Serum LDH level may predict outcome of chronic lymphocytic leukemia patients with a 17p deletion: a retrospective analysis of prognostic factors in China

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Abstract

Objective

This study aims to evaluate the natural history of patients with chronic lymphocytic leukemia (CLL) and a 17p deletion (17p-) and identify the predictive factors within this subgroup.

Methods

The sample of patients with CLL were analyzed by fluorescence in situ hybridization for deletions in chromosome bands 11q22, 13q14 and 17p13; trisomy of bands 12q13; and translocation involving band 14q32. The data from 456 patients with or without a 17p- were retrospectively collected and analyzed.

Results

The overall response rate (ORR) in patients with a 17p- was 56.9%, and patients with a high percentage of 17p- (defined as more than 25% of cells harbouring a 17p-) had a lower ORR. The median overall survival (OS) in patients with a 17p- was 78.0 months, which was significantly shorter than the OS in patients without this genetic abnormality (median 162.0 months, P<0.001). Within the subgroup with a 17p-, the progression-free survival was significantly shorter in patients at Binet stage B-C and patients with elevated lactate dehydrogenase (LDH), B symptoms, unmutated IGHV and a high percentage of 17p-.

Conclusions

These results indicated that patients with a 17p- CLL have a variable prognosis that might be predicted using simple clinical and laboratory characteristics.

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Most cited references 25

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Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

Jennifer R. Brown, John C. Byrd, Steven E Coutre … (2014)

In a phase 1 trial, idelalisib (GS-1101, CAL-101), a selective inhibitor of the lipid kinase PI3Kδ, was evaluated in 54 patients with relapsed/refractory chronic lymphocytic leukemia (CLL) with adverse characteristics including bulky lymphadenopathy (80%), extensive prior therapy (median 5 [range 2-14] prior regimens), treatment-refractory disease (70%), unmutated IGHV (91%), and del17p and/or TP53 mutations (24%). Patients were treated at 6 dose levels of oral idelalisib (range 50-350 mg once or twice daily) and remained on continuous therapy while deriving clinical benefit. Idelalisib-mediated inhibition of PI3Kδ led to abrogation of Akt phosphorylation in patient CLL cells and significantly reduced serum levels of CLL-related chemokines. The most commonly observed grade ≥3 adverse events were pneumonia (20%), neutropenic fever (11%), and diarrhea (6%). Idelalisib treatment resulted in nodal responses in 81% of patients. The overall response rate was 72%, with 39% of patients meeting the criteria for partial response per IWCLL 2008 and 33% meeting the recently updated criteria of PR with treatment-induced lymphocytosis.(1,2) The median progression-free survival for all patients was 15.8 months. This study demonstrates the clinical utility of inhibiting the PI3Kδ pathway with idelalisib. Our findings support the further development of idelalisib in patients with CLL. These trials were registered at clinicaltrials.gov as #NCT00710528 and #NCT01090414.

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Differences in incidence and trends of haematological malignancies in Japan and the United States

Dai Chihara, Hidemi Ito, Tomohiro Matsuda … (2013)

The incidence of a malignant disease reflects the genetic and cumulative exposure to the environment of a population. Therefore, evaluation of the incidence and trends of a disease in different populations may provide insights into its aetiology and pathogenesis. To evaluate the incidence of haematological malignancies according to specific subtypes, we used population-based registry data in Japan (N = 125 148) and the United States (US; N = 172 925) from 1993 to 2008. The age-adjusted incidence of haematological malignancies in Japan was approximately one-half that in the US but has been increasing significantly, whereas no significant change was seen in the US [annual percent change (95% C confidence interval): Japan, +2·4% (1·7, 3·1); US, +0·1% (−0·1, 0·2)]. Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL) showed the largest differences in incidence, with the most remarkable differences observed for chronic lymphocytic leukaemia, HL-nodular sclerosis, mycosis fungoides and cutaneous T-cell lymphoma. HL and NHL are increasing substantially in Japan but not in the US, suggesting that environmental exposures, such as Westernization of the life style may be causing this increase. Differences in the incidence and trends for specific subtypes also showed a marked contrast across subtypes, which, in turn, may provide significant new insights into disease aetiology in the future.

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Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value.

Gang An, Yan Xu, Lihui Shi … (2014)

Chromosome 1q21 aberrations have not been yet been made part of routine clinical tests and their effect in multiple myeloma is still under investigation. The prognostic value of copy number variation and percentage of plasma cells involved have remained unclear. In the present study, we analyzed the prognostic value of 1q21 in a series of 290 cases of newly diagnosed multiple myeloma treated in a prospective, non-randomized clinical trial (BDH 2008/02). We found that incidence of 1q21 aberration increased at relapse, but its copy numbers and proportion of cells involved did not change. Gains of 1q21 had no impact on survival in patients receiving thalidomide-based treatment but conferred a significantly inferior prognosis in patients under bortezomib-based chemotherapy and was an independent adverse prognostic factor for progression free survival (HR 3.831; 95%CI: 2.125-6.907; P<0.001) and overall survival (HR 3.245; 95%CI: 1.555-6.773; P=0.002). Strikingly, our results showed that the copy number variation and clone size harboring 1q21 gains carried no additional prognostic value and patients with 1q21 gains did not benefit significantly from regimens incorporating bortezomib. Our results indicate that three copies of 1q21 and 20% of plasma cells with this abnormality were enough to confer bortezomib resistance. Therefore, chromosome 1q21 gains should be considered a high-risk feature in multiple myeloma receiving bortezomib therapy.

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Author and article information

Contributors

Zengjun Li

Lugui Qiu

Journal

Journal ID (nlm-ta): Chin J Cancer Res

Journal ID (iso-abbrev): Chin. J. Cancer Res

Journal ID (publisher-id): CJCR

Title: Chinese Journal of Cancer Research

Publisher: AME Publishing Company

ISSN (Print): 1000-9604

ISSN (Electronic): 1993-0631

Publication date (Print): April 2017

Volume: 29

Issue: 2

Pages: 156-165

Affiliations

[1]State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China

Author notes

Prof. Lugui Qiu, MD. Department of Lymphoma and Myeloma, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. Email: qiulg@ihcams.ac.cn; Prof. Zengjun Li, MD. Department of Lymphoma and Myeloma, Institute of Hematology and Blood Disease Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin 300020, China. Email: zengjunli@163.com

Article

Publisher ID: cjcr-29-2-lizengjun

DOI: 10.21147/j.issn.1000-9604.2017.02.09

PMC ID: 5422418

PubMed ID: 28536495

SO-VID: 3adfb728-1bbb-493a-8faf-537ff1a85681

License:

This work is licensed under a Creative Commons Attribution-Non Commercial-Share Alike 4.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/

History

Date received : 7 September 2016

Date accepted : 10 March 2017

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Serum LDH level may predict outcome of chronic lymphocytic leukemia patients with a 17p deletion: a retrospective analysis of prognostic factors in China

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Abstract

Objective

Methods

Results

Conclusions

Related collections

New directions in predictive processing

Most cited references 25

Idelalisib, an inhibitor of phosphatidylinositol 3-kinase p110δ, for relapsed/refractory chronic lymphocytic leukemia.

Differences in incidence and trends of haematological malignancies in Japan and the United States

Chromosome 1q21 gains confer inferior outcomes in multiple myeloma treated with bortezomib but copy number variation and percentage of plasma cells involved have no additional prognostic value.

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Cited by 4

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