Exploring treatment regimens for relapsed ALL

As I looked forward to my trip home to California with my wife and daughter, where we would celebrate Christmas with my parents and siblings, I talked with my patients about their plans for gathering with family at the end of the year.

For some, these plans were poignant. A debilitated patient with progressive myelodysplasia looked forward to a last Christmas with her sisters in a warm house preparing a large feast, as they had many times before. An older patient with refractory myeloma savored these final weeks with her son and daughters, as the warmth and light of the holidays replaced, for a while, her myeloma as the dominant narrative in her life.

My first patient in the transplant clinic that week planned to spend Christmas in North Carolina with his wife. He was from Texas, and his wife from Pennsylvania, but he was too sick to travel far from Chapel Hill. Mr. M and his wife were each other’s greatest supports, and having each other was all they really needed for Christmas anyway.

Mr. M had lived a remarkable life full of adventure and bravery, all before the age of 25. On his way to New York City for New Year’s Eve, he’d met his future wife on a Greyhound bus, fallen in love and married not long afterward. He enlisted in the Army and fought in Iraq.

In the summer a year or so ago, he began to feel unwell. Nobody could figure out what was wrong with him, and he gamely continued to serve on his night patrols outside the borders of the compound. As he grew progressively fatigued, he was finally sent to a German hospital for a complete medical evaluation. He was diagnosed with Philadelphia chromosome negative acute lymphoblastic leukemia. Treated by German-speaking physicians, far away from the battlefields of Iraq or his wife and home in the United States, he underwent standard induction therapy on a German adult ALL protocol.

Treatment in the US

Eventually, Mr. M made his way back to the US, where he continued his first year of therapy. He was seen in the clinic of our cancer center, where one of my colleagues has been providing his ALL treatment. In late November, Mr. M was admitted to our hospital during what would have been week 51 out of 52 weeks of his first year of treatment.

William Wood

Unfortunately, he had been having aches and pains during the preceding weeks, which foreshadowed the relapse that a subsequent bone marrow biopsy confirmed. He was started on re-induction therapy modeled after an older Children’s Oncology Group salvage regimen. Having withstood the first few weeks of his new chemotherapy, he was sent to see me in the transplant clinic to discuss the role of a donor transplant for his disease.

The word of Mr. M’s illness and urgent need for a donor made its way to another battlefield halfway across the world, where his brother was serving. Both were HLA tested, and his brother, unfortunately, was not a match. I initiated an unrelated donor search and pondered how to proceed.

Young adults with Ph-ALL

Much has been made in recent years of the plight of adolescents and young adults (AYAs, aged 16 to 39) with Ph-ALL. Retrospective reports from Europe and the US have shown that AYAs seem to fare better when treated with pediatric rather than adult treatment regimens. Multiple explanations have been proposed to account for these discrepancies in outcomes, ranging from disease biology to adherence/compliance issues to differences in the agents, doses and intensities used in the different protocols.

Several groups have begun to enroll AYAs up to the age of 40 or even 50 onto pediatric-like treatment protocols, including a large phase 2 study through the adult cooperative groups in the US. Early reports from organizations around the world that use similar approaches have been encouraging.

Nonetheless, even with the best possible protocols, relapses occur — and transplant retains an important role in the treatment of relapsed disease.

Uncomfortable but necessary conversation

I had a conversation with Mr. M and his wife that, for me, is becoming increasingly routine, about the donor search and identification process, the pre-transplant work-up, and a prolonged hospitalization for conditioning, stem cell infusion and provision of supportive care. I talked about the need for frequent outpatient follow-up for several months following transplantation. I had an uncomfortable but necessary conversation about the risks of relapse and treatment-related mortality.

In the moment, my transplant discussions always seem a bit theoretical. My patients are often in remission or close to it, and although not feeling perfectly well, they are often in reasonable shape. The conversations about life-threatening complications and risk are discussions about possibilities that are terrifying, but still imagined, and not yet real. That day, I think that the three of us were ok with living in a bit of denial.

After my transplant clinic was over and I had returned home for the day, I packed for my cross-country trip. The holidays were as wonderful as expected, and after a 5-day vacation, I returned to Chapel Hill rested and energized to start work in 2011. Unfortunately, a few days after returning, I learned that Mr. M’s leukemia had recurred again. He was admitted to the hospital for consideration of additional treatment.

A few columns ago, I posed a clinical question to readers, and received several interesting and helpful responses. So again, I’ll do the same, this time with these questions: 1) What are your preferred treatment regimen(s) at your institution for multiply relapsed ALL, and in which investigational drugs or protocols do you have the most interest?; 2) What is your preferred conditioning regimen for young adults with ALL undergoing stem cell transplantation? I have my own answers to the above, of course, but there is always much that I can learn from the experiences of others from around the country and the world.

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.