodysplastic syndromes (MDS), addition of eprenetapopt to azacitidine (AZA) was safe and led to better clinical outcomes than AZA alone.

Major finding: The overall response rate in MDS patients was 62% including 47% complete remission. The median duration of response in MDS patients was 10.4 months. At a median follow-up of 9.7 months, the median overall survival in MDS patients was 12.1 months. Eprenetapopt plus AZA was generally well tolerated.

Study details: Phase 2 study of eprenetapopt plus AZA vs. AZA alone in 34 very high-risk TP53-mutated MDS patients.

Disclosures: The study was supported by Groupe Francophone des Myelodysplasies. The authors reported relationships with various pharmaceutical companies.

Source: Cluzeau T et al. J Clin Oncol. 2021 Feb 18. doi: 10.1200/JCO.20.02342.

Key clinical point: In patients with very high-risk TP53-mutated myelodysplastic syndromes (MDS), addition of eprenetapopt to azacitidine (AZA) was safe and led to better clinical outcomes than AZA alone.

Major finding: The overall response rate in MDS patients was 62% including 47% complete remission. The median duration of response in MDS patients was 10.4 months. At a median follow-up of 9.7 months, the median overall survival in MDS patients was 12.1 months. Eprenetapopt plus AZA was generally well tolerated.

Study details: Phase 2 study of eprenetapopt plus AZA vs. AZA alone in 34 very high-risk TP53-mutated MDS patients.

Disclosures: The study was supported by Groupe Francophone des Myelodysplasies. The authors reported relationships with various pharmaceutical companies.

Source: Cluzeau T et al. J Clin Oncol. 2021 Feb 18. doi: 10.1200/JCO.20.02342.

Allogeneic stem cell transplantation (SCT) remains the only potential curable option for patients with myelodysplastic syndromes (MDS). While MDS mainly occurs in older patients, MDS does occur in younger patients and prior studies have suggested better overall survival (OS) for younger patients undergoing allogeneic SCT.  Shimomura et al (BMT 2021) analyzed the outcome of 645 patients aged 16-39 years old who received allogeneic SCT in Japan. In this multicenter retrospective analysis, 3 year OS was 71%. In the cohort, 37% of patients had either intermediate-2 or high risk by IPSS, 41% had active disease prior to SCT, and 10% had secondary MDS.  In a multivariate analysis, active disease status, poor cytogenetic risk, and transplant other than from related donor were associated with poor 3 year OS. Cumulative 3 year relapse was 11% and 3 year non-relapse mortality was 19%, which is lower than those of older patients with MDS which ranges from 30-40%. Limitations from this analysis are lack of genetic mutation data, as well as lack of incorporation of prior MDS directed therapy with outcome analysis, however this analysis from a large retrospective cohort provides valuable information regarding outcome in young patients with MDS.

Use of melphalan in multiple myeloma is associated with increased risk of developing MDS and acute myeloid leukemia (AML).  Jonsdottir et al (European Journal of Hematology) reported results of a large population-based study using the Swedish cancer registry to determine relationship of exposure to melphalan treatment for multiple myeloma and development of subsequent MDS and AML. Out of 26,627 patients with multiple myeloma in the Swedish cancer registry, 0.5% (124) patients developed subsequent MDS or AML. The median time from multiple myeloma diagnosis to MDS or AML diagnosis was 3.8 years. There was about threefold higher cumulative exposure to melphalan among those who developed MDS or AML compared to those who did not develop MDS or AML (OR=2.8, 95% CI 1.7-5.2, P < 0.001). There was no difference among the groups in exposure and dosing of radiation therapy, cumulative dose of cyclophosphamide, or doxorubicine. This large population-based study confirms the association between melphalan therapy and development of MDS/AML.

Febrile neutropenia is a common complication for neutropenic patients undergoing therapy. Patients who develop febrile neutropenia are treated with empiric broad-spectrum antibiotics, however there is conflicting recommended duration of antimicrobial treatment in absence of evidence of bacterial infection. The Infectious Disease Society of America recommends antibiotic treatment until marrow recovery, while the European Conference of Infections in Leukemia guidelines suggest consideration of discontinuation after 72 hours if the patient is hemodynamically stable and afebrile for 48 hours. Schauwvlieghe et al (EClinical Medicine 2021) compared the outcome of MDS and AML patients with febrile neutropenia during induction chemotherapy receiving a shortened 3 day empiric antibiotic therapy in absence of documented infection to those receiving antibiotics until neutrophil recovery in a retrospective comparative cohort study in two hospitals in the HOVON network. The shorted antibiotic group received a median of 9 days of antibiotics, compared to 19 days. The primary endpoint was the rate of serious medical complications; there was no statistical difference between the two groups (12.5% for shortened antibiotics vs 8.9% for prolonged antibiotics, P = 0.17).  There was no difference in serious medical complications when adjusting for age, AML risk, non-pulmonary HCT-CI score, and year of admission. There was also no significant difference in infection-related 30-day mortality among the two groups. This study suggests that for patients who develop febrile neutropenia while receiving induction chemotherapy, it may be safe to consider stopping antibiotics after 3 days in absence of infection. A prospective trial should be considered to further evaluate the safety of shortened antibiotic course.

Allogeneic stem cell transplantation (SCT) remains the only potential curable option for patients with myelodysplastic syndromes (MDS). While MDS mainly occurs in older patients, MDS does occur in younger patients and prior studies have suggested better overall survival (OS) for younger patients undergoing allogeneic SCT.  Shimomura et al (BMT 2021) analyzed the outcome of 645 patients aged 16-39 years old who received allogeneic SCT in Japan. In this multicenter retrospective analysis, 3 year OS was 71%. In the cohort, 37% of patients had either intermediate-2 or high risk by IPSS, 41% had active disease prior to SCT, and 10% had secondary MDS.  In a multivariate analysis, active disease status, poor cytogenetic risk, and transplant other than from related donor were associated with poor 3 year OS. Cumulative 3 year relapse was 11% and 3 year non-relapse mortality was 19%, which is lower than those of older patients with MDS which ranges from 30-40%. Limitations from this analysis are lack of genetic mutation data, as well as lack of incorporation of prior MDS directed therapy with outcome analysis, however this analysis from a large retrospective cohort provides valuable information regarding outcome in young patients with MDS.

Use of melphalan in multiple myeloma is associated with increased risk of developing MDS and acute myeloid leukemia (AML).  Jonsdottir et al (European Journal of Hematology) reported results of a large population-based study using the Swedish cancer registry to determine relationship of exposure to melphalan treatment for multiple myeloma and development of subsequent MDS and AML. Out of 26,627 patients with multiple myeloma in the Swedish cancer registry, 0.5% (124) patients developed subsequent MDS or AML. The median time from multiple myeloma diagnosis to MDS or AML diagnosis was 3.8 years. There was about threefold higher cumulative exposure to melphalan among those who developed MDS or AML compared to those who did not develop MDS or AML (OR=2.8, 95% CI 1.7-5.2, P < 0.001). There was no difference among the groups in exposure and dosing of radiation therapy, cumulative dose of cyclophosphamide, or doxorubicine. This large population-based study confirms the association between melphalan therapy and development of MDS/AML.

Febrile neutropenia is a common complication for neutropenic patients undergoing therapy. Patients who develop febrile neutropenia are treated with empiric broad-spectrum antibiotics, however there is conflicting recommended duration of antimicrobial treatment in absence of evidence of bacterial infection. The Infectious Disease Society of America recommends antibiotic treatment until marrow recovery, while the European Conference of Infections in Leukemia guidelines suggest consideration of discontinuation after 72 hours if the patient is hemodynamically stable and afebrile for 48 hours. Schauwvlieghe et al (EClinical Medicine 2021) compared the outcome of MDS and AML patients with febrile neutropenia during induction chemotherapy receiving a shortened 3 day empiric antibiotic therapy in absence of documented infection to those receiving antibiotics until neutrophil recovery in a retrospective comparative cohort study in two hospitals in the HOVON network. The shorted antibiotic group received a median of 9 days of antibiotics, compared to 19 days. The primary endpoint was the rate of serious medical complications; there was no statistical difference between the two groups (12.5% for shortened antibiotics vs 8.9% for prolonged antibiotics, P = 0.17).  There was no difference in serious medical complications when adjusting for age, AML risk, non-pulmonary HCT-CI score, and year of admission. There was also no significant difference in infection-related 30-day mortality among the two groups. This study suggests that for patients who develop febrile neutropenia while receiving induction chemotherapy, it may be safe to consider stopping antibiotics after 3 days in absence of infection. A prospective trial should be considered to further evaluate the safety of shortened antibiotic course.

Allogeneic stem cell transplantation (SCT) remains the only potential curable option for patients with myelodysplastic syndromes (MDS). While MDS mainly occurs in older patients, MDS does occur in younger patients and prior studies have suggested better overall survival (OS) for younger patients undergoing allogeneic SCT.  Shimomura et al (BMT 2021) analyzed the outcome of 645 patients aged 16-39 years old who received allogeneic SCT in Japan. In this multicenter retrospective analysis, 3 year OS was 71%. In the cohort, 37% of patients had either intermediate-2 or high risk by IPSS, 41% had active disease prior to SCT, and 10% had secondary MDS.  In a multivariate analysis, active disease status, poor cytogenetic risk, and transplant other than from related donor were associated with poor 3 year OS. Cumulative 3 year relapse was 11% and 3 year non-relapse mortality was 19%, which is lower than those of older patients with MDS which ranges from 30-40%. Limitations from this analysis are lack of genetic mutation data, as well as lack of incorporation of prior MDS directed therapy with outcome analysis, however this analysis from a large retrospective cohort provides valuable information regarding outcome in young patients with MDS.

Use of melphalan in multiple myeloma is associated with increased risk of developing MDS and acute myeloid leukemia (AML).  Jonsdottir et al (European Journal of Hematology) reported results of a large population-based study using the Swedish cancer registry to determine relationship of exposure to melphalan treatment for multiple myeloma and development of subsequent MDS and AML. Out of 26,627 patients with multiple myeloma in the Swedish cancer registry, 0.5% (124) patients developed subsequent MDS or AML. The median time from multiple myeloma diagnosis to MDS or AML diagnosis was 3.8 years. There was about threefold higher cumulative exposure to melphalan among those who developed MDS or AML compared to those who did not develop MDS or AML (OR=2.8, 95% CI 1.7-5.2, P < 0.001). There was no difference among the groups in exposure and dosing of radiation therapy, cumulative dose of cyclophosphamide, or doxorubicine. This large population-based study confirms the association between melphalan therapy and development of MDS/AML.

Febrile neutropenia is a common complication for neutropenic patients undergoing therapy. Patients who develop febrile neutropenia are treated with empiric broad-spectrum antibiotics, however there is conflicting recommended duration of antimicrobial treatment in absence of evidence of bacterial infection. The Infectious Disease Society of America recommends antibiotic treatment until marrow recovery, while the European Conference of Infections in Leukemia guidelines suggest consideration of discontinuation after 72 hours if the patient is hemodynamically stable and afebrile for 48 hours. Schauwvlieghe et al (EClinical Medicine 2021) compared the outcome of MDS and AML patients with febrile neutropenia during induction chemotherapy receiving a shortened 3 day empiric antibiotic therapy in absence of documented infection to those receiving antibiotics until neutrophil recovery in a retrospective comparative cohort study in two hospitals in the HOVON network. The shorted antibiotic group received a median of 9 days of antibiotics, compared to 19 days. The primary endpoint was the rate of serious medical complications; there was no statistical difference between the two groups (12.5% for shortened antibiotics vs 8.9% for prolonged antibiotics, P = 0.17).  There was no difference in serious medical complications when adjusting for age, AML risk, non-pulmonary HCT-CI score, and year of admission. There was also no significant difference in infection-related 30-day mortality among the two groups. This study suggests that for patients who develop febrile neutropenia while receiving induction chemotherapy, it may be safe to consider stopping antibiotics after 3 days in absence of infection. A prospective trial should be considered to further evaluate the safety of shortened antibiotic course.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Human leukocyte antigen (HLA)-mismatched hematopoetic stem cell microtransplantation (MST) has previously been evaluated in AML in combination with chemotherapy and suggests potential improvement in outcomes. Li et al evaluated MST combined with decitabine in patients with intermediate or high risk MDS compared to decitabine alone.  Out of 22 patients in the study, the cohort that received MST with decitabine had higher median OS (24 vs 14.2 months, p=0.04), although there was no statistical significant difference in overall response rate. There was no reported graft vs host disease, and adverse events were similar between the two groups. The main limitation of the study was the very small sample size; further prospective studies utilizing MST in MDS are needed to demonstrate benefit.

MDS patients often present with neutropenia and develop worsening neutropenia due to myelosuppression from HMA therapy, resulting in increased risk of infections including invasive fungal infection (IFI). Tey et al reported a retrospective analysis of the rate of IFI in patients with MDS or low blast count AML receiving azacitidine. Out of 117 patients, 61% received antifungal prophylaxis, either with posaconazole (n=70) or voriconazole (n=1). The IFI rate was 7.7% in the cohort with median time of onset of 74 days from start of azacitidine treatment (range 1-226); the IFI rate did not differ statistically between those receiving prophylaxis vs not (5.6% vs 10.9%, p=0.30). However, presence of neutropenia at three months of treatment was associated with increased IFI risk (HR 8.29, p=0.01), and IFI was associated with increased mortality in a multivariate analysis (HR 8.37, p<0.0001). Anti-fungal prophylaxis is currently standard practice for MDS patients who present or develop neutropenia; however, HMA treatment is associated with prolonged neutropenia due to myelosuppression and time to response. A more effective therapy with less myelosuppression is needed for treatment of MDS.

Key clinical point: Combination of decitabine and human leukocyte antigen-mismatched hematopoietic stem cell microtransplantation (HLA-MST) could be an effective and safe treatment in patients with intermediate- or high-risk myelodysplastic syndrome (MDS).

Major finding: Overall survival was significantly higher in the decitabine and HLA-MST combination vs. decitabine alone group (24.00 vs. 14.13 months; hazard ratio, 0.32; P = .04). The incidence of hematological adverse events except thrombocytopenia and nonhematological adverse events was slightly lower in decitabine+HLA-MST vs. decitabine alone group.

Study details: Findings are from a retrospective study of 22 patients with intermediate- or high-risk MDS who were treated with decitabine (n=11) or decitabine and HLA-MST combination (n=11).

Disclosures: The study was funded by National Natural Science Foundation of China; the Science and Technology Planning Project of Guangdong Province, China; the Guangzhou Regenerative Medicine and Health Guangdong Laboratory; and the Project of Guangdong Province Traditional Chinese Medicine Bureau. The authors declared absence of any commercial or financial relationships during conduct of the study.

Source: Li MM et al. Front Oncol. 2021 Mar 31. doi: 10.3389/fonc.2021.628127.

Key clinical point: Combination of decitabine and human leukocyte antigen-mismatched hematopoietic stem cell microtransplantation (HLA-MST) could be an effective and safe treatment in patients with intermediate- or high-risk myelodysplastic syndrome (MDS).

Major finding: Overall survival was significantly higher in the decitabine and HLA-MST combination vs. decitabine alone group (24.00 vs. 14.13 months; hazard ratio, 0.32; P = .04). The incidence of hematological adverse events except thrombocytopenia and nonhematological adverse events was slightly lower in decitabine+HLA-MST vs. decitabine alone group.

Study details: Findings are from a retrospective study of 22 patients with intermediate- or high-risk MDS who were treated with decitabine (n=11) or decitabine and HLA-MST combination (n=11).

Disclosures: The study was funded by National Natural Science Foundation of China; the Science and Technology Planning Project of Guangdong Province, China; the Guangzhou Regenerative Medicine and Health Guangdong Laboratory; and the Project of Guangdong Province Traditional Chinese Medicine Bureau. The authors declared absence of any commercial or financial relationships during conduct of the study.

Source: Li MM et al. Front Oncol. 2021 Mar 31. doi: 10.3389/fonc.2021.628127.

Key clinical point: Combination of decitabine and human leukocyte antigen-mismatched hematopoietic stem cell microtransplantation (HLA-MST) could be an effective and safe treatment in patients with intermediate- or high-risk myelodysplastic syndrome (MDS).

Major finding: Overall survival was significantly higher in the decitabine and HLA-MST combination vs. decitabine alone group (24.00 vs. 14.13 months; hazard ratio, 0.32; P = .04). The incidence of hematological adverse events except thrombocytopenia and nonhematological adverse events was slightly lower in decitabine+HLA-MST vs. decitabine alone group.

Study details: Findings are from a retrospective study of 22 patients with intermediate- or high-risk MDS who were treated with decitabine (n=11) or decitabine and HLA-MST combination (n=11).

Disclosures: The study was funded by National Natural Science Foundation of China; the Science and Technology Planning Project of Guangdong Province, China; the Guangzhou Regenerative Medicine and Health Guangdong Laboratory; and the Project of Guangdong Province Traditional Chinese Medicine Bureau. The authors declared absence of any commercial or financial relationships during conduct of the study.

Source: Li MM et al. Front Oncol. 2021 Mar 31. doi: 10.3389/fonc.2021.628127.

Key clinical point: Higher doses of hypomethylating agents, azacytidine (AZA) and decitabine (DAC), can help achieve higher rates of transfusion independence (TI) in patients with low-risk myelodysplastic syndrome (MDS). However, benefits should be weighed against the risk for adverse events.

Major finding: TI rate was higher with AZA (75 mg/m²/day for 7 days) than other regimens (P less than .025). The rate of grade 3/4 anemia was higher (15.8% vs. 0.0%; P less than .0001) and that of diarrhea/constipation (6.9% vs. 25.0%; P = .002) was lower with DAC (20 mg/m²/day for 3 days) vs. AZA (75 mg/m²/day for 5 days).

Study details: Findings are from a meta-analysis of 19 prospective studies including 1,076 patients with low-risk MDS.

Disclosures: The study was funded by Beijing Natural Science Foundation, the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences, and the Non-profit Central Research Institute Fund of CAMS. The authors declared no potential conflicts of interest.

Source: Wan Z et al. Aging (Albany NY). 2021 Mar 26. doi: 10.18632/aging.202767.

Key clinical point: Higher doses of hypomethylating agents, azacytidine (AZA) and decitabine (DAC), can help achieve higher rates of transfusion independence (TI) in patients with low-risk myelodysplastic syndrome (MDS). However, benefits should be weighed against the risk for adverse events.

Major finding: TI rate was higher with AZA (75 mg/m²/day for 7 days) than other regimens (P less than .025). The rate of grade 3/4 anemia was higher (15.8% vs. 0.0%; P less than .0001) and that of diarrhea/constipation (6.9% vs. 25.0%; P = .002) was lower with DAC (20 mg/m²/day for 3 days) vs. AZA (75 mg/m²/day for 5 days).

Study details: Findings are from a meta-analysis of 19 prospective studies including 1,076 patients with low-risk MDS.

Disclosures: The study was funded by Beijing Natural Science Foundation, the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences, and the Non-profit Central Research Institute Fund of CAMS. The authors declared no potential conflicts of interest.

Source: Wan Z et al. Aging (Albany NY). 2021 Mar 26. doi: 10.18632/aging.202767.

Key clinical point: Higher doses of hypomethylating agents, azacytidine (AZA) and decitabine (DAC), can help achieve higher rates of transfusion independence (TI) in patients with low-risk myelodysplastic syndrome (MDS). However, benefits should be weighed against the risk for adverse events.

Major finding: TI rate was higher with AZA (75 mg/m²/day for 7 days) than other regimens (P less than .025). The rate of grade 3/4 anemia was higher (15.8% vs. 0.0%; P less than .0001) and that of diarrhea/constipation (6.9% vs. 25.0%; P = .002) was lower with DAC (20 mg/m²/day for 3 days) vs. AZA (75 mg/m²/day for 5 days).

Study details: Findings are from a meta-analysis of 19 prospective studies including 1,076 patients with low-risk MDS.

Disclosures: The study was funded by Beijing Natural Science Foundation, the Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences, and the Non-profit Central Research Institute Fund of CAMS. The authors declared no potential conflicts of interest.

Source: Wan Z et al. Aging (Albany NY). 2021 Mar 26. doi: 10.18632/aging.202767.

Key clinical point: Bridging therapy with hypomethylating agents (HMAs) did not provide long-term survival benefit in patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Overall survival was not significantly different among patients who received HMAs vs. best supportive care before allo-HSCT (hazard ratio, 0.86; P = .32).

Study details: Findings are from a meta-analysis of 7 retrospective studies including 820 patients with MDS, of which 395 patients received HMAs before allo-HSCT and the remaining patients received best supportive care.

Disclosures: The study was funded by Youth Science Foundation of National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Liu L et al. Clin Exp Med. 2021 Apr 17. doi: 10.1007/s10238-021-00712-0.

Key clinical point: Bridging therapy with hypomethylating agents (HMAs) did not provide long-term survival benefit in patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Overall survival was not significantly different among patients who received HMAs vs. best supportive care before allo-HSCT (hazard ratio, 0.86; P = .32).

Study details: Findings are from a meta-analysis of 7 retrospective studies including 820 patients with MDS, of which 395 patients received HMAs before allo-HSCT and the remaining patients received best supportive care.

Disclosures: The study was funded by Youth Science Foundation of National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Liu L et al. Clin Exp Med. 2021 Apr 17. doi: 10.1007/s10238-021-00712-0.

Key clinical point: Bridging therapy with hypomethylating agents (HMAs) did not provide long-term survival benefit in patients with myelodysplastic syndrome (MDS) receiving allogeneic hematopoietic stem cell transplantation (allo-HSCT).

Major finding: Overall survival was not significantly different among patients who received HMAs vs. best supportive care before allo-HSCT (hazard ratio, 0.86; P = .32).

Study details: Findings are from a meta-analysis of 7 retrospective studies including 820 patients with MDS, of which 395 patients received HMAs before allo-HSCT and the remaining patients received best supportive care.

Disclosures: The study was funded by Youth Science Foundation of National Natural Science Foundation of China. The authors declared no potential conflicts of interest.

Source: Liu L et al. Clin Exp Med. 2021 Apr 17. doi: 10.1007/s10238-021-00712-0.

Key clinical point: There could be a possible relationship between organizing pneumonia (OP) and karyotype der(1;7)(q10; p10) in myelodysplastic syndrome (MDS).

Major finding: Overall, 5 (3.1%) patients developed pathologically diagnosed OP, of which 3 had der(1;7)(q10; p10) abnormality. The chances of developing OP was higher among patients with vs. without der(1;7)(q10;p10) abnormality (odds ratio, 25.70; 95% confidence interval, 2.582-347.400).

Study details: Findings are from a retrospective analysis of 159 patients with high-risk MDS.

Disclosures: No funding source was identified. The authors declared no potential conflicts of interest.

Source: Matsunawa M et al. Br J Haematol. 2021 Apr 14. doi: 10.1111/bjh.17473.

Key clinical point: There could be a possible relationship between organizing pneumonia (OP) and karyotype der(1;7)(q10; p10) in myelodysplastic syndrome (MDS).

Major finding: Overall, 5 (3.1%) patients developed pathologically diagnosed OP, of which 3 had der(1;7)(q10; p10) abnormality. The chances of developing OP was higher among patients with vs. without der(1;7)(q10;p10) abnormality (odds ratio, 25.70; 95% confidence interval, 2.582-347.400).

Study details: Findings are from a retrospective analysis of 159 patients with high-risk MDS.

Disclosures: No funding source was identified. The authors declared no potential conflicts of interest.

Source: Matsunawa M et al. Br J Haematol. 2021 Apr 14. doi: 10.1111/bjh.17473.

Key clinical point: There could be a possible relationship between organizing pneumonia (OP) and karyotype der(1;7)(q10; p10) in myelodysplastic syndrome (MDS).

Major finding: Overall, 5 (3.1%) patients developed pathologically diagnosed OP, of which 3 had der(1;7)(q10; p10) abnormality. The chances of developing OP was higher among patients with vs. without der(1;7)(q10;p10) abnormality (odds ratio, 25.70; 95% confidence interval, 2.582-347.400).

Study details: Findings are from a retrospective analysis of 159 patients with high-risk MDS.

Disclosures: No funding source was identified. The authors declared no potential conflicts of interest.

Source: Matsunawa M et al. Br J Haematol. 2021 Apr 14. doi: 10.1111/bjh.17473.