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Table of Contents
LETTER TO EDITOR
Year : 2020  |  Volume : 3  |  Issue : 3  |  Page : 638-640

Outcome of chronic lymphocytic leukemia with deletion 17p


1 Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India
2 Department of Medical Oncology, Lab Oncology Unit, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi, India

Date of Submission31-May-2020
Date of Decision14-Jun-2020
Date of Acceptance11-Aug-2020
Date of Web Publication19-Sep-2020

Correspondence Address:
Ajay Gogia
Department of Medical Oncology, Dr. B.R.A. IRCH, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/CRST.CRST_215_20

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How to cite this article:
Gogia A, Kumar L, Sharma A, Gupta R, Rani L. Outcome of chronic lymphocytic leukemia with deletion 17p. Cancer Res Stat Treat 2020;3:638-40

How to cite this URL:
Gogia A, Kumar L, Sharma A, Gupta R, Rani L. Outcome of chronic lymphocytic leukemia with deletion 17p. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Oct 28];3:638-40. Available from: https://www.crstonline.com/text.asp?2020/3/3/638/295546



In chronic lymphocytic leukemia (CLL), deletion of the short arm of chromosome 17 (del17p) is a rare genomic aberration found in about 5%–9% of the untreated patients in the Western countries and in around 12% in India.[1],[2] The presence of this deletion is associated with an inadequate response to chemotherapy, thereby resulting in an unfavorable outcome.[3],[4] The data on the outcomes of Indian patients with CLL harboring del 17p are scarce. In this prospective study, we recruited all consecutive patients diagnosed with treatment naïve and relapsed/refractory (R/R) CLL, registered at the Department of Medical Oncology, of the All India Institute of Medical Sciences, New Delhi, between June 2013 and December 2018. The diagnosis of CLL and treatment response were assessed based on the guidelines from the International Workshop on CLL.[5] Fluorescence in situ hybridization was used for the diagnosis of del17p from the peripheral blood samples using the commercially available dual color Zytolight TP53/Cen17 probe as per the manufacturer's recommendations (Zytovision, GmbH, Germany). At least 200 interphase nuclei per patient were visualized using the Olympus fluorescence microscope (Japan). Those with a positive signal in ≥7.5% of the interphase nuclei were considered as harboring del17p.[2] The progression-free survival (PFS) was defined as the time from the date of initiation of treatment to relapse, disease progression, or death due to any cause.

A total of 220 patients were recruited in this study, of which 150 were newly diagnosed and 70 had R/R CLL. Of these, del17p was detected in a total of 36 patients, 18 (12%) with newly diagnosed, and 18 (25.5%) with R/R CLL. The baseline clinical and hematological parameters of the 36 patients are shown in [Table 1]. The median age of the cohort was 57 years (range, 35–80 years), and the female–to-male ratio was 1:5. Zeta-chain-associated protein kinase-70 was positive in 17 (58.6%, n = 29), CD 38 in 14 (45.1%, n = 31), and CD49d in 18 (66.6%, n = 27) patients; a total of 24 patients (13 with newly diagnosed and 17 with R/R CLL) did not harbor any mutations in the IGVH gene. The mutation status was documented only once during the course of treatment. Of the 18 patients with newly diagnosed CLL, 11 received treatment (4 with ibrutinib; 4 with bendamustine and rituximab [BR]; 2 with chlorambucil and prednisolone [CP]; and 1 with fludarabine, cyclophosphamide, and rituximab [FCR]), whereas 7 patients were kept under observation. The overall response rate (ORR) was 63.6% (7 out of 11 patients), and complete response (CR) was seen in 36.36% (4 out of 11) of the patients. Of 18 patients with R/R CLL, 15 received treatment (4 with ibrutinib; 4 with BR; 5 with rituximab, cyclophosphamide, doxorubicin, vincristine, prednisolone/rituximab, cyclophosphamide, vincristine, prednisolone; and 2 with CP); the observed ORR was 40%, and the CR rate was 13%. The different regimens used in the management of CLL in our cohort are listed in [Table 2]. Eighteen patients died, 11 due to disease progression, 4 due to infections, and 3 due to other reasons. In addition, 8 patients developed Richter's syndrome and died. The median PFS of the cohort was 14 months (16 months for those with newly diagnosed CLL and 7 months for those with R/R disease) during a median follow-up period of 29 months. The estimated 5-year overall survival rate of the cohort was 40%.
Table 1: Clinico-hematological parameters of patients with chronic lymphocytic leukemia with 17p del (de novo and relapsed/refractory)

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Table 2: Different treatment regimens used in the management of chronic lymphocytic leukemia with 17p deletion

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Del17p is usually seen in about 50% of the R/R CLL cases.[1] It is associated with high-risk disease in patients who have indications and progress to require treatment.[6] The response to standard first-line chemo-immunotherapeutic agents is inadequate in patients with CLL harboring del17p.[3],[4] The ORR reported with standard-of-care first-line FCR was 70%, with a median PFS of 11 months.[6],[7] The results of alemtuzumab (either as monotherapy or with steroids), BR, and lenalidomide with rituximab have been disappointing.[8],[9]

In the present study, the incidence of del17p was 25.5% in the R/R cases, which is comparatively lower than that reported in the literature from the Western world. This may be due to a selection bias, as we had not routinely tested for del17p at the time of second or third relapse and beyond. The most commonly used chemo-immunotherapeutic agent in our study was BR. FCR was used only in one patient in our study because of its unfavorable toxicity profile in our population.[10] Currently, newer oral drugs such as the Bruton kinase inhibitors (ibrutinib and acalabrutinib); BCL2 inhibitors (venetoclax), either alone or in combination with obinutuzumab; and phosphatidylinositol 3-kinase inhibitors (duvelisib and idelalisib) have been shown to have better efficacy and safety profiles over chemotherapy.[11] In our study, ibrutinib could be used in only eight patients because of financial constraints. Generic brands of ibrutinib and other oral drugs were not available in India during the study period. Our study was limited by the unavailability of testing facilities for the other cytogenetic abnormalities. To the best of our knowledge, ours is the first Indian study reporting the outcomes of patients with CLL harboring del17p.

In conclusion, the incidence of R/R CLL in our cohort was 25.5%, and the outcome was dismal with chemo-immunotherapeutic agents. The generic brand of Bruton kinase inhibitors is currently available at a lower cost in India, which might improve the survival outcomes in our population.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Hillmen P, Skotnicki AB, Robak T, Jaksic B, Dmoszynska A, Wu J, et al. Alemtuzumab compared with chlorambucil as first-line therapy for chronic lymphocytic leukemia. J Clin Oncol 2007;25:5616-23.  Back to cited text no. 8
    
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Badoux XC, Keating MJ, Wen S, Lee BN, Sivina M, Reuben J, et al. Lenalidomide as initial therapy of elderly patients with chronic lymphocytic leukemia. Blood 2011;118:3489-98.  Back to cited text no. 9
    
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Gogia A, Sharma A, Raina V, Kumar L, Vishnubhatla S, Gupta R, et al. Assessment of 285 cases of chronic lymphocytic leukemia seen at single large tertiary center in Northern India. Leuk Lymphoma 2012;53:1961-5.  Back to cited text no. 10
    
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