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The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis
SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm characterized by strong and uniform CD30 expression and, usually, the aberrant loss of one or more T-cell antigens. ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negativ...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699426/ https://www.ncbi.nlm.nih.gov/pubmed/34944936 http://dx.doi.org/10.3390/cancers13246316 |
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author | Qiu, Lianqun Medeiros, L. Jeffrey Tang, Guilin Khanlari, Mahsa Li, Shaoying Konoplev, Sergej Wang, Sa A. Yin, C. Cameron Khoury, Joseph D. Wang, Wei Miranda, Roberto N. Iyer, Swaminathan You, M. James Xu, Jie |
author_facet | Qiu, Lianqun Medeiros, L. Jeffrey Tang, Guilin Khanlari, Mahsa Li, Shaoying Konoplev, Sergej Wang, Sa A. Yin, C. Cameron Khoury, Joseph D. Wang, Wei Miranda, Roberto N. Iyer, Swaminathan You, M. James Xu, Jie |
author_sort | Qiu, Lianqun |
collection | PubMed |
description | SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm characterized by strong and uniform CD30 expression and, usually, the aberrant loss of one or more T-cell antigens. ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative types. ALCL rarely involves the peripheral blood. The reported leukemic phase ALCL cases are almost all pediatric patients with ALK-positive ALCL, which are frequently associated with the small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Leukemic phase ALK-negative ALCL is extremely rare, with approximately ten cases reported in the literature to date, mostly as single case reports. Here we report on nine patients with leukemic ALK-negative ALCL—the largest case series to date—and we compare these cases with 39 non-leukemic cases of ALK-negative ALCL. We show that the patients with leukemic ALK-negative ALCL have a greater frequency of absolute lymphocytosis, thrombocytopenia, bone marrow involvement, CD7 positivity, complex karyotype, TP53 deletion, and a dismal outcome. These data suggest that leukemic phase ALK-negative ALCL is associated with a number of poor prognostic factors and affected patients may need more aggressive treatment. ABSTRACT: Patients with anaplastic large cell lymphoma (ALCL) rarely develop a leukemic phase of the disease. The reported leukemic ALCL cases are almost all ALK-positive, which are frequently associated with small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Rare leukemic ALK-negative ALCL cases have been reported. In the present study, we investigated the clinical and pathologic features and outcomes of nine patients with leukemic ALK-negative ALCL and compared these features with 39 patients without leukemic disease. Compared with the non-leukemic ALK-negative ALCL group, patients with leukemic disease more often had absolute lymphocytosis (50% vs. 0%, p = 0.008), thrombocytopenia (60% vs. 11%, p = 0.03), bone marrow involvement (50% vs. 14%, p = 0.04), and CD7 positivity (71% vs. 19%, p = 0.02). Four of five (80%) patients with leukemic ALK-negative ALCL had a complex karyotype, which was significantly higher than that of the patients in the non-leukemic group. A fluorescence in situ hybridization for TP53 was performed on six leukemic ALK-negative ALCL cases and all (100%) had TP53 deletion. There were no significant differences in the other clinicopathologic features, treatment, and complete remission rates between patients in the leukemic versus non-leukemic group (all p > 0.05). The median follow-up of this cohort was 18 months with a range of 0.3–140 months. Eight of nine (90%) patients with leukemic ALK-negative ALCL died, and their overall survival was significantly shorter than that of the patients with non-leukemic disease (median 15.5 vs. 60 months, p = 0.001). In conclusion, we show that the leukemic phase of ALK-negative ALCL is associated with high-risk biologic features and, in particular, a complex karyotype and TP53 deletion. Compared with the non-leukemic ALK-negative ALCL patients, the patients with a leukemic phase of disease have poorer survival and may require more aggressive treatment. |
format | Online Article Text |
id | pubmed-8699426 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-86994262021-12-24 The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis Qiu, Lianqun Medeiros, L. Jeffrey Tang, Guilin Khanlari, Mahsa Li, Shaoying Konoplev, Sergej Wang, Sa A. Yin, C. Cameron Khoury, Joseph D. Wang, Wei Miranda, Roberto N. Iyer, Swaminathan You, M. James Xu, Jie Cancers (Basel) Article SIMPLE SUMMARY: Anaplastic large cell lymphoma (ALCL) is a systemic peripheral T-cell neoplasm characterized by strong and uniform CD30 expression and, usually, the aberrant loss of one or more T-cell antigens. ALCL is further classified into anaplastic lymphoma kinase (ALK)-positive and ALK-negative types. ALCL rarely involves the peripheral blood. The reported leukemic phase ALCL cases are almost all pediatric patients with ALK-positive ALCL, which are frequently associated with the small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Leukemic phase ALK-negative ALCL is extremely rare, with approximately ten cases reported in the literature to date, mostly as single case reports. Here we report on nine patients with leukemic ALK-negative ALCL—the largest case series to date—and we compare these cases with 39 non-leukemic cases of ALK-negative ALCL. We show that the patients with leukemic ALK-negative ALCL have a greater frequency of absolute lymphocytosis, thrombocytopenia, bone marrow involvement, CD7 positivity, complex karyotype, TP53 deletion, and a dismal outcome. These data suggest that leukemic phase ALK-negative ALCL is associated with a number of poor prognostic factors and affected patients may need more aggressive treatment. ABSTRACT: Patients with anaplastic large cell lymphoma (ALCL) rarely develop a leukemic phase of the disease. The reported leukemic ALCL cases are almost all ALK-positive, which are frequently associated with small cell morphology, t(2;5)(p23;q35), and a poorer prognosis. Rare leukemic ALK-negative ALCL cases have been reported. In the present study, we investigated the clinical and pathologic features and outcomes of nine patients with leukemic ALK-negative ALCL and compared these features with 39 patients without leukemic disease. Compared with the non-leukemic ALK-negative ALCL group, patients with leukemic disease more often had absolute lymphocytosis (50% vs. 0%, p = 0.008), thrombocytopenia (60% vs. 11%, p = 0.03), bone marrow involvement (50% vs. 14%, p = 0.04), and CD7 positivity (71% vs. 19%, p = 0.02). Four of five (80%) patients with leukemic ALK-negative ALCL had a complex karyotype, which was significantly higher than that of the patients in the non-leukemic group. A fluorescence in situ hybridization for TP53 was performed on six leukemic ALK-negative ALCL cases and all (100%) had TP53 deletion. There were no significant differences in the other clinicopathologic features, treatment, and complete remission rates between patients in the leukemic versus non-leukemic group (all p > 0.05). The median follow-up of this cohort was 18 months with a range of 0.3–140 months. Eight of nine (90%) patients with leukemic ALK-negative ALCL died, and their overall survival was significantly shorter than that of the patients with non-leukemic disease (median 15.5 vs. 60 months, p = 0.001). In conclusion, we show that the leukemic phase of ALK-negative ALCL is associated with high-risk biologic features and, in particular, a complex karyotype and TP53 deletion. Compared with the non-leukemic ALK-negative ALCL patients, the patients with a leukemic phase of disease have poorer survival and may require more aggressive treatment. MDPI 2021-12-16 /pmc/articles/PMC8699426/ /pubmed/34944936 http://dx.doi.org/10.3390/cancers13246316 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Qiu, Lianqun Medeiros, L. Jeffrey Tang, Guilin Khanlari, Mahsa Li, Shaoying Konoplev, Sergej Wang, Sa A. Yin, C. Cameron Khoury, Joseph D. Wang, Wei Miranda, Roberto N. Iyer, Swaminathan You, M. James Xu, Jie The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title | The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title_full | The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title_fullStr | The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title_full_unstemmed | The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title_short | The Leukemic Phase of ALK-Negative Anaplastic Large Cell Lymphoma Is Associated with CD7 Positivity, Complex Karyotype, TP53 Deletion, and a Poor Prognosis |
title_sort | leukemic phase of alk-negative anaplastic large cell lymphoma is associated with cd7 positivity, complex karyotype, tp53 deletion, and a poor prognosis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8699426/ https://www.ncbi.nlm.nih.gov/pubmed/34944936 http://dx.doi.org/10.3390/cancers13246316 |
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