Non-hematologic Malignancies Research Articles

Incidence, risk factors, and outcomes of patients with monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia who develop venous thromboembolism

BackgroundThe incidence, risk factors, and outcomes of venous thromboembolism (VTE) in patients with chronic lymphocytic leukemia (CLL) and monoclonal B-cell lymphocytosis (MBL) are not well described. ObjectivesWe aimed to determine the clinical characteristics, risk factors, and outcomes of incident VTE in patients with newly diagnosed MBL/CLL and compare the incidence to the age- and sex-matched general population. MethodsUsing the Mayo Clinic CLL Database, we identified 946 patients with newly diagnosed MBL/CLL between 1998 and 2021. Incidence of VTE was identified by querying the electronic health record for VTE-specific International Classification of Diseases-9 and -10 codes and reviewing results of radiographic studies. ResultsEighty patients developed VTE. The incidence of VTE in patients with newly diagnosed MBL/CLL was ∼1% per year. In multivariable analyses, prior history of VTE (hazard ratio [HR]: 5.33; 95% CI: 1.93-14.68, P = .001) and high/very high-risk CLL-International Prognostic Index score (HR: 2.63; 95% CI: 1.31-5.26; P = .006) were associated with an increased risk of VTE; receipt of CLL treatment or occurrence of nonhematologic malignancy was not. Development of VTE was associated with shorter overall survival (HR: 1.82, 95% CI: 1.30-2.55) after adjusting for age, sex, prior history of VTE, and Rai stage. The age- and sex-adjusted VTE incidence rate for patients with MBL/CLL and no prior history of VTE (n = 904) was 1254 per 100 000 person-years compared with 204 per 100 000 person-years in the general population, reflecting a 5.9-fold increase. ConclusionOur study demonstrates a 6-fold increased risk of VTE in patients with MBL/CLL compared with the age- and sex-matched general population.

A Review of the Prognostic Significance of Neutrophil-to-Lymphocyte Ratio in Nonhematologic Malignancies.

Biomarkers are crucial in cancer diagnostics, prognosis, and surveillance. Extensive research has been dedicated to identifying biomarkers that are broadly applicable across multiple cancer types and can be easily obtained from routine investigations such as blood cell counts. One such biomarker, the neutrophil-to-lymphocyte ratio (NLR), has been established as a prognostic marker in cancer. However, due to the dynamic nature of cancer diagnosis and treatment, periodic updates are necessary to keep abreast of the vast amount of published data. In this review, we searched the PubMed database and analyzed and synthesized recent literature (2018-February 2024) on the role of NLR in predicting clinical outcomes in nonhematologic malignancies. The search was conducted using the PubMed database. We included a total of 88 studies, encompassing 28,050 human subjects, and categorized the findings into four major groups: gastrointestinal cancer, cancers of the urinary tract and reproductive system, lung cancer, and breast cancer. Our analysis confirms that NLR is a reliable prognostic indicator in cancer, and we discuss the specific characteristics, limitations, and exceptions associated with its use. The review concludes with a concise Q&A section, presenting the most relevant take-home messages in response to five key practical questions on this topic.

Bone marrow disease profile in geriatric patients: An institutional study

For the diagnosis and treatment of numerous hematological and non-hematological disorders in patients of all ages, a bone marrow examination is a crucial investigation. Due to the growing elderly population and the paucity of published studies on bone marrow disorders that only affect the elderly, age-related health conditions are becoming more prevalent. In our study, we enrolled elderly patients >60 years old who had a bone marrow examination at GMC Jammu's pathology department.: To study the profile of various hematological and non-hematological lesions diagnosed on Bone Marrow aspiration and/or Trephine biopsy in Geriatric age group 2. To summarize an approach for evaluation of anemia in elderly patients for better management.: The study was conducted in two parts; a Retrospective study for 4 years and a prospective study of 1 year. It included all the patients >60 years of age who had undergone Bone marrow examination in the hematology section of the Department of Pathology.: 200 bone marrow aspirations and 40 trephine biopsies, as well as peripheral blood smears and biopsy imprint smears, were all examined. Aplastic anemia, Megaloblastic anemia, Iron deficiency anemia, chronic disease-related anemia, and ITP were among the non-malignant hematological disorders that affected 50.5% (n=101) of the patients; various hematological malignancies affected 40.5% (n=81) of the patients; and non-hematological malignancies affected 1% (n=2) of the patients. 1% (n=2) of the cases were insufficient, and 7% (n=14) of the cases in which BMA and/or BMB were used for lymphoma staging and follow-up did not show any signs of marrow infiltration. With the growing elderly population in India, it is important to pay more attention to diagnosing and treating easily treatable conditions like anemia as well as enhancing the general health of geriatric patients the elderly, bone marrow aspiration.

Policy and perspective on outpatient programs for autologous hematopoietic cell transplantation and immune-effector cell therapy administration.

High-dose chemotherapy with autologous hematopoietic cell transplantation (AutoHCT) has long been an integral treatment modality for multiple myeloma and non-Hodgkin lymphoma. Over the past 25 years, numerous institutions have shifted this practice from requiring hospitalization to one that can be performed in an ambulatory setting, resulting in cost savings and improved quality of life for patients. The recent advent immune-effector cell (IEC) therapies and expansion of their indications is changing the treatment landscape for hematologic and non-hematologic malignancies. However, current financial models and reimbursement structures threaten the viability and sustainability of this treatment modality should it continue to require inpatient administration and management. This threat is leading institutions to develop outpatient IEC programs based off the outpatient AutoHCT templates. Integral to the success of both is a cohesive program with outpatient-specific standard operating protocols, highly-trained providers and staff with expertise specific in these treatment modalities, evidenced-based supportive care and prophylaxis plans, extensive caregiver vetting and education, and the infrastructure to support all individuals involved. In this policy and practice review we provide an overview of the guidelines and published academic experiences, give a perspective-based description of the roles and responsibilities of the individuals involved in this process at our institution, and highlight actionable recommendations that could allow for the dissemination and implementation of outpatient AutoHCT and IEC programs more broadly.

Expression and Clinical Significance of LncRNA HEIH in Patients with Acute Myeloid Leukemia

To investigate the expression and clinical significance of long noncoding RNA(lncRNA) HEIH in patients with acute myeloid leukemia (AML). 50 newly diagnosed AML patients (except M3) admitted to the First Affiliated Hospital of Bengbu Medical College from January 2019 to December 2020 were included in the study, with 30 patients with non-hematological malignancies as controls. The relative expression level of lncRNA HEIH in all patients were detected, the correlation of clinical characteristics, gene mutations, FAB classification, efficacy, prognosis and overall survival (OS) of AML patients with the expression level of lncRNA HEIH were analyzed. The expression level of lncRNA HEIH in AML patients was significantly higher than that in patients with non-hematological malignancies (P <0.01). Moreover, AML patients with high white blood cell count (WBC), CEBPA and FLT3 mutations, poor efficacy, and poor prognosis often showed higher expression of lncRNA HEIH, and patients with high lncRNA HEIH expression showed a shorter overall survival (OS). lncRNA HEIH shows an unique molecular biological significance in AML patients, which may provide a new approach for diagnosis, monitoring and targeted therapy of AML.

Stereotactic Ablative Radiation for Oligoprogressive Cancers: Results of the Randomized Phase 2 STOP Trial

This trial examined if patients with ≤5 sites of oligoprogression benefit from the addition of stereotactic ablative radiotherapy (SABR) to standard of care (SOC) systemic therapy. We enrolled patients with 1-5 metastases progressing on systemic therapy, and after stratifying by type of systemic therapy (cytotoxic vs. non-cytotoxic), randomized 1:2 between continued SOC treatment vs. SABR to all progressing lesions plus SOC. The trial was initially limited to non-small cell lung cancer but was expanded to include all non-hematologic malignancies to meet accrual goals. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), lesional control, quality of life, adverse events (AEs), and duration of systemic therapy post-randomization. Ninety patients with 127 oligoprogressive metastases were enrolled across 8 Canadian institutions, with 59 randomized to SABR and 31 to SOC. Median age was 67 years and 39 (43%) were female. The most common primary sites were lung (44%), genitourinary (23%) and breast (13%). Protocol adherence in the SOC arm was suboptimal, with 11 patients (35%) either receiving high-dose/ablative therapies (conflicting with trial protocol) or withdrawing from the study. Median follow-up was 31 months. There was no difference in PFS between arms (median PFS 8.4 months in the SABR arm vs. 4.3 months in the SOC arm but curves cross and 2-year PFS was 9% vs. 24% respectively, p=0.91). Median OS was 31.2 months vs. 27.4 months, respectively (p=0.22). Lesional control was superior with SABR (70% vs. 38% respectively, p=0.0015). There were 2 (3.4%) grade 3 and no grade 4/5 AEs attributable to SABR. SABR was well-tolerated with superior lesional control but did not improve PFS or OS. Accrual to this study was difficult, and the results may have been impacted by an unwillingness to forgo ablative treatments on the SOC arm. (NCT02756793).

Hematologic Malignancies Influence the Accuracy of Prediction of Survival in Patients With Solid Tumor Spinal Metastases Undergoing Surgery.

There is no consensus on how to identify patients with multiple-level spinal metastases who would benefit from surgery. Previous studies have revealed that patients with hematologic malignancies have a significantly longer median survival time than those with solid tumor spinal metastases. We aimed to compare predictors and survival data between patients with spinal metastases, including hematologic malignancies (all-malignancies group), with only those with nonhematologic malignancies (nonhematologic malignancies group). This single-center retrospective study included all patients age >18 years who underwent surgery to treat spinal metastases in our department from 2008 to 2018. The patients' baseline characteristics, treatment modalities, and laboratory results were analyzed. Survival was calculated from the date of surgery to the date of confirmed death. Cox regression analysis was used to identify independent predictors of survival. The study cohort comprised 186 patients with a mean age of 57.1 ± 13.4 years, 101 of whom were male and 18 of whom had hematologic malignancies. The median survival time was 201 days in the all-malignancies group and 168 days in the nonhematologic malignancies group. Independent predictors of survival differed between the two groups. Eastern Cooperative Oncology Group status and response to preoperative chemotherapy were identified as independent factors in both groups. However, radiosensitivity and CNS metastases were identified only in the all-malignancies group, and tumor growth potential, albumin status, and number of vertebrae were identified only in the nonhematologic malignancies group. The receiver operating characteristics were comparable in the two groups: 0.75 in the all-malignancies group and 0.77 in the nonhematologic malignancies group. Longer survival in patients with hematologic malignancies influences the overall prediction of survival. Tumor-specific prognostic factors may improve the prediction of survival in patients with spinal metastases.

Effect of Clonal Hematopoiesis Mutations and Canakinumab Treatment on Incidence of Solid Tumors in the CANTOS Randomized Clinical Trial.

Clonal hematopoiesis (CH) is more common in older persons and has been associated with an increased risk of hematological cancers and cardiovascular diseases. The most common CH mutations occur in the DNMT3A and TET2 genes and result in increased proinflammatory signaling. The Canakinumab Anti-inflammatory Thrombosis Outcome Study (NCT01327846) evaluated the neutralizing anti-IL1β antibody canakinumab in 10,061 randomized patients with a history of myocardial infarction and persistent inflammation; DNA samples were available from 3,923 patients for targeted genomic sequencing. We examined the incidence of non-hematological malignancy by treatment assignment and CH mutations and estimated the cumulative incidence of malignancy events during trial follow-up. Patients with TET2 mutations treated with canakinumab had the lowest incidence of non-hematological malignancy across cancer types. The cumulative incidence of at least one reported malignancy was lower for patients with TET2 mutations treated with canakinumab versus those treated with placebo. These findings support a potential role for canakinumab in cancer prevention and provide evidence of IL1β blockade cooperating with CH mutations to modify the disease course. Prevention Relevance: We reveal that administering canakinumab is associated with a decrease in non-hematological malignancies among patients with clonal hematopoiesis (CH) mutations. These findings underscore canakinumab's potential in preventing cancer and provide proof of IL1β blockade collaborating with CH mutations to enhance its clinical benefits. See related Spotlight, p. 399.

Malignancy in systemic lupus erythematosus: relation to disease characteristics in 92 patients – a single center retrospective study

ObjectiveSystemic lupus erythematosus (SLE) is a chronic autoimmune disease with a variable clinical manifestation, potentially leading to death. Importantly, patients with SLE have an increased risk of neoplastic disorders. Thus, this study aimed to comprehensively evaluate the clinical and laboratory characteristics of patients with SLE and with or without malignancy.MethodsWe conducted a retrospective analysis of medical records of 932 adult Caucasian patients with SLE treated at the University Hospital in Kraków, Poland, from 2012 to 2022. We collected demographic, clinical, and laboratory characteristics, but also treatment modalities with disease outcomes.ResultsAmong 932 patients with SLE, malignancy was documented in 92 (9.87%), with 7 (7.61%) patients experiencing more than one such complication. Non-hematologic malignancies were more prevalent (n = 77, 83.7%) than hematologic malignancies (n = 15, 16.3%). Patients with SLE and malignancy had a higher mean age of SLE onset and a longer mean disease duration than patients without malignancy (p < 0.001 and p = 0.027, respectively). The former group also presented more frequently with weight loss (odds ratio [OR] = 2.62, 95% confidence interval [CI] 1.61–4.23, p < 0.001), fatigue/weakness (OR = 2.10, 95% CI 1.22–3.77, p = 0.005), and fever (OR = 1.68, 95% CI 1.06–2.69, p = 0.024). In the malignancy-associated group, we noticed a higher prevalence of some clinical manifestations, such as pulmonary hypertension (OR = 3.47, 95% CI 1.30–8.42, p = 0.007), lung involvement (OR = 2.64, 95% CI 1.35–4.92, p = 0.003) with pleural effusion (OR = 2.39, 95% CI 1.43–3.94, p < 0.001), and anemia (OR = 2.24, 95% CI 1.29–4.38, p = 0.006). Moreover, the patients with SLE and malignancy more frequently had internal comorbidities, including peripheral arterial obliterans disease (OR = 3.89, 95% CI 1.86–7.75, p < 0.001), myocardial infarction (OR = 3.08, 95% CI 1.41–6.30, p = 0.003), heart failure (OR = 2.94, 95% CI 1.30–6.17, p = 0.005), diabetes mellitus (OR = 2.15, 95% CI 1.14–3.91, p = 0.011), hypothyroidism (OR = 2.08, 95% CI 1.29–3.34, p = 0.002), arterial hypertension (OR = 1.97, 95% CI 1.23–3.23, p = 0.003), and hypercholesterolemia (OR = 1.87, 95% CI 1.18-3.00, p = 0.006). Patients with SLE and malignancy were treated more often with aggressive immunosuppressive therapies, including cyclophosphamide (OR = 2.07, 95% CI 1.30–3.28, p = 0.002), however median cumulative cyclophosphamide dose in malignancy-associated SLE subgroup was 0 g (0–2 g). Interestingly, over a median follow-up period of 14 years (ranges: 8–22 years) a total of 47 patients with SLE died, with 16 cases (5.28%) in the malignancy-associated SLE group and 31 cases (5.73%) in the non-malignancy SLE group (p = 0.76). The most common causes of death were infections (21.28%) and SLE exacerbation (8.51%).ConclusionThe study highlights the relatively frequent presence of malignancies in patients with SLE, a phenomenon that demands oncological vigilance, especially in patients with a severe clinical course and comorbidities, to improve long-term outcomes in these patients.

Engineered T Cell Receptor for Cancer Immunotherapy.

Among the therapeutic strategies in cancer immunotherapy-such as immune-modulating antibodies, cancer vaccines, or adoptive T cell transfer-T cells have been an attractive target due to their cytotoxicity toward tumor cells and the tumor antigen-specific binding of their receptors. Leveraging the unique properties of T cells, chimeric antigen receptor-T cells and T cell receptor (TCR)-T cells were developed through genetic modification of their receptors, enhancing the specificity and effectiveness of T cell therapy. Adoptive cell transfer of chimeric antigen receptor-T cells has been successful for the treatment of hematological malignancies. To expand T cell therapy to solid tumors, T cells are modified to express defined TCR targeting tumor associated antigen, which is called TCR-T therapy. This review discusses anti-tumor T cell therapies, with a focus on engineered TCR-T cell therapy. We outline the characteristics of TCR-T cell therapy and its clinical application to non-hematological malignancies.

Gene fusions: A retrospective analysis of therapies and treatments of MTB patients over 7 years.

e15183 Background: Gene fusions (GF) are less common than single nucleotide variants, amplifications, and deletions, but have been suggested to be more predictive of responses to specific molecularly targeted therapies than other types of molecular alterations. We reviewed our institutional trends for overall survival in our molecular tumor board database based on the receipt of molecularly targeted therapy. Methods: We identified patients with non-hematologic malignancies and gene fusions (GF) identified by DNA based next generation sequencing (NGS) and reviewed by the Inova Schar Cancer Institute Molecular Tumor Board (ISCI MTB) between March 1, 2016 and March 1, 2023. GFs were confirmed by re-evaluation of next generation sequencing, and we determined the number of patients who received molecularly targeted therapy (RTT) specific for the GF. We evaluated overall survival (OS) in the RTT cohort and in the cohort that did not receive targeted therapy (NTT). TMPRSS fusions in prostate cancer were excluded from this analysis. Results: There were 93 patients with gene fusions in advanced staged cancers that met study criteria. Twenty-three were lost to follow up, transferred care outside ISCI, or enrolled in hospice. Of 70 stage IV patients reviewed, thirty-seven were found to have received GF targeted therapy. OS for all patients was 28.5 months. Patients in the RTT cohort had a median OS of 45 months and patients in the NTT cohort had an OS of 26.8 months (p-value = 0.16, Log-rank test). Conclusions: Targeted therapy in solid tumors with gene fusions is associated with prolonged overall survival. It is critical for MTBs to use NGS platforms that identify GF. Further studies examining OS and GF are warranted. [Table: see text]

Risk of Secondary Malignancies After Multiple Myeloma: A Nationwide Case-Control Cohort Study

IntroductionIn light of improved survival rates among multiple myeloma (MM) survivors, we sought to assess their risk of secondary malignancies compared to the general population. Materials and MethodsThis nationwide population-based case-control cohort study utilized the Korea National Health Insurance Service (KNHIS) database incorporating data from 2009 to 2020. We analyzed a total of 7348 patients diagnosed with MM in the case cohort. We selected a control group of 29,351 individuals from the general population without MM, employing a 1:4 propensity score matching approach. Matching criteria included age, sex, and comorbidities to ensure a balanced and reliable comparison. ResultsThe cumulative incidence of any secondary malignancy was significantly higher in the case cohort than the control cohort (Hazard ratio [HR] 1.576, 95% confidence interval [CI], [1.381-1.798]). Hematologic malignancy risk was notably higher in the case cohort (HR 8.026, 95% CI, [5.402-11.924]), especially therapy-related myeloid neoplasms (t-MN) (HR 12.063, 95% CI, [6.839-21.278]). No significant difference was shown in nonhematologic malignancy incidence. In subgroup analysis, transplant-eligible MM patients had a significantly higher incidence of any secondary malignancy (HR 1.104, 95% CI, [1.003-1.214]) than transplant-ineligible patients. The incidence of secondary malignancy in MM patients in the lenalidomide-available era was not significantly increased compared to the prelenalidomide era. ConclusionWhile hematologic malignancies, particularly t-MN, are significantly elevated in MM patients compared to general population, nonhematologic malignancies do not appear to be significantly elevated.

"God is going to help me get through this": spirituality perspectives from Hispanic adolescent and young adult cancer survivors.

Describe spirituality's role in a sample of Hispanic adolescent and young adult (AYA) cancer survivors. This phenomenology-informed convergent parallel mixed-methods study aimed to explore participants' lived experiences with hope during cancer treatments and cancer survivorship. A purposive sample of Hispanic AYAs who completed cancer treatments 2-5years ago were virtually recruited for participation. Participants completed virtual semi-structured interviews about their experiences with hope during cancer treatments and cancer survivorship and prepared narratives about their experiences. Thematic analyses were iteratively performed across the data set to identify final themes. Ten Hispanic AYA cancer survivors (mean age 30.2, SD = 4.5) years participated in this pilot study. Seven participants (70%) were female, and three participants (30%) were male. Six participants (60%) experienced non-hematologic malignancies, and four participants (40%) experienced hematologic malignancies. Eight (80%) participants' language preference was Spanish, while two (20%) participants' language preference was English. The theme spirituality and subthemes living by faith, god as a resource, and spiritual gratitude were identified as concepts participants linked to their conceptualization of hope during cancer treatment and survivorship. Hope and spirituality may be conceptually linked to coping behaviors among Hispanic AYA cancer survivors. Hope through faith may be a learned spiritual value in Hispanic AYAs and might play a role in their spiritual and cognitive development. Further research is needed to explore the potentially protective value of hope and spirituality for the Hispanic AYA population.

Long-term outcomes of peripheral blood stem cell unrelated donors mobilized with filgrastim

AbstractAllogeneic hematopoietic cell transplantation is a life-saving procedure used to treat a variety of devastating diseases. It requires hematopoietic stem cells collected via filgrastim-mobilized peripheral blood stem cells (PBSCs) or bone marrow (BM) harvest from volunteer unrelated donors (URDs). There is a paucity of safety data regarding donors’ long-term adverse events. This prospective, observational study combined PBSC donors enrolled in the NMDP Investigational New Drug trial and BM donors between 1 July 1999 and 30 September 2015. The primary objective was to describe the long-term incidence of myeloid malignancies. The secondary objectives included describing the long-term incidence of lymphoid malignancies, nonhematologic malignancies, autoimmune disorders, and thrombotic events. A total of 21 643 donors (14 530 PBSCs and 7123 BM) were included. The incidence rate of myeloid disorders per 100 000 person-years in donors of PBSCs was 2.53 (95% confidence interval [CI], 0.82-7.84) and in donors of BM, it was 4.13 (95% CI, 1.33-12.8). The incidence rate ratio of PBSCs/BM donors was 0.61 (95% CI, 0.12-3.03; P = .55). The incidence of other malignancies, autoimmunity, and thrombosis did not differ between the donor types. This comprehensive study of the long-term effects of filgrastim in URDs of PBSCs provides strong evidence that donors who receive filgrastim are not at an increased risk of these events compared with BM donors. It also provides reassurance to current donors undergoing stem cell mobilization as well as individuals considering joining stem cell registries, such as NMDP.

Safety and biological outcomes following a phase 1 trial of GD2-specific CAR-T cells in patients with GD2-positive metastatic melanoma and other solid cancers

BackgroundChimeric antigen receptor (CAR) T cell therapies specific for the CD19 and B-cell maturation antigen have become an approved standard of care worldwide for relapsed and refractory B-cell malignancies. If...

Malaria and Malignancies- A review

Introduction: Malaria, a parasitic disease caused by Plasmodium sp. is a substantial threat to global health. In recent years, the association of malignancies and malaria has been an interesting field of research. To date, Burkitt's lymphoma has shown a close association with Malaria in the sub-Saharan nations. The latest research targets the current anti-malarial medicines as a promising approach towards novel anti-cancer therapies. The complicated relationship between malaria, genetics, immune response, and cancer might help in exploring various pharmacological approaches that might help in the therapeutic approach to malaria and cancer. Further, in-depth in-vivo and in-vitro studies are needed to establish the link between malaria infection and cancer progression. Aims and Objectives: This review aims to explore the key associations of malaria and various malignancies and the possible anti-cancer effects of anti-malarial drugs. Materials and Methods: A critical review of 53 articles from 1987 to 2023 was conducted. Conclusion: • Endemic Burkitt's lymphoma shows a synergy with malaria, but more studies are needed to explore, for correlating the possible associations of malaria with other malignancies. • Non-hematological malignancies were shown not to have a strong correlation with malaria. • Anti-malarial drugs displaying anti-cancer properties could be a promising adjunct to current routine cancer treatment

Outcome of Cancer Patients with an Unplanned Intensive Care Unit Admission: Predictors of Mortality and Long-term Survival.

Understanding the characteristics and outcomes of cancer patients with unplanned ICU admission is imperative for therapeutic decisions and prognostication purposes. To describe the clinical characteristics of patients with hematological and non-hematological malignancies (NHM) who require unplanned ICU admission and to determine the predictors of mortality and long-term survival. This retrospective study included all patients with cancer who had an unplanned ICU admission between 2011 and 2016 at a tertiary hospital in Saudi Arabia. The following variables were collected: age, gender, ICU length of stay (LOS), APACHE II score, type of malignancy, febrile neutropenia, source and time of admission, and need for mechanical ventilation (MV), renal replacement therapy (RRT), and treatment with vasopressors (VP). Predictors of mortality and survival rates at 28 days and 3, 6, and 12 months were calculated. The study included 410 cancer patients with 466 unplanned ICU admissions. Of these, 52% had NHM. The average LOS in the ICU was 9.6 days and the mean APACHE score was 21.9. MV was needed in 73% of the patients, RRT in 15%, and VP in 24%, while febrile neutropenia was present in 24%. There were statistically significant differences between survivors and non-survivors in the APACHE II score (17.7 ± 8.0 vs. 25.6 ± 9.2), MV use (52% vs. 92%), need for RRT (6% vs. 23%), VP use (42% vs. 85%), and presence of febrile neutropenia (18% vs. 30%). The predictors of mortality were need for MV (OR = 4.97), VP (OR = 3.43), RRT (OR = 3.31), and APACHE II score (OR = 1.10). Survival rates at 28 days, 3, 6, and 12 months were 52%, 28%, 22%, and 15%, respectively. The survival rate of cancer patients with an unplanned admission to the ICU remains low. Predictors of mortality include need for MV, RRT, and VP and presence of febrile neutropenia. About 85% of cancer patients died within 1 year after ICU admission.

Abstract 7450: The impact of prior history of non-hematologic malignancies on time to first treatment and overall survival among individuals with CLL or MBL

Abstract Background: The impact of a prior history of non-hematologic malignancy (NHM) on clinical outcomes among individuals with newly diagnosed chronic lymphocytic leukemia (CLL) or monoclonal B-cell lymphocytosis (MBL), the precursor to CLL, is not well known. Methods: In this prospective study, we identified individuals with CLL/MBL who were seen in the Division of Hematology at the Mayo Clinic, Rochester. Participants provided consent within nine months of diagnosis, had no prior history of hematological malignancy, and completed a self-reported risk-factor questionnaire, including a prior history of NHM. Time to first treatment (TTFT) was defined as the time between the date of diagnosis and the earliest date of the first CLL treatment, death, or the last known treatment-free follow-up date. Overall survival (OS) was defined as the time from diagnosis to death or the last follow-up. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between a prior history of a NHM with OS and TTFT. We adjusted for sex and the CLL International Prognostic Index (CLL-IPI), a score comprised of five key CLL prognostic factors, including age and Rai stage. Results: Among the 1,090 CLL/MBL individuals, 833 (76%) had CLL. The median age at diagnosis was 64 years (range 24-89), with 65% being men, and 230 (21%) reported a prior history of NHM. The most common tumor was non-melanoma skin cancer (NMSC, 8.9%, 96 individuals), followed by prostate, testicular, and penile tumors (7.3%, 51 individuals), and melanoma (1.9%, 20 individuals). CLL/MBL patients with a prior history of a NHM were more likely to be over 65 years old (29%) than under 65 years old (14%, p &amp;lt; 0.0001). After a median follow-up of 2.9 years (range 0-21), 470 CLL/MBL patients progressed, requiring CLL treatment. CLL/MBL individuals with a prior history of NHM had a longer TTFT compared to those without (HR=0.69; 95% CI: 0.53-0.90; p=0.006). Individuals with a prior history of NHM who had either intermediate or high-very high CLL-IPI score had significantly longer TTFT (HR= 0.55; 95% CI: 0.33-0.92; p=0.02, and HR=0.65; 95% CI: 0.43-0.97; p=0.03, respectively) compared to those without NHM. After a median follow-up of 8.6 years (range 0-21), 359 individuals died. CLL/MBL patients with a prior history of NHM also experienced reduced OS compared to those without (HR=1.46; 95% CI: 1.08-1.97, p=0.013), particularly among those with low (HR=1.70; 95% CI: 0.96-3.00, p=0.07) or intermediate-risk (HR=2.08; 95% CI: 1.24-3.51, p=0.006), according to CLL-IPI. After excluding NMSC, results remained constant. Conclusions: At the time of diagnosis, one out of five CLL/MBL individuals had a prior history of a NHM. These individuals had a longer time to first CLL directed treatment and reduced OS, even after accounting for other important CLL prognostic factors, which deserves additional studies. Citation Format: Bryan A. Vallejo, Cristine Allmer, Kari G. Rabe, Dennis P. Robinson, Yucai Wang, Paul J. Hampel, Esteban D. Braggio, Neil E. Kay, James R. Cerhan, Sameer A. Parikh, Susan L. Slager. The impact of prior history of non-hematologic malignancies on time to first treatment and overall survival among individuals with CLL or MBL [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7450.

Myeloid sarcoma with RBM15::MRTFA (MKL1) mimicking vascular neoplasm.

Extramedullary involvement of acute myeloid leukemia (AML), aka myeloid sarcoma, is a rare phenomenon in acute megakaryoblastic leukemia with RBM15:: MRTFA(MKL1) fusion, which might mimic non-hematologic malignancies. A 7-month-old infant presented with leukocytosis, hepatosplenomegaly, multiple lymphadenopathies, and a solid mass in the right thigh. Initially, the patient was diagnosed with a malignant vascular tumor regarding the expression of vascular markers from the biopsy of the right thigh lesion that was performed after the inconclusive bone marrow biopsy. The second bone marrow biopsy, which was performed due to the partial response to sarcoma treatment, showed hypercellular bone marrow with CD34 and CD61-positive spindle cell infiltration and > 20% basophilic blasts with cytoplasmic blebs. RNA sequencing of soft tissue biopsy revealed the presence of RBM15::MRTFA(MKL1) fusion. Based on these findings, myeloid sarcoma/AML with RBM15::MRTFA(MKL1) fusion diagnosis was made. AML with RBM15::MRTFA(MKL1) fusion can initially present as extramedullary lesions and might cause misdiagnosis of non-hematologic malignancies.

COVID-19 in Patients with Different Hematological Malignancies: Treatment Strategy and Outcome: An Iraqi Experience

Background: Patients with hematological malignancies may have higher rates of morbidity and mortality due to SARS-COVID-19 than those in the general population. Objectives: To evaluate the outcome of SARS-COVID-19 in patients with different hematological malignancies undergoing active or modified therapy. Settings: This was a retrospective cohort, multicenter study conducted on 167 patients diagnosed with SARS-COVID-19. The selected patients had been diagnosed with different hematological malignancies and had received treatment (chemotherapy or immunosuppressive). The study was carried out in different centers across Iraq between 1 December 2020 and 1 December 2021. Patients and Methods: This study was conducted in seven hematology centers across Iraq with 167 patients; of these, this study showed that 88 (52.7%) were males and 79 (47.3%) were females (mean age 51.9 ± 18.3 years). All patients had had a COVID-19 infection confirmed through RNA-specific fragments by real-time reverse transcriptase polymerase chain reaction (RT-PCR) of the nasopharyngeal swab specimens, and by computed tomography (CT) of the chest. Demographic data were obtained from patient files, which included the type of hematological malignancy, treatment (chemotherapy, immunotherapy, supportive), severity of COVID-19, modification of treatment and disease outcome for patients, whether alive or not. Patients identified as having benign or non-hematological malignancies were excluded. Results: The treatment protocol was modified in 124 patients (74.3%), while 43 patients (25.7%) continued on the same protocol. Regarding treatment outcomes, 77.2% of patients were alive at the end of the study and 22.8% had died. The survival of COVID-19 patients did not change significantly when the treatment protocol was modified compared to those who continued on treatment as per protocol. The death rate was significantly higher among patients with severe disease compared to those with mild and moderate disease (61.4% v. 0% and 5.0%, respectively) (p&lt;0.001). Conclusions: The management of patients with hematological malignancies during the COVID-19 pandemic may be challenging, with higher mortality in patients with concurrent hematological malignancies and COVID-19. The survival of COVID-19 patients did not change significantly when treatment was modified. Age groups, sex, type of hematological malignancy, and disease status did not affect the survival of these patients. The death rate was significantly higher among patients with hematological malignancies and severe COVID-19 compared with mild or moderate disease.