Quality of life (QoL) in patients with myelofibrosis (MF) is severely compromised by severe constitutional symptoms (i.e. fatigue, night sweats, fever, weight loss), pruritus, and symptoms from frequently massive hepatosplenomegaly. Given that no current instrument of patient reported outcomes (PRO) exists that covers the unique spectrum of symptomatology seen in MF patients, we sought to develop a new PRO instrument for MF patients for use in therapeutic clinical trials. Utilizing data from an international internet based survey of 458 patients with MF we created a 20 item instrument (MFSAF: Myelofibrosis Symptom Assessment Form) which measures the symptoms reported by >10% of MF patients, and includes a measure of QoL. We subsequently validated the MFSAF in a prospective trial of MF patients involving patient and provider feedback, as well as comparison to other validated instruments used in cancer patients. The MFSAF results were highly correlated with other instruments, judged comprehensive and understandable by patients, and should be considered for evaluation of MF symptoms in therapeutic trials.

Among 200 patients with primary myelofibrosis, karyotype at diagnosis was abnormal in 83 (42%). To assess their individual prognostic impact, specific cytogenetic abnormalities with more than or equal to 5 informative cases were identified and the rest grouped separately as "other abnormalities." Median survival in patients with sole ؉9 (n ‫؍‬ 6), sole 20q؊ (n ‫؍‬ 21), sole 13q؊ (n ‫؍‬ 8), normal karyotype (n ‫؍‬ 117), "other abnormalities" (n ‫؍‬ 28), complex karyotype (n ‫؍‬ 13), and sole ؉8 (n ‫؍‬ 7) were "not reached," 112, 105, 80, 46, 34, and 28 months, respectively (P ‫؍‬ .01). Accordingly, 4 cytogenetic risk groups were considered: (1) favorable (sole ؉9, 20q؊, or 13q؊), (2) normal, (3) unfavorable (complex karyotype or sole ؉8), and (4) "other abnormalities." Multivariable analysis confirmed the International Prognostic Scoring System (IPSS)-independent prognostic value of both 4-way and 2-way (ie, favorable/normal vs unfavorable/other abnormalities; IPSS-adjusted hazard ratio ‫؍‬ 0.37; 95% confidence interval, 0.24-0.58) cytogenetic risk categorization (P < .01). The ability to prognostically dissect a specific IPSS category has major therapeutic implications. (Blood. 2010;115:496-499)

Pretreatment with sheep anti-TNF-alpha Fab suppresses Jarisch-Herxheimer reactions that occur after penicillin treatment for louse-borne relapsing fever, reduces the associated increases in plasma concentrations of interleukin-6 and interleukin-8, and may be useful in other forms of sepsis.

No abstract

Myelofibrosis (MF) is a clonal hematopoietic stem cell disorder currently classified as a myeloproliferative neoplasm (MPN) (1). MF presents either de novo [primary MF (PMF)] or in the setting of either polycythemia vera (post-PV MF) or essential thrombocythemia (post-ET MF) (2). Clinical features include anemia that is often transfusion-requiring, marked splenomegaly that sometimes necessitates therapeutic splenectomy, constitutional symptoms that are often accompanied by cachexia, leukoerythroblastic blood smear, bone marrow fibrosis and extramedullary hematopoiesis. Median survival of PMF is approximately 69 months and causes of death include leukemic transformation and infection (3). Current therapy for MF includes allogeneic stem cell transplantation usually considered for transplant-eligible patients with high-risk disease. Drug therapy has not been shown to modify the natural history of the disease but alleviates anemia or splenomegaly in approximately 20% of patients (4).The primary disease-causing mutation(s) in MF is unknown. In 2005, a Janus kinase 2 (JAK2) gain-of-function mutation (JAK2V617F) was described in PV, . JAK2V617F is present in approximately 97% of patients with PV and 50% of those with either ET or PMF. In 2006 and 2007, additional JAK2 and MPL mutations were described in approximately 3% of patients with PV (JAK2 exon 12 mutations) and 5-10% of those with ET or PMF (MPLW515L ⁄ K and others) (5-10). These mutations occur at a primitive stem cell level but their precise pathogenetic contribution is still unclear. Diagnostic utility of JAK and MPL mutations in MPN has now been well established and their value as AbstractThe clinical phenotype of myelofibrosis (MF) is recognized either de novo (primary) or in the setting of polycythemia vera (post-PV) or essential thrombocythemia (post-ET). Approximately one-third of patients with primary MF (PMF) present with cytogenetic abnormalities; the most frequent are del(20q), del(13q), trisomy 8 and 9, and abnormalities of chromosome 1 including duplication 1q. Other less frequent lesions include )7 ⁄ del(7q), del(5q), del(12p), +21 and der(6)t(1;6)(q21;p21.3). In general, cytogenetic abnormalities are qualitatively similar among PMF, post-ET MF and post-PV MF although their individual frequencies may differ. Based on prognostic effect, cytogenetic findings in MF are classified as either 'favorable' or 'unfavorable'. The former include normal karyotype or isolated del(20q) or del(13q) and the latter all other abnormalities. Unfavorable cytogenetic profile in both PMF and post-PV ⁄ ET MF confers an independent adverse effect on survival; it is also associated with higher JAK2V617F mutational frequency. In addition to their prognostic value, cytogenetic studies in MF ensure diagnostic exclusion of other myeloid neoplasms that are sometimes associated with bone marrow fibrosis (e.g. BCR-ABL1-positive or PDGFRBrearranged) and also assist in specific treatment selection (e.g. lenalidomide therapy is active in MF associated with del(5q).