Hematologic Malignancy Patients Research Articles

Direct oral anticoagulants in patients with venous thromboembolism and hematological malignancies

Data are needed on direct oral anticoagulants (DOACs) for the treatment of venous thromboembolism (VTE) in hematological malignancies (HM). Retrospective studies to date lacked a control group and did not focus on patients with VTE. Out aim was toassess the incidence of VTE recurrence and bleeding in HM patients treated with low molecular weight heparin (LMWH) or DOACs for acute VTE. This is a retrospective cohort study including patients with active HM and newly-diagnosed VTE, indexed on the first day of anticoagulation and followed for 12months. The outcome was a composite of recurrent VTE, major bleeding or clinically relevant non-major bleeding. Cumulative incidence [95% confidence interval (CI)] was calculated for each anticoagulation group (LMWH, DOAC) and hazard ratios (HR) were calculated using cox-proportional hazards model, with death as a competing risk. 143 HM patients treated with LMWH (96) or DOACs (47) for acute VTE were included. The most common HM types were lymphoma in 83 (58%) and plasma cell dyscrasia in 32 (22.3%). The 12-month cumulative incidence of the composite outcome was 24.2% (95% CI 15.9-33.5%; n = 22) in the LMWH group and 18.5% (8.5-31.5%; n = 8) in the DOAC group (HR 1.51 [0.695-3.297]). Two recurrent VTE occurred (both in the DOAC group while off-treatment). Nine (9.4%) LMWH-treated patients had major bleeding compared to 1 (2.1%) DOAC-treated patient (HR 4.85 [0.64-36.56]). This study generates the hypothesis that DOACs may be a safe and effective alternative to LMWH for VTE in patients with HM types represented in the study.

Predicting outcomes of hematological malignancy patients admitted to critical care

BackgroundCritical care (CC) admission has traditionally been viewed as likely to result in a poor outcome for hematological malignancy (HM) patients. Such a view can have implications for decisions surrounding CC admission. Recent studies have challenged this poor prognostication, however, there still remains limited data to support CC admission and escalation decisions and to elucidate risk factors which independently predict short- and longer-term survival outcomes.MethodsWe retrospectively analyzed a large cohort of adult HM patients (n=437) admitted to CC over a sixteen-year period, with the specific aim of identifying risk factors present at CC unit admission that could help to predict outcome. We assessed all-cause mortality at CC discharge (CC mortality, primary outcome) and at further time points (hospital discharge and 12-months post-discharge from CC). Single variable and multivariate analyses were performed to identify independent predictors of outcome.ResultsCC unit and hospital mortality rates were 33.4% (146 patients) and 46.2% (202 patients) respectively. At six-month and one-year follow-up, mortality increased to 59.5% and 67.9% respectively. At single variable adjusted regression analysis, eight factors were associated with CC mortality: APACHE II score, the number of organs supported, requirement for continuous renal replacement therapy (CRRT), cardiovascular support, or respiratory support (invasive and non-invasive), the ratio between arterial partial pressure of oxygen (PaO2) and the inspired oxygen concentration (FiO2) (P/F ratio) on CC admission, and the lowest P/F ratio during CC admission. However, only three factors showed independent predictive capacity for CC outcome at multivariate logistic regression analysis; APACHE II score on admission, requirement for ventilation and lowest P/F ratio.ConclusionOne third of HM patients admitted to CC died on the unit and, following admission to CC, approximately one-third of HM patients survived over 1 year. Our data show that, while a diagnosis of HM should not preclude admission of patients who might otherwise benefit from CC support, the prognosis of those with a high APACHE II score upon admission, or those requiring IMV remains poor, despite considerable advances in IMV techniques.

High-titer post-vaccine COVID-19 convalescent plasma for immunocompromised patients during the first omicron surge.

Transplant and hematologic malignancy patients have high Coronavirus disease 2019 (COVID-19) mortality and impaired vaccination responses. Omicron variant evades several monoclonal antibodies previously used in immunocompromised patients. Polyclonal COVID-19 convalescent plasma (CCP) may provide broader neutralizing capacity against new variants at high titers. Vaccination increases severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer in convalescent donors. We conducted a retrospective chart review of hospitalized immunocompromised patients with COVID-19 who received high-titer CCP during the first omicron surge, collected from vaccinated donors within 6 months of pre-omicron COVID-19. Data on safety and outcomes were extracted. A total of 44 immunocompromised patients were included, 59.1% with solid organ transplant, 22.7% with hematopoietic cell transplant, 11.4% with hematologic malignancy, and 6.8% with autoimmune disease. Overall, 95% of CCP units transfused were from recently recovered and vaccinated donors and had SARS-CoV-2 antibody results 8- to 37-fold higher than the Food and Drug Administration's cutoff for high-titer CCP. There were two mild transfusion reactions. A total of 30-day mortality was 4.5%. There were no differences in 100-day mortality by underlying diagnosis, levels of immunosuppression, and timing of CCP administration. Patients with higher immunosuppression had significantly higher mean World Health Organization clinical progression scores at 30-day post-CCP compared to those with lower immunosuppression. CCP is a safe, globally available treatment for immunocompromised patients with COVID-19. Mortality was lower in our cohort than that of COVID-19 patients with similar immunocompromising conditions. Post-vaccine CCP with very high titers should be prioritized for study in immunocompromised patients. Post-vaccine CCP has the potential to keep pace with new variants by overcoming mutations at sufficiently high titer.

Outcome of COVID-19 patients with haematological malignancies after the introduction of vaccination and monoclonal antibodies: results from the HM-COV 2.0 study

Patients with haematological malignancies (HM) and SARS-CoV-2 infection present a higher risk of severe COVID-19 and mortality. The aim of the study was to investigate whether vaccination and monoclonal antibodies (mAbs) have modified the outcomes of HM patients with COVID-19. This is a single-centre retrospective study in HM patients hospitalized due to SARS-CoV-2 infection from March 2020 to April 2022. Patients were divided into PRE-V-mAb group (patients hospitalized before the introduction of vaccination and mAbs) and POST-V-mAb group (patients hospitalized after the use of vaccine and mAbs). A total of 126 patients were included (65 PRE-V-mAb and 61 POST-V-mAb). POST-V-mAb patients showed a significantly lower risk of intensive care unit (ICU) admission (8.2% vs. 27.7%, p = 0.005), shorter viral shedding [17 (IQR 10–28) vs. 24 days (IQR 15–50), p = 0.011] and shorter hospitalization length [13 (IQR 7–23) vs. 20 (IQR 14–41) days, p = 0.0003] compared to the PRE-V-mAb group. Nevertheless, both in-hospital and 30-day mortality rates did not significantly differ between the two groups (29.5% POST-V-mAb vs. 36.9% PRE-V-mAb and 21.3% POST-V-mAb vs. 29.2% PRE-V-mAb, respectively). At the multivariable analysis, an active malignancy (p = 0.042), a critical COVID-19 at admission (p = 0.025) and the need for high-level of oxygen support at respiratory worsening [either HFNC/CPAP (p = 0.022) or mechanical ventilation (p = 0.011)] were independently associated with in-hospital mortality. In the subgroup of POST-V-mAb patients, receiving therapy with mAbs was a protective factor (p = 0.033). Despite the new therapeutic and preventive strategies available, HM patients with COVID-19 disease represent an extremely vulnerable group with still high mortality rates.

Liquid Biopsies for Circulating Tumor DNA Detection May Reveal Occult Hematologic Malignancies in Patients With Solid Tumors.

High-risk clonal hematopoiesis (CH) is frequently incidentally found in patients with solid tumors undergoing plasma cell-free DNA sequencing. Here, we aimed to determine if the incidental detection of high-risk CH by liquid biopsy may reveal occult hematologic malignancies in patients with solid tumors. Adult patients with advanced solid cancers enrolled in the Gustave Roussy Cancer Profiling study (ClinicalTrials.gov identifier: NCT04932525) underwent at least one liquid biopsy (FoundationOne Liquid CDx). Molecular reports were discussed within the Gustave Roussy Molecular Tumor Board (MTB). Potential CH alterations were observed, and patients referred to hematology consultation in the case of pathogenic mutations in JAK2, MPL, or MYD88, irrespective of the variant allele frequency (VAF), or in DNMT3A, TET2, ASXL1, IDH1, IDH2, SF3B1, or U2AF1 with VAF ≥ 10%, while also considering patient cancer-related prognosis. TP53 mutations were discussed case-by-case. Between March and October 2021, 1,416 patients were included. One hundred ten patients (7.7%) carried at least one high-risk CH mutation: DNMT3A (n = 32), JAK2 (n = 28), TET2 (n = 19), ASXL1 (n = 18), SF3B1 (n = 5), IDH1 (n = 4), IDH2 (n = 3), MPL (n = 3), and U2AF1 (n = 2). The MTB advised for hematologic consultation in 45 patients. Overall, 9 patients of 18 actually addressed had confirmed hematologic malignancies that were occult in six patients: two patients had myelodysplastic syndrome, two essential thrombocythemia, one a marginal lymphoma, and one a Waldenström macroglobulinemia. The other three patients were already followed up in hematology. The incidental findings of high-risk CH through liquid biopsy may trigger diagnostic hematologic tests and reveal an occult hematologic malignancy. Patients should have a multidisciplinary case-by-case evaluation.

Treatment of Cancer-related-Fatigue in Acute Hematological Malignancies: Results of a Feasibility Study of using Cognitive Behavioral Therapy.

Despite cancer related fatigue (CRF) being the most common, and debilitating symptom in patients with recently diagnosed acute hematological malignancies (HM), there are limited effective treatments for CRF in HM. The aim of this study was to determine the feasibility of cognitive behavioral therapy (CBT) for CRF in HM. In this preliminary longitudinal prospective study, HM patients diagnosed a median of one month previously with moderate to severe fatigue were enrolled. Patients received CBT in seven weekly sessions for eight weeks. Change in Functional Assessment of Cancer Illness Therapy (FACIT) - Fatigue (primary), FACT-G, Pittsburg Sleep Quality Index (PSQI), Hospital Anxiety Depression Scale (HADS), M.D. Anderson Symptom Inventory - Acute Myeloid Leukemia (MDASI-AML/MDS), and Herth Hope Index (HHI) were analyzed. Twenty-seven of 36 (75 %) patients were evaluable. Adherence and satisfaction rates to the CBT intervention were 78.6% (95% CI 67.2%, 89.9%), and 92% (95% CI 76.7%, 98.3%) respectively. The median age 66, 64% female, the most common HM was AML (60%), median FACIT-F was 27. The mean (SD) improvement at end eight weeks for FACIT-F was 5.5(13.6), Cohen δ 0.4, P=0.046; and for PSQI total was 2.9 (3), Cohen δ -1, P=0.006. We also found significant improvement in HADS anxiety -2.7(4.5), P=0.049, MDASI Sleep -1.8(3.0), P=0.022, MDASI mean module symptom severity -0.7(1.6), P=0.006. However, no significant improvements were found in FACT-G, HHI, and HADS-depression scores. The use of CBT was feasible with improvement of CRF, sleep quality, and anxiety scores in HM. Randomized controlled trials are justified.

Serological and cellular response to mRNA-SARS-CoV2 vaccine in patients with hematological lymphoid malignancies: Results of the study "Cervax".

messenger RNA (mRNA)-Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) vaccines such as BNT162b2 became available in late 2020, but hematological malignancy patients (HM pts) were not evaluated in initial registration trials. We hereby report the results of a prospective, unicentric, observational study Response to COVID-19 Vaccination in hEmatological malignancies (CERVAX) developed to assess the postvaccine serological and T-cell-mediated response in a cohort of SARS-CoV2-negative HM pts vaccinated with BNT162b2. Patients with lymphomas [non-Hodgkin lymphoma (NHL) and Hodgkin lymphoma (HL)], chronic lymphocytic leukemia (CLL), and multiple myeloma (MM); off-therapy for at least 3 months; in a watch-and-wait program; or in treatment with ibrutinib, venetoclax, and lenalidomide were included. Different time points were considered to assess the serological response to the vaccine: before the second dose (T1), at 3-6-12 months after the first dose (T2-3-4, respectively). Since March 2021, 39 pts have been enrolled: 15 (38%) NHL, 12 (31%) CLL, and 12 (31%) MM. There were 13 of the 39 pts (33%) seroconverted at T1; an increase of the serological response was registered after the second dose (T2) (22/39 pts, 56%) and maintained after 6 months (22/39 pts, 56%) and 12 months (24/39 pts, 61%) from the first dose (T3-T4, respectively). Non-serological responders at T4 were 7/39 (18%): 0/15 NHL, 1/12 MM (8%), and 6/12 CLL (50%). All of them were on therapy (one lenalidomide, three ibrutinib, and three venetoclax). SARS-CoV2-reactive T-cell analysis (interferon gamma release assays) was available since June 2022 and was evaluated at 12 months (T4) from the first dose of vaccine in 31/39 pts (79%). T-cell-mediated-responders were 17/31 (55%): most of them were NHL and MM (47%, 41% and 12% for NHL, MM, and CLL, respectively). Both serological and T-cell non-responders were represented by pts on active therapy (venetoclax/ibrutinib). During the period of observation, eight (20.5%) pts developed mild SARS-CoV2 infection; no coronavirus disease 19 (COVID-19)-related deaths or hospitalizations were registered. In conclusion, in our cohort of lymphoproliferative pts receiving BNT162b2, CLL diagnosis and venetoclax/ibrutinib seem to be related with a lower humoral or T-mediated response. Nevertheless, the efficacy of mRNA vaccine in HM pts and the importance to continue the vaccine program even in non-responders after the first dose are supported in our study by demonstrating that a humoral and T-cell-mediated seroconversion should be observed even in the subsets of heavily immunocompromised pts.

Outcome of early treatment of SARS-CoV-2 infection in patients with haematological disorders.

Outcome of early treatment of COVID-19 with antivirals or anti-spike monoclonal antibodies (MABs) in patients with haematological malignancies (HM) is unknown. A retrospective study of HM patients treated for mild/moderate COVID-19 between March 2021 and July 2022 was performed. The main composite end-point was treatment failure (severe COVID-19 or COVID-19-related death). We included 328 consecutive patients who received MABs (n= 120, 37%; sotrovimab, n= 73) or antivirals (n= 208, 63%; nirmatrelvir/ritonavir, n= 116) over a median of two days after symptoms started; 111 (33.8%) had non-Hodgkin lymphoma (NHL); 89 (27%) were transplant/CAR-T (chimaeric antigen receptor T-cell therapy) recipients. Most infections (n= 309, 94%) occurred during the Omicron period. Failure developed in 31 patients (9.5%). Its independent predictors were older age, fewer vaccine doses, and treatment with MABs. Rate of failure was lower in the Omicron versus the pre-Omicron period (7.8% versus 36.8%, p< 0.001). During the Omicron period, predictors of failure were age, fewer vaccine doses and diagnosis of acute myeloid leukaemia/myelodysplastic syndrome (AML/MDS). Independent predictors of longer viral shedding were age, comorbidities, hospital admission at diagnosis, NHL/CLL, treatment with MABs. COVID-19-associated mortality was 3.4% (n= 11). The mortality in those who developed severe COVID-19 after early treatment was 26% in the Omicron period. Patients with HM had a significant risk of failure of early treatment, even during the Omicron period, with high mortality rate.

30 - Orca-T, a High-Precision Cell Therapy, for the Treatment of Hematologic Malignancies in Patients with 7/8 Mismatch Donors

30 - Orca-T, a High-Precision Cell Therapy, for the Treatment of Hematologic Malignancies in Patients with 7/8 Mismatch Donors

Clinico-Hematological Pattern of Haematological Malignancies in Patients Referred for Bone Marrow Examination

Background: Chromosomal translocation is a common cause among hematological malignancies thus. a different diagnostic and treatment approach is required in these cases. Aim: To determine frequencies and clinic-hematological features of different hematological malignancies among patients. Methodology: It was a descriptive cross sectional study. Patients (n=284) with hematological malignancy were enrolled from total 1080 bone marrow biopsies. Detailed history, clinical examination and hematological parameters were recorded at time of presentation. Bone marrow aspiration and trephine biopsy were done as per the clinical indication. Data was evaluated by using SPSS version 23. Chi-square test was applied with p-value of less than 0.05 was considered significant. Results: The study showed the high percentage of hematological malignancies (24%) were observed among enrolled patients with CML being the commonest cancer among them. Practical Implication: This study established the clinic-hematological correlation and provided study based suggestions for better diagnosis and treatment of hematological malignancies while using bone marrow microscopic examination as an important diagnostic tool. Conclusion: It was concluded that acute leukemias were common in younger age whereas chronic leukemias and lymphoproliferative disorders in more advanced ages. Keywords: Hematological Malignancies, Bone Marrow Examination and Diagnosis.

Early administration of SARS‐CoV‐2 monoclonal antibody reduces the risk of mortality in hematologic malignancy and hematopoietic cell transplant patients with COVID‐19

Data on severe acute respiratory distress syndrome coronavirus 2 monoclonal antibody (SARS-CoV-2-specific mAb) use in hematologic malignancy and hematopoietic cell transplantation (HM/HCT) patients are limited. Here, we describe our experience with the use of casirivimab-imdevimab or bamlanivimab for the treatment of coronavirus disease 2019 (COVID-19) in HM/HCT patients. This was a retrospective chart review at the University of Miami Hospital and Sylvester Comprehensive Cancer Center for HM/HCT patients with COVID-19 who received casirivimab-imdevimab or bamlanivimab from November 21, 2020, to September 30, 2021. Outcomes measured were mortality, hospital admission, and infusion reaction to SARS-CoV-2-specific mAbs. We identified 59 HM/HCT patients with mild to moderate COVID-19 who received casirivimab-imdevimab or bamlanivimab. Median age was 57 years (interquartile range [IQR]: 45-65). Among the 59 patients, 25 (42%) received cellular therapy: 14 (24%) had undergone allogeneic HCT, nine (15%) autologous HCT, and two (3%) received chimeric antigen receptor T-cell therapy. The median time from COVID-19 symptom onset to SARS-CoV-2-specific mAb administration was 4 (IQR: 3-6) days. Forty-six (78%) patients received SARS-CoV-2-specific mAbs as outpatients and 13 (22%) patients received SARS-CoV-2-specific mAbs during hospitalization. Among patients who received SARS-CoV-2-specific mAbs as outpatients, only four (9%) visited the emergency department at days 10, 11, 15, and 35 after SARS-CoV-2-specific mAb administration. None of these four patients required hospital admission. Among the hospitalized patients, five (38%) were admitted to the hospital with neutropenic fever, four (31%) were already hospitalized for transplantation and cellular therapy, three (23%) were admitted for monitoring of COVID-19 symptoms, and one (8%) was admitted with acute kidney injury. Three hospitalized patients (23%) died at 14, 35, and 59 days after SARS-CoV-2-specific mAb administration; two of these three deaths were attributed to COVID-19 infection. One patient developed an immediate infusion reaction to bamlanivimab, and no infusion reactions were reported to casirivimab-imdevimab use. During the alpha and delta variant surges, early administration of bamlanivimab or casirivimab-imdevimab prevented hospitalization and death when given in the outpatient setting. Among patients who received mAbs at or after hospital admission, the risk of COVID-19 disease progression and death remains significant. Larger studies of the use of mAb therapy to treat COVID-19 in this population are needed.

Prevalence and factors associated with carbapenem-resistant Enterobacterales (CRE) infection among hematological malignancies patients with CRE intestinal colonization

BackgroundKnowledge about the prevalence, factors and mortality associated with subsequent carbapenem-resistant Enterobacterales (CRE) infection among hematological malignancies (HM) patients colonized with CRE is limited.MethodsHM patients were screened for rectal CRE. A retrospective case–control study of subsequent CRE infection among HM patients colonized with CRE was conducted between January 1st, 2020 and January 31st, 2022. Cases were defined as CRE colonized patients with subsequent infection and controls were those without infection. Bacterial identification was performed using MALDI Biotyper and antimicrobial susceptibility testing of strains was carried out using the VITEK 2 system or standard broth microdilution method. Logistic analysis was used for analyzing associated factors and Kaplan–Meier method was used for survival estimates.ResultsA total of 953 HM patients were screened for rectal CRE and 98 (10.3%, 98/953) patients were colonized with CRE. Among the 98 colonized patients, 18 (18.4%, 18/98) patients developed subsequent infection. Most of the colonizing CRE isolates were Klebsiella pneumoniae (50.0%, 27/54), followed by Escherichia coli (27.8%, 15/54) and Enterobacter cloacae (9.3%, 5/54). As for the subsequent infecting CRE isolates, the dominated species was K. pneumoniae (55.6%, 10/18), followed by E. coli (33.3%, 6/18) and others (11.2%, 2/18). Receiving proton pump inhibitors and admission to ICU (P < 0.05) were the associated factors. Patients with subsequent CRE infection had significant higher mortality (33.3% vs 2.8%, P = 0.001) and shock was an associated factor (P = 0.008).ConclusionsKlebsiella pneumoniae was the dominate colonizing species and subsequent infecting species among HM patients with CRE colonization. Receiving proton pump inhibitors and admission to ICU increased the risk of subsequent CRE infection among CRE colonized HM patients. Implementing strict infection control measures targeting those high- risk patients may prevent subsequent CRE infection.

Prognostic factors of second hematopoietic allogeneic stem cell transplantation among hematological malignancy patients relapsed after first hematopoietic stem cell transplantation: A single center study.

We aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1). We retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021. The median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 -disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Trends in mortality from infection among patients with hematologic malignancies: differences according to hematologic malignancy subtype.

Infection is the most important cause of non-relapse mortality in hematologic malignancy patients, leading to increased costs and prolonged hospitalization times. However, comprehensive and comparable reports on infection-specific mortality (ISM) trends in hematologic malignancy patients are lacking. We aimed to provide updated ISM trends and factors associated with ISM among hematologic malignancy patients. This is a retrospective study. Patients diagnosed with the five most common hematologic malignancies from 1983 to 2016 from the Surveillance, Epidemiology, and End Results database were included. Joinpoint regression was used to analyze mortality trends. ISM decreased beginning in 1983, 1988, and 1994, with yearly decreases of -2.1% for acute leukemia (AL), -1.3% for Hodgkin lymphoma (HL), and -14.3% for non-Hodgkin lymphoma (NHL). In contrast, ISM in patients with chronic leukemia (CL) and multiple myeloma (MM) increased dramatically beginning in 2000, with yearly increases of 2.8% and 3.3%, respectively. ISM rates were higher in males than in females across all hematologic malignancy subtypes. The mortality trends significantly differed according to race, age, sex, and stage, which could help in further etiological investigations. Moreover, male sex, older age at diagnosis, black race, and unmarried status were poor prognostic factors for ISM across all hematologic malignancy subtypes. A promising downward trend in ISM in recent years occurred in patients with AL, HL, and NHL; however, ISM increased dramatically in patients with CL and MM. Our data suggest that risk assessment and careful infection monitoring are recommended for hematologic malignancy patients, particularly those with CL and MM.

Serial Transthoracic Ultrasonography Studies in Hematopoietic Cell Transplant Patients: A Tool for Early Lung Pathology Detection.

Early detection of pulmonary complications can improve outcomes for patients with hematological malignancy (HM). For detecting lung injuries, lung ultrasound (LUS) images have been found to be of greater sensitivity than radiographic images. Our group performed a pilot study of LUS imaging to enhance early detection of pulmonary complications in HM patients. This prospective single-center feasibility study evaluated LUS for detecting pulmonary complications in 18 HM patients enrolled while hospitalized for a hematopoietic cell transplant (HCT) (concurrent-HCT group) or re-hospitalized for complications (post-HCT group). Serial LUS exams were performed and assigned a score from 0 to 5 based on pleural line, B-line, consolidation and pleural effusion features. Correlations between patients' clinical characteristics and LUS features were analyzed. Comparisons between the LUS and radiographic images were evaluated. In the concurrent-HCT patients (79 LUS exams), non-significant fluctuating findings were commonly identified, but one-third of the patients presented pathologic findings (LUS scores ≥ 3). In the post-HCT patients (29 LUS exams), LUS images revealed severe pathologic findings (LUS score=5) in every patient and, compared with radiographic images, were more sensitive for detecting pleural effusions (p < 0.05). LUS can be routinely performed on hospitalized HM patients, allowing point-of-care early detection of pulmonary complications.

Risk factors for ICU mortality in patients with hematological malignancies: a singlecenter, retrospective cohort study from Turkey.

Patients with hematological malignancies (HM) often require admission to the intensive care unit (ICU) due to organ failure, disease progression or treatment-related complications, and they generally have a poor prognosis. Therefore, understanding the factors affecting ICU mortality in HM patients is important. In this study, we aimed to identify the risk factors for ICU mortality in our critically ill HM patients. We retrospectively reviewed the medical records of HM patients who were hospitalized in our medical ICU between January 1, 2010 and December 31, 2018. We recorded some parameters of these patients and compared these parameters by statistically between survivors and nonsurvivors to determine the risk factors for ICU mortality. The study included 368 critically ill HM patients who were admitted to our medical ICU during a 9-year period. The median age was 58 (49-67) years and 63.3% of the patients were male. Most of the patients (43.2%) had acute leukemia. Hematopoietic stem cell transplantation (HSCT) was performed in 153 (41.6%) patients. The ICU mortality rate was 51.4%. According to univariable analyses, a lot of parameters (e.g., admission APACHE II and SOFA scores, length of ICU stay, some laboratory parameters at the ICU admission, the reason for ICU admission, comorbidities, type of HM, type of HSCT, infections on ICU admission and during ICU stay, etc.) were significantly different between survivors and nonsurvivors. However, only high SOFA scores at ICU admission (OR:1.281, p = 0.004), presence of septic shock (OR:17.123, p = 0.0001), acute kidney injury (OR:48.284, p = 0.0001), and requirement of invasive mechanical ventilation support during ICU stay (OR:23.118, p = 0.0001) were independent risk factors for ICU mortality. In our cohort, critically ill HM patients had high ICU mortality. We found four independent predictors for ICU mortality. Yet, there is still a need for further research to better understand poor outcome predictors in critically ill HM patients.

The Burden of COVID-19 in Adult Patients With Hematological Malignancies: A Single-center Experience After the Implementation of Mass-vaccination Programs Against SARS-CoV-2.

Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece. From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed. Exploratory end-points included the incidence of intubation, probability of recovery, mortality, and duration of remdesivir (RDV) administration. Overall, mechanical ventilation (MV) was required for five patients and crude mortality was 8.3%. HM of lymphocytic origin (p=0.035) and obesity (p=0.03) were the main determinants of the risk of intubation and among several laboratory markers, only LDH>520 IU/l was proven to be an independent MV predictor (p=0.038). The number of co-existing comorbidities (p=0.05) and disease severity on admission (p<0.001) were found to rule the probability of recovery, and dexamethasone was associated with worse prognosis, particularly in patients with mild/moderate COVID-19. RDV was administered to the entire cohort, of whom 38 were managed with an extended course. In the multivariate analysis, patients with HM of lymphocytic origin were more likely to receive RDV for more than five days (p=0.002). Our study emphasizes the frailty of HM patients, even in the era of Omicron-variant predominance, and underlines the need to optimize therapy.

Invasive fungal infections in hematologic malignancies: Incidence, management, and antifungal therapy.

The incidence of invasive fungal infections (IFIs) has increased in recent years as a result of increasing the incidence of hematologic malignancies (HMs). IFIs, as the opportunistic diseases, are the most important concern in these patients with a high mortality rate. These infections are one of the leading causes of morbidity and mortality in HM patients and an important factor in increasing the costs of patients' management because of the prolonged hospitalization and the inevitable need to use antifungal agents. Due to the changes in the pattern of organisms causing IFIs, unavailability of effective and safe antifungal drugs, and high rate of drug resistance as well as lack of fast and accurate diagnostic methods, these infections have become a serious and life-threatening problem necessitating effective prevention and treatment strategies using suitable antifungal agents, especially in high-risk patients. The aim of the present study was to review the pathogens causing various types of IFIs, diagnostic methods, and novel prophylactic and therapeutic antifungal regimens in HM patients according to the new published studies and clinical trials.

Comparing the Quality of Life of Caregivers for Patients with Hematologic and Solid Malignancies in Kuwait: A Cross-Sectional Study

Cancer incidence is escalating globally, and the Middle East, including Kuwait, is no exception. This study delves into a comparative analysis of the Quality of Life (QOL) experienced by caregivers for patients with hematologic and solid malignancies in Kuwait. The prevalence of cancer in Kuwait is rising, becoming the second leading cause of death after cardiovascular diseases. Colorectal and breast cancer are predominant forms, with an increased occurrence in females. Notably, haematological malignancies, rooted partly in consanguineous marriages, exhibit a distinct prevalence pattern, accounting for a significant proportion of deaths. Kuwait has made substantial investments in bone marrow transplantation programs to address this issue. To understand the impact of caregiving on the QOL of individuals supporting cancer patients, a cross-sectional study was conducted. Caregivers were recruited from the Kuwait Cancer Control Centre outpatient clinics between February 25 and March 25, 2020. Caregivers’ QOL was assessed using the Caregiver Quality of Life Cancer Index (CQoLC) through face-to-face interviews. The study aimed to determine if caregivers were adequately informed before their patients’ discharge and analyse reasons for non-participation. Previous research on caregiver QOL has predominantly focused on Western societies, while this study addresses the Kuwaiti context. The expectation is that findings will contrast with Western studies due to unique cultural and societal dynamics, where women play a pivotal role in caregiving. While males may experience reduced QOL due to work-home time constraints, female caregivers in Arab countries tend to be efficient, albeit with potential skill deficiencies. The study enrolled 117 caregivers, with 65 supporting patients with solid malignancies and 52 caring for hematologic malignancy patients. The demographic characteristics of caregivers were analysed, revealing trends related to age, gender, marital status, employment, education, and living arrangements. Caregivers of solid malignancy patients displayed higher levels of burden compared to hematologic malignancy caregivers, with emotional strain, worry, and sadness being significant factors. While there was a notable refusal rate among potential participants, the study’s insights are valuable. To enhance the QOL of caregivers, especially those supporting outpatient cases, targeted interventions such as palliative care and training programs are crucial. The economic burden on caregivers necessitates policies addressing financial support. The findings of this study contribute to the ongoing efforts to improve the QOL of caregivers in Kuwait, thereby alleviating the multifaceted challenges posed by cancer and its care. This research underscores the importance of tailoring interventions to the specific cultural, social, and economic context of Kuwait to optimize caregiver well-being and patient outcomes.

Management of Latent Tuberculosis Infection Based on T-SPOT.TB Assay in Patients with Hematological Malignancies.

Patients with latent tuberculosis infection (LTBI) receiving chemotherapy for hematological malignancy (HM) are at high risk of developing active tuberculosis (TB) infection. The aim of this study is to show real-life data and results of the T-SPOT test and preventive isoniazid (INH) therapy in pre-chemotherapy LTBI screening in the HM patient group. This retrospective study includes 209 HM patients who had T-SPOT test between 2016 and 2021 in Sultan 2. Abdulhamid Han Training and Research Hospital in Istanbul, Turkey. The prevalence of LTBI was 26.8% in 209 patients (n=56). Preventive INH therapy was initiated in 82.1% (n=46) of 56 patients with LTBI. 23.9% (n=11) of the 46 patients who received preventive INH therapy were unable to complete the treatment. Nine patients died due to malignancy; one was lost to follow-up, and only one had to stop INH treatment due to elevated liver enzymes. Elevated liver enzymes occurred in 4 (8.7%) patients using INH, while gastrointestinal symptoms occurred in 3 (6.5%) patients. Active TB infection emerged in none of the T-SPOT positive or indeterminate individuals but in one HIV(+) patient in the T-SPOT negative group. The active TB infection incidence rate was 217 cases/100.000hab/year (95% CI, 29-748). INH treatment was generally well tolerated, and very few serious drug-related side effects were observed. Although LTBI cannot be demonstrated in patients with HIV(+) HM who are scheduled for chemotherapy, these patients should be closely monitored for the development of active TB infection.