Chemotherapy For Acute Myeloid Leukemia Research Articles

A multivalent Ara-C-prodrug nanoconjugate achieves selective ablation of leukemic cells in an acute myeloid leukemia mouse model

Current therapy in acute myeloid leukemia (AML) is based on chemotherapeutic drugs administered at high doses, lacking targeting selectivity and displaying poor therapeutic index because of severe adverse effects. Here, we develop a novel nanoconjugate that combines a self-assembled, multivalent protein nanoparticle, targeting the CXCR4 receptor, with an Oligo-Ara-C prodrug, a pentameric form of Ara-C, to highly increase the delivered payload to target cells. This 13.4 nm T22-GFP-H6-Ara-C nanoconjugate selectively eliminates CXCR4+ AML cells, which are protected by its anchoring to the bone marrow (BM) niche, being involved in AML progression and chemotherapy resistance. This nanoconjugate shows CXCR4-dependent internalization and antineoplastic activity in CXCR4+ AML cells in vitro. Moreover, repeated T22-GFP-H6-Ara-C administration selectively eliminates CXCR4+ leukemic cells in BM, spleen and liver. The leukemic dissemination blockage induced by T22-GFP-H6-Ara-C is significantly more potent than buffer or Oligo-Ara-C-treated mice, showing no associated on-target or off-target toxicity and, therefore, reaching a highly therapeutic window. In conclusion, T22-GFP-H6-Ara-C exploits its 11 ligands-multivalency to enhance target selectivity, while the Oligo-Ara-C prodrug multimeric form increases 5-fold its payload. This feature combination offers an alternative nanomedicine with higher activity and greater tolerability than current intensive or non-intensive chemotherapy for AML patients.

Social inequalities in treatment receipt for childhood cancers in Ireland: A population-based analysis.

Treatment advances over the past five decades have resulted in significant improvements in survival from childhood cancer. Although survival rates are relatively high, social disparities in outcomes have been sometimes observed. In a population-based study, we investigated social inequalities by sex and deprivation in treatment receipt in childhood cancer in Ireland. Cancers incident in people aged 0 to 19 during 1994 to 2012 and treatments received were abstracted from the National Cancer Registry Ireland. Multivariable modified Poisson regression with robust error variance (adjusting for age, and year) was used to assess associations between sex and deprivation category of area of residence at diagnosis and receipt of cancer-directed surgery, chemotherapy or radiotherapy. Three thousand seven hundred and four childhood cancers were included. Girls were significantly less likely than boys to receive radiotherapy for leukemia overall (relative risk [RR]=0.70; 95% confidence interval [CI]=0.50-0.98), and acute lymphoblastic leukemia specifically (RR=0.54; 95%CI=0.36-0.79), and surgery for central nervous system (CNS) overall (RR=0.83; 95%CI=0.74-0.93) and other CNS (RR=0.76; 95%CI=0.60-0.96). Girls were slightly less likely to receive chemotherapy for non-Hodgkin lymphoma and surgery for Hodgkin lymphoma (HL), but these results were not statistically significant. Children residing in more deprived areas were significantly less likely to receive chemotherapy for acute myeloid leukemia or surgery for lymphoma overall and HL, but more likely to receive chemotherapy for medulloblastoma. These results may suggest social inequalities in treatment receipt for childhood cancers. Further research is warranted to explore whether similar patterns are evident in other childhood cancer populations and to better understand the reasons for the findings.

Combining Atovaquone with Intensive Conventional Chemotherapy for Pediatric Acute Myeloid Leukemia (AML) Is Feasible and Well Tolerated

BackgroundRelapse free survival of pediatric AML remains only 60%. Current standard myelosuppressive therapy has been maximized, so novel therapies with minimal toxicities are needed to improve outcomes. Previously, we found atovaquone (AQ), an FDA-approved drug that treats pneumocystis jiroveci pneumonia (PJP), reduces AML burden - by suppressing oxidative phosphorylation (OXPHOS) - in xenograft mice. Clinically achievable concentrations of AQ for anti-PJP are 40-80µM, but the anti-leukemia effects are observed as low as 10µM (Stevens et al, Bld Adv, 2019). This makes AQ an ideal drug to incorporate into AML treatment. AQ is a daily administered oral medication, and plasma levels depend on patient compliance, absorption, and entero-hepatic recirculation, which can be compromised due to the patient population and adverse events (AE) of chemotherapy. Here we investigated the feasibility of incorporating AQ into standard pediatric AML treatment.MethodsPatients with de novo AML were enrolled at two children's hospitals in the USA. Daily administration of AQ at established PJP prophylaxis dosing was combined with standard chemotherapy for AML, based on the Medical Research Council (MRC) backbone of cytarabine 100mg/m2 q12h x 10 days, and daunorubicin 50mg/m2/dose on days 1, 3, and 5. As it was unclear if our AQ dosing would provide adequate PJP prophylaxis, it was left to provider discretion to give additional PJP protection. AQ compliance, AEs (per NCI CTCAE v5), parent/caregiver ease of administration score (scale: 1-5, 1=very difficult, 5=very easy to administer) and peripheral blood/bone marrow pharmacokinetics (PK) were collected during Induction 1. Real time AQ plasma concentration results were not provided. To address feasibility of achieving adequate levels, all gastrointestinal (GI) AEs ≥ grade 2 were collected, in addition to grade 4 or greater AEs. Patients who took at least 85% of planned doses and missed less than 2 consecutive doses of AQ were eligible for analyses. Correlative biology studies assessed AQ induced apoptosis at 30uM, effects on OXPHOS and relevant signaling activities. Patient derived xenografts (PDX) were established and treated with AQ. This trial is registered with ClinicalTrials.gov (NCT03568994).ResultsA total of 26 pediatric AML patients enrolled (ages 8 months - 19.7 years, mean 10.7 years); 24 patients were evaluable for this study. Two patients had Grade ≥ 3 GI toxicities that prohibited enteral administration so they were excluded from AQ PK and ease of administration analyses. We found that 14/24 (58%) patients achieved plasma levels above the target anti-leukemia concentration (10µM) by day 11. At the end of induction, 19/24 (75%) patients achieved plasma levels above 10µM, but only 7/24 (29%) patients achieved adequate levels for PJP prophylaxis (40µM). Only 1 patient achieved levels above 40µM throughout the trial [FIG A]. Mean ease of administration score was 3.8. For the youngest patients (x ≤ 2.6years), the average score was 3.4 which was not significantly different from older patients (ANOVA, p > 0.05) [FIG B]. Ease of administration scores showed no association with plasma levels (Pearson's correlation, p > 0.05). Finally, correlative biology studies in patient samples demonstrated robust AQ-induced apoptosis, OXPHOS suppression, and prolonged survival in a PDX model receiving AQ [FIG C].ConclusionOur data demonstrate the feasibility of combining AQ with traditional chemotherapy for pediatric AML. Patients of all ages were able to tolerate AQ and no AEs were attributable to AQ administration. The target anti-leukemic concentration of AQ in the plasma (> 10uM) was frequently achieved, but concentrations of > 40uM at standard dosing were rare. Low plasma levels of AQ did not correlate with the presence of GI related AEs or weight loss, so plasma levels should be monitored to ensure sufficient PJP prophylaxis. Our correlative biology results support suppression of OXPHOS as the primary mechanism of action by which AQ exerts its anti-leukemia effect, and AQ may be an active anti-leukemia agent for pediatric AML patients. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Associating Ex Vivo Drug Sensitivity with Differentiation Status Identifies Effective Drug Combinations for Acute Myeloid Leukemia

The development of molecularly-targeted therapies to improve outcomes relative to chemotherapy for acute myeloid leukemia (AML) is impeded by the heterogeneity of genetic aberrations that contribute to disease. Among the multitude of biological mechanisms that lead to AML disease initiation and progression is dysregulation of cytokine signaling pathways, a hallmark of chronic inflammation, which contribute to the growth, survival, and differentiation state of AML cells. We have previously shown that IL-1β, a pro-inflammatory cytokine expressed by many cell types including macrophages and monocytes, stimulates proliferation of leukemic blasts independent of mutational status in primary AML samples via enhanced phosphorylation of p38α MAPK, an effect that can be blocked by IL-1 receptor knockdown or by pharmacologic inhibition (Carey 2017). Additionally, recent studies have shown sensitivity to the approved BCL2 inhibitor venetoclax in AML associates with undifferentiated leukemic cells (Pei 2020; Zhang 2018; Majumder 2020). Based on these associations, we evaluated the combination of doramapimod (DORA), a p38 MAPK inhibitor, with venetoclax (VEN) for potential enhanced sensitivity on primary AML cells. Ex vivo drug screening of primary AML patient samples (n=335) revealed significantly enhanced efficacy of VEN+DORA compared to either single agent (Nemenyi test; p<0.0001). This broad sensitivity of the VEN+DORA combination was not significantly associated with an array of clinical, genetic, and mutational features in the patient samples tested, in contrast to single agents, particularly VEN. Analysis of blood cell differential counts of patient samples tested identified increased monocyte levels were significantly correlated with sensitivity to DORA and resistance to VEN as single agents (Spearman r = -0.3 and 0.6; p<0.0001), associations that were not apparent with the combination. For patient samples with accompanying FAB differentiation state-based designations (n=108), sensitivities of the combination were similar across classifications of undifferentiated (M0/M1) through monocytic (M4/M5) acute leukemia. In contrast, single-agent VEN was significantly more sensitive in undifferentiated compared to monocytic specimens, whereas DORA sensitivity showed the reverse trend (though to a lesser degree). These differences in sensitivity were further validated by immunophenotyping data where available (n=105), which showed surface markers associated with resistance to VEN (CD11b, CD14, CD16, CD56, CD64, HLADR; Wilcoxon Rank Sum, p<0.001 to p=0.007) or sensitivity to VEN (CD117; p=0.001) or DORA (CD14; HLADR; p=0.004). By contrast, none of these associations significantly distinguished sensitivity for the VEN+DORA combination. Expression levels of MAPK14 and BCL2, the respective primary targets of DORA and VEN, were concordant with their respective drug sensitivities associated with FAB classification; that is, significantly higher levels of BCL2 in M0/M1 leukemias and MAPK14 in M4/M5 cases (Mann-Whitney test; p<0.0001; n=145). Further dissection of transcriptomic and drug sensitivity data revealed strong correlation and gene set enrichment for DORA and VEN sensitivities with monocyte-like and progenitor-like signatures, respectively (n=225), for cell differentiation states previously described for AML (van Galen 2019), and these associations diminished for the combination treatment. Lastly, the VEN+DORA combination enhanced efficacy and synergistic inhibition was confirmed using human AML cell line models tested with a matrix of potential dose concentrations. Taken together, these findings suggest that exploiting distinct, complementary sensitivity profiles of targeted therapies with respect to leukemic differentiation state, such as dual targeting of p38 MAPK and BCL2, offers an opportunity for broad, enhanced efficacy across the clinically challenging heterogeneous landscape of AML. DisclosuresDruker: Novartis Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; Recludix Pharma, Inc.: Consultancy; EnLiven: Consultancy, Research Funding; Pfizer: Research Funding; The RUNX1 Research Program: Membership on an entity's Board of Directors or advisory committees; Merck & Co: Patents & Royalties; Aileron: Membership on an entity's Board of Directors or advisory committees; ALLCRON: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Aptose Therapeutics: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Blueprint Medicines: Consultancy, Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Research Funding; Cepheid: Consultancy, Membership on an entity's Board of Directors or advisory committees; GRAIL: Current equity holder in publicly-traded company; VB Therapeutics: Membership on an entity's Board of Directors or advisory committees; Iterion Therapeutics: Membership on an entity's Board of Directors or advisory committees; Nemucore Medical Innovations, Inc.: Consultancy; Third Coast Therapeutics: Membership on an entity's Board of Directors or advisory committees; Vincerx Pharma: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Vivid Biosciences: Membership on an entity's Board of Directors or advisory committees. Tyner: Genentech: Research Funding; Takeda: Research Funding; Astrazeneca: Research Funding; Constellation: Research Funding; Agios: Research Funding; Petra: Research Funding; Incyte: Research Funding; Array: Research Funding; Gilead: Research Funding; Janssen: Research Funding; Seattle Genetics: Research Funding; Schrodinger: Research Funding.

NT-Probnp As Personalized Medicine Tool and New Biomarker Predicting Response to Chemotherapy and Survival in AML

NT-Probnp As Personalized Medicine Tool and New Biomarker Predicting Response to Chemotherapy and Survival in AML

Non-Infectious Morbidity during Pediatric Acute Myeloid Leukemia Chemotherapy in the Netherlands: A 15-Year Overview

IntroductionTogether with considerable improvement in diagnostics and supportive care measures, treatment intensification has contributed to the improvement of pediatric acute myeloid leukemia (AML) survival outcomes. However, treatment-related toxicity is a consequence of intensified chemotherapy regimens, which has profound implications for both morbidity and mortality. Despite the known devastating impact of all types of toxicity on quality of life (QoL), studies presenting the different forms of non-infectious toxicity prevalent during the most recent Dutch pediatric AML protocols are lacking given that only prior protocols have been evaluated in this manner as of yet. Furthermore, the literature on non-infectious toxicity incidence in pediatric AML patients is relatively scarce. Therefore, the objectives of this study were to: 1) evaluate the cumulative incidence (C.I.) of severe, but non-lethal, non-infectious toxicity during AML treatment according to the last three consecutive protocols of the Dutch Childhood Oncology Group (DCOG), and 2) compare treatment-related toxicity frequencies between protocols.MethodsA retrospective chart review was performed on 245 Dutch patients diagnosed with de novo AML (acute promyelocytic leukemia, myeloid leukemia of Down Syndrome, and secondary AML were excluded) and treated according to ANLL-97/AML-12 (1998-2005) n=118, AML-15 (2005-2010) n=60, or DB-AML-01 (2010-2013) n=67. Table 1 details protocol specifics, including drug dosages per course. Grade 3-4 toxicities, including hematological toxicity, cardiotoxicity, respiratory toxicity, mucositis, typhlitis, nephrotoxicity, hepatotoxicity, neurotoxicity, pain, allergic anaphylactic reaction, and elevation of alanineaminotransferase or bilirubin were defined according to Common Terminology Criteria for Adverse Event version 4.0, excluding infectious toxicity. Grade 5 toxicity (treatment-related mortality) was beyond the scope of this study. Intensive care unit (ICU) admission data was additionally assessed. Toxicity C.I.s were determined via competing events analyses. Relapse and death were considered competing events. Patients were censored at time of stem cell transplantation. Per-protocol comparisons were conducted via Chi-square test, due to lack of sufficient power required to calculate C.I.s.ResultsMedian age at diagnosis was 6.0 years [interquartile range (IQR) 1.0-12.0], 58% were male. Mucositis was the most frequent form of non-hematological toxicity with a C.I. of 86.1% (standard error (S.E.) 3.5%), followed by hepatotoxicity (C.I. 27.4%, S.E. 2.9%), and respiratory toxicity (C.I. 24.6%, S.E. 3.0%) (Table 2). Eighty-three patients (C.I. 33.9%, S.E. 3.0%) were admitted to the ICU at least once, for a median of 6.0 days [IQR 2.0-15.0] (Table 2).Relatively more blood transfusions (both erythrocyte and thrombocyte) were administered to patients treated according to AML-15 (98.3%) and DB-AML-01 (97.0%) compared to AML-12 (86.4%) (p=0.01 and p=0.02, respectively). Relatively more patients suffered from severe mucositis during DB-AML-01 compared to AML-12 (43.4% vs. 25.4%, p=0.01). More patients treated according to AML-15 had bilirubin levels >3x upper limit of normal (ULN) compared to those treated according to AML-12 (13.3% vs. 3.4%, p=0.01). There were no differences in non-infectious toxicity frequency between AML-15 and DB-AML-01. Other forms of toxicity did not differ significantly between protocols. The percentage of patients admitted to the ICU at least once during treatment was 33.9% in AML-12, 26.7% in AML-15, and 40.3% in DB-AML-01.ConclusionsThe high incidence of severe short- and long-term toxicities during pediatric AML therapy poses substantial challenges for patients, families, and care providers. Mucositis was the most common form of non-hematological, non-infectious toxicity in the whole cohort and across all Dutch protocols. Toxicities were more prevalent during the more recent protocols (AML-15 and DB-AML-01) compared to AML-12. Therefore, our findings are important in that they substantiate the need to optimize pediatric AML care in a manner which decreases treatment-related toxicity and QoL impairment. High treatment-related morbidity rates stress the urge to improve supportive care and develop less toxic treatment, while maintaining efficacy. [Display omitted] DisclosuresZwaan: Sanofi: Consultancy.

EXPERIENCE OF GLASDEGIB IN PATIENTS WITH ELDERLY ACUTE MYELOID LEUKEMIA

Acute myeloid leukemia (AML) is characterized by the increase of high levels of myeloid cells in the bone marrow. In general, AML is a disease of older adults. Many adults with AML are unable to receive intensive chemotherapy because of its toxicity.In this study, it was aimed to retrospectively evaluate patients with AML who were treated Glasdegib-based regimens in our center. Case 1: A 75-year-old male patient was diagnosed with congestive heart failure + AML, and idarubicin and cytarabine chemotherapy protocol was started. The patient started to receive covid treatment due to covid lung involvement. The patient, whose treatment was interrupted for 1 month, received the second course as LDAC + glasdegib. In the bone marrow biopsy performed after the 5th cycle, it is observed in remission. Case 2: An 82-year-old male patient was diagnosed with chronic renal failure. With a diagnosis of AML intermediate risk LDAC+glasdegib treatment was given to the patient who did not go into remission after 4 cycles of decitabine treatment. The patient, who was followed in remission after 4 cycles, died due to pneumonia. Case 3: A 76-year-old male patient has a diagnosis of cerebrovascular disease. The patient, who was followed up in remission after 2 courses of azacitidine with a diagnosis of medium risk AML, was approved for glasdegib in the 3rd course of treatment, and he is being followed up with the 3rd course of LDAC+glasdegib therapy. The data of the patients who were treated Glasdegib-based regimens with the diagnosis of AML in the Bozyaka Training and Research Hospital Department of Hematology were scanned retrospectively from their files. In our 3 patients, 1 person died due to pneumonia, but the patient was being followed in remission. Our other 2 patients are still being actively followed up with LDAC + glasdegib treatments. In 2018, the FDA approved glasdegib, a Hedgehog signaling pathway inhibitor, in adults 75 years of age or older with a diagnosis of AML or those with comorbidities that preclude the use of low-dose cytarabine plus intensive induction chemotherapy. Approval is based on interim results from the phase 2 BRIGHT 1003 study evaluating glasdegib in combination with LDAC or LDAC alone. The median OS was 4.9 months for LDAC versus 8.8 months in patients treated with glasdegib+LDAC. This difference represented an approximately 50% reduction in mortality in patients treated with glasdegib+LDAC. The final result of the BRIGHT 1003 study confirmed that glasdegib LDAC significantly improved OS compared to LDAC alone (hazard ratio, 0.495 [95% CI, 0.325-0.752]; P =0.0004). Also, the addition of glasdegib to LDAC did not cause a significant increase in adverse events.

ACUTE UNDIFFERENTIATED LEUKEMIA WITH BCR-ABL TRANSLOCATION: CASE REPORT AND LITERATURE REVIEW

The 2016 WHO classification defines acute undifferentiated leukemia (AUL) as a rare type of acute leukemia (AL) without defining markers for either lymphoid or myeloid lineage commitment. Literature suggests AUL does not harbour the genetic mutations commonly seen in lymphoblastic leukemia or acute myeloid leukemia (AML) including FLT3, WT1, rearrangements of KMT2A or BCR-ABL1 and it highly expresses genes associated with poor prognosis in AML (BAALC, ERG, and MN1); therefore, AUL is often associated with dismal outcome (Arber et al. 2016). This case report depicts an unusual genetic presentation of an AUL with BCR-ABL fusion gene. A 54-year-old female patient presented to our hospital in July 2021 with fatigue and adynamia one month before. She was also found with deep vein thrombosis in the left leg and segmental pulmonary thromboembolism. Laboratory exams showed Hb 9,7 g/dL, WBC 75.77×10 9 /L (77% blasts), platelets 175×10 9 /L. Coagulogram and fibrinogen were normal. Bone marrow (BM) aspiration was hypercellular, showing 86% of agranular blasts. Flow cytometry (FC) from BM blasts exhibited expression of CD34, CD45, HLA-DR, CD33, CD38, and partial expression of CD10 and CD123. The blasts were negative for MPO, CD79a, CD19, CD7, CD3, CD13, C117, CD16, CD11b, CD64, CD15, CD14, CD300e, CD61, NG2, CD71, CD4, CD36, CD22, CD42b. Conventional cytogenetics revealed a Ph+ disease (46,XX,t(9;22)(q34q11.2)[7]/46, idem, add(4)(q35)[7]/46,XX[6]). Real-time quantitative PCR showed positive BCR-ABL with p190 transcripts. FLT3 and NPM1 were found negative. Diagnosis of AUL Ph+ was made. AML chemotherapy was started with 3+7 standard doses regimen plus imatinib 600 mg/day. On day 14th BM evaluation found 89% of blasts with the same immunophenotype as in the diagnosis. The patient presented neutropenic colitis with the need to delay rescue therapy. We searched articles in the Pubmed database using the following strategy: “Bcr-Abl Tyrosine Kinase”AND “undifferentiated leukemia”, “Philadelphia chromosome”AND “undifferentiated leukemia”between 1976 and 2021. We found two case reports that described patients with AUL and positive BCR-ABL gene. In 1983, Smadja, N et al. reported a patient with AL considered at diagnosis to be undifferentiated. Neither the diagnosis cytogenetic nor FC data was provided by the authors, and the AL classification was based only on morphological characteristics. After 17 months, the patient developed Ph+ chronic myelogenous leukemia with a complex translocation (2; 9; 22). Hattori, M et al., in 1995, described a patient that following treatment to non-Hodgkin lymphoma developed myelodysplastic syndrome (MDS) which progressed to AUL, both found with the presence of chimeric BCR-ABL transcripts. The FC showed blasts that expressed CD7 and HLA-DR, and were negative for lineage markers: CD14,CD33,CD2,CD3,CD4,CD5,CD8,CDl0,CD19,CD20 and CD41. Qasrawi, A. et al., in 2019 and 2020 performed two studies analyzing data from 24 and 1444 cases of AUL, respectively. The most common pathogenic mutations were PHF6, SRSF2, RUNX1, ASXL1, and BCOR. No BCR-ABL mutation was described. We believe that with the advent of target therapies, the prognosis of AUL can improve. The patient described has the BCR-ABL gene as a potential target to a tyrosine kinase inhibitor. Considering this is not a usual finding, we hope this report can further help treatment decisions.

Clinical impact of NPM1-mutant molecular persistence after chemotherapy for acute myeloid leukemia

AbstractMonitoring of NPM1 mutant (NPM1mut) measurable residual disease (MRD) in acute myeloid leukemia (AML) has an established role in patients who are treated with intensive chemotherapy. The European LeukemiaNet has defined molecular persistence at low copy number (MP-LCN) as an MRD transcript level <1% to 2% with a <1-log change between any 2 positive samples collected after the end of treatment (EOT). Because the clinical impact of MP-LCN is unknown, we sought to characterize outcomes in patients with persistent NPM1mut MRD after EOT and identify factors associated with disease progression. Consecutive patients with newly diagnosed NPM1mut AML who received ≥2 cycles of intensive chemotherapy were included if bone marrow was NPM1mut MRD positive at the EOT, and they were not transplanted in first complete remission. One hundred patients were followed for a median of 23.5 months; 42% remained free of progression at 1 year, either spontaneously achieving complete molecular remission (CRMRD−; 30%) or retaining a low-level NPM1mut transcript (12% for ≥12 months and 9% at last follow-up). Forty percent met the criteria for MP-LCN. Preemptive salvage therapy significantly prolonged relapse-free survival. Risk factors associated with disease progression were concurrent FLT3-internal tandem duplication at diagnosis and suboptimal MRD response (NPM1mut reduction <4.4-log) at EOT.

Risk Factors for Complications Associated with Peripherally Inserted Central Catheters During Induction Chemotherapy for Acute Myeloid Leukemia.

Objective Peripherally inserted central catheters (PICCs) are widely used in patients with hematologic malignancies. However, the risks of PICC-related complications during chemotherapy for acute myeloid leukemia (AML) are not fully understood. Methods We conducted a retrospective review of 128 adult patients with AML who received induction therapy by way of PICC insertion between 2012 and 2019. Results The median duration of PICC insertion was 30 days. The incidence rate of catheter-related bloodstream infection (CRBSI) was 2.4% at 30 days, and women were more likely to suffer from CRBSI than men. Local reactions at the insertion site were observed in 56 patients; however, these events did not predict CRBSI. The incidence rates of catheter-related thrombosis (CRT) were 1.6% at 30 days. Obesity put patients at an increased risk for CRT. Unexpected PICC removal occurred in 59 patients, and women were at a higher risk of catheter removal than men. Conclusion Low PICC-related complication rates, possibly associated with high rates of catheter removal, were observed during intensive chemotherapy for AML. Women and obese patients require careful monitoring of their PICC. Procedures to achieve appropriate PICC removal without increasing the complication rate need to be considered.

NOTCH-mediated exvivo expansion of human hematopoietic stem and progenitor cells by culture under hypoxia.

SummaryActivation of NOTCH signaling in human hematopoietic stem/progenitor cells (HSPCs) by treatment with an engineered Delta-like ligand (DELTA1ext-IgG [DXI]) has enabled ex vivo expansion of short-term HSPCs, but the effect on long-term repopulating hematopoietic stem cells (LTR-HSCs) remains uncertain. Here, we demonstrate that ex vivo culture of human adult HSPCs with DXI under low oxygen tension limits ER stress in LTR-HSCs and lineage-committed progenitors compared with normoxic cultures. A distinct HSC gene signature was upregulated in cells cultured with DXI in hypoxia and, after 21 days of culture, the frequency of LTR-HSCs increased 4.9-fold relative to uncultured cells and 4.2-fold compared with the normoxia + DXI group. NOTCH and hypoxia pathways intersected to maintain undifferentiated phenotypes in cultured HSPCs. Our work underscores the importance of mitigating ER stress perturbations to preserve functional LTR-HSCs in extended cultures and offers a clinically feasible platform for the expansion of human HSPCs.

3+7 Combined Chemotherapy for Acute Myeloid Leukemia: Is It Time to Say Goodbye?

With the recent approval of multiple new drugs for the treatment of acute myeloid leukemia (AML), the relevance of conventional treatment approaches, such as daunorubicin and cytarabine ("3+7") induction chemotherapy, has been challenged. We review the AML risk stratification, the efficacy of the newly approved drugs, and the role of "3+7". Treatment of AML is becoming more niched with specific subtypes more appropriately treated with gemtuzumab, midostaurin, and CPX-351. Although lower intensity therapies can yield high response rates, they are less efficient at preventing relapses. The only curative potential for poor-risk AML is still an allogeneic stem cell transplant. The number of AML subtypes where 3+7 alone is an appropriate therapeutic option is shrinking. However, it remains the backbone for combination therapy with newer agents in patients suitable for intensive chemotherapy.

Phase 3 randomized trial of chemotherapy with or without oblimersen in older AML patients: CALGB 10201 (Alliance)

AbstractOverexpression of B-cell leukemia/lymphoma 2 (BCL2) renders acute myeloid leukemia (AML) cells resistant to chemotherapy and has been associated with unfavorable outcomes. Oblimersen (G3139) is a phosphorothioate 18-mer antisense oligonucleotide directed against the first 6 BCL2 codons. In a phase 1 study of AML patients treated with G3139, cytarabine, and daunorubicin induction with cytarabine consolidation, no antisense-related toxicity was reported, and BCL2 downregulation occurred in patients achieving complete remission. In this phase 3 trial, untreated older AML patients were randomized to cytarabine (100 mg/m2 per day on days 4-10) and daunorubicin (60 mg/m2 per day on days 4-6) followed by cytarabine consolidation (2000 mg/m2 per day on days 4-8) with (arm A) or without (arm B) G3139 (7 mg/m2 per day on days 1-10 [induction] or days 1-8 [consolidation]). A total of 506 patients were enrolled. No differences in toxicity were observed between arms. Estimated overall survival (OS) at 1 year was 43% for arm A and 40% for arm B (1-sided log rank P = .13), with no differences in disease-free (DFS; P = .26) or event-free survival (P = .80). Subgroup analyses showed patients age <70 years in arm A had improved OS by 1 month vs those in arm B (P = .04), and patients with secondary AML in arm A had better DFS vs those in arm B (P = .04). We conclude that addition of G3139 to chemotherapy failed to improve outcomes of older AML patients. However, more effective means of inhibiting BCL2 are showing promising results in combination with chemotherapy in AML. This trial was registered at www.clinicaltrials.gov as #NCT00085124.

The Degree and Effect Of Weight Loss In Acute Myeloid Leukemia Patients Receiving Induction and Post-Remission Chemotherapy

▪ IntroductionInduction and post-remission chemotherapy for acute myeloid leukemia (AML) is an intensive regimen with significant toxicities performed almost exclusively in inpatient or closely monitored outpatient settings. Extreme weight loss is associated with poor outcomes in cancer. We studied whether treated AML patients (pts) lose a substantial amount of weight and whether weight loss affects overall survival (OS). MethodsAdult pts diagnosed with AML at the Cleveland Clinic from 08/08 - 11/12 were included. All pts completed intensive induction chemotherapy with 7+3 (cytarabine and anthracycline – daunorubicin, idarubicin, or mitoxantrone) as first-line therapy. Pts must have achieved complete remission (CR) by first-line induction or day 14 re-induction chemotherapy. Previously treated pts or those with relapsed or refractory disease were excluded. Co-morbidities and AML disease characteristics were assessed, in addition to weight and body-mass index (BMI) at baseline and throughout AML treatment course until disease relapse, stem cell transplantation (SCT), or loss-to-follow-up/death. The primary endpoints were change in BMI relative to completion of post-remission therapy (PRT), OS, and event-free survival (EFS). OS and EFS were measured from completion of PRT to the date of death (OS) and relapse or need for SCT (EFS). To assess impact of weight recovery on OS and EFS separate linear regression models were fit to each pt to determine rate and direction of change during the first 3 months following the completion of PRT. Pts whose fitted regression lines had slopes>0 were considered to have positive weight trajectories; pts with slopes<0, negative trajectories. Group comparisons were made using the Wilcoxon signed-rank test, logrank test, and proportional hazards models. ResultsOf 126 AML pts who met the inclusion criteria, 43% (n=54) were male and the median age at treatment start was 54 years (range 18-77). Disease characteristics were: acute promyelocytic leukemia 11% (n=14), other AML 89% (n=112); de novo 75% (n=94), secondary 24% (n=31); cytogenetic risk group - favorable 23% (n=29), intermediate 47% (n=59), unfavorable 21% (n=27), unknown 9% (n=11). Co-morbidities potentially impacting BMI and outcome included diabetes (11%), hypertension (42%), hyperlipidemia (28%), alcohol use (65%), use of steroids (13%) or oral contraceptives (16%). Median weight at the start of therapy was 84.9kg (range 37-159.5) and BMI was 29.6 (range 17.6-57.8). BMI groups included normal (18.5-24.9, 26%), overweight-moderately obese (>25-35, 54%), severely obese (>35, 20%). From the start of treatment, median weight loss was: 2% (range -21-53%, p=0.0001) at day 14; 6% (range -19-22%, p<0.0001) at time of CR determination; 4% (range -23-38%, p<0.0001) at end of PRT. With the exception of diabetes (time of CR, p=0.06) and alcohol use (time of CR and end of PRT, p=0.05 in both cases), none of the clinical or demographic factors examined impacted weight loss. In total, 29% of pts (n=37) had >10% weight loss at the completion of PRT, representing an absolute loss of 5.9-20.6kg; 40% of pts (n=50) had a loss<10%, and 31% of pts (n=39) had no change or weight gain. In the group with >10% loss, median time to recovery of >95% pre-treatment weight was 7 months; 11% of pts (n=4) exceeded their pre-treatment weight by >10%. Only age (p=0.06) was associated with weight recovery time, with younger pts recovering weight faster (Figure 1). 60% of pts (n=73) had disease progression and 36% of pts (n=44) had died; estimated EFS and OS are 10.1 (95% CI 6.6-14.7) and 28.2 months (95% CI 17.1-46.4), respectively. The degree of weight loss following completion of PRT was not associated with EFS (p=0.79) or OS (p=0.82). However, there was some indication that pts with positive weight trajectories had longer EFS than pts with negative trajectories, p=0.07 (Figure 2); OS was not impacted significantly (p=0.26). ConclusionAML pts achieving CR with induction therapy experience a median 6% weight loss from start of therapy, but recover by 7 months (median). Those with diabetes or alcohol use lose more weight. Weight changes were not associated with survival; however, there was some suggestion that pts who began to gain weight once PRT was completed had longer EFS than pts whose weight continued to decline. These data can be used to frame pt expectations about weight fluctuations going through AML treatment. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Is Need Chemotherapy Titration During Acute Myeloid Leukemia Treatment?

Persistent marrow aplasia is a rare complication with poor prognosis after intensive chemotherapy for acute myeloid leukemia. We present a 14-year-old boy with acute myeloid leukemia (AML), was complicated by chemotherapy induced persistent aplasia and he was expired because of prolonged neutropenia and pulmonary Aspergilosis. In this review we explain causes of persistent post chemotherapy persistent aplasia and prevention of this phenomenon during treatment with consideration of minimal residual disease (MRD) and response to question about chemotherapy titration dose.

#52: Clinical Features and Management of Pediatric Patients Presenting with New Onset Acute Leukemia and Concomitant COVID-19

Abstract Background Infections represent a significant cause of morbidity and mortality in pediatric patients undergoing treatment for hematologic malignancies. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has led to a worldwide pandemic of coronavirus disease 2019 (COVID-19) and pediatric patients with cancer appear to be at higher risk of severe disease than reported in the general pediatric population. Data are limited on the optimal management of children infected with SARS-CoV-2 and a new diagnosis of leukemia. The objective of this study was to describe our experience of six children who presented with a new diagnosis of acute leukemia and concurrent COVID-19. Methods The study was IRB approved and children were enrolled following informed consent and assent as appropriate for age. The clinical presentations, serologic responses, treatments, and outcomes of patients who presented with acute leukemia and concurrent SARS-CoV-2 infection were abstracted. Residual blood was tested by ELISA for quantitative IgG to the SARS-CoV-2 spike protein receptor binding domain (RBD). Results From March 1, 2020 to Dec 31, 2020, 6 patients were identified with a new diagnosis of acute leukemia and SARS-CoV-2 infection including 3 with acute myeloid leukemia (AML) and 3 with acute lymphoblastic leukemia (ALL). The median age of our cohort was 9 years old (range 1 to 19 years old), 5 of 6 were male, and 4 of 6 patients were Hispanic. All 6 patients presented with symptoms that could be attributed to COVID-19 or acute leukemia, with fever being the most common. All 3 of the AML patients presented with hyperleukocytosis (white blood cell count &amp;gt; 50 x 109/L) and required oxygen therapy and intensive care. At the time of presentation, all patients with specimens available (n=5) had IgG antibodies to SARS-CoV-2 RBD. All patients received COVID-19 directed therapy, with remdesivir (n=5) and convalescent plasma (n=5) being the most common. Chemotherapy was modified or delayed in 5 of the 6 patients. The patient who received standard AML chemotherapy without awaiting COVID-19 directed treatment had delayed serologic response, delayed viral clearance from the nasopharynx, protracted respiratory failure, and ultimately died. For patients with a 12-week follow-up (n=5), 2 patients with AML had died, and the ALL patients were in remission and continuing their leukemia treatment. Conclusion COVID-19 may present concurrently in children with new onset leukemia resulting in severe morbidity and mortality. Our experience adds to growing evidence that children with AML and SARS-CoV-2 infection are at risk for severe COVID-19. Screening for SARS-CoV-2 infection with subsequent delay in chemotherapy and administration of COVID-19 directed therapies should be considered for pediatric patients with newly diagnosed acute leukemia and COVID-19.

Prospective Evaluation of Galactomannan and (1→3) β-d-Glucan Assays as Diagnostic Tools for Invasive Fungal Disease in Children, Adolescents, and Young Adults With Acute Myeloid Leukemia Receiving Fungal Prophylaxis.

Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell β-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis. Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1-43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.

The Impact of Antimicrobial Prophylaxis during Induction Chemotherapy for Acute Myeloid Leukemia in the Current Era

Background:Induction chemotherapy for acute myeloid leukemia (AML) in adults is frequently associated with infectious complications that contribute to morbidity and mortality. Antimicrobial prophylaxis is often given during 7+3 induction to prevent such complications, but these regimens are not without risk: Clostridium difficile colitis and need for total parenteral nutrition (TPN), antimicrobial-associated toxicity, and drug resistance are considerations when choosing prophylaxis. In October 2015, Massachusetts General Hospital (MGH) implemented a change such that patients without active infection at diagnosis no longer received fluoroquinolone and fluconazole prophylaxis during induction chemotherapy. In this study, we evaluated infectious events among patients who received prophylaxis during AML induction therapy before this time point and among those who did not receive antibacterial or antifungal prophylaxis.Methods:We identified adults ages 18 or older with newly diagnosed AML, treated at MGH with 7 days of cytarabine and 3 days of an anthracycline (‘7+3‘) between September 2011 and June 2017. We excluded patients with APL. Patients who were febrile at diagnosis or had a suspected infection at the start of induction received broad spectrum anti-infective coverage and were excluded from this study. Forty-five consecutive eligible patients who did not receive antibacterial or antifungal prophylaxis were evaluated as well as 90 consecutive eligible patients who received ciprofloxacin and fluconazole prophylaxis prior to October 2015. The study period spanned days 1 to 60 following the beginning of induction. Bacteremia and fungemia were defined by culture data. Colitis was defined as symptoms with radiologic findings. The incidence of each infectious event in the two groups was compared using Fisher's exact test. Time to first infectious event was compared using the log rank test. Time to neutrophil recovery in patients who achieved neutrophil recovery was compared using Wilcoxon's rank sum test.Results:The two groups did not differ in median age at diagnosis (p = 0.88), ECOG performance score at diagnosis (p = 0.56), cytogenetic risk (p = 0.44), or rate of secondary AML (p = 0.55). There was a trend towards more fungemia in the group not receiving prophylaxis, but this did not reach statistical significance (9% vs 2%, p = 0.09). Of the 5 Candida organisms that grew in blood from patients who did not receive prophylaxis, 3 were sensitive to fluconazole and 2 sensitivities could not be obtained. There was no significant difference in the incidence of bacteremia (p = 0.66), but in those patients who did develop bacteremia, this complication occurred earlier if they did not receive prophylaxis (median 10 days vs 14 days from induction start, p = 0.03). There was no significant difference in multidrug resistant bacteremia (MRSA, VRE, or ESBL E. coli). In patients who did not receive prophylaxis and developed bacteremia, 53% of organisms isolated were gram-negative, half (50%) of which were susceptible to fluoroquinolones. In patients who received quinolone prophylaxis and developed bacteremia, 64% of organisms were gram-negative and all gram-negative organisms whose sensitivities were tested proved resistant to quinolones.The incidence of all colitis (36% no prophylaxis vs 23%, p = 0.15) and C. diff positive stool (11% vs 6%, p = 0.30) did not differ significantly between the groups. More patients who did not receive prophylaxis required TPN (47% vs 26%, p = 0.02). Time to neutrophil count recovery > 500/mL was longer in the group receiving prophylaxis (24 vs 22 days, p = 0.02). There was no significant difference in grade IV infection, ICU admission for infection, or rehab requirement upon discharge.Conclusions:AML patients who did not receive a fluoroquinolone and fluconazole prophylaxis during induction had infectious complications including bacteremia earlier in their treatment course than those who received prophylaxis. The incidence of colitis or C. diff positivity did not differ between the groups, but patients not receiving prophylaxis required TPN more often. A higher percentage of positive cultures were resistant organisms among those patients given prophylaxis. Further studies are needed to continue to characterize infectious outcomes and resistance patterns based on choice of prophylaxis. [Display omitted] DisclosuresFathi:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Honoraria; Juno: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Agios: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Medimmune: Consultancy, Membership on an entity's Board of Directors or advisory committees. Brunner:Takeda: Research Funding; Celgene: Research Funding.

Concurrent Treatment with Pim Kinase Inhibitor Downregulates Alternative Non-Homologous End-Joining Repair and Decreases Genomic Instability in FLT3-ITD Cells Treated with Topoisomerase 2 Inhibitor Chemotherapy Drugs

Internal tandem duplication of fms -like tyrosine like kinase 3 (FLT3-ITD) is present in 30% of acute myeloid leukemia (AML) cases, causing constitutive FLT3 signaling. While FLT3-ITD AML patients generally achieve remission following combination chemotherapy including cytarabine and a topoisomerase (topo) 2 inhibitor, they relapse rapidly, and FLT3-ITD AML cells frequently have new structural chromosome changes at relapse. Genomic instability in FLT3-ITD AML appears to result from increased generation of reactive oxygen species, which cause DNA double-strand breaks (DSBs), and upregulated DNA DSB repair by an error-prone alternative non-homologous end-joining (Alt-NHEJ) pathway.Pim-1 is an oncogenic serine/threonine kinase that is transcriptionally upregulated downstream of FLT3-ITD, contributes directly to the proliferative and anti-apoptotic effects of FLT3-ITD, and also phosphorylates and stabilizes FLT3, creating a positive feedback loop in FLT3-ITD cells. Pim kinase inhibitors are in clinical trials. We previously showed that concurrent treatment with a Pim kinase inhibitor enhances apoptosis induction by topo 2 inhibitors in FLT3-ITD cells. Here, we tested the effect of concurrent Pim kinase inhibitor treatment on Alt-NHEJ repair of topo 2 inhibitor-induced DNA DSBs and on genomic instability.Functional changes in DSB repair activities induced by treatment with the topo 2 inhibitor daunorubicin (DNR) in the absence and presence of the pan-Pim kinase inhibitor AZD1208 were studied in Ba/F3-ITD cells, with FLT3-ITD, using stably integrated green fluorescent protein (GFP)-based DSB repair reporter constructs DR-GFP, EJ5-GFP and EJ2-GFP, measuring homologous recombination (HR), classical (C-)NHEJ and Alt-NHEJ, respectively. DNR, which induced DNA DSBs, did not induce HR or C-NHEJ repair activity, but induced a 50% increase in Alt-NHEJ activity at 36 hours. Concurrent treatment with AZD1208, which increased DNR-induced DNA DSBs more than two-fold, completely abrogated the DNR-induced increase in Alt-NHEJ repair activity. Treatment of Ba/F3-ITD cells with the topo 2 inhibitors mitoxantrone (MXR) or etoposide (VP-16) also induced Alt-NHEJ repair activity, which was abrogated by concurrent treatment with AZD1208.We next studied mechanisms underlying Pim kinase inhibitor downregulation of Alt-NHEJ. The effects of DNR, MXR or VP-16 on cellular and nuclear expression of the Alt-NHEJ proteins poly (ADP-ribose) polymerase (PARP) 1, DNA polymerase θ, DNA ligase 3 and co-factor X-ray repair cross-complementing protein 1 (XRCC1) were measured in the FLT3-ITD cell lines Ba/F3-ITD, 32D-ITD, MV4-11 and MOLM-14 in the absence and presence of AZD1208. Cellular and nuclear expression of XRCC1 and DNA ligase 3, but not PARP or DNA polymerase θ, decreased in cells co-treated with AZD1208 and topo 2 inhibitors, compared to topo 2 inhibitors alone. XRCC1 was identified as a potential direct Pim-1 substrate by global profiling using the reverse in-gel kinase assay, and was confirmed as a robust Pim substrate in a reverse in-gel kinase assay. This provides a potential mechanistic link between Pim-1 kinase and ALT NHEJ.Alt-NHEJ repair is associated with genomic instability characterized by increased chromosome deletions, insertions and translocations. We studied induction of chromosome changes by topo 2 inhibitor treatment with and without Pim kinase inhibitor in FLT3-ITD cells. Ba/F3-ITD and 32D-ITD cells were incubated with DNR and/or AZD1208, or DMSO control, for 36 hours, then prepared for cytogenetic analysis.For each treatment, 20 consecutive metaphases were analyzed for induction of chromatid breaks and exchanges. No chromosome changes were seen in either cell line with DMSO or AZD1208 treatment. In Ba/F3-ITD cells, chromosome abnormalities were seen in 17 of 20 metaphases after DNR treatment, but only 8 of 20 after combination treatment (p=0.008). In 32D-ITD cells, chromosome abnormalities were seen in 8 of 20 metaphases with DNR, and 0 metaphases with combination (p=0.003).Thus concurrent treatment with Pim kinase inhibitor abrogates induction of Alt-NHEJ repair by topo 2 inhibitor treatment in FLT3-ITD cells and decreases the genomic instability that may contribute to rapid relapse of FLT3-ITD AML after chemotherapy. The data support further preclinical and clinical testing of Pim kinase inhibitors with chemotherapy in AML with FLT3-ITD. DisclosuresTron:AstraZeneca: Employment, Equity Ownership.

Low Risk for Viral Reactivation during Induction for Acute Myeloid Leukemia in Hepatitis B Silent Carriers Who Are Negativefor Hepatitis B Surface Antigen

Introduction: Latent hepatitis B virus (HBV) infection is a well-recognized risk factor for viral reactivation and life-threatening hepatitis during chemotherapy. Chronic HBV carriers, identified by the presence of hepatitis B antigen (HBsAg) in their serum, have a well-established high risk for reactivation. Patients, exposed to HBV, who have not become true carriers [HBsAg-negative, but anti-hepatitis B core antigen (HBc)-positive] are usually considered to have a “resolved” HBV infection. Current recommendations state that during chemotherapy all patients exposed to HBV in the past are to receive anti-HBV prophylaxis. However, these recommendations are based on data mainly driven from unselected series of cancer patients previously exposed to HBV. It has been clearly demonstrated that HBV reactivation is common in cases where immune suppressive therapy is applied (e.g., patients treated with corticosteroids and/or rituximab or those undergoing stem cell transplantation). Information regarding the incidence and risk factors of HBV reactivation in patients treated for acute myeloid leukemia (AML) is scarce. While some data support prophylaxis for chronic HBV carriers (HbSAg-positive) during chemotherapy for AML, it remains debatable whether this approach is required in AML patients with “resolved” HBV infection undergoing intensive chemotherapy.Methods: The current study reviewed medical files of 1200 patients who were diagnosed with AML between the years 2000-2017 and treated in three large hematology departments in Israel - at the Rambam Health Care Campus, Tel Aviv Sourasky Medical Center and Shaare Zedek Medical Center. Clinical characteristics and laboratory data were retrospectively analyzed. Each patient, diagnosed with AML, was tested for HbSAg, HbSAb, anti-HBc, anti-hepatitis C virus (HCV). Only patients who had not received prophylaxis with anti-HBV agents were included in the analysis.Results: A total of 38 patients with “resolved” HBV infection at the time of leukemia diagnosis were identified, including 15 females (39.5%) and 23 males (60.5%), with a median age of 59.5 years (range 35-80). Six (15.7%) patients were diagnosed with AML secondary to myelodysplastic syndromes (MDS). The following induction regimens were used: daunorubicin + cytarabine (“7+3”) in 34 patients (89.5%), clofarabine in two patients, and high-dose cytarabine (HIDAC) in two patients. Nine patients received re-induction with “7+3”. Twenty seven patients (71%) received consolidation - 26 with HIDAC and one with clofarabine (Table 1). Within 90 days following induction + consolidation therapy, no HBV reactivation was documented in any of the 38 patients. There was a mild and asymptomatic elevation in the levels of hepatocellular liver enzymes (up to 2.5 times the upper limit of normal) in some patients, which could also be attributed to other causes, such as drugs, sepsis, etc. In our cohort of patients, overall survival (OS) was identical to that observed in historical AML patients from our medical centers who were not HBV carriers (Fig. 1).Conclusions: AML patients with previous HBV infection (HBsAg-negative and anti-HBc-positive) undergoing intensive chemotherapy are not at an increased risk for virus reactivation. In the current study, none of the 38 patients had HBV reactivation, suggesting that omission of anti-HBV prophylaxis during induction and consolidation chemotherapy could be considered in select AML patients. Notably, two groups of AML patients with a higher risk of HBV reactivation, i.e., recipients of allogeneic stem cell transplantation and HbSAg-positive patients, were not included in the present study and the conclusions drawn are not applicable to these patient subsets. Larger studies are warranted to explore the role of HBV prophylaxis in “silent” carriers. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.