A hybrid protocol CLAG-M, a possible player for the first-line therapy of patients with mixed phenotype acute leukemia. A Polish Adult Leukemia Group experience.

Introduction: Mixed-phenotype acute leukemia (MPAL) is a rare disease with poor prognosis. So far, no standard approach has been established as the "know-how" of MPAL is based only on retrospective analyses performed on small groups of patients. Materials and methods: In this study, a retrospective analysis of the outcomes of adult MPAL patients included in the PALG registry between 2005 and 2024 who received the CLAG-M hybrid protocol as induction or salvage therapy was performed. Results: Sixteen of 98 MPAL patients received CLAG-M: eight as first-line and eight as salvage therapy. In the first line, two patients achieved partial response (PR), and six achieved complete remission (CR), of whom four successfully underwent allogeneic hematopoietic stem cell transplantation (alloHSCT). Two patients who did not undergo alloHSCT promptly relapsed. Within the whole group, the overall response rate (ORR) was 75% (n = 12/16). With the median follow-up of 13 months, six out of eight patients remain in CR, however, two of them died due to acute graft versus host disease. Out of eight patients who received CLAG-M in the second line, four patients (50%) obtained CR. AlloHSCT was conducted in seven cases, six of which were in CR. Only two patients remained in CR at the time of the last follow-up. Tolerance to treatment was good. The median times for severe neutropenia and thrombocytopenia were 22 days (range, 16-24) and 17 days (range, 12-24), respectively. Overall, grade 3-4 infections were observed in 12 cases, and all infections presented successful outcomes. Conclusions: CLAG-M is an effective first-line salvage regimen for MPAL with an acceptable safety profile. Early achievement of CR with prompt alloHSCT allows for satisfactory disease control.

The tumour suppressor Fat1 is dispensable for normal murine hematopoiesis.

Loss and overexpression of FAT1 occurs among different cancers with these divergent states equated with tumor suppressor and oncogene activity, respectively. Regarding the latter, FAT1 is highly expressed in a high proportion of human acute leukemias relative to normal blood cells, with evidence pointing to an oncogenic role. We hypothesized that this occurrence represents legacy expression of FAT1 in undefined hematopoietic precursor subsets that is sustained following transformation, predicating a role for FAT1 during normal hematopoiesis. We explored this concept by using the Vav-iCre strain to construct conditional knockout (cKO) mice where Fat1 expression was deleted at the hematopoietic stem cell stage. Extensive analysis of precursor and mature blood populations using multi-panel flow cytometry revealed no ostensible differences between Fat1 cKO mice and normal littermates. Further functional comparisons involving colony forming unit and competitive bone marrow transplantation assays support the conclusion that Fat1 is dispensable for normal murine hematopoiesis.

Donor's age influences outcome in haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide - a single center experience.

Haploidentical stem cell transplantation (haplo-SCT) using post-transplantation cyclophosphamide (post-Cy) is considered a reasonable therapeutic option for patients who lack matched donor or who urgently need transplant procedure due to high risk disease. We analyzed the results of haplo-SCT performed in years 2018-2023. Eighty one patients (46 males) at median age of 52 years underwent haplo-SCT using peripheral blood as a stem cell source in most cases. Indications included hematological malignancies (acute leukemias in 88% of cases). In 25 cases (31%) transplantation was performed in relapsed/refractory disease. Majority of patients (61%) presented with very high and high disease risk index (DRI). Conditioning regimens were as follows: nonmyeloablative - 46 cases (57%), myeloablative - in 18 (22%) and reduced intensity - 17(20%). 90% of patients engrafted. All patients received unified immunosuppressive treatment (post-Cy/TAC/MMF). Median follow-up time was 12 months The cumulative incidence of acute and chronic GVHD was 37.5% and 37.6%, respectively. Estimated 2-year overall survival (OS) was 43.1% and donor's age was the only factor influencing survival. The 2-year progression-free survival (PFS) was 42.5%, whereas relapse incidence (RI) - 35%. The cumulative incidence of non-relapse mortality (NRM) was 44% and was mostly due to infections. Haplo-SCT is a feasible treatment option for hematological patients. Younger donor improves post-transplant survival. Strategies to reduce infection-related mortality and relapse rate remain a challenge.

Molecular characterization of V(D)J rearrangements in immature acute leukemias.

Early T-cell Precursor Acute Lymphoblastic Leukemia (ETP-ALL), T-Lymphoid/Myeloid Mixed Phenotype Acute Leukemia (T/M-MPAL), and Acute Myeloid Leukemia with minimal differentiation (AML-M0) are immature acute leukemias (AL) that present overlapping T-cell lymphoid and myeloid features at different degrees, with impact to disease classification. An interesting strategy to assess lymphoid lineage commitment and maturation is the analysis of V(D)J gene segment recombination, which can be applied to investigate leukemic cells in immature AL. Herein, we revisited 19 ETP-ALL, 8 T/M-MPAL, and 12 AML-M0 pediatric patients to characterize V(D)J rearrangement (V(D)J-r) profiles associated with other somatic alterations. V(D)J-r were identified in 74 %, 25 %, and 25 % of ETP-ALL, T/M-MPAL, and AML-M0, respectively. Forty-six percent of ETP-ALL harbored ≥ 3 V(D)J-r, while there was no more than one V(D)J-r per patient in AML-M0 and T/M-MPAL. TCRD was the most rearranged locus in ETPALL, but it was not rearranged in other AL. In ETP-ALL, N/KRAS mutations were associated with absence of V(D)J-r, while NF1 deletion was most frequent in patients with ≥ 3 V(D)J-r. Relapse and death occurred mainly in patients harboring one or no rearranged locus. Molecular characterization of V(D)J-r in our cohort indicates a distinct profile of ETP-ALL, compared to T/M-MPAL and AML-M0. Our findings also suggest that the clinical outcome of ETP-ALL patients may be affected by blast cell maturity, inferred from the number of rearranged TCR loci.

Single-cell transcriptomic analysis of the immune microenvironment in pediatric acute leukemia.

Relapse and treatment resistance pose significant challenges in the management of pediatric B cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). The efficacy of immunotherapy in leukemia remains limited due to factors such as the immunosuppressive tumor microenvironment (TME) and lack of suitable immunotherapeutic targets. Thus, an in-depth characterization of the TME in pediatric leukemia is warranted to improve the efficacy of immunotherapy. Here, we used single-cell RNA sequencing (scRNA-seq) to characterize the TME of pediatric B-ALL and AML, focusing specifically on bone-marrow-derived T cells. Moreover, we investigated the transcriptome changes during the initiation, remission, and relapse stages of pediatric AML. Our findings revealed that specific functional expression programs correlated with fluctuations in various T cell subsets, which may be associated with AML progression and relapse. Furthermore, our analysis of cellular communication networks led to the identification of VISTA, CD244, and TIM3 as potential immunotherapeutic targets in pediatric AML. Finally, we detected elevated proportions of γδ T cells and associated functional genes in samples from pediatric patients diagnosed with B-ALL and AML, which could inform the development of novel therapeutic approaches, potentially focusing on γδ T cells.

Assessing the impact of COVID-19 on acute leukemia patients: a comparative analysis of hematological and biochemical parameters.

BACKGROUND: The impact of COVID-19 infection on the blood system remains to be investigated, especially with those encountering hematological malignancies. It was found that a high proportion of cancer patients are at an elevated risk of encountering COVID-19 infection. Leukemic patients are often suppressed and immunocompromised, which would impact the pathology following COVID-19 infection. Therefore, this research aims to bring valuable insight into the mechanism by which COVID-19 infection influences the hematological and biochemical parameters of patients with acute leukemia. METHODS: This retrospective investigation uses repeated measures to examine changes in hematological and biochemical parameters among patients with acute leukemia before and after COVID-19 infection at a major Saudi tertiary center. The investigation was conducted at the Ministry of National Guard-Health Affairs in Riyadh, Saudi Arabia, on 24 acute leukemia patients with COVID-19 between April 2020 and July 2023. The impact of COVID-19 on clinical parameters, comorbidities, and laboratory values was evaluated using data obtained from the electronic health records at four designated time intervals. The relative importance of comorbidities, testing preferences, and significant predictors of survival was ascertained. RESULTS: The majority of leukemic COVID-19-infected patients, primarily detected through PCR tests, were diagnosed with acute lymphoblastic leukemia (70.8%). The hematological and biochemical parameters exhibited stability, except for a brief increase in ALT and a sustained rise in AST. These changes were not statistically significant, and parameters remained normal at all time points. Additionally, an increase in monocyte count was shown at time point-3, as well as platelet counts at time point 2. CONCLUSION: While this study did not detect statistically significant effects of COVID-19 on biochemical and hematological parameters in acute leukemia patients, further investigation is needed to fully understand the potential adverse reactions and modifications following COVID-19 infection.

Atypical BCR-ABL1 transcript in mixed phenotype acute leukemia with bone marrow necrosis.

Mixed phenotype acute leukemia (MPAL) is a type of acute leukemia in which encompasses mixed features of myeloid, T-lymphoid, and/or B-lymphoid differentiation. Philadelphia chromosome-positive (Ph+) MPAL is a rare subgroup with a poor prognosis and accounts for ＜1% of adult acute leukemia. Until now, there is still no consensus on how to best treat Ph+ MPAL. Here, we report a 62-year-old male with Ph+ (atypical e13a2 BCR-ABL1 fusion protein) MPAL. This patient presented with recurrent and intense bone pain due to bone marrow necrosis (BMN). Besides, he did not achieve a complete remission for the first two chemotherapies, until he received flumatinib combined with hyper-CVAD (B) (a dose-intensive regimen include methotrexate and cytarabine). To our knowledge, this is the first report to describe the coexistence of BMN and atypical e13a2 BCR-ABL1 transcripts in patients with MPAL. This finding will bring new understandings in the diagnosis and treatment of Ph+ MPAL.

Management of acute appendicitis in pediatric patients with acute leukemia: Insights from a single-center study.

Acute appendicitis (AA) in pediatric patients with acute leukemia mandates prompt treatment. Diagnosis presents challenges, relying on clinical and radiological assessments, often leading to treatment delays that may disrupt leukemia management. Our study on 14 such cases underscores the pivotal role of swift intervention. While conservative AA treatment may pose no risk to healthy children, our findings mandate the performance of laparoscopic appendectomy within 24 hours of diagnosis. This strategy yielded successful surgical outcomes while ensuring uninterrupted leukemia care. Our experience contributes important insights to the limited understanding of navigating this complex clinical scenario.

Cyclopenta[b]indoles as novel antimicrotubule agents with antileukemia activity.

Acute leukemias present therapeutic challenges despite advances in treatments. Microtubule inhibitors have played a pivotal role in cancer therapy, inspiring exploration into novel compounds like C2E1 from the cyclopenta[b]indole class. In the present study, we investigated C2E1's potential as a therapeutic agent for acute leukemia at molecular, cellular, and genetic levels. C2E1 demonstrated tubulin depolarization activity, significantly reducing leukemia cell viability. Its impact involved multifaceted mechanisms: inducing apoptosis, arrest of cell cycle progression, and inhibition of clonogenicity and migration in leukemia cells. At a molecular level, C2E1 triggered DNA damage, antiproliferative, and apoptosis markers and altered gene expression related to cytoskeletal regulation, disrupting essential cellular processes crucial for leukemia cell survival and proliferation. These findings highlight C2E1's promise as a potential candidate for novel anti-cancer therapies. Notably, its distinct mode of action from conventional microtubule-targeting drugs suggests the potential to bypass common resistance mechanisms encountered with existing treatments. In summary, C2E1 emerges as a compelling compound with diverse effects on leukemia cells, showcasing promising antineoplastic properties. Its ability to disrupt critical cellular functions selective to leukemia cells positions it as a candidate for future therapeutic development.

Immune escape of B-cell lymphoblastic leukemic cells through a lineage switch to acute myeloid leukemia.

Acute leukemia (AL) with a lineage switch (LS) is associated with poor prognosis. The predisposing factors of LS are unknown, apart from KMT2A rearrangements that have been reported to be associated with LS. Herein, we present two cases and review all 104 published cases to identify risk factors for LS. Most of the patients (75.5%) experienced a switch from the lymphoid phenotype to the myeloid phenotype. Eighteen patients (17.0%) experienced a transformation from acute myelogenous leukemia (AML) to acute lymphoblastic leukemia (ALL). Forty-nine (46.2%) patients carried a KMT2A rearrangement. Most of the cases involved LS from B-cell ALL (B-ALL) to AML (59.4%), and 49 patients (46.2%) carried KMT2A-rearrangements. Forty patients (37.7%) received lineage-specific immunotherapy. Our findings suggest that the prevalence of KMT2A rearrangements together with the lineage-specific immunotherapy may trigger LS, which supports the thesis of the existence of leukemia stem cells that are capable of lymphoid or myeloid differentiation.

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.

Minnelide exhibits antileukemic activity by targeting the Ars2/miR-190a-3p axis.

BACKGROUND: The identification of a novel and effective strategy for the clinical treatment of acute leukemia (AL) is a long-term goal. Minnelide, a water-soluble prodrug of triptolide, has recently been evaluated in phase I and II clinical trials in patients with multiple cancers and has shown promise as an antileukemic agent. However, the molecular mechanism underlying minnelide's antileukemic activity remains unclear. PURPOSE: To explore the molecular mechanisms by which minnelide exhibits antileukemic activity. METHODS: AL cells, primary human leukemia cells, and a xenograft mouse model were treated with triptolide and minnelide. The molecular mechanism was elucidated using western blotting, immunoprecipitation, flow cytometry, GSEA and liquid chromatography-mass spectrometry analysis. RESULTS: Minnelide was highly effective in inhibiting leukemogenesis and improving survival in two complementary AL mouse models. Triptolide, an active form of minnelide, causes cell cycle arrest in G1 phase and induces apoptosis in both human AL cell lines and primary AL cells. Mechanistically, we identified Ars2 as a new chemotherapeutic target of minnelide for AL treatment. We found that triptolide directly targeted Ars2, resulting in the downregulation of miR-190a-3p, which led to the disturbance of PTEN/Akt signaling and culminated in G1 cell cycle arrest and apoptosis. CONCLUSIONS: Our findings demonstrate that targeting Ars2/miR-190a-3p signaling using minnelide could represent a novel chemotherapeutic strategy for AL treatment and support the evaluation of minnelide for the treatment of AL in clinical trials.

Single vs double umbilical cord blood transplantation in acute leukemia: Systematic review and meta-analysis.

BACKGROUND AND AIMS: Umbilical cord blood transplantation (UCBT) has emerged as a promising treatment option for patients with acute leukemia needing hematopoietic stem cell transplantation. Both single (sUCBT) and double cord blood units (dUCBT) demonstrate potential benefits, but studies comparing their effectiveness have shown mixed results. This meta-analysis aimed to determine the comparative safety and efficacy of sUCBT versus dUCBT in acute leukemia patients. METHODS: Electronic databases were systematically examined to identify relevant studies comparing single vs double UCBT published until November 2023. Nine studies involving 3864 acute leukemia patients undergoing UCBT were included. Outcomes analyzed were acute graft-versus-host disease (GVHD), chronic GVHD, relapse, non-relapse mortality, leukemia-free survival and overall survival. Pooled risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model. RESULTS: The risk of Grade II-IV acute GVHD (RR 1.55, 95% CI 1.19-2.03) and Grade III-IV acute GVHD (RR 1.25, 95% CI 1.07-1.46) were significantly higher with dUCBT. Relapse risk was lower with dUCBT (RR 0.57, 95% CI 0.38-0.88) while overall survival favored sUCBT (RR 1.25, 95% CI 1.06-1.46). No significant differences were observed for chronic GVHD, non-relapse mortality or leukemia-free survival. CONCLUSION: Both single and double UCBT have potential as effective treatments for acute leukemia. The choice of treatment should consider various factors, including the risk of GVHD, relapse, and mortality. More research, especially randomized trials, is needed to provide definitive guidance on the optimal use of single and double unit UCBT in patients with acute leukemia.

Production of donor-derived cytotoxic T lymphocytes with potent anti-leukemia activity for adoptive immunotherapy in high-risk pediatric patients given haploidentical hematopoietic stem cell transplantation.

BACKGROUND AIMS: Somatic cell therapy based on the infusion of donor-derived cytotoxic T lymphocytes (CTL) able to recognize patients' leukemia blasts (LB) is a promising approach to control leukemia relapse after allogeneic HSCT. The success of this approach strongly depends on the ex vivo generation of high-quality donor-derived anti-leukemia CTL in compliance with Good Manufacturing Practices (GMP). We previously described a procedure for generating large numbers of donor-derived anti-leukemia CTL through stimulation of CD8-enriched lymphocytes with dendritic cells (DCs) pulsed with apoptotic LB in the presence of interleukin (IL)-12, IL-7 and IL-15. Here we report that the use of IFN-DC and the addition of IFNα2b during the priming phase significantly improve the generation of an efficient anti-leukemia T cells response in vitro. METHODS: Using this approach, 20 high-risk pediatric patients given haploidentical HSCT for high-risk acute leukemia were enrolled and 51 batches of advanced therapy medical products (ATMP), anti-leukemia CTL, were produced. RESULTS: Quality controls demonstrated that all batches were sterile, free of mycoplasma and conformed to acceptable endotoxin levels. Genotype analysis confirmed the molecular identity of the ATMP based on the starting biological material used for their production. The majority of ATMP were CD3+/CD8+ cells, with a memory/terminal activated phenotype, including T-central memory populations. ATMP were viable after thawing, and most ATMP batches displayed efficient capacity to lyse patients' LB and to secrete interferon-γ and tumor necrosis factor-α. CONCLUSIONS: These results demonstrated that our protocol is highly reproducible and allows the generation of large numbers of immunologically safe and functional anti-leukemia CTL with a high level of standardization.

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

BACKGROUND: Family-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. OBJECTIVE: To evaluate the effect of a family empowerment program on the caregiving ability and adverse mood of caregivers of children with acute leukemia. METHODS: Sixty-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. RESULTS: After 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). CONCLUSION: Family empowerment program is beneficial in improving caregiving capacity and reducing disease uncertainty and anxiety among caregivers of children with acute leukemia. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073476 2023-07-12 Retrospectively registered.

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

PURPOSE: 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). METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Genomic Characterization of Partial Tandem Duplication Involving the KMT2A Gene in Adult Acute Myeloid Leukemia.

BACKGROUND: Gene rearrangements affecting KMT2A are frequent in acute myeloid leukemia (AML) and are often associated with a poor prognosis. KMT2A gene fusions are often detected by chromosome banding analysis and confirmed by fluorescence in situ hybridization. However, small intragenic insertions, termed KMT2A partial tandem duplication (KMT2A-PTD), are particularly challenging to detect using standard molecular and cytogenetic approaches. METHODS: We have validated the use of a custom hybrid-capture-based next-generation sequencing (NGS) panel for comprehensive profiling of AML patients seen at our institution. This NGS panel targets the entire consensus coding DNA sequence of KMT2A. To deduce the presence of a KMT2A-PTD, we used the relative ratio of KMT2A exons coverage. We sought to corroborate the KMT2A-PTD NGS results using (1) multiplex-ligation probe amplification (MLPA) and (2) optical genome mapping (OGM). RESULTS: We analyzed 932 AML cases and identified 41 individuals harboring a KMT2A-PTD. MLPA, NGS, and OGM confirmed the presence of a KMT2A-PTD in 22 of the cases analyzed where orthogonal testing was possible. The two false-positive KMT2A-PTD calls by NGS could be explained by the presence of cryptic structural variants impacting KMT2A and interfering with KMT2A-PTD analysis. OGM revealed the nature of these previously undetected gene rearrangements in KMT2A, while MLPA yielded inconclusive results. MLPA analysis for KMT2A-PTD is limited to exon 4, whereas NGS and OGM resolved KMT2A-PTD sizes and copy number levels. CONCLUSIONS: KMT2A-PTDs are complex gene rearrangements that cannot be fully ascertained using a single genomic platform. MLPA, NGS panels, and OGM are complementary technologies applied in standard-of-care testing for AML patients. MLPA and NGS panels are designed for targeted copy number analysis; however, our results showed that integration of concurrent genomic alterations is needed for accurate KMT2A-PTD identification. Unbalanced chromosomal rearrangements overlapping with KMT2A can interfere with the diagnostic sensitivity and specificity of copy-number-based KMT2A-PTD detection methodologies.

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

OBJECTIVE: This 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. METHODS: From 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. RESULTS: All 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 (ß=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 (ß=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 (ß=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. CONCLUSION: There 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 PRACTICE: It 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.

True Donor Cell Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Diagnostic and Therapeutic Considerations-Brief Report.

Donor cell leukemia (DCL) is a rare complication after allogeneic hematopoietic stem cell transplantation (HSCT) accounting for 0.1% of relapses and presenting as secondary leukemia of donor origin. Distinct in phenotype and cytogenetics from the original leukemia, DCL's clinical challenge lies in its late onset. Its origin is affected by donor cell anomalies, transplant environment, and additional mutations. A 43-year-old woman, treated for early stage triple-negative breast cancer, developed mixed-phenotype acute leukemia (MPAL), 12 years later. Following induction chemotherapy, myeloablative conditioning, and allo-HSCT from her fully HLA-matched brother, she exhibited multiple cutaneous relapses of the original leukemia, subsequently evolving into DCL of the bone marrow. Cytogenetic analysis revealed a complex male karyotype in 20 out of 21 metaphases, however, still showing the MPAL phenotype. DCL diagnosis was confirmed by 90.5% XY in FISH analysis and the male karyotype. Declining further intensive chemotherapy including a second allo-HSCT, she was subsequently treated with repeated radiotherapy, palliative systemic therapies, and finally venetoclax and navitoclax but died seven months post-DCL diagnosis. This case underlines DCL's complexity, characterized by unique genetics, further complicating diagnosis. It highlights the need for advanced diagnostic techniques for DCL identification and underscores the urgency for early detection and better prevention and treatment strategies.

Association between direct acting agents used for chronic hepatitis C virus infection and the occurrence of acute leukaemia - A disproportionality analysis.

BACKGROUND AND AIMS: A recent single-center study reported a significant increase in acute myeloid leukaemia (AML) cases, including mixed-phenotype acute leukaemia (MPAL), after exposure to direct acting agents (DAA). We investigated whether DAA use increased the risk of AML in patients with chronic hepatitis C virus (HCV) infection. METHODS: We conducted a disproportionality analysis of the WHO Pharmacovigilance database Vigibase up to 2020. Queries focused on all DAAs, subclasses, combinations or each DAA separately as well as interferon and ribavirin as negative controls. The primary outcome was AML. Secondary outcomes were AML without MPAL, MPAL, acute lymphoid leukemia (ALL) and acute leukemia (AL, high-level term encompassing AML, ALL, MPAL and unspecified acute leukemia [UAL]). The information component (IC0.25) and proportional reporting ratio (PRR0.25) were computed to assess a potential pharmacovigilance signal. RESULTS: We identified 49 notifications reporting any AL occurrence after anti-HCV treatments from June 1997 to December 2020: 23 (47%) involved a DAA, 24 (49%) interferon and 12 (24%) ribavirin. The DAAs sofosbuvir and ledipasvir were suspected in 74% (n = 17) and 39% (n = 9) of cases. The events reported were AML (n = 22), ALL (n = 11), AML and ALL (n = 1) and UAL (n = 15) and no MPAL. DAA, interferon or ribavirin were not significantly associated with AML, ALL or AL. CONCLUSION: This study did not find any association between DAA exposure and the occurrence of AML. Nevertheless, vigilance should remain, particularly for MPAL, which may not have been well captured in our study because of its rareness and high risk of misclassification.