Research Article, Clin Oncol Case Rep Vol: 8 Issue: 7

A Peculiar Case of Chronic Myelomonocytic Leukemia with Myelodysplastic Syndrome Overlap Presenting with Acute Renal Failure

Heenaben Patel^1*, John Patresan², Hashem Ayyad³, Andres Ramirez Gamero¹, Griffin Reynolds², Gerald A. Colvin²

¹Department of Medicine, Roger Williams Medical Center, Providence, RI

²Department of Hematology/Oncology, Roger Williams Medical Center, Providence, RI

³Department of Pathology, Roger Williams Medical Center, Providence, RI

*Corresponding Author:

Heenaben Patel
Department of Medicine, Roger Williams Medical Center, Providence, RI
E-mail: heenaben.patel@chartercare.org

Received: April 29, 2025; Manuscript No: COCR-25-165029; Editor Assigned: May 2, 2025; PreQC: COCR-25-165029(PQ); Reviewed: May 28, 2025; QC No: COCR-25-165029(Q); Revised: June 10, 2025; Manuscript No: COCR-25- 165029(R); Published: July 30, 2025, DOI: 10.4172/cocr.8(7).422

Citation: Patel H, Patresan J, Ayyad H, Gamero AR, Reynolds G, et al. (2025) A Peculiar Case of Chronic Myelomonocytic Leukemia with Myelodysplastic Syndrome Overlap Presenting with Acute Renal Failure. Clin Oncol Case Rep 8(7):422

Abstract

Keywords

Myelodysplastic Syndrome; Myeloproliferative Neoplasm; Chronic Myelomonocytic Leukemia

Introduction

Myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) overlap syndromes are relatively rare disorders with incidence ranging from 0.3 to 0.4 per 100,000 [1-2]. In adults, MDS/MPN can present as 4 different ways: chronic myelomonocytic leukemia (CMML), disorder with ring sideroblasts-thrombocytosis (MDS/MPN-RS-T), atypical chronic myeloid leukemia (aCML), BCR-ABL1 negative form and in an unclassifiable form (MDS/MPN-U) [3]. Patients with peripheral monocytosis with mutations of TET2, SRSF2, ASXL1 and SETBP1 in NGS (next generation sequencing) can suggest CMML type, however, needs careful interpretation as these mutations can also present in other types of myeloproliferative disorders. WHO diagnostic criteria are very helpful and reliable to aid in diagnosis of this rare disorder [4]. There is an inherent risk of transformation to leukemia for these cases, approximately 15% over the next 3-5 years [5]. Involvement of brain [6], lung [7], pericardial [8], and bone [9] is uncommon but can occur. The median survival is usually 31 months with treatment [10].

We herein present a case of 76-year-old male who presented with severe anemia, thrombocytopenia and renal failure who was diagnosed with MDS/MPN CMML, type 1 subtype via bone marrow biopsy with a prolonged hospitalization due to refractory anemia and thrombocytopenia.

Case Presentation

76-year-old male with no significant past medical history who presented to an outside hospital after a syncopal episode in the urgent care while providing a urine sample. The patient had not had any laboratory work or seen a physician in the last 5 years. He was not on any medication at the time of the presentation. Patient reported progressive fatigue, shortness of breath with activity and associated dizziness for which he visited urgent care. Past surgical history is significant for left hip arthroplasty. He denied any smoking, alcohol or drug use. No known drug allergies. The patient denied any age-appropriate cancer screening such as PSA testing or colonoscopy in the past. His vital signs were within normal limits upon admission, and he had no significant clinical findings on physical examination including lymphadenopathy or organomegaly. In the emergency department, the patient was found to be in acute renal failure with creatinine of 6.0 mg/dl along with profound microcytic anemia with hemoglobin of 3.5 g/dl and severe thrombocytopenia with platelet count of 13000/uL. Peripheral smear showed anisopoikilocytosis, with dichromate RBCs, some of which were hypochromic, tear drop cells and ovalocytes. There was subtle evidence of basophilic stippling. Very scant platelets, no schistocytes and the lymphocytes looked very atypical. A computed tomography (CT) of the chest, abdomen and pelvis on admission did not find any significant abnormalities. There was no clinical evidence of active bleeding that could explain severe anemia. The vitamin B12 level was 1300 pg/ml and folate level 7.6 ng/ml which were both not deficient. The stool occult blood test came back negative. It was not clear if the renal failure was acute or chronic given no recent labs for comparison. There were no signs of obstruction on CT imaging that would suggest a post-renal etiology of kidney injury. There was high concern for thrombotic thrombocytopenic purpura (TTP)/ atypical hemolytic uremic syndrome (HUS) upon admission given this constellation of findings, although nephrology was consulted who additionally recommended ADAMSTS13, anti-GBM antibody, vasculitis studies including anti-neutrophil cytoplasmic antibodies, complement C3 and C4 levels, hepatitis and HIV serology, serum protein electrophoresis with immunofixation. The patient was started on Solu-Medrol 500 mg IV every 24 hours for 3 days followed by prednisone 1 mg per kg for a suspected rapidly progressive glomerulonephritis. The case was discussed with hematology oncology as well, hemolysis labs such as reticulocyte count, indirect bilirubin, lactate dehydrogenase and haptoglobin were requested to help support the suspected diagnosis of microangiopathic hemolytic anemia (MAHA). In the interim, the patient was transferred for possible therapeutic plasma exchange.

Initial lab work showed Hemoglobin 3.5 g/dl, MCV 66.3 fL, platelet 13000/uL, total white counts 6800 per microliter (normal 4000-11,000), neutrophils 68% (normal 40-75), monocytes 8% (normal 2-12), lymphocyte 24 % (normal 20-46), PT 12.4 sec, INR 1.17, APTT 27.9 sec, D-dimer 4.17 mg/L, urine analysis showed 3+ blood 18 RBC, 6 WBC , 1+ uric acid crystals, creatinine 6.8 mg/dl, BUN 82 mg/dl, anion gap 15, potassium 5.0 mmol/L high, uric acid 18.4 mg/dl high, phosphorus 7.7 mg/dl high, calcium 8.8 mg/dl low, albumin 4 g/dl, bilirubin normal, LFTs normal, LDH total 168 U/L, HIV and hepatitis panel negative, COVID-negative (Table 1, 2). Additional testing revealed ANA negative, complement C3 71 low (normal range 79-152), complement C4 11 low (normal range 18-55).

Table 1: Laboratory values on Day 1 and Day 25 of hospital admission (available values)

Table 2: Other significant laboratory values on Day 1 of hospital admission

Given the hemolysis labs (including LDH, indirect Bilirubin, haptoglobin) did not suggest frank hemolysis, the initial theory of MAHA related disorders such as TTP or Atypical HUS were less likely. The labs did not suggest a disseminated intravascular coagulation either given the coagulation profile including fibrinogen was 229 mg/dl (normal range 200-400) as well as the patient not having any clinical evidence of bleeding or thrombosis. The diagnosis at the point remained nebulous, perhaps an autoimmune etiology or bone marrow failure. A bone marrow biopsy was performed. Arsenic, cadmium and lead level were sent due to occupational exposure history and ultimately came back negative. ADAMTS13 activity came back at 60%, which was clinically insignificant. Additionally, myeloperoxidase antibody, anti-proteinase 3 antibody, SSA/Anti-Ro IgG and SSB/Anti-La IgG antibody came back negative. Glomerular basement membrane antibody came back negative as well. Free kappa light chains 24 mg/L (normal 3.3-19.4), normal kappa/lambda ratio. The patient was found to have left gluteal hematoma after bone marrow biopsy which expanded despite conservative measures such as pressure dressing, tranexamic acid, DDaVP and blood product support. Throughout his hospital course, he received a total of 33 packed red cell transfusions, 2 units of fresh frozen plasma and 8 units of platelets without appropriate response. Due to this, additional blood bank tests were suggested including factor 11 to evaluate for coagulopathy which was 49% and 31% on repeat (normal 65-150%), which could have been explained by some consumptive process rather than an inherited process or severe liver disease. Given the refractoriness to platelet transfusions, platelet autoantibody test was sent which came back negative.

The hospital course otherwise was remarkable for atrial fibrillation with rapid ventricular response which resolved with administration of beta blocker. While awaiting the results of the bone marrow biopsy, the patient remained severely anemic, thrombocytopenic and transfusion dependent despite the high dose steroids initially during the hospital course. Other therapeutic strategies were employed such as IVIG without any dramatic improvement in the platelet count. Nephrology suggested performing a renal biopsy to help cinch the diagnosis, although this was extremely challenging as the patient was profoundly bicytopenic and the primary team was concerned for coagulopathy as well given the expanding gluteal hematoma. Given his tenuous clinical course, renal biopsy was not performed.

Fortunately, his creatinine started to improve and normalized on day 10 of admission, he did remain cytopenic however with his hemoglobin averaging in the 7 g/dL range and platelets 8-10k u/L. His bone marrow biopsy came back suggestive of CMML/MDS overlap syndrome. Bone marrow cytogenetics revealed multiple mutations including ASXL1, RUNX1, SRSF2, TET2, & deletion of chromosome 20 (del20); PNH clone was absent. No alterations seen in FLT3, IDH1, IDH2, NPM1, TP53. There were no blasts in the bone marrow. These findings were consistent with chronic myelomonocytic leukemia (CMML) and given the lack of bone marrow blasts (i.e. <10%), this was consistent with CMML-1. Although the patient had leukocytosis, he was on steroids and prior to steroid initiation, his white count was normal with associated anemia and thrombocytopenia only. The lack of specific cell line proliferation was consistent with MDS indicating a CMML-MDS overlap syndrome. Patient was not eligible for bone marrow transplant given his age. Risk stratification revealed international prognostic scoring system (IPSS) 0.5 points consistent with intermediate-1 prognostic risk. The patient started on azacitidine 75mg/m² for 7 days; every 4-week cycles, planned for 4-6 cycles while inpatient. His counts gradually started to improve, and his hematoma started to resorb. He was discharged after a 22-day (about 3 weeks) hospital course once he was stabilized and was planned to be followed closely in hematology clinic with blood work and continued azacitidine. In the outpatient setting to date, he has received 3 cycles of azacitidine (Day 1-7, every 28 days) with considerable improvement in his cell counts. His most recent CBC denotes a WBC 2.7 with ANC of 1.1, Hb of 11.1 with MCV of 100.8, and platelet count of 189. Clinically, he feels well and is living independently at home. The plan was to continue Azacitidine until unacceptable toxicity or progression.

Discussion

Our patient was presented with microcytic hypochromic anemia with severe thrombocytopenia and acute renal failure. There was no evidence of frank hemolysis on initial presentation or presence of schistocytes to suggest microangiopathic hemolytic anemia which is a common suspicion a clinician would have with that constellation of findings. His coagulation profile did not suggest disseminated intravascular coagulation either. A rapidly progressive glomerulonephritis was certainly in the differential, and it was even empirically treated as such with pulse dose steroids although a kidney biopsy was not feasible. There was also a possibility of other autoimmune processes such as vasculitis or neoplastic processes such as occult lymphoma, or bone marrow failure from chemical exposures given his occupational history. His basophilic stippling raised the question of lead poisoning especially given he was a carpenter, but that theory was debunked given normal lead levels. His autoimmune serology was unrevealing which then left a primary hematological process driving his clinical course. Although his imaging was not elucidating, his bone marrow biopsy was instrumental in deciphering his underlying syndrome and how to best treat the patient. Recall, bone marrow biopsy came back suggestive for CMML/MDS overlap which is rare and has an incidence of approximately 0.6 cases per 100,000 people in the United States [11]. There appears to be a predilection for males and the median age of diagnosis is 73[11]. There were also case reports in literature for cases such as this that can present as a separate entity known as TAFRO syndrome: Thrombocytopenia, anasarca, fever, reticulin fibrosis, renal dysfunction, and organomegaly [12].

The cytogenetics associated with CMML/MDS have some commonalities with acute myeloid leukemia (AML). Particularly, ASXL1 and RUNX1 are associated with poor prognosis in MDS, CMML, AML, MPN. SRSF2 is associated with poor prognosis in MDS, AML, primary myelofibrosis & polycythemia vera. TET2 is associated with improved response to hypomethylation but poor prognosis in MDS after HSCT. Poor clinical prognostic factors can also include leukocytosis at presentation, monocytosis, circulating immature myeloid cells, anemia, and thrombocytopenia [11]. The chronic myeloid leukemia (CML)-P190 variant can mimic CMML due to the presence of monocytosis and needs to be distinguished [5]. The mainstay of treatment remains allogenic stem cell transplant, as this is the only known curative strategy. However, transplant is not feasible for a large majority of patients (only 10% are eligible), given factors such as advanced age and performance status. Therefore, hypomethylating agents such as azacitidine or decitabine are now employed in the treatment of this disease, which are also used in MDS and AML patients who are not eligible for allogenic stem cell transplant. While there were no explicit trials in evaluating hypomethylating agents in CMML/MDS, they have been approved for use in this setting from data that was extrapolated from MDS-predominate phase III trials as the patient selection did include a minority of patients with the overlap syndrome. Hypomethylating agents in general work by inhibiting DNA methyltransferases. Methylation silences certain aspects of gene expression and that can contribute to neoplasia. The overall response rate can range from 40-50%, with a true remission on the order of <20% [11].

Kidney involvement can be multifactorial in MDS/MPN-CMML[13-14] In our case, we suspect that this might be due to tubulointerstitial damage from elevated uric acid deposition due to increased cell turnover, with acute tubular necrosis. Unfortunately, kidney biopsy could not be obtained due to persistently low platelets and bleeding risk, to help elucidate what truly caused the renal injury. Patients with CMML can have associated ITP [15]. However, despite all IVIG and steroid treatment, the patient’s platelet count remained refractory suggesting that a component of ITP was less likely in this case. Platelet dysfunction can also occur in patients with CMML. A case report of recurrent subdural hematoma responding to platelet transfusion is available in literature and high doses of vitamin C might have restored the function of the TET2 gene as concluded by authors [16].

An observational infrequent association has been seen with CMML and acquired dyserythropoietic syndromes such as congenital erythrocyte pyruvate kinase (PK) deficiency seen in 72-year-old female patient with CMML [17]. We have not tested our patient for this cause to rule out the cause of anemia as an acquired erythrocyte pyruvate kinase (PK) deficiency. However, bone marrow did show mild dyspoiesis with erythroid hyperplasia and slight increase in megakaryocytes without any significant dyshemopoietic changes in all blood cell lines and especially in erythroblasts. Granulocytic lineage shows progressive maturation segmented neutrophils with occasional pseudo-Pelger-Huët forms. Dyspoietic changes likely represent stress erythropoiesis. Additionally, the bone marrow examination did not suggest complete absence of erythropoiesis which can suggest pure red cell aplasia, which is also associated in patients with CMML [18].

MDS/CMML related systemic inflammatory and autoimmune diseases (SIADs) has been seen in approximately 10–20% of patients with the disease^. [19]. These cases may respond to steroids but very commonly lead to steroid dependence and relapse. There was no evidence of vasculitis or any other autoimmune condition in our case as ANA and ANCA panel was negative. RF, anti-cardiolipin antibodies, anti-phospholipid antibodies, ACE level, Cryoglobulins, anti-β2 glycoprotein antibodies, immunoglobulin levels test was not done. The complement levels for C3 and C4 level were low, which could be multifactorial.

In a presentation such as this, where the underlying culprit syndrome is nebulous, a bone marrow biopsy with ancillary testing for cytogenetics is essential. The diagnosis obtained from our bone marrow biopsy is what ultimately led to us treating the patient appropriately, which led to his discharge from the hospital and significant improvement of platelet count as an outpatient.

Conclusion

Peripheral monocytosis with severe anemia and thrombocytopenia should raise suspicion for MDS/MPN overlapping syndrome. Presenting symptoms can be a sequel of an organ failure, however if that happens in settings of bicytopenia refractory to multiple transfusion without obvious major bleeding or hemolysis, hematological malignancy should be in a top differential in older adults. The bone marrow biopsy with cytogenetics will require to elucidate the diagnosis.

Additional Information

Disclosures

Human subjects

Consent was obtained from the patient for this case report.

Conflicts of interest

In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work.

Financial relationships

All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work.

Other relationships

All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Acknowledgements

There is no funding or grant received for this project.

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