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- W2088422012 abstract "Pts with CLL refractory to fludarabine (FLU)-based chemotherapy have poor prognosis with a median survival of less than 1 year. We examined the safety and efficacy of NM-HCT for pts with CLL refractory to at least 1 cytotoxic regimen and ineligible for conventional allogeneic HCT due to age and/or comorbidities. Forty-seven pts with diagnoses of CLL (n = 42), small lymphocytic lymphoma (n = 2), or prolymphocytic leukemia (n = 3) were treated with NM-HCT from MRD (n = 33) and URD (n = 14). Median pt age was 58 (range 47–68) years (62% of pts >55 years). Median number of prior regimens was 4 (range 1–12) with 94% of pts refractory to at least 1 regimen. Thirty-six pts (77%) were refractory to FLU, 19 to alkylating agents and 6 to rituxumab. Two pts had prior autologous HCT. Nineteen pts (40%) had responsive disease to salvage chemotherapy given prior to HCT [partial (PR) (30%) or complete remission (CR) (10%)] while remaining pts were either nonresponsive (51%) or in relapse (9%). Median interval from diagnosis to HCT was 5 (0.6–25) years. Conditioning consisted of 2 Gy TBI alone (n = 19) or combined with FLU (n = 28), 90mg/m2 followed by mycophenolate mofetil and cyclosporine immunosuppression. All pts received G-CSF mobilized peripheral blood mononuclear cells as source of stem cells. After HCT, all pts became neutropenic (median ANC nadir=30 cells/ul) for a median of 11 days. Eighteen pts never had platelet counts below 20,000 cells/ul. Three pts had graft rejection; 1 died with aplasia and 2 had autologous recovery and are alive, 1 after multiple treatments and 1 relapsed at 2 years. Incidences of grades II, III, and IV acute GVHD were 38%, 15%, and 2% respectively and chronic extensive GVHD was estimated to be 48% at 4 years. With median follow up of 32 (range 6–69) months, overall response rate was 57% (CR = 43%). Overall, 26 patients are alive; 14 in CR, 4 in PR, 4 with stable disease, and 4 with progressive disease (PD). Seven patients died from PD, 9 from infections ± GVHD, 2 from cardiac problems, 1 from multiorgan failure, 1 from metastatic lung cancer, and 1 from rejection and aplasia. Estimated 2-year rates of non-relapse mortality, relapse-related mortality, progression free survival, and overall survival (OS) were 29%, 15%, 49%, and 56% respectively (Table 1). Projected 4-year OS was 47%. Conclusion: NM-HCT provides powerful graft-versus-leukemia activity in CLL and should be explored in phase II trials for treatment of pts with FLU-refractory disease. TableCLL Patients Treated with NM Conditioning and HCT with MRD and URDMRD (n = 33)URD (n = 14)Acute GVHD grades II, III, and IV36%, 15%, and 3%43%, 14%, and 0%Two-year Chronic extensive GVHD44%61%Median follow-up (range)37 (7–69) months19 (5–39) monthsOverall response rate (CR)55% (40%)64% (50%)Alive patients7 CR, 2 PR, 4 stable, 3PD7 CR, 2 PR, 1 PDTwo-year NRM31%23%Two-year relapse-related mortality16%8%Two-year PFS45%62%Two-year OS53%70%NRM, non-relapse mortality; PFS, progression-free survival. Open table in a new tab NRM, non-relapse mortality; PFS, progression-free survival." @default.
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- W2088422012 title "Treatment of patients (pts) with chemotherapy-refractory chronic lymphocytic leukemia (CLL) with nonmyeloablative (NM) conditioning and hematopoietic cell transplantation (HCT) from HLA-matched related (MRD) or unrelated donors (URD)" @default.
- W2088422012 doi "https://doi.org/10.1016/j.bbmt.2003.12.107" @default.
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