Two challenging cases pose treatment questions

In the past few months, I’ve discussed some clinical cases and have received some interesting and useful responses from many of you. By way of follow-up, my patient with chronic myelomonocytic leukemia was treated with pulse steroids after concurrent infectious diagnoses were thoroughly excluded, and her neurologic symptoms mildly improved. She went on to receive three cycles of 5-azacytidine, although her disease now appears to be progressing. I don’t think she’ll be able to tolerate or substantially benefit from further disease directed therapy. She is not yet at peace with this, although she understands.

The young man with Philadelphia chromosome acute lymphoblastic leukemia was treated by my colleagues with a clofarabine-containing regimen, and then a topotecan-containing combination, but still has persistent disease. He is currently undergoing a hospital-to-hospital transfer to another major center, where he will be considered for an anti-CD22 antibody-based study, among other clinical trial options. He still holds out hope that he’ll eventually go to transplant, even if the odds are long.

William Wood

Not all of the news is discouraging, though. The young woman with chronic phase chronic myeloid leukemia is enjoying a nice disease response now that she is taking the correct dose of her nilotinib (Tasigna, Novartis) and is back under the watchful supervision of my non-transplant colleagues. My older patient with chronic lymphocytic leukemia continues to maintain an excellent quality of life and disease control with single-agent oral chlorambucil (Leukeran, SmithKline Beecham), now 9 months into treatment.

Today, I have two challenging cases to discuss. I’ll present the issues that have engendered the most discussion and will be interested to hear your thoughts. In both instances, I’ve informally consulted with colleagues from around the country. As a side note: How often do you consult with individuals at other major academic medical centers, and do you do this formally or informally? If formally, by what process? And if informally, do you wish a formal mechanism existed to facilitate detailed consultations with off-campus colleagues?

Puzzling breast abnormality

My first patient is a delightful young woman who underwent a solid organ transplant several years ago for an uncommon, acquired disease that was cured by the transplant. Since then, she’s had at least one episode of rejection and has been maintained on dual long-term oral immune suppression. In the meantime, she’s gotten on with her life and is making the most of it; she’s scheduled to receive an advanced degree in the health professions within the next year.

A few months ago, she noted an abnormality in one of her breasts. A biopsy demonstrated a monoclonal B-cell malignancy, which by morphology appeared consistent with a plasmablastic lymphoma. CD20 staining showed positivity in scattered cells but not the bulk of the diseased tissue.

A PET-CT scan revealed three fluorine-18 fluorodeoxyglucose-avid lesions; two in the ipsilateral breast and one on the contralateral side, but no disease elsewhere in the body. Her performance status was excellent, and she had no B symptoms. She did not have HIV or other chronic illnesses, and basic laboratory studies, including an LDH and albumin, were within normal limits. A lumbar puncture did not demonstrate central nervous system (CNS) involvement, and bilateral bone marrow biopsies were clean.

As part of my discussions with individuals at other institutions, and with the patient and her mother, I considered the following questions: Should I include rituximab (Rituxan; Genentech, Biogen Idec) in this patient’s therapy? Should I use combination chemotherapy and, if so, with what regimen? Were there any reasons to use CHOP, dose-adjusted infusional etoposide, vincristine, doxorubicin, cyclophosphamide and prednisone (EPOCH), or even something else?

Given the plasmablastic phenotype, does bortezomib (Velcade, Millennium Pharmaceuticals) have a role, given recent studies demonstrating the feasibility of combining it with R-CHOP or EPOCH? What should I do, if anything, to provide CNS prophylaxis? And finally, how should I counsel this individual regarding fertility, and what options should I provide, especially given that she mentioned this issue as particularly important to her? If you’ll provide me with your thoughts, I’ll be happy to share what I did — and why — in a future column.

Disappearing skin lesions

My second clinical case for this column involves a man, just older than the age of 50, who works as a missionary in another country. About a year ago, he noted a raised, firm and mildly discolored facial lesion. During the ensuing months, several other lesions appeared, scattered across his trunk and extremities. A skin biopsy eventually demonstrated a diagnosis of leukemia cutis.

Peripheral blood counts were within normal limits, and a bone marrow biopsy did not show any involvement by AML. He was treated at another institution with 7+3+3 induction chemotherapy at the beginning of the summer, and his skin lesions entirely resolved. He later received two courses of consolidation with high-dose cytarabine.

Unfortunately, his skin lesions recurred about a month after the second course and were again biopsy positive for leukemia cutis. At that time, his marrow remained clear of disease (it had never been involved on multiple investigations). Because of an episode of questionable confusion, he received a lumbar puncture and a dose of intrathecal therapy at one point, although he has not had any documented involvement in the CNS.

Later, he went on to receive three courses of cyclophosphamide and etoposide. With each, his skin lesions regressed, flattened, became softer, lost coloration, and essentially disappeared. After each, however, the lesions returned, and sometimes new ones appeared. Systemically, he remained well without abnormal blood counts upon recovery from each cycle of treatment. He was referred to see me in the transplant clinic.

Major questions for this case arose, including the following: What is the best treatment for leukemia cutis? What is the role of electron beam therapy? Should further systemic therapy be given the next time the lesions recur? Does stem cell transplantation have a role in the management of this disease? If so, should the conditioning regimen include total body irradiation, and how much? If total body irradiation, should other agents be included? If not, what drugs should be used and at what intensity?

In subsequent columns, I’ll try to provide some additional details about the rationale for my decisions and references from the medical literature, if appropriate. In the meantime, thanks as always for your readership.

William Wood, MD, is assistant professor of medicine, division of hematology/oncology, at the University of North Carolina, Chapel Hill. Dr. Wood may be reached at william_wood@med.unc.edu. Disclosure: Dr. Wood reports no relevant financial disclosures.