Abstract

HCL is a chronic leukemia of B-lymphocyte with variable clinical course: symptomatic cytopenia and/or marked splenomegaly. Concomitant infections disease are often and transfusion are quite necessary. Current therapy includes interferon, 2′deoxycoformycin, 2′chlorodeoxyadenosine which induce profound and durable CD4 and CD8 T cells cytopenia inducing major infection risk. Fludarabine phosphate (F-AMP) had been extensively used in chronic B-cell leukemia and lymphomas; previous reports have shown response in pre-treated HCL patients (Kraut, 1991; Kantarjian, 1991). Herein we show our experience with 3 high risk-HCL patients treated with F-AMP in our institution between May 2001 and August 2002.

Pt 1: male 52 yo, debuted with splenomegaly (200 mm) and pancytopenia in 12/2000. Massive HCL involment in bone marrow (BM), flow showed positivity to CD20, CD 11c, CD 25 and CD103; TRAP test positive. At that point patient was at first splenectomized, with transient moderate blood count recovery. Five months later patient showed severe cytopenia and was started on F-AMP 25mg/m2 i.v. d1-5 each 28 days 6 cycles. Patient got complete haematological response with residual infiltration for HCL in BM; with a follow up of 51 months after F-AMP without cytopenias and infections.

Pt 2: male, 53 yo, debuted with splenomegaly (over 200 mm), pancytopenia and diffuse B-cell BM involvement in 03/2002. Lucid spleen spots were observed at CT scan, followed by fever and haemolytic anemia. Splenectomy was performed, final diagnosis included extra-pulmonary TBC for M. Tuberculosis and HCL. Flow showed: CD20 (+), CD11c (+), CD 25(+), CD103 (+), CD5 (−), CD10 (−); TRAP test positive. TBC treatment started and mild blood count recovery was observed, 10 months after splenectomy; villous lymphocytes appeared in peripheral blood. Patient was started on F-AMP 25mg/m2 i.v. d1-5 each 28 days 6 cycles. Patient got Complete Response (CR) with a follow up of 40 months without leukaemia or infection recurrence.

Pt 3: male 63 yo, with previous medullar thyroid carcinoma diagnosis three years ago. He debuted with splenomegaly (200 mm), mild cytopenia and serum creatinine 1.26 mg/dl by 01/2002. Typical HCL involvement in BM, flow showed positivity to CD20, CD 11c, CD 25 and CD103. Patient was started on F-AMP 25mg/m2 i.v. d1-5, one cycle (08/2002). Ten weeks later, previous to restart treatment a BM assessment showed CR with creatinine clearance range between 30–40 ml/min, therapy was stopped. Actually with a follow up of 36 months patient is without recurrence.

Our experience strongly suggests and confirms potential role of F-AMP, in the management of high risk HCL previously splenectomized or post infection disease. Interestingly one patient responded to a total dose of 125mg/m2. Base in our and others data, F-AMP should be considered for HCL treatment.

Table:

Blood counts at diagnosis and 6 months post treatment

NeutrophilsPlateletsHb
mpt = months post treatment 
Pt 1 Dx 225 22 K 6.5 
 6 mpt 4450 213 K 16.2 
Pt 2 Dx 686 57 K 8.3 
 6 mpt 2750 251 K 16.2 
Pt 3 Dx 1330 331 K 11.6 
 6 mpt 3400 176 K 12.4 
NeutrophilsPlateletsHb
mpt = months post treatment 
Pt 1 Dx 225 22 K 6.5 
 6 mpt 4450 213 K 16.2 
Pt 2 Dx 686 57 K 8.3 
 6 mpt 2750 251 K 16.2 
Pt 3 Dx 1330 331 K 11.6 
 6 mpt 3400 176 K 12.4 

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