Clinical advances improve survivorship
by Cathy Roberts, Ph.D., clinical research
When VCU Massey Cancer Center's Bone Marrow Transplant (BMT) Program team made plans to honor patients with a day-long event, we had no idea about how many would attend. Maybe 100 or even 150, we thought. “We were delightfully astonished when well over 400 survivors and family members showed up,” said John McCarty, MD, BMT director.
Not only was the inaugural Day of Celebration, Education and Commemoration a day to remember, the fact that there are so many survivors who could attend is a milestone worthy of celebration itself. Advances in science at Massey have led to more patients being eligible for transplantation and improved outcomes for those treated.
There are five factors influencing the general increase in survivorship; see endnotes for greater detail:
- More donors and better matching: there are more donors in the National Marrow Donors registry, and due to improved, DNA-based techniques for HLA (antigen) typing, more patients are able to receive an allogeneic transplant (where the stem cells come from a genetically similar, but not identical, donor) from within a larger pool of donors. Because more patients are able to be matched perfectly, they experience less incidence and severity of complications and graft rejection, leading to improved overall transplant survival.
- Improvements in transplant preparative regimen: Massey is developing a wider range of options, including a risk-adapted and individualized treatment plan with a tailored preparative regimen to address high-risk patients, and patients with high-risk disease. In addition to transplant preparative regimens which employ the traditional, fully myeloablative approach, Massey is pioneering brand new approaches, such as immunotherapy in reduced intensity and non-myeloablative regimens.
- Better infection prevention.
- Improved stem cell collection for autologous transplants: through a clinical trial, Massey developed a new stem cell mobilization paradigm involving the drug Mozobil. The process allows for stem cell collection with fewer delays, less chance for relapse and the opportunity for an autologous transplant for otherwise ineligible patients.
- Novel disease treatment agents: use of new drugs, and drugs for which there are new disease indications discovered through clinical trials, may result in a better response at the time of transplant and longer periods of remission
Massey’s Bone Marrow Transplant Program is the 14th largest transplant program in the nation (based on UHC data), up from 34th in 2003. The program continues to achieve lower than expected mortality overall, in both autologous and allogeneic transplant patients separately. The complex, older and high-risk patients treated at Massey and the increased volume has not resulted in poorer outcomes.
Clinical trials remain a vitally important engine for improving standards of care: four clinical trials since 2004 have been responsible for 138 transplants that would not have otherwise occurred, bringing curative options and hope to patients otherwise without curative options.
- DNA-based HLA typing results in increased accuracy and specificity, less incidence and severity of acute graft vs host disease (GVHD) and chronic graft vs host disease (cGVHD), less graft rejection, better engraftment and improved overall transplant survival.
- With a greater number of registry donors, more patients are able to be matched perfectly with donors and thus able to receive an allogeneic transplant.
2. Transplant preparative regimen
- Have employed a risk-adapted and individualized treatment plan with a tailored prep regimen to address high-risk patients and patients with high-risk disease. A variety of options in transplant treatment include not only the traditional fully myeloablative transplant preparative regimens but also reduced intensity and nonmyeloablative regimens. This customized approach means there is increased eligibility for allogeneic transplant in otherwise ineligible patient populations (MCC-11561, Toor ATGTBI study).
- The use of “targeted” busulfan doses based on individual patient pharmacokinetic data results in consistent therapeutic drug levels and less toxicity
- Therapy which relies on the immune system in addition to chemotherapy, radiotherapy to attack cancer cells (MCC-12430, Toor RevAza study) can be less toxic and may produce lasting remissions by triggering an immune response to residual disease cells
- The use of rabbit ATG in MUD transplants (Fletcher et.al, ASH 2009) reduces aGHVD incidence without delay in immune reconstitution and increased infection
3. Infection prevention
- Routine monitoring for positive titers and the use of pre-emptive therapy for CMV, EBV before infection occurs results in fewer transplant complications
4. Stem cell collection for autologous transplants
- Access to a new mobilization drug (Mozobil) through clinical trials lead to better collections in fewer days of apheresis, prompt engraftment and possibly higher quality cells
- A new mobilization paradigm involving the drug Mozobil allows for stem cell collection with fewer delays, less opportunity for relapse and the opportunity for an autologous transplant for otherwise ineligible patients, (MCC-12889 McCarty PEI/PE study)
5. Novel disease treatment agents
- Use of new drugs, and drugs for which there are new disease indications, through clinical trials may result in a better response at the time of transplant and longer remission (Velcade, Revlimid, Vidaza [MCC-11328 McCarty Aza study], Sprycel, Nilotinib)