Searching for the “exit ramp”: Bereaved caregivers (BCGs) describe discontinuation of transfusions at the end of life (EOL) for loved-ones (LOs) dying from acute myeloid leukemia (AML).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e24000-e24000
Author(s):  
Larry Dean Cripe ◽  
Caroline Martin ◽  
Katie Sargent ◽  
Layla Baker ◽  
Ann H. Cottingham
Keyword(s):  
Myeloid Leukemia ◽  
Research Team ◽  
Hospice Care ◽  
Care Transitions ◽  
Initial Response ◽  
Structured Interviews ◽  
Three Stages ◽  
The Right ◽  
Acute Myeloid ◽  
Exit Ramp

e24000 Background: Transfusions may delay hospice care. This study examined how transfusions and other factors influenced care transitions, including decisions related to hospice care, for patients with AML from diagnosis to death. Methods: Nineteen BCGs participated in semi-structured interviews about their experiences. Interviews were audio recorded, transcribed and qualitatively analyzed. Results: The research team identified three stages in BCG experience: 1. Acceptance and Hope: BCG initial response to an AML diagnosis was acceptance of chemotherapy and transfusions as necessary to extend life and potentially cure the AML. Benefits of treatment were emphasized over potential harms or details. 2. Reading the Signals: BCGs learned to interpret information from a variety of sources to appreciate whether their LO was heading in the right direction or not. The signals included discussions with or decisions of the oncologist, changes or no changes in lab results, changes in the LO’s physical condition, and changes in care location in the hospital (e.g., ward bed to ICU bed). Signals were either cautionary or hard stops. Cautionary were seen as conditional, e.g., if things did not improve then LO may be at EOL. Cautionary signals were described as vague and ambiguous. Hard stops were clearer and were typically a clinician decision or recommendation to discontinue treatment and/or transfusions because there was no longer a possibility of benefit. 3. Searching for the Exit-Ramp: Hard stops precipitated awareness that death was imminent and an often-rushed search for how to care for the LO at the EOL. In retrospect the transition made sense to the BCG but they often felt unprepared at the time of transition. Conclusions: The benefits and burdens of transfusions are important signals to BCG about the EOL. Early cautionary signals and discussion may prepare BCG for transitions. Continuation of transfusions in hospice may eliminate a chance for critical conversations.

Venetoclax for the treatment of elderly or chemotherapy-ineligible patients with acute myeloid leukemia: a step in the right direction or a game changer?

2021 ◽  
Vol 14 (2) ◽  
pp. 199-210
Author(s):  
Sonal Agarwal ◽  
Andrew Kowalski ◽  
Molly Schiffer ◽  
Jennifer Zhao ◽  
Jan Philipp Bewersdorf ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
The Right ◽  
Acute Myeloid ◽  
Game Changer

scholarly journals Health Care Use by Older Adults With Acute Myeloid Leukemia at the End of Life

2017 ◽  
Vol 35 (30) ◽  
pp. 3417-3424 ◽  
Author(s):  
Rong Wang ◽  
Amer M. Zeidan ◽  
Stephanie Halene ◽  
Xiao Xu ◽  
Amy J. Davidoff ◽  
...  
Keyword(s):  
Health Care ◽  
Acute Myeloid Leukemia ◽  
End Of Life ◽  
End Of Life Care ◽  
Older Patients ◽  
Myeloid Leukemia ◽  
Hospice Care ◽  
Life Care ◽  
To Receive ◽  
Acute Myeloid

Purpose Little is known about the patterns and predictors of the use of end-of-life health care among patients with acute myeloid leukemia (AML). End-of-life care is particularly relevant for older adults with AML because of their poor prognosis. Methods We performed a population-based, retrospective cohort study of patients with AML who were ≥ 66 years of age at diagnosis and diagnosed during the period from 1999 to 2011 and died before December 31, 2012. Medicare claims were used to assess patterns of hospice care and use of aggressive treatment. Predictors of these end points were evaluated using multivariable logistic regression analyses. Results In the overall cohort (N = 13,156), hospice care after AML diagnosis increased from 31.3% in 1999 to 56.4% in 2012, but the increase was primarily driven by late hospice enrollment that occurred in the last 7 days of life. Among the 5,847 patients who enrolled in hospice, 47.4% and 28.8% started their first hospice enrollment in the last 7 and 3 days of life, respectively. Among patients who transferred in and out of hospice care, 62% received transfusions outside hospice. Additionally, the use of chemotherapy within the last 14 days of life increased from 7.7% in 1999 to 18.8% in 2012. Patients who were male and nonwhite were less likely to enroll in hospice and more likely to receive chemotherapy or be admitted to intensive care units at the end of life. Conversely, older patients were less likely to receive chemotherapy or have intensive care unit admission at the end of life, and were more likely to enroll in hospice. Conclusion End-of-life care for older patients with AML is suboptimal. Additional research is warranted to identify reasons for their low use of hospice services and strategies to enhance end-of-life care for these patients.

scholarly journals Glucocorticoids enhance the antileukemic activity of FLT3 inhibitors in FLT3-mutant acute myeloid leukemia

Blood ◽  
2020 ◽  
Vol 136 (9) ◽  
pp. 1067-1079 ◽  
Author(s):  
Melat T. Gebru ◽  
Jennifer M. Atkinson ◽  
Megan M. Young ◽  
Lijun Zhang ◽  
Zhenyuan Tang ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Drug Exposure ◽  
Residual Disease ◽  
Initial Response ◽  
Antileukemic Activity ◽  
Proapoptotic Protein ◽  
Flt3 Inhibitors ◽  
Acute Myeloid

Abstract FLT3 is a frequently mutated gene that is highly associated with a poor prognosis in acute myeloid leukemia (AML). Despite initially responding to FLT3 inhibitors, most patients eventually relapse with drug resistance. The mechanism by which resistance arises and the initial response to drug treatment that promotes cell survival is unknown. Recent studies show that a transiently maintained subpopulation of drug-sensitive cells, so-called drug-tolerant "persisters" (DTPs), can survive cytotoxic drug exposure despite lacking resistance-conferring mutations. Using RNA sequencing and drug screening, we find that treatment of FLT3 internal tandem duplication AML cells with quizartinib, a selective FLT3 inhibitor, upregulates inflammatory genes in DTPs and thereby confers susceptibility to anti-inflammatory glucocorticoids (GCs). Mechanistically, the combination of FLT3 inhibitors and GCs enhances cell death of FLT3 mutant, but not wild-type, cells through GC-receptor–dependent upregulation of the proapoptotic protein BIM and proteasomal degradation of the antiapoptotic protein MCL-1. Moreover, the enhanced antileukemic activity by quizartinib and dexamethasone combination has been validated using primary AML patient samples and xenograft mouse models. Collectively, our study indicates that the combination of FLT3 inhibitors and GCs has the potential to eliminate DTPs and therefore prevent minimal residual disease, mutational drug resistance, and relapse in FLT3-mutant AML.

Burden of illness in patients with acute myeloid leukemia aged ò65 years ineligible for intensive chemotherapy.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e18529-e18529
Author(s):  
Marie-Helene Lafeuille ◽  
Murali Sundaram ◽  
Patrick Lefebvre ◽  
Bruno Emond ◽  
Hela Romdhani ◽  
...  
Keyword(s):  
Stem Cell ◽  
Myeloid Leukemia ◽  
Hospice Care ◽  
Stem Cell Transplant ◽  
Treatment Patterns ◽  
Cell Transplant ◽  
Intensive Chemotherapy ◽  
Office Visits ◽  
Acute Myeloid

e18529 Background: Management of older patients with acute myeloid leukemia (AML) is challenging due to a higher comorbidity burden, poorer performance status and less favorable biology. This study assessed treatment patterns and healthcare resource utilization (HRU) in the US in patients diagnosed with AML aged ≥65 years who did not receive intensive chemotherapy. Methods: Patients aged ≥65 years with ≥2 diagnoses for AML were identified from the Truven Health MarketScan Analytics Databases (01/01/2011-07/31/2016). Patients had ≥1 bone marrow diagnosis procedure (BX; first AML diagnosis following BX defined as the index date), ≥12 months of continuous eligibility pre-index, no treatment with intensive chemotherapy at any time, no diagnosis for AML relapse or remission or stem cell transplant before BX, and <2 diagnoses for other blood cancers pre-index. Post-index treatment patterns and HRU were reported. Results: 1,492 patients with AML were identified (mean [standard deviation] age: 76.8 [7.0] years; 61% males). Mean post-index follow-up was 212 (255) days and 43% were treated with antineoplastic agents (AA). Most common first-line treatments were azacitidine (35%), decitabine (32%) and hydroxyurea (16%). 4% received low-dose cytarabine. Patients with ≥1 blood transfusion (61%) received 8.9 (9.5) transfusions per month during 177 (244) days on average. A total of 3% received stem cell transplant. Patients had a mean of 3.7 (5.3; pre-index: 0.4 [0.7]) days of hospitalization, 0.2 (1.4; pre-index: 0.0 [0.2]) days of hospice care, and 5.2 (4.5; pre-index: 2.6 [2.4]) office visits per month post-index. Compared to treated patients, untreated patients (32%; i.e., patients with no AA, blood transfusion or stem cell transplant) had fewer days of post-index follow-up (106 vs. 263), more days of hospitalization (4.8 vs. 3.2), and of hospice care (0.4 vs. 0.1), and fewer office visits (3.8 vs. 5.8) per month (all P<0.01). Conclusions: Patients ≥65 years diagnosed with AML not receiving intensive chemotherapy incurred more HRU after AML diagnosis. About a third was untreated and had higher HRU than treated patients. This suggests major unmet needs for well-tolerated treatment options for these patients.

Dexrazoxane-Associated Risk for Acute Myeloid Leukemia/Myelodysplastic Syndrome and Other Secondary Malignancies in Pediatric Hodgkin's Disease

2007 ◽  
Vol 25 (5) ◽  
pp. 493-500 ◽  
Author(s):  
Cameron K. Tebbi ◽  
Wendy B. London ◽  
Debra Friedman ◽  
Doojduen Villaluna ◽  
Pedro A. De Alarcon ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myelodysplastic Syndrome ◽  
Incidence Rate ◽  
Hodgkin's Disease ◽  
Myeloid Leukemia ◽  
Topoisomerase Ii ◽  
Hodgkin’S Disease ◽  
Initial Response ◽  
Malignant Neoplasms ◽  
Acute Myeloid

Purpose Pediatric Oncology Group (POG) studies 9426 and 9425 evaluated dexrazoxane (DRZ) as a cardiopulmonary protectant during treatment for Hodgkin's disease (HD). We evaluated incidence and risk factors of acute myeloid leukemia (AML)/myelodysplastic syndrome (MDS) and second malignant neoplasms (SMNs). Patients and Methods Treatment for low- and high-risk HD with doxorubicin, bleomycin, vincristine, and etoposide (ABVE) or dose-intensified ABVE with prednisone and cyclophosphamide (ABVE-PC), respectively, was followed by low-dose radiation. The number of chemotherapy cycles was determined by rapidity of the initial response. Patients were assigned randomly to receive DRZ (n = 239) or no DRZ (n = 239) concomitantly with chemotherapy to evaluate its potential to decrease adverse cardiopulmonary outcomes. Results Ten patients developed SMN. Six of eight patients developed AML/MDS, and both solid tumors (osteosarcoma and papillary thyroid carcinoma) occurred in recipients of DRZ. Eight patients with SMN were first events. With median 58 months' follow-up, 4-year cumulative incidence rate (CIR) for AML/MDS was 2.55% ± 1.0% with DRZ versus 0.85% ± 0.6% in the non-DRZ group (P = .160). For any SMN, the CIR for DRZ was 3.43% ± 1.2% versus CIR for non-DRZ of 0.85% ± 0.6% (P = .060). Among patients receiving DRZ, the standardized incidence rate (SIR) for AML/MDS was 613.6 compared with 202.4 for those not receiving DRZ (P = .0990). The SIR for all SMN was 41.86 with DRZ versus 10.08 without DRZ (P = .0231). Conclusion DRZ is a topoisomerase II inhibitor with a mechanism distinct from etoposide and doxorubicin. Adding DRZ to ABVE and ABVE-PC may have increased the incidence of SMN and AML/MDS.

scholarly journals The More, The Better: “Do the Right Thing” For Natural Killer Immunotherapy in Acute Myeloid Leukemia

2017 ◽  
Vol 8 ◽  
Author(s):  
Sarah Parisi ◽  
Mariangela Lecciso ◽  
Darina Ocadlikova ◽  
Valentina Salvestrini ◽  
Marilena Ciciarello ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Natural Killer ◽  
Myeloid Leukemia ◽  
The Right ◽  
Do The Right Thing ◽  
Acute Myeloid

scholarly journals MANIFESTAÇÃO ORAL DA LEUCEMIA MIELÓIDE AGUDA COMO PRIMEIRO SINAL PARA O DIAGNÓSTICO: RELATO DE CASO

2014 ◽  
Vol 5 (2) ◽  
Author(s):  
Dhiancarlo Rocha Macedo ◽  
Carlos Henrique Alves De Rezende ◽  
Rogério Moreira Arcieri ◽  
Renata Silva Barbosa
Keyword(s):  
Bone Marrow ◽  
Acute Myeloid Leukemia ◽  
Case Report ◽  
Myeloid Leukemia ◽  
Cervical Lymph Node ◽  
Malignant Disease ◽  
Medical Service ◽  
Oral Manifestation ◽  
The Right ◽  
Acute Myeloid

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow that can present systemic and oral manifestation. In this case report we describe a patient, 16 years of age, who presented the oral manifestation ulcerated lesions on the dorsum of the tongue and cervical lymph node in the right region. After clinical examination and complementary tests, it was taken as a hypothesis the diagnosis of acute leukemia, and the patient was referred to a specialized medical service. Showing the importance of the dentist in the initial diagnosis of leukemia.

scholarly journals Massive Thrombosis of the Right Atrium Extended to the Superior Vena Cava at the Diagnosis of Acute Myeloid Leukemia

2016 ◽  
Vol 2016 ◽  
pp. 1-3
Author(s):  
Bienvenu Houssou ◽  
Gnon Gourou Orou-Guiwa ◽  
Rachida Habbal ◽  
Meryem Qachouh ◽  
Asmaa Quessar
Keyword(s):  
Acute Myeloid Leukemia ◽  
Superior Vena Cava ◽  
Right Atrium ◽  
Myeloid Leukemia ◽  
Superior Vena ◽  
Vena Cava ◽  
Venous Thromboembolic ◽  
Pubmed Search ◽  
The Right ◽  
Acute Myeloid

Introduction. Venous thromboembolic disease is a common complication found in 8% of patients with acute myeloid leukemia. The location at the right atrium is exceptional. These last fifty years, only 6 cases of thrombosis of the atrium in the diagnosis of acute myeloid leukemia were published on PubMed search engine. Case Presentation. 35-year-old farmer, who had been admitted by emergency department for superior vena cava syndrome and had a hyperleukocytic AML with complex karyotype associated with a significant thrombosis of the right atrium, extended all along the superior vena cava. He has been treated by the 2011 AML protocol using low molecular weight heparin and died from respiratory distress. Conclusions. If thrombosis is common in AML, the location in right atrium is rare. Its management requires surgery that is sometimes difficult to achieve.

Leukemia-Initiating Cells in Acute Megakaryoblastic Leukemia and Transient Leukemia of Down Syndrome.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3377-3377
Author(s):  
Jian Chen ◽  
Yue Li ◽  
Monica Doedens ◽  
John E. Dick ◽  
Alvin Zipursky ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myeloid Leukemia ◽  
Human Cells ◽  
Acute Megakaryoblastic Leukemia ◽  
Cell Injection ◽  
Megakaryoblastic Leukemia ◽  
Transient Leukemia ◽  
Human Acute Myeloid Leukemia ◽  
The Right ◽  
Acute Myeloid

Abstract Background. Children with Down syndrome (DS) have a 500-fold greater risk of developing Acute Megakaryoblastic Leukemia (AMKL) than the general population. In addition, approximately one out of ten newborns with DS has circulating blasts in the blood, a condition termed Transient Leukemia (TL). Unlike AMKL, TL resolves spontaneously within three months but in about 20% of cases is followed by AMKL later in life. Both the blasts of TL and AMKL of DS (DS-AMKL) show megakaryocytic differentiation and both harbor somatic mutations of GATA1, resulting in the expression of the N-terminally truncated mutant protein GATA1s. We hypothesize that the difference between the reversible and irreversible phenotype of TL and AMKL in DS, respectively, is due to a functional difference of the leukemia-initiating cells in both conditions. Methods. To characterize the leukemia-initiating cells we established experimental models of AMKL and TL of DS by transplanting cryopreserved primary human cells into NOD/SCID mice. Cell doses ranging from 0.5 to 20x106 were injected intrafemorally into 8-week-old irradiated recipients, which had also been treated with anti-NK cell antibody (anti-CD122). Human hematopoietic growth factors (stem cell factor, interleukin-3 and thrombopoietin) were administered intraperitoneally during the first two weeks following transplantation. Phenotypic analysis using standard cytological, histological and flowcytometric methods was carried out approximately 8 weeks after transplantation. Results. Recipients transplanted with 2 (of a total of 7) AMKL samples showed engraftment with 32% (range 26–44%; n=3) and 73% (range 16–95%; n=8) human cells at the site of the original cell injection (right femur) and 15% (n=3) and 38% (n=8) at distant medullary sites. The engrafted human cells were trisomic for human chromosome 21, expressed the megakaryocytic marker CD61 and, compared with the transplanted primary AMKL cell population, harbored the concordant GATA1 mutation. Bone marrow biopsy revealed increased reticulin fibres 8 weeks after transplantation of AMKL cells. In our experiments, DS-AMKL-initiating cells were found to occur within a broad range of frequency (18x10−4 to 20x10−6) but were not defined by their expression of CD34 and/or CD38. In keeping with the self-renewal capacity of leukemia-initiating cells in human acute myeloid leukemia, DS-AMKL cells collected from the right femur (site of initial cell injection) and from distant bone marrow sites of primary recipients were able to engraft secondary recipients. In contrast, only one of five primary TL cell samples showed engraftment within the right femur (21%, range 3–81%; n=5), the site at which TL cells had been injected 8 weeks earlier. No TL cells or engrafted human cells were detected in any distal bone marrow site or extramedullary compartment such as the spleen. Conclusion. Our results indicate that the function of leukemia-initiating cells in DS-AMKL but not TL parallels those of non-DS human acute myeloid leukemia. Our model provides an experimental approach to distinguish the role of the cellular target vs. mutations cooperating with GATA1 mutations in the development of AMKL and TL in DS.

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