Lymphoid leukemia occurs when the white blood cells in the bone marrow (which are also termed lymphocytes) are involved. It is also referred to as lymphoid or lymphoblastic leukemia (LL). It is also classified based on the progression of the disease. Acute leukemia develops as a result of the accumulation of rapidly developing immature blood cells in the bone marrow. Another type is chronic leukemia which develops more slowly compared to the acute type and contains abnormal white blood cells (cells are mature in comparison to the acute type).

Lymphoid leukemia is a monoclonal disorder, which develops in the white blood cells called lymphocytes in the bone marrow.

Symptoms

The symptoms of acute lymphoid leukemia (ALL) may vary from person to person and encompass:

• Rise in temperature of unknown origin along with body tiredness.

• Recurrent infections that persist for a long time.

• Bleeding all over the skin along with recurrent red spots.

• Tiny, flat itchy red patches that bleed.

• Difficulty in breathing.

• Unsteadiness.

• Pain in the abdomen, bones, joints, and back side of the body.

• Enlargement of the lymph nodes, liver, and spleen.

• Sudden loss of body weight along with nighttime sweating.

• Problems in vision (faded vision) and retinal detachment.

• Nausea, vomiting and diarrhea.

Chronic lymphocytic leukemia (CLL) has almost similar symptoms of ALL, but it contains additional symptoms such as:

• Swollen lymph nodes that are non-tender;

• Difficulty in the abdomen on the left upper side, along with pain (due to the encroachment of the spleen in the abdomen);

• Gradual decrease in the weight;

• Perspirations in the nighttime.

Diagnosis

A single test cannot determine the presence of lymphoid leukemia. Instead, a combination of the following tests is performed to provide a confirmatory diagnosis:

• Clinical and diagnostic interview: A diagnostic interview involves taking the patient's complete medical, familial, and occupational exposure histories and questioning the patient about their current symptoms. Clinical examination involves examining signs like bleeding spots on the skin and the presence of unusual growths on the abdomen, liver, and spleen.

• Blood tests: To ascertain the patient's immunological condition and the presence of risk factors, these blood tests are helpful. The complete blood count reveals increased lymphocytes (white blood cells) in lymphoid leukemia patients. They may also have decreased red blood cells and platelets in some patients. Blood tests are also used to collect genetic markers that predict the likelihood of the disease occurrence.

• Other lab investigations: Apart from the complete blood count, thyroid function tests, blood sugar tests, lipid profiles, and urine analysis are also done to rule out the presence of other diseases in LL patients.

• Imaging techniques: They are useful in identifying the spread of the disease (to other organs like the brain and spinal cord). Conventional X-ray, magnetic resonance imaging, and computed tomography are the different types of imaging techniques used in lymphoid leukemia.

• Bone marrow biopsy and aspiration: Due to the ease with which malignant cells may be seen in the blood, blood tests are typically used to detect LL. The diagnosis of LL often does not require a bone marrow biopsy, but it may be performed before starting therapy in some cases. A bone marrow aspiration and biopsy may be used to help some patients estimate their prognosis, or likelihood of recovery. Additionally, it might shed more light on the causes of other blood related diseases.

• Genetic tests: Specialized assays like fluorescence in situ hybridization (FISH) and polymerase chain reaction (PCR) are used to check for the presence of mutations in the genes (NOTCH 1, TP53, MYD88,SF3B1, and IGVH) that are involved in the pathogenesis of lymphoid leukemia.

• Other tests: Flow cytometry and cytochemistry tests involve the application of chemicals to leukemia cells in a lab setting. They reveal the type of leukemia and its subtype based on the color of the cell surface proteins that are found on the exterior of LL cells. These tests are used to separate CLL from other leukemias that can also include lymphocytes but are not as common as CLL.

Treatment

The best team to oversee the treatment plan is a multidisciplinary one made up of medical oncologists, radiologists, radiation oncologists, and pathologists. The factors that influence the type of treatment to be selected are the stage and cellular type of the tumor, the patients’ general health, and any other co-morbid conditions associated with lymphoid leukemia. The following is the mainstay of lymphoid leukemia treatment:

• Surgery:The role of surgery in the management of lymphocytic leukemia is quite restricted. Surgery cannot treat leukemia because the disease cells are dispersed widely throughout the bone marrow and blood. The primary function of surgery in these patients is to place catheters (tubes) inside the body to facilitate chemotherapy administration.

• Radiotherapy: Preoperative radiation therapy is usually used in patients with advanced or recurring leukemia to lessen the severity of the illness. It has been primarily usedin conjunction with chemotherapy as an adjuvant therapy. External radiation therapy and internal radiation therapy (brachytherapy) are the types of radiation therapy employed in LL patients.

• Chemotherapy: Vincristine, daunorubicin, cytarabine, L-asparaginase, 6-mercaptopurine, methotrexate, cyclophosphamide, prednisone, dexamethasone, and nelarabine are the medications that are employed in the chemotherapy of LL patients. Although they are effective in minimizing the disease, continuous monitoring is required during the period of their administration with respect to their unavoidable side effects like nausea, vomiting, diarrhea, loss of hair, mouth sores, and reduced blood cell counts.

• Stem cell transplantation: It can be done in cases where chemotherapy fails. It can also be used with other treatments (chemo/radio therapy) for better effectiveness. Stem cells are collected from the same patient from other sites (autologous) or from other patients (allogenic), stored, and infused into the patient. They help to restore the blood cell count to an optimal level.

• Combination of the above therapies: Chemotherapeutic drugs are given in conjunction with radiation therapy for better control of the disease in LL patients. It is indicated especially in recurrent /refractory cases.

• Targeted therapy: Targeted medications function differently and tend to have different adverse effects compared to conventional chemotherapy treatments. They can occasionally supplement chemotherapy or be used in conjunction with it to enhance its effectiveness.

• Other therapies: Immunotherapeutic drugs like blinatumomab, inotuzumab ozogamicin, rituximab, obinutuzumab, and ofatumumab (monoclonal antibodies), alemtuzumab (CD52 inhibitor), and CAR T-cell therapy are used in LL patients. On the other hand,drugs like imatinib, dasatinib, nilotinib, ponatinib, bosutinib, ibrutinib, acalabrutinib,zanubrutinib,idelalisib, duvelisib, and venetoclax are the targeted therapeutic drugs employed in this disease.

• Leukapheresis in CLL patients: Very high levels of white blood cells can interfere with regular blood circulation, which can result in heart failure and difficulty in breathing. These cells may not decline from chemotherapy immediately after the start of the treatment. Leukapheresis can be applied in these cases immediately before chemotherapy to overcome this delay.  In this procedure the patient's blood is put through a specialized machine and the white blood cells including leukemia cells are removed while the remaining blood cells and plasma are put back into the bloodstream. Care should be taken during this process as it may reduce the calcium levels, leading to side effects like numbness and muscle spasm. 

There has been a substantial improvement in both the knowledge and treatment of LL. Numerous environmental and genetic factors can affect its occurrence. The possibility of preventing this disease and developing potential remedies exists with greater understanding of these components. Combinations of targeted drugs are currently being researched to develop effective and possibly curative treatments for LL, and patients with refractory diseases require alternative therapy.