Clinical Case Discussion Forum

Thank you for this interesting case.

To summarise:

39M
06/25 -     CML-CP diagnosis. Hepatosplenomegaly with ascites.
            Started imatinib 400mg QD
11/25-     Switched to nilotinib 400mg BID on account of persisting hepatosplenomegaly with ascites
07/26 -     WCC under control, but with persistent hepatosplenomegaly and peripheral oedema

I suspect the current organomegaly with ascites is unlikely due to CML.
I note this patient had hepatomegaly with ascites at presentation. It is very unusual for this to occur if CML is the only diagnosis. CML causes splenomegaly, but almost never massive hepatomegaly with ascites. I also note the marrow fibrosis at diagnosis - this may be an incidental finding in some CML patients. I suspect that even at baseline, this patient had significant liver disease.

You have treated the CML and the WCC has fallen. QPCR information in this case will be very useful. If the BCR::ABL1 % is low, you can be further reassured that his CML is under control.

I'd probably do another liver ultrasound looking for liver pathology and portal hypertension. Hypersplenism secondary to portal hypertension will cause thrombocytopenia and complicates the treatment of CML. I'd probably ask for help from my hepatology colleagues as well.

Hope this helps – David

Dear Dr. Yeung,

Thanks a lot for your input in this challenging case.

Our patient has been seen by hepatology. They thought his portal hypertension could may be be attributed to CML but are contemplating a liver biopsy. This procedure may be more risky in view of the thrombocytopenia and might need platelet transfusion support.

We will definitely be ordering a PCR and a new liver imaging.

100% agree with David.

Pre-existing liver disease likely independent from CML.

Very complicated case. I think both Jaqueline and David are on the right track but perhaps have not gone far enough. There are two issues here - diagnosis and management.

Let's summarize diagnosis. As David has said, fibrosis is rare with CML but not unknown and usually not this pronounced. At one time, it was considered a sign of acceleration or if it developed on therapy, disease progression. If the fibrosis is due to the CML, it should respond to TKI. If in fact bcr::abl1 improves but splenomegaly does not, then we are likely dealing with a second diagnosis.

Checking JAK2 was on the right track but incomplete. There are now a number of cases in the literature of CALR MF also occurring with bcr::abl1. This should be checked.

Splenomegaly in the presence of liver disease usually occurs as hepatic fibrosis develops. The presence of both hepatomegaly and splenomegaly suggests a possible infiltrating process - malignancy, infectious, or metabolic. If CALR is negative, then this should be attacked aggressively and a risky biopsy considered. Transjugular would be the safest, but not without risk.

Treating co-existent CML and MF has been done with combination TKI and ruxolitinib.

A very aggressive approach which would help with diagnosis and perhaps management, would be splenectomy. Here pathology and microbiology could be done. Causes such as metabolic, infectious and other malignancy such as a hepatosplenic lymphoma could be looked for.

Splenectomy would also possibly reduce the bulk of whatever is going on here open other options.

I do not believe that organomegaly is a contraindication to allografting. The arguments for and against splenectomy in MF pre allografting exist and I have done it both ways. The spleen as the target for initial engraftment versus the sponge argument are both out there.
Finally, if this is really "resistant" CML and a transplant is completely out of the possibility, then I would go with a third generation TKI if it can be accessed.

Good luck and please keep us updated.

Thank you for sharing this interesting case. I also think that we might be dealing with more than one disease. Also to be sure we are getting a molecular response, it is a good idea to get a BCR-ABL1 % (IS) quantification as we continue with low dose TKI but we may need to change to another type.

i agree with David Yeung that this is a very unusual presentation for CML. In my opinion you should explore the possibility that there was a previous unrecognised myelofibrosis and then the onset of a Ph-positive clone on top of it. Of course the TKI therapy can reduce the Ph-positive clone, but not the original myelofibrotic clone. Did you test also JAK2, CALR etc.. and the other mol markers for myelofibrosis?

Dear Dr. Jacqueline, it is a very interesting case report. I would order (he is JAK 2 negat.) CALR, MPL and NGS MPN testing to rule out other non BCR::ABL mutations to get more information about his myelofibrosis, that was grade 3 at the diagnosis. I would also perform bone marrow rebiopsy and cytogenetic with BCR::ABL QPCR to reevaluate nilotinib effect on his CML and the grade of fibrosis or other Ph negative clonal disorder. If the response of nilotinib is optimal and there are no other cytogenetic and molecular abnormalities, then the primary liver disease is probably the cause of hepatosplenomegaly and ascites and liver biopsy should be considered.

Good luck with this patient!

Best regards, Katarina.

Thanks for sharing the difficult case. I agree with Dr. David Yeung that a CML in chronic phase extremely unlikly to present with marked hepatomegaly and especially with ascitis. Hepatic cirrhosis should be ruled out definitely. Especially if current BCR-ABL1 quantity shows reduction parallel with leukocyte response, there is strong possibility of 2nd condition (cirrhosis?) responsible for hepatomegaly and ascitis.
I would add that possibility of blastic phase is to be explored. Bone marrow aspirate from a marrow with grade III fibrosis certainly yield dry tap or blood tap and aspirate in this case may be just represented peripheral blood rather than marrow cellularity. CD34 staining of a good core biopsy would give better idea about marrow blast count. Moreover, extramedullary blast seedling may involve peritoneal cavity rarely and ascitic fluid cell count, morphology +/- flow cytometry would help to identify blastic transformation with peritoneal involvement.
Besides possibility of blastic CML, due to poor hematological response with Imatinib persistence of basophil on treatment with nilotinib, TKI resistance mutation should be tested in my opinion, and I would not prohibit dasatinib, if needed, merely for ascitis.

Regards - Akhil

​Thank you for sharing this complex case. We can see CML and myelofibrosis in the same patient and treat both diseases, so the overlap here is clinically familiar, but it does raise the question of whether this is CML alone with a fibrotic phenotype, or CML co-existing with (or evolving alongside) an independent myeloproliferative process.

I suggest:
-Molecular monitoring with quantitative BCR-ABL1 PCR: determine CML status
- CALR Mutations and repeat BM biopsy to reassess fibrosis grade and blast percentage: confirm MPN and add JAK2 inhibitor accordingly.
- New liver image
- Evaluate changing to allosteric TKI as Asciminib if possible.

This kind of scenario does occur, though not very common. Bone marrow function does not appear suppressed at all. The anaemia seen at presentation is not fully characterized, for example I haven't seen the mean red cell volume. Maybe I missed it. Portal hypertension from sheer high spleen blood volume or splenic vein thrombosis has not come out clearly. Chronic small GI bleeds can lead to this kind of anaemia I suggest this could be part of the problem that needs to be teased out before any drastic steps are taken.

I would like to thank all the most helpful inputs from all the colleagues in this difficult CML case.

I saw the patient today and he continues to feel well.
cbc 08/18/2026: hb=13.6 ht=42.87
wbc=8,410 (normal diff)
platelets= 68,000
Liver and spleen size are unaltered
An abdominal ultrasound was performed on 07/08/2026:
Liver with increased dimensions without focal lesions (Right lobe 16.9cm)
Portal vein with normal caliber (9mm)
Spleen with increased dimensions (22.6cm)
Multiple confluent expansive formations, with heterogeneous echotexture, cystic areas, lobulated contours. The biggest on supraumbilical mesogastrium 16.8X10cm

A quantitative pcr was collected today
CalR and MPL mutations will be checked
Extensive liver workout was done during his hospital admission including serologies and auto-imune liver disease - all negative
He will be readmitted to the hospital to plan a biopsy of the abdominal mass