How to Treat Algodystrophy and Rheumatic Comorbidity in Myelofibrosis: Three Case Reports.

Algodystrophy or complex regional pain syndrome is a chronic pain condition characterized by hyperalgesia and allodynia. Patients with algodystrophy present an amplified and persistent activation of the innate immune system, with subsequent proliferation of keratinocytes and release of proinflammatory cytokines including interleukin (IL)-6, IL-1ß, and tumor necrosis factor-α (TNF-α). Chronic inflammation and increased levels of cytokines are observed also in Ph-negative myeloproliferative neoplasms, including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Chronic myeloid neoplasms are characterized by overproduction of one or more mature non-lymphoid cell lineages, with erythrocytosis, thrombocytosis, and/or myeloproliferation. Three case reports described our experience in the treatment of algodystrophy and rheumatic conditions in patients with myelofibrosis; a literature search was also performed. The first patient was a 58-year-old woman who suffered from chronic myeloproliferative neoplasm in myelofibrotic evolution, under treatment with ruxolitinib and pre-treated with hydroxyurea; she reported inflammatory pain, and swelling of the tibiotarsal joints bilaterally. She was treated with neridronate 2 mg/kg for four days and methotrexate 15 mg per os per week, achieving a clinical benefit. The second patient was a 63-year-old woman diagnosed with polycythemia vera evolving to myelofibrosis. She experienced pain and swelling of the left tibiotarsal joint and difficulty walking. A therapy with low-dose steroid per os and intramuscular clodronate was administered for four months, followed by methotrexate at 15 mg per week. After two months, tenosynovitis significantly improved, as supported by the evidence of improved bone edema of the left tibiotarsal joint revealed in the magnetic resonance imaging, and pain symptoms were clinically ameliorated. The third patient was a 70-year-old male patient affected by essential thrombocythemia with myelofibrotic evolution and a paraneoplastic polymyalgia rheumatica treated with steroids and currently in remission. The patient received ruxolitinib for about two years; after the first year of treatment, he experienced pain and swelling of the right tibiotarsal joint with difficulty in walking, with a consequent diagnosis of edema and tenosynovitis, as per algodystrophy. After consulting a rheumatologist, the patient received therapy with neridronate intramuscularly with clinical benefit. As overlapping interactions and clinical manifestations between hematologic neoplasms and rheumatologic diseases exist, new clinical manifestations, such as algodystrophy, may emerge during myelofibrosis and need to be monitored in the long term by a multidisciplinary team.

Ruxolitinib - better prognostic impact in low-intermediate 1 risk score: evaluation of the 'rete ematologica pugliese' (REP) in primary and secondary myelofibrosis.

We evaluated ruxolitinib in 65 patients with myelofibrosis according to age, sex, time of diagnosis, grade of fibrosis, prognostic score risk, Janus kinase (JAK) status, primary or secondary myelofibrosis, previous treatment, and dosage. Outcome measures were response rate, time to response, duration of response, and event-free survival and survival. Kaplan and Meier curves show a significant difference in event-free survival according to the prognostic score, in favor of patients with low int1 (p = 0.0009). The Cox stepwise model confirmed the result, the int2 high-risk score being the most powerful negative independent parameter (0.001), followed by JAK (0.008); other parameters, such as diagnosis more than 5 years earlier, grade III-IV fibrosis, and ruxolitinib dose have a negligible impact. Time to response was shorter (p = 0.001) in primary myelofibrosis. In conclusion, ruxolitinib is effective, with a better outcome in patients with a low-int1 risk score. This may suggest considering an earlier administration in the disease course.

Romiplostim for severe thrombocytopenia in the treatment of chronic hepatitis C virus infection: a new option for clinicians?

We describe a case of a 64-year-old man with a history of ITP which had required several treatments including splenectomy, and with chronic hepatitis C virus (HCV) infection untreated due to severe thrombocytopenia. In March 2011, platelet count was 14,000/mmc and a thrombopoietic therapy with romiplostim was initiated at the dose of 2 mcg/kg/week that was increased to 8 mcg/kg/week. At week 32, platelet count was 65,000/mmc and an anti-HCV therapy with peginterferon and ribavirin was then started. At baseline laboratory tests indicated AST 99IU/l, ALT 125UI/l, HCV_RNA 3,220 UI/ml and HCV genotype 2a/2c. An early virological response (EVR) with normalization of transaminases in the course of antiviral therapy, such as a sustained virological response (SVR) after its interruption were recorded. Therefore a satisfactory platelet count (range 54.000-179.000/mmc) at the dose of 4 mcg/week during antiviral therapy, such as at the dose of 2 mcg/kg/week after antiviral interruption (range 65.000-292.000/mmc) was recorded. Romiplostim proved effective and safe in the course of antiviral treatment. Therefore it permitted the start of anti-HCV therapy despite severe thrombocytopenia and also avoided any peg-interferon dosage modification or discontinuation. Further prospective studies in larger patient cohort should be encouraged to validate this strategy.