No Evidence for Increased Transplant Related Complications in Ph+ Chronic Myelogenous Leukemia and Acute Lymphoblastic Leukemia with Prior Treatment with Dasatinib.

Stem cell transplantation (SCT) is frequently used as salvage or curative therapy in patients (pts) with advanced chronic myelogenous leukemia (CML) or Ph+ acute lymphoblastic leukemia(ALL) who were previously treated with Imatinib. While one study showed higher incidence of GVHD, VOD and TRM, most studies have demonstrated that Imatinib therapy prior to SCT does not adversely affect transplantation outcome. Dasatinib is a novel dual SRC/ABL kinase inhibitor currently being used in pts with Imatinib-resistant advanced CML or relapsed/efractory Ph+ ALL. Most of these pts will eventually undergo SCT, raising the question of whether Dasatinib therapy may adversely affect transplantation outcome. We report eight pts: CML -6 (CP1-4, low sokal score -3, high sokal score -1, CP2-1, AP-1) and Ph+ ALL -2 who received Dasatinib prior to alloSCT (n=7) or autoSCT (n=1). Donors were matched siblings -4, matched unrelated -2 or mismatch related donor (haploSCT) -1. Five were male and 3 female with a median age of 46.5 (16–56) years. First line therapies included Hydroxyurea or Interferon followed by Imatinib for the CP CML pts and chemotherapy followed by Imatinib for the advanced CML and Ph+ ALL pts. All pts subsequently received Dasatinib 70mg × 2/day due to resistance to Imatinib, resulting in complete hematological response in all, as well as complete (n=5) or partial cytogenetic response (CyR) (n=2) prior to SCT. One pt did not achieve CyR prior to SCT. The pts were conditioned with either a myeloablative protocol (n=5) or a reduced intensity protocol (n=3). GVHD prophylaxis consisted of CSA and MTX (n=6) or complete T-cell depletion (n=1). Pts received a mobilized peripheral blood stem cell graft with 11.4–19.8 × 10⁶ CD34+ cells/kg. The pt who underwent autoSCT was successfully mobilized (2 apheresis cycles yielding 5.7 × 10⁶ CD34+/kg). Dasatinib was stopped 6 days before mobilization. All pts successfully engrafted reaching ANC > 0.5×10⁹/L on day +14 (11–21) and PLT >20×10⁹/L on day +12.5 (11–17). Chimerism was 99.4 – 100%. Transplant related toxicities were minimal. Only one pt developed severe mucositis. No pt developed hyperbilirubinemia or VOD. There was no increased risk of infections. Acute GVHD (Gr II) was observed in only 1 pt, while 2 developed extensive chronic GVHD (1 after stopping immunosuppression). With a median follow-up of 8.5 (2–13) months, six pts are alive, 5 in CR, while 2 died of disease progression. We may conclude that in pts undergoing SCT following Dasatinib there is no evidence that Dasatinib adversely affect post SCT outcome, as no increased transplant related organ toxicities, non-engraftment, GVHD or infections were observed. Larger studies are obviously indicated to confirm our preliminary results.