High-risk Acute Lymphoblastic Leukemia Research Articles

P-1174. MBI-CLABSI Cluster in Pediatric Oncology Patients with Hematologic Malignancies Introduces New Barrier in Fluoroquinolone Prophylaxis

Abstract Background Levofloxacin is preferred for prophylaxis during neutropenic periods in pediatric patients with high-risk acute myeloid and lymphoblastic leukemias (AML and ALL, respectively). The goal is to decrease risk of morbidity and mortality from bacteremia related to central venous lines (CVL) and chemotherapy-induced mucosal barrier injury (MBI), but antibacterial resistance may develop. Our institution observed an unexpected increase in MBI-central line associated bloodstream infections (MBI-CLABSI) in 2023, prompting a multidisciplinary review of the MBI-CLABSI cluster. Methods Retrospective chart review was performed to characterize a cluster of MBI-CLABSI events occurring in pediatric patients with AML or ALL from 2020-2023 at our 220-bed, urban/suburban, free-standing children’s hospital. Descriptive analysis of the 2023 cluster events was performed, including patient demographics, diagnosis, transplant status, pathogen and prophylactic drug data to identify commonalities and potential harm-reduction interventions. Results Rate of MBI-CLABSI were steady from 2020-2022 (0.24) and increased to 1.11 per 1,000 central line days in 2023 in patients with AML or ALL. Standard infection ratio of 3.69, p-value 0.0001. 85.7% (n=12/14) MBI-CLABI occurred in patients who had received prophylactic levofloxacin. Almost all organisms causing the MBI-CLABSIs were levofloxacin resistant (98%) and most (58%) were resistant to at least one additional antibiotic. Patients with multiple MBI-CLABSI events with a levofloxacin-resistant organism during the cluster year was not uncommon (66.7%; n=8/12)). . In this subset, patients continued to receive prophylactic levofloxacin despite having earlier infections caused by a levofloxacin-resistant pathogen. Conclusion Use of levofloxacin prophylaxis for neutropenia episodes in high-risk AML and ALL patients may increase the risk of MBI-CLABSI events with levofloxacin-resistant organisms, thus reducing the effectiveness of the prophylaxis goal to prevent serious bacterial infections and reduce harm. Further studies are needed to better delineate optimal use of prophylactic antibiotics by incorporating population-level antibiograms and patient-specific infection histories. Disclosures All Authors: No reported disclosures

Delay in treatment for childhood Acute Lymphoblastic Leukemia at the University of Gondar Comprehensive Specialized Hospital, Northwestern Ethiopia

Background: Despite the critical importance of early blood cancer diagnosis in children for timely treatment, late presentation, delayed diagnosis, and delayed treatment initiation remain significant issues in developing countries, including Ethiopia. Addressing these delays requires improving healthcare infrastructure, public awareness, provider training, and reducing financial barriers. This study aimed to assess referral delays, diagnostic delays, and overall treatment delays among children with acute lymphoblastic leukemia at the University of Gondar Comprehensive Specialized Hospital. Methods: A facility-based cross-sectional study was conducted among pediatric acute lymphoblastic leukemia (ALL) patients under 18 years. Data were collected using a structured questionnaire administered to primary caregivers from December 29, 2022, to January 30, 2024. During the study, 90 ALL cases were included using a consecutive sampling technique. Data were entered and analyzed using SPSS version 25 software, with results presented through descriptive statistics, including frequencies, percentages, graphs, and tables. Binary logistic regression examined associations between sociodemographic factors and treatment delays among childhood ALL patients. Results: A total of 90 children participated, 63 (70.0%) male. Median time from first symptoms to medical consultation was 9.7 days, referral delay 51.3 days, diagnosis delay 3.2 days, and treatment initiation delay 4.6 days. Total delay to treatment was 69 days, with induction mortality at 22%. High-risk ALL, malaria, and delays of 30–90 days increased induction mortality risk. Conclusion: The study revealed significant delays in childhood ALL treatment, contributing to high mortality rates. Timely diagnosis and treatment initiation are critical, particularly for high-risk patients and those with malaria. Strengthening healthcare infrastructure, awareness, and provider training is vital to improve outcomes.

Contributions of Pediatric Hematology/Oncology to the Diagnosis, Treatment, and Cure of Acute Lymphoblastic Leukemia: Part 2a (Numbers 11 to 15)

Pediatric hematology/oncology as a subspecialty has made major contributions to the diagnosis and treatment of acute lymphoblastic leukemia, the most common malignancy in the pediatric population. This impressive progress has yielded complete response rates of 98%, median durations of complete continuous remissions of over 5 years, and long-term leukemia-free survival and probable cure in 80% to 85% of patients. Sixty-five years ago, such data could only be imagined as future goals. This offering, part 2 of a planned trilogy, represents the second historical review from an admittedly elderly investigator, proud to have witnessed firsthand many of these advances. Part 2a contains numbers 11 to 15 and Part 2b consists of numbers 16 to 20. In consecutive order from the first 10: (11) more clues to the causation of ALL relating to in utero events and after birth, very early responses to infection; (12) the superiority of pediatric-inspired ALL trials for adolescents and young adults; (13) L-asparaginase; (14) chimeric antigen receptor T-cell therapy (CART); and (15) aggressive multiagent therapy for high-risk ALL introduced by BFM and CCG. My involvement with colleagues in some of these advances has provided a 65-year odyssey and its accompanying gratification and sense of accomplishment. Mostly, our goals have been achieved and have benefitted substantially our patients.

Transplant in ALL: who, when, and how?

Allogeneic hematopoietic stem cell transplantation (allo-HCT) remains a cornerstone in the treatment of high-risk acute lymphoblastic leukemia (ALL), yet optimal patient selection is challenging in the era of rapidly changing modern therapy. Refined molecular characterization allows for better risk assessment, sparing low-risk patients from allo-HCT toxicity while identifying those who may benefit from intensified approaches. Measurable residual disease (MRD) has emerged as a powerful predictor of relapse irrespective of treatment strategy, challenging the necessity of transplant in MRD-negative patients. Further, expanded donor options, particularly haploidentical transplantation coupled with reduced intensity conditioning, have extended the applicability of allo-HCT to a broader range of patients. Finally, immunotherapies and targeted treatments are increasingly integrated into both initial and relapsed treatment protocols yielding deep remission and allowing for successful transplant in patients with a history of advanced disease. In this review, we provide an overview of the contemporary role of transplant in adult patients with ALL, focusing on indications for allo-HCT in first remission, optimal sequencing of transplant with novel therapies, and advancements in donor selection and conditioning regimens.

Association Between Socioeconomic Factors and Childhood Acute Lymphoblastic Leukemia Treatment- and Survival-Related Outcomes in Canada.

Studies examing the impact of socioeconomic factors on outcomes in childhood acute lymphoblastic leukemia (ALL) have yielded inconsistent findings. We aimed to determine whether socioeconomic status (SES) or healthcare access are associated with the presence of potentially time-sensitive high-risk features at diagnosis, times to diagnosis or treatment, or survival among children with ALL in Canada. We conducted a retrospective cohort study of all children aged less than 15years diagnosed with first primary ALL between 2001 and 2019 using the Cancer in Young People in Canada national Data Tool, which is population-based. SES was measured using neighborhood income quintiles, and healthcare access proxy measured as distance to treating center. We used logistic regression to examine the associations between income quintile and distance and two potentially time-sensitive indicators of high-risk ALL at diagnosis, white blood cell count (WBC) ≥50×109/L, and central nervous system (CNS) disease. We used Cox proportional hazards to examine associations with time-to-event outcomes (times to diagnosis and treatment, event-free survival [EFS], and overall survival [OS]). We included 4189 patients. In multivariable analyses, no associations were found between income quintile and potentially time-sensitive high-risk features at diagnosis, time to diagnosis or treatment, or OS. The only significant SES measure in multivariable survival analysis was superior EFS among those in income quintile 4 as compared to those in the lowest income quintile with a hazard ratio (HR) of 0.70 (confidence interval [CI]: 0.54-0.91). Living at increased distance from treating center was not associated with high WBC at diagnosis, time to diagnosis, EFS, or OS. Associations were seen between distance to treating center and CNS disease at diagnosis and time to treatment, but without a clear pattern across distance quartiles. Children diagnosed with ALL and treated within Canada's universal healthcare system experience similar treatment and survival outcomes regardless of SES and distance to treatment center. Further work is required using individual-level SES and demographic data to determine if any associations exist, and qualitative assessments to understand barriers to care.

NCMP-29. BRAIN LESIONS IN A TEEN WITH NEWLY DIAGNOSED T-CELL ALL AND SARS-COV-2 INFECTION

Abstract T-cell Lymphoblastic Leukemia (T-cell ALL) accounts for up to 15% of all newly diagnosed cases of acute lymphoblastic leukemia in pediatric patients (0-18 years old). Patients are at risk of opportunistic infections during induction therapy with up to 2% developing blood stream infections when their absolute neutrophil count is above 1,500. We report a case of a 15-year-old female with High-Risk T-cell ALL, CNS1 (negative CNS disease), presenting with three days of headaches, photophobia, and non-neutropenic fever. She completed induction chemotherapy one week earlier with vincristine, daunorubicin, calaspargase and a 28-day course of dexamethasone. On physical exam, she had no focal deficits or changes in sensation or strength. CBC was notable for a white blood cell count: 7500, hemoglobin: 8.6, platelets: 328,000 and ANC (Absolute Neutrophil Count): 4700. The patient was also COVID positive on admission. A contrast enhanced MRI brain demonstrated multiple diffusion restricting and peripherally enhancing lesions, concerning for intracranial abscesses. Neurosurgery performed a burr hole craniotomy and aspirated 5 mL of purulent drainage, the culture of which grew Aspergillus fumigatus complex. The patient was started empirically on Voriconazole, in addition to broad spectrum antibiotic coverage pending culture results, due to excellent CNS penetration and proven superiority to amphotericin-based therapy for invasive aspergillosis. Micafungin was added due to CT chest demonstrating nodular infiltrates, suggesting primary pulmonary aspergillosis with CNS dissemination. The patient improved symptomatically without further sequelae. Patients with COVID-19 on prolonged courses of corticosteroids are at higher risk of developing fungal co-infections regardless of neutrophil count. While pulmonary aspergillosis is the most common location of a COVID-19 aspergillus coinfection, there have been documented reports of intracranial micro-abscesses. Contrast-enhanced brain MRI should be obtained in any patient with a recent history of COVID-19 presenting with new neurological symptoms, especially in a patient with a recent history of corticosteroids.

Targeted Therapy with CX4945 Biomimetic Nanodrug Delivery System for High-Risk B-Cell Acute Lymphoblastic Leukemia

Targeted Therapy with CX4945 Biomimetic Nanodrug Delivery System for High-Risk B-Cell Acute Lymphoblastic Leukemia

Co-Targeting BCL-2 and MCL1 (via CDK9) in Pre-Clinical Models of High-Risk Acute Lymphoblastic Leukemia

Co-Targeting BCL-2 and MCL1 (via CDK9) in Pre-Clinical Models of High-Risk Acute Lymphoblastic Leukemia

Asciminib stands out as the superior tyrosine kinase inhibitor to combine with anti-CD20 monoclonal antibodies for the treatment of CD20+ Philadelphia-positive B-cell precursor acute lymphoblastic leukemia in preclinical models.

Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL) is a high-risk subtype of acute lymphoblastic leukemia characterized by the presence of the BCR::ABL1 fusion gene. Tyrosine kinase inhibitors (TKI) combined with chemotherapy are established as the first-line treatment. Additionally, rituximab, an anti-CD20 monoclonal antibody is administered to adult BCP-ALL patients with ≥20% CD20+ blasts. In this study, we observed a marked prevalence of CD20 expression in patients diagnosed with Ph+ BCP-ALL, indicating a potential widespread clinical application of rituximab in combination with TKI. Consequently, we examined the influence of TKI on the antitumor effectiveness of anti-CD20 monoclonal antibodies by evaluating levels of CD20 on the cell surface and conducting in vitro functional assays. All tested TKI were found to uniformly downregulate CD20 on leukemic cells, diminishing the efficacy of rituximab-mediated complement- dependent cytotoxicity. Interestingly, these TKI displayed varied effects on natural killer (NK) cell-mediated antibody- dependent cytotoxicity and macrophage phagocytic function. While asciminib demonstrated no inhibition of effector cell functions, dasatinib notably suppressed the anti-CD20-monoclonal antibody-mediated NK cell cytotoxicity and macrophage phagocytosis of BCP-ALL cells. Dasatinib and ponatinib also decreased NK cell degranulation in vitro. Importantly, oral administration of dasatinib, but not asciminib, compromised NK cell activity in patients' blood, as determined by an ex vivo degranulation assay. Our results indicate that asciminib might be preferred over other TKI for combination therapy with anti-CD20 monoclonal antibodies.

Educational outcomes school year nine in children treated for acute lymphoblastic leukemia: A nationwide registry-based study from Sweden.

Acute lymphoblastic leukemia (ALL) constitutes approximately 25% of pediatric cancers, and with contemporary protocols, the 5-year survival rate is over 90%. Despite improved survival, neurocognitive impairments from treatment raise concerns. This registry study aimed to explore the impact of ALL treatment on educational outcomes from school year nine in Swedish children. A population-based cohort of 503 children diagnosed with ALL from 1990 to 2010 was identified from the Swedish Childhood Cancer Registry and matched with five controls each. Assessed variables were delayed graduation, high school eligibility, total merit value, school grades in Swedish, English, mathematics, and physical education, and results in national tests. Analyses were performed between cases and controls and by sex, age at diagnosis, and risk group. Our results showed that, compared to controls, cases had higher odds for delayed graduation, poorer results in physical education, and higher rates of absence in national tests in English and mathematics. Children in the standard-risk group (treated with first-line chemotherapy only) exhibited similar results to matched controls whereas children in the high-risk group (treated with cranial irradiation, hematological stem cell transplantation, or/and for ALL relapse and thus likely received also radiotherapy) had lower total merit value compared to controls. We conclude that Swedish children diagnosed with ALL between the years 1990-2010 mainly exhibited comparable educational outcomes to controls, although children in the high-risk group had lower results. These findings highlight the importance of evaluating especially children with high-risk ALL in order to identify those requiring educational support and for designing targeted interventions.

Effects of asparaginase-associated pancreatitis in children with haematological tumours.

Asparaginase-associated pancreatitis (AAP) is a major challenge for continuing asparaginase therapy. We aimed to investigate the acute and long-term complications and survival rates related to first and second AAP episodes in Chinese children with haematological malignancies. We retrospectively analysed clinical data of children with pancreatitis who received asparaginase chemotherapy for acute lymphoblastic leukaemia (ALL), acute mixed cell leukaemia, and non-Hodgkin's lymphoma at Shanghai Children's Medical Center from November 2013 to November 2023. Of the 76 children included in the study, 12 had local complications (15.79%), with no deaths recorded. Systemic complications manifested in 28 patients (36.84%), resulting in 3 deaths (3.95%). Four patients (5.26%) developed long-term complications (chronic pancreatitis or insulin-dependent diabetes mellitus). No significant differences in local or long-term complications were recorded between children in the asparaginase re-exposed (n=39) and non-re-exposed (n=45) groups. Among the re-exposed patients, eight (25.81%) experienced a second attack without fatalities or complications. Survival analysis of intermediate- to high-risk patients revealed a significantly higher event-free survival (EFS) rate for the re-exposed group than for the non-re-exposed group. The second AAP episode's occurrence and severity had no relation to the first AAP episode's severity, and the second AAP episode was significantly less severe than the first (p<0.001). The second AAP episode's occurrence is unrelated to the first AAP episode's severity, and the second AAP episode's severity is significantly lower than that of the first. Further, asparaginase therapy could improve EFS in children with intermediate and high-risk ALL.

Comparable Results Between 8 and 12 Gray TBI in Combination With Fludarabine and Post-Transplant Cyclophosphamide in MRD-Negative but Not in MRD-Positive Acute Lymphoblastic Leukemia Patients Transplanted in First Complete Remission.

The optimal TBI dose for ALL patients undergoing allogeneic SCT is still not clearly defined. Single-center retrospective analysis of high-risk ALL patients in CR1 treated with 8 Gy (n = 22) or 12 Gy (n = 50) TBI in combination with fludarabine and PTCy. Median patient age in the 8 Gy TBI cohort was 63 (37-79) and 37 (18-56) in the 12 Gy TBI cohort and median follow-up time was 21 months (range 1-92). OS and LFS at 2 years after 8 Gy were 65% and 55% versus 74% and 74% after 12 Gy (p = 0.3 and p = 0.2, respectively). CIR and NRM at 2 years were 27% and 14% after 8 Gy versus 4% and 20% after 12 Gy (p = 0.004 and p = 0.4, respectively). MRD-positive (+) patients (n = 26) receiving 12 Gy (n = 19) showed better OS (p = 0.01), LFS (p = 0.009), GRFS, lower CIR (p = 0.02), and similar NRM than did MRD+ patients receiving 8 Gy (n = 7). MRD-negative (-) patients (n = 38) receiving 12 Gy (n = 27) had similar OS, LFS, GRFS, lower CIR, and higher NRM (p = 0.04) than did MRD- patients receiving 8 Gy (n = 11). Our study demonstrates that 8 Gy TBI in comparison to 12 Gy TBI results in low NRM but a high relapse rate with similar OS, LFS, and GRFS. In MRD+ high-risk ALL patients, allogeneic SCT with 12 Gy TBI leads to improved OS, LFS, GRFS, and a low relapse rate. Prospective studies comparing the different treatment regimens with larger MRD patient cohorts are needed to confirm this data.

Methotrexate induced hepatotoxicity in metabolic dysfunction-associated steatotic liver disease.

Hepatotoxicity is an under-recognized and potentially fatal side effect of high-dose methotrexate (HDMTX) chemotherapy, and this risk is compounded in children with metabolic dysfunction-associated steatotic liver disease and/or metabolic-associated steatohepatitis. We present the case of a 12-year-old obese, Hispanic male with elevated hepatic transaminases of unknown etiology at initiation of high-risk B-cell acute lymphoblastic leukemia chemotherapy. He developed acute kidney injury within 24 hours of receiving intravenous HDMTX which progressed to acute hepatic failure. Liver biopsy confirmed methotrexate toxicity aggravated by undiagnosed metabolic dysfunction-associated steatotic liver disease. Rapid deterioration precluded liver transplantation, and he died 21 days after HDMTX treatment. This case highlights the need for comprehensive hepatic evaluation in patients with known or suspected liver disease when administering HDMTX. Dialysis should be considered if delayed methotrexate clearance occurs due to potential for rapid, irreversible hepatotoxicity.

Attention and executive functioning in children and adolescents treated for high-risk acute lymphoblastic leukemia: A report from the Children's Oncology Group (COG).

Survivors of childhood B-acute lymphoblastic leukemia (B-ALL) are at risk for difficulties with attention and executive functioning (EF) as a late effect of treatment. The present study aimed to identify treatment and demographic factors associated with risk for difficulties with EF in youth treated for high-risk B-ALL. Children and adolescents with B-ALL treated on Children's Oncology Group (COG) protocol AALL0232 were randomized to high-dose or escalating-dose methotrexate (MTX), and either dexamethasone or prednisone during the induction phase. Neuropsychological functioning was evaluated via protocol AALL06N1, including performance-based and parent-report measures, for 177 participants (57% female, 81% white; mean age at diagnosis=8.4 years; SD=5.0) 8-24 months following treatment completion. Mean scores for all attention and EF measures were within the average range, with no significant differences as a function of MTX delivery or steroid treatment (all p >0.05). In multivariable models, participants with US public insurance exhibited significantly greater parent-reported EF difficulties than those with US private or non-US insurance (p ≤ 0.05). Additionally, participants diagnosed under 10 years of age performed significantly more poorly on measures of attention (i.e., continuous performance task, p ≤ 0.05) and EF (i.e., verbal fluency and tower planning task, p≤0.05). For survivors of pediatric B-ALL, treatment-related factors were not associated with attention or EF outcomes. In contrast, outcomes varied by demographic characteristics, including age and insurance type, an indicator of economic hardship. Future research is needed to more directly assess the contribution of socioeconomic status on cognitive outcomes in survivors.

Cost-effectiveness of blinatumomab for the treatment of B‑precursor acute lymphoblastic leukemia pediatric patients with high‑risk first‑relapse in Mexico

BackgroundBlinatumomab is a CD3/CD19-directed bispecific T-cell engager molecule that engages T cells to lyse CD19-expressing B cells. Based on a multicenter, open-label, phase 3, randomized clinical trial (Clinical Trials ID: NCT02393859), we aimed to evaluate the cost-effectiveness (CE) of blinatumomab compared to standard consolidation chemotherapy (SC) for the treatment of pediatric patients with high-risk first-relapsed Philadelphia chromosome-negative B-cell precursor acute lymphoblastic leukemia (B-ALL) from a Mexico healthcare payer perspective. MethodsA decision-analytic model, a partitioned survival model, was used to estimate the life-years (LYs) and costs over a lifetime horizon. We assumed that patients who remained alive beyond a 5-year period were cured. To account for the lingering impacts of cancer treatment, an excess mortality rate was incorporated into the model. Event-free survival (EFS) and overall survival (OS) were estimated by fitting mixture-cure and standard parametric survival distributions to the time-to-event data from the phase 3 trial. The model accounted for treatment costs, adverse event costs, follow-up costs, subsequent allogeneic hematopoietic stem cell transplantation (alloHSCT) costs, and subsequent treatment costs. ResultsBlinatumomab was associated with a lifetime gained of 5.11 years at an incremental cost of $621,111 MXN, relative to SC. The ICER for blinatumomab vs Standard of care was estimated to be $121,526 MXN/LY gained in the base case. Cost-effectiveness was sensitive to varying the time horizon. Blinatumomab had a probability of 99 % of being cost-effective, relative to SC, at the willingness to pay threshold defined in Mexico. LimitationsHealth-related quality of life values were not included in the analysis and therefore we did not estimate the quality-adjusted life-years gained. ConclusionsBlinatumomab was associated with greater benefit in terms of OS and EFS relative to SC. Probabilistic, deterministic, and scenario analyses indicate that blinatumomab represents the best value for money. Therefore, blinatumomab administered as part of consolidation therapy in B-ALL pediatric patients with high-risk first relapse is a cost-effective option.

Comparison of augmented Berlin-Frankfurt-Münster (BFM) and BFM 2000 treatment protocols in children diagnosed with high-risk acute lymphoblastic leukemia

Objectives: The main purpose of this study is comparing the augmented Berlin-Frankfurt-Münster (BFM) and BFM 2000 treatment protocols applied to pediatric patients diagnosed with high-risk acute lymphoblastic leukemia (ALL) in our clinic in different years in terms of relapse incidence and survival rates. Methods: When evaluated all patients considering the Children's Oncology Group (COG) criteria, 53 of our patients who were in the medium or high risk group according to the BFM 2000 protocol and were in the high risk group received treatment with Augmented BFM protocol and 17 of them received the BFM 2000 protocol. Age, gender, bone pathology, physical examination, hepatomegaly, splenomegaly, lymphadenopathy, presence of bleeding, hemogram values, immunophenotype, 8th, 14th and 33rd day treatment response, presence of translocation, central nervous system (CNS), extramedullary involvement, risk group, presence of relapse, time to relapse, follow-up period and hospital stay until maintenance treatment were examined. Results: Event-Free Survival (EFS) and Overall Survival (OS) values of patients were 83.6% and 90.1%, respectively. While EFS was 89.4% and OS was 90.6% in the group receiving the Augmented BFM treatment protocol, EFS was calculated as 71.7% and OS was 88.2% in those receiving the BFM-2000 treatment protocol. Accordingly, when the EFS values of those who received the Augmented BFM treatment protocol were compared with those who received BFM-2000, statistically significant values were found (P&amp;lt;0.01). Conclusions: It was observed that the augmented BFM treatment protocol was more protective against relapses and shortened the duration of hospitalization compared to the BFM 2000 treatment protocol.

Superior survival with allogeneic hematopoietic stem cell transplantation versus chemotherapy for high-risk adult acute lymphoblastic leukemia in a PDT-ALL-2016 pediatric-inspired cohort.

Not available.

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

Disease-burden-adapted immunotherapy protocol for primary refractory or high-risk relapsed pediatric acute lymphoblastic leukemia.

Structural and functional alterations in hematological parameters among individuals at clinically high risk for acute lymphocytic leukemia

Abstract: Acute lymphocytic leukemia (ALL) is a diverse category of hematological malignancies defined by the clonal proliferation of immature lymphoid cells. While advances in diagnostic procedures and treatment modalities have improved results for many patients, a group of them exhibit clinical characteristics that indicate a high risk of disease progression and unfavorable consequences. Understanding the underlying molecular processes and developing accurate prognostic indicators in this high-risk group is critical for personalized treatment approaches and better patient outcomes. Hematological markers, immunophenotyping profiles, and chromosomal defects in people who were clinically high risk (CHR) for ALL are discussed in this review. Alterations in hematological markers, such as elevated white blood cell counts, decreased hemoglobin levels, and thrombocytopenia, are indicative of the aggressive nature of high-risk ALL. Immunophenotyping investigations revealed abnormal expression patterns of lineage-specific markers, indicating clonal proliferation and differentiation arrest. Furthermore, cytogenetic examination revealed frequent chromosomal defects, such as the Philadelphia chromosome and hyperdiploidy, which have been linked to a poor prognosis in ALL patients. The combination of hematological, immunophenotypic, and cytogenetic data gives a thorough knowledge of disease biology and assists in risk assessment for patients with CHR for ALL. The present review elucidates the intricate interaction of hematological, immunophenotypic, and cytogenetic abnormalities in persons at clinically high risk for ALL, emphasizing the importance of integrated diagnostic techniques to enhance patient outcomes and optimize treatment strategies.

Anti-T-lymphocyte globulin (ATLG) compared to post-transplant cyclophosphamide as GvHD prophylaxis in ALL patients undergoing allogeneic stem cell transplantation

We retrospectively analyzed high-risk ALL patients in CR1 receiving total body irradiation based conditioning regimen with ATLG (n = 74) or PTCy (n = 73) for GVHD prophylaxis. The 3-year OS and LFS were similar in both groups: 65 and 60% in the ATLG group and 64 and 67% in the PTCy group (p = 0.9 and 0.5, respectively). CIR and NRM rate at three years was 12 and 21% after PTCy and 19 and 20% after ATLG (p = 0.4 and p = 0.9, respectively). Acute GvHD grades II-IV and grades III/IV at 100 days was 46 and 19% after PTCy and 33 and 10% after ATLG (p = 0.08 and p = 0.9, respectively). Chronic GvHD of all grade at two years was higher after PTCy: 55% versus 26% (p < 0.001). Based on the propensity score matching (PSM) analysis, aGvHD grades II-IV was trending higher in the PTCy group compared to the ATLG group (p = 0.07). In contrast to the PSM analysis, on multivariate analysis the receipt of PTCy compared with ATLG was associated with a reduced CIR (p = 0.026). Our retrospective single-center analysis shows a lower incidence of acute and chronic GvHD while displaying similar LFS and OS after ATLG compared to PTCy in TBI based allogeneic stem cell transplantation for high-risk ALL.