Using full-dose chemotherapy to treat elderly patient with DLBCL

A 75-year-old man presented in early 2011 to a genitourinary oncologist for a second opinion regarding a pelvic mass.

In 2007, he was diagnosed with prostate cancer (Gleason score 3+3 involving four of twelve cores) with PSA 4.4 ng/mL. He was treated using radioactive seeds placed into his prostate gland. He achieved PSA of less than 0.01 ng/mL 3 months after the treatment. He continued to have surveillance and oncological care periodically afterward.

In August 2010, the patient developed abdominal discomfort and bloating. He had no rectal bleeding, genitourinary complaints or changes in bowel habits. His PSA was 0.02 ng/mL and his carcinoembryonic antigen was 1.7. He underwent a CT scan of the abdomen and pelvis in December, which showed a large soft tissue mass, 8.8 × 6.3 × 5.8 cm, with a necrotic center, seeming to arise from the posterior superior prostate gland, abutting the anterior rectal wall and extending to the pelvic sidewalls. The liver, spleen, kidneys and adrenal glands were unremarkable. On PET scan, the mass was noted to be active with standard uptake value (SUV) of 21.

A subsequent colonoscopy was negative. The patient underwent a biopsy of the right lobe of the prostate, which was read as poorly differentiated prostatic adenocarcinoma, Gleason score of 10 (5+5). The tumor was seen in all tissue samples and composed 95% of the available tissue. Perineural invasion was seen, and no immunohistochemistry stains were available. The patient was started on androgen deprivation therapy with leuprolide and bicalutamide. He was referred to a genitourinary oncologist for further workup and opinion due to the discordance between the PSA levels and the biopsy results and concern that the tumor may have transformed into a poorly differentiated, aggressive prostate cancer.

Sheetal Shrimanker

The patient tolerated the hormonal therapy well for the first 6 weeks. However, during subsequent weeks, he developed mild lethargy and his appetite decreased. Laboratory evaluation revealed a corrected calcium level of 11.9 mg/dL. The patient was admitted to the hospital and given IV fluid hydration.

Despite the fact that his calcium level normalized and his mental status improved, the patient developed acute renal failure. Although no hydronephrosis was seen on ultrasound, the patient had bilateral percutaneous nephrostomy tubes placed, given the high suspicion for bilateral ureteral obstruction. Renal function normalized immediately upon placement of the nephrostomy tubes. Repeat CT scan of the abdomen and pelvis revealed a larger mass, now 11.3 × 12.3 × 9.7 cm, that displaced the rectum posteriorly and was inseparable from it, as well as abutting the bladder wall. Whole-body bone scan was negative.

PET scan showed the soft tissue pelvic mass, now with an SUV of 26. In addition, there was focal activity involving a mid-abdominal loop of bowel that demonstrated circumferential wall thickening with an SUV of 11, as well as a third metabolically active soft tissue density in the left lower quadrant with an SUV of 7. Repeat PSA was 0.1 ng/mL. The growth of the mass and presence of new sites of disease prompted a repeat biopsy.

The biopsy results demonstrated a predominantly diffuse proliferation of neoplastic lymphoid large cells with prominent nuclei, fine to dense chromatin and scant cytoplasm. Scattered and small aggregates of small lymphocytes were also seen. No prostatic tissue was identified.

Immunohistochemistry studies of the large cells were positive for CD10, CD20, CD45, PAX-5, BCL-6 and BCL-2, and negative for PSA, CK-8/18, pankeratin, and S100. Ki-67 was 80% to 90%. Cyclin D1 was negative. The small lymphocytes were positive for CD5, CD20, PAX-5 and CD23. Fluorescence in situ hybridization studies were negative for t(14;18) and BCR-ABL. MYC translocation was not seen. Thus, the pelvic mass biopsies were diagnostic for a CD10+ diffuse large B-cell lymphoma (DLBCL), germinal center type, as well as a chronic lymphocytic leukemia.

Flow cytometry studies confirmed these diagnoses. Bone marrow aspirate and biopsy were positive for CLL only. Pertinent laboratory studies now revealed a normal metabolic panel, liver function test, immunoglobulin level, white blood cell and platelet count, anemia with hemoglobin equal to 12.4 g/dL, and a slightly elevated lactate dehydrogenase (LDH) at 255. HIV and hepatitis studies were negative.

Throughout these numerous imaging studies, biopsies and bilateral nephrostomy tube placement, the patient’s performance status slowly deteriorated. His movements became limited to the hospital bed for more than 50% of the time, and he required help with self-care (ECOG performance status ≥ 3). Given his age (elderly is usually defined as age older than 65 years), and multiple comorbidities (including hypertension, coronary artery disease, atrial fibrillation and an ejection fraction of 52%), the risks of treatment with high-dose chemotherapy were numerous.

However, he had a rapidly growing large cell tumor, as evidenced by the high Ki-67 proliferation index, BCL-2 expression, and dramatic increase in size of the mass within 2 months’ time, which necessitated early treatment. According to the International Prognostic Index, the patient was high-risk, given that he initially had all of the following risk factors: age older than 60 years, performance status >1, elevated LDH, Ann Arbor stage III or IV disease and more than one extranodal site of disease involvement.

Case Discussion

This treatment challenge was recently discussed in an article in Blood. The article elucidates how initial treatment (termed as pre-phase therapy) with prednisone monotherapy can tremendously improve an elderly patient’s performance status, especially those with heavy tumor burden, as well as decrease the incidence of tumor lysis syndrome. The pre-phase treatment, thus, allows elderly patients to later receive standard chemotherapy for their large cell lymphoma while reducing the incidence of first-cycle side effects.

The patient was started on daily prednisone therapy for 1 week and had a dramatic improvement in performance status (ECOG PS=1-2). He also started prophylactic antiviral and antifungal therapy. Subsequent R-CHOP, followed by granulocyte colony-stimulating agent support, was administered while he was an inpatient, and the regimen was well tolerated. He has advanced stage DLBCL, germinal center-type, stage IV due to multiple extranodal sites of disease involvement, and high-risk based on having more than three adverse prognostic risk factors.

In keeping with the evidence as described in the review article, his treatment plan will involve R-CHOP followed by G-CSF support, for a total of six cycles. Given his atypical presentation, chemotherapy will be given every 3 weeks and interim imaging studies to assess disease response will be performed after two cycles. Cardiac function will be closely monitored. Given his atypical presentation, interim imaging studies to assess disease response will be performed after two cycles. Post-therapy staging will be performed 2 to 4 weeks after completion of the chemotherapy. If the patient is not in complete remission, we will consider radiation therapy to the site of bulky disease (>10 cm).

This case presents a clinical and diagnostic challenge, not only because it emphasizes the importance of re-evaluating a patient’s clinical diagnoses when the puzzle pieces do not fit together, but also because it demonstrates the feasibility of treating an elderly patient with full-dose chemotherapy in the setting of an aggressive large cell lymphoma.

Sheetal Shrimanker, MD, is a Chief Fellow in the Division of Hematology and Oncology at University of Medicine and Dentistry, New Jersey. Dr. Shrimanker would like to thank Dr. Biren Saraiya and Dr. Mark Stein for their guidance.

Disclosure: Dr. Shrimanker reports no relevant financial disclosures.

For more information:

• International Non-Hodgkin’s Lymphoma Prognostic Factors Project. N Engl J Med. 1993;329:987-994.
• Pfreundschuh M. Blood. 2010;116:5103-5110.