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Timing allogeneic transplant for CLL/SLL
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“So, my understanding is that you were diagnosed with your lymphoma 2 to 3 years ago.”
I was conversationally going through my patient’s past records to confirm that I had a clear understanding of his past medical history and treatment course. “Actually, 10 years ago,” he corrected me. My perspective on his illness shifted — 10 years ago seemed like forever, in cancer terms. I wondered if he might have been more heavily pretreated than I had originally thought. “On Sept. 11, in fact,” he continued. My perspective shifted again, as the date of Sept. 11, 2001, came into clearer focus. While others were processing a terrorist attack, he had been confronting a new cancer diagnosis, which, conveniently, he was able to hide for a little while by allowing his personal grief to be masked by the collective grief of everyone around him.
This was an otherwise healthy, well appearing, younger man with a diagnosis of small lymphocytic lymphoma (SLL). I reviewed the outside pathology to confirm my agreement. Although he was told about his diagnosis on Sept. 11, 2001, he had been observed without treatment for 6 years, eventually requiring treatment in 2007, at which time he received R-FND — rituximab (Rituxin, Genentech/Idec Pharmaceuticals), fludarabine, mitoxantrone, dexamethasone — followed by maintenance rituximab. This appeared to work fairly well for a while, although 3 months ago he noticed some gnawing back pain. This was followed more recently by some enlarging nodes. I reviewed his scans, which showed diffuse lymphadenopathy. I could easily palpate his cervical and axillary nodes on exam. He hadn’t lost any weight, felt systemically well and maintained an excellent performance status.
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One month ago, a few of my colleagues and I traveled to some nearby practices to discuss our clinical trials portfolio. We have a mostly young but enthusiastic hematologic malignancy faculty, with lots of trials newly opened or on the way. These range from upfront combinations of brentuximab vedotin (Adcetris, Seattle Genetics) for Hodgkin’s lymphoma (an exciting new drug that was recently FDA approved in the relapsed setting) to a variety of biochemotherapeutic approaches for the other diseases that we treat. In this instance, this patient’s referring physician had particular interest in a bortezomib (Velcade, Millennium Pharmaceuticals)/romidepsin (Istodax, Celgene Corp.) study for chronic lymphocytic leukemia/SLL that we have available. I thought this was a reasonable consideration and discussed it with my patient, who is weighing his options.
The bigger issue, of course, is the question about the role of transplant in this otherwise incurable disease. A recent review in Biology and Bone Marrow Transplant looked at the role of stem cell transplantation for indolent lymphomas and CLL. Consistent with clinical practice, most of the recent attention for transplant in CLL has focused on reduced-intensity conditioning allogeneic approaches. Generally, treatment-related mortality has limited the applicability of myeloablative approaches for CLL, although recent reduced-intensity approaches have demonstrated more acceptable treatment-related mortality rates of 13% to 25% and OS estimates of 50% to 70% at 2 to 5 years after transplantation. For appropriately selected patients, reduced-intensity transplants appear to offer the possibility of long-term cure.
Currently, our center is participating in CALGB 100701/BMT CTN 0804, a reduced-intensity allogeneic transplant approach for CLL or SLL. Patients can receive conditioning with either busulfan and fludarabine or cyclophosphamide and fludarabine. Both regimens include rituximab with conditioning and as maintenance. Graft-versus-host disease prophylaxis includes tacrolimus and methotrexate with or without sirolimus.
Eventually, this kind of strategy would be an appropriate one to consider for the patient whom I met in clinic. The question is, though — and a similar question for patients with other indolent lymphomas — when is the time right? Currently, he’s feeling well with fairly modest disease-related symptoms, albeit with growing and increasingly uncomfortable lymphadenopathy. Several other nontransplant therapies are available to him, many with reasonable expectations for (some) success. With each additional treatment, though, cumulative toxicity increases, as does the relative refractoriness of the underlying disease.
And so, my question for my readers in this month’s column: How do you sequence allogeneic transplantation for your patients with CLL/SLL or indolent lymphomas? When do you feel that the time is right, and how do you counsel patients about this?
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.
For more information:
- Gribben JG. Biol Blood Marrow Transplant. 2011;17(1 Suppl):S63-70.