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Efficacy and safety of low-dose alemtuzumab as treatment of autoimmune hemolytic anemia in pretreated B-cell chronic lymphocytic leukemia

Leukemia volume 21, pages 1819–1821 (2007)Cite this article

We read with interest the article by Karlsson et al.1 published in a recent issue of this journal. They reported five patients affected by advanced B-cell chronic lymphocytic leukemia (B-CLL) who developed severe transfusion-dependent autoimmune hemolytic anemia (AIHA) resistant to conventional therapy, including corticosteroides, rituximab and splenectomy. The patients were treated with subcutaneous or intravenous alemtuzumab, at a dose of 30 mg three times weekly for a maximum of 12 weeks. All patients showed a good and stable response. We here confirm the data by Karlsson et al. in three patients who developed severe AIHA in the setting of progressive B-CLL. In a previous report, we described the efficacy and safety of intravenous low-dose alemtuzumab (10 mg three times weekly for 10 weeks) in 12 patients with relapsed or refractory chronic lymphocytic leukemia.2 On the basis of these encouraging results, the same treatment schedule was continued in selected heavily pretreated patients. Three male patients from this series had developed direct antiglobulin test (DAT)-positive AIHA before the initiation of alemtuzumab therapy. AIHA developed at a median of 31 months from B-CLL diagnosis and 3 months from the last therapy. Previous treatments for B-CLL, clinical stage and hemoglobin (Hb) values before alemtuzumab therapy and other clinical, biologic and prognostic features of these three patients are shown in Tables 1 and 2. All patients received red blood cell (RBC) transfusions before alemtuzumab therapy, and one of them received an additional transfusion during treatment. The median Hb value at first alemtuzumab administration was 9.4 g/dl (Table 1).

Table 1 Patient's clinical characteristics
Full size table
Table 2 AIHA response to alemtuzumab therapy
Full size table

Alemtuzumab was given subcutaneously at 3 mg on day 1; from day 3, the target dose was raised to 10 mg three times weekly for 30 administrations (10 weeks). All patients were treated with prophylactic 960 mg co-trimoxazole twice daily for two consecutive days a week until 1 year after the end of the treatment. Acyclovir (800 mg) three times a day during treatment was given until 2 months after the end of alemtuzumab treatment. Patients received 1000 mg paracetamol and 10 mg chlorpheniramine before each administration during the first week of alemtuzumab therapy. Peripheral blood count and biochemical screening were performed before every administration of alemtuzumab. Reticulocyte counts and analysis of CMV antigenemia and CMV DNA performed weekly; DAT and IAT were performed every 2 weeks. Following the end of therapy, physical examination, blood counts, biochemical parameters, CMV antigenemia, CMV DNA and reticulocyte counts were performed weekly for the first 8 weeks (DAT/IAT every 2 weeks), then monthly for the next 6 months and every 3 months thereafter. Assessment of response, according to NCI-WG criteria, was performed after 2 months.3 AIHA response was defined as the independence from RBC transfusions and a concomitant>2.0 g/dl rise in Hb concentration. All three patients received 30 subcutaneous administration of alemtuzumab at the target dose of 10 mg (total dose 300 mg). Two patients (no. 2 and 3) showed CMV reactivation at the 5th and 6th week of therapy and were treated with oral ganciclovir for 14 and 21 days, respectively. The therapy was well tolerated, with mild hematological and extra-hematological side effects, such as fever, itch, rigor and headache (grade I). No episode of febrile neutropenia or bacterial/fungal infection occurred during the treatment. Immunological recovery was markedly delayed during and after alemtuzumab therapy, with a prominent reduction in the T-cell compartment.4 All three patients responded to alemtuzumab treatment with a>2 g/dl rise in Hb concentration after a median of 8 weeks. Patient no. 3 responded at week 11, but in this patient treatment had been discontinued for 3 weeks (from 6th to 8th week) because of CMV reactivation. The median total dose of alemtuzumab required to obtain the AIHA response was 220 mg. The median duration of the response was 10 months and only one patient experienced a new episode of AIHA after 26 months (Table 2).

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References

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  1. Istituto di Ematologia, Policlinico A Gemelli, Universita' Cattolica del Sacro Cuore, Roma, Italy

    L Laurenti, M Tarnani, P Chiusolo, L De Padua, S Sica & G Leone

  2. ICGEB Outstation CNR Monterotondo-Roma, Roma, Italy

    D G Efremov

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  1. L Laurenti
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  2. M Tarnani
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Correspondence to L Laurenti.

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Laurenti, L., Tarnani, M., Efremov, D. et al. Efficacy and safety of low-dose alemtuzumab as treatment of autoimmune hemolytic anemia in pretreated B-cell chronic lymphocytic leukemia. Leukemia 21, 1819–1821 (2007). https://doi.org/10.1038/sj.leu.2404703

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