Hematologic Malignancy Patients Research Articles

COVID-19-Associated Pulmonary Fungal Infection among Pediatric Cancer Patients, a Single Center Experience.

Patients with COVID-19 are at risk of developing secondary complications such as invasive pulmonary aspergillosis and mucormycosis. This is a retrospective study including all cancer children diagnosed with COVID-19-associated pulmonary fungal infection (CAPFI) during the period 2020–2021. A total of 200 patients were diagnosed with COVID-19, out of which 21 (10%) patients were diagnosed with CAPFI, 19 patients (90%) with COVID-aspergillosis (CAPA), and 2 (10%) patients with COVID-mucormycosis (CAM). Patients with CAPFI were classified using the “2020 ECMM/ISHAM consensus criteria”; proven in 2 (10%) patients, probable in 12 (57%), and possible in 7 (33%) patients. Although the hematological malignancy patients were already on antifungal prophylaxis, breakthrough fungal infection was reported in 16/21 (75%), 14 (65%) patients had CAPA while on echinocandin prophylaxis, while 2 (10%) patients had CAM while on voriconazole prophylaxis. Overall mortality was reported in 8 patients (38%) while CAPFI-attributable mortality was reported in 4 patients (20%). In conclusion, clinicians caring for pediatric cancer patients with COVID-19 should consider invasive pulmonary fungal infection, even if they are on antifungal prophylaxis, especially with worsening of the clinical chest condition. A better understanding of risk factors for adverse outcomes may improve clinical management in these patients.

Risk Factors for Mortality and Outcomes in Hematological Malignancy Patients with Carbapenem-Resistant Klebsiella pneumoniae Bloodstream Infections

BackgroundThis study aimed to identify risk factors for mortality and outcomes in hematological malignancy (HM) patients with bloodstream infection (BSI) caused by carbapenem-resistant Klebsiella pneumoniae (CRKP).MethodsA retrospective study was conducted at a tertiary teaching hospital in Henan Province, China, between January 2018 and December 2021. All BSIs caused by CRKP in hospitalized HM patients were identified. Data on patient demographics, disease, laboratory tests, treatment regimens, outcomes of infection, and the antimicrobial susceptibility of each isolate were collected from medical records.ResultsA total of 129 patients with CRKP BSI were included in the study, and the 28-day mortality rate was 80.6% (104/129). In Cox analysis an absolute neutrophil count < 500 at discharge (hazard ratio [HR] 6.386, 95% confidence interval [CI] 3.074–13.266, p < 0.001), intensive care unit admission (HR 1.834, 95% CI 1.065–3.157, p = 0.029), and higher Pitt bacteremia score (HR 1.185, 95% CI 1.118–1.255, p < 0.001) were independent risk factors associated with 28-day mortality. Survival curve analysis indicated that compared with ceftazidime-avibactam-based therapy, both polymyxin b (HR 8.175, 95% CI 1.099–60.804, p = 0.040) and tigecycline (HR 14.527, 95% CI 2.000–105.541, p =0.008) were associated with a higher risk of mortality.ConclusionIn HM patients CRKP BSI resulted in high mortality. Intensive care unit admission, higher Pitt bacteremia score, and absolute neutrophil count < 500 at discharge were independently associated with higher mortality. Early initiation of new agents such as ceftazidime-avibactam may improve outcomes.

Neutralizing monoclonal antibodies in haematological patients paucisymptomatic for COVID-19: The GIMEMA EMATO-0321 study.

COVID-19 continues to be a relevant issue among patients with haematological malignancies (HM). Vaccines are frequently not effective in subjects on active treatment. In this multicentre retrospective study of Gruppo Italiano Malattie EMatologiche dell'Adulto (GIMEMA), we collected data from 91 paucisymptomatic HM patients treated with anti-spike neutralizing monoclonal antibodies (nMoAbs) to determine time to viral clearance, referencing it to the expected value of 28 days from an historical group of untreated paucisymptomatic patients. Secondary endpoints included rate of hospitalization, intensive care unit (ICU) admission, COVID-19 related death and safety. SARS-CoV-2 molecular swab negativity was obtained in 86 patients (95%), with a median time of 18 days (IQR 13-26; p< 0.0001). We did not find significant variations according to age, diagnosis, treatment type, vaccination status or nMoAbs type. Rate of hospitalization due to COVID-19 progression was 12% (11/91), with 2 patients (2.2%) requiring ICU admission. With a median follow-up of 2.33 months, the overall mortality was 5.5% (5/91), with 3 deaths due to COVID-19. Side effects were rare and self-limiting. Our data suggest that nMoAbs can limit the detrimental effect of immunosuppressive treatments on COVID-19 clinical progression and time to viral clearance. The original trial was registered at www.clinicaltrials.gov as #NCT04932967.

Status of CMV IgM Seropositivity Before and After Starting Chemotherapy in Patients with Haematological Malignancies

Background: Even after significant improvement of management of haematological malignancy, post chemotherapy infection is still causing significant mortality and morbidity. Cytomegalovirus (CMV) is an important cause of morbidity and mortality in immunocompromised patients. This study was designed to assess prospectively the status of CMV IgM seropositivity in patients with haematological malignancy at diagnosis and after starting chemotherapy by serology test. In Bangladesh the prevalence IgG is high and IgM is low in general population but in patients with chemotherapy due to haematological malignancy status of CMV infection is not known. By finding out the infection rate we will be able to provide supportive care more effectively to patients of chemotherapy due to haematological malignancy. &#x0D; Methodology: This was a prospective type of observational study and patients were selected by purposive sampling. Assessment of CMV IgG and IgM antibody test had been done at the time of 1st diagnosis and IgM antibody for CMV reassessed 6 weeks after initial chemotherapy. Antibodies were detected by Chemiluminescence method from Virology department of BSMMU. Statistical analysis was done both manually and Windows based software device with Statistical Package for Social Science (SPSS). A p-value of &lt;0.05 was taken as significant during data calculation. Result: During 12 months study period a total 45 patients with haematological malignancy were included in the study. Out of 45 patients, 28 were male (62%) and 17 were female (38%), male female ratio was 1.65:1. The youngest of the participants was 15 and oldest was 70 years old. The mean age of the participants was 35.77 years with SD of 16.93. Among 45 patients of the study, ALL patients were 20 (44.4%), AML patients were 17 (37.8%), NHL patients were 5 (11.1%) and HD patients were 3 (6.7%). Before chemotherapy all participants were CMV IgG positive (100%) no one was CMV IgM Positive (0%). Six weeks after chemotherapy, 42 (93.3%) cases were CMV IgM antibody negative and only 3 (6.7%) cases were positive for CMV IgM antibody. McNemar test was done to measure the level of significance and p-value was 0.250, which was not significant statistically. Conclusion: This small study found that all participants were CMV IgG seropositive (100%). It indicates that higher percentages of haematological malignancy patients are previously infected with CMV so there is more risk of reactivation after chemotherapy or BMT. Post chemotherapy CMV IgM seropositivity (new infection or reactivation of CMV) was low 6.7% in this study. This percentage is low in comparison with other studies. Percentage could be high if the tests were carried out with more sensitive and specific tests for CMV like PCR, pp65 antigenaemia or CMV DNA.

Effects of Soy-Whey Protein Nutritional Supplementation on Hematopoiesis and Immune Reconstitution in an Allogeneic Transplanted Mice.

Profound malnutrition and immunodeficiency are serious negative effects of radiotherapy and bone marrow transplantation for hematologic malignancy patients. This study aimed to evaluate the effects of nutritional supplementation with a soy–whey protein mixture on hematopoietic and immune reconstitution in an allogeneic transplant mouse model. Male BALB/c (H-2Kd) mice, 6–8 weeks-old, were divided randomly into five groups and then provided with different protein nutrition support. After 28 days, blood samples, bone marrow, spleen, and thymus were harvested to measure the effects. The results showed that soy–whey blended protein supplements promoted hematopoietic stem cell engraftment, body weight recovery, and the recovery of white blood cells, lymphocytes, and neutrophils; triggered the expansion of hematopoietic stem cells and progenitor cell pools by increasing the numbers of the c-kit+ progenitor, Lin-Sca1+c-kit+, short-term hematopoietic stem cells, and multipotent progenitors; enhanced thymus re-establishment and splenic subset recovery in both organ index and absolute number; improved overall nutritional status by increasing total serum protein, albumin, and globulin; protected the liver from radiation-induced injury, and increased antioxidant capacity as indicated by lower concentrations of alanine aminotransferase, aspartate aminotransferase, malondialdehyde, and 4-hydroxynonenal. This study indicated that soy–whey blended protein as important nutrients, from both plant and animal sources, had a greater positive effect on patients with hematological malignancies to accelerate hematopoiesis and immune reconstitution after bone marrow transplantation.

Secondary Immune Deficiency and Primary Immune Deficiency Crossovers: Hematological Malignancies and Autoimmune Diseases.

Primary immunodeficiencies (PIDs), a heterogenous group of inborn errors of immunity, are predetermined at birth but may evolve with age, leading to a variable clinical and laboratory presentation. In contrast, secondary immunodeficiencies (SIDs) are acquired declines of immune cell counts and or/function. The most common type of SID is a decreased antibody level occurring as a consequence of extrinsic influences, such as an underlying condition or a side effect of some medications used to treat hematological malignancies and autoimmune disorders. Paradoxically, immune deficiencies initially attributed to secondary causes may partly be due to an underlying PID. Therefore, in the era of immune-modulating biologicals, distinguishing between primary and secondary antibody deficiencies is of great importance. It can be difficult to unravel the relationship between PID, SID and hematological malignancy or autoimmunity in the clinical setting. This review explores SID and PID crossovers and discusses challenges to diagnosis and treatment strategies. The case of an immunodeficient patient with follicular lymphoma treated with rituximab illustrates how SID in the setting of hematological cancer can mask an underlying PID, and highlights the importance of screening such patients. The risk of hematological cancer is increased in PID: for example, lymphomas in PID may be driven by infections such as Epstein-Barr virus, and germline mutations associated with PID are enriched among patients with diffuse large B-cell lymphoma. Clues suggesting an increased risk of hematological malignancy in patients with common variable immune deficiency (CVID) are provided, as well as pointers for distinguishing PID versus SID in lymphoma patients. Two cases of patients with autoimmune disorders illustrate how an apparent rituximab-induced antibody deficiency can be connected to an underlying PID. We highlight that PID is increasingly recognized among patients with autoimmune cytopenias, and provide guidance on how to identify PID and distinguish it from SID in such patients. Overall, healthcare professionals encountering patients with malignancy and/or autoimmunity who have post-treatment complications of antibody deficiencies or other immune abnormalities need to be aware of the possibility of PID or SID and how to differentiate them.

A critical care outreach team under strain - Evaluation of the service provided to patients with haematological malignancy during the Covid-19 pandemic.

PurposeCritical Care Outreach Teams (CCOTs) have been associated with improved outcomes in patients with haematological malignancy (HM). This study aims to describe CCOT activation by patients with HM before and during the Covid-19 pandemic, assess amny association with worse outcomes, and examine the psychological impact on the CCOT.Materials and methodsA retrospective, mixed-methods analysis was performed in HM patients reviewed by the CCOT over a two-year period, 01 July 2019 to 31 May 2021.ResultsThe CCOT increased in size during the surge period and reviewed 238 HM patients, less than in the pre- and post-surge periods. ICU admission in the baseline, surge and the non-surge periods were 41.7%, 10.4% and 47.9% respectively. ICU mortality was 22.5%, 0% and 21.7% for the same times. Time to review was significantly decreased (p = 0.012). Semi-structured interviews revealed four themes of psychological distress: 1) time-critical work; 2) non-evidence based therapies; 3) feelings of guilt; 4) increased decision-making responsibility.ConclusionsDespite the increase in total hospital referrals, the number of patients with HM that were reviewed during the surge periods decreased, as did their ICU admission rate and mortality. The quality of care provided was not impaired, as reflected by the number of patients receiving bedside reviews and the shorter-than-pre-pandemic response time.

Comparison of Outcomes of Haploidentical Peripheral Blood Stem Cell Transplantation Supported by Third-Party Cord Blood Versus Human Leukocyte Antigen-Matched Sibling Peripheral Blood Stem Cell Transplantation in Hematologic Malignancy Patients.

Recent studies have shown that haploidentical hematopoietic stem cell transplantation supported by third-party cord blood (haplo-cord-HSCT) results in rapid hematopoietic recovery, low incidences of graft-versus-host disease (GVHD), and relapse of hematologic malignancies. However, few reports on haploidentical peripheral blood stem cell transplantation supported by third-party cord blood (haplo-cord-PBSCT) have been published. To evaluate the outcomes of patients who underwent haplo-cord-PBSCT or human leukocyte antigen (HLA)-matched sibling donor peripheral blood stem cell transplantation (MSD-PBSCT), we retrospectively reviewed the clinical data of patients with hematologic malignancies who underwent haplo-cord-PBSCT (n = 93) or MSD-PBSCT (n = 72) in our hospital from March 2017 to December 2020. In the haplo-cord-PBSCT and MSD-PBSCT groups, the median time for neutrophil and platelet engraftment was 13 vs. 12 days (p = 0.07) and 16 vs. 13 days (p = 0.06), respectively. The 30-day cumulative incidences of neutrophil engraftment were 100.0% and 98.6% (p = 0.12). The 100-day cumulative incidences of platelet engraftment were 96.8% and 98.6% (p = 0.01). The 100-day cumulative incidences of grade II–IV and grade III–IV acute GVHD were 29.1% vs. 23.6% (p = 0.42) and 9.7% vs. 4.2% (p = 0.18). The cumulative incidences of total and moderate/severe chronic GVHD at 1 year were 26.5% vs. 17.4% and 8.1% vs. 4.5%, respectively, and at 3 years were 34.7% vs. 34.3% (p = 0.60) and 13.6% vs. 10.6% (p = 0.49), respectively. The cumulative incidences of relapse at 1 year were 9.3% and 7.2% and at 3 years were 17.0% and 17.0% (p = 0.98). Non-relapse mortality (NRM) at 1 year was 14.6% and 8.6% and at 3 years was 17.4% and 8.6% (p = 0.13) in two groups. The probabilities of overall survival (OS), disease-free survival (DFS), and GVHD-free/relapse-free survival (GRFS) at 1 year were 81.7% vs. 88.6%, 76.1% vs. 84.2%, and 71.7% vs. 79.7%, respectively, and at 3 years were 78.7% vs. 79.0%, 65.6% vs. 74.4%, and 55.5% vs. 63.6%, respectively, in the corresponding group, p > 0.05. In conclusion, for patients with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS) and acute lymphoid leukemia (ALL), haplo-cord-PBSCT results in similar outcomes compared with MSD-PBSCT, and it may be a valid alternative transplantation method.

A Systematic Review to Assess the Relationship between Disseminated Cerebral Aspergillosis, Leukemias and Lymphomas, and Their Respective Therapeutics.

Disseminated disease following invasive pulmonary aspergillosis (IPA) remains a significant contributor to mortality amongst patients with hematologic malignancies (HMs). At the highest risk of mortality are those with disseminated disease to the central nervous system, known as cerebral aspergillosis (CA). However, little is known about the risk factors contributing to disease amongst HM patients. A systematic review using PRISMA guidelines was undertaken to define HM patient subgroups, preventative measures, therapeutic interventions, and outcomes of patients with disseminated CA following IPA. The review resulted in the identification of 761 records, of which 596 articles were screened, with the final inclusion of 47 studies and 76 total patients. From included articles, the proportion of CA was assessed amongst HM patient subgroups. Further, pre-and post-infection characteristics, fungal species, and mortality were evaluated for the total population included and HM patient subgroups. Patients with acute myeloid leukemia and acute lymphoid lymphoma, patients receiving corticosteroids as a part of their HM therapeutic regimen, and anti-fungal prophylaxis constitute the top identified patient populations at risk for disseminated CA. Overall, information presented here indicates that measures for the prevention of IPA should be taken in higher-risk HM patient subgroups. Specifically, the type of anti-fungal therapy used should be carefully considered for those patients with IPA and increased risk for cerebral dissemination. Additional reports detailing patient characteristics are needed to define further the risk of developing disseminated CA from IPA in patients with HMs.

The Value of Metagenomic Next-Generation Sequencing in Hematological Malignancy Patients with Febrile Neutropenia After Empiric Antibiotic Treatment Failure.

BackgroundIt was crucial to use empirical antibiotics in febrile neutropenia (FN) patients. However, most patients still died from infection due to poor efficacy. Metagenomic next-generation sequencing (mNGS) is a rapid microbiological diagnostic method. The value of mNGS in patients with FN remains to be studied, especially after empiric antibiotic treatment.MethodsWe retrospectively analyzed the differences between mNGS and the traditional methods in 192 patients with hematological malignancies who have received empiric antibiotic treatment. Samples were collected when patient had chills or half an hour before peak body temperature. And we compared the differences between FN and non-FN patients, mainly including types of pathogens and the diagnostic value of different pathogens.ResultsDespite receiving empirical treatment, the pathogen detection rate of mNGS was significantly higher than the traditional method (80.21% vs 25.00%, P<0.001). And it has obvious advantages in detecting mixed pathogens infection (80.21% vs 4.17%, P<0.001). Then, we found that mNGS saw more pathogens in the FN than in the non-FN group, especially fungus. 21/33 (63.63%) of FN patients was diagnosed with fungal infections. The fungal detection rate in FN was significantly higher than non-FN group (32.35% vs 12.22%, P=0.001). Besides, the sensitivity of mNGS was higher than the traditional methods in both FN and non-FN group (P<0.001), but no significant difference in specificity (P>0.05). In the FN group, empiric antibiotic treatment of 46/102 (45.10%) patients did not treat all the pathogens detected by mNGS. After adjusting the antimicrobial regimen according to the results of mNGS, the effective rate at 72 hours and 7 days was 22/46 (47.83%) and 24/102 (52.17%), respectively.ConclusionmNGS had a significant impact on the diagnosis of infection and the second-line antimicrobial therapy in FN. mNGS plays a more important role in FN patients, especially in the diagnosis of fungal infections.PurposeFirstly, we compared the difference between mNGS and the traditional methods in the diagnosis of infection. Secondly, we assessed the value of mNGS in FN patients by comparing it with non-FN patients, including types of pathogens and the diagnostic value of different pathogens. In order to show that mNGS plays a more important role in FN.

P1745: ADHERENCE TO TREATMENT OF HEMATOLOGICAL MALIGNANCIES PATIENTS WITH ANXIETY AND DEPRESSION

Background: The issue of factors influencing adherence to treatment of patients with hematological malignancies (HM) has not been sufficiently studied. Aims: To establish the features of the influence of anxiety and depressive disorders on treatment adherence, as well as to clarify the factors associated with it in HM patients. Methods: The study included 117 patients: 51 men and 66 women, aged 19 to 67 years, with Hodgkin’s lymphoma (HL) - 88, acute lymphoblastic leukemia (ALL) - 16 and aplastic anemia (AA) - 13 patients. Patients were examined by psychiatrist using the Brief Psychiatric Rating Scale, as well as some psychometric methods. Results: Anxiety and depressive spectrum disorders were detected in 36 (40.9%) patients with HL and 8 (50%) with ALL, in the AA group there were three (23.1%) of such patients. It was found that the average adherence to treatment was in 2/3 of patients, low and high - in the remaining 1/3 of patients. The adherence to treatment it is significantly higher in patients older than 45 years. Signs of depression that negatively correlated with adherence to treatment, were pessimism (Fig.1) and disruption of social ties (Fig.2). Adherence to treatment significantly positively correlates with the following types of attitudes towards the disease: anosognosic, hypochondriac and egocentric, and significantly negatively correlates with the following types of attitudes towards the disease: anxious, melancholic and dysphoric. With medium and low adherence to treatment, the risk of adverse events increases by an average of 1.7 times (Fig.3). Image:Summary/Conclusion: Anxiety/depressive disorders contribute to reduced adherence of HM patients to treatment. Their correction and increased adherence should be carried out jointly by hematologists and mental health professionals.

P1203: THE OPTIMIZED HLH INFLAMMATORY (OHI) INDEX IDENTIFIES LYMPHOMA PATIENTS WITH UNEXPECTEDLY HIGH MORTALITY NOT RELATED TO DISEASE PROGRESSION

Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome that may complicate hematologic malignancies (HM). We recently developed a simplified diagnostic and prognostic index termed the ‘optimized HLH inflammatory’ (OHI) index comprising the combined elevation of sCD25 (> 3,900 U/mL) and serum ferritin (> 1,000 ng/mL), which in HM patients both identifies HLH and predicts mortality more accurately than conventional criteria for HLH. Aims: In this study, we examined whether mortality in our cohort is directly related to progressive malignancy vs. HLH-associated causes in OHI+ and OHI- patients. Methods: We performed a multicenter, retrospective study of patients with newly diagnosed Lymphoma from Israel, the USA, and Japan for whom sCD25 and ferritin levels were measured either as routine surveillance or during investigation for HLH classified patients by their OHI status. The International Prognostic Index, International Prognostic Score, and Follicular Lymphoma International Prognostic Index were used to estimate the predicted prognosis of T/B cell non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma, and follicular Lymphoma, respectively. The predicted five-year overall survival was calculated for each patient based on the relevant prognostic index and compared between OHI+ and OHI- patients using the unpaired t-test. The actual survival at five years/last follow-up was recorded, as was the cause of death. Finally, the odds ratios (ORs) for observed vs. predicted mortality and HLH- vs. malignancy-related death were calculated using the Chi-square test. Results: 100 lymphoma patients were studied: 65% with B cell NHL, 18% with natural killer/ T cell lymphoma, 17% with Hodgkin’s Lymphoma; 37 were OHI+, and 63 were OHI-. The disease-relevant international prognostic index-predicted five-year survival did not differ between OHI + and OHI- patients (a mean of 58% n OHI+ and 57% in OHI- p = 0.62). However, the observed five-year survival in OHI+ patients was lower (12%) than predicted, reflecting a mortality incidence that was four times higher than predicted by the relevant prognostic score (OR 3.9; CI 1.3-12.1). By contrast, OHI- patients had better survival (79%) than predicted by their prognostic scores (OR 0.15; CI 0.07-0.34). More than half of the OHI+ patients died from non-malignant causes (39% multi-organ dysfunction or HLH, 18% infection), while most OHI- patients (92%) died from progressive malignancy. The likelihood of dying from multi-organ dysfunction or HLH was 26 times higher in OHI+ vs. OHI- patients (OR 26.2; CI 4.1-286.7). Image:Summary/Conclusion: OHI index status strongly correlated with mortality in patients with lymphoma within our cohort, and death in OHI+ patients was largely due to causes other than progressive malignancy. The OHI index appears to identify a harmful inflammatory state and deserves further prospective study.

P1377: THE IMPACT OF THE TRAVELED DISTANCE TO THE TRANSPLANT CENTER ON THE CLINICAL OUTCOME OF ALLOGENIC BONE MARROW TRANSPLANT PATIENTS

Background: Several factors affect the outcome of allogeneic stem cell transplantation (Allo-SCT) in hematologic malignancy patients. The disease type, treatment modality and patients’ clinical profile largely determine the outcomes of Allo-SCT; however, the latter may vary among patients with similar aforementioned variables. Proximity to the transplant center could be an independent factor that affects the clinical outcome of Allo-SCT in patients. This is a retrospective study conducted at American University of Beirut Medical Center (AUBMC). Aims: The aim of this study is to determine the differences in the clinical outcome between Allo-SCT patients residing at different distances from the transplant center. Methods: We identified a total of 275 adult patients receiving Allo-SCT between January 2007 and June 2021. The patients were divided into three groups: patients residing within 20 km from AUBMC N=120 (44%) labeled as Urban, patients residing beyond 20 km from AUBMC N=111 (40%) labeled as Rural and patients who arrived from countries abroad N=44 (16%) labeled as Abroad. All patients received Allo-SCT along with the required follow up medical care at AUBMC. Using univariate and multivariate analysis, we examined the impact of distance from the transplant center along with other independent variables on the outcomes of Allo-SCT. Kaplan-Meier curves were also exploited to identify overall survival (OS), progression free survival (PFS) and transplant-related-mortality (TRM). Results: Male predominance is seen in all three groups. The distribution of disease types was similar in all three groups, where acute leukemia was the dominant hematological disease. However, a significant difference in age at transplant was noted, with the Urban group being the eldest (median age=43) and the Abroad group being the youngest (median age=35) (P=0.011). Also, the three groups differed in their median follow up whereby the Abroad group had the shortest (30 months) while the Urban group had the longest (55 months) (P<0.001). Concerning the pre-transplant conditioning regimen, there is no difference in the intensity in all three groups (P=0.052). 89% of patients of the Abroad group, 61% of the Urban and 65% of the Rural received their stem cells from a matched related donor (P=0.047). However, both Urban and Rural groups (35% and 34%) respectively received stem cells from a haplo-identical donor unlike the Abroad group only 9% (P=0.047). On multivariate analysis (Table 2) there was no statistically significant difference at 3 years in terms of OS, TRM and acute GVHD (aGVHD) between the three groups. However, the 3 years PFS was higher among patients from the Abroad group (26.8 months) compared to the Urban group (19.2 months) (P=0.035). Moreover, chronic GVHD (cGVHD) was higher the closer the patient was to the transplant center with a hazard’s ratio (HR) = 2.183 (P=0.044). Image:Summary/Conclusion: Distance didn’t show any significant difference in OS, TRM and aGVHD. On the other hand, the closer patients from the transplant center had higher risk for cGVHD and lower 3 years PFS most probably because they have more frequent and stricter follow up compared to others. More studies should be done on the current matter with adjustments for confounding variables.

P1592: MATCHED CONTROL COMPARISON OF SURVIVAL OF HOSPITALIZED COVID-19 PATIENTS WITH HEMATOLOGICAL MALIGNANCIES, DATA FROM A LARGE TERTIARY CENTER REGISTRY

Background: There is an increasing pool of evidence describing detrimental outcomes of patients with hematological malignancies with acute COVID-19. Aims: to evaluate risk of death with acute COVID-19 in patients with various hematological malignancies in comparison to matched control patients from a large single institution registry. Methods: We retrospectively analyzed all consecutive hospitalized COVID-19 patients treated in period 3/2020-3/2021 in our institution (University hospital Dubrava) that served as a regional COVID-19 referral center during the pandemic. Data from a hospital Registry project were used. Patients with hematological malignancies were compared to the case-control matched group of patients without malignant disease. Matching was performed according to age, sex and modified Charlson comorbidity index (with subtracting points provided for hematological malignancy in hematological malignancy patients). Results: Out of total 4014 consecutive hospitalized COVID-19 patients, there were 154 patients with hematological malignancies. There were 81/154 (52.6%) male patients. Median age was 71 years and median Charlson comorbidity index was 5 points. Most represented hematologic malignancy subtype was chronic lymphocytic leukemia (CLL) present in 37/154 (24%) patients, followed by aggressive lymphomas (30/154 (19.5%)), plasma cell dyscrasias (28/154 (18.2%)), acute leukemias (21/154 (13.6%)), indolent non Hodgkin lymphomas (18/154 (11.7%)), myelodysplastic syndromes (MDS, 12/154 (7.8%)) and chronic myeloproliferative leukemias (8/154 (5.2%)). Disease course significantly differed between disease subsets (P=0.004) as shown in Figure. Patients with CLL and indolent lymphomas experienced more favorable disease course comparable to matched control groups of COVID-19 patients without malignancies, whereas other subsets of patients experienced more rapid deterioration. Recent treatment (actual or in 3 months prior to admission) did not affect survival outcomes (P=0.402), as well as active disease status (P=0.076) but where tendency for worse survival was evident. Patients previously receiving autologous or allogeneic stem cell transplantation also did not significantly differ in survival in comparison to non-transplanted patients (P=0.425). In a multivariate survival analysis, acute leukemias (HR 5.88; P<0.001), MDS (HR 2.91; P=0.006), plasma cell dyscrasias (HR 4.68; P<0.001) and aggressive lymphomas (HR 2.53; P<0.001) were associated with worse survival in comparison to matched control patients independently of age (HR 1.04; P<0.001), modified Charlson comorbidity index (HR 1.1; P=0.017), and COVID-19 severity on admission (HR 5.98; P=0.003 for severe and HR 11.06; P<0.001 for critical vs mild disease). Image:Summary/Conclusion: Hospitalized COVID-19 patients with acute leukemias, MDS, plasma cell dyscrasias and aggressive lymphomas experience higher mortality irrespectively of age, comorbidity burden and COVID-19 severity on admission.

P1607: EPICOVIDEHA KIDS: A READY TO USE PLATFORM FOR EPIDEMIOLOGICAL STUDIES IN PEDIATRIC HEMATOLOGICAL PATIENTS WITH COVID-19

Background: The coronavirus disease 2019 (COVID-19) pandemic has direct impact on patients with active hematological malignancies (HM), who are at a continuous risk for severe disease course and delay of chemotherapy. The COVID-19 study of the European Hematology Association (EPICOVIDEHA) was initiated in February 2020 by an international steering committee. As of November 2021, more than 4,500 adult cases from 35 countries in five continents have been registered. From January 2022, EPICOVIDEHA will broaden its target population, in order to include children too, establishing the EPICOVIDEHA Kids registry. Aims: The aim is to enhance the knowledge of the outcome and clinical management of these patients. The incidence of severe COVID-19, admission to intensive care units (ICU), estimation of pre-existing comorbidities, or associated mortality rate will also be evaluated. Methods: The EPICOVIDEHA Kids survey will be online accessible at www.clinicalsurveys.net. All data will be collected anonymously: demographics, underlying diseases, hematological malignancy, COVID-19 infection, and outcome. Inclusion criteria will be: age below 18 years, active HM within the last 5 years prior to COVID-19, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive test. Each documented patient will be reviewed for data completeness and coherence by a panel of experts. Results: A general publication with the data from all patients will be performed at the end of 2022. Additionally, subset analyses on specific cutting-edge topics might be run after the proposal of any participant with the previous approval of the steering committee of the survey. Summary/Conclusion: EPICOVIDEHA Kids is a ready-to-use survey, whose focal point is to gather epidemiological data from pediatric hematological populations and COVID-19. This study will help to better understand the features of these patients and to ameliorate their clinical management. Additionally, EPICOVIDEHA Kids will enable the partnership of international groups of hematologists and infectious diseases specialists, in order to improve the clinical management of HM patients with COVID-19.

Long-Term Dominance of Carbapenem-Non-Susceptible Pseudomonas aeruginosa ST111 in Hematologic Malignancy Patients and Hematopoietic Cell Transplant Recipients.

An epidemiological study uncovered that fluoroquinolone (FQ) neutropenic prophylaxis in hematopoietic cell transplant and hematologic malignancy (HCT/HM) patients was associated with breakthrough Pseudomonas aeruginosa bloodstream infections (BSIs) with isolates non-susceptible to both FQs and meropenem. The molecular epidemiology of the FQ/meropenem-non-susceptible P. aeruginosa isolates causing FQ-breakthrough BSIs in the HCT/HM patients remains unclear. Through whole genome sequencing on 57 P. aeruginosa isolates from 54 patients diagnosed with HM or receiving an HCT, we found that ST111 strains predominated, accounting for 22 (38.6%) of the isolates. 17 of 33 (51.5%) FQ-breakthrough BSIs were caused by ST111 strains, of which 15 (88.2%) were meropenem non-susceptible. ST111 strains, but not other oprD-deficient, meropenem-non-susceptible clinical strains, were found to have a colonization advantage over P. aeruginosa strain PA14 in C. elegans and to outcompete PA14 in in vitro co-culture assays. Together, we found that breakthrough P. aeruginosa BSIs during FQ prophylaxis in HCT/HM patients are dominated by clonally-related FQ/meropenem non-susceptible strains, predominantly ST111 type, and that the dominance of ST111 strains may be explained by a relative fitness advantage over other clinical strains. Additional work is necessary to better understand the factors driving the dominance and persistence of these ST111 strains.

The Threat of Carbapenem-Resistant Gram-Negative Bacteria in Patients with Hematological Malignancies: Unignorable Respiratory Non-Fermentative Bacteria-Derived Bloodstream Infections.

BackgroundCarbapenem-resistant Gram-negative bacteria (CRGNB) bloodstream infection (BSI) pose a significant threat to the prognosis of hematologic malignancies (HM) patients. Understanding the distribution of pathogenic bacteria, changes in carbapenem-resistant trends, risk factors for CRGNB infections, and exploring the early detection measures can help reduce mortality.MethodsWe conducted a multicenter retrospective study of Gram-negative bacteria (GNB) BSI in patients with HM in three university-affiliated hospitals in Hunan Province, China, from January 2010 to December 2020. Demographic and clinical data were collected from the hospital electronic medical records system.ResultsCRGNB caused 138 (15.3%) of 902 GNB BSI. The detection rate of CRGNB increased from 6.4% in 2010–2012 to 35.4% in 2019–2020. The 7-day mortality rate was significantly higher in patients with CRGNB BSI than in patients with carbapenem-susceptible Gram-negative bacteria (CSGNB) BSI [31.9% (44/138) vs 9.7% (74/764), P < 0.001], and the mortality rate in patients with carbapenem-resistant non-fermenting bacteria (CRNFB) bloodstream infections was generally higher than that of carbapenem-resistant Enterobacteriaceae (CRE). Urinary catheter (OR, 2.814; CI=1.395–5.680; P=0.004) and prior exposure to carbapenem (OR, 4.372; CI=2.881–6.635; P<0.001) were independent risk factors for CRGNB BSI. Analysis of co-infections showed that 50%–85% of patients with CRGNB BSI had pulmonary infections, sputum culture results suggested that sputum culture positivity rate was as high as 57.1%–66.7% in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) and Stenotrophomonas maltophilia BSI, and the results of antimicrobial susceptibility testing of sputum cultures were consistent with the blood cultures.ConclusionCarbapenem resistance has dramatically increased in HM patients with GNB BSI in recent years and is associated with a worse outcome, especially for non-fermenting bacteria. In high-risk patients, early screening of the respiratory tract specimens may help to detect CRNFB colonization and protect patients from breakthrough BSI.

Characteristics of patients with hematologic malignancies without seroconversion post-COVID19 third vaccine dosing (3V): Real-world data from large midwestern healthcare system.

e19513 Background: Patients (Pts) with hematologic malignancies (HM) are at greater risk of severe morbidity and mortality caused by COVID19 and show a lower response to the two-dose COVID19 mRNA vaccine series. The primary vaccine series now includes a third dose of the COVID19 vaccine (3V) for immunocompromised Pts. The objective of this study was to explore the characteristics of HM patients who had no change in SARS-CoV-2 spike protein titer levels post 3V (-/-) to gain a better understanding of the drivers of serostatus. Methods: This retrospective cohort study analyzed Pt data on SARS-CoV-2 spike IgG antibody titers pre- and post- 3V across the healthcare system. This study included 268 fully vaccinated HM Pts diagnosed with HM between October 31, 2019 and January 31, 2022 and had a negative serostatus prior to 3V. Post 3V titers were obtained 21 days after 3V. Demographics, association between characteristics and seroconversion status, and odds ratios were all assessed (table). Results: Pts with Non-Hodgkin lymphoma (NHL) had 6 times the odds of not seroconverting compared to multiple myeloma (MM) (CI 1.88 – 19.12, P = .0010). NHL also have about 14 times the odds of not seroconverting compared to Pts diagnosed with other HM conditions, which included: neoplasms of uncertain behavior and disorders of white blood cells (CI 1.72 – 112.44, P = .0021). 90% of seronegative Pts showed no spike IgG antibody reaction to 3V as indicated by pre- and post- 3V index values. Demographics, previous COVID19 infection, and vaccine type were not significantly associated with seroconversion. Conclusions: HM patients who are not seroconverting after 3V, suggest a prioritized population for continued increased behavioral precautions, additional vaccination efforts, including a fourth dose of an mRNA COVID19 vaccine, as well as passive immunity boosting through monoclonal and polyclonal antibodies.[Table: see text]

The utility of the novel optimized HLH inflammatory (OHI) index for predicting the risk for mortality and causes of death in lymphoma.

7570 Background: Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening inflammatory syndrome that may complicate hematologic malignancies (HM). We recently developed a simplified diagnostic and prognostic index termed the ‘optimized HLH inflammatory’ (OHI) index comprising the combined elevation of sCD25 ( &gt; 3,900 U/mL) and serum ferritin ( &gt; 1,000 ng/mL), which in HM patients both identifies HLH and predicts mortality more accurately than conventional criteria for HLH. In this study, we examined whether mortality in our cohort is directly related to progressive malignancy vs. HLH-associated causes in OHI+ and OHI- patients. Methods: We performed a multicenter, retrospective study of patients with newly diagnosed lymphoma from Israel, the USA, and Japan for whom sCD25 and ferritin levels were measured either as routine surveillance or during investigation for HLH and classified patients by their OHI status. The International Prognostic Index, International Prognostic Score, and Follicular Lymphoma International Prognostic Index were used to estimate the predicted prognosis of T/B cell non-Hodgkin’s lymphoma (NHL), Hodgkin’s lymphoma, and follicular lymphoma, respectively. Predicted five-year overall survival was calculated based on the relevant prognostic index and was compared between OHI+ and OHI- patients using the unpaired t-test. The actual survival at five years/last follow-up was recorded, as was the cause of death. The odds ratios (ORs) for observed vs. predicted mortality, and for HLH- vs. malignancy-related death were calculated using the Chi-square test. Results: 100 lymphoma patients were studied: 65% with B cell NHL, 18% with natural killer/ T cell lymphoma, 17% with Hodgkin’s lymphoma; 37 were OHI+, and 63 were OHI-. The disease-relevant international prognostic index-predicted five-year survival did not differ between OHI + and OHI- patients (a mean of 58% n OHI+ and 57% in OHI- p = 0.62). However, the observed five-year survival in OHI+ patients was lower (12%) than predicted, reflecting a mortality incidence that was four times higher than predicted by the relevant prognostic score (OR 3.9; CI 1.3-12.1). By contrast, OHI- patients had better survival (79%) than predicted by their prognostic scores (OR 0.15; CI 0.07-0.34). More than half of the OHI+ patients died from non-malignant causes (39% multi-organ dysfunction or HLH, 18% infection), while most OHI- patients (92%) died from progressive malignancy. The likelihood of dying from multi-organ dysfunction or HLH was 26 times higher in OHI+ vs. OHI- patients (OR 26.2; CI 4.1-286.7). Conclusions: OHI index status strongly correlated with mortality in patients with lymphoma within our cohort, and death in OHI+ patients was largely due to causes other than progressive malignancy. The OHI index appears to identify a harmful inflammatory state and deserves further prospective study.

Infections in hematologic malignancy patients treated by CD19 chimeric antigen receptor T‐cell therapy

AbstractIncreasing use of chimeric antigen receptor‐T (CAR‐T) cell therapy has significantly improved the survival of hematologic malignancy patients, but CAR‐T cell treatment is also associated with increased risk of infection. Hence, understanding the characteristics of infection may improve disease prognosis. The data of post‐CAR‐T therapy infections were obtained from the VigiBase database. We identified a total of 554 infection reports (1001 infection events) involving CAR‐T therapy among the 3007 case reports. Infections occurred in 18.42% of cases reported in VigiBase with CAR‐T therapy and were most frequently occurred during the first month. Among cases reported in VigiBase, most of the infections were controllable, and only 4.4% of the cases were fatal. Bacteria (60.7%) and respiratory tract infection (50.9%) were the most common infection types. Compared with axicabtagene ciloleucel, infection in patients receiving tisagenlecleucel‐T therapy had a higher infection risk (ROR = 1.76; 95% CI = 1.46–2.12, p &lt; 0.001). Meanwhile, fungus infection and mixed infection had poorer prognoses than virus infection. Concerning the disease prognoses, fungal and mixed infection should be given more attention, and extensive prospective studies are much needed to verify these findings.