Non-Myeloablative Allografting from HLA-Identical Sibling Donors for Treatment of CML.

We retrospectively analyzed data from 24 patients with chronic myeloid leukemia (CML) treated with HLA-matched related donor hematopoietic cell transplantation (HCT) after non-myeloablative conditioning with 2 Gy total body irradiation (TBI), given either alone (n=8) or in combination with 3 days of fludarabine, 30mg/m²/day (n=16). Postgrafting immunosuppression consisted of cyclosporine and mycophenolate mofetil. CML patients in first chronic phase (CP1) (n=14), second chronic phase (n=4) or accelerated phase (n=6) who were not candidates for conventional HCT, were enrolled in a median of 28.5 (range, 11–271) months after diagnosis. The median age at HCT was 58 (range, 27–71) years. Unmodified G-CSF mobilized peripheral blood stem cell grafts containing medians of 7.9 (range, 2–18.1) x10⁶ CD34+ cells/kg and 3.4 (range 1.7–2.4) x 10⁸ CD3+ cells/kg, respectively, were infused. The median number of days in which ANC was less than 0.5 x 10⁹/L was 5 (range, 0–8) days and 12 patients maintained ANCs greater than 0.5 x 10⁹/L after HCT. Only 2 patients developed platelet counts less than 20 x 10⁹/L. All patients had initial donor engraftment (>5% donor T-cell chimerism) at day 28 after transplant, and 17 (71%) achieved sustained full donor chimerism (>95% donor T-cell chimerism). There were 4 rejections followed by autologous hematopoietic reconstitution among 8 patients not given fludarabine, and donor lymphocyte infusions (DLI) were ineffective to reverse rejections. Fifteen (60%) patients achieved CR and 13 (54%) had complete molecular remissions, (defined as RT-PCR negativity for bcr-abl). Thirteen of 24 patients (54%) were alive and in CR at a median of 36 (range, 4–49) months after HCT. There were 5 (21%) deaths from non-relapse causes, one of them (4%) during the first 100 days. The incidences of grade II, III and IV acute GVHD were 38%, 4%, and 8%, respectively. The 2-year incidence of chronic extensive GVHD was 32%. The 2-year estimated overall survivals for patients in CP1 (n=14) and beyond CP1 (n=10) were 70% and 56%, respectively. Ten patients in CP1 received conditioning with fludarabine in addition to 2 Gy TBI; all ten achieved CR and 9 complete molecular remissions. Seven of 10 patients are alive in molecular remissions with a median follow-up of 36 (range, 6–49) months. In summary, non-myeloablative HCT were well tolerated in a group of patients who were older and/or medically infirm and therefore ineligible for myeloablative HCT. This approach should be considered for patients who fail to respond to initial conventional therapy and are not eligible for myeloablative conditioning regimens. The effectiveness of non-myeloablative compared to conventional myeloablative HCT will need to be definitively assessed in Phase III clinical trials.