Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma

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Chapter 35 Diagnosis and Treatment of Diffuse Large B-Cell Lymphoma and Burkitt Lymphoma

Kieron Dunleavy, Wyndham H. Wilson

Hepatitis B Prophylaxis and Therapy During Lymphoma Treatment

There is a risk of hepatitis B reactivation both from chemotherapy and rituximab, and this is a potentially fatal complication. We check hepatitis serology (hepatitis B surface antigen [HBsAg], hepatitis B surface antibody [anti-HBs], and hepatitis B core antibody [anti-HBc]) in all patients at diagnosis. Patients with active hepatitis B receive antiviral medication and LFTs, and hepatitis B viral loads are monitored closely. Patients with a history of hepatitis B infection should either receive antiviral prophylaxis or have the hepatitis B viral load monitored very closely (ideally on each cycle) with a low threshold to commence antiviral medications.

Table 35-1 Staging Evaluation for Diffuse Large B-Cell Lymphoma

All Patients As Clinically Indicated
History and physical examination Other viral studies
CBC and chemistry (including LDH) CT or MRI of the head
HIV and hepatitis B and C serology Body PET scan
Chest radiograph Additional imaging
CT scan of the chest, abdomen, and pelvis CSF evaluation by cytology or flow cytometry
BM aspirate and biopsy Other tests indicated by results of staging

BM, Bone marrow; CBC, complete blood count; CSF, cerebrospinal fluid; CT, computed tomography; LDH, lactate dehydrogenase; MRI, magnetic resonance imaging; PET, positron emission tomography.

Table 35-2 Ann Arbor Staging System for Lymphomas

Stage* Cotswold Modification of Arbor Classification
I Involvement of a single LN region or lymphoid structure
II Involvement of two or more LN regions on the same side of the diaphragm (the mediastinum is considered a single site, but the hilar LNs are considered bilaterally); the number of atomic sites should be indicated by a subscript (e.g., II3)
III Involvement of LN regions on both sides of the diaphragm: III1 (with or without involvement of splenic hilar, celiac, or portal nodes) and III2 (with involvement of paraaortic, iliac, and mesenteric nodes
IV Involvement of one or more extranodal sites in addition to a site for which the designation E has been used

LN, Lymph node.

*All cases are subclassified to indicate the absence (A) or presence (B) of the systemic symptoms of significant fever (>38.0° C [100.4° F]), night sweats, and unexplained weight loss exceeding 10% of normal body weight within the previous 6 months. The clinical stage (CS) denotes the stage as determined by all diagnostic examinations and a single diagnostic biopsy only. In the Ann Arbor classification, the term pathologic stage (PS) is used if a second biopsy of any kind has been obtained, whether the result was negative or positive. In the Cotswold modification, the PS is determined by laparotomy; X designates bulky disease (widening of the mediastinum by more than one-third or the presence of a nodal mass >10 cm), and E designates involvement of a single extranodal site that is contiguous or proximal to the known nodal site.

Table 35-3 Revised International Prognostic Index (R-IPI)*

image

ECOG, Eastern Cooperative Oncology Group; IPI, International Prognostic Index; LDH, lactate dehydrogenase

* One point is given for the presence of each of the following characteristics: age older than 60 years, elevated serum LDH level, ECOG performance status ≥2, Ann Arbor stage III or IV, and more than two extranodal sites.

From Sehn LH, Berry B, Chhanabhai M, et al: The revised International Prognostic Index is a better predictor of outcome than the standard IPI for patients with diffuse large B-cell lymphoma treated with R-CHOP. Blood 109:1857, 2007.

Intrathecal Prophylaxis in Diffuse Large B-Cell Lymphoma

In DLBCL, the role of intrathecal prophylaxis to prevent CNS recurrence is controversial and poorly studied, and there are several different approaches. Our approach is as follows. All patients at risk for CNS disease undergo a lumbar puncture at diagnosis, and CSF is checked by cytology and flow cytometry; if the results are positive, patients receive active treatment of the CNS. We administer intrathecal prophylaxis to all patients who fulfill either of the following criteria:

1. Two or more extranodal sites of disease involvement and an elevated LDH level

2. Certain extranodal sites of involvement that have been associated with an increased risk of CNS spread such as BM and testis

We use intrathecal methotrexate at a dose of 12 mg. We commence prophylaxis on cycle 3 day 1 and administer it on days 1 and 5 of cycles 3 through 6.

Treatment of Primary Mediastinal B-Cell Lymphoma

Patients with a diagnosis of PMBL undergo routine CT staging of chest, abdomen, and pelvis. We administer 6 cycles of DA-EPOCH-R. After 4 cycles of therapy, we repeat CT staging, and after 6 cycles, we perform CTs and an FDG-PET scan. If patients have responded and the posttherapy PET scan result is negative, we repeat CT scans every few months. If the FDG-PET result is positive, we attempt to perform a biopsy, and if there is residual disease, patients undergo mediastinal radiation treatment. If the FDG-PET result is suspicious (low SUV values), we repeat it in 4 to 6 weeks. If at this time, the result becomes negative, patients go into routine follow-up, and if it remains abnormal, we perform a biopsy and administer radiation if the biopsy confirms residual disease.

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