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Routine genetic profiling of acute myeloid leukemia (AML) at initial diagnosis has allowed subgroup specific prognostication, drug development, and clinical management strategies. The optimal approach for treatment response assessment for AML subgroups has not yet however been determined. A nationwide cohort of 257 adult patients in first remission (CR1) from AML associated with an IDH2 mutation (IDH2m) undergoing allogeneic transplant during the period 2013-2019 in the United States had rates of relapse and survival three years after transplantation of 24% and 71%, respectively. Pre-transplant clinical flow cytometry assessment was not useful in stratifying patients based on risk of post-transplant relapse or death. DNA-sequencing was performed on CR1 blood collected within 100 days before transplant. Persistent detection of IDH2m was common (51%) and associated with increased relapse and death compared to testing negative. Co-mutation at initial diagnosis with mutated NPM1 and/or FLT3-ITD was common in this cohort (41%) and use of these validated MRD markers provided superior stratification compared to IDH2m testing. Patients testing negative for IDH2m prior to transplant had low relapse-related death, regardless of conditioning intensity. Post-transplant relapse rates for those with persistently detectable IDH2m in pre-transplant remission were lower after the FDA approval of enasidenib in August 2017., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: Protected health information for research was collected and maintained in CIBMTR’s capacity as a public health authority under the Health Insurance Portability and Accountability Act (HIPAA) privacy rule. All patients provided written informed consent for participation in the National Marrow Donor Program institutional review board–approved CIBMTR database (NCT01166009) and repository (NCT04920474) research protocols. Research was performed in compliance with all applicable federal regulations pertaining to the protection of human research participants and with the approval of the CIBMTR observational research group., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

The use of measurable residual disease (MRD) as a biomarker for prognostication, risk stratification, and therapeutic decision-making in acute myeloid leukemia (AML) is gaining prominence. MRD monitoring for NPM1-mutated and core-binding factor AML using PCR techniques is well-established for assessing disease after intensive chemotherapy. AML with persistent FLT3-ITD MRD post-intensive chemotherapy and pre-allogeneic hematopoietic cell transplantation (pre-allo-HCT) is associated with an increased risk of relapse and lower survival. Pre-allo-HCT MRD is an independent risk factor for post-allo-HCT outcomes, including relapse and death. Therefore, preemptive interventions on the natural history of MRD positivity are an active area of research beyond its initial prognostic function. Targeting MRD in AML with innovative treatment strategies can improve patient outcomes., Competing Interests: Competing interests: AMZ received research funding (institutional) from Celgene/BMS, Abbvie, Astex, Pfizer, Kura, Medimmune/AstraZeneca, Boehringer-Ingelheim, Incyte, Takeda, Novartis, Shattuck Labs, Geron, Foran, and Aprea. AMZ participated in advisory boards, and/or had a consultancy with and received honoraria from AbbVie, Pfizer, Celgene/BMS, Jazz, Incyte, Agios, Servier, Boehringer-Ingelheim, Novartis, Astellas, Daiichi Sankyo, Geron, Taiho, Seattle Genetics, Otsuka, BeyondSpring, Takeda, Ionis, Amgen, Janssen, Genentech, Epizyme, Syndax, Gilead, Kura, Chiesi, ALX Oncology, BioCryst, Notable, Orum, Mendus, Zentalis, Schrodinger, Regeneron, Syros, and Tyme. AMZ served on clinical trial committees for Novartis, Abbvie, Gilead, Syros, BioCryst, Abbvie, ALX Oncology, Kura, Geron and Celgene/BMS. FEC is a consultant for SPD Oncology, Amgen, CTI BioPharma, AbbVie, MorphoSys, Association of Community Cancer Centers, PharmaEssentia, BMS, Geron, Sobi, and DAVA Oncology. He received Clinical Trial Grant Support (PI) to the University of Virginia from Amgen, Celgene, SPD Oncology, Sanofi, Bristol Myers Squibb, FibroGen, PharmaEssentia, BioSight, MEI Pharma, Novartis, and Arog Pharmaceuticals. He also received a travel grant from DAVA Oncology. Sanam Loghavi received research funding from Amgen, Astellas. She is a consultant and/or received honorarium from Guidepoint, QualWorld, Gerson Lehrman Group, Abbvie, Daiichi Sankyo, BluePrint medicine, Caris Diagnostics, Recordati, BMS, Servie, Alphasight, Arima, Qiagen, Cogent Biosciences. She owns stocks with Abbvie. AP has no COI to report., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Patients with cancer are at elevated risk for tuberculosis (TB) reactivation. Diagnosis of latent TB infection and TB disease remains challenging in this patient population despite the advent of interferon-γ release assays (IGRA)., Methods: We retrospectively reviewed medical records of all patients with cancer who had IGRA testing (QuantiFERON-TB [QFT-TB] or T-SPOT.TB) at a major cancer center in the United States from June 2010 to July 2017. The results were analyzed with respect to the likelihood of latent TB infection and TB disease., Results: A total of 1299 patients were included with 1599 tests performed: 586 QFT-TB and 1013 T-SPOT.TB. Forty-nine (4%) patients were diagnosed with latent TB, and four (1%) with TB disease. T-SPOT.TB was more likely to yield an actionable result (positive or negative) than QFT-TB (89% vs. 65%, p < 0.001). The rate of indeterminate results for QFT-TB was higher than the rate of invalid results for T-SPOT.TB (35% and 10%, respectively, p < 0.001). On multivariate analysis, independent predictors of an invalid T-SPOT.TB included prior receipt of alemtuzumab, lower hemoglobin, absolute lymphocyte count, or serum albumin (p < 0.05 each), whereas the independent predictors of an indeterminate QFT-TB were female gender, prior receipt of systemic corticosteroids, and lower hemoglobin, or serum albumin or higher absolute neutrophil count (p < 0.05 each)., Conclusions: T-SPOT.TB yielded more actionable results than QFT-TB in patients with cancer. T-SPOT.TB might be a better IGRA for screening for latent TB infection in patients with cancer, although a direct comparison would be needed to definitively determine this., (© 2024 Wiley Periodicals LLC.)

Gemtuzumab ozogamicin (GO) is a CD33-targeting antibody-drug conjugate approved for the treatment of CD33-positive de novo and relapsed and refractory acute myeloid leukemia (AML). Subset analyses have demonstrated improved clinical outcomes in patients with favorable-risk disease. It is unclear whether the addition of GO to cytarabine and anthracycline chemotherapy (7+3) improves clinical outcomes compared with other conventional regimens for AML. We evaluated the real-world experience with GO added to 7+3 chemotherapy for patients with favorable risk AML. This retrospective analysis included 174 patients with de novo favorable risk AML undergoing induction chemotherapy between 2010 and 2020. The primary outcome was overall survival (OS) and secondary outcomes included rates of remission, measurable residual disease (MRD), and toxicity. Eighteen patients received GO, 37 received a high-dose (HD) anthracycline, and 119 received an intermediate-dose anthracycline. Composite complete remission was achieved in 162 patients (93.1%). Among the 54 patients who were assessed for MRD at remission, 66.7% were undetectable. An improvement in OS was seen for patients who received GO and those treated with HD anthracycline, which was better explained by differences in patient performance status and comorbidities. Patients who received GO did not show increased toxicity., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Purpose of Review: Measurable residual disease (MRD) is integral in the management of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL). This review discusses the current methods used to evaluate MRD as well as the interpretation, significance, and incorporation of MRD in current practice., Recent Findings: New molecular technologies have allowed the detection of MRD to levels as low as 10 - 6 . The most used techniques to evaluate MRD are multiparametric flow cytometry (MFC), quantitative reverse transcription polymerase chain reaction (RT-qPCR), and high-throughput next-generation sequencing (NGS). Each method varies in terms of advantages, disadvantages, and MRD sensitivity. MRD negativity after induction treatment and after allogeneic hematopoietic cell transplantation (HCT) is an important prognostic marker that has consistently been shown to be associated with improved outcomes. Blinatumomab, a new targeted therapy for Ph + ALL, demonstrates high efficacy in eradicating MRD and improving patient outcomes. In the relapsed/refractory setting, the use of inotuzumab ozogamicin and tisagenlecleucel has shown promise in eradicating MRD. The presence of MRD has become an important predictive measure in Ph + ALL. Current studies evaluate the use of MRD in treatment decisions, especially in expanding therapeutic options for Ph + ALL, including tyrosine kinase inhibitors, targeted antibody therapies, chimeric antigen receptor cell therapy, and HCT., (© 2024. The Author(s).)

Importance: Persistence of FLT3 internal tandem duplication (ITD) in adults with acute myeloid leukemia (AML) in first complete remission (CR) prior to allogeneic hematopoietic cell transplant (HCT) is associated with increased relapse and death after transplant, but the association between the level of measurable residual disease (MRD) detected and clinical outcome is unknown., Objective: To examine the association between pre-allogeneic HCT MRD level with relapse and death posttransplant in adults with AML in first CR., Design, Setting, and Participants: In this cohort study, DNA sequencing was performed on first CR blood from patients with FLT3-ITD AML transplanted from March 2013 to February 2019. Clinical follow-up was through May 2022. Data were analyzed from October 2022 to December 2023., Exposure: Centralized DNA sequencing for FLT3-ITD in pre-allogeneic HCT first CR blood using a commercially available kit., Main Outcomes and Measures: The primary outcomes were overall survival and cumulative incidence of relapse, with non-relapse-associated mortality as a competing risk post-allogeneic HCT. Kaplan-Meier estimations (log-rank tests), Cox proportional hazards models, and Fine-Gray models were used to estimate the end points., Results: Of 537 included patients with FLT3-ITD AML from the Pre-MEASURE study, 296 (55.1%) were female, and the median (IQR) age was 55.6 (42.9-64.1) years. Using the variant allele fraction (VAF) threshold of 0.01% or greater for MRD positivity, the results closely aligned with those previously reported. With no VAF threshold applied (VAF greater than 0%), 263 FLT3-ITD variants (median [range] VAF, 0.005% [0.0002%-44%]), and 177 patients (33.0%) with positive findings were identified. Multivariable analyses showed that residual FLT3-ITD was the variable most associated with relapse and overall survival, with a dose-dependent correlation. Patients receiving reduced-intensity conditioning without melphalan or nonmyeloablative conditioning had increased risk of relapse and death at any given level of MRD compared with those receiving reduced-intensity conditioning with melphalan or myeloablative conditioning., Conclusions and Relevance: This study provides generalizable and clinically applicable evidence that the detection of residual FLT3-ITD in the blood of adults in first CR from AML prior to allogeneic HCT is associated with an increased risk of relapse and death, particularly for those with a VAF of 0.01% or greater. While transplant conditioning intensification, an intervention not available to all, may help mitigate some of this risk, alternative approaches will be necessary for this high-risk population of patients who are underserved by the current standard of care.

Over the last decade, the therapeutic landscape for hematological malignancies (HMs) has witnessed a remarkable surge in the development of novel biological and small-molecule-targeted immunomodulatory agents. These therapies have drastically improved survival, but some come at the cost of increased risk of bacterial, viral, and/or fungal infections and on-target off-tumor immunological side effects. To mitigate such risks, physicians must be well informed about infectious complications and necessary preventive measures, such as screening, vaccinations, and antimicrobial prophylaxis. Furthermore, physicians should be vigilant about the noninfectious side effects of these agents that can mimic infections and understand their potential drug-drug interactions with antimicrobials. Strengthening and harmonizing the current surveillance and reporting system for drug-associated infections in real-world settings is essential to better ascertain the potential infections associated with these agents. In this review, we aimed to summarize the infection risks associated with novel agents used for specific HMs and outline recommended strategies for monitoring and prophylaxis., (© 2024 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

Purpose of Review: Acute lymphoblastic leukemia (ALL) is a rare hematologic neoplasm in adults, with most cases defined by pathology related to abnormal B cell proliferation known as B-cell ALL. The course is challenging, with less-than-optimal survival outcomes, even with aggressive multiagent chemotherapy and consideration for stem cell transplantation. Novel therapies focused on targetable pathways are being investigated to improve outcomes while simultaneously decreasing toxicity. In our review, we aim to evaluate the utilization of blinatumomab in B-cell ALL and provide insight on how this guides our management., Recent Findings: Blinatumomab is a bispecific T-cell engager (BiTE) immunotherapy that neutralizes malignant cells by instigating CD3-positive T cells to target CD19-positive B cells. However, this therapy targets both malignant and non-malignant lymphocytes with potentially severe side effects such as cytokine release syndrome or neurotoxicity. Evidence evaluating utilization in the relapsed or refractory setting has been most supported; however, newer trials have also indicated improved survival in the frontline treatment of B-cell ALL. As this therapy is relatively new, the treatment team may include members who are less experienced with the typical treatment course and drug mechanics. This review synthesized available data investigating the effectiveness of blinatumomab effectiveness and its adverse events in addition to providing guidance on safe administration methods utilizing a multidisciplinary healthcare team. When care is coordinated in these settings, serious side effects can be recognized early, allowing for necessary intervention leading to improved quality of life and overall survival. Future research will continue to evaluate blinatumomab in different lines of therapy and expand its way into community settings., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The existence of two acute myeloid leukaemia classification systems-one put forth by WHO and one by the International Consensus Classification in 2022-is concerning. Although both systems appropriately move towards genomic disease definitions and reduced emphasis on blast enumeration, there are consequential disagreements between the two systems on what constitutes a diagnosis of acute myeloid leukaemia. This fundamental problem threatens the ability of heath-care providers to diagnose acute myeloid leukaemia, communicate with patients and other health-care providers, and deliver appropriate and consistent management strategies for patients with the condition. Clinical trial eligibility, standardised response assessments, and eventual drug development and regulatory pathways might also be negatively affected by the discrepancies. In this Viewpoint, we review the merits and limitations of both classification systems and illustrate how the coexistence, as well as application of both systems is an undue challenge to patients, clinicians, hematopathologists, sponsors of research, and regulators. Lastly, we emphasise the urgency and propose a roadmap, by which the two divergent classification systems can be harmonised., Competing Interests: Declaration of interests RMS has served in a consulting or advisory role for Bristol Myers Squibb, Curio Science, Gilead Sciences, and Sciences, Servier, and Rigel. ND has received research funding from Daiichi Sankyo, Bristol Myers Squibb, Pfizer, Gilead, Sevier, Genentech, Astellas, Daiichi Sankyo, AbbVie, Hanmi, Trovagene, Fate Therapeutics, Amgen, Novimmune, Glycomimetics, Trillium, and ImmunoGen. ND has served in a consulting or advisory role for Daiichi-Sankyo, Bristol Myers Squibb, Arog, Pfizer, Novartis, Jazz Pharmaceuticals, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen, Shattuck labs, and Agios. JKA has received institutional research funding from AbbVie, Agios, ALX Oncology, Amgen, Amphivena, Aprea AB, Aptose Biosciences, Astellas Pharma, BioSight, Boehringer Ingelheim, Bristol Myers Squibb, Celgene, Cyclacel, Fujifilm, Immunogen, Kartos Therapeutics, Kura Oncology, Loxo, Pfizer, and Telios; has served in a consulting or advisory role for AbbVie, Astellas Pharma, BioSight, Bluebird Bio, Curio, Gilead, Kura Oncology, Kymera, Stemline Therapeutics, and Syros; and has served on a data monitoring committee for GlycoMimetics. DAP has served as a consultant or advisor for AbbVie, Novartis, Karyopharm, Syndax, Jazz, Syros, Bristol Myers Squibb, BeiGene, Bergen Bio, Arcellx, Genentech, Immunogen, AstraZeneca, Kura, Ryvu, Magenta, Qihan, Zentalis, Medivir, Hibercell, Link, Daiichi Sankyo, Schrodinger, Aptevo, Rigel, Sumitomo, Adicet, Gilead, and Oncoverity; he has received research funding from AbbVie, Karyopharm, Teva, and Bristol Myers Squibb. TB has served as a consultant or advisor for Pfizer and Takeda. VRB reports participating in safety monitoring committee for protagonist. VRB receives consulting fees from Imugene, research funding from AbbVie, Pfizer, Incyte, Jazz Pharmaceuticals, and National Marrow Donor Program, and provided drug from Chimerix for a trial. AdlFB received research funding from Janssen-Cilag, Novartis, BTG Pharmaceuticals, and AbbVie; has served on advisory boards for Abbvie, Astellas, Bristol Meyers Squibb, Curis, Daiichi Sankyo, Incyte, Immunogen, Jazz Pharmaceuticals, Novartis, Pfizer, Roche, and Servier. AdlFB has received speakers' fees from Abbvie, Astellas, Celgene-BMS, Daiichi Sankyo, Incyte, Janssen Cilag, Jazz Pharmaceuticals, Novartis, Pfizer, Roche, and Servier. HEC received research funding from Celgene and has served as a consultant or advisor for Bristol Myers Squibb, Jazz Pharmaceuticals, Novartis, Daiichi, Genentech and Stemline. She has received speakers fees from Jazz, Novartis, BMS and Stemline; she has been on Data Safety Monitoring Board Committees for AbbVie, ASTEX, Syndax, and Takeda. FEC has received institutional research funding from Celgene, Bristol Myers Squib, Amgen, Fibrogen, Sumitomo Pharma Oncology, and AbbVie, and is a consultant for the Association of Community Cancer Centers. ATF has received research funding from Celgene, AbbVie, and Servier, and has served in a consulting or advisory role for Genentech, Celgene, Foghorn, Kite, Morphosys, AbbVie, Takeda, Ipsen, Forma, Amgen, Novartis, Astellas, Immunogen, Mablytics, EnClear, Orum, PureTech, Pfizer, Daiichi Sankyo, Minovia, Rigel, and Servier. IG has received research funding from Merck, Amgen, Gilead, Incyte, and Genentech, and has served as a consultant and advisor for Immunogen, Bristol Meyer Squibb, Amgen, ClearView, Curio, and Nkarta. MRG has stock ownership in Medtronic, received research support from Incyte and Jannsen, and received consulting fees from AbbVie, Amgen, Astellas, Blueprint Medicines, Bristol Myers Squibb, Cardinal Health, CTI BioPharma, Daiichi Sankyo, Gamida Cell, Genentech, Gilead, GSK, Sierra Oncology, Incyte, Invitae, Jazz, Karius, Novartis, Ono Pharmaceutical, Pfizer, Pharmacosmos, Premier, Servier, and Stemline Therapeutics. BAJ has served as a consultant and advisor for AbbVie, Bristol Meyers Squibb, Daiichi Sankyo, Genentech, Gilead, GlycoMimetics, Jazz, Kymera, Pfizer, Rigel, Servier, and Takeda; was on the protocol steering committee for GlycoMimetics, data monitoring committee for Gilead; and received travel reimbursement and [ support from AbbVie and Rigel; BAJ received institutional research funding from AbbVie, Amgen, Aptose, AROG, Bristol Meyers Squibb, Celgene, Daiichi Sankyo, F Hoffmann-La Roche, Forma, Forty Seven, Genentech, Gilead, GlycoMimetics, Hanmi, Immune-Onc, Incyte, Jazz, Loxo Oncology, Pfizer, Pharmacyclics, Sigma Tau, and Treadwell. GNM has received research funding from Bristol Meyers Squibb, Celgene, Glycomimetics, Forty Seven, Jazz, Astex, Syndax, Immune Onc, and Immunogen; has served as a consultant and advisor for AbbVie, Agios, Macrogenics and Pfizer, and has served on a scientific advisory committee for Abbvie, Agios, Astellas, Bristol Myers Squibb, Forty Seven, Genentech, and Stemline. JM has received institutional research funding from Incyte, Novartis, Bristol Meyers Squibb, CTI Bio, Geron, AbbVie, Kartos, and PharmaEssentia, and has received consulting fees from Bristol Meyers Squibb Incyte, Novartis, Roche, CTI Bio, Geron, Kartos, GSK, MorphoSys, PharmaEssentia, Imago, and Galecto. LCM has received institutional research funding from Jazz Pharmaceuticals, has served in a consulting or advisory role for AbbVie, Curio Science, Celgene Corp, Sierra Oncology, and Nkarta; has received honoraria from the American Society of Hematology, the American Board of Internal Medicine, and the Society of Hematologic Oncology; received royalties from Wintrobe's Publishing; and has served as an expert witness for Incyte Corporation. ASM has served in a consulting or advisory role for AbbVie, Servier, Syndax Pharmaceuticals, Bristol Meyers Squibb, Astellas, Rigel, Zentalis, and Ryvu Therapeutics; has served on a data monitoring safety committee for Jazz Pharmaceuticals, Daiichi Sankyo, and Foghorn Therapeutics; and has served as a medical monitor for the Leukemia and Lymphoma Society Beat AML Study. OP has served in a consulting or advisory role for Scopio Labs, Sysmex America, and F Hoffman-La Roche. KWP Research funding from AbbVie, Agios, Daiichi Sankyo, Millennium; was an advisory board member for AbbVie, Astellas, AstraZeneca, Boston BioMedical, Bristol Myers Squibb, Celgene, Novartis, Roche, Jazz Pharmaceuticals, and Servier. MAS has served on advisory boards for Bristol Meyers Squibb, Novartis, Kurome, and Gilead. CCS has received research funding from AbbVie, Bristol Myers Squibb, Erasca, Revolution Medicines, and Zentalis, and has served on a board of advisory committee for Astellas Pharma, Daichi Sanyko, and Genentech. MSt served on the advisory board for Novartis, Kymera, Sierra Oncology, GSK, and Rigel; consulted for Boston Consulting and Dedham group and participated in GME activity for Novartis, Curis Oncology, Haymarket Media and Clinical care options. MSu receives industry research support from Amgen, Bristol Myers Squibb, Gilead, Janssen, Miltenyi Biotec, Morphosys, Novartis, Roche, Seattle Genetics, and Takeda; serves as a consultant and advisor to AvenCell, CDR-Life, Ichnos Sciences, Incyte Biosciences, Janssen, Molecular Partners, and Takeda; and serves on the speakers' bureau at Amgen, AstraZeneca, Bristol Meyers Squibb, Gilead, GSK, Janssen, Novartis, Pfizer, Roche, and Takeda. GLU served in a consulting role for Novartis and Jazz. MTV received compensation for being a speakers from AbbVie, Bristol Myers Squibb, Astellas, Jazz, Novartis, and Servier; has served in a consulting or advisory role for Jazz and Syros Pharmaceuticals. RBW received laboratory research grants and clinical trial support from Amgen, Aptevo, Celgene, ImmunoGen, Janssen, Jazz Pharmaceuticals, Kura, MacroGenics, and Pfizer; has ownership interests in Amphivena; and served in a consulting role to AbbVie, Adicet, Amphivena, BerGenBio, Bristol Myers Squibb, GlaxoSmithKline, ImmunoGen, Kura, and Orum. ESW has served in a consulting and advisory role for AbbVie, Astellas, Bristol Meyers Squibb, Daiichi Sankyo, Genentech, Gilead, GlaxoSmithKline, Janssen, Jazz, Kite, Kura, Novartis, NuProbe, Pfizer, Rigel, Sellas, and Sumitomo Pharma; has received speaking fees from AbbVie, Astellas, Dava Oncology, Kura Oncology, Novartis, and Pfizer; has served on a data monitoring committee for Abbvie and Gilead; and has served on a research committee for Gilead. JFZ has received honoraria from AbbVie, Bristol Myers Squibb, Daiichi Sankyo, Genentech, Gilead, Immunogen, Servier, and Shattuck Labs; has served as a consultant for AbbVie, Foghorn, Gilead and Servier; and has received research funding from AbbVie, Arog, Astex, Gilead, Jazz, Merck, Shattuck Labs, Stemline, Sumitomo Dainippon Pharma, and Takeda. AZ has served in a consulting or advisory role for AbbVie, Astellas, Jannsen, Novartis, and Pfizer, and received honoraria from AbbVie, Astellas, Jannsen, Novartis, and Takeda. AMZ has served in a consulting or advisory role for AbbVie, Acceleron, Agios, Amgen, Aprea, Astellas, AstraZeneca, BeyondSpring, Boehringer Ingelheim, Cardiff Oncology, Bristol Meyers Squibb, Daiichi Sankyo, Epizyme, Genentech, Gilead, Kura, Incyte, Ionis, Loxo Oncology, Janssen, Novartis; served on clinical trial committees for AbbVie, BioCryst, Bristol Meyers Squibb, Geron, Gilead, Kura, Loxo Oncology, Novartis; has received research funding from AbbVie, Acceleron, ADC Therapeutics, Amgen, Aprea, Astex, Boehringer Ingelheim, Cardiff Oncology, Bristol Meyers Squibb, Incyte, Jasper, Jazz, Novartis, and Pfizer. JPB, RSK, SdB, PD, RD, ND, SDF, MK, TLL, PM, and ACS declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Measurable residual disease (MRD) in adults with acute myeloid leukemia (AML) in complete remission is an important prognostic marker, but detection methodology requires optimization. The persistence of mutated NPM1 or FLT3 -ITD in the blood of adult patients with AML in first complete remission (CR1) prior to allogeneic hematopoetic cell transplant (alloHCT) has been established as associated with increased relapse and death after transplant. The prognostic implications of persistence of other common AML-associated mutations, such as IDH1 , at this treatment landmark however remains incompletely defined. We performed testing for residual IDH1 variants ( IDH1 m) in pre-transplant CR1 blood of 148 adult patients undergoing alloHCT for IDH1 -mutated AML at a CIBMTR site between 2013-2019. No post-transplant differences were observed between those testing IDH1 m positive (n=53, 36%) and negative pre-transplant (overall survival: p = 0.4; relapse: p = 0.5). For patients with IDH1 mutated AML co-mutated with NPM1 and/or FLT3 -ITD, only detection of persistent mutated NPM1 and/or FLT3 -ITD was associated with significantly higher rates of relapse (p = 0.01). These data, from the largest study to date, do not support the detection of IDH1 mutation in CR1 blood prior to alloHCT as evidence of AML MRD or increased post-transplant relapse risk., Competing Interests: Conflicts of Interest Statements Hourigan: The National Heart, Lung, and Blood Institute receives research funding for the laboratory of Dr. Hourigan from the Foundation of the NIH AML MRD Biomarkers Consortium. Auletta: Advisory Committee: AscellaHealth and Takeda El Chaer: Consultant: SPD Oncology, Amgen, Association of Community Cancer Centers; Clinical Trial Grant Support (PI) to the University of Virginia: Amgen, BMS, Celgene, SPD Oncology, Sanofi, Bristol Myers Squibb, FibroGen, PharmaEssentia, BioSight, MEI Pharma, Novartis, Arog pharmaceuticals; Travel grant: DAVA Oncology E Chen: Consultant: Rigel Pharmaceuticals and AbbVie Corner: Employment: Bio-Rad Laboratories Jimenez Jimenez: Funding: Abbvie De Lima: Advisory Board: Pfizer, Bristol Myers Squibb; Data Safety Monitoring Board: Novartis, Abbvie; Research Funding: Miltenyi Biotec Kebriaei: Consultant: Pfizer, Jazz Pharmaceuticals

The European LeukemiaNet recently revised both the clinical (2022) and measurable residual disease testing (2021) guidelines for acute myeloid leukemia (AML). The updated World Health Organization and International Consensus Classification for myeloid neoplasms were also published in 2022. Together, these documents update the classification, risk stratification, prognostication, monitoring recommendations, and response assessment of patients with AML. Increased appreciation of the genetic drivers of AML over the past decade and our increasingly sophisticated understanding of AML biology have been translated into novel therapies and more complex clinical treatment guidelines. Somatic genetic abnormalities and germ line predispositions now define and guide treatment and counseling for the subtypes of this hematologic malignancy. In this How I Treat article, we discuss how we approach AML in daily clinical practice, considering the recent updates in the context of new treatments and discoveries over the past decade., (Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution.)

Importance: Preventing relapse for adults with acute myeloid leukemia (AML) in first remission is the most common indication for allogeneic hematopoietic cell transplant. The presence of AML measurable residual disease (MRD) has been associated with higher relapse rates, but testing is not standardized., Objective: To determine whether DNA sequencing to identify residual variants in the blood of adults with AML in first remission before allogeneic hematopoietic cell transplant identifies patients at increased risk of relapse and poorer overall survival compared with those without these DNA variants., Design, Setting, and Participants: In this retrospective observational study, DNA sequencing was performed on pretransplant blood from patients aged 18 years or older who had undergone their first allogeneic hematopoietic cell transplant during first remission for AML associated with variants in FLT3, NPM1, IDH1, IDH2, or KIT at 1 of 111 treatment sites from 2013 through 2019. Clinical data were collected, through May 2022, by the Center for International Blood and Marrow Transplant Research., Exposure: Centralized DNA sequencing of banked pretransplant remission blood samples., Main Outcomes and Measures: The primary outcomes were overall survival and relapse. Day of transplant was considered day 0. Hazard ratios were reported using Cox proportional hazards regression models., Results: Of 1075 patients tested, 822 had FLT3 internal tandem duplication (FLT3-ITD) and/or NPM1 mutated AML (median age, 57.1 years, 54% female). Among 371 patients in the discovery cohort, the persistence of NPM1 and/or FLT3-ITD variants in the blood of 64 patients (17.3%) in remission before undergoing transplant was associated with worse outcomes after transplant (2013-2017). Similarly, of the 451 patients in the validation cohort who had undergone transplant in 2018-2019, 78 patients (17.3%) with residual NPM1 and/or FLT3-ITD variants had higher rates of relapse at 3 years (68% vs 21%; difference, 47% [95% CI, 26% to 69%]; HR, 4.32 [95% CI, 2.98 to 6.26]; P < .001) and decreased survival at 3 years (39% vs 63%; difference, -24% [2-sided 95% CI, -39% to -9%]; HR, 2.43 [95% CI, 1.71 to 3.45]; P < .001)., Conclusions and Relevance: Among patients with acute myeloid leukemia in first remission prior to allogeneic hematopoietic cell transplant, the persistence of FLT3 internal tandem duplication or NPM1 variants in the blood at an allele fraction of 0.01% or higher was associated with increased relapse and worse survival compared with those without these variants. Further study is needed to determine whether routine DNA-sequencing testing for residual variants can improve outcomes for patients with acute myeloid leukemia.

Allogeneic hematopoietic cell transplantation (allo-HCT) represents an important and potentially curative treatment option for adult patients with acute lymphoblastic leukemia. Relapse continues to remain the most important factor influencing overall survival post allo-HCT. We discuss early identification, clinical manifestations, and management of relapsed disease. Routine evaluation of measurable residual disease (MRD) and change in donor chimerism play a crucial role in early detection. Pivotal clinical trials have led to FDA approval of multiple novel agents like blinatumomab and inotuzumab. Combining targeted therapy with cellular immunotherapy serves as the backbone for prolonging overall survival in these patients. Donor lymphocyte infusions have traditionally been used in relapsed disease with suboptimal outcomes. This review provides insight into use of cellular therapy in MRD positivity and decreasing donor chimerism. It also discusses various modalities of combining cellular therapy with novel agents and discussing the impact of chimeric antigen receptor T-cell therapy in the setting of post allo-HCT relapse both as consolidative therapy and as a bridge to second transplant., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Varadarajan et al.)

Immunotherapy poses new considerations and alterations to the management of metastatic colorectal carcinoma (mCRC), where chemotherapy achieves complete radiological response but yields complete pathological response in few patients only. Immunotherapy may be superior in the conversion of unresectable disease to resectable liver lesions from mCRC and downsizing borderline lesions for more feasible resectability and achieving complete pathologic response, with the potential for cure and to alter current, established guidelines for surgical resection with a shift from chemotherapy. We present two patients with hepatic lesions from mCRC characterized by deficient mismatch repair (dMMR) which were unresectable after traditional chemotherapy but were converted to resectable lesions with a complete histopathological response following immunotherapy. Complete histopathologic response and radiologic regression or disappearance of liver lesions was observed in patients with dMMR mCRC after pembrolizumab. Immunotherapy exhibits notable potential for cure, achieving complete, successful surgical resection and improving prognosis., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2022.)

Patients with hematologic malignancies and recipients of hematopoietic cell transplantation (HCT) are more likely to experience severe coronavirus disease 2019 (COVID-19) and have a higher risk of morbidity and mortality after infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Compared with the general population, these patients have suboptimal humoral responses to COVID-19 vaccines and subsequently increased risk for breakthrough infections, underscoring the need for additional therapies, including pre- and postexposure prophylaxis, to attenuate clinical progression to severe COVID-19. Therapies for COVID-19 are mostly available for adults and in the inpatient and outpatient settings. Selection and administration of the best treatment options are based on host factors; virus factors, including circulating SARS-CoV-2 variants; and therapeutic considerations, including the clinical efficacy, availability, and practicality of treatment and its associated side effects, including drug-drug interactions. In this paper, we discuss how we approach managing COVID-19 in patients with hematologic malignancies and recipients of HCT and cell therapy., (© 2022 by The American Society of Hematology.)

Purpose of Review: Measurable residual disease (MRD) is an important monitoring parameter that can help predict survival outcomes in acute lymphoblastic leukemia (ALL). Identifying patients with MRD has the potential to decrease the risk of relapse with the initiation of early salvage therapy and to help guide decision making regarding allogeneic hematopoietic cell transplantation. In this review, we discuss MRD in ALL, focusing on advantages and limitations between MRD testing techniques and how to monitor MRD in specific patient populations., Recent Findings: MRD has traditionally been measured through bone marrow samples, but more data for evaluation of MRD via peripheral blood is emerging. Current and developmental testing strategies for MRD include multiparametric flow cytometry (MFC), next-generation sequencing (NGS), quantitative polymerase chain reaction (qPCR), and ClonoSeq. Novel therapies are incorporating MRD as an outcome measure to demonstrate efficacy, including blinatumomab, inotuzumab ozogamicin, and chimeric antigen receptor T (CAR-T) cell therapy. Understanding how to incorporate MRD testing into the management of ALL could improve patient outcomes and predict efficacy of new therapy options., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Variant acute promyelocytic leukemia (vAPL) is a rare leukemia characterized by rearrangement between RARα and a non-PML partner gene. This type of leukemia can be difficult to recognize by histomorphologic evaluation, particularly in patients with few or no Auer rods, and by flow cytometry, but it can be identified by distinct cytogenetic features. Herein, we report on a patient with vAPL with t(11;17)(q23;q21) who presented an initial diagnostic challenge. Detailed flow cytometry findings are presented for this rare entity. Our case study also presents novel treatment (chemotherapy in combination with venetoclax) chosen based on mechanistic data from preclinical studies., (© American Society for Clinical Pathology, 2021. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose of Review: The incorporation of pegaspargase in chemotherapy regimens has significantly improved the prognosis of ALL in adults. However, pegaspargase use poses many challenges due to its unique toxicity profile. Here, we review pegaspargase's most clinically significant toxicities, and provide guidance for their prevention and management in order to avoid unnecessary drug discontinuation and achieve maximum clinical benefit., Recent Findings: Clinically significant toxicities of pegaspargase include thrombosis, hypersensitivity and inactivation, hepatotoxicity, pancreatitis, and hypertriglyceridemia. The majority of these toxicities are temporary, nonfatal, and can be managed supportively without permanent pegaspargase discontinuation. Special attention should be paid to inactivation, which can lead to treatment failure, as well as pancreatitis, which necessitates complete cessation of asparaginase therapy. The question of how to best proceed in patients who cannot tolerate pegaspargase remains unanswered, and is an important area of future investigation. Pegaspargase is an essential component of the pediatric-inspired regimens that have improved survival in adult ALL. Although pegaspargase's toxicity profile is unique, it is also highly manageable and should not be a barrier to achieving maximum clinical benefit using this drug.

The significance of FLT3 -ITD in acute promyelocytic leukemia (APL) is not well-established. We performed a bi-center retrospective study of 138 APL patients, 59 (42.8%) of whom had FLT3 -ITD. APL patients with FLT3 -ITD had higher baseline white blood cell counts (WBCs) ( p < 0.001), higher hemoglobin, ( p = 0.03), higher aspartate aminotransferase ( p = 0.001), lower platelets ( p = 0.004), lower fibrinogen ( p = 0.003), and higher incidences of disseminated intravascular coagulation ( p = 0.005), M3v variant morphology ( p < 0.001), and the bcr3 isoform ( p < 0.001). FLT3 -ITD was associated with inferior post-consolidation complete remission (CR) ( p = 0.02) and 5-year overall survival (OS) of 79.7%, compared to 94.4% for FLT3 -WT (wild-type) ( p = 0.02). FLT3 -ITD was strongly associated with baseline WBCs ≥ 25 × 10 9 /L (odds ratio (OR): 54.4; 95% CI: 10.4-286.1; p < 0.001). High FLT3 -ITD allelic burdens correlated with high-risk (HR) Sanz scores and high WBCs, with every 1% increase in allelic burden corresponding to a 0.6 × 10 9 /L increase in WBC. HR APL was associated with a 38.5% increase in allelic burden compared with low-risk (LR) APL (95% CI: 19.8-57.2; p < 0.001). Our results provide additional evidence that FLT3 -ITD APL is a distinct subtype of APL that warrants further study to delineate potential differences in therapeutic approach.

Introduction: Obesity has become increasingly prevalent worldwide and is a risk factor for many malignancies. We studied the correlation between body mass index (BMI) and the incidence of acute promyelocytic leukemia (APL), non-APL acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and control hospitalized patients without leukemia in the same community., Methods: Multi-center, retrospective analysis of 71,196 patients: APL (n=200), AML (n=437), ALL (n=103), non-leukemia hospitalized (n=70,456) admitted to University of Maryland and Johns Hopkins Cancer Centers, and University of Maryland Medical Center., Results: Patients with APL had a significantly higher unadjusted mean and median BMI (32.5 kg/m 2 and 30.3 kg/m 2 ) than those with AML (28.3 kg/m 2 and 27.1 kg/m 2 ), ALL (29.3 kg/m 2 and 27.7 kg/m 2 ), and others (29.3 kg/m 2 and 27.7 kg/m 2 ) (p<0.001). Log-transformed BMI multivariable models demonstrated that APL patients had a significantly higher adjusted mean BMI by 3.7 kg/m 2 (p<0.001) or approximately 10% (p<0.01) compared to the other groups, when controlled for sex, race, and age., Conclusions: This study confirms that when controlled for sex, age, and race there is an independent association of higher BMI among patients with APL compared to patients with ALL, AML, and hospitalized individuals without leukemia in the same community., Competing Interests: Conflicts of Interest: All authors declare that they do not have relevant competing interests.

Background: CD19-directed chimeric antigen receptor (CAR) T-cell therapy (CAR-T) has emerged as effective for relapsed/refractory large B-cell lymphoma (R/R LBCL). The neurologic toxicity seen with CAR-T, referred to as immune effector cell-associated neurotoxicity syndrome (ICANS), is poorly understood. To better elucidate the clinical characteristics, treatment outcomes, and correlative biomarkers of ICANS, we review here a single-center analysis of ICANS after CAR T-cell therapy in R/R LBCL., Methods: Patients (n = 45) with R/R LBCL treated with axicabtagene ciloleucel (axi-cel) were identified. Data regarding treatment course, clinical outcomes, and correlative studies were collected. Patients were monitored and graded for ICANS via CARTOX-10 scoring and Common Terminology Criteria for Adverse Events (CTCAE) v4.03 criteria, respectively., Results: Twenty-five (56%) patients developed ICANS, 18 (72%) of whom had severe (CTCAE grades 3-4) ICANS. Median time to development of ICANS was 5 days (range, 3-11). Elevated pre-infusion (day 0 [D0]) fibrinogen (517 vs 403 mg/dL, upper limit of normal [ULN] 438 mg/dL, P = 0.01) and D0 lactate dehydrogenase (618 vs 506 units/L, ULN 618 units/L, P = 0.04) were associated with ICANS. A larger drop in fibrinogen was associated with ICANS (393 vs 200, P < 0.01). Development of ICANS of any grade had no effect on complete remission (CR), progression-free survival (PFS), or overall survival (OS). Duration and total dose of steroid treatment administered for ICANS did not influence CR, PFS, or OS., Conclusions: ICANS after CAR-T with axi-cel for R/R LBCL was seen in about half of patients, the majority of which were high grade. Contrary to previous reports, neither development of ICANS nor its treatment were associated with inferior CR, PFS, or OS. The novel finding of high D0 fibrinogen level can identify patients at higher risk for ICANS., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The role of hematopoietic cell transplantation (HCT) in the management of newly diagnosed adult acute myeloid leukemia (AML) is reviewed and critically evaluated in this evidence-based review. An AML expert panel, consisting of both transplant and nontransplant experts, was invited to develop clinically relevant frequently asked questions covering disease- and HCT-related topics. A systematic literature review was conducted to generate core recommendations that were graded based on the quality and strength of underlying evidence based on the standardized criteria established by the American Society of Transplantation and Cellular Therapy Steering Committee for evidence-based reviews. Allogeneic HCT offers a survival benefit in patients with intermediate- and high-risk AML and is currently a part of standard clinical care. We recommend the preferential use of myeloablative conditioning in eligible patients. A haploidentical related donor marrow graft is preferred over a cord blood unit in the absence of a fully HLA-matched donor. The evolving role of allogeneic HCT in the context of measurable residual disease monitoring and recent therapeutic advances in AML with regards to maintenance therapy after HCT are also discussed., (Copyright © 2020 The American Society for Transplantation and Cellular Therapy. All rights reserved.)

Since Jehovah's Witness (JW) patients diagnosed with leukaemia refuse blood transfusions, they are often denied intensive chemotherapy for fear they could not survive myeloablation without blood transfusion support. Treatment of JW patients with acute leukaemia is challenging and carries a higher morbidity and mortality; however, the refusal of blood products should not be an absolute contraindication to offer multiple treatment modalities including haematopoietic stem cell transplantation. In this review we discuss their optimal management and describe alternative modalities to blood transfusions to provide sufficient oxygenation and prevent bleeding., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Purpose of Review: Rearrangements of the histone lysine [K]-MethylTransferase 2A gene (KMT2A) gene on chromosome 11q23, formerly known as the mixed-lineage leukemia (MLL) gene, are found in 10% and 5% of adult and children ALL cases, respectively. The most common translocated genes are AFF1 (formerly AF4), MLLT3 (formerly AF9), and MLLT1 (formerly ENL). The bimodal incidence of MLL-r-ALL usually peaks in infants in their first 2 years of life and then declines thereafter during the pediatric/young adult phase until it increases again with age. MLL-rearranged ALL (MLL-r-ALL) is characterized by hyperleukocytosis, aggressive behavior with early relapse, relatively high incidence of central nervous system (CNS) involvement, and poor prognosis., Recent Findings: MLL-r-ALL cells are characterized by relative resistance to corticosteroids (due to Src kinase-induced phosphorylation of annexin A2) and L-asparaginase therapy, but they are sensitive to cytarabine chemotherapy (due to increased levels of hENT1 expression). Potential therapeutic targets include FLT3 inhibitors, MEK inhibitors, HDAC inhibitors, BCL-2 inhibitors, MCL-1 inhibitors, proteasome inhibitors, hypomethylating agents, Dot1L inhibitors, and CDK inhibitors. In this review, we discuss MLL-r-ALL focusing on clinical presentation, risk stratification, drug resistance, and treatment strategies, including potential novel therapeutic targets.

The day 14 bone marrow aspirate and biopsy (D14BM) is regularly used to predict achievement of complete remission (CR) with induction chemotherapy in acute myeloid leukemia (AML), however its utility has been questioned. Clearance of peripheral blood blasts (PBB) may serve as an early measure of chemosensitivity. PBB rate of clearance (PBB-RC) was calculated for treatment-naive AML patients (n = 164) undergoing induction with an anthracycline and cytarabine (7+3) and with detectable PBB at diagnosis. PBB-RC was defined as the percentage of the absolute PBB count on the day of diagnosis that was cleared with each day of therapy, on average, until D14 or day of PBB clearance. Each 5% increase in PBB-RC approximately doubled the likelihood of D14BM clearance (OR = 1·81; 95% CI: 1·24-2·64, P < 0·005). PBB-RC was also associated with improved CR rates (OR per 5% = 1·97; 95% CI: 1·27-3·01, P < 0·005) and overall survival (OS) [hazard ratio (HR) per 5% = 0·67; 95% CI: 0·52-0·87]. African American patients had poorer OS adjusted for PBB-RC (HR = 2·18; 95% CI: 1·13-4·23), while race was not associated with D14BM or CR rate. PBB-RC during induction chemotherapy is predictive of D14BM clearance, CR, and OS, and can therefore serve as a prognostic marker for clinical outcomes in AML., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Currently, no standard of care exists for the treatment of relapsed or refractory acute myeloid leukemia (AML). We present our institutional experience with using either CLAG-M or HAM-pegA, a novel regimen that includes pegaspargase. This is a retrospective comparison of 34 patients receiving CLAG-M and 10 receiving HAM-pegA as first salvage cytotoxic chemotherapy in the relapsed or refractory setting. Composite complete response rates were 47.1% for CLAG-M and 90% for HAM-pegA ( p = 0.027). Event-free survival was significantly different in favor of HAM-pegA ( p = 0.045), though overall survival was similar between groups. There were no significant differences in toxicities experienced by patients treated with the two regimens, including adverse events of special interest related to pegaspargase (venous thromboembolism, hemorrhage, hepatotoxicity, pancreatitis, and hypersensitivity reactions). HAM-pegA is a novel regimen for relapsed or refractory AML that resulted in improved response rates and similar toxicities compared to CLAG-M.

Background: Morbidity and mortality from Mycobacterium tuberculosis (Mtb) infection remain significant in cancer patients. We evaluated clinical characteristics, management, and outcomes in patients with active Mtb infection at our institution who had cancer or suspicion of cancer., Methods: We retrospectively examined medical records of all patients with laboratory-confirmed active Mtb infection diagnosed between 2006 and 2014., Results: A total of 52 patients with laboratory-confirmed active Mtb infection were identified during the study period, resulting in an average rate of 6 new cases per year. Thirty-two (62%) patients had underlying cancer, while 20 (38%) patients did not have cancer but were referred to the institution because of suspicion of underlying malignancy. Among patients with cancer, 18 (56%) had solid tumors; 8 (25%) had active hematologic malignancies; and 6 (19%) had undergone hematopoietic-cell transplantation (HCT). Patients with and without cancer were overall similar with the exception of median age (61 years in cancer patients compared to 53 years in noncancer patients). Pulmonary disease was identified in 32 (62%) patients, extrapulmonary disease in 10 (19%) patients, and disseminated disease in 10 (19%) patients. Chemotherapy was delayed in 53% of patients who were to receive such treatment. Eleven patients (all of whom had cancer) died; 3 of these deaths were attributable to Mtb infection., Conclusions: Although not common, tuberculosis remains an important infection in patients with cancer. Approximately one-third of patients were referred to our institution for suspicion of cancer but were ultimately diagnosed with active Mtb infection rather than malignancy.

Patients infected with HIV remain at increased risk of mortality and morbidity from diseases that are preventable with vaccines partly due to the persisting immunopathology that results in impaired responses to vaccination despite virologic suppression. Because data on clinical effectiveness in patients who are immunocompromised remain limited, undervaccination of individuals with HIV poses a major concern. Multiple societies have published recommendations on vaccination in individuals infected with HIV. Many of these recommendations are based on extrapolation of data from clinical trials that usually exclude patients with HIV, although there is a growing body of data from patients infected with HIV as well. In this review, we describe the available literature on vaccine response in the adult patient with HIV as measured by immunogenicity or vaccine efficacy., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Cytomegalovirus (CMV) infections in hematopoietic cell transplant (HCT) recipients cause substantial morbidity and mortality. CMV cell-mediated immunity (CMV-CMI) can be determined by levels of interferon gamma (IFN-γ) production using an enzyme-linked immunospot (ELISPOT) CMV assay (T-SPOT.CMV assay). In this study, we evaluated the ability of this assay to predict the outcome of low-level CMV reactivation in HCT recipients., Methods: We followed 55 HCT recipients with low-level CMV reactivation up to 8 weeks from enrollment. Progression to clinically significant CMV infection (CS-CMVi) was defined as a CMV load >1000 IU/mL or > 500 IU/mL in patients receiving matched related/autologous or matched unrelated transplants, respectively, and initiation of antiviral treatment., Results: Progression to CS-CMVi occurred in 31 (56%) of the HCT recipients. Spot counts of CMV-specific pp65 and IE1 antigens were significantly lower in patients who had CS-CMVi than in patients who did not. On multivariate analysis, the ELISPOT CMV responses and steroids use were the only predictors of progression to CS-CMVi., Conclusions: A strong association between low CMV-CMI and progression to CS-CMVi was observed in HCT recipients. The implementation of serial monitoring of CMV-CMI may identify patients at risk of progression to CS-CMVi that require antiviral therapy., (© The Author(s) 2018. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) treated with conventional chemotherapy have dismal outcomes. Novel immunotherapies targeting CD19, including the bispecific T-cell engager blinatumomab and chimeric antigen-receptor T (CAR-T) cells, have revolutionized the treatment of R/R B-ALL. Robust response rates to CAR-T cell therapy after blinatumomab have recently been reported, but it is unknown whether blinatumomab can be effective following failure of anti-CD19 CAR-T cell therapy. Herein, we describe a patient with Philadelphia chromosome-positive B-ALL who relapsed after CD19-directed CAR-T therapy, but subsequently responded to the combination of blinatumomab and the tyrosine kinase inhibitor ponatinib, with the achievement of a complete remission lasting 12 months., (© 2018 S. Karger AG, Basel.)

We describe two patients with acute promyelocytic leukemia (APL) with an unusual immunophenotype with co-expression of myeloperoxidase (MPO) with cytoplasmic CD3 (cCD3) representing myeloid and T-lineage differentiation. Both harbored FLT3 -ITD mutations. One additionally had a deletion in the PML gene affecting the primer binding site, thus limiting measurable residual disease (MRD) analysis during follow-up. Both patients achieved durable remission with all-trans retinoic acid (ATRA) and arsenic trioxide (ATO)-based therapy, thus mitigating the need for repetitive conventional chemotherapy cycles and allogeneic stem cell transplantation. Our report highlights the complexity and challenge of diagnosis and management of APL due to the variant immunophenotype and genetics, and underscores the importance of synthesizing information from all testing modalities. The association of the unusual immunophenotype and FLT3 -ITD mutation illustrates the plasticity of the hematopoietic stem cell and the pathobiology of leukemia with mixed lineage or lineage infidelity., Competing Interests: Conflict-of-interest disclosure: The authors declare no competing financial interests.

Relapsed Philadelphia chromosome (Ph) positive Acute Lymphoblastic Leukemia (ALL) is an aggressive lymphoid malignancy with a poor prognosis and no randomized studies demonstrating superiority of any single salvage regimen. We present the case of a 33-year-old woman with relapsed Ph positive precursor (pre) B-cell ALL with rapidly rising peripheral blasts while on blinatumomab monotherapy initially, but ultimately responded with the addition of Vincristine Sulfate Liposome Injection (VSLI). Ponatinib was added later when it became available for the patient, and she ultimately achieved a complete remission. Further study is warranted to explore mechanisms of potential synergy, and the safety and efficacy of the combination of blinatumomab and VSLI.

Objective: Geographic and racial disparities may contribute to variation in the incidence and outcomes of HIV-associated cancers in the United States., Method: Using the Surveillance, Epidemiology, and End Results (SEER) database, we analyzed Kaposi sarcoma (KS) incidence and survival by race and geographic region during the combined antiretroviral therapy era. Reported cases of KS in men from 2000 to 2013 were obtained from 17 SEER cancer registries. Overall and age-standardized KS incidence rates were calculated and stratified by race and geographic region. We evaluated incidence trends using joinpoint analyses and calculated adjusted hazard ratios (aHR) for overall and KS-specific mortality using multivariable Cox proportional hazards models., Results: Of 4,455 KS cases identified in men younger than 55 years (median age 40 years), the annual percent change (APC) for KS incidence significantly decreased for white men between 2001 and 2013 (APC -4.52, p = 0.02). The APC for AA men demonstrated a non-significant decrease from 2000-2013 (APC -1.84, p = 0.09). Among AA men in the South, however, APC has significantly increased between 2000 and 2013 (+3.0, p = 0.03). In addition, compared with white men diagnosed with KS during the same time period, AA men were also more likely to die from all causes and KS cancer-specific causes (aHR 1.52, 95% CI 1.34-1.72, aHR 1.49, 95% CI 1.30-1.72 respectively)., Conclusion: Although overall KS incidence has decreased in the U.S., geographic and racial disparities in KS incidence and survival exist.