Prognostic significance of immunophenotypic and karyotypic features of Philadelphia positive B‐lymphoblastic leukemia in the era of tyrosine kinase inhibitors

Abstract

Background Philadelphia (Ph) positive B-lymphoblastic leukemia exhibits immunophenotypic, karyotypic, and molecular genetic heterogeneity. The prognostic significance of these parameters was assessed in the context of intensive tyrosine kinase inhibitor (TKI)-based chemotherapy. Methods We studied 65 cases of adult Ph-positive ALL treated with TKI-based therapy, correlated their clinicopathologic heterogeneity with patient outcome, and compared the findings with 60 cases of adult diploid B-ALL treated with similar chemotherapy without TKI. Results Ph-positive ALL was associated with older age (p=0.01) and common-B immunophenotype characterized by higher a frequency of co-expression of CD13 (p=0.004), CD66c (p=0.007), and CD25 (p<0.001) with a lower frequency of CD15 expression (p<0.001). Conventional karyotypic analyses showed the Ph chromosome was the sole abnormality in 19 cases (30%), present with other aberrancies in 43 cases (65%), and absent (detectable only by fluorescence in situ hybridization [FISH] or quantitative RT-PCR) in 3 cases (5%). BCR-ABL was confirmed in all cases by FISH or RT-PCR [p190 in 49 (77%) and p210 in 15 (23%), respectively]. Supernumerical Ph correlated with a higher incidence of CD20 expression (p<0.001), whereas p210 correlated with aberrant CD25 expression (p=0.05). Outcomes were not influenced by the degree of karyotypic complexity (including presence or absence of supernumerical Ph); CD20 expression, or myeloid antigen expression (CD13, CD33, CD66c). CD25 expression was associated with an inferior survival in univariate analysis (p=0.051), but not by multivariable analysis (p=0.092). Conclusions In the context of intensive TKI-based chemotherapy, the immunophenotypic, karyotypic, and molecular heterogeneity of Ph-positive ALL no longer influences outcome.

Precursor B-acute lymphoblastic leukemia occurring in patients with a history of prior malignancies: is it therapy-related?

“…9 All precursor B-ALL cases expressed CD19 in conjunction with at least one other B-lineage marker (CD22, CD79a, and/or cIgM), and were negative for cCD3 and myeloproxidase. These results were essential to confirm a diagnosis of precursor B-ALL.…”

“…8 Patients with Ph-positive precursor B-ALL were treated with the hyper-CVAD regimen concurrently with either imatinib mesylate or dasatinib as previously reported. 9 Treatment was not different for patients with either secondary or de novo precursor B-ALL.…”

Impact of minimal residual disease kinetics during imatinib-based treatment on transplantation outcome in Philadelphia chromosome-positive acute lymphoblastic leukemia

“…However, in their separate analysis, including only patients allografting in first CHR, this additional aberration was not correlated with outcome. Another study from Jaso et al 8 has also showed no adverse prognostic factors to allow risk stratification. Main limitations of these studies were the short follow-up duration (o3 years) and lack of analysis regarding the role of minimal residual disease (MRD) monitoring.…”

Philadelphia-Positive B-Acute Lymphoblastic Leukemia: Does it Differ from Philadelphia-Negative One in Egyptian Populations?

“…This finding compared to older studies prior to use of Imatinib in Ph+ ALL showed that Ph+ patients had poorer outcome. [7][8][9] International Journal of Hematology and Oncology Concerning Molecular response (MR), in the present study after receiving chemotherapy accompanied with Imatinib, minor BCR-ABL fusion gene was expressed in mRNA of patient leukocyte (Mean ± SD = 0.006± 0.006), with a 3 log reduction from baseline ratio. This is in accordance with the results previously reported that when Imatinib is added to induction therapy, minor BCR-ABL , mRNA was reduced at least 1 log from baseline after the first induction therapy.…”