DR 2-Chlorodeoxyadenosine treatment for cutaneous T-cell lymphoma Małgorzata Sokołowska-Wojdyło, Magdalena Trzeciak, Jadwiga Roszkiewicz Department of Dermatology, Venereology and Allergology, Medical University of Gdańsk, Gdańsk, Poland Abstract The primary cutaneous lymphomas are often indolent but difficult to treat. In the early stages psoralen and ultraviolet-A therapy is the standard treatment whereas at the tumor stage chemotherapy (e.g. pegylated doxorubicin) is often used for debulking. The purine analog 2- chlorodeoxyadenosine (2CdA) acts in non- Hodgkin’s lymphoma and has been used in our center for the treatment of advanced primary cutaneous T-cell lyphomas (CTCL). Here, we report on the efficacy and side effects of 2CdA in six patients with CTCL. One patient died owing to myelosuppression. Partial responses were seen in four cases but full remission was observed in only one case. We concluded that 2CdA has a limited usefulness in the manage- ment of advanced CTCL. Introduction A purine analog 2-chlorodeoxyadenosine (2- CdA) has been accepted as the treatment of choice in hairy cell leukemia and low-grade non-Hodgkin’s lymphomas. It has also been rec- ommended in stage IV A/B of cutaneous T-cell lymphomas (CTCL), along with chlorambucil, liposomal doxorubicin, CHOP polychemother - apy, denileukin difitox, and others.1-11 The aim of our study was to analyze the efficacy and side effects of 2CdA treatment for CTCL. Materials and Methods We treated six CTCL patients (five with mycosis fungoides; four in stage IIB, one in IVB, and one with peripheral cutaneous T-cell lymphoma (PTCL), unspecified) with 2CdA (pulses of 0.12 mg/kg/day/5 days).10,12-20 The patients failed standard therapies including glucocorticoids, retinoids, methotrexate, radiotherapy, and phototherapy. The efficacy of the treatment was established based on the clinical evaluation of skin lesions and internal involvement. Results The patients received 1-8 pulses of 2CdA (Table 1, Figures 1-4). One patient achieved total remission (patient 46/F, Figure 2A and B), lasting six months. Partial remission was achieved in four cases. Progression of the dis- ease during treatment appeared in one case (patient 71/F, Figure 4). One patient died because of myelosupression and staphylococ- cal sepsis just after the second pulse with 2CdA (patient 43/F, Figure 1). We tried to avoid the Dermatology Reports 2010; volume 2:e12 Correspondence: Jadwiga Roszkiewicz, Depart - ment of Dermatology, Venereology and Allergology, Medical University of Gdańsk, 7th Debinki Street, 80-211 Gdańsk, Poland. E-mail: mwojd@amg.gda.pl Key words: 2-chlorodeoxyadenosine (2CdA), cutaneous T-cell lymphoma, mycosis fungoides, Sézary syndrome, treatment, side effect. Received for publication: 17 February 2010. Revision received: 16 April 2010. Accepted for publication: 26 July 2010. This work is licensed under a Creative Commons Attribution 3.0 License (by-nc 3.0). ©Copyright M. Sokołowska-Wojdyło et al., 2010 Licensee PAGEPress, Italy Dermatology Reports 2010; 2:e12 doi:10.4081/dr.2010.e12 Table 1. Characteristics of the patients. Age/Gender Diagnosis and stage1 Duration of the disease Previous treatment 43/F (Fig. 1) MF IIB 13 mth Prednison, PUVA, RePUVA cyclofosphamid 46/F (Fig. 2A, B) MF IVB 31 mth PUVA 46/F PTCL 6 mth Acitretin 65/F (Fig. 3A, B) MF IIB 6 mth acitretin, acitretin + MTX 58/M MF IIB 16 mth Acitretin, MTX, local electron beam therapy (Department of Radiotherapy) 71/F (Fig. 4A, B) MF IIB 4 yr Prednisone, MTX, UVB311, acitretin, bexaroten (severe side effects: total skin peeling, bullae, and progression of the disease to MF IV) MF, mycosis fungoides; PTCL, primary cutaneous peripheral T-cell lymphoma. [page 28] [Dermatology Reports 2010; 2:e12] Figure 1. (A and B) Before 2CdA treat- ment: patient died of S. aureus sepsis after the second pulse. A B No n- co mm er cia l u se on ly Article [Dermatology Reports 2010; 2:e12] [page 29] Figure 3. (A) Patient 65/F before2CdA treatment; and (B) after treatment (remis- sion but new tumors have appeared). Table 2. Response to 2-chlorodeoxyadenosine. Patient No of cycles/dose Duration of the Lymph node Outcome per cycle (1 cycle = 5 d) cutaneous response status (response) 43/K (Fig. 1) 2/0.12 mg/kg (7 mg/d) No response Slight Death because of S. aureus sepsis 46/K (Fig. 2A-E) 8/0.12 mg/kg (7 mg/d) 6 mounth Total Death because of dissemination of MF (6 mth after end of 2CdA) 46/K 3/0.12 mg/kg (8 mg/d) 6 mounth Total Death, metastasis of lymphoma to central nervous system 65/K (Fig. 3A, B) 6/0.12 mg/kg (7 mg/d) 2 weeks Moderate Progressive disease 58/M 6/0.12 mg/kg (13 mg/d) 8 mounth Not applicable Progressive disease 71/K (Fig. 4A, B) 1/0.12 mg/kg (7 mg/d) Progressive disease Not applicable Progressive disease Response: slight, <25%; moderate, 25-50%; significant, 50-75%; total, 100%; PTCL, primary cutaneous peripheral T-cell lymphoma. Figure 2. (A, B and C) Before 2CdA treatment; (D and E) after six pulses of 2CdA (MF mimicking lichen planus). A C B D A B E No n- co mm er cia l u se on ly infections by chemoprophylaxis with co-tri- moxazol and acyclovir during and after 2CdA treatment. One patient died because of pro- gression of the lymphoma to the central ner - vous system a few months after the end of treatment (patient 46/F with PTCL). The other two patients achieved partial remission and required further chemotherapy (Table 2). Discussion 2CdA therapy was mostly well tolerated in view of the known side effects (Table 4) although one patient died just after the second pulse because of myelosupression. The observed remissions were short-lasting. Table 3 shows the experience with 2CdA in other Article Table 4. Dose-dependent side effects after 2-chlorodeoxyadenosine, based on data in the literature8,13,21-23 Side effect Time of appearance (*) Headache (22%, 7% >2nd week) Immediate Erythema (5-27%, 10% >2nd week) Early Nausea (0-28%) Immediate Myelosupression (neutropenia, thrombocytopenia, lymphocytopenia) Early, distant, late Cutaneous side effects, including panniculitis (19%) Immediate Paraparesis, tetraparesis (rare) Distant Hyperuricemia Immediate Renal finction disturbances (rare) Early Fever (46%) Immediate Fatigue (45%, 11% >2nd week) Immediate *The time of side effects’ appearance: immediate, hours; early, days, weeks; distant, weeks, months; late, months, years. [page 30] [Dermatology Reports 2010; 2:e12] Figure 4. (A) Patient 71/F before 2CdA treatment; and (B, C and D) after one pulse of 2CdA treatment: rapid progression just after the treatment showing faces leonona. This was followed by seven pulses of CHOP with only 7-10 days’ lasting remission, then by TSEB. Table 3. Response to 2-chlorodeoxyadenosine in CTCL patients – results from different centers and from the Dermatological Department, Gdansk, Poland. Number Complete (%) Partial No response (%) of patients remission remission (%) Bouwhius et al., 2002, USA3 6 13 50 37 Kuzel et al., 1996, USA12 21 14 14 72 Saven et al., 1992, Canada25 16 20 27 47 Rummel et al., 1998, Germany20 66 38 ND ND Kay et al., 1992, Canada9 40 20 22.5 57.5 Kong et al., 1997, USA11 24 12 12 76 O’Brien et al., 1994, USA23 22 18 23 59 Dept. of Dermatology, Poland 6 33 50 17 (present report) ND, no data. A B C D No n- co mm er cia l u se on ly