293: Allogeneic Hematopoietic Cell Transplantation (HCT) in Chemotherapy Refractory Chronic Lymphocytic Leukemia (CLL)

Allogeneic HCT (Allo-HCT) is an effective treatment option for CLL due to both cytoreductive therapy from the conditioning regimen as well as the graft versus leukemia (GVL) effect. Traditionally, chemosensitivity is a pre-requisite for Allo-HCT; however, this may not be necessary in CLL due to the GVL effect. We identified a consecutive case-series of 29 patients who underwent an Allo-HCT at the City of Hope Medical Center between1993 and 2006. The median age at transplantation was 48 years (38–68). The median time from diagnosis to transplant was 49 months (13–157). Median number of prior chemotherapy regimens was 3(1–6). Twenty four patients had prior fludarabine therapy and 10 were considered refractory. Sixteen patients received prior anthracycline therapy. Twenty two patients had chemosensitive disease, defined as ≥a partial response to salvage chemotherapy just prior to Allo-HCT. The conditioning regimens used consisted of Fludarabine+Melphalan n = 13, FTBI+Cytoxan n = 11, Fludarabine+Cytoxan+Rituximab n = 1, FTBI+Etoposide n = 1, FTBI+Etoposide+Cytoxan n = 1, Etposide+Cytoxan+BCNU n = 1, and Busulfan+Cytoxan n = 1. Nine patients received an unrelated donor graft and 20 received a sibling graft, including one patient who received a syngeneic transplant. Thirteen patients received a stem cell product derived from bone marrow, 16 from peripheral blood. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine-based regimen (n = 22), Tacrolimus+Sirolimus (n = 3), Methotrexate+Tacrolimus (n = 2), Methotrexate +Methylprednisolone (n = 1), and none in the syngeneic transplant. The non-relapse mortality was 34% at five years. Five pateints(17%) relapsed post Allo-HCT, 3 of them died of relapsed disease. Ten patients(34%) developed grade 3–4 acute GVHD, and 18(62%) developed chronic GVHD; 71% extensive. The median follow up for the 12 surviving patients is 67 months (9–163 months). The projected 5-year overall survival (OS) and disease-free survival (DFS) rates for all patients were 59% (CI: 47–69) and 48% (CI: 39–57) respectively. OS for the chemosensitive and the chemorefractory patients were 71(CI: 54–82) and 29(CI: 20–38) (p = .07) respectively. The DFS, was 56(CI: 43–67) in the chemosensitive patients and 29(CI: 20–38) in the chemorefractory patients (p = .14).Conclusion: Allo-HCT is effective and feasible in chemorefractory patients and offers disease free survival not significantly different from patients with chemosensitive disease. Allogeneic HCT (Allo-HCT) is an effective treatment option for CLL due to both cytoreductive therapy from the conditioning regimen as well as the graft versus leukemia (GVL) effect. Traditionally, chemosensitivity is a pre-requisite for Allo-HCT; however, this may not be necessary in CLL due to the GVL effect. We identified a consecutive case-series of 29 patients who underwent an Allo-HCT at the City of Hope Medical Center between1993 and 2006. The median age at transplantation was 48 years (38–68). The median time from diagnosis to transplant was 49 months (13–157). Median number of prior chemotherapy regimens was 3(1–6). Twenty four patients had prior fludarabine therapy and 10 were considered refractory. Sixteen patients received prior anthracycline therapy. Twenty two patients had chemosensitive disease, defined as ≥a partial response to salvage chemotherapy just prior to Allo-HCT. The conditioning regimens used consisted of Fludarabine+Melphalan n = 13, FTBI+Cytoxan n = 11, Fludarabine+Cytoxan+Rituximab n = 1, FTBI+Etoposide n = 1, FTBI+Etoposide+Cytoxan n = 1, Etposide+Cytoxan+BCNU n = 1, and Busulfan+Cytoxan n = 1. Nine patients received an unrelated donor graft and 20 received a sibling graft, including one patient who received a syngeneic transplant. Thirteen patients received a stem cell product derived from bone marrow, 16 from peripheral blood. Graft versus host disease (GVHD) prophylaxis consisted of cyclosporine-based regimen (n = 22), Tacrolimus+Sirolimus (n = 3), Methotrexate+Tacrolimus (n = 2), Methotrexate +Methylprednisolone (n = 1), and none in the syngeneic transplant. The non-relapse mortality was 34% at five years. Five pateints(17%) relapsed post Allo-HCT, 3 of them died of relapsed disease. Ten patients(34%) developed grade 3–4 acute GVHD, and 18(62%) developed chronic GVHD; 71% extensive. The median follow up for the 12 surviving patients is 67 months (9–163 months). The projected 5-year overall survival (OS) and disease-free survival (DFS) rates for all patients were 59% (CI: 47–69) and 48% (CI: 39–57) respectively. OS for the chemosensitive and the chemorefractory patients were 71(CI: 54–82) and 29(CI: 20–38) (p = .07) respectively. The DFS, was 56(CI: 43–67) in the chemosensitive patients and 29(CI: 20–38) in the chemorefractory patients (p = .14). Conclusion: Allo-HCT is effective and feasible in chemorefractory patients and offers disease free survival not significantly different from patients with chemosensitive disease.

Topic: Chronic Lymphocytic Leukemia Research
Subfield: Genetics
Field: Medicine
Domain: Health Sciences