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There is no good alternative therapy available for elderly patients with advanced myeloproliferative disorders (MPD) who failed on conventional therapies and are not candidates for bone marrow transplant. We report here an effective therapy that induced exceptionally long-lasting remissions and improved quality of life. Eighteen elderly patients (mean age: 70·6 years) (16 myelofibrosis and 2 thrombocythemia) who had failed on conventional therapies were treated. Danazol was administered daily at 200-800 mg throughout the study. Chemotherapy was applied intermittently as needed to reduce spleen size and blood counts. Busulfan (2-4 mg/day) was used most often and 6-mercaptopurine (6-MP) (50-100 mg/day) and/or cytarabine (100-200 mg/m(2)) if the white blood cell (WBC) count rose rapidly. When MPD stabilized, chemotherapy was discontinued and dosage of danazol was reduced. Therapy was well tolerated. Overall, 61% of patients responded with unexpectedly long-lasting remissions and improved quality of life. Three (17%) had excellent (E) response, defined by normalization of blood counts and non-palpable spleen, while eight (44%) had good (G) response, defined by rise of Hct by ≥7% and ≥50% reduction of spleen. Mean duration of remission was 45 months (10-78 months) in E responders and 11 months in G responders (2-22 months). This regimen offers a safe and effective alternative for advanced MPD in the elderly.

Introduction: Platelets play an important role in inflammatory and immune responses. We report interstitial lung disease (ILD) developing during the acute phase of severe thrombocytopenia in 3 patients with severe refractory ITP., Methods and Results: We identified 3 cases with severe ITP who developed ILD in the course of refractory chronic ITP. The thrombocytopenia was severe in all cases. ILD was an incidental finding at the presentation and often misdiagnosed as lung infections. ILD was documented by lung biopsy in cases 1 and 2, supplemented by serial chest X-rays and/or CAT scan. As the ITP improved, ILD regressed in case 1, persisted in case 2, and progressed to advanced pulmonary fibrosis in case 3., Conclusion: We report an association of ILD with severe refractory ITP. ILD was detected in acute phase of platelet destruction, suggesting that platelet destruction may have triggered inflammation in the lung, leading to ILD.

Introduction: Risk factors for thrombosis (TB) in thrombocythaemia (TC) associated with myeloproliferative disorder (MPD) are not well defined., Methods: We measured antiphospholipid antibodies (APLA) in 35 patients with TC associated with MPD. Fourteen had TB and 21 did not. We assayed IgG and IgM APLA by ELISA for 6 antigens: beta2GP1, cardiolipin (CL), phosphatidylcholine (PC), phosphatidylserine (PS), phosphatidylethanolamine (PE) and FVII/VIIa, together with markers of activation of platelets (CD62P) and endothelium [endothelial microparticles (EMP)]., Results: At least one positive APLA was detected in 66% of TC patients overall. The incidence was significantly higher in the TB subgroup (92.8%) than non-TB (47.6%, p < 0.05). Multiple APLA (positive for more than one antigen) were also more frequent in TB, for both IgG and IgM, for all 6 antigens tested (p < 0.05). However, IgM APLA predominated, being about 2-fold more frequently positive than IgG for all 6 antigens. Platelet CD62P was significantly higher in the TB group (p < 0.05). EMP did not differ between TB and non-TB. The most frequent thrombotic complication was recurring ischemic cerebral vascular accidents (ICVA), leading to progressive cognitive impairment. Venous TB often developed at unusual sites. Recurring and reversible TB were common features in TC., Summary: This study suggests that APLA and platelet activation are risk factors for TB in TC. APLA are prevalent in TC, and IgM APLA predominated over IgG. Activation of platelets but not of endothelium may be consistent with the reversible and recurrent features of TB in TC.