A. Tefferi et al., 2-CHLORODEOXYADENOSINE TREATMENT AFTER SPLENECTOMY IN PATIENTS WHO HAVE MYELOFIBROSIS WITH MYELOID METAPLASIA, British Journal of Haematology, 99(2), 1997, pp. 352-357
2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with th
erapeutic activity in low-grade lymphoproliferative disorders. In addi
tion, 2-CdA has a potent myelosuppressive effect, and it has been show
n to be toxic to malignant myeloid cells both in vitro and in vivo. In
this pilot study we treated nine patients who had advanced myelofibro
sis with myeloid metaplasia (MMM) and progressive hepatomegaly or symp
tomatic thrombocytosis after therapeutic splenectomy. 2-CdA was admini
stered at 0.05-0.1 mg/kg/d for 7 d for one to five treatment cycles, A
reduction in liver size associated with marked improvement in fatigue
and control of thrombocytosis and leucocytosis was achieved in seven
of the nine patients (78% response rate). In four of the seven respond
ing patients the reduction in liver size was durable (4-28 months) and
was associated with a decrease in serum alkaline phosphatase levels.
However, no patient had improvement in anaemia, and two of the seven i
nitially responding patients hare since died of acute leukaemia or pro
gressive disease. improvement in bone marrow fibrosis was noted in two
of fire available posttreatment marrow examinations. Toxicity was mai
nly myelosuppression, which was severe in two patients, 2-CdA may be c
onsidered a palliative therapeutic agent after splenectomy in noncytop
enic patients with MMM who have progressive hepatomegaly or extreme th
rombocytosis.