AML

Key clinical point: The detection of measurable residual disease (MRD) using next-generation sequencing (NGS) has a prognostic value before and 1 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), depending on the conditioning intensity.

Major finding: In patients receiving myeloablative conditioning, pre-allo-HSCT NGS-MRD detection was associated with posttransplant relapse. Conversely, in patients receiving reduced intensity conditioning 1 month post-allo-HSCT, NGS-MRD was associated with posttransplant relapse (both P less than .001).

Study details: This study included 146 patients with AML who underwent allo-HSCT in complete remission between 2013 and 2018.

Disclosures: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim HJ et al. Blood Cancer J. 2021 Jun 4. doi: 10.1038/s41408-021-00500-9.

Key clinical point: The detection of measurable residual disease (MRD) using next-generation sequencing (NGS) has a prognostic value before and 1 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), depending on the conditioning intensity.

Major finding: In patients receiving myeloablative conditioning, pre-allo-HSCT NGS-MRD detection was associated with posttransplant relapse. Conversely, in patients receiving reduced intensity conditioning 1 month post-allo-HSCT, NGS-MRD was associated with posttransplant relapse (both P less than .001).

Study details: This study included 146 patients with AML who underwent allo-HSCT in complete remission between 2013 and 2018.

Disclosures: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim HJ et al. Blood Cancer J. 2021 Jun 4. doi: 10.1038/s41408-021-00500-9.

Key clinical point: The detection of measurable residual disease (MRD) using next-generation sequencing (NGS) has a prognostic value before and 1 month after allogeneic hematopoietic stem cell transplantation (allo-HSCT), depending on the conditioning intensity.

Major finding: In patients receiving myeloablative conditioning, pre-allo-HSCT NGS-MRD detection was associated with posttransplant relapse. Conversely, in patients receiving reduced intensity conditioning 1 month post-allo-HSCT, NGS-MRD was associated with posttransplant relapse (both P less than .001).

Study details: This study included 146 patients with AML who underwent allo-HSCT in complete remission between 2013 and 2018.

Disclosures: This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Kim HJ et al. Blood Cancer J. 2021 Jun 4. doi: 10.1038/s41408-021-00500-9.

Key clinical point: Clonal hematopoiesis (CH) persisted after complete remission (CR) in patients with acute myeloid leukemia (AML) and was resistant to consolidation and maintenance therapies, except for allogeneic stem cell transplantation (allo-SCT). However, the presence of postremission CH did not affect clinical outcomes.

Major finding: Following induction chemotherapies, 48% of patients had post-CR CH, and it persisted in 91% of patients during and postremission chemotherapies, but disappeared in 95% of patients after allo-SCT. However, the risk for relapse (P = .174) and nonrelapse mortality (P = .827) was similar in patients with vs. without post-CR CH.

Study details: Findings are from assessment of 164 patients with AML who achieved morphological CR following induction chemotherapies.

Disclosures: This work was supported by grants from the Cancer Prevention and Research Institute of Texas, Welch Foundation, University of Texas System STARS Award, Lyda Hill Foundation, Charif Souki Cancer Research Fund, Japan Society for the Promotion of Science, Sabin Family Foundation Fellowship, and various funding programs at the MD Anderson Cancer Center. The authors declared no conflicts of interest.

Source: Tanaka T et al. Blood. 2021 Jun 3. doi: 10.1182/blood.2020010483.

Key clinical point: Clonal hematopoiesis (CH) persisted after complete remission (CR) in patients with acute myeloid leukemia (AML) and was resistant to consolidation and maintenance therapies, except for allogeneic stem cell transplantation (allo-SCT). However, the presence of postremission CH did not affect clinical outcomes.

Major finding: Following induction chemotherapies, 48% of patients had post-CR CH, and it persisted in 91% of patients during and postremission chemotherapies, but disappeared in 95% of patients after allo-SCT. However, the risk for relapse (P = .174) and nonrelapse mortality (P = .827) was similar in patients with vs. without post-CR CH.

Study details: Findings are from assessment of 164 patients with AML who achieved morphological CR following induction chemotherapies.

Disclosures: This work was supported by grants from the Cancer Prevention and Research Institute of Texas, Welch Foundation, University of Texas System STARS Award, Lyda Hill Foundation, Charif Souki Cancer Research Fund, Japan Society for the Promotion of Science, Sabin Family Foundation Fellowship, and various funding programs at the MD Anderson Cancer Center. The authors declared no conflicts of interest.

Source: Tanaka T et al. Blood. 2021 Jun 3. doi: 10.1182/blood.2020010483.

Key clinical point: Clonal hematopoiesis (CH) persisted after complete remission (CR) in patients with acute myeloid leukemia (AML) and was resistant to consolidation and maintenance therapies, except for allogeneic stem cell transplantation (allo-SCT). However, the presence of postremission CH did not affect clinical outcomes.

Major finding: Following induction chemotherapies, 48% of patients had post-CR CH, and it persisted in 91% of patients during and postremission chemotherapies, but disappeared in 95% of patients after allo-SCT. However, the risk for relapse (P = .174) and nonrelapse mortality (P = .827) was similar in patients with vs. without post-CR CH.

Study details: Findings are from assessment of 164 patients with AML who achieved morphological CR following induction chemotherapies.

Disclosures: This work was supported by grants from the Cancer Prevention and Research Institute of Texas, Welch Foundation, University of Texas System STARS Award, Lyda Hill Foundation, Charif Souki Cancer Research Fund, Japan Society for the Promotion of Science, Sabin Family Foundation Fellowship, and various funding programs at the MD Anderson Cancer Center. The authors declared no conflicts of interest.

Source: Tanaka T et al. Blood. 2021 Jun 3. doi: 10.1182/blood.2020010483.

Key clinical point: Increased accumulation of unconventional CD56⁻CD16⁺ natural killer (NK) cells in patients with newly diagnosed acute myeloid leukemia (AML) was associated with poor clinical outcomes.

Major finding: Accumulation of CD56⁻CD16⁺ NK cells, representing up to 80.8% of total NK cells, was observed in 27.1% of patients with AML. Overall survival (hazard ratio [HR], 0.13; P less than .001) and event-free survival (HR, 0.33; P less than .05) were significantly reduced in patients with high CD56⁻CD16⁺ vs. patients with conventional NK cell profile.

Study details: This study conducted deep phenotyping of NK cells using peripheral blood from 48 patients with newly diagnosed nonacute promyelocytic leukemia AML and 18 healthy control participants.

Disclosures: This work was supported by grants from the Institut National du Cancer, Fondation de France, Sites de Recherche Intégrée sur le Cancer Marseille, Cancéropôle Provence-Alpes-Côte d’Azur, Groupement d’intérêt scientifique-Infrastructures pour la Biologie, la Santé et l’Agronomie, and Agence Nationale de la Recherche. The authors declared no conflicts of interest.

Source: Chretien AS et al. Proc Natl Acad Sci USA. 2021 May 28. doi: 10.1073/pnas.2020459118.

Key clinical point: Increased accumulation of unconventional CD56⁻CD16⁺ natural killer (NK) cells in patients with newly diagnosed acute myeloid leukemia (AML) was associated with poor clinical outcomes.

Major finding: Accumulation of CD56⁻CD16⁺ NK cells, representing up to 80.8% of total NK cells, was observed in 27.1% of patients with AML. Overall survival (hazard ratio [HR], 0.13; P less than .001) and event-free survival (HR, 0.33; P less than .05) were significantly reduced in patients with high CD56⁻CD16⁺ vs. patients with conventional NK cell profile.

Study details: This study conducted deep phenotyping of NK cells using peripheral blood from 48 patients with newly diagnosed nonacute promyelocytic leukemia AML and 18 healthy control participants.

Disclosures: This work was supported by grants from the Institut National du Cancer, Fondation de France, Sites de Recherche Intégrée sur le Cancer Marseille, Cancéropôle Provence-Alpes-Côte d’Azur, Groupement d’intérêt scientifique-Infrastructures pour la Biologie, la Santé et l’Agronomie, and Agence Nationale de la Recherche. The authors declared no conflicts of interest.

Source: Chretien AS et al. Proc Natl Acad Sci USA. 2021 May 28. doi: 10.1073/pnas.2020459118.

Key clinical point: Increased accumulation of unconventional CD56⁻CD16⁺ natural killer (NK) cells in patients with newly diagnosed acute myeloid leukemia (AML) was associated with poor clinical outcomes.

Major finding: Accumulation of CD56⁻CD16⁺ NK cells, representing up to 80.8% of total NK cells, was observed in 27.1% of patients with AML. Overall survival (hazard ratio [HR], 0.13; P less than .001) and event-free survival (HR, 0.33; P less than .05) were significantly reduced in patients with high CD56⁻CD16⁺ vs. patients with conventional NK cell profile.

Study details: This study conducted deep phenotyping of NK cells using peripheral blood from 48 patients with newly diagnosed nonacute promyelocytic leukemia AML and 18 healthy control participants.

Disclosures: This work was supported by grants from the Institut National du Cancer, Fondation de France, Sites de Recherche Intégrée sur le Cancer Marseille, Cancéropôle Provence-Alpes-Côte d’Azur, Groupement d’intérêt scientifique-Infrastructures pour la Biologie, la Santé et l’Agronomie, and Agence Nationale de la Recherche. The authors declared no conflicts of interest.

Source: Chretien AS et al. Proc Natl Acad Sci USA. 2021 May 28. doi: 10.1073/pnas.2020459118.

Key clinical point: No association was observed between runt-related transcription factor 1 gene mutation (RUNX1+) and inferior outcomes after allogeneic stem cell transplantation (alloSCT) in the first complete remission (CR). These findings suggest that early cell transplantation could probably overcome the negative effects of RUNX1 mutation on patients with acute myeloid leukemia (AML).

Major finding: Patients with vs. without RUNX1 mutation had similar rates of overall survival (OS; P = .65), leukemia-free survival (P = .60), and relapse (P = .83) after alloSCT in the first CR.

Study details: Findings are from a retrospective analysis of 674 adult patients with AML (de novo AML, n=584) who underwent alloSCT in the first CR between January 2013 and June 2019.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Waidhauser J et al. Bone Marrow Transplant. 2021 May 31. doi: 10.1038/s41409-021-01322-w.

Key clinical point: No association was observed between runt-related transcription factor 1 gene mutation (RUNX1+) and inferior outcomes after allogeneic stem cell transplantation (alloSCT) in the first complete remission (CR). These findings suggest that early cell transplantation could probably overcome the negative effects of RUNX1 mutation on patients with acute myeloid leukemia (AML).

Major finding: Patients with vs. without RUNX1 mutation had similar rates of overall survival (OS; P = .65), leukemia-free survival (P = .60), and relapse (P = .83) after alloSCT in the first CR.

Study details: Findings are from a retrospective analysis of 674 adult patients with AML (de novo AML, n=584) who underwent alloSCT in the first CR between January 2013 and June 2019.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Waidhauser J et al. Bone Marrow Transplant. 2021 May 31. doi: 10.1038/s41409-021-01322-w.

Key clinical point: No association was observed between runt-related transcription factor 1 gene mutation (RUNX1+) and inferior outcomes after allogeneic stem cell transplantation (alloSCT) in the first complete remission (CR). These findings suggest that early cell transplantation could probably overcome the negative effects of RUNX1 mutation on patients with acute myeloid leukemia (AML).

Major finding: Patients with vs. without RUNX1 mutation had similar rates of overall survival (OS; P = .65), leukemia-free survival (P = .60), and relapse (P = .83) after alloSCT in the first CR.

Study details: Findings are from a retrospective analysis of 674 adult patients with AML (de novo AML, n=584) who underwent alloSCT in the first CR between January 2013 and June 2019.

Disclosures: Open Access funding was enabled and organized by Projekt DEAL. The authors declared no conflicts of interest.

Source: Waidhauser J et al. Bone Marrow Transplant. 2021 May 31. doi: 10.1038/s41409-021-01322-w.

Key clinical point: The second allogeneic hematopoietic cell transplantation (HCT) may be feasible in a selected subset of patients with relapsed acute myeloid leukemia (rAML) after the first HCT (HCT1). Specifically, patients with chronic graft vs. host disease (cGVHD) after HCT1 and high HCT comorbidity score at the second transplant show poor survival following the second HCT.

Major finding: At 2 years after the second HCT, the cumulative incidence of progression, overall survival (OS), progression-free survival (PFS), and nonrelapse mortality was 42%, 36%, 27%, and 18%, respectively. cGVHD after HCT1 and HCT comorbidity index 2 or higher at the second HCT were associated with significantly worse OS (adjusted hazard ratio [aHR], 2.9; P = .001 and aHR, 2.6; P = .003, respectively) and PFS (aHR, 3.4; P less than .001 and aHR, 2.1; P = .01, respectively) after the second HCT.

Study details: Findings are from a retrospective analysis of 91 adult patients who received the second HCT for rAML between January 2000 and August 2019.

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

Source: Yalniz FF et al. Transplant Cell Ther. 2021 May 20. doi: 10.1016/j.jtct.2021.05.007.

Key clinical point: The second allogeneic hematopoietic cell transplantation (HCT) may be feasible in a selected subset of patients with relapsed acute myeloid leukemia (rAML) after the first HCT (HCT1). Specifically, patients with chronic graft vs. host disease (cGVHD) after HCT1 and high HCT comorbidity score at the second transplant show poor survival following the second HCT.

Major finding: At 2 years after the second HCT, the cumulative incidence of progression, overall survival (OS), progression-free survival (PFS), and nonrelapse mortality was 42%, 36%, 27%, and 18%, respectively. cGVHD after HCT1 and HCT comorbidity index 2 or higher at the second HCT were associated with significantly worse OS (adjusted hazard ratio [aHR], 2.9; P = .001 and aHR, 2.6; P = .003, respectively) and PFS (aHR, 3.4; P less than .001 and aHR, 2.1; P = .01, respectively) after the second HCT.

Study details: Findings are from a retrospective analysis of 91 adult patients who received the second HCT for rAML between January 2000 and August 2019.

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

Source: Yalniz FF et al. Transplant Cell Ther. 2021 May 20. doi: 10.1016/j.jtct.2021.05.007.

Key clinical point: The second allogeneic hematopoietic cell transplantation (HCT) may be feasible in a selected subset of patients with relapsed acute myeloid leukemia (rAML) after the first HCT (HCT1). Specifically, patients with chronic graft vs. host disease (cGVHD) after HCT1 and high HCT comorbidity score at the second transplant show poor survival following the second HCT.

Major finding: At 2 years after the second HCT, the cumulative incidence of progression, overall survival (OS), progression-free survival (PFS), and nonrelapse mortality was 42%, 36%, 27%, and 18%, respectively. cGVHD after HCT1 and HCT comorbidity index 2 or higher at the second HCT were associated with significantly worse OS (adjusted hazard ratio [aHR], 2.9; P = .001 and aHR, 2.6; P = .003, respectively) and PFS (aHR, 3.4; P less than .001 and aHR, 2.1; P = .01, respectively) after the second HCT.

Study details: Findings are from a retrospective analysis of 91 adult patients who received the second HCT for rAML between January 2000 and August 2019.

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

Source: Yalniz FF et al. Transplant Cell Ther. 2021 May 20. doi: 10.1016/j.jtct.2021.05.007.

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

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

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

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

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: In patients with acute myeloid leukemia (AML), in addition to the induction regimen, only mean platelet volume (MPV) at diagnosis influenced all short- and long-term outcomes. Thus, patients with higher MPV at diagnosis need careful evaluation.

Major finding: In addition to the induction regimen (odds ratio [OR] for hypomethylating agents, 15.879; 95% confidence interval [CI], 4.956-48.881), MPV (OR, 1.694; 95% CI, 1.122-2.556) was the only factor that influenced short- and long-term outcomes including achievement of complete response, overall survival, and progression-free survival.

Study details: This retrospective study included 148 adult patients with AML followed up for a median of 7.4 months.

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

Source: Tığlıoğlu M et al. Leuk Lymphoma. 2021 May 20. doi: 10.1080/10428194.2021.1929962.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: Autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with acute myeloid leukemia (AML) receiving intensive chemotherapy and antibiotics.

Major finding: After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms.

Study details: Findings are from the phase 2 ODYSSEE trial evaluating AFMT treatment in 25 patients with AML treated with intensive chemotherapy and antibiotics.

Disclosures: This study was sponsored by MaaT Pharma. Some investigators including the lead author reported ties with various pharmaceutical companies including MaaT Pharma.

Source: Malard F et al. Nat Commun. 2021 May 25. doi: 10.1038/s41467-021-23376-6.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML), the detection of measurable/minimal residual disease (MRD) via next-generation sequencing (NGS) after the first consolidation (MRD^2nd) might provide better prognostic insight than after the first complete response (CR) postinduction chemotherapy (MRD^1st).

Major finding: Patients with detectable MRD at either time point had a higher cumulative incidence of relapse (CIR), shorter relapse-free survival (RFS), and poorer overall survival (OS; all P less than .001). However, patients with positive MRD^1st but negative MRD^2nd had good prognosis similar to those with negative MRD at both time points (CIR, P = .140; RFS, P = .231; OS, P = .188).

Study details: Findings are from a retrospective study that analyzed 1,005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy, and after the first consolidation chemotherapy from 335 patients with de novo AML.

Disclosures: This study was funded by grants from the Ministry of Science and Technology (Taiwan) and the Ministry of Health and Welfare (Taiwan). Some investigators reported research funding from Celgene. Other authors declared no conflicts of interest.

Source: Tsai CH et al. Blood Adv. 2021 May 17. doi: 10.1182/bloodadvances.2020003738.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Key clinical point: In patients with acute myeloid leukemia (AML) receiving induction chemotherapy, the incidence of breakthrough invasive fungal diseases (IFDs) and consequent use of therapeutic antifungal agents were significantly lower in patients who received posaconazole prophylaxis vs. those who did not.

Major finding: The incidence of proven or probable IFDs and the need for therapeutic antifungal therapies because of IFDs were significantly lower in patients receiving posaconazole prophylaxis vs. those not receiving any prophylaxis (2.5% vs. 9.4%; P = .03). Mold infection, especially invasive aspergillosis, was the most common IFD in both groups.

Study details: Findings are from a retrospective analysis of 247 adult patients with AML who received induction chemotherapy with (n=162) or without (n=85) posaconazole prophylaxis.

Disclosures: This study was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea. The authors declared no conflicts of interest.

Source: Yang E et al. Medicine (Baltimore). 2021 May 21. doi: 10.1097/MD.0000000000025448.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.

Measurable residual disease (MRD) in acute myeloid leukemia (AML) is both predictive and prognostic. However, the best time and method to define its prognostic role remains unclear. This month, 2 papers evaluate the role of MRD testing at different time points during therapy.

The first paper by Tsai et al studied MRD by next-generation sequencing (NGS) after induction and consolidation. The second paper by Kim et al evaluated the role of NGS MRD before and after allogeneic hematopoietic cell transplantation (allo-HCT).

The study by Tsai et al was a retrospective study that analyzed 1005 bone marrow samples serially collected at diagnosis, the first CR after induction chemotherapy (MRD^1st), and after the first consolidation (MRD^2nd) chemotherapy from 335 patients with de novo AML. Patients with antecedent cytopenia, hematologic diseases, and therapy-related AML (t-AML) were excluded. Patients who achieved complete remission with incomplete hematologic recovery (CRi) or had DNMT3A, TET2, and ASXL1 (DTA) only mutations were not included in the analysis. Multiple previous studies have demonstrated that persistence of DTA only mutations have no prognostic impact. Patients with positive MRD^1st (MRD^1st-)but negative MRD^2nd (MRD^2nd-)had good prognosis similar to those with negative MRD at both time points (cumulative incidence of relapse (CIR), P = .140; relapse-free survival (RFS), P = .231; overall survival (OS), P = .188). The median OS for patients with MRD^1st-MRD2^nd- (n = 147), and MRD^1st+MRD^2nd- (n = 60) was not reached compared to 3.1 years for patients with MRD^1st+MRD^2nd+ (n = 75). Only 9 patients progressed from MRD^1st- to MRD^2nd+ and their median survival was 3.6 years.

In the study by Kim et al utilizing NGS pre- and postHCT, the detection of MRD using NGS had a prognostic value before and 1 month after allo-HCT. This study included 146 patients with AML who underwent allo-HCT in complete remission between 2013 and 2018. The OS was 82%, 64%, and 44% for patients who were MRD negative both pre and post HCT, MRD+ then MRD- after alloHCT and MRD+ both pre- and postHCT respectively. In this study, myeloablative conditioning (MAC) pre allo-HCT did not overcome the negative prognostic value of MRD+ disease prior to allo-HCT. This is in contradiction to the BMT CTN0901 where MAC did overcome the negative prognostic impact of MRD+ disease prior to alloHCT. The authors suggest that this difference could be due to the limited number of genes assessed in the BMT CTN0901 study. Both of those studies demonstrate that achieving NGS MRD negativity either with chemotherapy consolidation or alloHCT leads to better outcome and can be used as a meaningful endpoint in AML studies.

Another completely different direction to improve patient outcomes is the evaluation of the gut microbiota. Several studies have demonstrated the negative impact of disturbed gut microbiota on several outcomes in patients with AML receiving intensive chemotherapy. A study by Malard et al demonstrated that autologous fecal microbiota transfer (AFMT) was safe and effective for gut microbiota restoration in patients with AML receiving intensive chemotherapy and antibiotics. After AFMT treatment, α-diversity indices returned to their initial median levels (Shannon index, P = .70; Inverse Simpson index, P = .90) and the b-diversity index showed the restoration of microbial communities, particularly for Lachnospiraceae and Ruminococcaceae families. Gut microbiota composition was preserved even after consolidation chemotherapy with high-dose cytarabine. No serious adverse events were reported, and only 3 patients experienced transient gastrointestinal symptoms. This approach may be considered in the future to improve the outcome of patients or allogeneic stool transfer is another option currently being studied. Clearly gut microbiota have an effect on outcome, and future studies will demonstrate the best and safest way to reconstitute gut microbiota in patients with hematological malignancies.