2‐Chlorodeoxyadenosine treatment after splenectomy in patients who have myelofibrosis with myeloid metaplasia

Abstract

Summary. 2-Chlorodeoxyadenosine (2-CdA) is a purine nucleoside analogue with therapeutic activity in low-grade lymphoproliferative disorders. In addition, 2-CdA has a potent myelosuppressive effect, and it has been shown to be toxic to malignant myeloid cells both in vitro and in vivo. In this pilot study we treated nine patients who had advanced myelofibrosis with myeloid metaplasia (MMM) and progressive hepatomegaly or symptomatic thrombocytosis after therapeutic splenectomy. 2-CdA was administered 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 responding 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 initially responding patients have since died of acute leukaemia or progressive disease. Improvement in bone marrow fibrosis was noted in two of five available posttreatment marrow examinations. Toxicity was mainly myelosuppression, which was severe in two patients. 2-CdA may be considered a palliative therapeutic agent after splenectomy in noncytopenic patients with MMM who have progressive hepatomegaly or extreme thrombocytosis.

Choosing between stem cell therapy and drugs in myelofibrosis

“…No patient was successfully brought to allogeneic transplant, suggesting that transplant should be considered well in advance of BP if desired. (further details are as per authors 63,66,68,69 given in Table 4). …”

Modern management of myelofibrosis

“…2-Chlorodeoxyadenosine, a purine nucleoside analogue of intravenous administration, has been reported to have a palliative role for progressive hepatomegaly and symptomatic thrombocytosis developing after splenectomy (Tefferi et al, 1997).…”

Myelofibrosis with Myeloid Metaplasia: New Developments in Pathogenesis and Treatment

“…The drug of choice to control splenomegaly is hydroxyurea since it is well tolerated and dose adjustments can be easily performed to correct for responses (60,61). If therapy with hydroxyurea fails, other drugs such as busulfan, melphalan and 2-chlorodeoxyadenosine may also be used for this purpose (62)(63)(64)(65). While there have been reports that alfa interferon may control splenomegaly, in general it is poorly tolerated by patients with this disease (66)(67)(68).…”