Precursor B-lymphoblastic Lymphoma Recurrent

When B-lymphoblastic lymphoma returns after treatment, patients face challenging decisions about next steps. Understanding what happens when this aggressive blood cancer comes back can help patients and families navigate treatment options and maintain hope.

Table of contents

• What is Precursor B-Lymphoblastic Lymphoma?
• Understanding Recurrent Disease
• Signs and Symptoms of Relapse
• Diagnosing Recurrent Disease
• Treatment Options for Relapsed Disease
• Where the Disease Can Relapse

What is Precursor B-Lymphoblastic Lymphoma?

Precursor B-lymphoblastic lymphoma (B-LBL) is a rare and aggressive form of cancer that begins in immature white blood cells called lymphoblasts (young immune cells that normally develop into infection-fighting B lymphocytes). This disease belongs to a larger group of blood cancers classified by the World Health Organization as precursor lymphoid neoplasms.^[1]

B-LBL is closely related to B-cell acute lymphoblastic leukemia (B-ALL). The main difference lies in where the cancer cells are found. When the disease primarily affects lymph nodes and other tissues outside the bone marrow, it is called lymphoblastic lymphoma. If more than 20% of bone marrow cells are lymphoblasts, the diagnosis becomes acute lymphoblastic leukemia.^[1][2]

The lymphoblasts in B-LBL are typically small to medium-sized cells with limited surrounding fluid (scant cytoplasm), condensed genetic material (chromatin), and small or barely visible structures inside the cell nucleus (inconspicuous nucleoli).^[1]

B-LBL comprises only approximately 10% of all lymphoblastic lymphomas. The disease most frequently affects the skin, soft tissue, bone, and lymph nodes.^[4]

Understanding Recurrent Disease

Relapsed (or recurrent) B-lymphoblastic lymphoma refers to cancer that has returned after a period of remission following previous treatment.^[8] This means the disease had responded to initial therapy and disappeared for a time, but lymphoblast cells have begun growing again.

When B-lymphoblastic lymphoma returns, it can be particularly challenging to treat. Although combination chemotherapy is the standard treatment for lymphoblastic lymphoma, relapse can occur even after seemingly successful initial treatment.^[2]

The risk of relapse and the approach to treatment depend on several factors, including how long the first remission lasted. If the disease relapses after a long remission, it may respond to the same drugs used in the original treatment. However, if relapse occurs after a short remission, doctors typically use different medications.^[8]

Signs and Symptoms of Relapse

The symptoms of recurrent B-lymphoblastic lymphoma are similar to those seen at initial diagnosis. Patients may experience:

• Decreased appetite or unintentional weight loss
• Difficulty breathing
• Easy bruising or excessive bleeding, especially from the nose and gums
• Fatigue or feeling extremely tired
• Pain in joints, bones, or abdomen
• Recurrent fevers or frequent infections
• Swelling of lymph nodes^[3]

Some patients may present with fever and abdominal pain, as documented in case reports of relapsed disease.^[2]

Diagnosing Recurrent Disease

To diagnose relapsed B-lymphoblastic lymphoma, doctors use several testing methods similar to those used for initial diagnosis. These tests help confirm that the cancer has returned and determine its extent.

Blood tests count the number of different blood cells (platelets, white blood cells, and red blood cells) and can reveal abnormal cells. These tests also analyze liver and kidney function and detect signs of inflammation and infection.^[3]

Bone marrow aspiration or biopsy involves using a thin, hollow needle to remove small samples of bone marrow or bone tissue for detailed examination under a microscope. This remains the most common and reliable method for diagnosing lymphoblastic conditions.^[3]

Imaging tests help determine cancer severity, locate affected lymph nodes and tumors, and detect enlarged organs such as the liver or spleen. Various imaging techniques may be used, including chest X-rays, computed tomography (CT) scans, magnetic resonance imaging (MRI) scans, and positron emission tomography (PET) scans.^[3] PET/CT imaging with fluorodeoxyglucose (18F-FDG) can be particularly useful for monitoring treatment response in B-lymphoblastic lymphoma.^[6]

Pathology examination of tissue samples is essential for confirming the diagnosis. In B-LBL, the lymphoblasts are often negative for CD20 but positive for other B-cell markers including CD19, CD22, and CD79a. Many cases also show strong positivity for CD10 and variable expression for CD34 and TdT.^[4]

Treatment Options for Relapsed Disease

Immunotherapy

Immunotherapy helps strengthen or restore the immune system’s ability to fight cancer. It has become an important treatment option for relapsed or refractory B-cell lymphoblastic lymphoma.^[8]

CAR T-cell therapy is a type of immunotherapy that takes millions of T cells (a type of immune cell) from the patient. In the laboratory, these cells are modified to have chimeric antigen receptors (CARs) on their surface. These receptors recognize a specific protein called CD19 found on the leukemia cells. The modified T cells are then returned to the patient, where they multiply, attack, and destroy the cancer cells.^[8]

Tisagenlecleucel (Kymriah) is a CAR T-cell therapy approved to treat young adults (up to age 25) with B-cell lymphoblastic conditions that have not responded to other treatment or have returned after a stem cell transplant or other therapies. It may also be used for patients with relapsed or refractory disease who cannot have a stem cell transplant.^[8]

Blinatumomab is another immunotherapy that has shown promise for patients with B-cell disease and detectable evidence of remaining cancer cells (measurable residual disease).^[5]

Chemotherapy

When chemotherapy is given for relapsed disease, it is called reinduction chemotherapy. For B-cell lymphoblastic lymphoma, immunotherapy is mainly used for relapsed disease, though chemotherapy remains an important treatment option.^[8]

Treatment may involve different drugs or more intense doses of medications the patient has already received, depending on how the disease responds and when relapse occurs.^[8]

Stem Cell Transplant

A stem cell transplant replaces damaged stem cells found in bone marrow, blood, and umbilical cords. This complex treatment with significant risks must be performed in a special transplant center or hospital.^[8]

Patients may be offered a stem cell transplant after the lymphoma relapses if another complete or sometimes partial remission is achieved, or if the disease did not fully respond to initial treatment and only a partial remission was ever reached.^[8]

Targeted Therapies

For adult patients with relapsed B-cell disease, significant improvements in available treatment options have occurred following regulatory approval of novel cellular and immunotherapy approaches.^[5] These newer treatments offer hope for patients whose disease has returned after initial therapy.

Where the Disease Can Relapse

B-lymphoblastic lymphoma that relapses (returns after treatment) can affect various parts of the body. The involvement of unusual sites as a location of relapse is rare but has been documented.^[2]

Case reports have documented relapsed B-cell lymphoblastic lymphoma presenting as a uterine mass, mimicking other types of cancer.^[2] The disease can also involve the central nervous system, including the brain and spinal cord. One documented case showed a solitary large mass primarily involving the frontotemporal lobes and extending into nearby areas.^[6]

When B-cell lymphoblastic conditions relapse, they frequently affect the central nervous system (brain and spinal cord).^[12] Because of this risk, treatment given to prevent cancer cells from spreading to these areas, called central nervous system prophylaxis, is an important part of managing the disease.^[8]

• Bone marrow
• Lymph nodes
• Skin
• Soft tissue
• Bone
• Central nervous system (brain and spinal cord)
• Uterus (rare)

B-cell lymphoblastic lymphoma recurrent, B-LBL recurrent, relapsed precursor B-cell lymphoblastic lymphoma, recurrent B-ALL/LBL