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Recombinant interferon alpha (rIFNα-2b) may retard progression of early primary myelofibrosis

Leukemia volume 23, pages 1366–1369 (2009)Cite this article

The disappointing results in the treatment of primary myelofibrosis (PM) with interferon, reviewed by Kiladjian et al.,1 with no objective responses in 84 PM patients, have prompted us to submit this letter regarding our success of using low-dose interferon in treating early-stage PM. In this study, we sought to avoid the progression of disease in patients who had early-stage disease. Those treated with interferon were good-risk patients, with relatively good blood cell counts and minimal to moderate bone-marrow fibrosis. We report here that early treatment in this good-risk group showed an improvement in bone-marrow fibrosis and in the control of splenomegaly. The use of interferon is based on its effects on megakaryopoiesis, which include decreasing megakaryocyte density and size,2 inhibiting thrombopoietin-induced signaling,3 suppressing the expression of transcription factors4 and reducing levels of platelet-derived growth factor,5 all of which play a major role in the pathogenesis of myelofibrosis.1

The diagnosis of PM was established clinically, hematologically and by bone-marrow trephine biopsy, consistent with published criteria.4, 5, 6 Pretreatment evaluation included history, physical examination, complete blood cell count and differential CD34 count, BCR–ABL and JAK2V617F allele burden determinations, serum chemistries and thyroid function tests. Spleen size was categorized as not enlarged, slightly enlarged (1–3 cm), moderately (4–9 cm) or markedly enlarged (>9 cm), as palpated below the costal margin in the mid-clavicular line. Exclusion criteria included marrow findings as below, and the usual contraindications to recombinant interferon alpha-2b (rIFNα).7 The bone-marrow biopsy specimens, routinely processed, were stained with hematoxylin–eosin and giemsa, and for reticulin and collagen, quantified by the method of Manoharan, et al.6 Excluded patients showed advanced fibro-osteosclerosis, grade 3 or 4 reticulin deposition, coarse bundles of collagen fibers6 and no residual hematopoiesis. Patients considered for study required hematopoietic foci occupying at least 30% of the marrow biopsy, and no more than grade 2 reticulin or collagen fibrosis. Before treatment, nine patients had a Lille8 risk score of 0, three had a score of 1 and one patient had a score of 2. None of the patients required transfusions. After treatment, 11 patients had a Lille risk score of 0 and two had a score of 1 (Table 1). We began treatment with rIFNα-2b at 500 000–1 000 000 units, subcutaneously, thrice weekly, increasing the dose gradually to 2–3 million units thrice a week, as tolerated and if necessary, in order to reduce the spleen size when present. Spleen size was used as a clinical marker of drug effect in patients with splenomegaly. Toxicity was evaluated using the International Common Toxicity Criteria, version 3.0 (http://ctep.cancer.gov/reporting/ctc.html). Approval for this retrospective analysis was obtained from the Weill Cornell Medical College Institutional Review Board.

Table 1 Clinical findings before and after treatment
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Acknowledgements

This work was supported by a grant form the William and Judy Higgins Trust of the Cancer Research and Treatment Fund, Inc., New York, NY, USA.

We acknowledge the measurement of JAK2V617F allele burden by Dr Lynn Wang, Dr Nicholas CP Cross and Amy Jones. Drs Attilio Orazi, Wayne Tam and Amy Chadburn independently reviewed marrow biopsies for this study. Paul Christos provided statistical assistance.The Weill Cornell Medical College Institutional Review Board has approved this retrospective review of patients treated with interferon. Presented in part at the 50th Annual Meeting of the American Society of Hematology, 6–9 December, 2008, San Francisco, CA, USA.

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  1. Department of Medicine, Division of Hematology and Medical Oncology, Weill Medical College of Cornell University, New York, NY, USA

    R T Silver & K Vandris

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Correspondence to R T Silver.

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Silver, R., Vandris, K. Recombinant interferon alpha (rIFNα-2b) may retard progression of early primary myelofibrosis. Leukemia 23, 1366–1369 (2009). https://doi.org/10.1038/leu.2009.90

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