Matthew S Alkaitis, MD PhD

All Publications

• A case of true acute eosinophilic leukemia arising from myelodysplastic syndrome. Journal of hematopathology Li, Q., Alkaitis, M. S., Shomali, W., Mannis, G. N., Zhang, T. Y., Gotlib, J., Fernandez-Pol, S. 2026; 19 (1)

  Abstract

  Acute leukemias of the myeloid lineage most commonly show myeloid and/or monocytic differentiation. Leukemias with erythroid, megakaryoblastic, and basophilic differentiation are more rare but are well documented. In contrast, acute leukemia showing marked morphologic and immunophenotypic features of eosinophilic differentiation is not a defined entity. When acute leukemias do show a prominent population of cells with eosinophilic differentiation, the eosinophil populations typically show morphologic features of mature eosinophils and the eosinophilic population may be clonally related to the neoplastic cells or may be reactive. In this case report, we describe an unusual case of acute myeloid leukemia evolving from a myelodysplastic neoplasm with low blasts in which the predominant cell population in the peripheral blood and bone marrow were cells with round nuclei and immature chromatin with prominent eosinophilic granules and immunophenotypic features suggestive of maturation arrest at an eosinophilic promyelocyte-like stage. At the time of leukemic transformation, molecular studies showed acquisition of NRAS G13R, NRAS Q61K, and KRAS G12R mutations in addition to the TET2 variants (N582fs and E1357X), del(20q), and 7q- abnormalities detected in the antecedent myelodysplastic neoplasm. No PDGFRA, PDGFRB, FGFR1, JAK2, or FLT3 rearrangements were detected by FISH or in sequencing assays. BCR::ABL1 testing was also negative. Whole-genome sequencing did not detect additional abnormalities to explain the differentiation block. In summary, this is, to our knowledge, the only reported case of an acute leukemia in which the immature cells themselves demonstrate morphologic and immunophenotypic features of eosinophilic promyelocytes.

  View details for DOI 10.1007/s12308-026-00719-0

  View details for PubMedID 42455472

  View details for PubMedCentralID 9479031

• Circulating Tumor DNA (ctDNA) Enables Superior and Universal Measurable Residual Disease (MRD) Monitoring in Acute Myeloid Leukemia (AML) Highly Predictive of Relapse Free and Overall Survival Gunaratne, R., Zhou, C., Tai, J. W., Kim, S., Tanaka, K., Rajaram, S., Carleton, M., Yin, R., Alkaitis, M., Schwede, M., Sworder, B. J., Khodadoust, M. S., Majeti, R., Kurtz, D., Zhang, T. Y. ELSEVIER. 2024: 2955-2956

  View details for DOI 10.1182/blood-2024-201701

  View details for Web of Science ID 001461519900048

• Development of Circulating Tumor DNA (ctDNA) for Molecular Measurable Residual Disease (MRD) in Acute Myeloid Leukemia (AML) Gunaratne, R., Zhou, C., Tai, J. W., Schwede, M., Tanaka, K., Alkaitis, M., Yin, R., Sworder, B. J., Mannis, G., Majeti, R., Khodadoust, M. S., Kurtz, D. M., Zhang, T. Y. AMER SOC HEMATOLOGY. 2023

  View details for DOI 10.1182/blood-2023-181459

  View details for Web of Science ID 001159740307053

• Comparison of History of Present Illness Summaries Generated by a Chatbot and Senior Internal Medicine Residents. JAMA internal medicine Nayak, A., Alkaitis, M. S., Nayak, K., Nikolov, M., Weinfurt, K. P., Schulman, K. 2023

  View details for DOI 10.1001/jamainternmed.2023.2561

  View details for PubMedID 37459091

• Automated NLP Extraction of Clinical Rationale for Treatment Discontinuation in Breast Cancer. JCO clinical cancer informatics Alkaitis, M. S., Agrawal, M. N., Riely, G. J., Razavi, P., Sontag, D. 2021; 5: 550-560

  Abstract

  Key oncology end points are not routinely encoded into electronic medical records (EMRs). We assessed whether natural language processing (NLP) can abstract treatment discontinuation rationale from unstructured EMR notes to estimate toxicity incidence and progression-free survival (PFS).We constructed a retrospective cohort of 6,115 patients with early-stage and 701 patients with metastatic breast cancer initiating care at Memorial Sloan Kettering Cancer Center from 2008 to 2019. Each cohort was divided into training (70%), validation (15%), and test (15%) subsets. Human abstractors identified the clinical rationale associated with treatment discontinuation events. Concatenated EMR notes were used to train high-dimensional logistic regression and convolutional neural network models. Kaplan-Meier analyses were used to compare toxicity incidence and PFS estimated by our NLP models to estimates generated by manual labeling and time-to-treatment discontinuation (TTD).Our best high-dimensional logistic regression models identified toxicity events in early-stage patients with an area under the curve of the receiver-operator characteristic of 0.857 ± 0.014 (standard deviation) and progression events in metastatic patients with an area under the curve of 0.752 ± 0.027 (standard deviation). NLP-extracted toxicity incidence and PFS curves were not significantly different from manually extracted curves (P = .95 and P = .67, respectively). By contrast, TTD overestimated toxicity in early-stage patients (P < .001) and underestimated PFS in metastatic patients (P < .001). Additionally, we tested an extrapolation approach in which 20% of the metastatic cohort were labeled manually, and NLP algorithms were used to abstract the remaining 80%. This extrapolated outcomes approach resolved PFS differences between receptor subtypes (P < .001 for hormone receptor+/human epidermal growth factor receptor 2- v human epidermal growth factor receptor 2+ v triple-negative) that could not be resolved with TTD.NLP models are capable of abstracting treatment discontinuation rationale with minimal manual labeling.

  View details for DOI 10.1200/CCI.20.00139

  View details for PubMedID 33989016

  View details for PubMedCentralID PMC8462597

• Recoupling the cardiac nitric oxide synthases: tetrahydrobiopterin synthesis and recycling. Current heart failure reports Alkaitis, M. S., Crabtree, M. J. 2012; 9 (3): 200-10

  Abstract

  Nitric oxide (NO), a key regulator of cardiovascular function, is synthesized from L-arginine and oxygen by the enzyme nitric oxide synthase (NOS). This reaction requires tetrahydrobiopterin (BH4) as a cofactor. BH4 is synthesized from guanosine triphosphate (GTP) by GTP cyclohydrolase I (GTPCH) and recycled from 7,8-dihydrobiopterin (BH2) by dihydrofolate reductase. Under conditions of low BH4 bioavailability relative to NOS or BH2, oxygen activation is "uncoupled" from L-arginine oxidation, and NOS produces superoxide (O (2) (-) ) instead of NO. NOS-derived superoxide reacts with NO to produce peroxynitrite (ONOO(-)), a highly reactive anion that rapidly oxidizes BH4 and propagates NOS uncoupling. BH4 depletion and NOS uncoupling contribute to overload-induced heart failure, hypertension, ischemia/reperfusion injury, and atrial fibrillation. L-arginine depletion, methylarginine accumulation, and S-glutathionylation of NOS also promote uncoupling. Recoupling NOS is a promising approach to treating myocardial and vascular dysfunction associated with heart failure.

  View details for DOI 10.1007/s11897-012-0097-5

  View details for PubMedID 22711313

  View details for PubMedCentralID PMC3406312