Fludarabine, Melphalan and Alemtuzumab Conditioned Reduced Intensity (RIC) Allogeneic Hematopoietic Cell Transplantation for Adults Aged >40 Years with De Novo Acute Lymphoblastic Leukemia: A Prospective Study from the UKALL14 Trial (ISRCTN 66541317)
Dina OkashaAmy A. KirkwoodMhairi CoplandEmma LawrieAndrew McMillanTobias MenneNicholas MorleyClare RowntreeDeborah RichardsonPaul A. SmithAdele K. FieldingDavid I. Marks
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Melphalan
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In present study the immediate and long-term therapy results of 14 patients with refractory chronic lymphocytic leukemia (CLL) are analyzed. Treatment program included alemtuzumab alone or in combination with fludarabine.
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Minimal Residual Disease
CD52
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The humanized anti-CD52 monoclonal antibody alemtuzumab is an effective therapy for chronic lymphocytic leukemia (CLL). We examined the impact of alemtuzumab treatment after initial fludarabine treatment for feasibility and safety. Patients (N = 85) with previously untreated symptomatic CLL received fludarabine (25 mg/m(2)/day) for 5 days every 4 weeks for four cycles followed by 2 months of observation. Patients with stable disease or better response then received alemtuzumab 30 mg three times weekly for 6 weeks either intravenously (IV; cohort 1; N = 39) or subcutaneously (SC; cohort 2; N = 20). Of the 85 evaluable patients enrolled on our study, four (5%) attained a complete response (CR) and 43 (51%) attained a partial response after fludarabine induction for an overall response rate (ORR) of 55%. Thirty-nine patients received IV alemtuzumab for consolidation with improvement in CR to 27% and ORR to 73%. Twenty patients received SC alemtuzumab consolidation with improvement in CR to 17% and ORR to 69%. Toxicity from IV alemtuzumab included infusion-related reactions and infection. Mild local inflammation was common from SC alemtuzumab but there were virtually no systemic side effects. Nine of 59 (15%) patients had cytomegalovirus (CMV) infections; one patient died. The administration of alemtuzumab as consolidation therapy following an abbreviated fludarabine induction is feasible but requires close monitoring for CMV infection and other infectious events.
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Although in recent years chemoimmunotherapeutic combinations such as fludarabine,cyclophosphamide,and rituximab have induced response rates of 95% in previously untreated patients and increased the rates of failure-free survival,Cll remains incurable for many patients because of a lack of disease response or the development of refractoriness to fludarabine.Salvage therapeutic strategies include alemtuzumab-containing regimens,targeted agents and allogeneic stem cell transplantation.Single-agent alemtuzumab induces response in up to 40% of patients with fludarabine-refractory CLL,but responses are not durable,and the median survival is approximately 1 to 2 years.Alemtuzumab is also combined with fludarabine,cyclophosphamide,and/or rituximab,and other agents such as lenalidomide and flavopiridol,as well as targeted agents,and used in fludarabine-refractory CLL.In conclusion,chemoimmunotherapy regimens that include alemtuzumab and/or rituximab and allogeneic stem cell transplantation improve the prognosis of this disease,but there is a need for novel,more effective therapies.
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