Imatinib-Dependent Ascites as a Side Effect of Abdominal Surgery

Jeffrey H Lipton

doi:10.37871/jbres1988

ISSN: 2766-2276

Medicine Group. 2024 August 31;5(8):1060-1062. doi: 10.37871/jbres1988.

Subject area(s)

Surgery
Oncology

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Mini Review

Imatinib-Dependent Ascites as a Side Effect of Abdominal Surgery

Jeffrey H Lipton*

Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada

*Corresponding authors: Jeffrey H Lipton, Medical Oncology and Hematology, Princess Margaret Cancer Centre, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada E-mail:

Received: 09 July 2024 | Accepted: 28 August 2024 | Published: 31 August 2024

How to cite this article: Lipton JH. Imatinib-Dependent Ascites as a Side Effect of Abdominal Surgery. J Biomed Res Environ Sci. 2024 Aug 31; 5(8): 1060-1062. doi: 10.37871/jbres1951, Article ID: jbres1757

Keywords

Chronic Myeloid Leukemia (CML)
Fluid retention
Imatinib

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Abstract

Atypical fluid retention is an uncommon side effect of imatinib therapy. This case report describes ascites that developed post-Abdominal Aortic Aneurysm (AAA) repair in a man on imatinib for Chronic Myeloid Leukemia (CML), and only resolved on cessation of imatinib therapy.

Abbreviations

CML: Chronic Myeloid Leukemia; GIST: Gastrointestinal Stromal Cell Tumor; MMR: Major Molecular Remission; BCR: Breakpoint Cluster Region; Abl: Abelson Rearrangement; PCR: Polymerase Chain Reaction

Introduction

Fluid retention is a well-known side effect of imatinib therapy for Chronic Myeloid Leukemia (CML) [1,2], but is not unique to this Tyrosine Kinase Inhibitor (TKI) [3-5] This commonly takes the form of peripheral edema or peri-orbital edema, but other rare presentations have been noted [6-9]. CML can even present with ascites as a manifestation of extra-medullary disease, but when this occurs, it is staged as blast crisis [10]. Imatinib is also used in the therapy of GIST (Gastrointestinal Stromal Cell) tumors where ascites have been reported [11]. I wish to report an unusual case of CML-treated, imatinib-dependent ascites that developed as a side effect in a man post-surgery for an Abdominal Aortic Aneurysm (AAA).

Case

A 70-year old male presented with chronic phase CML, Philadelphia-chromosome positive, bcr::abl (the molecular rearrangement in most CML) positive. Past medical history was positive for myocardial infarction treated with triple vessel by-pass surgery and a subsequent angioplasty. He was initially treated briefly with hydroxyurea, then with alpha-interferon (Intron-A), remaining on various doses for about 18 months and achieving Fluorescence In Situ Hybridization (FISH)-negativity for bcr::abl. Bcr::abl could be detected by a non-quantitative PCR (Polymerase Chain Reaction) assay at that time. He did not tolerate interferon very well, with chronic fatigue and at least one episode of febrile neutropenia. In July 2001, he was started on STI571 (signal transduction inhibitor 571) now known as imatinib, on a phase 2 compassionate use study. By 2 and ½ years of therapy, he had achieved what could then be determined as MMR (0.1% international standard or IS) with a now established quantitative assay. By 2008, he had a stable 4-log (0.01% IS) reduction in transcripts and other than mild periorbital edema was doing well.

In January 2009 some seven and a half years after starting imatinib, he underwent AAA repair for an aneurysm that had been diagnosed several years earlier, was noted to be expanding. Surgery was complicated by bleeding and post-operatively, by ascites, which developed within a month of the surgery, requiring drainage on multiple occasions, approximately every two weeks. His surgeon felt that this was not a post-operative complication. Given the association of fluid retention with imatinib, I raised the possibility that this was related to his CML therapy and triggered by the surgery. I held the imatinib as a therapeutic trial. At the time of holding the imatinib, his pcr for bcr::abl showed >4-log (>0.01% IS) response. With gentle diuresis and an imatinib holiday, the ascites resolved within about 4 weeks. At that point, given the lack of knowledge about what in the future might be successful stopping of therapy, I resumed the imatinib and within four weeks, the ascites returned. I repeated the unsuccessful attempt to withhold and restart therapy twice more and eventually the patient and I conceded defeat in May 2009. His pcr remained at a >4-log (>0.01% I) response. With no other tyrosine kinase inhibitor available to us in that time period, I elected just to monitor him. Off therapy, his ascites completely resolved, his activity level and quality of life improved to normal. He remains alive and well off therapy with a molecular response of 0.001% IS now 23 years after starting imatinib, 15 years after stopping and never having been treated with anything further for his CML and no recurrence of any intra-abdominal events.

Patient consent was provided to discuss this case.

Discussion and Conclusion

Ascites as a sign of GIST tumors is well known and imatinib as a therapy for this tumor type is standard with resolution or improvement of the ascites [11]. There is even a single report of a CML patient presenting with ascites (blast crisis) which resolved transiently on successful therapy of the CML with imatinib [10]. A single case of ascites in an imatinib-treated patient after an abdominal procedure has been reported [12]. In the case described here, the patient had been on imatinib for more than seven years with no ascites, but then developed them after the surgery.

Congestive heart failure can be seen with all TKIs and needs to be ruled out [3-5,13]. A good physical examination, echocardiogram and even BNP (B-type Natriuretic Peptide) may be helpful [14]. In this situation, heart failure therapy with or without discontinuation of the TKI is the approach [15]. In the case discussed here, given his pre-morbid history, heart failure was ruled out.

On rare occasions when all other work-up still leaves doubt and diuretic therapy is not effective, tapping of the fluid site if possible, should be done as there may be other causes of fluid collections that need to be ruled out and treated [16,17]. This may be due to cirrhosis, infection, malignancy in the case of ascites, just to name a few. Today, with at least six CML drugs commercially available, a drug switch may be all that is necessary, as side effects are not necessarily present with all drugs [18]. In addition, we now know that in about half of cases where there is a deep molecular remission, drugs may be stopped permanently [19]. This was not the situation 15 years ago and imatinib was only stopped for medical complications.

Unusual presentations of fluid retention due to imatinib are rare, but should be considered in the case of patients on therapy who develop otherwise unexplained collections. It is possible that such collections are a response, perhaps inflammatory or immunological, to another event that if not immediately obvious, should be investigated. Patient monitoring for adverse events is as important as monitoring for efficacy [3,19]. In some cases such as GIST, imatinib is the treatment for ascites. In this case, it appears to have been the cause but with an outside trigger. The cause of fluid retention with tyrosine kinase therapy in CML is unknown, with the exception possibly of dasatinib where it is felt to be autoimmune. Even in 2024 after almost 30 years of use of the drug, the mechanism of imatinib induced fluid retention is uncertain as has been recently reviewed [20]. In the past, attempts have been made to look at imatinib drug levels as a cause of toxicity, but with the exception of cytopenias, no correlation was found [21].