Adult T-cell acute lymphoblastic leukemia: biologic profile at presentation and correlation with response to induction treatment in patients enrolled in the GIMEMA LAL 0496 protocol

Abstract

Between 1996 and 2000, 90 newly diagnosed adult patients with T-acute lymphoblastic leukemia (T-ALL) were registered in the Gruppo Italiano Malattie Ematologiche dell'Adulto (GIMEMA) Leucemia Acuta Limfoide (LAL) 0496 protocol. Cases were centrally processed for morphology, immunophenotype, cytogenetics, molecular biology, and multidrug resistance (MDR). Twenty-two patients were females and 68 were males. Four percent of cases were pro-T, 47% pre-T, 39% cortical T, and 10% mature T-ALL. Fifty-six percent of patients with pro-T ؉ pre-T-ALL achieved complete remission (CR) compared with 91% for cortical ؉ mature cases (P ‫؍‬ .002). CD34 expression was associated with a significantly lower CR rate: 54% versus 84% (P ‫؍‬ .009). Thirtyone (36.5%) of 85 patients had an abnormal karyotype, the most common abnormality (15%) being a partial del(6q). The cytogenetic profile did not impact on CR achievement. MDR1 function, present in 26% of cases, correlated significantly with CR achievement (P ‫؍‬ .004). A highly significant (P ‫؍‬ .001) difference in CR rate was observed between patients who did not express the CD13/CD33/CD34 antigens and were MDR functionally negative (96%) compared with patients positive for at least one of these markers (57% IntroductionAcute lymphoblastic leukemia (ALL) is characterized by the proliferation of lymphoid blast cells but represents indeed a heterogeneous group of diseases that vary with respect to the morphologic, cytogenetic, molecular, and immunologic features of the neoplastic cells. A progressive understanding of the biologic and genetic characteristics of ALL has not only improved our knowledge of leukemogenesis but also allowed us to identify different prognostic subgroups with specific molecular and cellular features. It is well established that the malignant clones in patients with ALL are characterized by the expansion of lymphoid progenitor cells blocked at early stages of B-or T-lymphocyte ontogeny. While cells from the majority of patients express B-lineage-associated antigens, T-ALL accounts for approximately 20% to 25% of patients. T-ALL has clinical, immunologic, cytogenetic, molecular, and genomic features that are distinct from those of B-lineage ALL. 1-8 Although many reports 1,9-11 have generally described an unfavorable outcome for patients with T-lineage ALL, both in children and in adults, more recent studies have suggested an improved outcome through the use of highly intensive treatment protocols. 4,[12][13][14] These less unfavorable results have motivated attempts to identify subgroups of patients within T-ALL who may exhibit a more or less favorable response to treatment.Only a few studies have analyzed the presentation features of relatively large series of adult patients with T-ALL in relation to the response to treatment and complete remission (CR) induction. 1,3,15 In the present work, we have investigated the clinical and biologic features of 90 adult patients with T-ALL at diagnosis. Our analysis Reprints: Antonella Vitale, Division of Hematology, Depar...

The novel Akt inhibitor, perifosine, induces caspase-dependent apoptosis and downregulates P-glycoprotein expression in multidrug-resistant human T-acute leukemia cells by a JNK-dependent mechanism

“…41 P-gp overexpression is also detected in T-ALL patients (24%) and negatively correlates with complete remission achievement. 42 Therefore, it is likely that some T-ALL patients would exhibit PI3K/Akt upregulation together with P-gp overexpression, even if this has not been shown in a conclusive manner. In conclusion, our pre-clinical studies support the concept that inhibition of PI3K/Akt signaling with perifosine may have clinical application for treatment of drug resistant disease or elimination of leukemic stem cells.…”

Treatment of Adult Acute Lymphoblastic Leukemia

“…According to drug resistance: Expression of MDR-1 (multidrug resistance gene 1) has been associated with a poorer prognosis in ALL. 17,31 Also, in-vitro sensitvity testing was able to identify patients with resistance to conventional cytostatic drugs which was associated with an inferior prognosis. More recently it was demonstrated that in-vitro resistance is associated with distinct gene expression profiles.…”

“…35 Other "clinical" factors such as obesity, underweight, or even female gender have been proposed as high-risk features in different studies. 7,31 Certainly the prognostic relevance of new "clinical" or "molecular" prognostic factors also depends on the applied treatment regimen. Therefore, and also to keep risk stratification practicable, the integration of new prognostic factors in risk models has to be done carefully, particularly because risk factors generally lead to the indication of SCT in CR1 with considerable morbidity and mortality.…”

Adult T Lymphoblastic Leukemia (Pro-T ALL) with Reactive Monocytosis: A Case Report

“…Despite complete remission rates up to 80-90 %, similar to those obtained in children, the prognosis in adults is less favourable, mainly because of high rates of relapse. The relative rarity of T cell ALL in adults has made it difficult to describe clinical and biologic factors determining outcome [3]. Our case was diagnosed as Pro-T ALL based on cyCD3?/CD7?/CD2-/CD5-/ sCD3-/CD34-immunophenotype.…”