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Results for “Precursor Cell Lymphoblastic Leukemia-Lymphoma”

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PubMed1992

Cytomegalovirus infection in children with blood diseases.

The study included 68 children aged from 1 to 16 years treated for acute leukemias and bone marrow aplasia. Cytomegalovirus antigen (CMV) was detected by immunofluorescence in urinary sediment cells and in cell cultures after their inoculation with CMV. Besides, the activity of IgG and IgM classes of antibodies against CMV was determined. Presence of one or more markers of CMV infection was demonstrated in 31 children, i.e., 45.5%. In eight children (11.7%) clinical manifestation of CMV infection were demonstrable with fever, hepatitis, pneumonia, rash. In all the children who completed the treatment with hyperimmune globulin, regression of clinical symptoms and signs of CMV infection with the elimination of virus antigen from urine was achieved.

Adolescent↗
PubMed1992

Intraobserver and interobserver reproducibility of the FAB classification in acute leukaemia.

Intraobserver and interobserver reproducibility of FAB classification for acute leukaemia was assessed using the modified criteria of the FAB classification. Leishman stained peripheral smear and May Grunwald Giemsa stained bone marrow smears from 72 cases of acute leukaemia were used for this purpose. Cytochemical stains used were peroxidase, PAS and Sudan black B. Intraobserver and interobserver concordance/discordance was calculated. Kappa statistic was used to correct the chance expected agreement. Intraobserver and interobserver concordance was 76% which improved to 91% when cytochemistry was included. Lymphocytic/Nonlymphocytic concordance was 87.5% and 90% respectively for intraobserver and interobserver groups.

Blood Cells↗
PubMed1992

[Abnormal CT brain scan during acute lymphoblastic leukemia in children].

The results of CT brain scans were evaluated in 96 children with acute lymphoblastic leukemia in different stages of the disease. Practically normal findings were recorded at establishing the diagnosis (17 children), with the exception of infiltration of the brain and meninges in one patient. Examinations performed after induction chemotherapy (31 children) revealed abnormal CT scans in 55% of the children concerning most frequently dilatation of the cerebrospinal fluid pathways and exhibiting less frequently hypodense foci in the white matter. At check-up examinations after 9 months (following prophylaxis of CNS leukemia) these deviations from the norm had disappeared in some patients, in others they persisted and in the rest of the patients they were found to be aggravated. Examinations carried out several years after treatment completion (40 patients) showed abnormal CR scans in 43% of the patients. These involved particularly derangements in the density of the white matter which were of leuko-dystrophic type and atrophic changes characterized by dilatation of the cerebrospinal fluid pathways. The recorded changes in the CT brain scans were more pronounced in patients with high-risk forms of leukemia and intensive prophylaxis of CNS leukemia.

Adolescent↗
PubMed1992

Plasma ammonia in patients with acute leukemia.

Plasma ammonia level (PAL) was studied in 43 cases of acute leukemia (AL). PAL was 39.21 +/- 26.2 mumol/L in normal controls and 38.8 +/- 16.6 mumol/L in leukemic patients before chemotherapy. High PAL was found in 40 cases after chemotherapy. Six cases showed clinical manifestations due to severe hyperammonemia, including dizziness, lethargy, confusion, coma and mental changes of various degree, and there was also respiratory alkalosis. After ammonia-trapping therapy, 4 of the 5 patients recovered. The authors believe that high PAL is not uncommon after chemotherapy in leukemic patients. Respiratory alkalosis and unexplained mental and neurologic changes following intensive chemotherapy are useful clues for the diagnosis of hyperammonemia syndrome. Early diagnosis and treatment with ammonia-trapping may improve the rates of remission and survival.

Adolescent↗
PubMed1992

[Acute lymphoblastic leukemias off therapy: course of 80 cases after treatment cessation].

PURPOSE: To retrospectively analyse all the patients diagnosed and treated in the same hospital for acute lymphoblastic leukaemia (ALL) in whom therapy was suppressed after sustained complete remission (CR) for a variable period. PATIENTS AND METHODS: Eighty cases of ALL treated at the Jiménez Díaz Foundation between 1968 and 1991 were revised. Treatment had been suppressed after 60 months of maintained CR (1968-1974) or after 28 months (1986-1991), with a median follow-up after suppression of 6 years. All the patients had been treated with several protocols (FJD-68, FJD/BFM, APO, BFM-83, BFM-86 and BFM-90). Maintained CR, relapses and course after therapy cessation were analysed. Actuarial curves of RC duration and survival were drawn according to the Cutler and Ederer life tables. RESULTS: The age at diagnosis ranged from 1.5 to 68 years. Childhood (< 15 years) ALL presented in 49 cases; 25 were young adults (15-30 years), and 6 others were over 30 years of age. Two of the 80 patients (2.5%) died in CR (astrocytoma and demyelinating leukoencephalopathy). Fifty-eight patients (72.5%) are living in maintained CR; 20 others relapsed (25%), 14 of them (70%) attaining a second CR. Allogenic BMT was carried out in 4 such cases. Four patients are out of any treatment after the second CR. The actuarial curves of CR duration after suppression of therapy gave a stable plateau at 73% for children, at 75% for young adults and at 22% for patients over 30 years. The survival after suppression of therapy showed a plateau at 75% for children and at 86% for young adults. CONCLUSIONS: 1) Relapse was seen in 25% of the patients after cessation of therapy. 2) Relapse occurred in the first two years after therapy cessation in 75% of the instances. 3) At this writing, 78.7% of the patients keep up the CR. 4) Adults over 30 years of age comprise the poorest prognosis. 5) The course of young adults in this series after cessation of therapy is as good as that of children.

Adolescent↗
PubMedDate not supplied

[Morpho-functional considerations on the annulate lamellae of the human oocyte].

Ovarian biopsy specimens from four girls in complete remission state of acute lymphoblastic leukemia, previously treated with antiblastic chemotherapy for about three years, were examined by means of electron microscopy. The normal morphology of residual follicles and, in particular, the observation that annulate lamellae were always present in oocytes of primordial and primary follicles, gave the chance to consider a possible functional role and to suggest a prognosis for future fertility. The similarities in structure to the nuclear envelope and the relation between annulate lamellae and other cellular organelles (especially endoplasmic reticulum and ribosomes) suggest that lamellae may be involved in the release, assembly or activation of stored development information. The annulate lamellae could prove to be an important organelle that participates in the regulation of gene expression. Therefore, the presence of annulate lamellae in oocytes of primordial and primary follicles may present the possibility of a normal development for these cells in which long-lived gene products are synthesized and transported to the cytoplasm for storage and use later in development. The above hypothesis, while leads to consider these patients at risk for low fertility and early menopause, does not consider them as definitely infertile.

Adolescent↗
PubMed1979

Complications of tumour overkill when associated with high dose methotrexate therapy.

Three patients, in whom tumour overkill by cytotoxic treatment, including high dose methotrexate with folinic acid rescue, resulted in the 'phosphate shower syndrome' (hyper-uricaemia, hyperkalaemia and hyperphosphataemia with hypocalcaemia and tetany, with metabolic acidosis and acute renal impairment) are described. Severe methotrexate toxicity occurred in two of these patients. High dose methotrexate would appear contra-indicated in situations where massive tumour lysis is possible.

Adolescent↗
PubMed2026

Case Report: Immune-driven clonal selection underlying lineage switch from B-Precursor acute lymphoblastic leukemia to acute myeloid leukemia following inotuzumab ozogamicin.

Lineage switch (LS), defined as a change in leukemic lineage during the disease course, is a rare but clinically significant event in acute leukemia and is typically associated with poor prognosis. Although LS has been increasingly reported following targeted immunotherapies, the clonal mechanisms underlying this phenomenon remain incompletely understood, particularly in cases without KMT2A rearrangement. We report a case of LS from B-precursor acute lymphoblastic leukemia (BCP-ALL) to acute myeloid leukemia (AML) following treatment with the CD22-targeted antibody-drug conjugate inotuzumab ozogamicin. To elucidate the clonal architecture underlying LS, targeted next-generation sequencing was performed on bone marrow samples obtained at multiple time points throughout the disease course. Genomic analysis demonstrated that the lymphoid and myeloid disease phases shared ancestral genetic alterations but displayed distinct mutational profiles. At the time of LS, TP53 and SMC1A mutations newly emerged, whereas only a subset of mutations detected at ALL relapse was retained. These findings suggest that the AML phase most likely resulted from the selective expansion of a genetically distinct subclone derived from a common progenitor, rather than the direct transdifferentiation of the dominant ALL clone, consistent with immunotherapy-driven clonal selection. Longitudinal genomic profiling revealed stepwise clonal evolution during disease progression, supporting a model of immunotherapy-driven clonal selection leading to LS. This case provides molecular evidence suggesting that immune-targeted therapy can promote expansion of minor pre-existing subclones with alternative lineage potential within a common progenitor even in non-KMT2A-rearranged leukemia. Our findings highlight the importance of comprehensive genomic monitoring during immunotherapy to identify therapy-resistant subclones and better understand mechanisms of lineage plasticity in acute leukemia.

Humans↗
PubMed2025

Cytogenetic and molecular characterization of an atypical ETP-ALL case with BCL2 dependency: therapeutic implications for Venetoclax use.

BACKGROUND: Early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) is a rare, high-risk subtype of T-ALL characterized by distinctive immunophenotypic and genomic features. It is often associated with induction failure and frequent relapses. Despite recent advances in its molecular characterization, the prognosis remains dismal, and effective targeted therapies are limited. METHODS AND RESULTS: We report a pediatric, multi-refractory ETP-ALL case with novel cytogenetic alterations, including a 4q deletion and a t(16;18)(q24;q21) translocation. Molecular profiling revealed progressive activation of the BCL2 pathway and disruption of Th17-related immune markers. Ex vivo sensitivity assays performed at different disease stages demonstrated increasing BCL2 dependency. Based on these findings, venetoclax was administered on a compassionate-use basis, resulting in rapid hematologic recovery and a marked reduction in blast percentage. CONCLUSIONS: This case highlights the role of clonal evolution and immune deregulation in accompanying BCL2 addiction in relapsed ETP-ALL. Altogether, our findings underscore the therapeutic potential of venetoclax in refractory pediatric ETP-ALL cases with progressive BCL2 dependency.

Humans↗
PubMed2026

Late acquisition of BCR::ABL1 during clonal evolution of SAMD9-associated MDS with phenotypic shift from AML to B-ALL.

We describe a unique case of SAMD9-associated myelodysplastic syndrome (MDS) with monosomy 7 that evolved over 16&#xa0;years into BCR::ABL1-positive acute myeloid leukemia (AML) and subsequently manifested as B-cell acute lymphoblastic leukemia (B-ALL). Genomic analysis at AML diagnosis revealed a germline SAMD9 mutation together with somatic RUNX1 and PPM1D mutations, supporting stepwise clonal evolution, with BCR::ABL1 emerging as a late leukemogenic event. The dominant leukemic population at AML onset showed myeloid morphology and immunophenotype, whereas a minor CD19+CD10+ population was already detectable. Following venetoclax and azacitidine therapy, the dominant leukemic phenotype shifted to B-ALL while retaining BCR::ABL1 positivity. Detection of the Philadelphia chromosome in mature neutrophils at both AML onset and ALL relapse supported multilineage involvement of a multipotent BCR::ABL1-positive clone. Ponatinib achieved disease control. This case highlights late acquisition of BCR::ABL1 during SAMD9-associated clonal evolution and therapy-driven phenotypic shift within a shared Ph-positive leukemic stem-cell hierarchy.

Humans↗
PubMed2026

Clinical and molecular prognostic factors in newly diagnosed pediatric T-cell lymphoblastic lymphoma: a prospective, multicenter, single-arm phase 2 clinical trial.

BACKGROUND: Poor early treatment response in T-cell lymphoblastic lymphoma (T-LBL) is associated with an unfavorable prognosis. This multicenter prospective study evaluated the efficacy of the response-adjusted Chinese Children's Cancer Group (CCCG-LBL-2016) protocol for pediatric T-LBL and examined clinical and molecular prognostic factors. METHODS: Clinical and laboratory data from seven pediatric oncology centers were analyzed. A sub-cohort of 23 patients underwent exploratory integrated genomic analysis, including targeted next-generation sequencing, RNA sequencing, and copy-number array analysis. Survival was evaluated using the Kaplan-Meier method, and prognostic factors were analyzed using multivariable Cox proportional hazards regression. RESULTS: A total of 163 patients (median age: 108&#xa0;months; 116 males, 47 females) were enrolled, most with advanced disease (stage III: 81.0%; stage IV: 17.8%). Patients were stratified into the low-risk (R1, n&#x2009;=&#x2009;2) and intermediate-risk groups (R2, n&#x2009;=&#x2009;161); thirty one patients in the R2 group were escalated to the high-risk intensified regimen (R3) due to poor early response. The 3-year overall survival (OS) was 78.6%&#x2009;&#xb1;&#x2009;3.3% and event-free survival (EFS) was 73.9%&#x2009;&#xb1;&#x2009;3.5%. Outcomes differed by risk group (P&#x2009;<&#x2009;0.05), with 3-year OS and EFS of 100% and 100% in R1, 82.6%&#x2009;&#xb1;&#x2009;3.4% and 79.5%&#x2009;&#xb1;&#x2009;3.4% in R2, and 58.6%&#x2009;&#xb1;&#x2009;9.1% and 48.3%&#x2009;&#xb1;&#x2009;9.1% in R3. Progression or recurrence occurred in 42 patients (median: 7&#xa0;months; 3-year OS: 17.1%&#x2009;&#xb1;&#x2009;6.3%). Clinical risk factors included R3 assignment and elevated lactate dehydrogenase. In the exploratory molecular sub-cohort, recurrent alterations included CDKN2A (39.1%), NOTCH1 (26.1%), FBXW7 (21.7%), and MTAP/PIK3R1/NRAS (13.0%). Exploratory multivariable Cox regression analysis identified that CDKN2A alteration was associated with an increased risk of progression or recurrence (hazard ratio&#x2009;=&#x2009;35.89, 95% confidence interval: 3.07-419, P&#x2009;=&#x2009;0.004). CONCLUSIONS: Adjusting the risk stratification based on treatment response significantly improved the overall prognosis of T-LBL. However, survival rates remain very low among patients who experience disease progression or recurrence. The preliminarily explored molecular genetic risk factors might contribute to further risk stratification and provide potential therapeutic targets.

Humans↗
PubMed2025

The super-enhancer regulatory gene SH2D1A promotes the progression of T cell acute lymphoblastic leukemia by activating CHI3L2.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive leukemia subtype and a prevalent malignancy in children, with poor prognosis, high relapse rates, and drug resistance. Recent research has shown that super-enhancer-regulated genes play crucial roles in T-ALL progression. In this study, we identified SH2 domain containing 1&#xa0;A (SH2D1A) as a gene regulated by super-enhancers, and is overexpressed, which correlates with unfavorable clinical outcomes in T-ALL. To investigate its role, we silenced SH2D1A expression in T-ALL cell models using RNA interference. This led to a significant reduction in cell proliferation, colony formation, and promoted apoptosis, as demonstrated by CCK-8 assays, soft agar colony formation, and flow cytometry analysis. In vivo, knockdown of SH2D1A significantly inhibited tumor growth and prolonged survival in mice bearing T-ALL. Mechanistically, we found that SH2D1A contributes to T-ALL progression by upregulating CHI3L2, a downstream effector that promotes cell proliferation and inhibits apoptosis. Using ChIP-Seq and RNA-seq technologies, we confirmed that SH2D1A regulates CHI3L2 expression through super-enhancer-mediated regulation in T-ALL cells. Our findings suggest that SH2D1A and CHI3L2 act as oncogenes in T-ALL, and may represent novel therapeutic targets. This research offers new insights into the molecular mechanisms of T-ALL and highlights potential avenues for therapeutic intervention.

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma↗
PubMed2026

Deletion of 9p drives B-ALL through heterozygous inactivation of Pax5 and Cd72 in preleukemic cells.

The contribution of 9p deletion to B cell acute lymphoblastic leukemia (B-ALL) has remained elusive since its discovery more than 40 years ago. Here we show that loss of CD72 is recurrent in B-ALL cases containing PAX5 deletions, and that Cd72 haploinsufficiency drives B-ALL development in Pax5+/- mice. Mechanistically, Cd72+/-;Pax5+/- precursor B cells exhibited an inflammatory transcriptional profile characterized by a decrease in Myd88 expression, a finding that aligns with our previous studies of B-ALL development in Pax5+/- mice following exposure to immune stressors. These combined genomic analyses and functional models provide compelling evidence that co-deletion of 2 contiguous genes, Pax5 and Cd72, drives B cell leukemogenesis.

Animals↗
PubMed2026

Inhibition of the atypical kinase WNK1 as a therapeutic strategy in TAL-related T-cell acute lymphoblastic leukemia.

Driver mutations in T-cell acute lymphoblastic leukemia (T-ALL) rarely affect druggable kinases. However, these kinases can be aberrantly activated or repressed as secondary oncogenic events. Thus, integrating unbiased phosphoproteomics with genomic approaches may offer novel opportunities for target discovery and therapeutic interventions. In our study, we identified WNK1 (with no lysine [K]) as a potential target in T-ALL by pairing a list of vulnerable kinases with data from a phosphoproteomic screen of T-ALL cell lines. We subsequently validated WNK1 by loss-of-function-based studies and tested WNK inhibitors in several in vitro and in vivo T-ALL models and clinical T-ALL samples. We showed that therapeutic WNK1 repression promotes polyploidy, resulting in cell proliferation arrest, and morphometric changes, such as incomplete cell division or chromosome segregation through altered mitotic spindle assembly and abscission defects. Furthermore, we found that WNK1 is overexpressed in the TAL1/2-related subgroup, but not in normal thymus or lymph nodes, suggesting a potential translational area for clinical exploitation in poor-prognosis T-ALL carrying PTEN mutations and del(6q). Our work also reports a functional contribution of WNK1 in the leukemia establishment and progression. Structurally WNK1 is an atypical serine/threonine kinase that diverges from canonical kinases by lacking the conserved lysine in subdomain II, instead featuring a cysteine in subdomain I, which is critical for adenosine triphosphate (ATP) binding. This unusual structural configuration creates a distinct ATP-binding pocket with limited sequence similarity to conventional kinases, offering a unique opportunity to develop highly selective small molecules. Targeting this atypical ATP domain could thus provide a therapeutic advantage and broaden the treatment landscape for T-ALL.

WNK Lysine-Deficient Protein Kinase 1↗