BTK inhibition sensitizes acute lymphoblastic leukemia to asparaginase by suppressing the amino acid response pathway.

Asparaginase (ASNase) therapy has been a mainstay of acute lymphoblastic leukemia (ALL) protocols for decades and shows promise in the treatment of a variety of other cancers. To improve the efficacy of ASNase treatment, we used a CRISPR/Cas9-based screen to identify actionable signaling intermediates that improve the response to ASNase. Both genetic inactivation of Bruton's tyrosine kinase (BTK) and pharmacological inhibition by the BTK inhibitor ibrutinib strongly synergize with ASNase by inhibiting the amino acid response pathway, a mechanism involving c-Myc-mediated suppression of GCN2 activity. This synthetic lethal interaction was observed in 90% of patient-derived xenografts, regardless of the genomic subtype. Moreover, ibrutinib substantially improved ASNase treatment response in a murine PDX model. Hence, ibrutinib may be used to enhance the clinical efficacy of ASNase in ALL. This trial was registered at www.clinicaltrials.gov as # NCT02884453.

Heat shock factor 1 (HSF1-pSer326) predicts response to bortezomib-containing chemotherapy in pediatric AML: a COG report.

Bortezomib (BTZ) was recently evaluated in a randomized phase 3 clinical trial by the Children's Oncology Group (COG) that compared standard chemotherapy (cytarabine, daunorubicin, and etoposide [ADE]) vs standard therapy with BTZ (ADEB) for de novo pediatric acute myeloid leukemia (AML). Although the study concluded that BTZ did not improve outcome overall, we examined patient subgroups benefiting from BTZ-containing chemotherapy using proteomic analyses. The proteasome inhibitor BTZ disrupts protein homeostasis and activates cytoprotective heat shock responses. Total heat shock factor 1 (HSF1) and phosphorylated HSF1 (HSF1-pSer326) were measured in leukemic cells from 483 pediatric patients using reverse phase protein arrays. HSF1-pSer326 phosphorylation was significantly lower in pediatric AML compared with CD34+ nonmalignant cells. We identified a strong correlation between HSF1-pSer326 expression and BTZ sensitivity. BTZ significantly improved outcome of patients with low-HSF1-pSer326 with a 5-year event-free survival of 44% (ADE) vs 67% for low-HSF1-pSer326 treated with ADEB (P = .019). To determine the effect of HSF1 expression on BTZ potency in vitro, cell viability with HSF1 gene variants that mimicked phosphorylated (S326A) and nonphosphorylated (S326E) HSF1-pSer326 were examined. Those with increased HSF1 phosphorylation showed clear resistance to BTZ vs those with wild-type or reduced HSF1-phosphorylation. We hypothesize that HSF1-pSer326 expression could identify patients who benefit from BTZ-containing chemotherapy.

Prognostication of DNA Damage Response Protein Expression Patterns in Chronic Lymphocytic Leukemia.

Proteomic DNA Damage Repair (DDR) expression patterns in Chronic Lymphocytic Leukemia were characterized by quantifying and clustering 24 total and phosphorylated DDR proteins. Overall, three protein expression patterns (C1-C3) were identified and were associated as an independent predictor of distinct patient overall survival outcomes. Patients within clusters C1 and C2 had poorer survival outcomes and responses to fludarabine, cyclophosphamide, and rituxan chemotherapy compared to patients within cluster C3. However, DDR protein expression patterns were not prognostic in more modern therapies with BCL2 inhibitors or a BTK/PI3K inhibitor. Individually, nine of the DDR proteins were prognostic for predicting overall survival and/or time to first treatment. When looking for other proteins that may be associated with or influenced by DDR expression patterns, our differential expression analysis found that cell cycle and adhesion proteins were lower in clusters compared to normal CD19 controls. In addition, cluster C3 had a lower expression of MAPK proteins compared to the poor prognostic patient clusters thus implying a potential regulatory connection between adhesion, cell cycle, MAPK, and DDR signaling in CLL. Thus, assessing the proteomic expression of DNA damage proteins in CLL provided novel insights for deciphering influences on patient outcomes and expanded our understanding of the potential complexities and effects of DDR cell signaling.

DNA Damage Response-Related Proteins Are Prognostic for Outcome in Both Adult and Pediatric Acute Myelogenous Leukemia Patients: Samples from Adults and from Children Enrolled in a Children's Oncology Group Study.

The survival of malignant leukemic cells is dependent on DNA damage repair (DDR) signaling. Reverse Phase Protein Array (RPPA) data sets were assembled using diagnostic samples from 810 adult and 500 pediatric acute myelogenous leukemia (AML) patients and were probed with 412 and 296 strictly validated antibodies, respectively, including those detecting the expression of proteins directly involved in DDR. Unbiased hierarchical clustering identified strong recurrent DDR protein expression patterns in both adult and pediatric AML. Globally, DDR expression was associated with gene mutational statuses and was prognostic for outcomes including overall survival (OS), relapse rate, and remission duration (RD). In adult patients, seven DDR proteins were individually prognostic for either RD or OS. When DDR proteins were analyzed together with DDR-related proteins operating in diverse cellular signaling pathways, these expanded groupings were also highly prognostic for OS. Analysis of patients treated with either conventional chemotherapy or venetoclax combined with a hypomethylating agent revealed protein clusters that differentially predicted favorable from unfavorable prognoses within each therapy cohort. Collectively, this investigation provides insight into variable DDR pathway activation in AML and may help direct future individualized DDR-targeted therapies in AML patients.

Reverse Phase Protein Array Profiling Identifies Recurrent Protein Expression Patterns of DNA Damage-Related Proteins across Acute and Chronic Leukemia: Samples from Adults and the Children's Oncology Group.

DNA damage response (DNADR) recognition and repair (DDR) pathways affect carcinogenesis and therapy responsiveness in cancers, including leukemia. We measured protein expression levels of 16 DNADR and DDR proteins using the Reverse Phase Protein Array methodology in acute myeloid (AML) (n = 1310), T-cell acute lymphoblastic leukemia (T-ALL) (n = 361) and chronic lymphocytic leukemia (CLL) (n = 795) cases. Clustering analysis identified five protein expression clusters; three were unique compared to normal CD34+ cells. Individual protein expression differed by disease for 14/16 proteins, with five highest in CLL and nine in T-ALL, and by age in T-ALL and AML (six and eleven proteins, respectively), but not CLL (n = 0). Most (96%) of the CLL cases clustered in one cluster; the other 4% were characterized by higher frequencies of deletion 13q and 17p, and fared poorly (p < 0.001). T-ALL predominated in C1 and AML in C5, but both occurred in all four acute-dominated clusters. Protein clusters showed similar implications for survival and remission duration in pediatric and adult T-ALL and AML populations, with C5 doing best in all. In summary, DNADR and DDR protein expression was abnormal in leukemia and formed recurrent clusters that were shared across the leukemias with shared prognostic implications across diseases, and individual proteins showed age- and disease-related differences.

Clinical relevance of proteomic profiling in de novo pediatric acute myeloid leukemia: a Children's Oncology Group study.

Pediatric acute myeloid leukemia (AML) remains a fatal disease for at least 30% of patients, stressing the need for improved therapies and better risk stratification. As proteins are the unifying feature of (epi)genetic and environmental alterations, and are often targeted by novel chemotherapeutic agents, we studied the proteomic landscape of pediatric AML. Protein expression and activation levels were measured in 500 bulk leukemic patients' samples and 30 control CD34+ cell samples, using reverse phase protein arrays with 296 strictly validated antibodies. The multistep MetaGalaxy analysis methodology was applied and identified nine protein expression signatures (PrSIG), based on strong recurrent protein expression patterns. PrSIG were associated with cytogenetics and mutational state, and with favorable or unfavorable prognosis. Analysis based on treatment (i.e., ADE vs. ADE plus bortezomib) identified three PrSIG that did better with ADE plus bortezomib than with ADE alone. When PrSIG were studied in the context of cytogenetic risk groups, PrSIG were independently prognostic after multivariate analysis, suggesting a potential value for proteomics in combination with current classification systems. Proteins with universally increased (n=7) or decreased (n=17) expression were observed across PrSIG. Certain proteins significantly differentially expressed from normal could be identified, forming a hypothetical platform for personalized medicine.

Reverse phase protein arrays in acute leukemia: investigative and methodological challenges.

INTRODUCTION: Acute leukemia results from a series of mutational events that alter cell growth and proliferation. Mutations result in protein changes that orchestrate growth alterations characteristic of leukemia. Proteomics is a methodology appropriate for study of protein changes found in leukemia. The high-throughput reverse phase protein array (RPPA) technology is particularly well-suited for the assessment of protein changes in samples derived from clinical trials. AREAS COVERED: This review discusses the technical, methodological, and analytical issues related to the successful development of acute leukemia RPPAs. EXPERT COMMENTARY: To obtain representative protein sample lysates, samples should be prepared from freshly collected blood or bone marrow material. Variables such as sample shipment, transit time, and holding temperature only have minimal effects on protein expression. CellSave preservation tubes are preferred for cells collected after exposure to chemotherapy, and incorporation of standardized guidelines for antibody validation is recommended. A more systematic biological approach to analyze protein expression is desired, searching for recurrent patterns of protein expression that allow classification of patients into risk groups, or groups of patients that may be treated similarly. Comparing RPPA protein analysis between cell lines and primary samples shows that cell lines are not representative of patient proteomic patterns.

Antibody Screening.

Antibodies are among the most frequently used tools in research and have had a profound impact on the discovery of diagnostic and therapeutic targets and the understanding of the molecular background of diseases. In particular in reverse phase protein arrays (RPPA), where there is no separation of the proteins according to molecular weight, it is crucial that antibodies are proven to be highly specific, selective, and reproducible. However, numerous studies have shown that many antibodies frequently do not recognize the protein that they are supposed to detect, that multiple antibodies do often function in one application but not in another, and that antibodies are not stable over time or between different batches. So far, no universally accepted guidelines or standardized methods for determining the validity of antibodies have been established. This chapter discusses the urgent need for antibody validation, current strategies that are used for (RPPA) antibody validation, as well as proposes a new strategy about how to report, score, and integrate antibody validation from multiple users.

Histone Modification Patterns Using RPPA-Based Profiling Predict Outcome in Acute Myeloid Leukemia Patients.

Posttranslational histone tail modifications are known to play a role in leukemogenesis and are therapeutic targets. A global analysis of the level and patterns of expression of multiple histone-modifying proteins (HMP) in acute myeloid leukemia (AML) and the effect of different patterns of expression on outcome and prognosis has not been investigated in AML patients. Here we analyzed 20 HMP by reverse phase protein array (RPPA) in a cohort of 205 newly diagnosed AML patients. Protein levels were correlated with patient and disease characteristics, including survival and mutational state. We identified different protein clusters characterized by higher (more on) or lower (more off) expression of HMP, relative to normal CD34+ cells. On state of HMP was associated with poorer outcome compared to normal-like and a more off state. FLT3 mutated AML patients were significantly overrepresented in the more on state. DNA methylation related mutations showed no correlation with the different HMP states. In this study, we demonstrate for the first time that HMP form recurrent patterns of expression and that these significantly correlate with survival in newly diagnosed AML patients.

Shining a light on cell signaling in leukemia through proteomics: relevance for the clinic.

INTRODUCTION: Although cure rates for acute leukemia have steadily improved over the past decades, leukemia remains a deadly disease. Enhanced risk stratification and new therapies are needed to improve outcome. Extensive genetic analyses have identified many mutations that contribute to the development of leukemia. However, most mutations occur infrequently and most gene alterations have been difficult to target. Most patients have more than one driver mutation in combination with secondary mutations, that result in a leukemic transformation via the alteration of proteins. The proteomics of acute leukemia could more directly identify proteins to facilitate risk stratification, predict chemoresistance and aid selection of therapy. Areas covered: This review discusses aberrantly expressed proteins identified by mass spectrometry and reverse phase protein arrays and their relationship to survival. In addition, we will discuss proteins in the context of functionally related protein groups. Expert commentary: Proteomics is a powerful tool to analyze protein abundance and functional alterations simultaneously for large numbers of patients. In the forthcoming years, validation of tools to quickly assess protein levels to enable routine rapid profiling of proteins with differential abundance and functional activation may be used as adjuncts to aid in therapy selection and to provide additional prognostic insights.

A Novel Subtype of Acquired Generalized Lipodystrophy Associated With Subcutaneous Panniculitis-Like T-cell Lymphoma.

Acquired generalized lipodystrophy (AGL) is an extremely rare disease that is characterized by loss of body fat affecting nearly all parts of the body. It is often associated with autoimmune diseases or panniculitis, whereas in other patients the underlying etiology is unclear. We report a 52-year-old male individual who was diagnosed with subcutaneous panniculitis-like T-cell lymphoma (SPTCL) that spontaneously went into remission. Years later he developed new subcutaneous nodules most concerning for relapse SPTCL or lupus panniculitis, followed by onset of hemophagocytic lymphohistiocytosis (HLH) that was treated with allogeneic stem cell transplantation. Notably, around the same time, he also developed generalized subcutaneous fat loss of both upper and lower extremities, chest, abdomen, and face that persisted after treatment of the HLH. Whole exome sequencing was performed to search for pathogenic variants that are associated with SPTCL, including those in hepatitis A virus cellular receptor 2 (HAVCR2), but did not detect any potential disease-causing variant. Our report brings to the attention a novel subtype of panniculitis-variety of AGL. Whether generalized loss of subcutaneous fat in this patient is due to lymphoma-associated panniculitis or due to development of adipose tissue-directed autoantibodies as a paraneoplastic "autoimmune" manifestation of SPTCL remains unclear.

Early-onset diabetes mellitus as a presenting feature of Werner's syndrome in an Indian family.

BACKGROUND: Diabetes mellitus (DM) in children and adolescents is typically caused by type 1 DM, followed by type 2 DM and maturity-onset diabetes of the young (MODY). We report an unusual Asian Indian family in which three members presented with DM at ages 15, 20, and 30, but not fitting the typical clinical picture of type 1 DM, type 2 DM, or MODY. The primary objective was to elucidate the molecular genetic basis of DM in this family. METHODS: The proband, a 22-year-old man, had short stature, gray hair, osteoporosis, and markedly reduced subcutaneous fat on the body, especially on the extremities along with acanthosis nigricans, and developed myxoid malignant peripheral nerve sheath tumor. Detailed family history revealed multiple loops of consanguinity. The proband underwent whole-genome sequencing, and seven relatives underwent whole-exome sequencing. RESULTS: The proband and three additional family members were found to have the homozygous c.561A>G nucleotide variant of WRN RecQ-like helicase (WRN) gene consistent with the diagnosis of Werner's syndrome. The c.561A>G variant induces a new splicing site on exon 6 resulting in a truncated WRN protein, p.Lys187Trpfs*13. CONCLUSION: Our report brings to attention the onset of DM during childhood or early adulthood in patients with Werner's syndrome who typically develop type 2 DM around the age of 30-40 years. Presence of consanguinity among parents, dysmorphic features, and malignancy should prompt consideration of diagnosis of Werner's syndrome.

Once-weekly versus twice-weekly bortezomib in newly diagnosed multiple myeloma: a real-world analysis.

Induction regimens for multiple myeloma (MM) commonly include bortezomib, which has typically been administered twice weekly despite studies demonstrating comparable efficacy and less peripheral neuropathy (PN) with once-weekly bortezomib. We aimed to analyze the real-world prevalence and efficacy of once-weekly versus twice-weekly bortezomib regimens in newly diagnosed MM. We analyzed 2497 US patients aged 18-70 years treated with commercial first-line bortezomib using nationwide Flatiron Health electronic health record-derived data, including 910 (36.4%) patients who received twice-weekly and 1522 (63.2%) who received once-weekly bortezomib. Once-weekly bortezomib use increased over time, from 57.7% in 2017 to 73.1% in 2022. Multivariate analysis identified worsened performance status and more recent year of diagnosis with higher odds of receiving once-weekly bortezomib. Real-world progression-free survival (median 37.2 months with once-weekly versus 39.6 months with twice-weekly, p = 0.906) and overall survival (medians not reached in either cohort, p = 0.800) were comparable. PN rates were higher in patients receiving twice-weekly bortezomib (34.7% versus 18.5%, p < 0.001). In conclusion, once-weekly bortezomib is clearly associated with similar efficacy and fewer toxicities compared to twice-weekly bortezomib. Our findings support once-weekly bortezomib as a standard-of-care regimen for newly diagnosed patients with MM.

Chromatin Profiles Are Prognostic of Clinical Response to Bortezomib-Containing Chemotherapy in Pediatric Acute Myeloid Leukemia: Results from the COG AAML1031 Trial.

The addition of the proteasome inhibitor bortezomib to standard chemotherapy did not improve survival in pediatric acute myeloid leukemia (AML) when all patients were analyzed as a group in the Children's Oncology Group phase 3 trial AAML1031 (NCT01371981). Proteasome inhibition influences the chromatin landscape and proteostasis, and we hypothesized that baseline proteomic analysis of histone- and chromatin-modifying enzymes (HMEs) would identify AML subgroups that benefitted from bortezomib addition. A proteomic profile of 483 patients treated with AAML1031 chemotherapy was generated using a reverse-phase protein array. A relatively high expression of 16 HME was associated with lower EFS and higher 3-year relapse risk after AML standard treatment compared to low expressions (52% vs. 29%, p = 0.005). The high-HME profile correlated with more transposase-accessible chromatin, as demonstrated via ATAC-sequencing, and the bortezomib addition improved the 3-year overall survival compared with standard therapy (62% vs. 75%, p = 0.033). These data suggest that there are pediatric AML populations that respond well to bortezomib-containing chemotherapy.

Beat-AML 2024 ELN-refined risk stratification for older adults with newly diagnosed AML given lower-intensity therapy.

ABSTRACT: Although the 2022 European LeukemiaNet (ELN) acute myeloid leukemia (AML) risk classification reliably predicts outcomes in younger patients treated with intensive chemotherapy, it is unclear whether it applies to adults ≥60 years treated with lower-intensity treatment (LIT). We aimed to test the prognostic impact of ELN risk in patients with newly diagnosed (ND) AML aged ≥60 years given LIT and to further refine risk stratification for these patients. A total of 595 patients were included: 11% had favorable-, 11% intermediate-, and 78% had adverse-risk AML. ELN risk was prognostic for overall survival (OS) (P < .001) but did not stratify favorable- from intermediate-risk (P = .71). Within adverse-risk AML, the impact of additional molecular abnormalities was further evaluated. Multivariable analysis was performed on a training set (n = 316) and identified IDH2 mutation as an independent favorable prognostic factor, and KRAS, MLL2, and TP53 mutations as unfavorable (P < .05). A "mutation score" was calculated for each combination of these mutations, assigning adverse-risk patients to 2 risk groups: -1 to 0 points ("Beat-AML intermediate") vs 1+ points ("Beat-AML adverse"). In the final refined risk classification, ELN favorable- and intermediate-risk were combined into a newly defined "Beat-AML favorable-risk" group, in addition to mutation scoring within the ELN adverse-risk group. This approach redefines risk for older patients with ND AML and proposes refined Beat-AML risk groups with improved discrimination for OS (2-year OS, 48% vs 33% vs 11%, respectively; P < .001), providing patients and providers additional information for treatment decision-making.

Molecular Drivers of Myelodysplastic Neoplasms (MDS)-Classification and Prognostic Relevance.

Myelodysplastic neoplasms (MDS) form a broad spectrum of clonal myeloid malignancies arising from hematopoietic stem cells that are characterized by progressive and refractory cytopenia and morphological dysplasia. Recent advances in unraveling the underlying pathogenesis of MDS have led to the identification of molecular drivers and secondary genetic events. With the overall goal of classifying patients into relevant disease entities that can aid to predict clinical outcomes and make therapeutic decisions, several MDS classification models (e.g., French-American-British, World Health Organization, and International Consensus Classification) as well as prognostication models (e.g., International Prognostic Scoring system (IPSS), the revised IPSS (IPSS-R), and the molecular IPSS (IPSS-M)), have been developed. The IPSS-M is the first model that incorporates molecular data for individual genes and facilitates better prediction of clinical outcome parameters compared to older versions of this model (i.e., overall survival, disease progression, and leukemia-free survival). Comprehensive classification and accurate risk prediction largely depend on the integration of genetic mutations that drive the disease, which is crucial to improve the diagnostic work-up, guide treatment decision making, and direct novel therapeutic options. In this review, we summarize the most common cytogenetic and genomic drivers of MDS and how they impact MDS prognosis and treatment decisions.

Long-term outcome of progressive multifocal leukoencephalopathy with recombinant interleukin-2 treatment and an associated increase in the number of HPyV-2-specific T-cells: a case report.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease caused by reactivation of the human polyomavirus 2 (HPyV-2). PML is associated with a high morbidity and mortality rate and there is currently no standard curative therapy. We report short-term immunologic response and long-term clinical outcomes in a patient diagnosed with follicular lymphoma (FL) who developed PML. Diagnosis of PML was established conclusively based on findings from a brain biopsy. The patient was treated with recombinant interleukin 2 (IL-2) and showed rapid clinical improvement. HPyV-2-specific T-cells were tracked longitudinally and correlation with clinical status, viral load, and radiographic imaging was documented. After the progression of the patient's FL, which required an allogeneic bone marrow transplant, the patient prophylactically received human leukocyte antigen-matched donor-derived HPyV-2 T-cells to prevent the recurrence of the PML as part of a clinical trial. Twelve years after the initial diagnosis of PML, he did not develop a relapse of his PML, supporting data that therapies that increase HPyV-2-specific T-cells, including IL-2, may be effective in the management of PML.

Real-world outcomes of frontline venetoclax-based therapy in older adults with acute myeloid leukemia: an analysis utilizing EHR data.

Venetoclax (VEN) in combination with hypomethylating agents (HMA) or low-dose cytarabine has become the standard of care for patients with acute myeloid leukemia (AML) who are ineligible to receive intensive induction chemotherapy. Clinical trials are performed in a controlled setting that can be difficult to emulate in the real world. We sought to investigate outcomes of patients treated with VEN-based therapy in the real world. Patients with an age of ≥65 years who received frontline VEN-based therapy were identified using the COTA database (n = 112). The majority of patients (91%) were treated in the community setting and had adverse-risk AML (63%). The real-world overall response rate (rwORR) was 55% with a median real-world overall survival (rwOS) of 13 months after VEN/HMA. The rwORR was lower and median rwOS was shorter than those reported in the VIALE-A trial, underscoring the importance of studying novel therapies using real-world data.

Post-transplant cyclophosphamide and early mixed donor Chimerism in myeloid malignancies; a single-center experience.

BACKGROUND: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the only curative option for high-risk myeloid malignancies. Post-transplant cyclophosphamide (PT-Cy) has proven to be effective for graft versus host disease (GVHD) prophylaxis. Given that graft-versus-tumor (GVT) effect plays a major role in reducing the risk of disease relapse, the application of PT-Cy must balance the risk of relapse. Mixed chimerism (MC) refers to a state of concurrent presence of recipient and donor cells post allo-HSCT which may precede relapse disease. OBJECTIVE: We investigated the impact of PT-Cy on early MC (EMC) and disease relapse in patients with a myeloid malignancy post allo-HSCT. STUDY DESIGN: This retrospective single-center study included patients that underwent allo-HSCT between 2015 and 2021. Patient and disease characteristics were collected from the electronic health records. EMC was defined as <95% donor cells at day 90-120 post allo-HSCT. RESULTS: A total of 144 patient that received an allo-HSCT were included in the study. One hundred and eight (75%) patients received PT-Cy as part of the GVHD prophylaxis regimen. The majority underwent allo-HSCT for acute myeloid leukemia (62%) or myelodysplastic syndrome (31%). Sixty-five percent received allo-HSCT from a matched unrelated donor transplant and 65% received a myeloablative conditioning regimen. A lower rate of chronic GVHD (p = 0.03) and a higher rate of EMC (p = 0.04) were observed in patients that received PT-Cy. PT-Cy was not associated with overall survival (OS) and relapse-free survival (RFS). Multivariable analysis identified measurable residual disease status (p = 0.003), hematopoietic cell transplantation-specific comorbidity index (p = 0.012) and chronic GVHD (p = 0.006) as independent prognostic variables for OS. AML-adverse risk (p = 0.004) and EMC (p = 0.018) were independently prognostic for RFS. While EMC overall was not significantly associated with higher risk of relapse, EMC was associated with shorter RFS within adverse-risk AML patients. CONCLUSION: Our study shows that PT-Cy was associated with an increased risk of EMC. The predictive value of EMC for relapse remains unclear and may depend on the underlying disease, which should be validated in a larger cohort.

SARS-CoV-2 Vaccination IgG Antibody Responses in Patients with Hematologic Malignancies in a Myeloid Enriched Cohort: A Single Center Observation.

OBJECTIVE: Patients diagnosed with hematologic malignancies are at increased risk for severe SARS-CoV-2 infection. We evaluated the serological IgG response following two doses of the SARS-CoV-2 vaccine in patients with hematologic malignancies. METHODS: Patients treated at UT Southwestern Medical Center with a diagnosis of a myeloid or lymphoid neoplasm were included. SARS-CoV-2 vaccination response was defined as a positive quantifiable spike IgG antibody titer. RESULTS: Sixty patients were included in the study and 60% were diagnosed with a myeloid neoplasm. The majority (85%) of the patients with a myeloid malignancy and 50% of the patients with a lymphoid malignancy mounted a serological response after receiving two doses of the vaccine. CONCLUSION: Vaccination should be offered irrespective of ongoing treatment or active disease. Findings require validation in a larger cohort of patients.