can cll cause diarrhea?

Q1. When I was first diagnosed with CLL, I was having a lot of pain in my stomach. Does that go along with CLL? I felt better for a while, but now that pain is back. Should I be worried about the pain? It seems to be in the entire abdomen.

There are many potential causes for abdominal pain, but two come immediately to my mind. First, CLL can cause enlargement of lymph nodes and the spleen that can be quite significant. Just having enlarged organs can cause pain. Second, CLL (and a particular lymphoma with which it is often confused called mantle cell lymphoma) can sometimes grow in the lining of the stomach and intestines, which causes cramping, weight loss, diarrhea and reflux. In either case, treatment of the underlying CLL might lead to relief. Alternatively, specific measures such as removal of the spleen (if the spleen is enlarged) or drugs to treat reflux symptoms might provide some relief from the pain.

Q2. I was diagnosed with CLL two years ago. I have mild symptoms and am not undergoing any treatment at this time. I experience severe fatigue from time to time, but more troublesome is leg and joint pain, which also occurs from time to time. Is this pain caused by CLL? I also have restless legs syndrome (though the symptoms have become more infrequent of late) and some varicose veins.

— Sallie, Mexico

Leg and joint pain are common symptoms of many diseases. In the case of CLL, increasing disease activity in the bone marrow may cause leg and possibly joint pain — however, this is rare. The more likely explanation is simple aging. For example, the development of osteoarthritis in your joints may cause some of the discomfort. I have many patients (including some family members) whose varicose veins also cause their legs to ache. Although many patients believe it is superficial to treat varicose veins, pain can be overwhelming and treatment might be warranted. If you suspect that varicose veins may be the culprit, a visit to a vascular surgeon's office might be in order.

Q3. I have had CLL for about four years now with no treatment and am at stage II. Recently, my legs have been aching at night so bad that I need to get up and take aspirin. My most recent lab work showed white cells at 32,000 and red cells at 10. Could the low red cells make my legs ache?

If a person has poor circulation (atherosclerotic disease) to the legs, a lower blood level might result in pain. If there is testing that demonstrates reduced blood flow in the legs, raising the red cell count might alleviate pain. However, a hemoglobin count of 10 is relatively good and probably not low enough to explain your leg pain, especially at rest. (It is unusual that the pain is at night when the legs are not active.) You should ask your doctor for a thorough evaluation to find alternative causes for the pain in your legs.

Q4. I have CLL. I have been treated with radiation, chemotherapy, bone surgery, and two stem cell transplants. My primary means of pain management is OxyContin. I asked my daughter to help pay for my prescriptions, but she refuses and says I'm a drug addict. What can I tell her?

— John, Ohio

Rarely, the treatments for CLL or the disease itself can leave a patient with chronic pain syndrome. After exhausting the nonnarcotic options for pain management, the treating physicians or pain specialists often offer long-acting narcotics. Unfortunately, the stigma of abuse is associated with medications for chronic pain. The vast majority of patients with chronic pain are not abusers. This stereotype is propagated unfairly through depictions in film, in literature, and on television. Indeed, patients themselves often become concerned and undermedicate themselves because of it.

I usually confront my patients and their resistant family members early on about concerns or allegations of abuse. Chronic pain is really no different from any other chronic medical problem. Taking your daughter’s reasoning to its logical conclusion would mean that diabetic children are "addicted" to insulin; patients with hypertension, to blood pressure medications; and patients with high cholesterol, to their cholesterol-lowering medicines. Once patients start these medicines, they almost never get to the point at which they can stop using them without suffering consequences. Your circumstances are no different.

If your daughter won't accept the explanation from you directly, take her with you to the doctor and ask the doctor to explain this to her clearly. In the end, if she can’t understand your medical needs, then kindly ask her to stay out of your medical affairs. At present, she is only making your chronic pain worse.

Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. It has a variable presentation with most patients having asymptomatic lymphocytosis. Many other patients present with lymphadenopathy or enlargement of other organs of the reticuloendothelial system. However, CLL can present with extramedullary involvement. Most commonly, this is in the form of skin or central nervous system involvement, though rarely it can present with gastrointestinal involvement. Here, we present the case of a 70-year-old Caucasian male who presented with chronic diarrhea for over 4 months. After failing conservative treatment, a colonoscopy was performed which showed diffuse mucosal nodularities with a biopsy revealing CLL. The patient was treated successfully with chemotherapy and his diarrhea improved. This is a differential to keep in mind in patients with chronic diarrhea, once the more common causes have been ruled out.

B-cell chronic lymphocytic leukemia (CLL) is the most common form of leukemia in the United States, accounting for almost 25 to 30% of all leukemias . CLL is a progressive accumulation of functionally inert lymphocytes in the blood, lymphoid tissues, and bone marrow. It most commonly affects elderly patients with a median age of diagnosis being 70 years of age . The presentation of CLL can be very variable ranging from asymptomatic lymphocytosis to painless lymphadenopathy, hepatomegaly, splenomegaly, cytopenias, and infections. Patients can also sometimes present with typical B-symptoms such as fever, night sweats, and unintentional weight loss. Sometimes, CLL can transform into a more aggressive form of large B-cell lymphoma called Richter’s transformation which can occur in up to 10% of CLL patients and is associated with poor prognosis.

Extramedullary involvement of CLL is rare, but if it occurs, it most commonly involves the skin and central nervous system . While gastrointestinal involvement can occur rarely in patients with CLL, it mostly occurs in patients with Richter’s transformation and is very unusual to occur in patients with CLL .

A 70-year-old Caucasian male presented with complaints of diarrhea for the last 4 months. He had associated fecal urgency and incontinence at times. He was having 4-5 bowel movements a day ranging from semisolid to watery stools. He denied any history of fevers, abdominal pain, vomiting, weight loss, night sweats, or skin rashes. He denied any recent travel history or exposure to anyone with similar symptoms.

On physical examination, his abdomen was soft and nontender. There was no apparent hepatomegaly or splenomegaly. The rest of the cardiovascular, respiratory, and nervous system examinations were unremarkable. Initial laboratory evaluation showed a hemoglobin of 15.5 g/dL (14–18), WBC of 8.3 K/uL (4.5–11), leucocyte fraction of 45.7% (15–50%), platelet count of 187 K/uL (140–440), creatinine of 0.9 mg/dL (0.7–1.3), AST of 34 U/L (13–39), ALT of 25 U/L (4–33), ALP of 102 U/L (34–104), albumin of 4 g/dL (3.5–5.7), and globulin of 3.1 g/dL (1.5–4.5).

Further workup was done for finding the etiology of the chronic diarrhea. Work up for infection, including parasitic infection and bacterial infections including Clostridium difficile, was negative. He underwent colonoscopy for further evaluation. This revealed a normal mucosa but diffuse submucosal nodularity through the large intestine (Figure 1). Biopsies were taken from multiple sites, and histopathology of the biopsied revealed multiple aggregates for small mature lymphocytes in the submucosa (Figure 2). There was no large cell transformation. Histopathology was negative for CMV colitis. Immunohistochemical stains revealed neoplastic lymphocytes positive for PAX5 (Figure 3), BCL-2, dim BCL-6, CD5, partial CD20, and CD23 and negative for CD3, cyclin D1 (Figure 4), and CD10. A diagnosis of chronic lymphocytic leukemia/small lymphocytic lymphoma was made.

The patient then underwent CT chest, abdomen, and pelvis with IV contrast for evaluation which revealed extensive bilateral axillary, hilar, abdominal, and pelvic lymphadenopathy. He subsequently underwent bone marrow biopsy histopathology which revealed hypercellular bone marrow, with 50% involved by lymphoid cells; flow cytometric immunophenotyping studies revealed monoclonal B-cell lymphoid population with kappa light chain restriction with CD5 and CD23 coexpression consistent with CLL. The patient did not have any abnormal cell clone harboring deletion of 11q, 13q, or 17p. His Rai staging was Stage I and Binet staging was Stage B, putting him at intermediate risk. The patient was referred to oncology that started him on obinutuzumab and venetoclax chemotherapy for the CLL.

The patient went into remission from his CLL on treatment with chemotherapy. The patient improved significantly, and the diarrhea resolved. On 3- and 6-month follow-ups, the patient experienced significant symptomatic improvement with resolution of chronic diarrhea.

A review of the literature revealed a total of n = 5 reported cases including ours, where the initial presentation of CLL/SLL was chronic diarrhea . This is presented in Table 1. While GI manifestation can occur in CLL, especially in advanced stages or during blast transformation, diarrhea as the initial presentation is rare. In the existing case reports with similar presentation, the mean age of presentation ranged from 65 to 81 years. Associated symptoms were fecal urgency, abdominal pain, and weight loss. One patient presented with abdominal pain and hematochezia and was found later to have intussusception. The duration of symptoms ranged from 4 weeks to 6 months. Three patients had no history of CLL, and one patient had history of CLL that was treated and was thought to be in remission.

Endoscopic evaluation with colonoscopy was notable for variable findings ranging from polypoid mass, multiple linear ulcerations, and ulcerations with mucosal inflammation and friability. Imaging with contrast enhanced CT in all cases revealed abdominal and pelvic lymphadenopathy. Colonic histopathology in all cases revealed lymphocytic infiltration. Treatment details were available for two patients; polypectomy was done for one patient, and rituximab was used to treat for the other patient with resultant resolution of symptoms. In the remaining two patients, one patient decided to pursue comfort care measures and passed away shortly after hospital discharge. No treatment details were available for the other patient who also passed away few weeks after diagnosis.

Of these cases, there are two cases of CCL involving the large intestine including our patient . A case of 66-year-old male who came in whose initial presentation of CLL was abdominal pain and hematochezia and was found to have intussusception on abdominal ultrasound. On further evaluation with colonoscopy, the patient was found to have intraluminal mass in the hepatic flexure. Our patient on the other hand presented with diarrhea and colonoscopy revealed submucosal nodularity in the large intestine. Histopathology of both patients revealed lymphocytic infiltrates. The patient who presented with the colonic mass died within days of diagnosis . Our patient received chemotherapy and is currently in remission.

(1) Chronic lymphocytic leukemia (CLL) is the most common lymphoproliferative disorder in the United States. (2) It has a very variable presentation with most patients having asymptomatic lymphocytosis. (3) CLL can also present with extramedullary involvement, most commonly the skin or central nervous system. (4) Rarely, it can also present with chronic diarrhea, which typically resolves after treatment of the CLL.

• more than 10% weight loss in 6 months.
• extreme tiredness.
• fever for more than 2 weeks without any signs of infection.
• night sweats for longer than 1 month.
• bone marrow failure that gets worse and lower numbers of healthy red blood cells (called anemia) or platelets (called thrombocytopenia)

(3) CLL can also present with extramedullary involvement, most commonly the skin or central nervous system. (4) Rarely, it can also present with chronic diarrhea, which typically resolves after treatment of the CLL.

Doctors do not yet have a way to prevent leukemia. However, some types of leukemia, including CLL, may have links to toxins, such as herbicides, pesticides, radon, and tobacco exposure. People can help reduce the risk of CLL by avoiding or practicing extreme caution around these toxins.

Many people do not experience symptoms of CLL for years and do not require treatment. However, as the disease progresses, these individuals may need treatment to extend their lives.

When and how a doctor treats someone’s CLL depends on a few factors, including:

Chemotherapy is typically the first-line therapy for CLL.

Doctors may use chemotherapy in conjunction with other treatment options, such as monoclonal antibody therapy. This therapy binds antibodies to cancer cells and destroys them. Treatment can also include medications to treat or prevent infections or improve low blood cell levels.

For instance, some people may take a combination of the monoclonal antibody rituximab and the chemotherapy drugs fludarabine and cyclophosphamide. Alongside the oral chemotherapy medication chlorambucil, doctors use obinutuzumab or ofatumumab, which have the same drug target as rituximab.

Small molecule inhibitors, such as bendamustine hydrochloride, idelalisib, and ibrutinib, can also sometimes form part of a CLL treatment regimen.

In 2017, the Food and Drug Administration (FDA) approved the combination medication Rituxan Hyecela (rituximab and hyaluronidase human) for CLL treatment.

In recurring or aggressive cases of CLL, an individual may have a blood or bone marrow stem cell transplant. This procedure replaces diseased cells with healthy blood cells that are able to mature into bone marrow cells.