Comparative Analysis of Immaturity CD Markers Expression between Pediatric and Adult Acute Lymphoblastic Leukemia: Insights and Implications for Diagnostic and Therapeutic Strategies.

High-Risk Subtype of Ph-like Acute Lymphoblastic Leukemia (ALL) in Adults: Dismal Outcomes of CRLF2+ ALL Patients Treated with Intensive Chemotherapy

The Role of Cytotoxic Therapy with Hematopoietic Stem Cell Transplantation in the Treatment of Adult Acute Lymphoblastic Leukemia: Update of the 2006 Evidence-Based Review

Genomic Heterogeneity Contributed to the Different Prognosis of Adult and Pediatric Acute Lymphoblastic Leukemia

Purpose Philadelphia chromosome (Ph) -like acute lymphoblastic leukemia (ALL) is a high-risk subtype of childhood ALL characterized by kinase-activating alterations that are amenable to treatment with tyrosine kinase inhibitors. We sought to define the prevalence and genomic landscape of Ph-like ALL in adults and assess response to conventional chemotherapy. Patients and Methods The frequency of Ph-like ALL was assessed by gene expression profiling of 798 patients with B-cell ALL age 21 to 86 years. Event-free survival and overall survival were determined for Ph-like ALL versus non-Ph-like ALL patients. Detailed genomic analysis was performed on 180 of 194 patients with Ph-like ALL. Results Patients with Ph-like ALL accounted for more than 20% of adults with ALL, including 27.9% of young adults (age 21 to 39 years), 20.4% of adults (age 40 to 59 years), and 24.0% of older adults (age 60 to 86 years). Overall, patients with Ph-like ALL had an inferior 5-year event-free survival compared with patients with non-Ph-like ALL (22.5% [95% CI, 14.9% to 29.3%; n = 155] v 49.3% [95% CI, 42.8% to 56.2%; n = 247], respectively; P < .001). We identified kinase-activating alterations in 88% of patients with Ph-like ALL, including CRLF2 rearrangements (51%), ABL class fusions (9.8%), JAK2 or EPOR rearrangements (12.4%), other JAK-STAT sequence mutations (7.2%), other kinase alterations (4.1%), and Ras pathway mutations (3.6%). Eleven new kinase rearrangements were identified, including four involving new kinase or cytokine receptor genes and seven involving new partners for previously identified genes. Conclusion Ph-like ALL is a highly prevalent subtype of ALL in adults and is associated with poor outcome. The diverse range of kinase-activating alterations in Ph-like ALL has important therapeutic implications. Trials comparing the addition of tyrosine kinase inhibitors to conventional therapy are required to evaluate the clinical utility of these agents in the treatment of Ph-like ALL.

Acute Lymphoblastic Leukemia

Low Expression of IL-15 in Adult B-Lineage Acute Lymphoblastic Leukemia Is Associated with Central Nervous System Involvement at Initial Presentation.

A five-gene signature may associate with central nervous system dissemination in adult acute lymphoblastic leukemia.

ETV6 Is An Early T-Cell Progenitor (ETP) Specific Tumor Suppressor Gene in Adult T-ALL

Homozygous Deletion of p16, p14 and p15 Is a Poor Prognostic Factor in Adult B-Lineage Acute Lymphoblastic Leukemia, Not in Childhood B-ALL: A Comparison through Deletion and Hypermethylation Study

The published literature on hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically important genetic subtypes of acute lymphoblastic leukemia (ALL) is scarce from low-income countries. For newer classifications such as BCR::ABL1-like ALLs, the scarcity of patient-level data is even more pronounced. The authors performed comprehensive detection of recurrent gene fusions and BCR::ABL1-like ALL cases followed by immunophenotypic profiling and obtained clinical outcome parameters for a large cohort (n=1021) of patients from India. This cohort included a significant number of patients with BCR::ABL1-like ALL subtype and other genetic subtypes of ALL. Patients with BCR::ABL1-positive and BCR::ABL1-like ALL were significantly older, had male preponderance, and expressed a higher white blood cell count than BCR::ABL1-negative cases (p<.05). Logistic regression modeling of B-lineage-ALL (B-ALL) subtypes revealed that cluster of differentiation (CD)36 is a strong statistically significant predictive marker of BCR::ABL1-like ALL (p<.05). Furthermore, patients with BCR::ABL1-like ALLs show a significantly higher frequency of CD36 expression compared to BCR::ABL1-negative ALLs (p<.05). In terms of clinical symptoms, lymphadenopathy is a strong statistically significant predictive marker in BCR::ABL1-like ALLs compared to BCR::ABL1-negative ALL cases (p<.05). In terms of treatment outcomes, minimal residual disease (MRD) positivity in BCR::ABL1-positive ALL cases were statistically significant (p<.05), and BCR::ABL1-like ALL cases had high MRD-positivity as compared to BCR::ABL1-negative ALL cases but did not show statistical significance. The findings evince the use of novel therapies and personalized treatment regimens to improve the overall survival of the newer incorporated entities in B-ALLs. This is the first report characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes of ALLs in patients from India. Characterizing the hematological, clinical, flowcytometric-immunophenotyping, and minimal residual disease outcomes of the prognostically significant subtypes (n=1021) of acute lymphoblastic leukemia (ALLs) in patients from India. We have made two independent logistic regression models of cluster of differentiation (CD) markers and clinical symptoms to differentiate prognostically significant subtypes of ALLs. Logistic regression analysis of CD markers revealed CD36 as a strong predictor in BCR::ABL1-like ALL cases compared to BCR::ABL1-negative ALL cases. Logistic regression analysis of clinical symptoms revealed lymphadenopathy significantly predicts BCR::ABL1-like ALLs (p<.05). In terms of treatment outcomes, BCR::ABL1-positive ALL had statistically significant minimal residual disease (MRD) (p<.05), and BCR::ABL1-like ALL cases had high MRD-positivity but did not show statistical significance as compared to BCR::ABL1-negative ALLs.

Low Expression Of BCL11B Predicts Poor Overall Survival In Adult Standard Risk T-ALL

Acute lymphoblastic leukemia (ALL) affects both children and adults. However, the prognosis of the two cohorts is quite different. The present aim was to review and evaluate one potential cause of why survival is poorer in adult ALL than pediatric ALL via fluorescence in situ hybridization (FISH). Clinical significant features were analyzed in 282 ALL cases. FISH was performed to study mixed lineage leukemia (MLL) translocation and the Philadelphia (Ph) chromosome in newly diagnosed patients, and was used to detect trisomy 4 or 10 and the translocation ETS leukemia-acute myeloid leukemia 1 (TEL-AML1) fusion gene. The overall survival/event-free survival (OS/EFS) outcome of adult ALL and pediatric ALL was analyzed using Kaplan-Meier analysis. Adult ALL had a higher median leukocyte count and lower hemoglobin level than pediatric ALL. FISH revealed that Ph positivity (Ph+) was associated with the high-risk feature of older age. In pediatric ALL, trisomy 4 or 10 was present in 71/207 cases (34.3%), while the TEL-AML1 fusion gene was present in 16/207 cases (7.7%). By contrast, there were very few such positive cases in adult ALL. Survival analysis revealed that, in adult ALL, the 3-year OS and EFS rates were higher in the Ph-negative group than in the Ph+ group. Adult or pediatric ALL is an independent prognostic factor of OS. The present analysis of the clinical and biological features between adult and pediatric ALL indicates that adult ALL has a poorer prognosis than pediatric ALL based on Ph+ status and presence of trisomy 4 or 10. Ph+ ALL is an independent prognosis factor of ALL. FISH may serve an important role in the comparison of prognostic factors in adult and pediatric ALL.

5 Therapy and prognostic factors in adult acute lymphoblastic leukaemia

The difference in the current cure rates between adult and childhood acute lymphoblastic leukaemia (ALL) may be caused by differences in drug resistance. Earlier studies showed that in vitro cellular drug resistance is a strong independent adverse risk factor in childhood ALL. Knowledge about cellular drug resistance in adult ALL is still limited. The present study compared the in vitro drug resistance profiles of 23 adult ALL patients with that of 395 childhood ALL patients. The lymphoblasts were tested by the MTT assay. The group of adult ALL samples was significantly more resistant to cytosine arabinoside, L-asparaginase, daunorubicin, dexamethasone and prednisolone. The resistance ratio (RR) was highest for prednisolone (31.7-fold) followed by dexamethasone (6.9-fold), L-asparaginase (6. 1-fold), cytosine arabinoside (2.9-fold), daunorubicin (2.5-fold) and vincristine (2.2-fold). Lymphoblasts from adult patients were not more resistant to mercaptopurine, thioguanine, 4-HOO-ifosfamide, mitoxantrone and teniposide. There were no significant differences in drug resistance between adult T-cell (T-) ALL (n = 11) and adult common/pre-B-cell (B-) ALL (n = 10). Additionally, adult T-ALL did not differ from childhood T-ALL (n = 69). There were significant differences between adult common/pre-B-ALL and childhood common/pre-B-ALL (n = 310) for prednisolone (RR = 302, P = 0.008), dexamethasone (RR = 20.9, P = 0.017) and daunorubicin (RR = 2.7, P = 0.009). Lymphoblasts from adults proved to be relatively resistant to drugs commonly used in therapy. This might contribute to the difference in outcome between children and adults with ALL.

CD10− Pre-B Acute Lymphoblastic Leukemia (ALL): A Distinct High-Risk Subgroup of Adult ALL.