Acute Leukemia Research Articles

Management of hematological patients requiring emergency chemotherapy in the intensive care unit.

Hematological malignancies may require rapid-onset treatment because of their short doubling time, notably observed in acute leukemias and specific high-grade lymphomas. Furthermore, in targeted onco-hematological scenarios, chemotherapy is deemed necessary as an emergency measure when facing short-term, life-threatening complications associated with highly chemosensitive hematological malignancies. The risks inherent in the disease itself, or in the initiation of treatment, may then require admission to the intensive care unit (ICU) to optimize monitoring and initial management protocols. Hyperleukocytosis and leukostasis in acute leukemias, tumor lysis syndrome, and disseminated intravascular coagulation are the most frequent onco-hematological complications requiring the implementation of emergency chemotherapy in the ICU. Chemotherapy must also be started urgently in secondary hemophagocytic lymphohistiocytosis. Tumor-induced microangiopathic hemolytic anemia and plasma hyperviscosity due to malignant monoclonal gammopathy represent infrequent yet substantial indications for emergency chemotherapy. In all cases, the administration of emergency chemotherapy in the ICU requires close collaboration between intensivists and hematology specialists. In this review, we provide valuable insights that aid in the identification and treatment of patients requiring emergency chemotherapy in the ICU, offering diagnostic tools and guidance for their overall initial management.

Comprehensive analysis of the efficacy and safety of CAR T-cell therapy in patients with relapsed or refractory B-cell acute lymphoblastic leukaemia: a systematic review and meta-analysis

Background Relapse/refractory B-cell acute lymphoblastic leukaemia (r/r B-ALL) represents paediatric cancer with a challenging prognosis. CAR T-cell treatment, considered an advanced treatment, remains controversial due to high relapse rates and adverse events. This study assessed the efficacy and safety of CAR T-cell therapy for r/r B-ALL. Methods The literature search was performed on four databases. Efficacy parameters included minimal residual disease negative complete remission (MRD-CR) and relapse rate (RR). Safety parameters constituted cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Results Anti-CD22 showed superior efficacy with the highest MRD-CR event rate and lowest RR, compared to anti-CD19. Combining CAR T-cell therapy with haploidentical stem cell transplantation improved RR. Safety-wise, bispecific anti-CD19/22 had the lowest CRS rate, and anti-CD22 showed the fewest ICANS. Analysis of the costimulatory receptors showed that adding CD28ζ to anti-CD19 CAR T-cell demonstrated superior efficacy in reducing relapses with favorable safety profiles. Conclusion Choosing a more efficacious and safer CAR T-cell treatment is crucial for improving overall survival in acute leukaemia. Beyond the promising anti-CD22 CAR T-cell, exploring costimulatory domains and new CD targets could enhance treatment effectiveness for r/r B-ALL.

Clinical Features and Treatment Outcome of Pediatric Acute Promyelocytic Leukemia in Combined Military Hospital, Dhaka

Background: Acute promyelocytic leukemia (APML) is a relatively rare blood disease in children that is highly curable with current treatment strategies. It is a distinct type of AML characterized by chromosomal translocations involving the retinoid acid receptor (RAR-A) gene on chromosome 17. It accounts for 20-25% of all AML cases. The aim of this study was to describe the diagnostic features of pediatric APL and the result with ATRA and ATO based protocol. Methods: It was a descriptive type of cross-sectional study with purposively selected 10 newly diagnosed APML patients treated in the Pediatric Oncology unit of the Department of Pediatrics in CMH Dhaka during the period of 2018 to 2022. Diagnosis of all patients were done by aspirating bone marrow morphology and cytogenetic t(15:17) or t(11:17) transcript. Informed written consent was taken from parents. Data were collected by semi-structured questionnaire and analyzed by Statistical Package for Social Sciences (SPSS version 25). Results: Among 10 respondents median age was 4.2 years with female predominant (60%). Most common clinical presentations at diagnosis were fever (100%), bleeding manifestations (100%), Hepatomegaly (90%) bony tenderness (90%), splenomegaly (70%), and lymphadenopathy (70%). Almost all the patients had low Hb & low platelet count & WBC were variable. Cytogenetic analysis revealed 90% had PML/RARA positive & 30% had FLT3/ITD positive. All of these patients were treated with trans-retinoic acid (ATRA) based treatment, which led to 80% cases ATRA syndrome. Other common toxicities noticed febrile neutropenia (50%), severe headache (30%), hyperpigmented skin (10%), pseudotumor cerebri (10%) and others. There were 10% relapse cases, which later proceeded to relapse protocol and were in remission. The remaining 90% of patients were alive and in remission until the last day of follow-up. Conclusion: With ATRA-based treatment overall survival is good achieved remission and only 10% of patients developed relapse. Bangladesh Armed Forces Med J Vol 56 No (2) December 2023, pp 1-9

CURRENT USE AND OUTCOMES OF HEMATOPOIETIC STEM CELL TRANSPLANTATION: BRAZILIAN SUMMARY SLIDES – 2024

The development of the Brazilian Registry of Hematopoietic Cell Transplantation in collaboration with the Center for International Blood and Marrow Transplant Research (CIBMTR) allowed for an assessment of the activity and general outcomes of transplants in Brazil. Here, we report an updated activity. Brazilian transplant centers report their data to the CIBMTR, using the FormsNet3 platform. Information returns to Brazilian Cellular Therapy and Bone Marrow Transplant Society (SBTMO) through the Data Back to Centers (DBtC) tool. Data from patients who received an HCT from 2012 to 2023 from Brazilian centers were extracted from CIBMTR. Descriptive analysis was carried out by patient-, disease- and transplant-specific variables and overall survival analysis using Kaplan Meyer. A total of 12,230 patients were eligible for this study (5,573 autologous and 6,657 allogeneic transplants). The number of reporting centers increased from 40 to 44 during the period. The most common HCT indication in Brazil is AML for allogeneic HCT with 152 transplants year and multiple myeloma for autologous HCT with 245 transplants per year. Among allogeneic HCT, in the last 4 years, mismatched related donor was the main source of donors. Regarding the graft source for allogeneic transplants, BM was the most frequent among pediatric transplants, while PBSC was the most used in adults. Infections were the leading cause of death in the first 100 days after all types of transplants. Patients with acute leukemia who underwent HCT with advanced stage disease had lower survival rates compared to those at other stages. Despite the differences in the number of cases and follow-up time, the results in this study were similar to those presented in the United States (US) Summary Slides.

Valrubicin-loaded immunoliposomes for specific vesicle-mediated cell death in the treatment of hematological cancers

We created valrubicin-loaded immunoliposomes (Val-ILs) using the antitumor prodrug valrubicin, a hydrophobic analog of daunorubicin. Being lipophilic, valrubicin readily incorporated Val-lLs that were loaded with specific antibodies. Val-ILs injected intravenously rapidly reached the bone marrow and spleen, indicating their potential to effectively target cancer cells in these areas. Following the transplantation of human pediatric B-cell acute lymphoblastic leukemia (B-ALL), T-cell acute lymphoblastic leukemia (T-ALL), or acute myeloid leukemia (AML) in immunodeficient NSG mice, we generated patient-derived xenograft (PDX) models, which were treated with Val-ILs loaded with antibodies to target CD19, CD7 or CD33. Only a small amount of valrubicin incorporated into Val-ILs was needed to induce leukemia cell death in vivo, suggesting that this approach could be used to efficiently treat acute leukemia cells. We also demonstrated that Val-ILs could reduce the risk of contamination of CD34+ hematopoietic stem cells by acute leukemia cells during autologous peripheral blood stem cell transplantation, which is a significant advantage for clinical applications. Using EL4 lymphoma cells on immunocompetent C57BL/6 mice, we also highlighted the potential of Val-ILs to target immunosuppressive cell populations in the spleen, which could be valuable in impairing cancer cell expansion, particularly in lymphoma cases. The most efficient Val-ILs were found to be those loaded with CD11b or CD223 antibodies, which, respectively, target the myeloid-derived suppressor cells (MDSC) or the lymphocyte-activation gene 3 (LAG-3 or CD223) on T4 lymphocytes. This study provides a promising preclinical demonstration of the effectiveness and ease of preparation of Val-ILs as a novel nanoparticle technology. In the context of hematological cancers, Val-ILs have the potential to be used as a precise and effective therapy based on targeted vesicle-mediated cell death.

A Difficult Case of Ventriculitis in a 40-Year-Old Woman with Acute Myeloid Leukemia

Ventriculitis and nosocomial meningitis caused by carbapenem-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria represent a growing treatment challenge. A case of ventriculitis and bacteremia caused by carbapenem-resistant, KPC-producing Klebsiella pneumoniae and vancomycin-resistant Enterococcus faecium in a young woman with acute leukemia who was successfully treated with meropenem/vaborbactam (MVB), rifampicin, and linezolid is described in this paper. This case report emphasizes the importance of a multidisciplinary strategy, including infectious focus control, for the treatment of device-associated central nervous system (CNS) infections from multidrug-resistant bacteria. Considering the novel resistance patterns, more research on drug penetration into the central nervous system, as well as on the necessity of association therapies, is needed.

Minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) masquerading as acute leukemia.

Drug reaction with eosinophilia and systemic symptoms (DRESS) is an idiosyncratic drug reaction characterized by fever, rash, and lymphadenopathy associated with atypical lymphocytosis and eosinophilia. Visceral organ involvement is also seen and hence it often mimics hematolymphoid malignancies. A 19-year-old girl presented with generalized pruritic rash, fever, lymphadenopathy, and lymphocytosis. Subsequently, she developed respiratory distress with a fall in SpO2. Flow cytometry, bone marrow studies, and infectious workup were normal. Skin biopsy and clinical assessment criteria established the diagnosis of DRESS secondary to minocycline intake. Discontinuation of the offending drug is most important to abet the hypersensitivity reaction. Visceral organ involvement requires the use of steroids and immunosuppressive agents. Our patient responded well to treatment and is presently symptom-free and on follow-up for the last 6 months.

Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.

Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.

Targetable leukaemia dependency on noncanonical PI3Kγ signalling.

Phosphoinositide-3-kinase-γ (PI3Kγ) is implicated as a target to repolarize tumour-associated macrophages and promote antitumour immune responses in solid cancers1-4. However, cancer cell-intrinsic roles of PI3Kγ are unclear. Here, by integrating unbiased genome-wide CRISPR interference screening with functional analyses across acute leukaemias, we define a selective dependency on the PI3Kγ complex in a high-risk subset that includes myeloid, lymphoid and dendritic lineages. This dependency is characterized by innate inflammatory signalling and activation of phosphoinositide 3-kinase regulatory subunit 5 (PIK3R5), which encodes a regulatory subunit of PI3Kγ5 and stabilizes the active enzymatic complex. We identify p21 (RAC1)-activated kinase 1 (PAK1) as a noncanonical substrate of PI3Kγ that mediates this cell-intrinsic dependency and find that dephosphorylation of PAK1 by PI3Kγ inhibition impairs mitochondrial oxidative phosphorylation. Treatment with the selective PI3Kγ inhibitor eganelisib is effective in leukaemias with activated PIK3R5. In addition, the combination of eganelisib and cytarabine prolongs survival over either agent alone, even in patient-derived leukaemia xenografts with low baseline PIK3R5 expression, as residual leukaemia cells after cytarabine treatment have elevated G protein-coupled purinergic receptor activity and PAK1 phosphorylation. Together, our study reveals a targetable dependency on PI3Kγ-PAK1 signalling that is amenable to near-term evaluation in patients with acute leukaemia.

Analysis of retinal and choroidal microvascular changes using optical coherence tomography and optical coherence tomography angiography in patients with acute leukemia.

Although leukemic retinopathy accounts for 80% of ocular complications in acute leukemia, its pathogenesis remains unclear. To evaluate changes in retinal and choroicapillaris and structural parameters in patients with acute leukemia, we analyzed the correlation between vascular perfusion metrics and laboratory parameters and assessed the changes after hematopoietic stem cell transplantation (HSCT). Herein, 104 eyes of 52 patients aged 18 and above with acute leukemia were enrolled. 80 eyes of 40 healthy patients were recruited as control participants. All participants underwent optical coherence tomography (OCT) and OCT angiography (OCTA) at baseline. Patients with acute leukemia had a significantly thicker ganglion cell-inner plexiform layer (GCIPL) and lower circularity index than the control participants. Post-HSCT perfusion metrics did not differ significantly, but parafoveal thickness decreased significantly. During the active phase of acute leukemia, lower platelet levels were associated with significant GCIPL thickening and increased foveal avascular zone and perimeter. D-dimer levels positively correlated with GCIPL thickness. Patients with acute leukemia had subclinical retinal microvascular deficits on OCTA and GCIPL thickening on OCT, possibly associated with bone marrow function. GCIPL thickness may indicate acute ischemia in such patients. Further studies must elucidate their clinical and prognostic significance.

Case report of anti JMH: A high-titer, low-avidity antibody posing difficulty in immunohematological tests

This report presents a patient with anti-John Milton Hagen (JMH) posing difficulties in the immunohematological test in the Blood Bank Unit of Universiti Kebangsaan Malaysia Medical Center. A 1-year-8-month-old boy was referred to our center to rule out acute leukemia from a private hospital. A crossmatch request was sent to the Blood Bank before the bone marrow biopsy. Our testing revealed his blood grouping as O Rh-D positive. His Direct Antiglobulin Test was positive, and his antibody screening and antibody identification showed weak pan-reactivity. However, reactions were negative with enzyme-treated cells. Red cell elution showed interestingly no reaction in the eluate, suspected to be due to drug-induced autoantibody. Further tests of antibody titration and neutralization test suggest it could be a high-titer low avidity (HTLA) antibody, most likely Anti-JMH. Although HTLA antibodies are clinically insignificant, they can cause confusion and delay in issuance of blood products. There are also cases of clinically significant HTLA antibodies. Determining the type of HTLA antibody may guide the extent of further testing required to utilize resources best and, most importantly, to assure patient safety.

Haploidentical hematopoietic cell transplantation with or without an unrelated cord blood unit for adult acute myeloid leukemia: a multicenter, randomized, open-label, phase 3 trial

sCoinfusion of unrelated cord blood (UCB) units in haploidentical hematopoietic cell transplantation (haplo-HCT) (haplo-cord HCT) for hematopoietic malignancies showed promising results in previous reports, but the efficiency of haplo-cord HCT in acute myeloid leukemia (AML) still lacks sufficient evidence. This multicenter, randomized, phase 3 trial (ClinicalTrials.gov NCT03719534) aimed to assess the efficacy and safety of haplo-cord HCT in AML patients. A total of 268 eligible patients aged 18–60 years, diagnosed with measurable residual disease in AML (excluding acute promyelocytic leukemia), with available haploidentical donors and suitable for allotransplantation, were randomly allocated (1:1) to receive haplo-cord HCT (n = 134) or haplo-HCT (n = 134). The 3-year overall survival (OS) was the primary endpoint in this study. Overall median follow-up was 36.50 months (IQR 24.75–46.50). The 3-year OS of Haplo-cord HCT group was better than haplo-HCT group (80.5%, 95% confidence interval [CI]: 73.7–87.9 vs. 67.8% 95% CI 60.0–76.5, p = 0.013). Favorable progression-free survival (70.3%, 95% CI 62.6–78.8 vs. 57.6%, 95% CI 49.6–67.0, p = 0.012) and cumulative incidence of relapse (12.1%, 95% CI 12.0–12.2 vs. 30.3%, 95% CI 30.1–30.4, p = 0.024) were observed in haplo-cord HCT group. Grade 3–4 adverse events (AEs) within two years posttransplantation in the two groups were similar. Haplo-cord HCT patients exhibited a faster cumulative incidence of neutrophil recovery (p = 0.026) and increased T-cell reconstitution in the early period posttransplantation. Haplo-cord HCT can improve OS in AML patients without excessive AEs, which may exert additional benefits for recipients of haplo-HCT.

Clinical characteristics of acute myeloid leukaemia patients with a large number of azurophilic granules: A single-centre retrospective study.

Large amounts of azurophilic granules are considered to be a morphological feature of acute promyelocytic leukaemia (APL). However, a small percentage of acute myeloid leukaemia (AML) patients also have a large number of azurophilic granules. A large cohort of 3210 AML patients in our hospital was screened to identify AML patients who had a large number of azurophilic granules. The clinical parameters of these patients were collected and compared with typical AML patients (control Group 1) and APL patients (control Group 2). The incidence of AML with a large number of azurophilic granules was 1.26%. The fibrinogen and D-dimer levels of patients in the study group were more similar to those of patients in control Group 2, as was the incidence of bleeding events. Additionally, patients in the study group had higher FLT3-ITD and NPM1 mutation rates than patients in control Group 1. Finally, patients in the study group had a higher 30-day mortality rate than those in control Group 2 (24.2% vs. 9.09%) and showed a higher 30-day mortality trend than those in control Group 1. Therefore, we should pay more attention to the prevention of coagulation dysfunction and bleeding events for these patients.

MATERNAL LIFESTYLE AND PRENATAL RISK FACTORS FOR CHILDHOOD LEUKEMIA: A REVIEW OF THE EXISTING EVIDENCE.

Acute leukemia is the most common pediatric cancer, with an incidence peak at 2-5 years of age. Despite the medical advances improving survival rates, children suffer from significant side-effects of treatments as well as its high social and economic impact. The frequent prenatal origin of this developmental disease follows the two-hit carcinogenesis model established in the 70s: a first hit in prenatal life with the creation of genetic fusion lesions or aneuploidy in hematopoietic progenitor/stem cells, and usually a second hit in pediatric age that converts the preleukemic clone into clinical leukemia. Previous research has mostly focused on postnatal environmental factors triggering the second hit. There is scarce evidence on prenatal risk factors associated with the first hit. Mainly retrospective case-control studies suggested several environmental and lifestyle determinants as risk factors. If these associations could be confirmed, interventions focused on modifying prenatal factors might influence the subsequent risk of leukemia during childhood and reveal unexplored research avenues for the future. In this review, we aim to comprehensively summarize the currently available evidence on prenatal risk factors for the development of childhood leukemia.

Pseudotumor Cerebri Secondary to All-Trans Retinoic Acid/Arsenic Trioxide Therapy in Acute Promyelocytic Leukemia: A Case Report and Review of the Literature.

Pseudotumor Cerebri Secondary to All-Trans Retinoic Acid/Arsenic Trioxide Therapy in Acute Promyelocytic Leukemia: A Case Report and Review of the Literature.

Health locus of control and symptom distress: The mediating role of illness acceptance and symptom severity in acute leukemia patients

ObjectiveThis study aims to explore the multiple mediating roles of illness acceptance and symptom severity between health locus of control and symptom distress in acute leukemia patients. MethodsFrom June 2022 to March 2023, a convenience sampling method was used to recruit 208 acute leukemia patients in the inpatient center of a hospital in Hebei. The Chinese versions of Multidimensional Health Locus of Control Scale, Illness Acceptance Scale, and Anderson Symptom Assessment Scale was used in the cross-sectional study. ResultsAll participants reported the presence of symptom distress. Symptom distress was significantly correlated with chance health locus of control, illness acceptance, and symptom severity (P＜0.05). Illness acceptance alone played a mediating role in the relationship between chance health locus of control and symptom distress in acute leukemia patients (β=0.087, 95%CI 0.030–0.167). The indirect role of chance health locus of control on symptom distress through symptom severity alone was also statistically significant (β=0.131, 95%CI 0.008–0.252). Furthermore, the multiple mediating role of chance health locus of control and symptom distress through illness acceptance and symptom severity combined was verified (β=0.027, 95%CI 0.001–0.089). The alternative model is also valid, indicating bidirectional relationships between symptom severity, illness acceptance, and chance health locus of control, collectively influencing symptom distress. ConclusionThere is a positive relationship between chance health locus of control and symptom distress; additionally, increasing social psychological interventions for illness acceptance and strengthening the management of core symptoms will help alleviate the impact of health chance locus of control on symptom distress in acute leukemia patients. Longitudinal studies are needed to confirm the causal relationships among the variables explored within the model. Impact on nursing practiceIt is recommended that healthcare professionals pay attention to the assessment of health locus of control in patients, identify patients with health chance locus of control in a timely manner, take measures to enhance their disease acceptance, and strengthen the management of core symptoms, thereby reducing their level of symptom distress.

Efficacy of Episil® in patients with hematologic malignancies: a comparative study

BackgroundEpisil® is a nonabsorbable liquid medical material used to coat and protect the mucosa in patients with oral mucositis. A few studies have reported its efficacy in patients with head and neck cancer. However, reports on its use in patients with hematologic malignancies are scarce. Thus, we aimed to evaluate the efficacy of Episil for the treatment of oral mucositis in patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome.MethodsBetween May 2018 and March 2019, a total of thirty-seven patients with acute myelogenous leukemia, malignant lymphoma, acute lymphocytic leukemia, multiple myeloma, and myelodysplastic syndrome who received Episil® for the treatment of oral mucositis were included in this study. All patients were treated at the Hiroshima Red Cross and Atomic-bomb Surgery Hospital. To determine the severity of oral mucositis, 22 out of the 37 patients were interviewed and compared objectively using the Common Terminology Criteria for Adverse Events, version 3.0. In addition, subjective measures of the effects of oral mucositis were assessed using an original evaluation protocol (a unique evaluation chart specific to the Department of Oral Surgery, Hiroshima Red Cross & Atomic-bomb Survivors Hospital).ResultsOut of 37 participants recruited in the study, 31 (84%) described the sensation of Episil® as very good or good. Moreover, the severity of mucositis was found to decrease after the use of Episil® in seven patients out of 22 (19%), particularly in those with mucositis at multiple sites. Participants' evaluations revealed pain relief and improvement in speech and feeding functions. Participants with grade 3 mucositis reported a greater improvement in pain relief, speech, and feeding functions than those with grade 2 mucositis.ConclusionsThis study suggests the efficacy of Episil® in treating oral mucositis in patients with hematologic malignancies, particularly in those with oral mucositis at multiple sites. In addition to pain relief, Episil® may improve speech and feeding functions.

Biochemical risk factors and outcomes of acute promyelocytic leukemia patients with thrombotic events: a matched pair analysis.

Acute promyelocytic leukemia (APL) stands out as a distinctive form of acute leukemia, exhibiting a higher occurrence of thrombotic events when contrasted with other leukemia subtypes. Since thrombosis is a relatively rare but unfavorable condition with poor prognostic implications, it is crucial to determine the risk factors for thrombotic events in APL(thrombosis in large venous or arterial from onset to differentiation therapy in 30d). We performed a retrospective study involving 950 APL patients between January 2000 and October 2022, from which 123 were excluded by younger than 16years of age, 95 were excluded by incomplete data, and 6 were excluded by thrombosis related to CVC or PICC. A total of 23 APL patients with thrombosis for inclusion in our analysis were performed a 1:5 ratio matching based on sex (perfect match) and age (within 5years) to patients without thrombosis. These patients were continuously monitored in the outpatient department over a period of 5years. We meticulously examined clinical and laboratory data to pinpoint the risk factors related to thrombotic events in APL. Our primary clinical endpoints were all-cause mortality and achieving complete remission, while secondary clinical outcomes included APL relapse. Thrombotic events were observed in 2.4% (23/950) of APL patients. Compared to patients without thrombosis, patients with thrombosis had higher lactate dehydrogenase (LDH) [313 (223, 486) vs. 233 (188, 367) U/L, p = 0.020], higher indirect bilirubin [11.2 (7.4, 18.6) vs.8.3 (6.0, 10.7) umol/L, p = 0.004], higher creatinine [72 (62, 85) vs. 63 (54, 74) umol/L, p = 0.026], higher CD2 expression (65.2 vs. 15.2%, p < 0.001), higher CD15 expression (60.9 vs. 24.3%, p = 0.001), and PML/RARαisoforms (p < 0.001). Multivariate-logistic-regression analysis revealed several factors that were markedly related to thrombosis, including LDH (OR≈1.003, CIs≈1.000-1.006, p = 0.021), indirect bilirubin (OR≈1.084, CIs≈1.000-1.188, p = 0.043), CD2 expression positive (OR≈16.629, CIs≈4.001-62.832, p < 0.001), and CD15 expression positive (OR≈7.747, CIs≈2.005-29.941, p = 0.003). The S-type (OR≈0.012, CIs≈0.000-0.310, p = 0.008) and L-type (OR≈0.033, CIs≈0.002-0.609, p = 0.022) PML/RARα isoforms were negatively associated with thrombosis. Kaplan-Meier curves indicated that the survival rates were remarkably varied between APL patients with and without thrombosis (HR:21.34, p < 0.001). LDH and indirect bilirubin are variables significantly associated with thrombosis in APL, S-type and L-type PML/RARαisoforms exhibit a negative association with thrombotic events. The thrombotic events of APL can predict the subsequent survival of thrombosis. The findings of our study have the potential to facilitate early detection of thrombosis and enhance the prognosis for individuals with APL who develop thrombosis. Further validation of our findings will be essential through future prospective or multicenter studies.

Effectiveness of a family empowerment program on caregiving capacity and adverse mood in caregivers of children with acute leukemia: a quasi-experimental study

BackgroundFamily-centered empowerment programs have been widely used in the pediatric field. Therefore, the current study investigated the effectiveness of family empowerment programs on caregiving ability and adverse mood among caregivers of children with acute leukemia.ObjectiveTo evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia.MethodsSixty-eight children with acute leukemia and their family caregivers admitted to our hospital were selected for the study. The control group received routine care during hospitalization, and the family empowerment program was implemented in the intervention group to compare the changes in caregiving capacity (FCTI), illness uncertainty (PPUS) and anxiety(SAS)of the caregivers of the two groups.ResultsAfter 8 weeks of intervention, the FCTI score of the intervention group was significantly lower than that of the control group (P < 0.001), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the PPUS score of the intervention group was significantly lower than that of the control group (P < 0.05), and the difference between the scores before and after the intervention was statistically significant (P < 0.001); the SAS score of the intervention group was lower than that of the control group after intervention(P < 0.05), and the score difference before and after intervention was statistically significant (P < 0.001).ConclusionFamily empowerment program is beneficial in improving caregiving capacity and reducing disease uncertainty and anxiety among caregivers of children with acute leukemia.Trial registrationChinese Clinical Trial Registry ChiCTR2300073476 2023-07-12 Retrospectively registered.

Acute lymphocytic leukemia detection and subtype classification via extended wavelet pooling based-CNNs and statistical-texture features

Acute lymphoblastic leukemia (ALL) is considered the most fatal form of leukemia (also known as blood cancer). It propagates quickly among adults and children and could lead to their death. Early detection of ALL and ALL subtypes is the key factor in selecting effective treatment types and improving survival rates. However, routine diagnostic approaches have several drawbacks. Computer-assisted diagnosis (CAD) is the perfect solution to avoid these challenges and achieve a fast and accurate diagnosis. Current CAD models require enhancement/segmentation processing. Besides, they are either dependent on deep learning (DL) models or handcrafted features along with machine learning. Those CADs that employed DL approaches relied solely on spatial information during the training procedure. However, learning them with spectral temporal and temporal representations could improve performance. Furthermore, integrating deep features from DL models along with handcrafted features can increase the discrimination ability of attributes in medical image classification. This study aims to propose a novel CAD for ALL detection and subtype classification without pre-segmentation or enhancement steps. The proposed CAD extends the conventional DL models of convolutional neural networks by introducing an additional wavelet pooling, accompanied by a dense layer or a long-short-term memory (LSTM) layer, and then a SoftMax layer, acquiring spectral-temporal information along with temporal information. To further improve the framework's ability to discriminate, the introduced CAD then combines the wavelet-based deep features of every CNN with numerous handcrafted attributes. Afterward, a feature selection methodology is utilized to create a model with limited features and improved accuracy. The performance results show that the novel CAD is capable of achieving 100% ALL detection accuracy, as well as 100% ALL-subtype classification accuracy with just 88 and 146 features. Thus, this CAD can be employed to assist pathologists in the rapid and precise ALL identification and subcategories recognition.