The Use of Low-Dose Alemtuzumab as Single Agent in the Treatment of Complication in Advanced Chronic Lymphocytic Leukaemia

There are some report in literature about the use of Alemtuzumab in patients affected by advanced B-cell chronic lymphocytic leukaemia who developed severe transfusion-dependent autoimmune haemolytic anaemia (AIHA) resistant to conventional therapy or cutis involvement. We report the use of low-dose Alemtuzumab in 4 AIHA patients and in 1 case of eyelid leukaemia cutis. Alemtuzumab was given subcutaneously at 10 mg three times weekly for 30 administrations (10 weeks). Treatment was stopped for progression disease, grade IV thrombocytopenia and/or infections or Cytomegalovirus (CMV) reactivation. Prophylaxis consiste on co-trimoxazole and aciclovir from the start of the treatment until 2 months after the end of treatment. Peripheral blood count, biochemical screening, antigenemia and CMV DNA analysis, reticulocyte count were conducted weekly. DAT and IAT were studied every two weeks during the treatment. Patient with eyelid leukaemia cutis underwent to histological examination before and after the end of treatment. AIHA response, was defined as the independence from RBC transfusion and a concomitant > 2.0 g/dl rise in Hb concentration. Four male patients developed DATpositive AIHA at a median of 44.5 months from the B-CLL diagnosis. Previous treatment for B-CLL, stage and haemoglobin (Hb) values at Alemtuzumab administration are shown in table 1. Three patients underwent to RBCu transfusion before Alemtuzumab treatment, and one also during the treatment (2RBCu). The median haemoglobin value at first Alemtuzumab administration was 8.25 gr/dl. (table1) Two patients showed CMV reactivation at 5th and 6th week of therapy and were treated with oral ganciclovir for 14 and 21 days respectively. AIHA response was reached at median of 7 weeks of Alemtuzumab therapy in all patients while the median duration time of response to Alemtuzumab therapy was 10 months. Two patients underwent to further treatment for DAT negative progressive disease after 9 and 10 months from the end of Alemtuzumab therapy respectively, one patients was treated after 26 months for AIHA relapse, while the last patients even if showed AIHA remission is currently at 6th week of Alemtuzumab treatment (Hb 8g/dl). At the end of Alemtuzumab administrations the median Hb concentration was 12.7 g/dl regarding clinical responses, the patient no.1 obtained SD, the other 2 PR. Patient with leukemia cutis (LC) showed a constant reduction of eyelid involvement until clinical resolution after 240 mg of Alemtuzumab. Now a day, a manteinance therapy is ongoing with Alemtuzumab 30 mg monthly maintaining complete remission of eyelid localization and partial remission of CLL 10 months after induction therapy. In All patients the therapy has been well tolerated, with mild haematological and extra-haematological side effects (grade I). No episode of febrile neutropenia or bacterial/fungal infection occurred during the treatment. Our data confirmed the literature data about the use of Alemtuzumab, even if with low-dose, as salvage treatment for transfusion-dependent and resistant AIHA in pre-treated B-CLL patients and show a new indication for LC involvement. Table 1: Patient’s clinical characteristics Age/Sex Binet/Rai Stage Months from B-CLL diagnosis and AIHA/LC Previous treatment for B-CLL (number of cycles) Biological Parameter Months between last B-CLL therapy-AIHA/LC Hb at baseline Alemtuzumab treatment (gr/dl) DAT/IAT 68/M C/IV 9 CHOP(6), CVP(3) Unmutated IgVH
 Zap-70 +
 CD38 +
 Del17p 1 9.4 DAT 4+
 (IgG 4+)
 IAT 4+ 53/M C/IV 31 Chl/Pdn(6), FC(6), Pdn(6), Ig, Splenectomy Mutated
 Zap-70 −
 Normal karyotipe 3 7.1 DAT 2+
 (IgG 1+)
 IAT 2+ 46/M C/III 58 CHOP(8), HD-CTX, aPBSCT Unmutated IgVH
 Normal Kariotype 38 10.1 DAT 4+
 (IgG 3+; C3d 1+)
 IAT − 56/M C/IV 64 FC, chl, fludarabine, RIC transplant Unmutated IgVH Zap-70 + CD38 −Del 17p, Del 13q 28 4.9 DAT 4+
 (IgG 4+)
 IAT 2+ 61/M B/II 108 Fludarabine, CHOP, INFa, chl/pdn Mutated IgVH
 Zap-70 +
 CD38 +
 Del 17p, +12 24 14.3 Negative M: male, Chl: chlorambucil, Pdn: prednisone, FC: fludarabine+cyclophosphamide, Ig: intravenous immunoglobulin, HD-CTX: high dose-cyclophosphamide, aPBSCT: autologous peripheral blood stem cell transplantation.