Nonmyeloablative conditioning for stem cell allografts with low-dose tbi: An update of toxicity and outcome

Based on a preclinical canine model of low-dose TBI (200 cGy) given in combination with postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP), the feasibility of performing allogeneic hematopoietic stem cell transplants in older or debilitated patients (pts) was established. In this report we provide an update on 56 pts treated for malignancies with the diagnoses of AML (n=12), CML (n=10), CLL (n=10), multiple myeloma (n=9), Hodgkin disease (n=4), NHL (n=3), MDS (n=4), and others (n=4). The follow-up was a median of 332 days (range 100–723). The median age was 56 years (range 31–71). All pts were conditioned with 200 cGy TBI and 6 received, in addition, fludarabine 30 mg/m2/day × 3. Short-term (35 or 56 days) MMF/CSP was given after transplant to prevent GVHD and graft rejection, and donor lymphocyte infusions were given in pts with persistent disease and/or mixed chimerism. Overall, transplants were well tolerated. The median number of days of hospitalization in the first 60 days for eligible pts was 0. All pts had initial engraftment with median donor T-cell chimerisms of 60% and 70% on days 28 and 56, respectively. Nonfatal graft rejection occurred in 16% of pts. Grade II–III acute GVHD occurred in 26 of 45 pts with sustained engraftment. Eight pts (14.3%) died of transplant complications between days 54 and 361, and 7 pts (12.5%) died of disease progression between days 38 and 408. Twenty-six pts (46.4%) were in CR, and an additional 9 (14.3%) were in PR at the point of last contact. In summary, successful allografts in pts otherwise ineligible for conventional allografting can be done with minimal regimen-related toxicities. Remissions of the underlying diseases, including molecular remissions, have been seen in almost 50% of pts.