The many challenges to success
Since the establishment of Stanford BMT program in 1987, many aspects of the clinical practice have changed. First, the number of transplants has increased dramatically in recent years. For the 2016-2017 academic year, 446 patients have received transplantation at Stanford with autologous and allogeneic about equally. Second, the upper age limit for transplant has also increased significantly. While most myeloablative regimen is limited to patients younger than 60 years, the reduced intensity regimens have been offered to patients up to 75 years old. In addition, our unique non-myeloablative regimen using total lymphoid irradiation (TLI)/anNthymocyte globulin (ATG) has no upper age limit due to its low toxicity and excellent safety record. Third, due to the smaller family size, it becomes harder to find a HLA-matched sibling donor. Therefore, the number of transplants with unrelated donor or alternative graft source including haploidentical graft and double cord blood stem cells have increased.
While modern-day supportive measures have provided better ways to manage side effects/complications associated with transplant, there are still numerous challenges. One challenge is to assess the risk of a patient regarding potential toxicity/mortality prior to transplant. With the complexity of an older patient population and different transplant regimens, it becomes a difficult task. To this end, Dr. Laura Johnston has analyzed the value of Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) in predicting the outcome of patients who underwent TLI/ATG non-myeloablative regimen at Stanford. In this cohort, about 1/3 of the patients each fell into the HCT-CI low, intermediate and high categories. While the higher HCT-CI correlated with lower overall survival, in contrast to previous studies, higher HCT-CI did not predict higher transplant related transplant related mortality (TRM) or risk for graft-versus-host disease (GVHD) in this specific cohort. This can be due to the overall low TRM and low incidence of GVHD using TLI/ATG regimen. This result suggests that the adverse effect of pre-transplant comorbidities can be alleviated with a safer or less toxic regimen. However, it also showed that we need more sophisticated tools in assessing patients’ risk, especially for the elderly population.
With safer regimens and better supportive measures, more patients achieve long term survival after transplant. Different challenges arise in these patients, mostly related to late complications that might be associated with transplantation procedure. These include cardio-pulmonary compromise, renal insufficiency, hormonal disturbance such as hypothyroidism and early menopause, and secondary malignancy. One of the most common secondary malignancy is skin cancer, especially the squamous cell carcinoma. To understand the incidence and risk for skin cancer, Drs. Wen-Kai Weng and Bernice Kwong (Dermatology) have conducted a retrospective cohort study with the entire Stanford BMT clinical database. With 2600+ patients included in this analysis, they found an increased risk for developing skin squamous cell carcinoma (6 Nmes risk) and basal cell carcinoma (3 times risk) in patients with allogeneic transplant compared to the ones with autologous transplant. The median time to diagnosis ranged from 1.6 to 2.9 years after transplant. In addition, they found an 80% increase in risk for squamous cell carcinoma for allogeneic transplant patients who received voriconazole.
These are the two examples of different challenges to success, which will require team work and the dedication of the BMT team to overcome.