Do somatic mutations in de novo MDS predict for response to treatment?

Abstract A 68-year-old male with history of hypertension and arthritis presented with bruising and increasing fatigue over several months. He was found to be thrombocytopenic (platelets 30), WCB 2.0 K/mm3, Hg 11.6 g/dL, ANC 870, and 1% circulating blasts. Bone marrow biopsy revealed 40%-50% cellular with multilineage dysplasia and 10% blasts. Cytogenetic genetic studies showed trisomy 2, and translocation (3;21). FISH studies for 5q, 7p, 8, 17p, and 20q abnormalities were negative. Molecular diagnostics were sent to a commercial laboratory to aid in prognostication. These studies showed mutations in TET2 (exons 1- 9 tested) and PHF6 (exons 1-9 tested). No abnormalities in other epigenetic regulators (DNMT3A, ASXL1), RNA splicing (SF3B1, SRSF2, URAF1, ZRSR2), transcription factors (RUNX1 or ETV6), or signaling (CBL, NRAS, KIT, JAK2, MPL) were detected. He was referred for consultation regarding initial treatment. In this elderly patient with preserved organ function and good performance status who is being considered for reduced intensity conditioned allogeneic hematopoietic cell transplant, what should the initial treatment be and can we use the molecular diagnostic results to guide therapy?

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Comparable outcomes post allogeneic hematopoietic cell transplant for patients with de novo or secondary acute myeloid leukemia in first remission

Bone Marrow Transplantation ◽

10.1038/bmt.2015.59 ◽

2015 ◽

Vol 50 (7) ◽

pp. 907-913 ◽

Cited By ~ 11

Author(s):

F V Michelis ◽

E G Atenafu ◽

V Gupta ◽

D D Kim ◽

J Kuruvilla ◽

...

Keyword(s):

Acute Myeloid Leukemia ◽

Myeloid Leukemia ◽

De Novo ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant ◽

Secondary Acute Myeloid Leukemia ◽

First Remission ◽

Acute Myeloid

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Does intensity of induction chemotherapy affect the impact of measurable residual disease (MRD) on prognosis in acute myeloid leukemia (AML)?

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.7031 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. 7031-7031 ◽

Cited By ~ 2

Author(s):

Michael Jamie Hochman ◽

Megan Othus ◽

Carole Shaw ◽

Kelda Gardner ◽

Mary-Elizabeth M. Percival ◽

...

Keyword(s):

Induction Chemotherapy ◽

High Intensity ◽

De Novo ◽

Residual Disease ◽

Performance Status ◽

Multiparameter Flow Cytometry ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Low Intensity ◽

The Impact

7031 Background: Absence of MRD in first complete remission (CR1) of AML decreases the probability of subsequent relapse both in patients given more (e.g. 7+3 or FLAG) or less (e.g. azacitidine) intense induction. Although high-intensity induction seems to increase the chance of CR without MRD, it is unknown whether induction intensity affects outcomes beyond eradication of MRD. Methods: We retrospectively studied adults with newly diagnosed AML or MDS with 10-20% blasts who received induction at the University of Washington from 2008 through 2015. Induction was classified as high or low intensity, CR defined by standard criteria, and marrow MRD by presence of blasts on multiparameter flow cytometry within 1-2 weeks of CR. Post-remission therapy in 10 patients included allogeneic hematopoietic cell transplant (HCT). Multivariate regression analysis examined the independent effects of age, initial cytogenetics (favorable, intermediate, adverse), performance status, de novo vs secondary AML, induction intensity, and MRD on post-CR outcomes. Results: 217 patients received high- and 38 low-intensity induction. 75% of the former vs. 42% of the latter achieved CR without MRD. Although high-intensity therapy was associated with longer overall survival (OS), this difference disappeared after accounting for the above covariates (HR 0.94, 95% CI 0.58 1.52, P = 0.8) and OS was poor regardless of chemotherapy intensity if MRD was present. Multivariate analysis found no interaction between the presence or absence of MRD and induction intensity (HR 0.95, 95% CI 0.4 2.29, P = 0.9). Conclusions: Receiving high-intensity induction chemotherapy does not appear to confer a separate advantage in long-term outcomes once CR without MRD is achieved, at least in patients mostly not receiving HCT. We are currently including more such patients who received HCT. Our results suggest that any effect of high-intensity induction largely reflects its association with a higher probability of achieving an MRD-negative CR.

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Delivering intensive therapies to older adults with hematologic malignancies: strategies to personalize care

Hematology ◽

10.1182/hematology.2019001300 ◽

2019 ◽

Vol 2019 (1) ◽

pp. 63-70

Author(s):

Rebecca L. Olin

Keyword(s):

Older Adults ◽

Best Practice ◽

Treatment Plan ◽

Performance Status ◽

Intensive Therapy ◽

Hematologic Malignancies ◽

Hematopoietic Cell ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Allogeneic Hematopoietic Cell Transplant

Abstract Intensive therapies are often medically indicated for older adults with hematologic malignancies. These may include induction chemotherapy for acute myeloid leukemia (AML), as well as autologous hematopoietic cell transplant (autoHCT) and allogeneic hematopoietic cell transplant (alloHCT). However, it is not always clear how to best deliver these therapies, in terms of determining treatment eligibility, as well as adjusting or adding supportive measures to the treatment plan to maximize successful outcomes. Beyond performance status and presence of comorbidities, comprehensive geriatric assessment and individual geriatric metrics have increasingly been used to prognosticate in these settings and may offer the best approach to personalizing therapy. In the setting of AML induction, evidence supports the use of measures of physical function as independent predictors of survival. For patients undergoing alloHCT, functional status, as measured by instrumental activities of daily living (IADL) and gait speed, may be an important pretransplant assessment. IADL has also been associated with post-autoHCT morbidity and mortality. Current best practice includes assessment of relevant geriatric metrics prior to intensive therapy, and work is ongoing to develop complementary interventions.

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